Post on 31-Mar-2023
CASE REPORT – OPEN ACCESSInternational Journal of Surgery Case Reports 77 (2020) 161–164
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International Journal of Surgery Case Reports
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Laparoscopic approach to ureteroinguinal hernia
Praveen Lakshmi Narayanan, C.D. Narayanan ∗, Vishnu Sekar, Akshita Reddy VadyalaDepartment of General Surgery, Sri Ramachandra Institute of Higher Education and Research, No.1, Ramachandra Nagar, Porur, Chennai, 600116, India
a r t i c l e i n f o
Article history:Received 28 September 2020Received in revised form 27 October 2020Accepted 27 October 2020Available online 2 November 2020
Keywords:Uretero-inguinal herniaLaparoscopic approachHydro-ureteronephrosis
a b s t r a c t
INTRODUCTION: Herniation of the ureter into the inguinal canal is a rare occurrence. There have beenreports of inadvertent injury to the ureter during routine inguinal hernia repair. After an extensive searchof the literature, we believe that this is the first case to be managed via laparoscopic Trans AbdominalPre-Peritoneal Repair and would like to highlight the technical details of the laparoscopic procedure andis presented in line with SCARE 2018 Guidelines [1].PRESENTATION OF CASE: A 60-year-old male presented with left inguinal hernia. He also complained ofan increase in frequency of micturition, with an occasional radiating pain from loin to the groin. Imagingrevealed the left ureter coursing into the left inguinal canal, descending into the scrotum, and loopingback to enter the bladder with mild hydroureteronephrosis. Patient underwent a laparoscopic repair ofthe inguinal hernia with reduction of ureter under ureteroscope guidance and stent placement.DISCUSSION: The presence of ureter buried in a large amount of fat can be mistaken for a lipoma of the cordor extraperitoneal fat and injured with blind clamping and division. Presence of fat without an obvioussac should alert the surgeon to the possibility of ureter being a content.CONCLUSION: Laparoscopy is safe, technically feasible, offers good visualization of all hernial orifices,demonstrates complete reduction of ureter from inguinal canal under vision, allows manipulation ofureter under the vision for ureteroscopy and stenting, making sure there are no loops or kinking andallows placement of mesh in the preperitoneal space.
© 2020 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd. This is an openaccess article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
1. Introduction
Herniation of the ureter into the inguinal canal is a rare occur-rence. It was first reported in 1880 as an autopsy finding [2]. Sincethen, there have been reports of inadvertent injury to the ureterduring routine inguinal hernia repair. It has been associated withcongenital anomalies like renal agenesis [3] or crossed renal ectopia[4] and has also known to be acquired following renal transplant[5]. It may remain asymptomatic and present as a surprise to thehernia surgeon or present with abdominal pain and obstructiveuropathy. Men are most commonly affected and presents in thefifth decade of life [2]. Two anatomical variants of uretero-inguinalhernia have been described, para-peritoneal and extraperitoneal.The para-peritoneal type (80%) has a peritoneal indirect sac whichpulls the ureter, where the bladder forms the wall, similar to asliding hernia to some extent. This hernia has expansile impulseon coughing and is well visualized on laparoscopy as a peritonealdefect. The extraperitoneal type (20%) occurs without a peritonealsac, as in our case; There is no expansile impulse, and it does not
∗ Corresponding author.E-mail addresses: lpraveenkapv@gmail.com (P. Lakshmi Narayanan),
cdnarayan24@yahoo.com (N. C.D.), vishnusekar97@gmail.com (V. Sekar),akshita.reddy@gmail.com (A.R. Vadyala).
reduce completely, by non-communication with peritoneal cav-ity. The ureter slides along with the retroperitoneal fat into thescrotum and this is thought to be due to the failure of separa-tion of Wolffian duct from the ureteric bud [6]. There have beenvaried presentations and management of this unique condition.Majority of the cases where the preoperative diagnosis was notavailable have resulted in injury to ureter; most often presentingin the postoperative period. Management ranged from percuta-neous nephrostomy to nephrectomy, exploratory laparotomy andresection of the ureter with reimplantation [7]. Due to delay inrecognition of ureteric injury following hernia repair, mortality hasbeen described in paediatric age group [8]. In cases where a pre-operative diagnosis has been made, the management ranged froma simple reduction in open hernia surgery to a complex proce-dure like ureteroneocystostomy to deal with the redundant ureter[7,9]. Laparoscopy has gained wide acceptance and popularity inthe management of hernia and has the benefit of decreased post-operative pain and neuralgic complications. Our patient presentedwith a groin swelling, and the preoperative imaging confirmed thediagnosis of ureteroinguinal hernia. He had obstructive uropathyand the extraperitoneal variant of ureteral herniation. This was suc-cessfully managed by laparoscopy, which offers good visualizationof the redundant ureter, helps in removal of adhesions and kinks,assists in straightening the ureter under vision, and has an addedadvantage of guiding ureteroscopy and stenting. After an extensive
https://doi.org/10.1016/j.ijscr.2020.10.1272210-2612/© 2020 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
CASE REPORT – OPEN ACCESSP. Lakshmi Narayanan et al. International Journal of Surgery Case Reports 77 (2020) 161–164
Fig. 1. A plain CT of KUB showing the left ureter coursing into the left inguinal canal,descending into the scrotum, and looping back to enter the bladder (arrow).
search of the literature, we believe that this is the first case to bemanaged via laparoscopic Trans-Abdominal Pre-Peritoneal Repairand would like to highlight the technical details of the procedure.This case report is presented in line with SCARE-2018 Guidelines[1].
2. Patient information
A 60-year-old male presented to outpatient department withcomplaints of swelling on the left groin for eight months withassociated discomfort, and a noticeable increase in the size of theswelling upon straining, which reduced spontaneously on lyingdown. He complained of an increased frequency of micturition,with an occasional radiating pain from loin to groin which wasnot associated with any nausea or vomiting. Clinical examinationrevealed a boggy swelling in the left inguinal region which seemedto partially decrease in size on compression. A non-expansileimpulse was noted on coughing. The other hernial orifices werenormal. Clinically, the patient was diagnosed to have a left inguinalhernia. He has no relevant personal or family medical history.
3. Diagnostic assessment
Because of increased frequency of micturition, and renal colic, anUltrasound KUB was requested, which showed a tubular fluid-filledstructure looping around the left inguinal canal, and passing backinto the abdominal cavity. A plain CT-KUB showed the left uretercoursing into the left inguinal canal, descending into the scrotum,and looping back to enter the bladder (Fig. 1). There was also a leftproximal hydroureteronephrosis. Renal function tests were withinnormal range.
4. Therapeutic intervention
The patient was planned for a Laparoscopic Trans-AbdominalPre-Peritoneal repair for ureteric herniation by laparoscopicsurgeons. Under General anaesthesia, with patient in supine Tren-delenburg position, one 10 mm camera port, and two 5 mm workingports were created. Upon entering the peritoneal cavity, there wasno hernial sac. The peritoneum was incised 2 cm above the internalring and extended medially up to the medial umbilical ligamentand laterally up to the anterior superior iliac spine. The peritoneal
flap was raised as in routine Inguinal hernia repair. The Bogros andretropubic space were dissected. The Inferior Epigastric artery wasidentified and preserved. At the level of the internal ring, therewas a large tubular structure extensively covered by fat (Fig. 2),which was dissected slowly by traction and counter-traction uti-lizing both blunt and sharp dissections, till the apex of the U-shapedsling. There was extensive retroperitoneal fat which had herniatedalong with the ureter, similar to lipoma of cord. After dissection, theureter was found grossly dilated and redundant as a sigmoid ureter.To straighten the ureter and to keep it in position, the plan wasmade to stent the ureter by urologist. A Ureteroscope was passedover the double guidewire and stenting was done. The redundantand tortuous ureter made it extremely difficult for stenting andoften an alpha loop would form (Fig. 3) akin to a colonoscopy.Ultimately, this could be achieved by laparoscopic guidance andvisualization and endoscopic stenting was done. Once the stentreached the renal pelvis, the ureter straightened out and remainedin place. The Bogros space was dissected as in conventional herniarepair. A 12 × 10 cm polypropylene mesh was placed and the peri-toneum was closed using 3-0 v-loc sutures. Post-operative periodwas uneventful. Patient was discharged on post-operative day-2with ureteric catheter in-situ.
5. Outcomes and follow-up
The patient was followed up at 1 week, 1 month and 12 monthsby both urologist and laparoscopic surgeons. The ureteric catheterwas removed in 4 weeks. At 12-months follow-up, patient wassymptom free and had no urinary complaints.
6. Discussion
Inguinal hernia repair is among the commonest surgeries per-formed. The contents of the hernia are usually small bowel, colon,omentum or urinary bladder which happens commonly in a directsac or as a part of a sliding hernia. One may encounter the appendix(Amyand’s hernia) and Meckel’s diverticulum(Littre’s hernia) ascontent in an inguinal hernia, albeit rarely [6]. These may pose atechnical difficulty concerning decision-making, regarding place-ment of mesh when they are infected. In contrast, a rare contentthat might surprise the surgeon and maybe inadvertently injured isthe ureter. The first intraoperative diagnosis was by Reichel and thepreoperative diagnosis was by Dourmashkin [2]. High morbidityand even mortality are encountered in cases where a preopera-tive diagnosis was not made. The presence of ureter, buried in alarge amount of fat, can be mistaken for lipoma of the cord orextraperitoneal fat and injured with blind clamping and division.Presence of fat without an obvious sac should alert the surgeon tothe possibility of ureter being a content [6]. Considering the vol-ume of hernia surgeries globally, a routine CT scan is not justifiedbut advisable in patients with urinary complaints and derangedrenal function tests. Laparoscopy has never been attempted inthe uretero-inguinal hernia [6]. Laparoscopy offers a tremendousadvantage in the visualization of anatomy before division. In theextraperitoneal type, there is no sac on entering, but on rais-ing a peritoneal flap, a large tubular structure was seen enteringthe inguinal canal from the retroperitoneum forming a loop, andreturning to the bladder. Our management was made easier by pre-operative diagnosis with imaging. Once the ureter was mobilizedalong with the retroperitoneal fat into the abdominal cavity, wecould appreciate a redundant sigmoid ureter, and prone for a kinkor volvulus. Ureteroscopy with stenting was achieved by a com-bination of laparo-endoscopy, albeit with difficulty as the ureterwas very tortuous. Zarif Vahya Et al. reported a patient who hadto undergo stenting followed by repair and required a second sit-
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CASE REPORT – OPEN ACCESSP. Lakshmi Narayanan et al. International Journal of Surgery Case Reports 77 (2020) 161–164
Fig. 2. At the level of the internal ring, there was a large tubular structure extensively covered by fat.I. White arrow showing the extraperitoneal fat surrounding the ureter.II. Black arrow showing tortuous ureter.
Fig. 3. Figure showing tortuous ureter. (arrow).
ting for stone retrieval once the ureter was straightened out [6].Laparoscopy offers the advantage of a combined laparo-endoscopy,in dealing with the redundant ureter. The decision to stent wasbased on the urologist, to keep the ureter in place till adhesionsform, to straighten out the ureter and also relieve the obstruc-tion caused by kinking. This anomaly of extraperitoneal type hasalso been documented in association with other congenital abnor-malities (agenesis of the gall bladder and left kidney) [3]. Anotherassociation of ureter herniation is in post-renal transplant, pos-sibly due to neopositioning without any adhesions [2]. Majorityof inguinal hernia is dealt by general surgeons without imagingas it is cost-effective. Ultrasound or CT-KUB should be consid-ered in patients with urinary complaints, altered renal functiontests, and also in groin swellings which are irreducible. Unilat-eral hydronephrosis or tubular fluid-filled loop in the inguinalcanal must nudge the surgeon for a preoperative assessment whichincludes CT-Urogram.
7. Conclusion
Finally, laparoscopy is safe, technically feasible, offers good visu-alization of all hernial orifices, demonstrates complete reductionof ureter from inguinal canal under vision, allows manipulation ofureter under the vision for ureteroscopy and stenting, making sure
there are no loops or kinking and allows placement of mesh in thepreperitoneal space.
Declaration of Competing Interest
The authors report no declarations of interest.
Funding
Nil source of funding.
Ethical approval
No ethics required for this case report. An ethics approval fromthe institution is exempt.
Consent
Written informed consent was obtained from the patient forpublication of this case report and accompanying images. A copyof the written consent is available for review by the Editor-in-Chiefof this journal on request.
163
CASE REPORT – OPEN ACCESSP. Lakshmi Narayanan et al. International Journal of Surgery Case Reports 77 (2020) 161–164
Author contribution
Praveen Lakshminarayanan: Conceptualization, Methodology,Software, Formal analysis, Data curation, Writing – review andediting, Project administration.
C.D. Narayanan: Conceptualization, Methodology, Validation,Formal analysis, Data curation, Writing – original draft, Writing –review and editing, Visualization, Supervision.
Akshita Reddy Vadyala: Conceptualization, Software, Valida-tion, Formal analysis, Data curation, Writing – review and editing,Visualization.
Vishnu Sekar: Conceptualization, Software, Validation, Datacuration, Writing – review and editing, Investigation, Resources,Data curation.
Registration of research studies
1. Name of the registry: RESEARCH REGISTRY2. Unique identifying number or registration ID: researchreg-
istry61583. Hyperlink to your specific registration (must be publicly acces-
sible and will be checked): https://www.researchregistry.com/browse-the-registry#home/registrationdetails/5f958697e0d0d70015951a4d/
Guarantor
C.D. Narayanan.
Provenance and peer review
Not commissioned, externally peer-reviewed.
References
[1] R.A. Agha, M.R. Borrelli, R. Farwana, K. Koshy, A. Fowler, D.P. Orgill, For theSCARE Group, The SCARE 2018 statement: updating consensus surgical CAseREport (SCARE) guidelines, Int. J. Surg. 60 (2018) 132–136.
[2] M. Masood Sidiqi, Geoffrey Menezes, Asymptomatic herniation of ureter in theroutine inguinal hernia: a dangerous trap for general surgeons, Int. J. Surg. CaseRep. 49 (2018) 244–246, http://dx.doi.org/10.1016/j.ijscr.2018.07.013.
[3] Ronaldo de Carvalho Neiva, Carlos Eduardo, Garcia Westin, et al., Inguinalhernia with ureter in patient with single kidney, AME Case Rep. 2 (5) (2018),http://dx.doi.org/10.21037/acr.2018.01.05.
[4] Marc S. Rocklin, Keith N. Apelgren, et al., Scrotal incarceration of ureter withcrossed renal ectopia: case report and literature review, J. Urol. 142 (1989)366–368, http://dx.doi.org/10.1016/S0022-5347(17)38761-X.
[5] Sameer Vyas, Neha Chabra, et al., Inguinal herniation of bladder and ureter: anunusual cause of obstructive uropathy in a transplant kidney, Saudi J. KidneyDis. Transpl. 25 (1) (2013) 153–155, http://dx.doi.org/10.4103/1319-2442.124549.
[6] Zarif Yahya, Yahya Al-Habbal, Sayed Hassen, Ureteral inguinal hernia: anuncommon trap for general surgeons, BMJ Case Rep. 2017 (2017), http://dx.doi.org/10.1136/bcr-2017-219288.
[7] Erik Anderson, Anthony Corcoran, Obstructive uropathy due to incarceratedureteroinguinal hernia, World J. Nephrol. Urol. 4 (3) (2015) 237–239, http://dx.doi.org/10.14740/wjnu218w.
[8] Ralph L. Dourmashkin, Scrotal hernia of ureter, associated with a unilateralfused kidney: a case report, J. Urol. 38 (5) (1937) 455–467, http://dx.doi.org/10.1016/S0022-5347(17)71975-1.
[9] E.S. Allam, D.Y. Johnson, S.G. Grewal, F.E. Johnson, Inguinoscrotal herniation ofthe ureter: description of five cases, Int. J. Surg. Case Rep. 14 (2015) 160–163,http://dx.doi.org/10.1016/j.ijscr.2015.06.044.
Open AccessThis article is published Open Access at sciencedirect.com. It is distributed under the IJSCR Supplemental terms and conditions, whichpermits unrestricted non commercial use, distribution, and reproduction in any medium, provided the original authors and source arecredited.
164
O R I G I N A L R E S E A R C H
A Study on Clinical and Pathological Responses to Neoadjuvant Chemotherapy in Breast Carcinoma
This article was published in the following Dove Press journal: Breast Cancer: Targets and Therapy
Supreeth Kumar Reddy Kunnuru1
Manuneethimaran Thiyagarajan 1
Jovita Martin Daniel2
Balaji Singh K 1
1General Surgery Department, Sri Ramachandra Medical University, Chennai 600116, India; 2Medical Oncology Department, Sri Ramachandra Medical University, Chennai 600116, India
Aim and objectives: To assess the effectiveness of neo-adjuvant chemotherapy and its impact on the clinical and pathological response in locally advanced breast cancer. To compare molecular subtypes of breast cancer with response to neo-adjuvant chemotherapy.Patients and methods: This was a prospective study on patients who received neoadju-vant chemotherapy for breast carcinoma for a 3-year period. A total of 60 patients who presented with locally advanced breast cancer (LABC) were treated with neoadjuvant chemotherapy. Forty patients were treated with the 5-fluorouracil, epirubicin, and cyclopho-sphamide (FEC) schedule, 16 patients were treated with Adriamycin and cyclophosphamide (AC), and four patients were treated with oral cyclophosphamide, intravenous methotrexate, and fluorouracil (CMF). Taxol was added in all node-positive cases, triple negative breast cancer (TNBC), and Her 2 positive cases. The clinical response was assessed with RECIST criteria after neoadjuvant chemotherapy. The response was compared with molecular sub-types of carcinoma breast and receptor status individually.Results: A total of 60 female patients receiving primary chemotherapy for locally advanced breast malignancy were studied. The median age of the patients at the time of diagnosis was 44 years (range=24–73). In terms of menopausal status, 25 (42%) patients were pre-menopausal and 35 (58%) patients were post-menopausal. Histological classifi-cation showed invasive ductal carcinoma in 72% of patients, invasive lobular carcinoma in 15% of patients, and other types including mixed patterns in 13% of patients. Among 60 patients, 16 patients (26.6%) had clinically complete remission (cCR), 30 patients (50%) had partial remission, eight patients (13.3%) had stable disease, and six patients (10%) had progressive disease. Following neoadjuvant chemotherapy, 46 (76.6%) patient underwent Modified radical mastectomy surgery. Target therapy was given for Her2 neu patients after surgery. Hormonal therapy was added to hormone ER PR positive cases postoperatively. Eight patients (13.3%) among this operated cases attained complete pathological response.Conclusion: Preoperative chemotherapy downstages the primary tumors and axillary metas-tasis in patients with locally advanced breast carcinoma. Comparison of molecular subtypes with chemotherapy response is a better way to find out the predictors of response to chemotherapy.Keywords: neoadjuvant chemotherapy, carcinoma breast, predictors of NACT response, clinical and pathological response to NACT
IntroductionWorldwide, locally advanced breast carcinoma is a significant problem. Bulky primary tumor of the chest wall with or without axillary lymph nodes is defined as locally advanced malignancy (involvement of axillary and/or internal mammary nodes with matting).1 In metastatic disease limited to supra clavicular nodes,
Correspondence: Manuneethimaran Thiyagarajan General Surgery Department, Sri Ramachandra Medical University, 9036, Tower 9b, Prestige, Iyyapanthanagal, Chennai 614613, India Tel +91 9952044955 Email profmaran@gmail.com
Jovita Martin Daniel Medical Oncology Department, Sri Ramachandra Medical University, Porur, Chennai 600116, India Porur Email jovimartin4@gmail.com
submit your manuscript | www.dovepress.com Breast Cancer: Targets and Therapy 2020:12 259–266 259
http://doi.org/10.2147/BCTT.S277588
DovePress © 2020 Kunnuru et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the
work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
Breast Cancer: Targets and Therapy Dovepressopen access to scientific and medical research
Open Access Full Text Article
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survival increased by multi-modality mode of treatment.2
After this isolated supraclavicular metastasis was included in the stage III/LABC category.3 However, in spite of radical surgery there is reduced long-term survival due to the high incidence of loco-regional recurrences.4 In locally advanced breast carcinoma, neo-adjuvant systemic therapy (also called primary systemic therapy or induction ther-apy) has become a valuable strategy. But not all patients in this category respond well to Neo-adjuvant chemotherapy (NACT). Only in 30% of patients does complete or partial response occur after neoadjuvant chemotherapy. If che-motherapy is given early for micro-metastasis, the disease can be controlled.5
Moreover, NACT prior to surgery can make inoperable tumor operable and increase the rate of breast conservative surgery.6
The overall survival is improved by NACT in women with LABC. The prognosis is better for early breast dis-ease. It is better in axillary lymph node negative patients than axillary lymph node positive patients.7 There is poor survival in patients with a great number of axillary lymph nodes and higher nodal status. Patients with a larger size breast tumor have poorer survival than small tumor patients.7,8 Valagussa et al8 show 5 years survival was 65% in tumors less than 5 cm. It also shows the survival rate of 36% and 16% in breast tumors of size 5–10 cm and more than 10 cm, respectively.
In addition to this, there is equally comparable survival in patients treated with NACT and directly operable breast tumor patients.9,10 There are many studies which com-pared the response to NACT with receptor status, Her2 neu, and menopausal status. If we include molecular sub- types also in this comparison we can derive correct pre-dictors for response to NACT.
Aim and ObjectivesIn our study the aim was to assess the effect of neoadju-vant chemotherapy and its impact on clinical and patholo-gical responses.
To compare the patients characteristic, receptor status, and molecular subtypes of carcinoma breast with response to NACT.
Patients and MethodsThis was a prospective study on patients who received neoadjuvant chemotherapy in carcinoma breast for a 3-year period in Sri Ramachandra medical university hospital in 2015. A total of 60 patients who presented
with LABC were treated with NACT. In the TNM staging classification, LABC is represented by stage IIB (T2-N1; T3-N0), IIIA (T0-N2; T1/2-N2; T3-N1/2), stage IIIB (T4, N0-2) and stage IIIC disease (any T, N3). Early breast carcinoma (less than stage 2b), metastatic breast carci-noma, and those who missed follow-up or were not willing to be included were excluded.
The consent for study was obtained from all patients. A complete explanation of the study purpose and nature of study was given to the patients. The participants were assured that participation was voluntary and they could withdraw from the study at any stage. We assured that the data collected would be kept confidentially and would be used only for research purposes. Institutional Ethics com-mittee approval was obtained.
The standard neoadjuvant treatment regimen of 5-fluor-ouracil, epirubicin, and cyclophosphamide (FEC) with two schedules was used: 500 mg/m2 5-fluorouracil, 75 mg/m2
epirubicin, and 500 mg/m2 cyclophosphamide or 600 mg/ m2 5-fluorouracil, 60 mg/m2 epirubicin and 600 mg/m2
cyclophosphamide, both for six cycles on a 21-day cycle. Forty patients were treated with the FEC schedule. Other chemotherapy schedules used included AC (Adriamycin 60 mg/m2, cyclophosphamide 600 mg/m2 q21 for four cycles, 16 patients), CMF (oral cyclophosphamide 100 mg/m2 on days 1–14 and intravenous methotrexate 40 mg/m2 and 5-fluorouracil 600 mg/m2 on days 1 and 8, q28 for six cycles, for four patients). Paclitaxel was added 175 mg/m2 for a 3-week interval in node-positive cases.
Chemotherapy plan:
1. Triple negative/node positive with HER2 neu + cases received AC + Taxol (16 cases)
2. Node-negative with HER2 neu negative cases, received FEC regimen alone of six cycles (10 cases). Those patients with Her 2 Positive were treated (24 patients) with FEC x4 cycles NACT + Adjuvant Taxol x4 cycles. Among those who received Taxol in the adjuvant setting, eight patients received Taxol and Trastuzumab in the adjuvant setting. The overall number of patients who received FEC as NACT was 40 patients.11,12
3. Patients who did not tolerate anthracyclines, old, and frail patients with poor performance status received the CMF regimen (4 patients).
Baseline patient and tumor characteristics recorded included age, tumor stage, nodal stage, tumor grade,
submit your manuscript | www.dovepress.com
DovePress
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estrogen receptor (ER) status, progesterone receptor (PR) status, and HER2-neu. Clinical assessment and Sono- mammogram were used to assess the tumor size and nodal status. Tru-cut biopsy was done for all patients. Histologic grade, immunohistochemistry (IHC) for estro-gen/progesterone expression, HER2-neu expression via IHC or fluorescent in situ hybridization (FISH) was done for all patients. IHC analyses were performed on formalin- fixed paraffin-embedded tissue sections. Positive ER and PR status was defined as at least >1% of tumor cells with nuclear staining. Tumors were considered HER2 positive with a score of 3+ on IHC and/or a FISH ratio of greater than 2.0. Clinical response was assessed after three cycles of chemotherapy and at the end of the treatment. According to RECIST criteria tumors, size and node size were measured after chemotherapy. RECIST 1.16 utilized the following classifications for therapeutic response: com-plete response (CR), primary tumor disappearance; partial response (PR), 30% or greater decrease in longest diameter of primary tumor; progressive disease (PD), 20% or greater increase in longest diameter of primary tumor; stable disease (SD), tumors that did not show either suffi-cient shrinkage to be classified as PR or sufficient increase to be classified as PD.
Pathological response was assessed on completion of NACT and completion of surgery. The pCR was defined as having no residual invasive carcinoma in the breast and no tumor in the axillary lymph nodes. Patients with residual ductal carcinoma in-situ (DCIS) and no evidence of resi-dual invasive disease were included in this category.13 The pCR rate was compared by clinical response category after three cycles of chemotherapy. All summary statistics were stated with 95% confidence limits. SPSS version 17 was used to analyze statistical results. A P-value<0.05 was considered as a statistically significant value.
Breast cancer is broadly divided into distinct molecular subtypes (luminal A, luminal B, HER2, and triple negative) by gene expression profiling with prognostic significance.14
Our 60 cases were divided into four groups based on molecular sub-types:
1. Luminal A: Hormone positive and HER2 neu-2. Luminal B: Hormone positive and Her2neu positive3. Triple negative: Hormone negative and HER2 neu-4. HER2: hormone negative and Her2neu positive
Comparison of clinical pathological response to che-motherapy was also performed with these sub-groups. All
patients who responded to chemotherapy were operated on, and the rest of the patients (static and progressive patients) continued chemotherapy for another three cycles and were assessed. For paients with node positive, TNBC, and Her2 neu positive adjuvant Taxol was given. Target therapy was given for Her2 neu patients after surgery since our study was conducted with free medication side. Only for patients who could afford it was target therapy added after surgery. Hormonal therapy was added to hormone ER PR positive cases in the post-operative period. Post-operative radiother-apy was also given to all patients. Since not all patients were followed-up after therapy, exact 5-year survival rate could not be calculated.
ResultsSixty female patients receiving primary chemotherapy for locally advanced breast malignancy were studied. The median age of the patients at the time of diagnosis was 44 years (range=24–73). In terms of menopausal status, 25 (42%) patients were pre-menopausal and 35 (58%) patients were post-menopausal . The mean tumor diameter measured clini-cally before starting chemotherapy was 9.2 cm (range=3– 17 cm). Axillary nodal status was N0 in eight patients (13.3%), N1 in 40 patients (66.6%), and N2 in 12 patients (20%).
A histological classification was done which showed invasive ductal carcinoma in 72% of patients, invasive lobular carcinoma in 15% of patients, and other types including mixed patterns in 13% of patients. Malignancy grading before starting chemotherapy, showed grade (1 + 2) in 21 (35%) patients and grade 3 with 39 (65%) patients. Estrogen receptors showed positive results in 36 patients (60%) and negative results in 24 patients (40%). Progesterone receptors showed positive results in 31 (51.6%) patients and negative results in 29 (48.3%) patients. HER-2-neu receptor status was shown to be posi-tive in 32 patients (53.3%) and negative in 28 patients (46.6%).
Table 1 Clinical Response Rate (RECIST Criteria)15
Clinical Response Frequency Percent
Complete Response 16 26.6%
Partial Response 30 50%
No Response 8 13.3%Progressive Disease 6 10%
Total 60 100%
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According to Table 1, among the 60 patients 16 patients (26.6%) had clinical complete remission (cCR), 30 patients (50%) had partial remission, eight patients (13.3%) had stable disease, and six patients (10%) had progressive disease.
According to Table 2, post chemotherapy 16 (26.7%) patients had complete remission (T0). Amongst the 32 (53.3%) patients with pre-chemotherapy T4 disease, only eight (13.3%) patients remained in T4 stage after che-motherapy. This shows a statistically significant reduction of T stage after chemotherapy (P<0.05). T3 disease also responded significantly well to chemotherapy (40% reduced to 13%).
According to Table 3, clinical examination of axilla showed at the pre-chemotherapy stage, only eight (13.3%) patients were in N0 stage. But, after NACT, there were 40 (66.7%) patients with N0 disease. Hence, 32 (53.3%)
patients had a complete nodal response after chemotherapy. In addition to this, N2 stage disease was in 12 (20%) patients (pre-chemotherapy), which reduced to four (6.7%) patients after chemotherapy. This is statistically significant, with P<0.05. Comparatively, N1 disease also responded well with chemotherapy (66.7% reduced to 26.7%).
According to Table 4, after NACT the response rate was good in those aged over 50 years, with a P-value<0.05. The NACT response rate was better in the post-menopausal group than in the premenopausal group, with a P-value<0.05. ER positive patients had a better clinical response rate than ER negative patients for NACT (P-value<0.05). But there was no statistical differ-ence in PR status and HER2-neu status in view of response rate after NACT (P=0.385 and P=0.309). According to tumor grade, complete and partial response were better in low grade (1 and 2) tumors than high grade tumors (3), but it was not statistically significant (P=0.143). While com-paring the response rate to the tumor histology, invasive ductal CA has a significant response over other types (P<0.05).
While analyzing the number of molecular subtypes of our cases there were 19 (31.6%) Luminal A cases and 22 (36.6%) luminal B cases, nine (15%) triple negative cases, and 10 (16%) HER 2 cases were identified.
According to Table 5, complete response was 45% in Luminal B, and it is statistically significant (P<0.05). But partial response is high (P-value >0.05) in Luminal A cases (68.5%).
If we combined both partial and complete response to chemotherapy, clinical response is good in luminal A (90%) compared to luminal B (77%). In TNBC, total clinical response is 78%. While comparing complete
Table 2 Pre-NACT T-Stage vs Post-NACT T-Stage
Post Chemotherapy Tumor Stage Total
T0 T1 T2 T3 T4
Pre-Chemotherapy Tumor Stage T2 2 0 2 0 0 43.3% 0.0% 3.3% 0.0% 0.0% 6.6%
T3 12 5 3 4 0 2420% 8.3% 5% 6.6% 0% 40.0%
T4 2 10 8 4 8 32
3.3% 16.6% 13.3% 6.6% 13.3% 53.3%
Total 16 15 13 8 8 60
26.7% 25% 21.6% 13.3% 13.3% 100.0%
Note: P-value<0.05.
Table 3 Pre-NACT Nodal Stage vs Post-NACT Nodal Stage
Post- Chemotherapy Nodal Stage
Total
N0 N1 N2
Pre-Chemotherapy Nodal
Stage
N0 8 0 0 813.3% 0.0% 0.0% 13.3%
N1 26 14 0 40
43.3% 23.3% 0.0% 66.7%
N2 6 2 4 12
10.0% 3.3% 6.7% 20.0%
Total 40 16 4 6066.7% 26.7% 6.7% 100.0%
Note: P-value<0.05.
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pathological response (pCR) in this sub-group shows 22.2% of triple negative patients and 15.7% of luminal A patients had good response, which is not statistically sig-nificant (P>0.05)
Following NACT, 46 (76.6%) patients underwent mod-ified radical mastectomy surgery. All patients had axillary lymph node dissection (ALND). The other 14 patient continued their cycles of chemotherapy.
Among the operated cases eight patients (13.3%) attained pCR. Although 16 patients (26.6%) had complete clinical response (cCR), eight patients had residual disease in pathological specimens. At follow-up we found 5 year survival of these eight pCR patients was 100%.
DiscussionUsage of NACT in LABC is very effective. In our study, the overall clinical response rate was 76.6% (complete + partial). In patients who achieved complete clinical response, residual tumor might still persist histologically.16–18 In our study, 16 patients (26.6%)
had cCR. Eight of them (13.3%) had pCR, and the other eight (13.3%) had residual disease histologically.
While comparing with another study, complete clinical response in our study (26.6%) was comparable with Alvarado et al,19 which showed a cCR of 12%, and Garbhi olfa et al,20 which showed a cCR of 14%. The partial response rate in our study was 50%. In Alvarado et al and Garbhi et al it was 28% and 49%, respectively. pCR was 13.3% in our study, while it was 8% and 7% in Alvarado et al and Garbhi et al, respectively.
In Garbhi et al, the clinical response rate was assessed by univariate analysis: 63% in ER-positive tumors, 84% in ER-negative, 59% in PR-positive, 62% in PR-negative, 64% in HER2-positive, and 62% in HER 2 negative. These results were comparable to our study. In our study group the clinical response rates by each factor were as follows: 94% in ER-positive tumors, 50% in ER-negative, 83.8% in PR-positive, 68.8% in PR-negative, 84.2% in HER2-positive, and 87.8% in HER2-negative after three cycles of chemotherapy.
Table 4 Post-NACT Response Rate Compared with Age, Menopausal State, ER, PR Her2neu, Tumor Grade, and Tumor Histology (Percentage within Group)
Complete Response
Partial Response
Stable Progressive Total
Age <50 1 (2.7%) 23 (63.8%) 6 (16.6%) 6 (16.6%) 36
(P<0.05) 51 and above 15 (62.5%) 7 (29%) 1 (4%) 1 (4%) 24
Menopausal state
Pre- menopausal 4 (16%) 10 (4%) 5 (2%) 6 (24%) 25(P<0.05) Post- menopausal 12 (34.2%) 20 (57%) 3 (8.5%) 0 (0%) 35
ER status
(P<0.05) Positive 14 (38.8%) 20 (55.5%) 2 (5.5%) 0 (0%) 36
Negative 2 (8.3%) 10 (41.6%) 6 (25%) 6 (25%) 24
PR status
(P=0.385) Positive 10 (32.2%) 16 (51.6%) 3 (9.6%) 2 (6.4%) 31Negative 6 (20.6%) 14 (48.2%) 5 (17.2%) 4 (13.7%) 29
Her2 -neu(P=0.309) Positive 10 (31.2%) 17 (53%) 3 (9.3%) 2 (6.2%) 32
Negative 6 (21.4%) 13 (46.4%) 5 (17.8%) 4 (14.2%) 28
Grade
(P=0.143) 1 and 2 6 (28.5%) 11 (52%) 3 (14.2%) 1 (4.7%) 21
3 10 (25.6%) 19 48.7%) 5 (12.8%) 5 (12.8%) 39
Histology
(P<0.05) Invasive ductal CA 14 (32.5%) 22 (51%) 5 (11.5%) 2 (4%) 43Invasive lobular CA 0 (0%) 5 (55.5%) 1 (11%) 3 (33.3%) 9
Others and mixed 2 (25%) 3 (37.5%) 2 (25%) 1 (12.5%) 8
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Del Prete et al21 shows good pathological responses of ER positive tumors, which is similar to our study.
In our study there was no significant difference in response rate in PR receptor status or Her2-neu status. In Miglietta et al,22 a good response was seen with Her2-neu over-expressed tumors. Resende et al23 showed no rela-tionship with HER2–neu status of the patients. In our study the post-menopausal group and those aged above 51 had a better clinical response (P<0.05) than those who were pre-menopausal and those aged below 50 years. Resende et al23 shows no relationship with menopausal state. Del Prete et al21 showed good pathological response in premenopausal patients.
In our study, there is no statistically significant differ-ence in grade of the tumor and clinical response. Overall clinical response was 80.5% in low grade (1 and 2) and 74.3% in high grade tumors. In contrast, Awad et al showed better responses in rapidly proliferating tumors with a higher grade.24 Resende et al23 also showed good response in high grade tumors.
While comparing clinical response and histological types, our study shows a more statistically significant clinical response in invasive ductal carcinoma than other types (P<0.05). Similarly, Beresford et al25 reported a highly sig-nificant clinical response in patients with invasive ductal carcinoma. In addition to this, Alawad24 also showed 72 out of 76 patients diagnosed as invasive ductal carcinoma achieved a clinical response (complete or partial) to NACT. In Alawad, no lobular carcinomas had a complete pathologi-cal response to NACT. From this we can understand that histological type in breast carcinoma may play an important role in predicting the degree of clinical response to NACT.
While comparing this study based on molecular sub- types, Luminal B tumor had a complete clinical response (45%), but total clinical response was better in Luminal A (90%) tumors than Luminal B (only 77%). This shows hormone positive, HER negative tumors will have good clinical response to NACT. Luminal A and Her2 patients had no progressive disease when compared to other groups. In addition to this, triple negative patients had a higher total clinical response in 78% of patients.
Pathological response is more valuable than clinical response, since it shows the histology proof for response. The pathologic complete response (pCR) after NACT is probably most predictive with respect to long-term treat-ment outcomes.26
The triple negative tumor is basically ER/PR negative, and evidence suggests that the negative hormone receptor status is one of the strongest predictive markers associated with the higher likelihood of pCR to NACT.27,28 In our study, triple negative patients had a good pathological response (22.2%) followed by luminal A patients (15.7%). In Kim et al,29 the cPR rate was high in triple negative patients (21.1%), which is comparable to our study. In their study triple negative and Her 2 were more sensitive to NACT.
Incorporation of Trastuzumab with neoadjuvant che-motherapeutics is a promising alternative for the HER2 subtype.30 Phung et al31 shows neoadjuvant treatment with trastuzumab and chemotherapy combined in patients with HER2 positive breast cancer yielded a pathological com-plete response rate of 64.1%.
In our study, due to logistic reasons, Trastuzumab was not given as NACT, and it was given only in the adjuvant
Table 5 Clinical and Pathological Response in Molecular Sub-types
Luminal A (19) 31.6%
Luminal B (22) 36.6%
TNBC (9)15%
HER2 (10)16%
P-value
Complete response (16) 4 (21.1%) 10 (45.5%) 2 (22.2%) 0 0.046
(<0.05)
Partial response (30) 13 (68.4%) 7 (31.6%) 5 (55.6%) 5 (50%) 0.133 (>0.05)
Total response 17 (90%) 17 (77%) 7 (78%) 5 (50%) 0.126
(>0.05)Static disease (8) 2 (10.5%) 3 (13.6%) 0 3 (30%) 0.270
(>0.05)
Progressive disease (6) 0 2 (9.1%) 2 (22.2%) 2 (20%) 0.192 (>0.05)
Pathological response (8) 3 (15.7%) 3 (13.6%) 2 (22.2%) 0 0.324 (>0.05)
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setting. If we add it as a neo-adjuvant regimen it might improve the response rate in HER2 cases.
ConclusionThe preoperative chemotherapy (NACT) downstages the primary tumors and axillary metastasis in patients with LABC to operable tumors. The anthracycline-based che-motherapy along with Taxol gives good clinical and patho-logical responses in locally advanced breast CA. Though clinical response varies in tumor sub-types, pathological response is good in triple negative and Luminal A patients. Comparison of molecular sub-types with chemotherapy response is a better way to find out the predictors of response to chemotherapy. Adding Trastuzumab in NACT would improve the response rate in Her2 cases. Further studies with a larger number of cases are needed to come to the conclusion for predictors in molecular sub-types for NACT.
Ethics ApprovalThis study was approved by the Institutional Research Ethics Committee of Sri Ramachandra Medical University. It was conducted in accordance with the Declaration of Helsinki.
FundingThere was no funding from any organization or institute.
DisclosureThe authors report no conflicts of interest for this work.
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11. Kayal S, Biswajit D, Cyriac SL, et al. Comparison of neoadjuvant chemotherapy (NACT) with 5-fluorouracil, epirubicin (100mg), cyclophosphamide (FEC100) followed by docetaxel (D) (75mg) ver-sus adriamycin and cyclophosphamide (AC) followed by docetaxel (100mg) in locally advanced breast cancer (LABC): a randomized clinical study. J Clin Oncol. 33(15_suppl). doi:10.1200/jco.2015. 33.15_suppl.e12002
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European Journal of Molecular & Clinical Medicine
ISSN 2515-8260 Volume 07, Issue 05, 2020 55
55
DNA based CGB methylation in breast cancer –
a case control study
Dr. Anjana Vasudevan1, Dr. Vasugi. G. A.
2, Dr. R. Ponniah Iyyappan
3, Dr. Harpreet Kaur
4,
Dr. Balaji Singh5, Dr. C. Kaliyappa
5, Dr. Guru Prasad
6, Dr. C. S. Subramanium
7
1,3,5,6Department of General Surgery, Sri Ramachandra Institute of Higher Education and
research, Chennai, India. 4Department of Human Genetics, Sri Ramachandra Institute of Higher Education and
research, Chennai, India. 2Department of pathology, Sri Ramachandra Institute of Higher Education and research,
Chennai, India. 7Department of General Surgery, ACS Medical College and Hospital, Chennai, India.
8Department of General Surgery, Annamalai University, Tamil Nadu, India.
Name of Author / Co-
author
Designation University
Dr. Anjana Vasudevan Assistant Professor,
Department of General
Surgery
ACS Medical College and
Hospital, Chennai, India
Dr. Vasugi. G. A. Assistant Professor,
Department of pathology
Sri Ramachandra Institute of
Higher Education and
research, Chennai, India
Dr. R. Ponniah Iyyappan Associate Professor,
Department of General
Surgery
Sri Ramachandra Institute of
Higher Education and
research, Chennai, India
Dr. Harpreet Kaur Associate professor,
Department of Human
Genetics
Sri Ramachandra Institute of
Higher Education and
research, Chennai, India
Dr. Balaji Singh Professor, Department of
General Surgery
Sri Ramachandra Institute of
Higher Education and
research, Chennai, India
Dr. C. Kaliyappa Professor, Department of
General Surgery
Sri Ramachandra Institute of
Higher Education and
research, Chennai, India
Dr. Guru Prasad,
corresponding author
Assistant Professor,
Department of General
Surgery
ACS Medical College and
Hospital, Chennai, India
Dr. C. S. Subramanium Professor (retired),
Department of General
Surgery
Annamalai University, Tamil
Nadu, India
European Journal of Molecular & Clinical Medicine
ISSN 2515-8260 Volume 07, Issue 05, 2020 56
56
Abstract: Breast carcinoma is the most commonly diagnosed cancer and the leading cause
of cancer death. Breast cancer also produces and is influenced by ectopic hormones. Beta
Human Chorionic Gonadotropin (hCG) is one such hormone and is encoded by chorionic
gonadotropin beta (CGB) genes. The aim of this study was to determine the CGB gene
methylation in breast cancer tissues and compare them with normal tissues.
Materials and methods: After approval from Institutional Ethical Committee (IEC),
consent from patients were obtained. Normal and tumour tissues from breast cancer
patients were taken. DNA was isolated from normal and tumour tissues. Post bisulfate
conversion samples were processed for qPCR using methylation specific primers for the set
of selected CGB genes and SYBR green.
Results: 1-2M was found to be significantly higher among the normal tissues (50.22). 3-9M
was found to be 65.93 in tumour tissues and 5.05 in normal tissues and this was
significant.
Conclusion: 3-9 M is significantly higher in tumour tissues compared to normal tissues
and 1-2 M is significantly higher in normal tissues. This suggests that there are 2 different
types of beta hCG secreted by two different types of genes and this can be used for further
analysis as a part of future projects. This may help in formulating a new treatment process
and may also be used as a tumour marker in high risk patients.
KeyWords: Breast Cancer, genetics, cgb genes, methylation specific PCR, bisulfite
conversion,
1. INTRODUCTION:
Human Chorionic Gonadotrophin or hCG. It is heterodimeric and has two parts. An alpha and
a beta component. Elevated levels of beta hCG is most commonly associated with pregnancy.
But it is also seen in bladder cancer, colonic cancer and many others. The beta hCG is
encoded by cgb genes. It has various subtypes. (1–6)
The role of beta hCG in breast cancer is still speculative. The literature review for Beta hCG
as an indicator of prognosis both good and bad is equivocal. The role of beta hCG in
oncogenesis is complex and there is no clear explanation for the same. There are a lot of
studies from 1995 by Alverado et al to studies in 2019 by Aleksandra, who have done various
researches and given different conclusions.(2,3,7–9)
The breast has always been a symbol of vitality, fertility, beauty and motherhood. Especially
in India, from before the Indus valley civilisation till the Islamic and British invasion, the
female breasts were considered to belief giving, reason for sustenance of humanity and
divinity. Female breasts are still considered to be potent talisman, symbol of maternity,
empowerment and erotism. When there occurs a disease in such vital part, women are faced
with fear of mutilation, loss of beauty and a dread for life. It is well known that, breast cancer
is one of the most commonly diagnosed cancer and the leading cause of cancer death.(10)(11)
More frequently than not breast cancer presents as a painless lump and is frequently
diagnosed in the late stages in our country. (12)
Hence, the purpose of this study was to take an initiative in finding something good for the
patients suffering for breast cancer and if possible, to make an early diagnosis.
European Journal of Molecular & Clinical Medicine
ISSN 2515-8260 Volume 07, Issue 05, 2020 57
57
Aim:
To find and compare the cgb gene methylation among breast cancer tissues and normal breast
tissues.
2. METHODOLOGY:
After obtaining Institutional ethical clearance (CSP-MED/16/Jan/27/29), this study was
conducted in a total of 250 patients. Patients were explained in detail about this study and
their written informed consent was obtained.
Inclusion criteria:
Females who were more than 18 years, multiparous and with proven breast carcinoma
with or without nodal metastasis (Stages 1, 2 and 3)
Exclusion criteria:
Males, nulliparous women, Pregnant or nursing mothers, patients with distant
metastasis (stage 4), Patients with gynaecological or any other carcinoma, Neoadjuvant
chemo or radiotherapy, patients who have undergone prior surgery for breast cancer, Patients
who did not consent to take part in the study
A detailed history and a through physical examination was done and recorded. Triple
assessment was done for all patients. Tissue biopsy and radiological screening was done
followed by metastatic workup for each of these patients. Patients underwent modified
radical mastectomy on the affected side after obtaining anaesthetist fitness.
About 5cms of tissue was taken from the tumour site and from the normal quadrant after
discussion with the pathologist. This was then processed to extract DNA using QIAamp DNA
Mini Kit. (13)(14)
All these samples underwent bisulfite conversion using a commercially available
kit.(15)(12,14) Following this these samples were processed for qPCR using methylation
specific primers and SYBR green with set of primers for 1-2 CGB and 3-9 CGB genes which
were obtained from a previous study (16)(17)(3)(18)(14)
RT - PCR was performed on Rotor – gene 10 µL reaction mixture. A methylated DNA
sample obtained from the manufacturer was used as a control for calculating the Ct values.
From these 2^ (Delta Delta CT) values were calculated.
Statistical analysis was then performed using SPSS 18.0 (PASW Statistic, SPSS Inc., IBM,
Chicago, IL).
3. RESULTS:
This study was conducted among 250 patients. All of these patients were females who were
proved to be positive for breast cancer and were taken up for Modified Radical Mastectomy
before giving neoadjuvant chemotherapy or radiation.
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Molecular analysis:
Fold change was calculated with the Ct values obtained from RT-PCR.
The mean fold change amongst the study population was 15.09. Highest value being 253.7649 and the
lowest recorded was 0.0009.
Fold change among tumour and normal:
TYPE
Fold
change Std. Deviation Std. Error Mean
P Value
N 10.119 2.0445 1.2256 0.008
(<0.05) T 32.6662 12.6625 5.6625
Fold change among tumour and normal (Table 1)
The p value for this was calculated to be 0.007 using the Mann-Whitney test. Hence the Fold change
values were significantly higher amongst the tumour tissues than the normal tissues.
Fold change among methylated and unmethylated regions:
The fold change in methylated regions were significantly higher than the unmethylated counterparts.
The p value was 0.000 (<0.05).
Primers Fold change Std. deviation Std. error Mean p Value
1-2 M 32.9998 16.6665 2.65656
0.002
(<0.05)
1-2 UM 4.4203 17.7654 4.4321
3-9 M 40.6228 8.2256 6.95517
3-9 UM 6.2567 16.55234 1.198766
Fold change among methylated and unmethylated regions (Table 3)
Fold change between tumour tissues and normal tissues for CGB1-2 and CGB3-9:
CGB 1-2M was found to have significantly higher fold change among the normal tissues (30.22). p
value was 0.017 which is less than 0.05.
The fold change of CGB 3-9M was 61.93 in tumour tissues and 3.77 in normal tissues. The difference
between this was significant as the p value was 0.00 (<0.05). this suggests that 3-9 M is significantly
higher in tumour tissues compared to normal tissues.
There was no significant difference between the unmethylated primers.
Mean Std. Deviation Std. Error Mean p Value
1-2 M T 15.5522 10.6652 2.2265 0.009
(<0.05) N 50.219 12.66523 3.25617
1-2 UM
T 8.6622 16.6652 5.22278 0.325
N 6.5523 12.6225 3.9872
3-9 M
T 65.9295 21.09224 8.62254 0.001
(<0.05) N 5.0556 3.22765 1.76294
3-9 UM T 5.65432 2.6225 1.6987 0.435
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N 4.6625 1.62254 1.06349
Fold change between tumour tissues and normal tissues for CGB1-2 and CGB3-9 (Table 4)
4. DISCUSSION:
As we know breast cancer is the commonest cancer diagnosed and it is curable not just
treatable.
Demographic results:
There were 250 multiparous females with proven breast cancer as a part of this study.
The mean age of diagnosis was 55.65 years and a majority of about 62% of the patients were
between 41 to 60 years of age. Almost 95% of breast cancer was diagnosed in women older
than 40 years.(19) the risk of breast cancer increases with an increase in age. The incidence of
breast cancer reaches a peak of 421.3 cases per 100,000 at 70 to 80 years of age. It is
suggested that 95% of new cases occur in the perimenopausal age group or around 50 years
of age and this was in line with our findings.
Molecular analysis:
The difference in methylation levels of cgb genes between the mean of tumour and normal
tissues were significant with a p Value of 0.008 (<0.05). A higher expression of CBG genes
were noted in tumour tissues with a mean of 32.66 while compared to normal tissues
with 10.119. In 2014, a study by Xin-hua Liao, et al, showed higher expression of beta hCG
in tumour tissues.(20) Another study in 2019 done in ovarian tissues, by Sliwa Aleksandra .et
al, also showed higher expression of Beta hCG in tumour tissues compared to normal tissue.
(3) This was consistent with our study.
Higher expression of Beta hCG was seen in methylated counterparts with a p value of 0.002
(<0.05) in comparision with their unmethylated counterparts. Whereas, a study conducted in
2019 by Sliwa Aleksandra, et al, showed only a slight difference in expression between
methylated and unmethylated counterparts of beta hCG.(3) In 2010, increased CGB 5 gene
expression was concluded in a study by R K Iles, et al. (2)
In our study, higher CBG 1-2 M and CGB 3-9 M expressions were found in normal and
tumour tissues respectively with a statistical significance. The above finding were consistent
with Sliwa Aleksandra,et al’s study in 2019 .The study also showed higher expression of
CGB3 to CGB9 among ovarian cancer tissues and CGB1, CGB2 genes in normal ovarian
tissue. (3)
In 2012 and 2013, an increased expression of CGB 5 and CGB 8 were found by Kristiina
Rull, et al. The study also showed that any mutations in these gene were tolerated better and
in 2013, it was suggested that CGB5 gene without mutation offered protection against
recurrent miscarriages but their similar effect in various ethnic groups have not been
documented yet. (7,21) CGB 5 mutations associated with pregnancy loss and CGB 8 under
expression in mothers with recurrent pregnancy loss, was suggested by Liis Uuskula ,et al in
2011. (22) The protection offered bypregnancy induced beta hCG against breast cancer was
suggested by Xing-hua Liao,et al in 2014. the study also showed reduced proliferation of
MCF -7 cell by downregulating certain antigens by beta hCG , inadditon to cellular
differentiation when the same is upregulated.(20)
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All these results were in line with our pilot study done with 20 patients in 2019. Vasudevan
A, Iyyappan R ponniah, Kaur H, Ramalingam R, Singh B, Kaliyappa C, et al. BETA HCG
EXPRESSION AND CGB METHYLATION IN BREAST CANCER. Int J Sci Res.
2020;9(7):1–5 (14)
5. CONCLUSION:
cgb 1-2 Methylation was found to be significantly higher among the normal tissues and cgb
3-9 Methylation was significantly higher in tumour tissues. This suggests that there are 2
different types of beta hCG secreted by two different types of genes and this can be used for
further analysis as a part of future projects. This may help in formulating a new treatment
process and may also be used as a tumour marker in high risk patients.
Declarations: Not applicable
Funding: This article is a part of the PhD thesis, funded by ICMR (TSS fellowship), India.
Conflict of Interest: None.
This study was conducted on human breast tissue from patients undergoing surgery for breast
cancer. Written informed consent from each patient was obtained prior to initiation of the
project. Consent for images and other clinical information was also obtained. The patients
understand that their names and initials will not be published and due efforts will be made to
conceal their identity, but anonymity cannot be guaranteed.
Acknowledgements:
We would like to take this opportunity to thank ICMR (Indian Council of Medical Research)
for the funding of this project and our institutions SRI HER (Sri Ramachandra Institute of
Higher Education and Research) and ACSMCH (ACS Medical College and Hospital) for
their support and encouragement.
6. REFERENCES:
[1] Cole LA. Biological functions of hCG and hCG-related molecules. Cole Reprod Biol
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[2] Iles RK, Delves PJ, Butler SA. Does hCG or hCG play a role in cancer cell biology ?
Mol Cell Endocrinol Elsevier. 2010;329(1–2):62.
[3] Aleksandra Ś, Kubiczak M, Szczerba A, Walkowiak G, Nowak-markwitz E, Burczy B,
et al. Regulation of human chorionic gonadotropin beta subunit expression in ovarian
cancer. BMC Cancer. 2019;19(746):1–9.
[4] Rubin MR, Bilezikian JP, Birken S, Silverberg SJ. Human chorionic gonadotropin
measurements in parathyroid carcinoma. Eur J Endocrinol. 2008;159:469–74.
[5] Venyo Kodzo-Grey A, Herring D, Greenwood H, Maloney DJL. The expression of
Beta Human Chorionic Gonadotrophin (β-HCG) in human urothelial carcinoma. Pan
Afr Med J. 2010;20.
[6] NJ A, F P, L K, S F. Immunohistochemical expression of subunit beta HCG in breast
cancer. Eur J Gynaecol Oncol. 1992;13(6):461–6.
[7] Rull K, Ph D, Christiansen B, Ph D, Nagirnaja L, Sc M. A modest but signi fi cant
effect of CGB5 gene promoter polymorphisms in modulating the risk of recurrent
miscarriage. Fertil Steril. 2013;99(7).
[8] Hallast P, Nagirnaja L, Margus T, Laan M. Segmental duplications and gene
conversion : Human luteinizing hormone / chorionic gonadotropin  gene cluster.
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[9] Span PN, Manders P, Heuvel JJTM, Thomas CMG, Bosch RR, Beex LVAM, et al.
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[10] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer
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[11] Mannan AU, Singh J, Lakshmikeshava R, Thota N, Singh S, Sowmya TS, et al.
Detection of high frequency of mutations in a breast and / or ovarian cancer cohort :
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Genet. Nature Publishing Group; 2016;61(October 2015):515–22.
[12] Vasudevan A, Iyyappan P, Kaliyappa C, Singh KB. Clinico-pathological presentation
of breast carcinoma and its correlation with β hCG. J Exp Ther Oncol. 2019;13(8):139–
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[13] Ip SC, Lin SW, Lai KM. An evaluation of the performance of five extraction methods :
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[14] Vasudevan A, Iyyappan R ponniah, Kaur H, Ramalingam R, Singh B, Kaliyappa C, et
al. BETA HCG EXPRESSION AND CGB METHYLATION IN BREAST CANCER.
Int J Sci Res. 2020;9(7):1–5.
[15] Holmes EE, Jung M, Meller S, Leisse A, Sailer V, Zech J, et al. Performance
Evaluation of Kits for Bisulfite-Conversion of DNA from Tissues , Cell Lines , FFPE
Tissues , Aspirates , Lavages , Effusions , Plasma , Serum , and Urine. PLoS One.
2014;9(4):e93933.
[16] Huang G, Zhang X, Guo G, Huang K. Clinical significance of miR-21 expression in
breast cancer : of invasive ductal carcinoma. Oncol Rep. 2009;21:673–9.
[17] Aleksandra G, Kubiczak MJ, Walkowiak GP, Nowak-Markwitz E, Jankowska A.
Methylation status of human chorionic gonadotropin beta subunit promoter and
TFAP2A expression as factors regulating CGB gene expression in placenta. Fertil
Steril. 2014;102(4):1175–82.
[18] Sajid M, Akash H, Rehman K, Fiayyaz F, Sabir S, Khurshid M. Diabetes ‑ associated
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[19] Susan P Helmrich, SHAPIRO S, LYNN. Risk factors for breast cancer cancer. Am J
Epidemiol. 1983;117(1):35–45.
[20] Xing-Hua L, Wang Y, Wang N, Yan T-B, Xing W-J, Zheng L, et al. Human chorionic
gonadotropin decreases human breast cancer cell proliferation and promotes
differentiation. Int Union Biochem Mol Biol. 2014;66(5):352–360.
[21] Rull K, Jonas KC, Nagirnaja L, Peltoketo H, Christiansen OB, Kairys V, et al.
Structural and functional analysis of rare missense mutations in human chorionic
gonadotrophin b -subunit. Mol Hum Reprod. 2012;18(8):379–90.
[22] Uusküla L, Rull K, Nagirnaja L, Laan M. Methylation Allelic Polymorphism ( MAP )
in Chorionic Gonadotropin β5 ( CGB5 ) and Its Association with Pregnancy Success. J
Clin Endocrinol Metab. 2011;96(1):199–207.
ORIGINAL RESEARCH PAPER
BETA HCG EXPRESSION AND CGB METHYLATION IN BREAST CANCER
Dr. Anjana Vasudevan
Department of General Surgery, Sri Ramachandra Institute of Higher Education and research, Chennai, India.
Dr. R. Ponniah Iyyappan*
Department of General Surgery, Sri Ramachandra Institute of Higher Education and research, Chennai, India. *Corresponding Author
Dr. Harpreet KaurDepartment of General Surgery, Sri Ramachandra Institute of Higher Education and research, Chennai, India.
Mr. Ravi Ramalingam
Department of General Surgery, Sri Ramachandra Institute of Higher Education and research, Chennai, India.
Dr. Balaji SinghDepartment of General Surgery, Sri Ramachandra Institute of Higher Education and research, Chennai, India.
Dr. C. KaliyappaDepartment of General Surgery, Sri Ramachandra Institute of Higher Education and research, Chennai, India.
Dr. C. S. Subramanium
Department of General Surgery, Annamalai University, Tamil Nadu, India.
INTRODUCTION:The breast has always been a symbol of beauty, womanhood and fertility. As a result, both disease and surgery of the breast evoke fear of mutilation and loss of feminity. Cosmetic considerations and false vanity and fear of infertility have hindered early diagnosis and prompt treatment of breast cancer from times of earliest recorded history until today.
Worldwide, breast carcinoma is the most commonly diagnosed cancer and the leading cause of cancer death.(1)(2) Many early breast carcinomas are asymptomatic; pain or discomfort is not usually a symptom of breast cancer. Breast cancer is often rst detected as an abnormality on a mammogram before it is felt by the patient or healthcare provider.
Breast cancer like all other non-trophoblastic cancers are known to produce ectopic hormones (3). One among this is Human Chorionic Gonadotropin (hCG), a glycoprotein with 237 amino acids. It has two subunits α (alpha) and β (beta). Elevated β -hCG levels are most commonly associated with pregnancy. Recent studies have found elevated β -hCG levels in urinary bladder carcinoma, prostate cancers and breast cancers. The presence of β -hCG receptors in breast cancer tissues is associated with a speculative role. While some studies report the presence of β -hCG receptors is indicative of a good prognosis, (4) there are studies which counter this hypothesis.(5)
The hCG-beta subunit is encoded by a cluster of genes (chorionic
gonadotropin beta (CGB)) and contains several glycosylation sites. It consists of one LHB gene, four beta-hCG coding genes (CGB, CGB5, CGB8 and CGB7) and two gene copies with unknown function (CGB1 and CGB2).(6,7)
LH/hCG receptor expressions were reported to be higher in normal breast tissue than in breast cancer, suggesting that the effect of hCG on normal breast tissue might be more pronounced than its effect on breast cancer tissue.(8–11)
Previous reports showed that β -hCG can inuence the differentiation of mammary tissue. Moreover, how hCG regulates the balance of proliferation and differentiation is not well understood. Human chorionic gonadotropin also plays a role in cellular differentiation and/or proliferation and may activate apoptosis. (5)
The purpose of this study was to take an initiative in nding the status of beta hCG receptors and to assess its role in patients with breast carcinoma reporting to Sri Ramachandra Institute of Higher Education and Research.
Aim:To nd the difference in methylation pattern of CGB gene in breast cancer tissue and normal tissue samples.
Methodology:I n s t i t u t i o n a l e t h i c a l c l e a r a n c e w a s o b t a i n e d ( C S P -MED/16/Jan/27/29). Patients were explained regarding the study in detail and their written informed consent was obtained.
INTERNATIONAL JOURNAL OF SCIENTIFIC RESEARCH
Clinical Research
International Journal of Scientific Research 1
Volume - 9 | Issue - 7 | July - 2020 | PRINT ISSN No. 2277 - 8179 | DOI : 10.36106/ijsr
ABSTRACTBreast carcinoma is the most commonly diagnosed cancer and the leading cause of cancer death. Breast cancer produces ectopic hormones called beta Human Chorionic Gonadotropin [hCG] and is encoded by CGB genes. The aim of this study was to determine the CGB gene methylation in breast cancer. After approval from Institutional Ethical Committee, consent from patients were obtained. Normal and tumour tissues from breast cancer patients were taken. IHC for beta hCG receptors were done. Beta hCG was found to be higher amongst the normal tissues than the tumour tissues. There was a signicant relation between beta hCG and ER, Beta hCG and HER 2 neu receptors. DNA was isolated from normal and tumour tissues. Post bisulfate conversion samples were processed for qPCR using methylation specic primers and SYBR green. 1-2M was found to be signicantly higher among the normal tissues. 3-9M was found to be signicantly higher in tumour tissues. This suggests that beta hCG receptors are higher in normal tissues and the hormone itself is higher in cancer tissues. This is probably due to the lower receptor levels in cancer tissues.Summary: This study was done on patients with breast cancer, to know the beta hCG receptor status and to further know the CBG gene status of the patients with hCG positive and negative receptor status.
KEYWORDSBreast Cancer, genetics, cgb genes, methylation, beta hCG
Volume - 9 | Issue - 7 | July - 2020
2 International Journal of Scientific Research
Patients who satised the inclusion criteria were considered as a part of the study.
Inclusion criteria:Ÿ FemalesŸ Greater than 18 yearsŸ proven breast carcinoma with or without nodal metastasis (Stages
1, 2 and 3)
Exclusion criteria:Ÿ MalesŸ Pregnant or nursing mothersŸ patients with distant metastasis, stage 4Ÿ Patients with gynaecological or any other carcinomaŸ Neoadjuvant chemo or radiotherapyŸ patients who have undergone prior surgery for breast cancerŸ Patients who did not consent to take part in the study
A detailed history was collected from all the patients and a through physical examination was done. Mammography and biopsy were done to conrm the diagnosis. Patients who were enrolled in the study, all tests including metastatic work up were done. Patients underwent modied radical mastectomy on the affected side after being declared t by the anaesthetist.
A sliver of tissue was obtained from the tumour itself and a sliver of tissue was taken from the normal quadrant of the same specimen after consultation with the pathologist. These tissues were xed using neutral buffered formalin and were embedded in parafn blocks at the department of pathology.
Immunohistochemical analysis was done on each of these parafn embedded sections. Detection system used was HRP polymer. Antigen retrieval was done by heat induction in a pressure cooker. Immunohistochemistry for beta hCG was done using ab-53087 at 1:50 dilutions. This anti hCG beta antibody was obtained from rabbit and detects endogenous levels of total hCG beta protein. This is a synthetic peptide derived from human hCG beta. The positive control used was parafn embedded human breast carcinoma tissue.(12)
Picture 1: Immunohistochemical analysis of paraffin embedded human breast cancer tissue using ab53087, at 1/50 dilution.
Following this the stained specimen were assessed using a semi-quantitative score according to Remmele and Stegner, comprising optical staining intensity (graded as 0=no, 1 = weak, 2 = moderate, and 3 = strong staining) and the percentage of positively stained cells (0 = no, 1=< 10%, 2 = 11-50%, 3 = 51-80% and 4 = > 81% cells). (7,13)
According to Miriam Lenhard, et al., the tumour was scored as positive if more than 10% of cells were scored with an immunoreactive score (IRS) higher than 2. The slides were reviewed in a blinded fashion by two independent observers at two separate times with an interval of 2 weeks.(7)
Following this, 40 tissue samples were selected by the pathologist for DNA analysis. Of these, 20 samples were strong positive and 20 samples with strong negativity for beta hCG.
Selection criteria of samples:Positive samplesStrongly positive among both cancer and normal counterparts Intensity of staining should be 3 or strong staining and percentage of cells stained should be more than 90% Negative samples Strongly negative among both cancer and normal counterparts Intensity of staining should be 0 or no staining and percentage of cells stained should be 0%
Breast tumour and normal tissue (25 mg) were grinded in liquid
nitrogen with motor and pestle, and the powdered tissue was treated with tissue lysis buffer and proteinase-K. The mixture was incubated at 56°C for 3 hours and another lysis buffer was added for complete lyses of cells. DNA was precipitated using 100% ethanol and sample was passed through a spin column which was washed with buffer and then eluted in 200 µL of elution buffer. The sample was stored at -20 °C till further processing.(14)
For bisulfate conversion 20µL of DNA samples was mixed with respective amount of bisulfate mix, DNA protect buffer and RNase free water and was placed in thermocycler programmed as per manufacturer protocol. The reaction mixture was then transferred to another vial, to which 560 µL freshly prepared BL buffer containing carrier RNA was added and later was passed through spin column. The column was then treated with BD buffer and washed with buffer following which the sample was eluted using 20 µL of elusion buffer and stored at -20°C.(15)
After bisulfate conversion the samples were processed for qPCR using methylation specic primers and SYBR green with set of primers for 1-2 CGB and 3-9 CGB genes which were obtained from a previous study (16)(17)(18).
Picture 2: Sequence of primers obtained from previous article.
Picture 3: Gel electrophoresis
Real time PCR was performed on Rotor – gene 10 µL reaction mixture. A methylated DNA sample obtained from the manufacturer was used as a control for calculating the delta Ct values.
Statistical analysisStatistical analysis was performed using SPSS 18.0 (PASW Statistic, SPSS Inc., IBM, Chicago, IL). Correlation analysis of the receptor expression was performed for the histological subtype, tumor stage, grading and clinical data using the non-parametric Kruskal-Wallis rank-sum test and the non-parametric Spearman correlation coefcient. For the comparison of survival times, Kaplan-Meier curves were drawn. The chi-square statistic of the log-rank test was calculated to test differences between survival curves for signicance. P values below 0.05 were considered statistically signicant.
RESULTS:This study was conducted among 254 patients. All of these patients were females who were proved to be positive for breast cancer and were taken up for Modied Radical Mastectomy before giving neoadjuvant chemotherapy or radiation.
IHC result analysis:All patients were between 18 and 80 years of age. 53.9% of the patients were between 41 and 60 years. 18.5% of patients were <40 years and 27.6% of patients were more than 60 years of age. 59% of the patients were post-menopausal. 2% of the patients had bilateral tumour, 50% of patients had left sided tumour and the rest had right sided tumour. 38.6% of patients had tumour in the upper outer quadrant,28.7% of patients had central quadrant tumours, 16.5% of patients had upper inner quadrant tumours, 16% of patients had lower inner and lower outer quadrant tumours. 58.7% patients had tumour stage 2 (T2), 19% and 17% patients had T1 and T3 stage tumours respectively and 5% patients had T4 stage tumour. 45.3% patients had no nodal involvement.25% and 21% patients belonged to N1 and N2 stages respectively. The rest belonged to N3 stage. A vast majority of 48% patients belonged to TNM stage 2, 16% and 36% patients belonged to stage 1 and stage 3 respectively. 55% patients showed ER positivity, 57.5% patients showed PR negativity and 72.4% patients showed HER 2 neu negativity.
PRINT ISSN No. 2277 - 8179 | DOI : 10.36106/ijsr
International Journal of Scientific Research 3
Beta hCG was found to be positive 83% of normal tissues and 49% in cancer tissues. On comparing beta hCG receptor status with TNM staging of tumours, there was a signicant relation with p value of 0.018, suggesting a beta hCG positivity when T stage increases. On comparing the ER, PR and HER 2 neu status with beta hCG receptor status, there was again a signicant relation between ER and beta hCG with a p value of 0.022. there was yet another signicant relation between HER 2 neu and beta hCG, the p value was 0.000.
Molecular analysis:Fold change was calculated with the Ct values obtained from RT-PCR.The mean fold change amongst the study population was 15.09. Highest value being 253.7649 and the lowest recorded was 0.0009.
Fold change among tumour and normal: The p value for this was calculated to be 0.007 using the Mann-Whitney test. Hence the Fold change values were signicantly higher amongst the tumour tissues than the normal tissues.
Table 1: Fold change among tumour and normal
IHC results in relation to fold change: Fold change among Beta hCG positive patients was 8.560 and among Beta hCG negative patients was 27.64. the p value for this was <0.01, and this is signicant. Hence if IHC for beta hCG is positive, the 2^(DD-Ct) values were lower and vice-versa.
Table 2: Beta hCG and Fold change
Fold change among methylated and unmethylated regions:The fold change in methylated regions were signicantly higher than the unmethylated counterparts. The p value was 0.000 (<0.05).
Table 3: Fold change among methylated and unmethylated regions
Fold change between tumour tissues and normal tissues for CGB1-2 and CGB3-9:CGB 1-2M was found to have signicantly higher fold change among the normal tissues (30.22). p value was 0.017 which is less than 0.05.
The fold change of CGB 3-9M was 61.93 in tumour tissues and 3.77 in normal tissues. The difference between this was signicant as the p value was 0.00 (<0.05). this suggests that 3-9 M is signicantly higher in tumour tissues compared to normal tissues.There was no signicant difference between the unmethylated primers.
Table 4: Fold change between tumour tissues and normal tissues for CGB1-2 and CGB3-9
DISCUSSION:Invasive breast carcinoma is one of the common malignancies affecting women worldwide and in India. Breast cancer is one of the most common malignancies in females that presents with varied behaviours and different response to treatment.(2) The involvement of lymph nodes, distant metastasis, primary tumour size, tumour grade, hormone receptor status and lympho-vascular invasion determine poor prognosis on initial diagnosis.
Demographic results:There were 254 patients in this study. All of them were females with proven breast cancer.
The mean age of patients in this study was 53 years and about 54% of the patients were between 41 to 60 years of age. It is proven that incidence of breast cancer increases with age to reach a peak of 421.3 cases per 100,000 at 70 to 80 years of age. It is suggested that 95% of new cases occur in women older than 40 years.(19) This was consistent with our study.
A majority of the study subjects were post-menopausal, constituting for about 60%. The other 40% belonged to pre or peri-menopausal group. A study by Chung-Cheng Hsieh, in 1990 suggested that the prevalence of breast cancer is high among peri-menopausal women, who are in their 60's.(20,21)
In our study, 7% of the patients had a positive family history for breast cancer. Breast cancer in the rst-degree relatives increases the risk among patients by 2 to 3 times.(9)
There was no difference between tumour favouring a particular side. 50% of the tumours were left sided, 48% of the tumours were right sided and 2% of the patients had bilateral tumours.
Upper outer quadrant had the majority of tumours, 39%, followed by 29% in the central quadrant. Tumours are most commonly found in the upper outer quadrant because of a higher breast tissue content in that area. (22)
In regards to TNM staging, T2 had maximum patients (59%), N0 had 45% of the patients and all patients belonged to M0. This indicates stage 2 to have a majority of patients (48%). In 2002, Lebeau, suggested that maximum patients belonged to stage 2 and stage 3 among developing countries and maximum patients belonged to stage 1 in among the developed countries.(23)
Nottingham's grade 2 had majority 62% of patients followed by grade 1 with 20% of patients and grade 3 with 18% of patients. In 2008, Rakha, et al, have suggested the signicance of histological grading in breast cancer. It is both of diagnostic and prognostic value. Lower the grade, better the prognosis.(24) According to a study conducted by Signe Borgquist, in 2015, grade 3 had the maximum number of patients (52%), which is controversial to our study.(25)
In our study, there were 55% patients with ER positivity, 42% with PR positivity and 72% with HER 2 neu negativity. This suggests that luminal type A had a majority of 43% of patients. In 2015, Ajith Vettuparambil, et al, suggested that ER and PR positivity was approximately 56% and 60% respectively. (26) Similarly Eundeok Chang, et al in 2005 stated that patients with ER and PR positivity and HER 2 neu negativity were high (56%, 63% and 60% respectively).(8)Immunohistochemistry for beta hCG in normal tissues showed maximum positivity (83%), whereas in cancer cells the beta hCG showed 51% negativity. A study by Eundeok Chang, et al, in 2005 showed that hCG expression in cancer cells showed a 86% negativity.(8) another study by NJ, Agnantis, et al, in 2005, showed that 55.5% of cancer cells were strongly positive for beta hCG. (27)
Comparative analysis with obtained IHC results:About 60 patients who were premenopausal showed beta hCG negativity and 81 patients who were postmenopausal showed beta hCG positivity. Comparative analysis between beta hCG and menopausal status of the patients showed no signicance as the p value was 0.067 (>0.05)
There were 33 patients in stage T1 who were negative for beta hCG, 68 patients in stage T2 showing beta hCG negativity, 24 patients in stage
Volume - 9 | Issue - 7 | July - 2020 PRINT ISSN No. 2277 - 8179 | DOI : 10.36106/ijsr
TYPE Fold change Std. Deviation Std. Error Mean P Value
N 11.1565 21.05682 2.35422 0.007*(<0.05)T 25.0454 38.13463 4.26358
Fold change among tumour and normal (Table 1)
BETA hCG IHC
Fold change
Std. Deviation Std. Error Mean
p value
POSITIVE 8.5600 14.10692 1.57720 0.000***(<0.001)NEGATIVE 27.6419 40.14902 4.48880
Beta hCG and Fold change (Table 2)
Primers Fold change Std. deviation Std. error Mean p Value
1-2 M 23.5187 26.79847 4.23721 0.000***(<0.001)1-2 UM 8.1303 21.15731 3.34526
3-9 M 32.8563 46.43433 7.34191
3-9 UM 7.8984 16.05362 2.53830
Fold change among methylated and unmethylated regions (Table 3)
Mean Std. Deviation Std. Error Mean p Value
1-2 M T 16.8077 14.50535 3.24350 0.017*(<0.05)N 30.2298 34.18905 7.64490
1-2 UM T 9.1363 28.53280 6.38013 0.110
N 7.1244 10.12779 2.26464
3-9 M T 61.9337 51.14170 11.43563 0.000***(<0.001)N 3.7789 5.50605 1.23119
3-9 UM T 12.3041 21.57589 4.82452 0.152
N 3.4928 4.75607 1.06349
Fold change between tumour tissues and normal tissues for CGB1-2 and CGB3-9 (Table 4)
T3 and 4 patients in stage T4 who were negative for beta hCG receptors. On comparing T staging with beta hCG receptor status, the p value 0.018 thus indicating a signicance. Among patients who were beta hCG positive there were 55 patients in N0 stage, 34 patients in N1 stage, 30 patients in N2 stage and 6 patients in N3 stage. Beta hCG positivity is reducing with increase in nodal staging, but this comparison was not signicant as the p value was 0.075 (>0.05). A study by Miriam Lenhard, et al in 2012, suggested that there was no signicant correlation between beta hCG expression and tumour or nodal staging or grading. (7)
On comparing nottingham's histological grading with beta hCG receptor status, there were 18 patients with grade 1 tumours, 82 patients with grade 2 tumours and 25 patients with grade 3 tumours who were also beta hCG positive. But there was no signicance, as the p value was 0.345 (>0.05) In 2008, Rakha, et al, have suggested the signicance of histological grading in breast cancer. It is both of diagnostic and prognostic value.(24) Eundeok Chang, et al in 2005, suggested a signicant relation between histological types of tumour and beta hCG receptor status.(8) A study by Miriam Lenhard, et al in 2012, suggested that there was a signicant association between tissue expression of beta hCG and tumour grade (p = 0.022).(7)
On comparing beta hCG receptor status and estrogen receptor status: 78 patients or 31% of patients were positive for both receptors and 67 patients or 26% of patients were negative for both receptors. The p-value was 0.022 (<0.05). this suggests that if ER is positive beta hCG also shows positivity and vice- versa. Similarly, between progesterone receptors and beta hCG receptor status, there was no signicance and the p value was 0.829 (>0.05). yet again, the comparison between her2neu receptors and beta hCG receptor status was signicant. 23 patients were positive for both receptors and 78 patients were negative for both receptors. The p-value was 0.000 (<0.05). this again suggests that if HER2neu was positive for a patient, beta hCG was negative and vice-versa. According to Reimer, et al in 2000, there was a signicant correlation between beta hCG receptor status and progesterone receptor status. He stated that “progestins regulate the expression of hCG in breast epithelial cells”. (28) Another study by Eundeok Chang, et al in 2005, suggested no correlation between estrogen receptor status or progesterone receptor status or HER 2 neu receptor status.(8)There is also a signicant comparison between luminal types and beta hCG receptor status suggesting a higher beta hCG positivity among luminal types A and B, and higher beta hCG negativity among triple negative and HER 2 neu types. The p value for this was 0.000 (<0.05). A study by Miriam Lenhard, et al in 2012, suggested a signicant correlation between beta hCG and lutenising hormone receptor in ovarian cancer. (7)
Molecular analysis:The difference in methylation levels of CGB genes between the mean of tumour and normal tissues were signicant with a p Value of 0.007 (<0.05). The mean amongst tumour tissue was 25.04 and normal tissue was 21.05, suggesting a higher expression in tumour tissues. This was supported by Śliwa Aleksandra, et al, in 2019, who also stated that expressions of beta hCG is higher among tumour tissues compared to normal tissues, although the study was done in ovarian tissue. (18) Yet another breast cancer study done by Xing-hua Liao, et al in 2014, also suggests that the beta hCG expressions were higher in tumour tissues compared to normal tissues.(5).
The immunohistochemical results were signicantly associated with the expression of beta hCG through RT-PCR (p value = 0.000 which is less than 0.05). this suggests that if beta hCG receptors were positive the expression of beta hCG was low and vice-versa. The higher expression of beta hCG could be compensating the receptor negative status as suggested in a 2010 article by R K Iles, et al.(29) A 2012 article by Miriam Lenhard, suggests that the discrepancy in literature with respect to beta hCG can be explained by the variations in the hCG hormone and the hormone receptor levels.(7)
On comparing the methylated and unmethylated counterparts, the methylated components showed a higher expression of beta hCG. This was signicant with a p value of 0.00 (<0.05). According to Śliwa Aleksandra, et al in 2019 there was only a slight difference between beta hCG expression among the methylated and unmethylated.(18)
In our study, the expression of CGB 1-2 M was found to be higher in normal tissues and the expression of CGB 3-9 M was found to be
higher among tumour tissues. This was statistically signicant with a p value of 0.017 and 0.00 respectively. Both of these are consistent with a study by Śliwa Aleksandra, et al in 2019. The study states that the expression of CGB1 and CGB2 was higher among normal ovarian tissue and CGB3 to CGB9 were higher among ovarian cancer tissues. (18) R K Iles, et al in 2010 have suggested an increase in CGB 5 expression among the cancer tissues. (29)
Kristiina Rull, et al in 2012 and 2013 have suggested that there is an increased expression of CGB 5 and CGB 8 in cancer cells and any mutations in these major CGB genes were tolerated better. They also suggested in 2013 that CGB 5 with no mutations may protect against recurrent miscarriages. They have also suggested that these genes may act differently across various ethnic groups. (30,31) Liis Uusküla, et al in 2011 suggested that mutations in CGB 5 might lead to pregnancy loss and CGB 8 may be under expressed in mothers with recurrent pregnancy loss.(6) Xing-hua Liao, et al in 2014 suggested that beta hCG is responsible for pregnancy induced protection against breast cancer and beta hCG also helps in reducing the proliferation of MCF-7 cells by downregulating certain antigens. They have also suggested that beta hCG when upregulated helps in cellular differentiation.(5)
CONCLUSION:A 2012 article by Miriam Lenhard, suggests that the discrepancy in literature with respect to beta hCG can be explained by the variations in the hCG hormone and the hormone receptor levels.(7)
Our study suggests that presence of hCG receptors in cancer tissues is lower when compared to normal tissues. 3-9 M is signicantly higher in tumour tissues compared to normal tissues and 1-2 M is signicantly higher in normal tissues. This suggests that hCG may be elevated in breast cancer because of an upregulation in CGB 3-9 genes, and this is probably because there is a decrease in hCG receptors in cancer tissues.Therefore, future studies can be based on hormone levels and receptor levels separately to validate the same.
Funding: This article is a part of the PhD thesis, funded by Indian Council of medical Research, Talent Search Scheme 2015, India.
Acknowledgements:We would like to take this opportunity to thank ICMR (Indian Council of Medical Research) for the funding of this project and our institution SRI HER (Sri Ramachandra Institute of Higher Education and Research) for allowing us to conduct this study inside the campus premises.
Conflict of Interest: None.
This study was conducted on human breast tissue from patients undergoing surgery for breast cancer. Written informed consent from each patient was obtained prior to initiation of the project. Consent for images and other clinical information was also obtained. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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2. Mannan AU, Singh J, Lakshmikeshava R, Thota N, Singh S, Sowmya TS, et al. Detection of high frequency of mutations in a breast and / or ovarian cancer cohort�: implications of embracing a multi-gene panel in molecular diagnosis in India. J Hum Genet. Nature Publishing Group; 2016;61(October 2015):515–22.
3. Vasudevan A, Iyyappan P, Kaliyappa C, Singh KB. Clinico-pathological presentation of breast carcinoma and its correlation with β hCG. JETO. 2019;13(2):139–46.
4. Schüler-toprak S, Treeck O, Ortmann O. Human Chorionic Gonadotropin and Breast Cancer. Int J Mol Sci. 2017;18(1587):1–13.
5. Liao X, Wang Y, Wang N, Yan T, Xing W, Zhao D, et al. Human Chorionic Gonadotropin Decreases Human Breast Cancer Cell Proliferation and Promotes Differentiation. IUBMB Life. 2014;66(5):352–60.
6. Uusküla L, Rull K, Nagirnaja L, Laan M. Methylation Allelic Polymorphism ( MAP ) in Chorionic Gonadotropin β5 ( CGB5 ) and Its Association with Pregnancy Success. J Clin Endocrinol Metab. 2011;96(1):199–207.
7. Lenhard M, Tsvilina A, Schumacher L, Kupka M, Ditsch N, Mayr D, et al. Human chorionic gonadotropin and its relation to grade , stage and patient survival in ovarian cancer. BMC Cancer. 2012;12(2):1–8.
8. Chang E, Lee E, Oh SJ, Kim JS. T he Im m unoexpressions and Prognostic Signicance of Inhibin A lpha and Beta H um an C horionic G onadotrophins ( hC G ) in Breast C arcinom as. Cancer Res Treat. 2005;37(4):241–6.
9. Bernstein L, Sullivan-halley J, Ross K. Treatment with Human Chorionic Gonadotropin Risk of Breast cancer. Cancer Epidemiol Biomarkers Prev. 1995;4:437–41.
10. Hoon DSB, Sarantou T, Doll F, Chi DDJ, Kuo C, Peter AJCONRAD, et al. DETECTION OF METASTATIC BREAST CANCER BY P-hCG POLYMERASE. Int J Cancer (Pred Oncol). 1996;69:369–74.
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11. Lopez D, Sekharam M, Coppola D, Carter WB, Wallace E, Breast C, et al. Puried human chorionic gonadotropin induces apoptosis in breast cancer. Mol Cancer Ther. 2008;7(9):2837–45.
12. Vasudevan A, Iyyappan P, Kaliyappa C, Singh KB. Clinico-pathological presentation of breast carcinoma and its correlation with β hCG. J Exp Ther Oncol. 2019;13(8):139–46.
13. W R, Stegner HE. Recommendation for uniform denition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe. 1987;8(3):138–40.
14. Ip SC, Lin SW, Lai KM. An evaluation of the performance of ve extraction methods�: Chelex ® 100 , QIAamp ® DNA Blood Mini Kit , Investigator ® Kit and DNA IQ TM . Sci Justice. 2015;55(3):25934373.
15. Holmes EE, Jung M, Meller S, Leisse A, Sailer V, Zech J, et al. Performance Evaluation of Kits for Bisulte-Conversion of DNA from Tissues , Cell Lines , FFPE Tissues , Aspirates , Lavages , Effusions , Plasma , Serum , and Urine. PLoS One. 2014;9(4):e93933.
16. Huang G, Zhang X, Guo G, Huang K. Clinical signicance of miR-21 expression in breast cancer�: of invasive ductal carcinoma. Oncol Rep. 2009;21:673–9.
17. Aleksandra G, Kubiczak MJ, Walkowiak GP, Nowak-Markwitz E, Jankowska A. Methylation status of human chorionic gonadotropin beta subunit promoter and TFAP2A expression as factors regulating CGB gene expression in placenta. Fertil Steril. 2014;102(4):1175–82.
18. Aleksandra Ś, Kubiczak M, Szczerba A, Walkowiak G, Nowak-markwitz E, Burczy B, et al. Regulation of human chorionic gonadotropin beta subunit expression in ovarian cancer. BMC Cancer. 2019;19(746):1–9.
19. Susan P Helmrich, SHAPIRO S, LYNN. Risk factors for breast cancer cancer. Am J Epidemiol. 1983;117(1):35–45.
20. Hsieh C, Trichopoulos D, Katsouyanni K, Yuasa S. Age at menarche , age at menopause , height and obesity as risk factors cancer� : associations and interactions in an international case-control study. Int J cancer. 1990;46(5):796–800.
21. Million Women Study Collaborators. Breast cancer and hormone- replacement therapy in the Million Women Study. Lancet. 2003;362(9382):419–27.
22. Zucca-matthes G, Urban C, Vallejo A. Anatomy of the nipple and breast ducts. Gland Surg. 2016;5(1):32–6.
23. Lebeau A. Prognostische Faktoren beim duktalen Carcinoma in situ. Pathologe. 2006;27:326–36.
24. Rakha EA, El-Sayed ME, Lee AH, Elston CW, Grainge MJ, Hodi Z, et al. Prognostic signicance of histologic grade in carcinoma invasive carcinoma. J Clin Oncol. 2008;26(19):3153–8.
25. Borgquist S, Zhou W, Jirström K, Amini R, Sollie T, Sørlie T, et al. The prognostic role of HER2 expression in ductal breast carcinoma in situ ( DCIS ); a population-based cohort study. BMC Cancer [Internet]. BMC Cancer; 2015;15(468):1–10. Available from: http://dx.doi.org/10.1186/s12885-015-1479-3
26. Vettuparambil A, Chirukandath R, Culas TB, Vijayan SM. Hormone-receptor expression and survival patterns in operated cases of female invasive ductal breast carcinoma in Kerala�: a retrospective cohort study. World J Surg Oncol. Open Access; 2015;13(160):1–6.
27. NJ A, F P, L K, S F. Immunohistochemical expression of subunit beta HCG in breast cancer. Eur J Gynaecol Oncol. 1992;13(6):461–6.
28. Reimer T, Koczan D, Müller H, Friese K, Krause A, Thiesen HJ, et al. Human chorionic gonadotrophin- transcripts correlate with progesterone receptor values in breast carcinomas. J Mol Endocrinol. 2000;24:33–41.
29. Iles RK, Delves PJ, Butler SA. Does hCG or hCG play a role in cancer cell biology�? Mol Cell Endocrinol Elsevier. 2010;329(1–2):62.
30. Rull K, Jonas KC, Nagirnaja L, Peltoketo H, Christiansen OB, Kairys V, et al. Structural and functional analysis of rare missense mutations in human chorionic gonadotrophin b -subunit. Mol Hum Reprod. 2012;18(8):379–90.
31. Rull K, Ph D, Christiansen B, Ph D, Nagirnaja L, Sc M. A modest but signi cant effect of CGB5 gene promoter polymorphisms in modulating the risk of recurrent miscarriage. Fertil Steril. 2013;99(7).
International Journal of Scientific Research 5
Volume - 9 | Issue - 7 | July - 2020 PRINT ISSN No. 2277 - 8179 | DOI : 10.36106/ijsr
INTRODUCTION:Appendicitis – acute inammation of vermiform appendix is
the most common cause of intra-abdominal infection both in
developed and developing countries and appendicectomy in
the most common emergency surgical operation. Lifetime risk
for appendicitis for full population is 6%, so early diagnosis
and treatment is important [1,2] The clinical picture may not
be classical and the policy of early operation in such cases
may lead to large number of normal appendix being removed. [3]
Early stage of appendicitis symptoms overlaps with other
emergency conditions which makes the diagnosis challenge
[4]. Failure of an early diagnosis could lead to the risk of
perforation and peritonitis with its consequent increase in the
morbidity and mortality [5] In 1986, MANTRELS scoring was
constructed by Alvarado for clinical diagnosis of appendicitis
with score of 10 [6]. Latter it was modied as modied
Alvarado with 9 score excluding the shift to left of neutrophil.
Some studies combined USG with Alvarado scoring to make
more accurate diagnosis [7]. In our study we included USG
nding also in the MASS to make Ultra sound combined
modied Alvarado scoring System with a score of 10 for
making the diagnosis more accurate.
AIM AND OBJECTIVES:To analyze the efcacy of Ultra sound combined modied
Alvarado scoring system [UcMASS] in diagnosis of acute
appendicitis by comparing the histopathological examination
of appendicectomy specimens.
MATERIALS AND METHODS:This study was conducted on 120 patients who came to Sri
Ramachandra Hospital and Research Institute with
complaints of pain in right lower abdomen with clinical
suspicious of appendicitis . study done for three years period.
Appendicitis with generalized peritonitis, Appendectomy
combined with any other abdominal procedures, Appendicitis
in pregnancy, Appendicular mass and Patients below the age
of 15 years were excluded from study.
All patients included in our study were admitted in our hospital
with clinical diagnosis of Appendicitis. The decision for
surgery was primarily done by concern surgical team based
on clinical nding and investigation not based on UcMASS.
We have done USG abdomen for all patients included in our
study.Scoring was done by principle investigator for each
patient simultaneously. The data were collected and coded in
software analysis using SPSS statistical software version 11.5.
The both groups were cross tabled against gold standard
conrmatory histopathology reports. The sensitivity,
specicity, positive predictive value and negative predictive
value were calculated.
OBSERVATION AND RESULTS:Table 1: age distribution, sex distribution and score in
UcMASS
VALIDATION OF ULTRASOUND COMBINED MODIFIED ALVARADO SCORING SYSTEM IN ACUTE APPENDICITIS PATIENTS
Original Research Paper
Supreeth kumar reddy Kunnuru
Senior resident General surgery department, Sri Ramachandra medical university,
Surgery
Objectives: Acute appendicitis, though one of the common emergencies in surgical practice, at times can confuse the best clinicians. There are lot of scoring system used to diagnose the appendicitis. We
used Combination of USG abdomen with Modied Alvarado scoring system to make UcMASS and was compared with Histopathology reports to identify the sensitivity and specicity. Totally 120 patients with clinically Material and methods:suspected appendicitis patients were included in our study. Although decision making was not done based on Uc MASS , study was conducted and data were collected simultaneously .Comparison was done with conrmatory histopathology reports and cross table was made with two groups of UcMASS(group 1 score seven and above, group 2 score <7). Sensitivity specicity, PPV and NPV were collected. Maximum number of patient included in our study belongs to 21- 30 yrs of age group Results:(53.3%). Out of 120 patients in the study 90(75%) patients were male and 30(25%) were female (with M: F ratio of 4:1). Out of 120 patients 96 (80%)patients score was above 7 in which histopathological report was positive for 83(69%) patients and rest of 13 (10.8%) only histopathology negative patients. Out of 120 patients 24(20%) patients score was below 7 in which histopathological report was negative for 23(19.1%) patients. This is Statistically signicant with p value < .001 = 99.9% signicant. Sensitivity of the Uc MASS in appendicitis is 98.8% And Specicity is 63.8 %. . Its Positive Predictive Value is 86.4% Negative Predictive Value is 95.8% In this study,the diagnostic score may be used as a guide to evaluate the Conclusion:patients need for surgery or observation. so we conclude that UcMASS can be used routinely to diagnose the acute appendicitis and decision making can be done on score basis.
ABSTRACT
KEYWORDS : Modied Alvarado scoring system, appendicitis, appendicectomy, scoring system, ultrasound
combined Alvarado
Selvapriya Bharathi
Assistant professor General surgery department, Sri Ramachandra medical university,
Manuneethimaran Thiyagarajan*
Associate professor of surgery General surgery department, Sri Ramachandra medical university, *Corresponding Author
Balaji Singh K Professor of surgery and HOD General surgery department, Sri Ramachandra medical university,
Arulappan.TProfessor of surgery General surgery department, Sri Ramachandra medical university,
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VOLUME - 9, ISSUE - 7, JULY - 2020 • PRINT ISSN No. 2277 - 8160 • DOI : 10.36106/gjra
A total 120 patient enrolled in our study. In Table 1, Maximum number of patient included in our study belongs to 21- 30 yrs of age group (53.3%). Out of 120 patients in the study 90(75%) patients were male and 30(25%) were female (with M: F ratio of 4:1)
‘UcMASS more than seven was 96 patients (80%) and less than seven was 24 patients (20%). Laparoscopy surgery was done in 100(83.3%)patients and open surgery was done in 20(16.7%) patients
TABLE 2: Intra operative ndings with position of appendix
Table 2 shows the intraoperative nding of appendicectomy patients. Commonest intraoperative nding is inamed appendix (81.7%) and perforated appendix was 8.3%. According to the position of appendix ,98(81.7%) patients had retrocaecal appendix, 14(11.6%) patients had pelvic appendix, 4(3.3%) patients had Preileal appendix, 2(1.7%) patients had paracolic appendix
TABLE 3: UcMASS VS Histopathology report cross table:
In table 3, out of 120 patients, histopathology positive rate is 84 patients (70%) and remaining 36 patients (30%) have normal appendix. so negative appendicectomy rate is 30%. Out of 120 patients 96 (80%)patients score was above 7 in which histopathological report was positive for 83(69%) patients and rest of 13 (10.8%) only histopathology negative patients. Out of 120 patients 24(20%) patients score was below 7 in which histopathological report was negative for 23(19.1%) patients. This is Statistically signicant with p value < .001 = 99.9% signicant.
From this cross table, Sensitivity of the UcMASS in appendicitis is 98.8% And Specicity is 63.8 %. . Its Positive Predictive Value is 86.4% Negative Predictive Value is 95.8%.
The histopathological examination ndings observed in this study includes :Acute appendicitis (35%), Acute appendicitis with periappendicitis (25%), Eosinophilic appendicitis(10%), Reactive lymphoid hyperplasia (12%), Chronic lymphoid hyperplasia (11%) and Sclerosed appendix(7%). Among these Acute appendicitis, Acute appendicitis with periappendicitis, and Eosinophilic appendicitis were taken as positive and remaining as negative.
DISCUSSION:The present study is done to evaluate the validation of Ultra sound combined modied Alvarado scoring system in acute appendicitis versus histopathological examination reports in our institute. UcMASS is inclusion of ultrasound nding and exclusion of shift to left in modied Alvarado scoring system. If USG shows features of appendicitis one score included.
Results of our study shows that acute appendicitis is most common in the age group 21 to 30 years (53.3%). Next common group is 31 to 40 years (18.3%). Epidemiological studies have shown that appendicitis is more common in the 10 to 29 years of age group [8]
Our study reveals that acute appendicitis is more common in males 74 (61.7%). Lone et al [9] has shown in their study that appendicitis was common in male gender. Retrocaecal position of appendix is most common presentation in our study 49(81.7%). Different literatures also support this observation [10]
Comparison shows the sensitivity of our study is high as 98.8%. Other studies only used modied Alvarado scoring system , Al-hashemyetal 53.9% [11], Kalen et al 81.63%[12], Shrivastava uk et al 92.4%[13], Fengo et al 90.2%[14] sensitivity only. Since we included USG in scoring system the sensitivity is higher than other studies .Specicity of our study is 63.8 % and it has been compared with other studies like Mohd. Saleem and Ahmed M 80%[15], Khuram Siddique 78%[16].The overall negative appendicectomy rate is high in our study ( 30% )although it is comparable with Emmanuel S Kanumba et all -33.1% [17].
In our study UcMASS is having high sensitivity with high positive predictive value. So ultrasound combined modied
Age n=120 Number percentage
<20 yrs. 18 15%
21-30 yrs. 64 53.3%
31-40 yrs. 22 18.3%
41-50 yrs. 10 8.3%
>50 yrs. 6 5%
Sex n=120
Male 90 75%
Female 30 25%
Type of
surgery
n=120
laparoscopy 100 83.3%
Open 20 16.7%
UC MAS
Score
7&above
96 80%
Score<7 24 20%
Intra operative
findings
number Percentage
Inflamed 98 81.7%
Perforated 10 8.3%
Gangrenous 4 3.3%
Fecolith 5 4.1%
Fibrosis 3 2.5%
position of
appendix
Retrocaecal 98 81.7%
Pelvic 14 11.6%
Preileal 4 3.3%
paracolic 2 1.7%
HPE Total
POSITIVE
NEGATIVE
UcMASS > 7 Count
% of Total
83
69%
13
10.8%
96
80.0%
< 7 Count
% of Total
1
0.8%
23
19.1%
24
20.0%
Total Count
% of Total
84
70.0%
36
30%
120
100.0%
X 35GJRA - GLOBAL JOURNAL FOR RESEARCH ANALYSIS
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Alvarado score can be used as a routine scoring system for diagnosing acute appendicitis and decision making for surgery can be done based on this scoring system.
CONCLUSION:Although modied Alvarado scoring system used widely to diagnose the acute appendicectomy, by including USG abdomen in the scoring system the diagnostic accuracy can be improved. In our study by comparing gold standard HPE with UcMASS, the sensitivity and positive predictive value were found high. Score 7 and above indicate conrmatory appendicitis diagnosis and can proceed with surgery .so we conclude that UcMASS can be used routinely to diagnose the acute appendicitis and decision making can be done on score basis .
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17. Emmanuel S etal.modied Alvarado scoring system as a diagnostic tool for acute appendicitis ar bugando medical centre, Mwanza,Tanzania.BMC surgery.2011;11:4 doi:10.1186/1471-2482-11-4 [pub med]
36 X GJRA - GLOBAL JOURNAL FOR RESEARCH ANALYSIS
VOLUME - 9, ISSUE - 7, JULY - 2020 • PRINT ISSN No. 2277 - 8160 • DOI : 10.36106/gjra
Received 04/27/2020 Review began 04/29/2020 Review ended 05/02/2020 Published 05/09/2020
© Copyright 2020Karthikeyan et al. This is an openaccess article distributed under theterms of the Creative CommonsAttribution License CC-BY 4.0., whichpermits unrestricted use, distribution,and reproduction in any medium,provided the original author andsource are credited.
Lost Denture Found in Esophagus After aDecade: A Rare Case ReportRaveena Karthikeyan , Chandramohan S M , Sakthivel Harikrishnan , Vigneshwaran VB ,Balaji Singh
1. Suregry, Madras Medical College, Chennai, IND 2. Surgery, Sri Ramachandra Institute of HigherEducation and Research, Chennai, IND 3. Surgery, Esoindia - Centre for Gastro Esophageal Disorders,Chennai, IND 4. Surgical Gastroenterology and Liver Transplant, Government Stanley Medical College,Chennai, IND 5. Surgery, Madras Medical College, Chennai, IND 6. General Surgery, Sri RamachandraInstitute of Higher Education and Research, Chennai, IND
Corresponding author: Chandramohan S M, smchandra@yahoo.com
AbstractDentures are accidentally ingested foreign bodies, especially in the geriatric population. Theyget frequently lodged in the esophagus because of their larger size, rigidity, and pointed edges.But, it is unusual for a denture to remain asymptomatic in the esophagus for a decade. Wereport a case of 45-year-old female who presented with the complaints of progressivedysphagia for six months. Endoscopy revealed an impacted denture in the mid-esophagus. Thepatient recollected that she lost her denture 13 years back and was unaware that she swallowedit. Right thoracotomy and esophagotomy were done to remove the impacted denture. Theesophagotomy site was buttressed with vascularised intercostal muscle flap.
Categories: Cardiac/Thoracic/Vascular Surgery, Gastroenterology, General SurgeryKeywords: esophageal foreign body, denture, thoracotomy, intercostal muscle flap
IntroductionAccidental ingestion of foreign bodies is commonly seen in the extremes of age group (childrenand elderly). Dentures, meat boluses, and fish bones are the most commonly ingested foreignbodies in the elderly population [1]. Once a foreign body has passed beyond the cricopharynx, itfrequently gets lodged in the esophagus because it has weak peristalsis and multiple anatomicalnarrowings [1,2]. Longstanding impaction might lead to mucosal ulceration, perforation,sepsis, and death [2]. This article reports an interesting case of the impacted denture in theesophagus of a 45-year-old female for more than a decade. This case is unique because of theduration for which the denture remained asymptomatic in the esophagus and for its successfulsurgical management.
Case PresentationA 45-year-old female presented with complaints of progressive dysphagia for six months.Outside endoscopy showed a friable and fixed lesion in the esophagus suspicious of malignantgrowth and biopsy was taken. She was referred to us after the biopsy came out to benegative. We did a repeat endoscopy that revealed an impacted denture in the mid-esophagus.On eliciting the history, the patient recollected that she lost her denture 13 years back and wasunaware that she swallowed it. On examination, the patient was hemodynamically stable. X-rayand CT scan revealed a crescent-shaped hyperdense foreign body in the esophagus at the levelof aortic arch T4 (Figure 1).
1 2, 3 4 5
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Open Access CaseReport DOI: 10.7759/cureus.8042
How to cite this articleKarthikeyan R, S M C, Harikrishnan S, et al. (May 09, 2020) Lost Denture Found in Esophagus After aDecade: A Rare Case Report. Cureus 12(5): e8042. DOI 10.7759/cureus.8042
FIGURE 1: CT scan showing crescent-shaped foreign body inthe esophagus
Under general anesthesia, the patient was positioned in left lateral side and thoracotomy wasmade in the right fifth intercostal space. The impacted denture was identified and removed byesophagotomy (Figures 2-3).
FIGURE 2: Removal of denture through the esophagotomy site(arrow)
2020 Karthikeyan et al. Cureus 12(5): e8042. DOI 10.7759/cureus.8042 2 of 5
FIGURE 3: Intra-operative picture showing removed denture
The esophagotomy site was closed with interrupted 3-0 polydioxanone (PDS) sutures andreinforced with viable pedicled muscle flap from right fifth intercostal space (Figure 4).
FIGURE 4: Esophagotomy site is reinforced with intercostalmuscle flap (arrow)
The patient had an uneventful postoperative recovery. Oral intake was started on postoperativeday three and the patient was discharged on postoperative day seven.
2020 Karthikeyan et al. Cureus 12(5): e8042. DOI 10.7759/cureus.8042 3 of 5
DiscussionAccidental ingestion of a foreign body is common in both children and adults. In adults, it ismostly observed in the elderly population and psychiatric individuals [3,4]. In children, coinsand button batteries are the commonly ingested foreign bodies, whereas, in adults, dentures aremost common [1,5]. This is because dentures cause a gradual loss of sensation of the oral cavityand laryngopharynx. Besides, there is also an increase in the denture-wearing population thatleads to an increase in the incidence of denture ingestion [2].
The most common presenting symptom following the accidental swallowing of a denture isdysphagia [6]. The other symptoms include hypersalivation, retrosternal fullness, andregurgitation of foods. The incidence and type of complications correlate with the site andduration of the impaction. If a denture gets impacted in the mid-esophagus, the incidence ofcomplications is quite high, owing to its proximity to the anatomical structures [7]. If it getsimpacted for a long period, it will cause mucosal ulceration, perforation, para or retro-esophageal abscess, mediastinitis, empyema, or even tracheo and aorta-esophageal fistula[3,5]. But it is rare for a foreign body to remain in the esophagus for a long period without anycomplications. There was nothing peculiar about the denture characteristics, nor did thepatient have any psychiatric illness to remain asymptomatic for such a long time. After athorough review of the literature, we found some long-lasting esophageal foreign bodies inchildren, but only two reported in adults (Table 1) [8]. The denture was lodged in theesophagus for less than a year in both these cases. But, in our case, the denture remainedasymptomatic in the mid-esophagus for more than a decade.
Author YearPatientage/sex
Type of foreignbody
Site oflodgement
Duration oflodgement
Treatment
Kropf JA etal. [9]
2013 82/FEndoscopecapsule
Zenkerdiverticulum
Four months Removal by laryngoscopy
Mohajeri etal. [6]
2015 57/M DentureMid-esophagus
Nine monthsMini-laparotomy andgastrotomy
Our case 2020 45/F DentureMid-esophagus
13 yearsThoracotomy andesophagotomy
TABLE 1: Summary of the articles published about a long-lasting esophageal foreignbody in an adult
A soft tissue neck and chest radiograph is the initial investigation of choice. Dentures, however,are frequently made of acrylic resin, which is a radiolucent material, and they are difficult toassess on plain X-rays. But the radio-opaque wire hooks of the dentures can be seen [5]. It isdifficult to assess the relationship between the impacted denture and the surrounding tissuewith an X-ray. An unenhanced CT scan has 100% sensitivity, 92.6% specificity, 97.9% positivepredictive value, and 100% negative predictive value in the diagnosis of the esophageal foreignbodies [7,10]. Hence, CT scan is a gold standard for identifying the foreign body location and itsassociated complications and thereby helps the surgeon in preoperative planning [7].
The management strategies for the removal of the esophageal foreign body include endoscopic
2020 Karthikeyan et al. Cureus 12(5): e8042. DOI 10.7759/cureus.8042 4 of 5
removal and surgery. Attempts at endoscopic removal of the impacted dentures may causeintramural perforation or a full-thickness tear owing to the possible entrapment of wire hooksin the esophageal wall [1]. Therefore, surgery remains a safe and effective treatment forpatients with impacted dentures in the esophagus.
ConclusionsTo the best of our knowledge, this is the first case in the literature reporting a foreign body thatremained asymptomatic in the esophagus for more than a decade. Endoscopic removal of long-standing impacted dentures will cause extensive laceration of the esophagus and is thereforecontraindicated. Surgery remains a safe and effective treatment for patients with such long-standing impacted dentures in the esophagus.
Additional InformationDisclosuresHuman subjects: Consent was obtained by all participants in this study. Conflicts of interest:In compliance with the ICMJE uniform disclosure form, all authors declare the following:Payment/services info: All authors have declared that no financial support was received fromany organization for the submitted work. Financial relationships: All authors have declaredthat they have no financial relationships at present or within the previous three years with anyorganizations that might have an interest in the submitted work. Other relationships: Allauthors have declared that there are no other relationships or activities that could appear tohave influenced the submitted work.
References1. Mohanty HS, Shirodkar K, Patil AR, Mallarajapatna G, Kumar S, Deepak KC, Nandikoor S:
Oesophageal perforation as a complication of ingested partial denture . BJR. 2016, 2:4.10.1259/bjrcr.20150348
2. Thapar VK, Jagtap S, Barve DJ, Savarkar DP, Garle MN, Shukla AP: Thoracoscopic removal ofimpacted denture: report of a case with review of literature. J Min Access Surg. 2010, 6:119-121. 10.4103/0972-9941.72600
3. Mughal Z, Charlton AR, Dwivedi R, Natesh B: Impacted denture in the oesophagus: review ofthe literature and its management. BMJ Case Rep. 2019, 12:e229655. 10.1136/bcr-2019-229655
4. Dörner J, Spelter H, Zirngibl H, Ambe PC: Surgical retrieval of a swallowed denture in aschizophrenic patient: a case report. Patient Saf Surgery. 2017, 11:28. 10.1186/s13037-017-0147-8
5. Singh P, Singh A, Kant P, Zonunsanga B, Kuka AS: An impacted denture in the oesophagus-an endoscopic or a surgical emergency-a case report. J Clin Diagn Res. 2013, 7:919-920.10.7860/JCDR/2013/5337.2976
6. Mohajeri G, Fakhari S, Ghaffarzadeh Z, Piri-Ardakani M: A case of the long time presence of alarge foreign body in esophagus without complication. Adv Biomed Res. 2016, 5:205.10.4103/2277-9175.191001
7. Wang F, Yang N, Wang Z, Guo X, Hui L: Clinical analysis of denture impaction in theesophagus of adults. Dysphagia. 2019, 10.1007/s00455-019-10048-3
8. Miller RS, Willging JP, Rutter MJ, Rookkapan K: Chronic esophageal foreign bodies in pediatricpatients: a retrospective review. Int J Pediatr Otorhinolaryngol. 2004, 68:265-272.10.1016/j.ijporl.2003.09.021
9. Kropf JA, Jeanmonod R, Yen DM: An unusual presentation of a chronic ingested foreign bodyin an adult. J Emerg Med. 2013, 44:82-84. 10.1016/j.jemermed.2011.06.061
10. Liu YC, Zhou SH, Ling L: Value of helical computed tomography in the early diagnosis ofesophageal foreign bodies in adults. Am J Emerg Med. 2013, 31:1328-1332.10.1016/j.ajem.2013.05.049
2020 Karthikeyan et al. Cureus 12(5): e8042. DOI 10.7759/cureus.8042 5 of 5
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How to manage the COVID-19 pandemic?Surgeon’s perspectiveSupreeth Kumar Reddy Kunnuru, MS, MCh, MRCS, FRCSa, Manuneethimaran Thiyagarajan, MS, MRCS, FMASb,*,Deepak V.S. Kurmanadh, MBBSb, Nandita P. Vennugoal Rao, MBBSb, Rishikesh Venkataramanan, MBBSb
AbstractThis current pandemic situation medical professionals are working like warriors. Day by day cases are increasing throughout theworld although certain countries contained the spread. More than general population health care workers are under very high risk.The death rate in health care workers are increasing. Among these HCW, surgeons are in high risk category because of handlingmore aerosol generating procedure. There are many guidelines published by various organization. In this article we try to concise therecommendations for surgeons in various aspects. Elective cases can be prioritized bases on elective surgery acuity scale. Level 3personal protective equipment are recommended for operation theaters. Even powered air purifying respirator will give betterprotection. Laparoscopy surgeries can be still done with smoke evacuator and low pressure settings. On the whole this currentpandemic can be handled by surgeons with proper utilization of recommendations and protective measures.
Keywords: Surgery in COVID pandemic, Guideline for surgery in pandemic, Corona and surgery, Safe surgery in corona patient
Background
The Corona virus infection first started in Wuhan, Hubei, Chinain December 2019 with a cluster of patients with pneumonia[1].Following this, first case outside China was reported in Thailandon January 13, 2020[2] and WHO announced COVID-19 aspandemic on March 11, 2020. Now this pandemic shows16,922,232 new cases and 664,172 deaths.
The current virus SARS-2 virus is a single strand RNA viruswhich belongs to a large family of viruses called Corona virus andthis is the seventh Avian influenza virus that is known to infecthumans and other after (229E, NL63, OC43, HKU1) Coronavirus and the original SARS virus[3,4].
Among all population, health care workers are at very highrisk of virus exposure. Because of a shortage in protectiveequipment and knowledge about disease infection rate, in healthcare workers it is high[5]. The death rate in health care workers
continues to grow, with nearly 200 deaths highlighted, of which157 were confirmed as of May 3, 2020[6]. The front-line healthcare workers are at high risk of COVID-19 infection. In Italy20% of responding health care workers were infected withCOVID-19 infection[7].
Patients undergoing surgery are a vulnerable group to getCOVID-19 infection while in the hospital. Due to immune-sup-pressant state in surgery and because of proinflammatory cyto-kine release, pulmonary complications are more[1,8]. There aremany recommendations mentioned in various article. Onerecommendation is that a negative pressure room is necessary foraerosol-generating endoscopy room[9].
The main purpose of this article is to identify and provide safetymeasures and precautions for surgeons and other health careworkers involved in peroperative period and to prevent infection ofpatients during treatment. We have collected information fromvarious national health care guidelines and publications. Amongthese the guideline from organization include American College ofSurgeon, Society of American Gastrointestinal and EndoscopicSurgeons (SAGES), and Royal College of Surgeon England.
Available protective measures
In this pandemic we need all level of protection to preventCOVID-19 infection. Work uniform, disposable surgical cap,N95 mask, N99 mask, face shield, visor, goggles, gowns, shoecovers, disposable medical protective uniform, disposable latexgloves, half face mask particulate respirator, full-face mask par-ticulate respirator, and powered air-purifying respirator areavailable personal protective equipment (PPE).
Commonest mode of infection spread is from respiratorydroplets and body fluids. N95masks or nonvalve respirators withhead elastic loops provide good protection. According to Europestandards filtering face piece (FFP) score of 2 or 3 is better. It willfilter at least 94% of particles that are 0.3 μm in diameter. N99 or
aNarayanaMedical College, Nellore, Andhra Pradesh and bSri Ramachandra Instituteof Higher Education and Research (SRIHER), Chennai, Tamil Nadu, India
This manuscript has been peer reviewed.
Sponsorships or competing interests that may be relevant to content are disclosed atthe end of this article.
Published online 10 November 2020
*Corresponding author. Address: Sri Ramachandra Institute of Higher Education andResearch (SRIHER), 9036, Tower 9B, prestige Bella Vista, Iyyapanthangal, Chennai,Tamil Nadu 600056, India. Tel: + 0091-9952044955. E-mail address:profmaran@gmail.com (M. Thiyagarajan).
Received 29 July 2020; Accepted 29 September 2020
Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalfof IJS Publishing Group Ltd. This is an open-access article distributed under theterms of the Creative Commons Attribution-Non Commercial-No Derivatives License4.0 (CCBY-NC-ND), where it is permissible to download and share the workprovided it is properly cited. The work cannot be changed in any way or usedcommercially without permission from the journal.
International Journal of Surgery: Global Health (2020) 3:e37
http://dx.doi.org/10.1097/GH9.0000000000000037
’Review Article
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FFP 3 filter mask have 99% filtration capacity. It is better to usedome-shaped mask than duck bill mask as study found highfailure in facial fitness rate in duck bill[10]. Respirators can be usedin operation theaters. There are 3 types of respirators available. Acomparative study shows the protective factors of respirators inhalf face mask, full face mask, and powered air-purifyingrespirators are 14, 112, and 1328, respectively[11]. Powered air-purifying respirator is seeming to be more protective in operationtheaters. For endo-nasal surgery we can utilize full powered airpurifying respirator (an enclosed powered system with high effi-ciency particulate air filter[12] (Figs. 1, 2).
There are 3 levels of PPE available (Table 1).
Is there any role of hydroxy chloroquine as apreventive medicine?
If there is no contraindication and no drug interaction, 400mg ofHCQ as an initial dose for first 4 days followed by 400mg/wk for6 months can be used. This is one of the prophylaxis used inclinical trials[13]. There are 41 clinical trials going throughout theworld to find out benefit and side effect of this drug in health careworkers in COVID-19 pandemic[14]. A study conducted in SouthKorea shows the efficacy of postexposure prophylaxis of hydroxychloroquine[15]. While considering the risk benefit analysis HCQin selected group of high risk contacts is a prudent approach[16].Initial dose of 400mg twice a day on day 1 followed by 400mg/wk for 6 weeks is the prophylactic dose of HCQ advised by
Indian medical council for health care workers at risk and household contacts with confirmed cases[17]. However, it should beconsidered carefully before drawing definitive conclusions,since no data has been provided yet to support this announce-ment. The final interpretation is therefore technically demanding,and in the absence of published data, it is difficult to reach anyfirm conclusion[18].
Figure 1. Full face respirators, level 1 personal protective equipment (PPE) in OPD, half face respirator.
Figure 2. Powered air purifying respirator (PARP).
Kunnuru et al. International Journal of Surgery: Global Health (2020) 3:e37 International Journal of Surgery: Global Health
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Outpatient management
Managing the outpatient treatment in COVID-19 Pandemic is adifficult scenario. Chances of infection from patient to patient orpatient to doctors and nurses and spreading infection fromasymptomatic carriers are more challenging issue. Online con-sultation before patient comes to hospital will reduce the numberof patients. For many cases we can give online medication whichprovide safety for surgeon and patient. According to the SAGESguideline all nonurgent in-person clinic/office visits should becanceled or postponed, unless needed to triage active symptomsor manage wound care.
All surgicalOPDpatient should go in to a separate triage roomorfever clinic to rule out fever and respiratory symptoms and contacthistory before entering to surgical OPD. If there are any suspicioussymptoms, patient directly needs to follow the COVID-19 screeningmedical department and needs further evaluation.
Only restricted number of persons should stay inside OP roomand patient’s attender can stay outside the consultation room.Surgeon and nurse should wear N95 mask with face shield and ifpossible PPE. Distance between Doctors and patients should beadequately maintained except examination time. No aerosol-generating procedure to be done in OPD. Wound dressing mustbe done in separate room with all precautions and protections.Doctors and nurses should follow hand hygienic with propertechnique. Before and after examination of each patient doctorneeds to change the gloves and sanitize the hands. Medicineprescription should go to pharmacy directly by digital prescrip-tion and it is better to prescribe the medicine longer and saferperiod to avoid repeated patient visits. Fumigation of the OPDroom at the end of the day is very important to preventinfection[19].
Considerations in admissions
As per the SAGES guideline, virtual meeting with multi-disciplinary team with core team members which includes sur-geon, pathologist, oncologist, radiologist, and coordinator ishelpful in decision making for admitting the patients for surgery.All patients who needs emergency procedure must be admitted.Elective surgeries like malignancies needs admission. The RoyalCollege of Surgeon Edinburgh guideline shows all preoperativesurgery patients needs isolation for 14 days before and aftersurgery.
The gold standard test RT-PCR in pharyngeal swab must bedone for all admitted patients. Same test to be done even for theattender who will stay together. Attender should not changeduring hospital course. These test to be done for elective cases 24hour before the admission and for emergency patients test to bedone at the time of admission. If test become positive patientsmust be isolated and need to follow the national COVID-19public health protocols[20]. The median incubation time forpatients is 5.1 days (mean IT 5.5 d). The estimated median IT tofever was 5.7 days. So, we must always assume the admittedpatients to be potential carriers of virus throughout the hospital.So RT-PCR test must repeated every week in hospital stay.Unfortunately, the false-negative rate of RT-PCR testing is 67%in the first 5 days of infection and 21% on day 8 of infection[21].
Chest computed tomography (CT) has a high sensitivity fordiagnosis of COVID-19. Chest CT may be considered as a pri-mary tool for the current COVID-19 detection in epidemicareas[22]. In corona high prevalent countries pooled sensitivity ofCT-chest is 94% and sensitivity for RT-PCR is 89%. In lowprevalent countries positive predictive value for CT-chest is low(1.5%–30.7%)[23].
Perioperative measures
Preoperative considerations
We must consider all patients as a suspected patients and extraprecautions must be taken. In operation theater level 3 PPE needsto be used. Separate rooms used for donning and doffing of PPE.All medical staff involved in surgery must be screened properlybecause of chances of cross infection between staffs and to thepatient. So daily assessment of personal health care status andrecording temperature should be followed. Any suspicioussymptoms in medical staffs should be isolated and must undergofurther investigations.
Anesthesia considerations
Anesthetic equipment must be used by one person only andanesthesia machine is strictly disinfected every new cases.Intubation carries high risk due to close proximity to the patient’soropharynx and exposure to airway secretions is high with highviral loads[24]. Level 3 PPE must be used by anesthetist withrespirators. Awake intubation should be avoided. First timesuccessful intubation is better than repeated attempts. Rapid
Table 1Shows the 3 levels of PPE and its usage in various working areas.
PPE Level Face Mask Gown and Body Cover Eye Protections Area Used
1 3ply mask Or N95 mask Only if direct physical contact + gloves OHP face shield (1) Outpatient department(2) Triage
2 N95 mask/FFP2 Full sleeved gown + gloves + capand foot cover
Visor, face shield,goggles
(1) CT room(2) Emergency room(3) Transferring patient to ward
and OR room(4) Ward rounds
3 N-99/FFP3 Respirators PARP (powered airpurifying respirators)
Fluid repellents hooded cover allwith foot wear and head cover + double glove
Visor, face shield,goggles
(1) Operation theater(2) Any aerosol generating procedure(3) Intubation/extubation Ryle’s
tube insertion
We must know about personal protective equipment (PPE) donning and doffing steps and proper disposal of PPE.
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sequence intubation should be considered to avoid manual ven-tilation and potential aerosolization. High quality heat andmoisture exchange filter, HMEF is ideal to remove 99.97% ofairborne particles equal to or greater than 0.3 μm. HEPA filtercan be connected to both inlet and outlet tubes of patients withventilator[25]. If patient shifted with endotracheal tube to ICU,separate dedicated ventilator must be connected. While changingthe ventilator the ET tube to be clamped to avoid spillage.
Intraoperative considerations
Minimal number of persons in surgical team will reduce theinfection rate. All staffs need thermal screening before surgery.All instruments in the operative field must be kept dry in all timeto avoid spillage of fluid. smoke evacuators must be used toreduce the smoke from electrocautery. Spray mode must beavoided and need to use the minimal effective power to reduce thesmoke. Caremust be taken for aerosol-generating procedures likebronchoscopy, endoscopy laparoscopy and Ryle’s tube insertion,chest tube insertion, intubation, and extubation. Fluid spillage ismore in laparotomy cases, cesarean section, trauma surgerycases, and orthopedic procedure like nailing drilling the bone.Both electro-cautery and harmonic produce smoke with hydro-carbon but comparatively harmonic is preferable than electro-cautery[26].
Care for emergency surgeries
For emergency department separate triage and early recognition ofpossibleCOVID-19patients and immediate isolation is essential. Adoor to door connectivity between emergency room, CT room,and operating room (OR) is better for infection control.
For trauma patients primary and secondary survey must bedone with effective protection. Dynamic evaluation strategiesshould be followed in trauma care. Injury assessment directly tobe done by radiology. FAST scan and complete x-ray includingchest x-ray will assess the injury. In major trauma and bluntinjury abdomen cases complete CT screening to be done. In thatCT, chest images can help to identify the changes for COVID-19patients like small plaque shadows, interstitial changes, andground glass appearance. For patients like splenic injury andpenetration chest and abdominal injuries lifesaving proceduremust be done faster. Tertiary protection measures are needed forboth anesthesia and surgical procedure. As in trauma protocolmore critical patients to operated first. Before operating next case,30 minutes disinfection of operating room to be done[27]. Aftersurgery patients needs to go to isolation room.
Care for elective surgery
According to American College of Surgeon elective surgery acuityscale surgeries are classified in to various tires. Up to tire 2b, caseslike ureteral colic, low risk cancer, nonurgent spine surgeries canbe delayed and rescheduled. But cases in tire 3a (high acuity withhealthy patient) and 3b (high acuity with unhealthy patients) needelective surgery without postponement[28].
According to Surgical Society of Oncology, decision must betaken on individual case basis considering the cancer biology.
Patients undergoing elective surgery should be given reason-able recommendations regarding follow-up. Patient should beshifted to high care facility if COVID-19 is suspected and testsshould be ordered.
Laparoscopic surgery
Many surgical societies recommend laparoscopy surgery but theyalso recognize that the risk of aerosolization of virus is unclear.The Royal College of Surgeon recommends to choose thelaparoscopy in selected cases. According to the American collegeof Surgeon there is no data to compare the laparoscopy versusopen surgery in COVID-19 pandemic. SAGES advice to use filtersfor released CO2 in laparoscopic and robotics surgery.
Recommendations in laparoscopy:(1) The valve less access port with small circumferential CO2
nozzles within the trocar as opposed to a 1-way valve willminimizes loss of pneumo-peritoneum during instrumentexchange.
(2) Need to close all ports tap before insertion.(3) To use small incision to avoid side leak from port site.(4) Attaching a CO2 filter system to one of the port tap to open
it during surgery to deliver smoke evacuation. Rest of portstap never to be opened during surgery.
(5) It is better to minimize the usage of cautery system to avoidsmoke formation.
(6) Certain gas insufflators with inbuilt smoke evacuators likeConmed-air seal or Pneumoclear can be used. If smokeevacuator not available suction with filter can be used butsafety is not equivalent to smoke evacuator.
(7) End of surgery desuflation of gas must be done with suctionor smoke evacuator to avoid gas leak into room.
(8) Specimen removal also should be done after desuflationof gas.
(9) We propose that the use of lower pneumoperitoneumpressures 10–12mmHg which lower the risk and reducethe volume of aerosolized particles.
(10) Deep neuromuscular blockade to optimize the surgicalspace in laparoscopy with low CO2 pressure
[29].
Surgery in COVID positive patient—recommendations
(1) Very first operating room in or block must be allottedseparately for COVID positive patients in order to avoidenvironmental contamination, so that simultaneously theother operating rooms can work for non-COVID patients.
(2) Swift transfer of patient in and out must be followed.(3) Separate pathway for transfer is safe to minimize the
contamination. While transferring the patients, transferperson must be a trained person with PPE. Lifts and areathrough which patient transferred to be sanitized.
(4) Only for operating COVID-19 positive patients, separateon-call shift to be used. The operating team should havequarantine period of 14 days.
(5) Negative pressure operating room with high air exchangerate helps in reducing the viral load.
(6) In order to reduce the infection risk staff in and out must bereduced. whoever entered into OR should not leave the ORuntil procedure over and once exit the OR the personshould not reenter.
(7) All requirement for the surgery should be planned beforestarting surgery and all must be kept ready to avoidconfusions and contamination.
(8) Separate set of instruments to be used for COVID-19patients. Generally disposable material is preferable includ-ing drapes and linen.
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(9) All staffs and doctors must enter on time in OR withoutdelay. All possibilities must be used to reduce theoperating time.
(10) At all-time surgical instruments needs to be kept dry andonce procedure over used instruments to be kept undersodium hypochloride solution or any other disinfectantsolution.
(11) All potentially infected disposable material must be trans-ferred in separate container and must be sealed. Reusablematerials should be decontaminated meticulously.
(12) Once surgery completed the OR and surrounding exchangeareas must be sanitized. All electro medical equipment likeventilator must be cleaned with chloro-derived solution.
(13) Specimen should be labeled separately as COVID-19positive and should be handled as infective specimen forpathology department.
Postoperative considerations
COVID-19 negative patient can be transferred to regular surgicalward and regular monitoring of patient is important dailyassessment of temperature and breathing pattern must be fol-lowed. New onset of fever and respiratory symptoms needs fur-ther evaluation for COVID-19.
For COVID-19 positive and suspected patients should be keptseparately in negative pressure isolation room. Postoperativerounds and dressing must be done carefully by surgical teamwithall protective measures.Medical staffs involved in suspected casesor confirmed cases needs quarantine and observation for 14 days.
Ethical approval
None.
Sources of funding
No funding support for this publication.
Author contribution
S.K.R.K.: contributed in conception and design of work. M.T.:contributed in drafting the work and final approval. V.S.D.K.,N.P.V., and R.V.: helped in revising it critically for importantintellectual content.
Conflict of interest disclosures
The authors declare that they have no financial conflict of interestwith regard to the content of this report.
Research registration unique identifying number (UIN)
None.
Guarantor
Dr Manuneethi Maran Thiyagarajan.
Acknowledgments
The authors acknowledge the immense help received from thescholars whose articles are cited and included in references of thismanuscript. The authors are also grateful to authors/publishers ofall those articles, journals, and books from where the literaturefor this article has been reviewed and discussed.
References[1] Huang C, Wang Y, Li X, et al. Clinical features of patients infected with
2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497–506.[2] World Health Organization. WHO Timeline—COVID-19. 2020.[3] Alwan A, Mahjour J, Memish ZA. Novel coronavirus infection: time to
stay ahead of the curve. East Mediterr Health J 2013;19(suppl 1):S3–4.[4] Laude H, Rasschaert D, Delmas B, et al. Molecular biology
of transmissible gastroenteritis virusac. Vet Microbiol 1990;23:147–54.
[5] Huh S. How to train the health personnel for protecting themselves fromnovel coronavirus (COVID-19) infection during their patient or suspectedcase care. J Educ Eval Health Prof 2020;17:10.
[6] Kursumovic E, Lennane S, Cook TM. Deaths in healthcare workers dueto COVID-19: the need for robust data and analysis. 2020. Available at:https://doi.org/10.1111/anae.15116Citations. Accessed June 5, 2020.
[7] The Lancet. COVID-19: protecting health-care workers. Lancet 2020;395:922.
[8] Besnier E, Tuech JJ, Schwarz L.We asked the experts: Covid-19 outbreak:is there still a place for scheduled surgery? “Reflection from pathophy-siological data”. World J Surg 2020;44:1695–8.
[9] Repici A, Maselli R, Colombo M, et al. Coronavirus (COVID-19) out-break: what the department of endoscopy should know. GastrointestEndosc 2020;92:192–7.
[10] Degesys NF, Wang RC, Kwan E, et al. Correlation between N95 exten-ded use and reuse and fit failure in an emergency department. JAMA2020;324:94–6.
[11] GaneshG, Patkulkar DS, KulkarniMS. Evaluation of protection factor ofrespiratory protective equipment using indigenously developed protec-tion factor test facility. Radiat Prot Environ 2019;42:77–83.
[12] Tingbo L, ed. Handbook of COVID-19 Prevention and Treatment TheFirst Affiliated Hospital. Zhejiang University School of Medicine.Compiled According to Clinical Experience. Received by ZMP andPHH via personal communication from colleagues in Beijing. Hangzhou,China: Zhejiang University school of medicine; 2020.
[13] Pre-exposure prophylaxis with hydroxychloroquine for high-risk healthcareworkers during the COVID-19 Pandemic (PrEP_COVID). NCT04331834.2020. Available at: clinical trial.gov. Accessed April 7, 2020.
[14] Bienvenu A-L, Marty AM, Jones MK, et al. Systematic review ofregistered trials of Hydroxychloroquine prophylaxis for COVID-19health-care workers at the first third of 2020. One Health 2020;10:100141.
[15] Lee SH, Son H, Peck KR. Can post-exposure prophylaxis for COVID-19be considered as an outbreak response strategy in long-term care hospi-tals? Int J Antimicrob Agents 2020;55:105988.
[16] Tilangi P, Desai D, Khan A, et al. Hydroxychloroquine prophylaxis forhigh-risk COVID-19 contacts in India: a prudent approach. Lancet InfectDis 2020;20:1119–20.
[17] National Taskforce for COVID-19 Advisory on the use of hydroxy-chloroquine as prophylaxis for SARS-CoV-2 infection. 2020. Availableat: https://www.mohfw.gov.in/pdf/. Accessed April 7, 2020.
[18] Touret F, deLamballerie X. Of chloroquine and COVID-19. Antivir Res2020;177:104762. Available at: https://doi.org/10.1016/j.antiviral.2020.104762.
[19] Lal H, Sharma DK, Patralekh MK, et al. Out Patient Department prac-tices in orthopedics amidst COVID-19: the evolving model. J Clin OrthopTrauma 2020;11:700–12.
[20] Al-Muharraqi MA. Testing recommendation for COVID-19 (SARS-CoV-2) in patients planned for surgery—continuing the service and“suppressing” the pandemic. Br J Oral Maxillofac Surg 2020;58:503–5.
[21] Kucirka LM, Lauer SA, Laeyendecker O, et al. False-negative rate ofRT-PCR SARS-CoV-2 tests. Am Coll Cardiol 2020;173:262–7.
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[22] Ai T, Yang Z, Hou H, et al. Correlation of chest CT and RT-PCR testingin Coronavirus Disease 2019 (COVID-19) in China: a report of 1014cases. Radiology 2020;296:2.
[23] Kim H, Hong H, Yoon SH. Diagnostic performance of CT and reversetranscriptase-polymerase chain reaction for coronavirus disease 2019: ameta-analysis. 2020.
[24] DediegoML, Pewe L, Alvarez E. Pathogenicity of severe acute respiratorycoronavirus deletion mutants in hACE-2 transgenic mice. Virology 2008;376:379–89.
[25] Wong J, Goh QY, Tan Z, et al. Preparing for a COVID-19 pandemic: areview of operating room outbreak response measures in a large tertiaryhospital in Singapore. Can J Anaesth 2020;67:732–45.
[26] Edward JFF, Malik M, Ahmed I. A single-blind controlled study of electro-cautery and ultrasonic scalpel smoke plumes in laparoscopic surgery. SurgEndosc 2012;26:337–42.
[27] Li Y, Zeng L, Li Z, et al. Emergency trauma care during the outbreak ofcorona virus disease 2019 (COVID-19) in China. World J Surg 2020;15:33.
[28] American College of Surgeons. COVID-19: Guidance for triage of non-emergent surgical procedures. 2020.
[29] Bruintjes MH, van Helden EV, Braat AE, et al. Deep neuromuscularblock to optimize surgical space conditions during laparoscopic surgery:a systematic review and meta-analysis. Br J Anaesth 2017;118:834–42.
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International Journal of Medical Science and Advanced Clinical Research (IJMACR) Available Online at: www.ijmacr.com Volume – 3, Issue – 2, March - April - 2020, Page No. : 12 - 15
Corresponding Author: Dr Naveen Alexander, ijmacr, Volume - 3 Issue - 2, Page No. 12 - 15
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ISSN: 2581 – 3633 PubMed - National Library of Medicine - ID: 101745081
A Rare Case of Right Inguinal Hernia in a Patient with MRKH Syndrome 1Dr Pradushana V P, Department of General Surgery, Sri Ramachandra Institute of Higher Education And Research,
Porur, Chennai. 2Dr Naveen Alexander, Department of General Surgery, Sri Ramachandra Institute of Higher Education And Research,
Porur, Chennai.
Corresponding Author: Dr Naveen Alexander, Department of General Surgery, Sri Ramachandra Institute of Higher
Education and Research, Porur, Chennai.
Type of Publication: Case Report
Conflicts of Interest: Nil
Abstract
Inguinal hernia in females is relatively uncommon as
compared to males.Inguinal hernias containing ovary have
a documented incidence of 2.9% and most of these cases
are associated with congenital anomalies of genital
tract.(1) This is the case of a 16 year old female who
presented to our institution with pain and swelling in the
right side of the groin. On examination the patient had an
irreducible swelling in the right inguinal region. MRI
abdomen showed right inguinal hernia with ovary as its
content. Laparoscopic right inguinal hernioplasty was
done.
Keywords: MRKH syndrome, inguinal hernia, ovarian
hernia
Introduction
Repair of groin hernia is one of the most common
operations performed in general surgery, with over 20
million operations per year. Only 8 percent of all groin
hernia repairs are performed in women.The disparity
between outcomes after groin hernia repairs in women and
men stems from differences in anatomy.The shape of the
pelvis differs between the sexes as do the
musculoaponeurotic attachments and the structures
passing through the inguinal canal.
Mostly inguinal hernial sac contains omentum or small
bowel, but caecum, appendix,sigmoid colon or urinary
bladder are also seen occasionally. Ovarian hernia in
female infants and paediatric patients are often associated
with congenital genitourinary tract anomalies such as
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome.(2)
MRKH syndrome refers to congenital aplasia of the uterus
and the upper two-thirds of the vagina in females with
normal ovaries and fallopian tubes, secondary sexual
characteristics and 46XX karyotype. MRKH syndrome is
classified into two types based on associated anatomical
features. It was earlier considered as sporadic but now the
theory of being autosomal dominant has been
incorporated. The incidence is 1 out of 4500 females.Type
I MRKH syndrome is usually isolated type while Type II
MRKH syndrome (MURCS association or genital renal
ear syndrome) is associated with renal,vertebral,and to a
lesser extent, auditory and cardiac defects.(2) We report a
case of a MRKH syndrome with right inguinal hernia with
ovary as content.
Case Report
A 16 year old female presented to the opd with complaints
of swelling in the right side of her groin since two days
associated with pain. She is a known case of MRKH
syndrome with karyotyping done earlier for primary
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amenorrhoea. On examination she had an irreducible
swelling in the right side of the groin. Further evaluation
with MRI abdomen revealed right inguinal hernia with
ovary as content. Size, morphology and location of both
the kidneys were normal without any evidence of
anomalies.The patient was planned for laparoscopic right
inguinal hernioplasty. Right preperitoneal flap was created
and the sac was dissected. The hernial sac contained the
right rudimentary horn of the uterus, round ligament and
the right ovary. Round ligament was divided and the
contents were reduced. Prolene mesh was placed in the
preperitoneal plane and anchored to the pubis using
tackers. Right oophoropexy was done. Post operative
period was uneventful.
Figure 1:contents of the Right inguinal hernia
Figure 2: Mesh placement
Figure 3:Right Oophoropexy
Discussion
A hernia is defined as the protrusion of a portion of an
organ or tissue through the wall normally containing it.
Inguinal hernias are more common in males than in
females. Inguinal hernias in infants and young adults
result from the persistence of a patent peritoneal pocket. In
males it is the patent processus vaginalis and it
accompanies the testicle through the abdominal wall as it
descends into the scrotum. In females the ovaries also
descend into the pelvis but do not exit from the abdominal
cavity. The peritoneal extension, if it remains patent in
females, is known as the diverticulum of Nuck and leads
to indirect inguinal hernia.(3)
The mullerian duct and the mesonephric duct are
intimately related in the first months of fetal life.Toward
the third month the renal and the genital system are well
separated. When the ovary passes into the true pelvic
cavity it stops in its descent because of the fixation of the
gubernaculum of the ovary. The other end of the
gubernaculum of the ovary reaches the base of the labium
majus. The canal of Nuck, which extends into the labium
majus at this point, usually becomes obliterated at the
eighth month of fetal life. If, however, the canal of Nuck
remains open along with shortening of the distal end of the
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gubernaculum, it causes the ovary to be pulled into the
canal of Nuck lying within the inguinal canal.(4) An
inguinal ovary is at risk of torsion and infarction.
Management therefore is aimed at preservation of ovarian
function by repositioning the gonad to ensure an adequate
source of oocytes and estrogen production. Repositioning
and herniorrhaphy are advisable as soon as the condition
is recognized, irrespective of mullerian status. This
repositioning may be performed by an open or
laparoscopic approach.(5)
In our case laparoscopic reduction of the rudimentary horn
of the uterus, round ligament and right ovary was done.
Right Trans Abdominal Preperitoneal mesh plasty was
done. Most of the cases reported in literature underwent
open method. We decided laparoscopy due to the young
age of the patient and unmarried status. Right
oophoropexy by suturing it to the lateral pelvic wall was
done to prevent torsion.
Omari et al performed Herniorrhaphy with repositioning
of the uterus, fallopian tube, ovary and Williams vulvo
vaginoplasty for a 31 year old married women with
MRKH syndrome with rudimentary uterus,round ligament
and ovary as content in inguinal hernia.(5)
Open inguinal hernioplasty with excision of the mullerian
tissue was done by Verma et al in a 45 year old female
with MRKH syndrome with congenital agenesis of left
kidney.(6)
Laparoscopic Left inguinal hernioplasty was performed by
Khan et al in a 18 year old female with left inguinal hernia
with left ovary and fallopian tube as content.The patient
also had an left renal agenesis. (7)
Bilateral inguinal hernia with torsion of ovary as content
was noted by Palepu S et al for which Bilateral open
inguinal hernioplasty was done.(8)
Demirel F et al report the case of a 10 year old girl who
underwent left inguinal hernioplasty with ovary as
content. Karyotyping later revealed her with MRKH
syndrome.(9)
Conclusion
Most of the studies reported in literature involves open
method for management of an inguinal ovary.Since our
patient is young and unmarried we decided to go ahead
with an Laparoscopic approach.Since ovary was preserved
in this patient she can have genetic children through IVF
with embryo transfer to a gestational carrier.
References
1. Gurer A, Ozdogan M, Ozlem N, Yildirim A,
Kulacoglu H, Aydin R. Uncommon content in groin
hernia sac. Hernia. 2006 Apr 1;10(2):152-5.
2. Mohanty HS, Shirodkar K, Patil AR, Rojed N,
Mallarajapatna G, Nandikoor S. A rare case of adult
ovarian hernia in MRKH syndrome. BJR| case reports.
2017 Jan 1:20160080.
3. George EK, Oudesluys-Murphy AM, Madern GC,
Cleyndert P, Blomjous JG. Inguinal hernias
containing the uterus, fallopian tube, and ovary in
premature female infants. The Journal of pediatrics.
2000 May 1;136(5):696-8.
4. MAYER V, TEMPLETON FG. Inguinal ectopia of
the ovary and fallopian tube: review of the literature
and report of the case of an infant. Archives of
Surgery. 1941 Sep 1;43(3):397-408.
5. Al Omari W, Hashimi H, Al Bassam MK. Inguinal
uterus, fallopian tube, and ovary associated with adult
Mayer-Rokitansky-Küster-Hauser syndrome. Fertility
and sterility. 2011 Mar 1;95(3):1119-e1.
6. Verma R, Shah R, Anand S, Vaja C, Gaikwad K.
Mayer-Rockitansky-Kuster-Hauser Syndrome
Presenting as Irreducible Inguinal Hernia. Indian
Journal of Surgery. 2018 Feb 1;80(1):93-5.
7. Khan WF, Rathore YS, Pol MM, Singh G. Inguinal
hernia with ovary as content-laparoscopic repair in a
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Mayer–Rokitansky–Küster–Hauser syndrome patient:
case report. International Surgery Journal. 2019 Mar
26;6(4):1421-3.
8. Palepu S, Kumar U, Akhter J, Avinash Y. Torsion of
ovary in MRKH syndrome presenting as irreducible
sliding inguinal hernia. J Evol Med Dent Sci. 2015
Sep 10;4(73):12796-9.
9. Demirel F, Kara O, Esen I. Inguinal ovary as a rare
diagnostic sign of Mayer-Rokitansky-Küster-Hauser
syndrome. Journal of Pediatric Endocrinology and
Metabolism. 2012 Apr 1;25(3-4):383-6.
How to citation this article: Dr Pradushana V P, Dr
Naveen Alexander, “A Rare Case of Right Inguinal
Hernia In A Patient With MRKH Syndrome”, IJMACR-
March - April - 2020, Vol – 3, Issue -2, P. No. 12 – 15.
Copyright: © 2020, Dr Pradushana V P, et al. This is an
open access journal and article distributed under the terms
of the creative commons attribution noncommercial
License 4.0. Which allows others to remix, tweak, and
build upon the work non-commercially, as long as
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1Anandan Y, et al. BMJ Case Rep 2020;13:e236423. doi:10.1136/bcr-2020-236423
Salmonella Typhi: a rare cause of parotid abscessYamini Anandan,1 Tessa Antony ,1 Swati Kumari,1 Naveen Alexander2
Case report
To cite: Anandan Y, Antony T, Kumari S, et al. BMJ Case Rep 2020;13:e236423. doi:10.1136/bcr-2020-236423
1Microbiology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India2General Surgery, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
Correspondence toDr Tessa Antony; drtessa82@ gmail. com
Accepted 20 October 2020
© BMJ Publishing Group Limited 2020. No commercial re- use. See rights and permissions. Published by BMJ.
SUMMARYThe incidence of extraintestinal infection caused by Salmonella spp has been increased during the past decade. Here we report a case of a parotid abscess caused by Salmonella enterica subspecies enterica serotype Typhi (S. Typhi) in an individual without any significant abnormality of the parotid gland. A 68- year- old man presented to the surgical department with high- grade intermittent fever associated with painful swelling over the right side of the face, extending into the neck. An ultrasound of the neck revealed an abscess of the right parotid gland. S. Typhi was isolated from the pus drained from the parotid gland. The patient was treated with intravenous followed by oral cephalosporin for a period of 7 days. This case gives an insight into one of the rarer aetiological agents causing parotid abscess.
BACKGROUNDParotid gland is the largest of the salivary glands, located lateral to the masseter muscle anteriorly and extending posterior over the sternocleido-mastoid muscle behind the angle of the mandible. Parotid gland can become infected via ascending route through Stensen's duct, haematogenous route or contiguous spread following trauma.1 Parotid gland is much more susceptible to infection due to its serous secretion which is devoid of anti-bodies, lysosomes and mucins. Acute parotitis is the inflammation of the parotid gland that commonly arises due to a viral or bacterial infection. Acute inflammation can lead to abscess formation over a period of time.2 It is common in patients who are elderly, dehydrated, malnourished with additional predisposing factors like poor oral hygiene, ductal obstruction, gland tumours, diminished salivary flow, xerostomia, sialolithiasis and post dental procedures.3 Acute bacterial parotitis can result from stasis of salivary flow that may allow retro-grade introduction of bacterial pathogens into the gland, resulting in localised infection.4
The most common pathogens associated with acute parotitis are Staphylococcus aureus, Strepto-coccus species, Escherichia coli, Klebsiella pneumo-niae and anaerobic bacteria like Peptostreptococcus, Bacteroides, Fusobacterium and Prevotella. Less common agents include Hemophilus influenzae, Pseudomonas aeruginosa, Salmonella spp, Barton-ella henselae, Eikenella corrodens, Treponema pallidum and in endemic areas, Mycobacterium tuberculosis. Staphylococcus aureus is the most common pathogen associated with bacterial parotitis, accounting for 80% of cases.5
The cardinal signs and symptoms of acute parotitis include pain which is aggravated during eating, fever, chills, swelling at the angle of the jaw,
tenderness and erythema of the parotid region. It can be associated with trismus, facial asymmetry, facial nerve palsy, frank suppuration, dysphagia, odynophagia, difficulty in swallowing and marked systemic toxicity. Complications include respi-ratory obstruction due to massive swelling of the neck, infection of deep spaces of the head and neck, fistula formation, osteomyelitis of adjacent bones, septic jugular thrombophlebitis, septicaemia and meningitis.6
Infection with Salmonella spp is mainly seen in the tropical and subtropical areas where it is endemic. S. Typhi is a facultatively anaerobic, gram- negative bacilli which belongs to the family Entero-bacteriaceae. Serotypes are differentiated based on the characterisation of the heat stable O antigen, heat labile flagellar H antigen and heat labile capsular Vi antigen. It is transmitted by fecal–oral route through contaminated food and water from a patient or a carrier. It is isolated from humans at times of infection and does not form a part of normal microbiota of the bowel.7 Carrier state can been identified by performing stool culture, urine culture and bile culture. S. Typhi causes enteric fever which manifests as prolonged fever with abdominal pain, diarrhoea or constipation.
Salmonella spp is known to cause focal infections following entry into gastrointestinal tract. Dissem-ination of Salmonella occurs through bloodstream. It causes abscesses in many internal organs like liver, spleen, gall bladder, breast, ovary and chest wall. It is also known to colonise the diseased tissues and sites of trauma.8 Here we report a case of Salmo-nella parotitis.
CASE PRESENTATIONA 68- year- old man presented to the surgical depart-ment with complaints of high- grade intermittent fever for 20 days duration. It was associated with painful swelling over the right side of the face for 4 days. The patient had a history of intake of anti-pyretics and antibiotics (unknown) for 5 days prior to the hospital admission. The swelling progres-sively increased in size. He had a past history of two surgical procedures done in the oral cavity (1 year and 5 years back). Physical examination revealed the patient to be febrile (temperature 100 °F). Local examination of the right side of the face revealed a warm, fluctuant, tender swelling of 5×3 cm which was extending into the neck. Other systemic exam-ination was unremarkable. Patient was admitted to the hospital for further evaluation.
INVESTIGATIONSUltrasound of the neck was done that showed an impression of a heterogeneous echotexture of the right parotid gland with hypoechoic areas of
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abscess due to the edematous state of the parenchyma (figure 1). Pus collected from the incision and drainage of the abscess was sent for bacterial culture. Gram stain showed occasional pus cells and occasional gram- negative bacilli (figure 2). Culture was performed on 5% sheep blood agar, chocolate agar and MacConkey agar. In sheep blood agar, non- lytic grey moist colonies were observed. On MacConkey agar, non- lactose fermenting colonies were observed. The organism was found to be motile, catalase positive and oxidase negative. It was found to produce hydrogen sulphide in triple sugar iron agar and ferment glucose and mannitol. It did not produce indole, utilise citrate, nor hydrolyse urea.
Slide agglutination with antisera to somatic antigen D (sero-group 9) confirmed it to belong to Salmonella serogroup D. The organism was identified as Salmonella enterica subspecies enterica serotype Typhi in microscan walkaway 96 (Beckman Coulter, USA) with 99.9% probability. It was found to be suscep-tible to ampicillin, cefotaxime, ceftriaxone, cotrimoxazole, azithromycin, chloramphenicol and resistant to ciprofloxacin (according to Clinical and Laboratory Standards Institute, 2019 guidelines). Blood and urine cultures were found to be sterile.
TREATMENTIncision and drainage of the abscess was done under general anaes-thesia. Sterile compression dressing was applied. After the culture report, the patient was started on intravenous cefotaxime 500 mg two times per day for 3 days followed by oral cefixime 200 mg two times per day for 5 days, analgesics and chlorhexidine mouthwash.
OUTCOME AND FOLLOW-UPThe patient improved considerably and the fever subsided. He was discharged on the third postoperative day and was asked to review to the general surgery department after 7 days for follow- up. The patient was lost to follow- up.
DISCUSSIONParotid gland disease include viral and bacterial infections, autoim-mune diseases and tumours of the salivary glands.9 The patient had undergone oral surgery which would have resulted in trauma to the tissues and made it favourable for the bacteria to multiply and lead to abscess formation.10 Parotid gland infection with Salmonella spp is rare. Treyce et al reported a case of parotitis caused by S. Typhi with abscess formation in a patient with HIV infection in 1997. The patient rapidly recovered after incision and drainage of the lesion and initiation of trimethoprim- sulfamethoxazole therapy.11 In 1984, S. Typhi was isolated from a 15- year- old adolescent in India who developed bilateral parotid gland swelling following enteric fever.12 A few cases of non- typhoidal Salmonella species like S. schwarzen-grund, was isolated from a parotid abscess in a 79- year- old man with known cystic parotid disease after an episode of enterocolitis.13
In our case, the patient had no previous history of enteric fever. The blood culture was found to be sterile, which may be due to consumption of broad- spectrum antibiotics before the patient presented to surgical department and the blood sample was collected in the third week from the onset of fever. Blood culture is the ideal method for diagnosis of enteric fever and the rate of culture posi-tivity is 90% in the first week. Thereafter the positivity declines to 75% in the second week and 60% in the third week and 25% until the fever subsides. Following initial bacteraemia, abscess formation can occur in 10% of patients after months or years.14
Among different imaging techniques available for the study of parotid gland diseases, ultrasonogram is useful in the evaluation as it is rapid, non- invasive, less expensive, easy to perform and provides detailed morphological evaluation.15
The treatment of parotid abscess is incision and drainage, followed by the correct antimicrobial based on pus culture and sensi-tivity. Based on the antimicrobial susceptibility pattern, the choice of antimicrobial agent for treatment can be selected. It is ideal that the patient should be on follow- up and carrier state should be ruled out.
Current recommendations suggest that it is ideal to treat the patient with antimicrobial agent for 7 to 14 days to ensure complete eradication and to prevent recurrence. Failure to select appropriate antibiotics leads to clinical failure.16 Antimicrobial agents play an important role in therapy for infections caused by S. Typhi. Poten-tially effective agents include ampicillin, chloramphenicol, fluoro-quinolones, azithromycin, trimethoprim/sulfamethoxazole and third generation cephalosporins such as ceftriaxone.
However, S. Typhi has been known to exhibit resistance to fluo-roquinolones, cotrimoxazole and ceftriaxone.17 Recurrence of the infection can be controlled by counselling the patient on good oral hygiene and maintaining sufficient hydration. Hence a clinical prac-titioner and microbiologist must have a high index of suspicion for early diagnosis, prompt treatment to prevent lethal complications and recurrence from incomplete therapy.
Contributors All the authors have contributed to the making of this case report. TA conceptualised the case report and drafted the manuscript. YA performed the experiments and wrote the manuscript. SK supervised the work. NA provided detailed information of the clinical findings.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not- for- profit sectors.
Competing interests None declared.
Patient consent for publication Obtained.
Figure 1 Ultrasonogram showing heterogeneous echotexture of right parotid gland with hypoechoic areas of abscess.
Figure 2 Gram stain of pus from parotid abscess showing long gram- negative bacilli.
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Provenance and peer review Not commissioned; externally peer reviewed.
ORCID iDTessa Antony http:// orcid. org/ 0000- 0001- 9485- 8005
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6 Guralnick WC, Donoff RB, Galdabini J. Tender parotid swelling in a dehydrated patient. J Oral Surg 1968;26:669.
7 Petersdorf RG, Forsyth BR, Bernanke D. Staphylococcal parotitis. N Engl J Med 1958;259:1250–4.
8 Giglio MS, Landaeta M, Pinto ME. Microbiology of recurrent parotitis. Pediatr Infect Dis J 1997;16:386–90.
9 Nusem- Horowitz S, Wolf M, Coret A, et al. Acute suppurative parotitis and parotid abscess in children. Int J Pediatr Otorhinolaryngol 1995;32:123–7.
10 Chi TH, Yuan CH, Chen HS. Parotid abscess: a retrospective study of 14 cases at a regional hospital in Taiwan. B- ENT 2014;10:315–8.
11 Knee TS, Ohl CA. Salmonella parotitis with abscess formation in a patient with human immunodeficiency virus infection. Clin Infect Dis 1997;24:1009–10.
12 Kayaa H, Durdu B, Koc AK, et al. Egyptian Journal of ear, nose throat and allied sciences.A rare cause of parotid abscess; Salmonella enterica subsp. Arizonae 2015;16:291–3.
13 Kim YY, Lee DH, Yoon TM, et al. Parotid abscess at a single Institute in Korea. Medicine 2018;97:e11700.
14 Reyes CV, Jensen JD. Parotid abscess due to Salmonella enteritidis: a case report. Acta Cytol 2006;50:677–9.
15 Grossenbacher R, Steiner D. Salmonella parotitis with abscess formation. Otolaryngol Head Neck Surg 1992;106:98–100.
16 Rodríguez M, de Diego I, Mendoza MC. Extraintestinal salmonellosis in a general Hospital (1991 to 1996): relationships between Salmonella genomic groups and clinical presentations. J Clin Microbiol 1998;36:3291–6.
17 Brook I. Diagnosis and management of parotitis. Arch Otolaryngol Head Neck Surg 1992;118:469–71.
Learning points
► Salmonella Typhi can cause parotid abscess. ► Early diagnosis and surgical intervention, usually incision and drainage, can help prevent the spread of infection and hasten recovery.
► Antibiotic treatment to be based on antimicrobial susceptibility pattern due to emerging multidrug resistant strains.
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International Surgery Journal | September 2020 | Vol 7 | Issue 9 Page 3009
International Surgery Journal
Ganesh P et al. Int Surg J. 2020 Sep;7(9):3009-3011
http://www.ijsurgery.com pISSN2349-3305 | eISSN 2349-2902
Original Research Article
Prevalence of Helicobacter pylori infection in dyspeptic patients
undergoing upper gastrointestinal endoscopy in a
tertiary-care teaching hospital
Pranav Ganesh1*, Ramya Ramakrishnan2, Sandhya Sundaram3
INTRODUCTION
Helicobacter pylori is a gram-negative, microaerophilic
bacterium usually found in the stomach. The bacterium is
transmitted by feco-oral route and is associated with
peptic ulcer, duodenal ulcer and gastric carcinoma. H.
pylori infection is widely prevalent in the world
especially in the developing countries. Approximately
half of the world population is known to be infected with
this bacterium.1 Infected patients are usually
asymptomatic, but clinical manifestations can range from
acute gastritis and abdominal pain to chronic gastritis and
dyspepsia. A major post-infection complication of this
disease is gastric carcinoma. Laboratory diagnosis of H.
pylori can be done by invasive methods such as upper
gastrointestinal endoscopy with biopsy and rapid urease
test. Non-invasive methods of testing are less sensitive
and include blood antibody test, H. pylori stool antigen
ABSTRACT
Background: Helicobacter pylori infection is widely prevalent in the world especially in the developing countries.
The common clinical presentation of this disease includes peptic and duodenal ulcer. A major post-infection
complication of this disease is gastric carcinoma. The scope of this study was to determine the prevalence of active H.
pylori infection in the local population by retrospective review of patient records, which can give a better picture of
the current situation and estimate the at-risk population of gastric carcinoma. Objective of the study was to determine
the prevalence of H. pylori infection in biopsy specimens obtained from upper gastrointestinal endoscopy performed
in dyspeptic patients in a tertiary-care hospital.
Methods: The study was performed as a retrospective review of biopsy reports of 262 dyspeptic patients with
previously unknown H. pylori status who underwent upper gastrointestinal endoscopy during the months of January
2018 to May 2018. Biopsy obtained from stomach was evaluated for the presence of H. pylori infection by Rapid
Urease Test (RUT) or histopathological examination.
Results: The prevalence of H. pylori infection in dyspeptic patients obtained from the above study was 44.7% and
was found to be more common in males compared to females.
Conclusions: H. pylori is a risk factor for gastric carcinoma. Determining the prevalence with early identification of
active infections results in better treatment and post infection monitoring for malignancy.
Keywords: Dyspepsia, Helicobacter pylori, Prevalence, Rapid urease test, Upper gastrointestinal endoscopy
1Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
2Department of General Surgery, 3Department of Pathology, Sri Ramachandra Institute of Higher Education and
Research, Chennai, Tamil Nadu, India
Received: 17 June 2020
Revised: 13 July 2020
Accepted: 16 July 2020
*Correspondence:
Dr. Pranav Ganesh,
E-mail: pranavganesh510@gmail.com
Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI: http://dx.doi.org/10.18203/2349-2902.isj20203785
Ganesh P et al. Int Surg J. 2020 Sep;7(9):3009-3011
International Surgery Journal | September 2020 | Vol 7 | Issue 9 Page 3010
test and carbon urea breath test. The scope of this study is
to determine the prevalence of active H. pylori infection
in the local population, which can give a better picture of
the current situation and estimate the at-risk population of
gastric carcinoma.
Aim of the study was to determine the prevalence of H.
pylori infection in biopsy specimens obtained from upper
gastrointestinal endoscopy performed in dyspeptic
patients in a tertiary-care hospital.
METHODS
The study was performed as a cross-sectional, hospital-
based retrospective review of 262 patient records for a
period of 5 months (January 2018 to May 2018) at Sri
Ramachandra Institute of Higher Education and Research
(SRIHER), Porur, Chennai, India. The criterion for
inclusion was dyspeptic patients whose Helicobacter
pylori status was unknown at the time of study. There
were no exclusion criteria for the study population. The
parameters of this study included the results obtained
from biopsy taken in upper gastrointestinal endoscopy
through two testing modalities, rapid urease test (RUT)
and histopathological examination of biopsy specimens.
The required sample size was calculated based on the
formula n= Za2pq/l2. Recorded patient data was analysed
using the JASP 0.8.6 statistical package, developed by
the University of Amsterdam, The Netherlands.
Individuals in the participant population were considered
positive for the infection if they tested positive through
either of the two testing modalities.
RESULTS
This study was performed with the aim of calculating the
prevalence of Helicobacter pylori infection among
dyspeptic patients who underwent upper gastrointestinal
endoscopy. The parameters of the study were the rapid
urease test (RUT) results and histopathological
examination of the biopsy obtained from the endoscopic
procedure.
The study included 262 individuals of which 139 were
males and 123 were females, comprising 53% and 47%
of the study population respectively. The study
population were divided into 3 age groups - 18 to 35
years, 36 to 50 years and above 50 years. The age group
of 18-35 years reported the highest frequency of
dyspeptic patients who underwent upper gastrointestinal
endoscopy while the age group of above 50 years
reported the lowest frequency of dyspeptic individuals
who underwent upper gastrointestinal endoscopy (Figure
1).
Rapid urease test (RUT) was performed on 222 out of
262 individuals. Out of the 222 individuals, 91 tested
positive for H. pylori infection and 131 tested negative
for H. pylori infection (Figure 2). Histopathological
examination of the biopsy was performed in 42 out of
262 individuals. Out of the 42 individuals, 26 tested
Positive for H. pylori and 16 tested negatives for H.
pylori (Figure 2).
Figure 1: Age distribution of the study population.
Figure 2: The number of samples positive and
negative for Helicobacter pylori in the study
population by both testing modalities.
Figure 3: The sex distribution of samples positive and
negative for H. pylori in the study population.
Positivity of H. pylori infection was considered based on
results obtained from rapid urease test and
histopathological examination of biopsy. A patient was
considered positive for H. pylori infection if either of
these test results were positive. Considering the sample
consisting of 262 patients, 117 tested positive for H.
pylori infection while 145 tested negative for H. pylori
infection by either of the testing modalities. Among the
117 patients tested positive for H. pylori, there were 60
males and 57 females (Figure 3).
Ganesh P et al. Int Surg J. 2020 Sep;7(9):3009-3011
International Surgery Journal | September 2020 | Vol 7 | Issue 9 Page 3011
The age group of 18 to 35 years had the highest
prevalence with 46 patients positive for H. pylori
infection (Figure 4). The prevalence of H. pylori infection
among dyspeptic patients was calculated to be 44.7%
(Figure 5).
Figure 4: The age distribution of samples positive and
negative for H. pylori in the study population.
Figure 5: The prevalence of H. pylori infection in the
study population.
DISCUSSION
This study determined the prevalence of H. pylori
infection in dyspeptic patients who underwent upper
gastrointestinal endoscopy to be 44.7% using two testing
modalities, RUT and histopathological examination of
biopsy. The infection was found to be more prevalent in
males and in the age group of 18 to 35 years.
The results obtained from this study gave a quantitative
descriptive analysis of the active cases of infection in the
local population. The prevalence obtained from this study
was found to be in accordance with similar studies
performed in the region.2,3 In comparison to similar
studies performed in other regions of the world, it was
found that prevalence of H. pylori infection in the local
population was lesser than West Indies, whereas it was
greater than estimates obtained in Poland.4,5
The prevalence obtained is an estimate of the population at risk of developing post – infection complications such as gastric carcinoma. The prevalence of H. pylori
infection in non-cardia gastric carcinoma from another study was found to be 6.2% and the attributable fraction was 89.0%.6
Limitations
This study was performed retrospectively, hence a prospective randomized controlled trial is the best way forward. The study could have given a broader perspective if there had been a proportionate number of biopsy reports as compared to RUT results.
CONCLUSION
The wide prevalence of H. pylori infection in the general population necessitates a quantitative estimation of the magnitude of the problem, which this study has determined. The RUT was useful as a quick screening tool to determine if the patients were infected. Prompt treatment and post-infection monitoring of active cases can lead to reduced incidence of complications such as gastric carcinoma.
Funding: No funding sources Conflict of interest: None declared Ethical approval: The study was approved by the Institutional Ethics Committee
REFERENCES
1. Hooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE, Tanyingoh D, et al. Global prevalence of helicobacter pylori infection: systematic review and meta-analysis. Gastroenterol. 2017;153(2):420-9.
2. Dutta AK, Reddy VD, Iyer VH, Unnikrishnan LS, Chacko A. Exploring current status of Helicobacter pylori infection in different age groups of patients with dyspepsia. Indian J Gastroenterol. 2017;36(6):509-13.
3. Jeyamani L, Jayarajan J, Leelakrishnan V, Swaminathan M. CagA and VacA genes of Helicobacter pylori and their clinical relevance. Indian J Pathol Microbiol. 2018;61(1):66-9.
4. Whittle DO, Ewing R, Lee MG. The prevalence of Helicobacter pylori infection in patients undergoing upper gastrointestinal endoscopy in the Turks and Caicos Islands. West Indian Med J. 2010;59(3):309-11.
5. Tascikowski T, Bawa S, Gajewska D, Ryciak MJ, Bujko J, Rydzewska G. Current prevalence of Helicobacter pylori infection in patients with dyspepsia treated in Warsaw, Poland. Przegla̜d Gastroenterol. 2017;12(2):135-9.
6. Plummer M, Franceschi S, Vignat J, Forman D, Martel C. Global burden of gastric cancer attributable to Helicobacter pylori. Int J Cancer. 2014;136(2):487-90.
Cite this article as: Ganesh P, Ramya R, Sundaram
S. Prevalence of Helicobacter pylori infection in
dyspeptic patients undergoing upper gastrointestinal
endoscopy in a tertiary-care teaching hospital. Int
Surg J 2020;7:3009-11.
Rajasenthil V et al., Int. J. Res. Pharm. Sci., 2020, 11(2), 1352-1357
ORIGINAL ARTICLE
INTERNATIONAL JOURNAL OF RESEARCH INPHARMACEUTICAL SCIENCES
Published by JK Welfare & Pharmascope Foundation Journal Home Page: www.pharmascope.org/ijrps
Comparative study of time taken for skin closure, infection rate andpostoperative pain in skin closure with sutures and staplers in openinguinal hernioplasty
Rajasenthil V*, Sriraman K B, Kaliyappa C
General Surgery, Sri Ramachandra University, Chennai, Tamil Nadu, India
Article History:
Received on: 03.08.2019Revised on: 18.11.2019Accepted on: 27.11.2016
Keywords:
Inguinal Hernia,Skin staplers,Sutures
ABSTRACT
Wound healing is a complex and dynamic process and is in luenced by sur-gical technique. Optimal wound healing, with a minimal scar that compro-mises neither appearance nor function, is the desired result. This process isaffected by both local and systemic factors. Many local conditions are readilycontrolled at the time of wound closure, and several fundamental principlesof surgical wound closure exist that should be adhered to in the management.Skin is usually closed with sutures then later with skin staplers. Skin sta-plers are quick and easy to use, but an assistant is usually required to hold theskin edges accurately with forceps or skin hooks. Stapler’s closure also causesconsiderably less damage to wound defenses than closure with least reactivenon-absorbable suture. Standard suturing causes signi icantly more necrosisthan stapling in myocutaneous laps. We did this study to compare the timerequired for the closure of skin, infection rate, pain at the operated site withsutures and staplers in open inguinal hernia repair. 80 patients who wereposted for elective open inguinal hernia surgery at Sri Ramachandra MedicalCollege & Research Institute, porur, Chennai was included in this study. Timetaken for closure of skin, infection rate and the pain was less in patients withstapler closure than with skin sutures
*Corresponding Author
Name: Rajasenthil VPhone: 9962758494Email: rajasenthilv@gmail.com
ISSN: 0975-7538DOI: https://doi.org/10.26452/ijrps.v11i2.1998
Production and Hosted by
Pharmascope.org© 2020 | All rights reserved.
INTRODUCTION
An incision over the skin is properly planned as toshape, direction, and size. In general, incisions aremade along the normal skin lines or along Langerlines (Son and Harijan, 2014). Skin management isaimed to prevent skin necrosis.
In closing wounds, sutures are either used in an
interrupted or continuous fashion. The purpose ofa suture is to hold tissues in apposition to leave agood scar. The surgical technique, surgical sutures,staplers, and a needle is quite important to achieveoptimumwound healing.
Sutures are conveniently classi ied into two broadgroups (Table 1)
1. Absorbable
2. Non-absorbable
Advantages and Disadvantages of suturemateri-alsMono ilamentRussel (2000) consists of the single strand on syn-thetic material. The resistance of the suture isreduced after each time it passes the tissues, and thebacterial adherence is decreased due to its smoothsurface contour. But any crushing or kinking of
1352 © International Journal of Research in Pharmaceutical Sciences
Rajasenthil V et al., Int. J. Res. Pharm. Sci., 2020, 11(2), 1352-1357
Table 1: Types of suture materialsSuture Materials Absorbable Non-Absorbable
Mono ilament 1. Surgical gutPlain and Chromic2.CollagenPlain ad Chromic3. Monocryl4. PDS II5. Polyglactin 910
1. Polypropylene2. Stainless steel3. Polyester
Multi ilament 1. Polygycolic Acid2. Polyglacting 910
1. Surgical silk2. Surgical linen3. Cotton4. Polyamide braided5. Polyester braided6. Stainless steel
Others 1.Surgical Stapler
the suture may result in a weak spot in the strandand can lead to surface breakage. Knot slippage isgreater with mono ilament suture.
Braided materials have the advantage of adjustingthe knot and its tension accurately.
They have a high degree of drag when they passthrough the tissues, and due to their capillary action,they cause tissue reaction, which may lead to stitchabscess.
The quantity of suture used must be adequate tosecure the tissue, but excess material increases tis-sue reaction (foreign body) and in lammation ofhealthy tissues.
An absorbable suture is prepared from either fromanimal tissue or synthetic polymers. Those fromnatural sources elicit a foreign body responsefrom tissues with resultant digestion from tissueenzymes, where as synthetic absorbable polymersare hydrolyzed to smaller monomers, which aremetabolized by tissues.
Non-absorbable sutures are permanent and resistdigestion by body enzymes or hydrolysis by tissue.
Strength of Suture
1. Strength of suture material is expressed usingthe terms Stress and Strain.
2. Strength represents the instantaneous forceapplied to the sutures (N/Msq).
3. Strain is a measure of instantaneouslength/starting length (Units).
4. Strength is peak stress at the point of suturerupture, whereas the toughness is the energyrequired to rupture the suture (J/mtq).Table 2 Kudur et al. (2009)
Nylon
Nylon is available in both mono ilament and Multiilament form. Nylon is non-absorbable, but thereis progressive hydrolysis of the nylon in vivo mayresult in gradual loss of tensile strength over time.So nylon suture should not be used in suturisationwhen permanent retention of tensile is required.
Prolene (Polypropylene)
Stockley and Elsom (1987); Johnson et al. (1981)Is a mono ilament synthetic suture material and ischemically extruded from a puri ied and dyed poly-mer, which is neither absorbed nor weakened bythe action of tissue enzymes. It has an extremelyhigh tensile strength, which it retains inde initely onimplantation. This lack of adherence to tissues facil-ities its use as a permanent suture. It can extend upto 30% before breaking and hence is useful in situ-ations to accommodate the post-operative swelling,and there by helps to prevent tissue strangulation.Handling is good, and knotting is very secure sincethe material deforms on knotting and allows theknot to bend down on itself. It has no coef icient offriction and slides through tissue readily. By taper-ing the end of the suture, it may be swaged in toa needle of a similar diameter, which provides ahaemostatic advantage in vascular anastomosis.
© International Journal of Research in Pharmaceutical Sciences 1353
Rajasenthil V et al., Int. J. Res. Pharm. Sci., 2020, 11(2), 1352-1357
Table 2: Strengths and Toughness of Commonly UsedSutureMaterial Strength (10 10 n/m2) Toughness (107 J/m2)
polyester 2 32 6.20Silk 0.85 2.35polyglyconate 0.83 2.36PDS 0.97 2.38Nylon 2.54 5.55Prolene 2.99 4.87
(Measurement made with 60 suture materials after six weeks of incubation in a rat model).
It is extremely smooth, and it is less thrombogenic ascompared to silk. It is inert and non-biodegradable.Being mono ilament, it should be carefully handledduring surgery, as rough handling and inadvertentcrushing will damage it. Rough handling may causea fracture on the strand, which may break later inthe postoperative period. It is sterilized by ethyleneoxide.
Staplers
Hulti Humer, in 1908, introduced surgical skinstaplers, which was massive by today’s standardsweighing 7.5 pounds. Von Petz modi ied it into alighter and simpler device, and in 1934 Fredrickof Ulm designed an instrument that resembled themodern linear stapler. The next major advancescame from Russia after World War II. In 1958,Ravich, who, through research and development,re ined the instruments to their current state. Themost signi icantmodi ication has been the introduc-tion of absorbable staples. When these are used ingynecological operations,morbidity related to infec-tious granulomas and dysparunia has been dimin-ished. They are best avoided in the face and hand.Skin staplers are easy to use, less time consuming,but an assistant is usually required to hold the skinedges accurately with forceps or skin hooks. Theapplication is then alignedon thewound, often thereis an arrow or mark to assist, and the trigger ispulled. In one action, a staple is driven into the tis-sues and closed.
For removal, a special extractor is required, whichbends the staple back with its original con igurationwhere upon it can be withdrawn.
MATERIALS ANDMETHODS
80 patients who undergoing elective open inguinalhernia surgery at Sri Ramachandra Medical College& Research Institute, porur, Chennai was taken intothe study.
Inclusion criteria
1. Age > 18 years.
2. Patients undergoing uncomplicated inguinalhernia surgeries.
Exclusion criteria
1. Age < 18 years.
2. Patientswith complicated hernias. (obstructed,strangulated hernia)
3. Patient not willing to give consent
Skin closure was measured in seconds, the length ofthe wound was measured, and the time taken percentimeter of a wound is calculated.
Staples were removed with a device that painlesslyopened them sideways, while sutureswere removedin a conventional way. Wound closures were gener-ally removed at ten days, and the ease or dif iculty ofremoval was recorded. Pain attributable to the skinclosure was assessed by a verbal numerical scale onpod 1, pod3, and on day of removal. Wound assess-ment was done using the Hollanders score.
Hollanders scale
1. Step off borders
2. Contour irregularity - puckering.
3. Scar width: greater than 2 mm
4. Edge inversion or sinking or curling
5. In lammation: redness and discharge
6. Overall cosmoses
The total score is the addition of all the scores, A’WES scale’ used for evaluation of the wound. Ineach of the six variables, the score of 0 is given foryes and 1 for no.
1354 © International Journal of Research in Pharmaceutical Sciences
Rajasenthil V et al., Int. J. Res. Pharm. Sci., 2020, 11(2), 1352-1357
RESULTS AND DISCUSSION
38 patients underwent wound closure by staplers,and 42 patients underwent wound closure withmono ilament nylon matress suturing.
Time
The time taken for stapling had a statistically signif-icant advantage over the suture group with stapletaking an average time of 9.05 seconds per centime-ter and sutures taking 22.19 seconds per centimeter.
Skin site infection
3 patients among the 42 patients in the suture groupdeveloped skin and subcutaneous infection, and noinfections noted in the stapler group, which is notstatistically signi icant.
Pain
Pain on post operative day 1 and at times of sutureremoval were observed and were not statisticallysigni icant, but pain on post operative day 3 showeda statistically signi icant advantage over the suturegroup.
Cosmesis
The overall appearance and wound evaluation wassigni icantly better in the stapler group over thesuture group, and patient acceptance was also bet-ter in the stapler group.
Collected data were analyzed with IBM.SPSS statis-tics software 23.0 Version. Percentage analysiswereused for categorical variables, and themean,median& S.D were used for continuous variables. To indthe signi icant differencebetween thebivariate sam-ples in Independent groups (Sutures& Staplers), theUnpaired sample t-test was used for normal data,and the Mann-Whitney U test was used for skeweddata. To ind the signi icance in categorical data, theFisher’s Exact was used. In all the above statisticaltools, the probability value .05 is considered as a sig-ni icant level.
1. P – Value : Highly Signi icant at P < .01
2. P – Value : Signi icant at P < .05
3. P – Value : Signi icant at P > .05
Pain
1. Pain on postoperative day 1 does not show anystatistical signi icant with P-value of 0.1 29
2. Pain on postoperative day 3 is signi icantly bet-ter in the stapler group with P-value of 0.045
3. P-value on time of suture removal is 0.193,which is not statistically signi icant.
Wound scoreThe stapler group shows better wound cosmosiswith a P-value of 0.0005, which is statistically highlysigni icant.
Wound closure results in a healthy scar; it is thesurgeon’s responsibility to ensure its aestheticallypleasing appearance. Skin staples offer an alterna-tive to regular sutures in improving the aesthesis.
Time taken to complete wound closure was signif-icantly less with the use of staplers as compared tosutures. The average time taken to approximate1cmof the wound was 9.05 seconds with the staplerswere as with sutures; it was 22.19 seconds in ourstudy (Table 3).
Ranaboldo et al. (1992) analyzed skin staplerand subcuticular suture in 48 patients undergo-ing abdominal exploration and concluded that thetime taken in stapler closure was less, but thecost was ive times greater with staples.The rate ofwound closurewas 8 seconds/cmwith a stapler and12.7 seconds/cm with sutures in a study by Ran-aboldo et al. (1992). Kanegaye et al. (1997) observedthat staplers were six times faster than standardsuture in skin closure for scalp lacerations in chil-dren (Kanegaye et al., 1997).In our study, postoperative pain on 3rd day washigher in the suture group than the stapler group.
Eldrup et al. (1981) studied 137 patients under-going abdominal and breast surgery in a random-ized control study, which found that time was savedin staple closure, as with mechanical sutures tookone-third of the time required for the conventionalmethod and found pain was present in the staplegroup (Eldrup et al., 1981).The overall appearance and wound evaluation wassigni icantly better in the stapler group over thesuture group, and patient acceptance was also bet-ter in the stapler group.
Meiring et al. reported slightly better cosmeticresults in a group of 40 patients undergoing laparo-tomywith an 80% time saved in stapler closure overskin suturing (Meiring et al., 1982).Harvey and Logan studied a group of 20 patientsundergoing surgery for varicose veins in both lowerlimbs, using a different method of skin closure ineach leg. They reported a saving of 66.6% in clo-sure time and a similar cosmetic result (Harvey andLogan, 1986).
Zwart and Ruiter achieved better cosmetic resultswith the sub cuticular suture thanwithmetal suture
© International Journal of Research in Pharmaceutical Sciences 1355
Rajasenthil V et al., Int. J. Res. Pharm. Sci., 2020, 11(2), 1352-1357
Table 3: Time taken for skin closure in secondsSkin Closure Times in Seconds
Sutures 22.19 seconds per centimetreStaplers 9.05 seconds per centimetre
Stapler group has an advantage over the suture group, and it is statistically highly signi icant with P-value of 0.0005
Table 4: Infection * Groups Cross tabulationGroups Total
Sutures Staplers
Infection no Count 39 38 77%within 92.9% 100.0% 96.3%Groupsyes Count 3 0 3%within 7.1% 0.0%, 3.8%GroupsTotal Count 42 38 80%within 100.0% 100.0% 100.0%Groups
Wound infection does not show statistical signi icant with P-value of 0.093
1 month after surgery; however, after 6 months,the results of both the methods were similar. Theyargued that it is advantageous to use sutures withstaples in contaminated surgery (Zwart et al., 1989;Kumar, 2017)
In the present study, three complications wereencountered in the suture group in the form ofwound infection. In the stapler group wound infec-tions were absent (Table 4 )
Luiz R Medina dos Santos et al. in their study of 20consecutive patients during head and neck surgeryconcluded that the use of skin staplers closure savestime by 80%, with better cosmetic results, and doesnot increase the incidence of infections, althoughthe slightly higher cost was involved (Santos et al.,1995). It had wound infection in 8 patients (5 in thestapled group : 3 in suture group )
According to the study by Tuuli Mehodinn et al., therisk of developing a wound infection was four timesgreater after staple closure than in subcuticular skinclosure in caesarean section (Tuuli et al., 2011).
CONCLUSIONS
Considerable evolution has taken place from theconventional skin suture technique and switch overto the new era of cosmoses, in the form of skin sta-pling to achieve a near virgin scar less skin. Further,it helps to bring down the time required for skin clo-sure and achieving better cosmesis.
REFERENCES
Eldrup, J., Wied, U., Anderson, B. 1981. Randomisedtrial comparing Proximate® stapler with conven-tional skin closure. Acta Chirurgica Scandinavica,147:501–502.
Harvey, C. F., Logan, C. J. H. 1986. A prospective trialof skin staples and sutures in skin closure. IrishJournal of Medical Science, 155(6):194–196.
Johnson, A., Rodeheaver, G. T., Durand, L. S., Edger-ton, M. T., Edlich, R. F. 1981. Automatic dispos-able stapling devices for wound closure. Annals ofEmergency Medicine, 10(12):80086–80094.
Kanegaye, J. T., Vance, C. W., Chan, L., Schonfeld, N.1997. Comparison of skin stapling devices andstandard sutures for pediatric scalp lacerations: Arandomized study of cost and time bene its. TheJournal of Pediatrics, 130(5):808–813.
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Kumar, R. 2017. Sutures versus staplers for skin clo-sureofmidline incision in laparotomypatients andtheir outcome. International Journal of Surgeryand Medicine, 1.
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© International Journal of Research in Pharmaceutical Sciences 1357
Jemds.com Original Research Article
J. Evolution Med. Dent. Sci./eISSN- 2278-4802, pISSN- 2278-4748/ Vol. 9/ Issue 08/ Feb. 24, 2020 Page 6808
Usefulness of Modified Alvarado Score in Acute Appendicitis Incorporating Ultrasound
P. Prabhu1, D. Rajiv Raj2
1Department of Surgery, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamilnadu, India. 2Department of Surgery, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamilnadu, India.
ABS TRACT
BACKGROUND
Acute appendicitis affects human beings irrespective of age, nationality and region.
Acute appendicitis is the most common surgical cause of emergency laparotomy.
Considering the difficulties and challenges involved in accurate clinical diagnosis,
there is a need for a validated, objective protocol for enabling the diagnosis. This
study was carried out to validate the modified Alvarado score (MASS) and correlate
with ultrasound and post-operative histopathological examination.
METHODS
This cohort study was carried out among 100 patients who were suspected with
acute appendicitis. Upon clinical evaluation and ultrasound evaluation, Modified
Alvarado Score was computed, and patients were taken up for laparotomy/
laparoscopic surgery. The resected specimens were sent for histopathological
examination.
RESULTS
Majority of the participants had a score >7 (74%) of which 51 were males, 21 were
females and two were children. Ultrasound detected positive cases in 90% of the
participants, while acute appendicitis by histopathology was present in 54% of the
participants. There was a statistically significant correlation with Modified Alvarado
score (p<0.0001). Negative appendicectomy was prevalent in 21% of the
participants.
CONCLUSIONS
Modified Alvarado Scoring system is ideal for the diagnosis of acute appendicitis since
it is simple to use, easy to apply and relies only on history, clinical examination and
basic lab investigations.
KEY WORDS
Acute Appendicitis, Modified Alvarado Score, Laparotomy, Perforation
Corresponding Author:
Dr. D. Rajiv Raj,
Department of Surgery,
Sri Ramachandra Institute of Higher
Education and Research, Chennai,
Tamilnadu, India.
E-mail: drrajiv20012001@yahoo.com
DOI: 10.14260/jemds/2020/0000
Financial or Other Competing Interests:
None.
How to Cite This Article:
Prabhu P, Raj DR. Usefulness of modified
alvarado score in acute appendicitis
incorporating ultrasound. J. Evolution Med.
Dent. Sci. 2020;9 (08):0000-0000, DOI:
10.14260/jemds/2020/0000
Submission 18-12-2019, Peer Review 30-01-2020, Acceptance 05-02-2020, Published 00-02-2020.
Jemds.com Original Research Article
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BACK GRO UND
Acute appendicitis affects human beings irrespective of age,
nationality and region. In Asia and African countries the
incidence is a comparatively lower than those in the Americas
and majority of these could be attributed to the diet and
lifestyle patterns in these geographic areas. The incidence of
appendicitis peaks by 10 years of age and it declines in the
geriatric age group. It is highly prevalent in the adolescent age
group and in recent years the number of adults in presenting
with the acute appendicitis has increased to 6.3%.[1] several
factors have been attributed to the etiology of the acute
appendicitis. Among the most common demographic and
intrinsic factors, diet has been said to play a major role in
determining the incidence of acute appendicitis. Individuals
who live on a diet rich in dietary fiber in the form of cellulose
are usually immune from the disease but when they adopt life
style consisting of increase intake of processed food and
refined grains, the incidence rapidly raises.
The diagnosis of acute appendicitis is always being
challenging to the surgeons. Acute appendicitis is the most
common surgical cause of emergency laparotomy. The disease
often progresses to obstructive appendicitis which further
leads to perforation and is therefore associated with high rates
of morbidity and mortality. In order to combat this, the
surgeons are frequently forced to open up the abdomen during
emergency, instead of waiting for a definitive diagnosis. The
accuracy of clinical examination has been reported to range
from 71% to 91% depending on the experience of the
examiner. However weighing the risk and benefit of certain
complications like rupture of appendicitis and other dire
consequences, surgeons traditionally prefer to open up the
abdomen for acute appendicitis management, thereby
accepting a 20% rate of negative appendectomy and resulting
in removal of normal appendicitis.[2]
Considering the difficulties and challenges involved in
accurate clinical diagnosis there is a need for a validated,
objective protocol for enabling the diagnosis. Although there
are several radiological investigations like ultrasound, CT-Scan
and laparoscopy, there is always a need for non-invasive and
clinically valid method. One of the recently evolved systems of
diagnosis has been the Alvarado score which was described
and validated in adult surgical practices since 1986. [3] This
objective scoring system has a proven to reduce the negative
appendicitis rate to 0 to 5%.[4] The Alvarado score was
modified in recent times by M. Kalan, D. Talbat, WJ Cunliffe, A.
J. Rich. [5] This scoring system takes in to account variety of
symptom complexes including migratory right iliac fossa pain,
nausea, vomiting and rebound tenderness in the RIF. The
modification carried out by Kalan’s and its Cunliffe were mild
consisting of minor modifications. However the efficacy and
validity of the modified Alvarado scoring system has been
seldom explored. The thorough application and validation in
the general population will help in implementing the Alvarado
score as routine diagnostic tool in clinical practice thereby
minimizing the waiting period, and negative appendectomy
rates and also ensuring rapid clinical assessment of acute
appendectomy.
We wanted to estimate the frequency of acute appendicitis
in our tertiary care centre, validate the modified Alvarado
score (MASS) and correlate it with post-operative
histopathological report.
ME TH OD S
This prospective cohort study was carried out in the
Department of Surgery of our tertiary teaching institution for
a period of one year in 2011. All the patients admitted with a
suspicion of acute appendicitis namely right iliac fossa pain or
tenderness with or without fever during the study period were
taken up for the study. A total of 100 patients were included
for the study. Patients visiting the hospital with pain abdomen
and professionally diagnosed as acquired appendicitis with
willingness to undergo surgery were included in the study.
Exclusion Criteria
1. Diagnoses with pelvic pathology.
2. Appendicular mass.
3. Pregnant females.
4. Patient not willing for surgery.
Ethical Approval and Inform Consent
Approval was obtained from institutional ethic committee
prior to the commencement of the study. Each participant was
explained in detail about the study, and informed consent was
obtained prior to the commencement of data collection.
Data Collection
On admission, the patients were subjected to clinical
assessment, ultrasound and modified Alvarado score was
applied and the score was calculated and noted. (table 1)
Ultrasound was done to detect the presence of non-
compressible tubular, non-peristaltic, blind ending structure
in the right iliac fossa with a diameter >7 mm. Following a
work-up for the surgical intervention the surgery was carried
out on the general anaesthesia or spinal anaesthesia. In certain
cases laparoscopic appendectomy was also carried out. On
identifying the appendicitis it was assessed and resected and
the specimen was send for a histopathological examination.
The modified Alvarado score was also compared with the
histopathological report.
Sl. No. Alvarado Scoring System Symptom Score
1 Migratory RIF pain 1 2 Anorexia 1
3 Nausea and vomiting 1
4 Tenderness over RIF 2 5 Rebound tenderness in RIF 1
6 Fever 1
7 Leucocytosis 2 Total Score 9
Grading
<5 Normal
5-6 Mild 7-9 Acute
Table 1. Modified Alvarado Scoring[6]
Data Analysis
Data was entered and analyzed using SPSS Ver. 20 software.
The modified Alvarado score was computed as percentages.
The correlation with histopathological findings and
ultrasound findings carried out using chi square test. A p value
< 0.05 was consider statistically significant.
RES ULT S
This study was carried out among 100 patients admitted for
evaluation of various symptoms indicative of acute
Jemds.com Original Research Article
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appendicitis. Majority of the participants belonged to 21-30
years of age (39%) and were males (64%). Pain in the right
iliac fossa (RIF) was present in all the participants and RIF
tenderness was present in 94% of them. (table 2). Modified
Alvarado score was computed and presented in table 3.
Majority of the participants had a score >7 (74%) of which 51
were males, 21 were females and two were children. (table 3)
Sl. No. Characteristics Frequency Percentage
1
Age (in Years) ≤10 2 2.0
11-20 18 18.0
21-30 39 39.0 31-40 23 23.0
41-50 15 15.0
>50 3 3.0
2
Sex
Males 64 64.0
Females 36 36.0
3
Clinical Presentation*
Right Iliac Fossa pain 100 100.0
Anorexia 67 67.0 Nausea/Vomiting 78 78.0
Right Iliac Fossa Tenderness 94 94.0
Rebound Tenderness 60 60.0 Fever 70 70.0
Leukocytosis 70 70.0
Table 2. Background Characteristics of the Study Participants
*N will not tally to 100.
Sl. No. Modified Alvarado
Score Adults N=98 n (%) Children N= 2 n
(%) Males Females 1 <5 6 (6.1) 4 (4.1) - 2 5-6 7 (7.1)) 9 (9.2) -
3 7-9 51 (52.04) 21 (21.4) 2 (100)
Table 3. Findings of Modified Alvarado Score
Sl. No. Diagnostic Finding Frequency (N=100) %
1.
Ultrasonogram
Positive 90 90
Negative 10 10
2.
Histopathology
Lymphoid Hyperplasia 25 25
Acute Appendicitis 54 54 Acute Ulcerative 12 12
Acute Gangrenous 6 6
Acute Perforative 3 3
Table 4. Diagnostic Findings of Appendicitis
among the Study Participants
Sl. No.
Diagnostic Test
MAS Score N (%) Chi Square
Test p <5
N=10 5-6
N=16 >7
N=74
1 Ultrasonogram
Positive 9 (90) 10 (62.5) 71 (96) 155.228
0.006 (significant) Negative 1 (10) 6 (37.5) 3 (4)
2 Histopathology
Lymphoid Hyperplasia 10 (100) 7 (43.75) 4 (5.4) 146.275
0.0001 (significant) Acute appendicitis 0 (0) 9 (56.25) 70 (94.59)
Table 5. Association of MAS with Ultrasonogram and Histopathology
Sl. No. Negative Appendicectomy Frequency (N=21) (%) 1. Male 11 52.38
2. Female 10 47.62
3. Children 0 0
Table 6. Percentage of Negative Appendicectomy
Sl. No. MAS Score Frequency (N) Appendicitis Frequency (%)
1.
Score >7
Men 51 48 96 Women 23 20 90
2.
Score 5-6
Men 7 4 57.14
Women 9 5 55.55
Table 7. Validity of MASS
The diagnostic modalities used were ultrasound before the
surgery and histopathological examination after the surgery.
Ultrasound detected positive in 90% of the participants, while
acute appendicitis by histopathology was present in 54% of
the participants. (table 4). On comparing ultrasound and
histopathology findings with MAS score, there was a
statistically significant correlation between Modified Alvarado
score and the confirmatory tools, indicating validity of
Modified Alvarado Score in detecting acute appendicitis. The
association was statistically significant (p<0.0001). (table 5).
Negative appendicectomy was prevalent in 21% of the
participants, of which 11 belonged to males and 10 belonged
to females. (table 6) The sensitivity of MAS score when it is >7
was 96% in males and 90% in females. (table 7)
DI SCU S SI ON
Acute appendicitis remains a common abdominal emergency
throughout the world. The diagnosis of acute appendicitis
continues to be a challenge due to the variable presentation of
the disease and lack of reliable diagnostic test, despite several
technological advances in the radiological diagnosis. None of
the investigations like USG, CT scan conclusively diagnose
appendicitis. When only direct visualization and basic
haematological parameters provide a guide towards diagnosis,
laparotomy was considered the only choice, despite being
invasive in nature. With this background many eminent
surgeons and physicians have been adopting different scoring
systems in order to decrease negative appendicectomy.
Although there had been considerable advancements in
developing a diagnostic protocol for the diagnosis of acute
appendicitis over the past several decades, the percentage of
normal appendices reported in various series varies from 8 to
33%.[7,8] Therefore, the advent of clinical scoring system has to
an extent eased out the challenge of diagnosis. In the past few
years various scores have been developed to aid the diagnosis
of acute appendicitis. However, most of these are complex and
difficult to implement in the clinical situation. The Alvarado
score, is a simple scoring system that can be instituted easily.
The present study was undertaken to evaluate the usefulness
of Modified Alvarado scoring system in reducing the number
of negative appendicectomy and to evaluate the sensitivity of
MASS with ultrasound in the diagnosis of acute appendicitis.
The age group in which acute appendicitis occurred
commonly was between 11 and 40 years. It is clear that
incidence is less in younger and older age groups with peak
incidence in 2nd, 3rd and 4th decade. In the present series the
males outnumbered females in the ratio of 1.7:1. Pain in the
right iliac fossa was the most common presenting symptom
and has been observed in all the cases (100%) in the present
series. The classical shifting of pain from umbilical region to
RIF was seen in majority cases. Next common symptoms
observed were nausea/ vomiting in 78% of cases and anorexia
in 67% of cases. Fever was of low grade with corresponding
rise in pulse rate and was present in 70% of cases. Majority of
the patients presented within 24 hrs. after the onset of pain,
with most of them presenting between 12-24 hrs. of onset of
pain. On clinical examination, tenderness at McBurney’s point
was the commonest sign (94%). Rebound tenderness was
present in 60%. Abdominal rigidity in 8% was due to
perforated appendix or gangrenous appendix.
In the present study the Total Leukocyte Count was
increased in 70%. For assessment, the patients were
Jemds.com Original Research Article
J. Evolution Med. Dent. Sci./eISSN- 2278-4802, pISSN- 2278-4748/ Vol. 9/ Issue 08/ Feb. 24, 2020 Page 6811
categorized into 3 groups namely, male, female and children.
Out of 100 cases studied, 64 were male, 36 were female and 2
were children (<12 yrs). Majority (98%) of the participants
underwent laparoscopic Appendicectomy and remaining two
participants underwent open appendicectomy for non-
medical reasons. In this study, 79.6% of the males and 63.8%
of the females had a score of > 7-9. All the 2 children had score
>7-9. Acute appendicitis was present in 34% of the total study
participants. In our series a score of 7-9 using modified
Alvarado system had a total sensitivity of 94.59%. Our study
findings were consistent with other study findings.[9] When
compared with other study it is evident that Modified Alvarado
scoring system more sensitivity, thereby proving that it can be
used as a complementary method in diagnosing acute
appendicitis.
With regards to negative appendicectomy, increased
proportion (43.75%) of negative appendicectomy is noticed
for the Modified Alvarado Score 5-6 and significantly
decreased proportion (5.40%) negative appendicectomy is
noticed for the modified Alvarado score 7-9 (p value-0.0001).
In our series negative appendicectomy rate in females with
score 5-6 was 44.44 % and with score 7-9 was 8.69%. Men
with score 5-6 had negative appendicectomy rate of 42.85%
and with score 7-9 had negative appendicectomy rate of
3.92%. Hence in the overall females (27.8%) had more
negative appendicectomy rate compared to males (17.18%).
This may be justified by the fact that females are prone for
other diseases like pelvic inflammatory diseases, especially in
the reproductive age group. Since intra-abdominal infection in
females, particularly lower abdomen, can be quite challenging
in terms of diagnosis, it is difficult to differentiate acute
appendicitis from gynecological conditions like twisted
ovarian cyst and PID.
The modified Alvarado score >7 has got more sensitivity
(94.59%) and diagnostic accuracy for appendicitis. Those
patients who scored < 5 did not require subsequent
laparotomy, indicating the usefulness of the system in ruling
out acute appendicitis. This indicates that by particularly
adopting this system, negative laparotomies can be reduced by
a figure of 21%. While comparing USG with MASS score >7 has
more sensitivity (95.59%) thereby increasing diagnostic
accuracy (p value 0.006). Ultrasonography, in this study
detected 86% of cases of histologically proven cases of
appendicitis. This study showed ultrasound to have sensitivity
of 86%, specificity of 75% and positive predictive value of
about 86% (p value 0.0001). Ultrasound remains to be
operator dependent. This study shows along with clinical
examination and in doubtful cases to rule out other conditions
causing pain, ultrasound proves to be a valuable tool.
CONC LU S ION S
It is clear that incidence of acute appendicitis is less in younger
and older age groups with peak incidence in 2nd, 3rd and 4th
decade. Our study correlated the Modified Alvarado score with
the histopathological reports of the appendix and found that
there is 94% sensitivity. Modified Alvarado Scoring system is
ideal for the diagnosis of acute appendicitis since it is simple
to use, easy to apply and relies only on history, clinical
examination and basic lab investigations. It is cost-effective
and can be used by junior residents in all district general
hospitals with basic lab facilities. Modified Alvarado Score
complimented with ultrasound, increased the diagnostic
accuracy resulting in avoiding negative laparotomy. Based on
our study, it may be recommended that emergency
appendectomy can be carried out in all patients whose clinical
score is more than 7. Modified Alvarado scoring system
significantly reduces the number of negative laparotomies
without increasing overall rate of appendicular perforation.
REF ER ENC E S
[1] Lohar HP, Calcuttawala MAS, Nirhale DS, et al.
Epidemiological aspects of appendicitis in a rural set up.
Med J DY Patil Univ 2014;7 (6):753-7.
[2] John H, Neff U, Kelemen M. Appendicitis diagnosis today:
clinical and ultrasonic deductions. World J Surg 1993;17
(2):243-9.
[3] Jones PF. Suspected acute appendicitis: trends in
management over 30 years. Br J Surg 2001;88 (12):1570 -
7.
[4] Lee SL, Walsh AJ, Ho HS. Computed tomography and
Ultrasonography do not improve and may delay the
diagnosis and treatment of acute appendicitis. Arch Surg
2001;136 (5):556-61.
[5] Kakande I, Kavuma J, Kampala E. Alvarado Score. East Afr
Med J 1978;55 (4):172-6.
[6] Alvarado A. A practical score for the early diagnosis of
acute appendicitis. Ann Emerg Med 1986;15 (5):557-64.
[7] Fitz RH. Perforating inflammation of the veriform
appendix: with special reference to its early diagnosis and
treatment. Am J Med Sci 1886;92:321-46.
[8] Teicher I, Landa B, Cohen M, et al. Scoring system to aid in
diagnosis of appendicitis. Ann Surg 1983;198 (6):753-9.
[9] Kalan M, Rich AJ, Talbot D, et al. Evaluation of the modified
Alvarado score in the diagnosis of acute appendicitis: a
prospective study. Ann R Coll Surg Engl 1994;76 (6):418-
9.
Jemds.com Original Research Article
J Evolution Med Dent Sci / eISSN - 2278-4802, pISSN - 2278-4748 / Vol. 9 / Issue 44 / Nov. 02, 2020 Page 3310
Effectiveness of Foot Reflex Therapy in Post-Operative Pain among Patients Subjected to Major Abdominal Surgery
Poongodi Ramalingam1, Ramya Ramakrishnan2, Rajeswari Singaravelu3, Aruna Subramaniam4
1, 4 Department of Community Health Nursing, Sri Ramchandra College of Nursing, Sri Ramachandra Institute of Higher Education And Research (Du), Porur, Chennai, Tamil Nadu, India. 2Department of
General Surgery, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra Institute of Higher Education And Research (Du), Porur, Chennai, Tamil Nadu, India. 3Department of Obstetrics and
Gynaecological Nursing, Sri Ramchandra College of Nursing, Sri Ramachandra Institute of Higher Education and Research (Du), Porur, Chennai, Tamil Nadu, India.
ABS TRACT
BACKGROUND
Most patients experience post–operative pain and it is unavoidable. It is the duty of
the nurses to ensure that patients' pain is assessed and managed effectively when
they are at the hospital. Foot reflex therapy is one effective way nurses can adopt to
manage the patient with pain after surgery. We wanted to evaluate the effectiveness
of foot reflex therapy on post-operative pain in patients who are subjected to major
abdominal surgery.
METHODS
This is a descriptive randomized control study that was conducted at Sri
Ramachandra Medical College and Hospital, among 360 patients who underwent
major abdominal surgery. They were equally divided into two groups as control and
study groups and the results were analyzed statistically.
RESULTS
Majority of the patients in the study group showed a positive effect on pain control
during 4th and 5th [ (Mean: 1.27 with SD: 1.12) (Mean: 0.03 with SD: 0.32) at p < 0.001]
post-operative day following foot reflex therapy.
CONCLUSIONS
The existing pain and the post-operative pain can be managed by nurses, patients,
their care takers or families together, whenever appropriate, in a multidisciplinary
manner. Foot reflex therapy is one such alternative complementary therapy which
the nurses can adopt to implement the techniques independently.
KEY WORDS
Foot Reflex Therapy, Foot Reflexology, Alternative Medicine, Complementary
Therapy, Post-Operative Day (POD)
Corresponding Author:
Dr. Poongodi Ramalingam,
Sri Ramachandra College of Nursing,
Sri Ramachandra Institute of
Higher Education and Research
(DU), Porur, Chennai, Tamil Nadu,
India.
E-mail:
poongodimohan@sriramachandra.edu.in
DOI: 10.14260/jemds/2020/727
How to Cite This Article:
Ramalingam P, Ramakrishnan R.
Singaravelu R, et al Effectiveness of foot
reflex therapy in post-operative pain
among patients subjected to major
abdominal surgery. J Evolution Med Dent
Sci 2020;9(44):3310-3314, DOI:
10.14260/jemds/2020/727
Submission 29-07-2020, Peer Review 25-09-2020, Acceptance 01-10-2020, Published 02-11-2020.
Copyright © 2020 Poongodi Ramalingam
et al. This is an open access article
distributed under Creative Commons
Attribution License [Attribution 4.0
International (CC BY 4.0)]
Jemds.com Original Research Article
J Evolution Med Dent Sci / eISSN - 2278-4802, pISSN - 2278-4748 / Vol. 9 / Issue 44 / Nov. 02, 2020 Page 3311
BACK GRO UND
Pain is the first and most frequent complication following any
surgical procedure.1 It refers to the subjective physical
discomfort experienced due to tissue trauma by the patient
after a major abdominal surgery as measured using the Visual
Analog Scale (VAS) and reflected by physiological parameters
which includes pulse rate, respiratory rate, blood pressure and
oxygen saturation.2 Pain management in hospitals becomes a
major factor to attend especially after major surgeries as it
greatly influences the treatment outcome and it affects the
patients psychology which cause threat to their comfort.3
Experience of discomfort over a period of time hampers a
person’s self-care and role obligations that can impair the
quality of life.4 Pain can cause personal hardships and it is the
most common reason for physician consultation all over the
world.5 It is also a major symptom in various medical and
surgical conditions that significantly interferes with a person’s
quality of life.
The only management of pain which many people cannot
cope up is through surgical procedure. Pain when cannot be
managed adequately it will cost more for the patient, their
families and society.6 The common pain in the abdominal
surgery is the post-operative pain which is also a symptom of
warning.7 Analgesics and anaesthetic techniques are available
to control the post-operative pain. Still the prevalence rate of
pain after surgery is reported high.
Post-operative pain is very common and around 80 % of
the patients are reporting pain after surgery. Another study on
patients who underwent various surgeries like abdominal,
spinal and extremity surgery complained severe pain after the
surgical procedure.9 It was noted that most of the patients
expressed more pain during day 0, A similar study reported
that the percentage of postoperative pain experienced by
patients after abdominal surgery varied from 22 % to 67 %
and was severe to unbearable pain.10 Preoperative pain and
poorly controlled postoperative pain have been in high
association with development of chronic postsurgical pain.
One of the effective ways to manage pain is to administer
analgesics (NSAIDs or opioid analgesics). While pain relief may
sometimes be inadequate with the use of analgesics,
development and improvement of alternative interventions
became necessary for a more effective pain control
strategy.11,12 Foot reflex therapy, a modified form of
reflexology is an effective, acceptable and complementary
intervention.13 To find the impact on foot reflex therapy in
post-operative surgical pain control, there is very less data
available, thus this study focuses on determining the
effectiveness of foot reflex therapy on post-operative pain
following major abdominal surgeries.
ME TH OD S
This descriptive randomized control study was conducted at
the Department of General surgery, Sri Ramachandra Medical
College Hospital, Porur, Chennai during the time period Jan
2012 to Sep 2013. The target population of the study included
patients who underwent major abdominal surgery between
the age group 20 and 60 years. The sample comprised of 360
patients equally distributed among the control and study
groups. The sample size was determined by power analysis
and effect size. The patients who underwent abdominal
surgery were included in this study. Subjects were included
based on their willingness. Patients who had foot wounds,
burns infections, deep vein thrombosis, who had history of
removal of malignant tumour, who has underwent
laparoscopic abdominal surgery were not included in the
study. The investigator used Visual Numeric Pain Scale to
assess the pain in patients in study and the control groups.
Minimum score in Visual Numeric Pain Intensity Scale is 0 and
maximum score is 10. The pain intensity was classified for the
visual analogue scale is as follows: 0 – no pain, 1 to 3 – mild
pain, 4 to 6 – moderate pain and 7 to 10 – severe pain.
The pain scale was administered during the pre-
assessment and the post-assessment of foot reflex therapy
from 1st to 5th post-operative day. Foot reflex therapy was
provided by a foot reflex therapist for 30 minutes per day from
the 1st to 5th post-operative day and thereafter the procedures
has been carried out by the patient’s caregivers for a period of
21 days at their home.
Foot reflex therapy performance was classified into 3
categories. The total score range from 1 to 24. A score of one
was given for correct performance and zero for wrong
performance. The level of practice was grouped as follows: 71
to 100 % - satisfactory practice, 34 – 70 % - moderate
satisfactory practice and < 33 % is poor practice. Data was
collected in three phases and analysed statistically using
paired ‘t’ test.
RES ULT S
The study was conducted among 360 patients who underwent
major abdominal surgery under general anaesthesia. They
were divided into two groups of 180 each as study group and
control group. The major abdominal surgeries that were
included in this study are inguinal hernia (37.44 % in study
group and 40 % in control group), incisional hernia (30.55 %
in study group and 33.33 % in control group), umbilical hernia
(16.66 % in study group and 19.46 % in control group),
appendicectomy (5.56 % in study group and 1.66 % in control
group) and cholecystectomy (9.46 % in study group and 5.55
% in control group) [Figure 1]
Hypertension was the most commonly existing comorbid
condition in this study followed by diabetes mellitus.
Hypothyroidism and asthma were also observed in a few
patients. A majority of the patients in both the groups did not
have any existing comorbid conditions. Foot reflex therapy
was given to the patients in the study group and their pre and
post-test pain scores were assessed. The mean pain scores in
the study group and control group during the 1st and 5th post-
operative day is 6.23 to 0.03 and 7.01 to 1.31 respectively.
On day 1 majority of the samples, 84 (46.7 %) in the study
group and 139 (41.68 %) in the control group had severe pain.
92 (51.1 %) in the study and 40 (56.66 %) in the control group
had moderate level of pain. 4 (2.2 %) in the study and 1 (0.66
%) in the control had reported mild pain. All of them reported
pain during pre-test. The p value indicated the homogeneity
between the group. During post-test majority of the study
group samples 135 (75 %) reported moderate pain whereas in
the control group 117 (65 %) of them reported severe pain.
Jemds.com Original Research Article
J Evolution Med Dent Sci / eISSN - 2278-4802, pISSN - 2278-4748 / Vol. 9 / Issue 44 / Nov. 02, 2020 Page 3312
Duration of
the Study Mean SD
Mean
Difference
Paired t
Value
(P-
Value)
Day 1 Pre-test 6.23 1.36
0.28 5.571 0.000*** Post-test 4.05 2.30
Day 2 Pre-test 5.87 1.11
2.51 0.45 0.000*** Post-test 3.36 1.51
Day 3 Pre-test 2.88 1.42
1.16 8.88 0.000*** Post-test 1.72 1.25
Day 4 Pre-test 3.33 1.53
2.05 8.45 0.000*** Post-test 1.27 1.12
Day 5 Pre-test 0.66 0.79
0.62 11.15 0.000*** Post-test 0.03 0.32
Table 1. Comparison of Day 1 to 5, Mean Score of Pain
among Patients in the Study Group
***p < 0.001, n = 180
Duration of
the Study Mean SD
Mean
Difference
Paired t
Value
(P-
Value)
Day 1 Pre-test 7.01 1.04
0.29 3.163 0.000*** Post-test 6.72 1.42
Day 2 Pre-test 6.18 0.92
0.61 6.82 0.000*** Post-test 5.57 1.49
Day 3 Pre-test 4.41 1.49
0.5 3.936 0.000*** Post-test 3.92 1.86
Day 4 Pre-test 3.86 1.59
0.7 5.657 0.000*** Post-test 3.16 1.74
Day 5 Pre-test 1.69 1.68
0.38 3.127 0.000*** Post-test 1.31 1.58
Table 2. Comparison of Day 1 to 5, Mean Score of Pain
among Patients in the Control Group
*** P < 0.001, n = 180
Figure 1. The Total Percentage Distribution-Type of Surgery (N = 360)
Figure 2. Level of Pain in the Pre-Assessment Day 1
in the Student of Control Group (N = 360)
Figure 3. Level of Pain in the Post Assessment Day 5
in the Study and Control Groups (N = 360)
The level of severe pain had reduced 28.88 % in the study
group whereas in the control group, the level of reduction was
only 12.22 %
On day 2, 64 (35.6 %) in the study group, and 70 (38.9 %)
in the control group samples reported severe pain during pre-
test. Majority of the samples 91 (50.6 %) in the study and 119
(66.1 %) in the control group reported moderate pain during
post-test. The level of severity of pain was reduced in 34.5 %
in the study group whereas in the control group the level of
reduction was only 13.9 %.
On day 3, in pre-test none of them reported severe pain in
the study group whereas in the control group, 13 (7.3 %) had
severe pain and during post-test in the study group none of
them reported severe pain and majority of the samples, 130
(72.2 %) reported mild level of pain whereas in the control
group, 12 (6.7 %) of them had severe and 98 (54.7 %) of them
had mild pain.
On day 4, majority of the samples 88 (48.9 %) in the study
group and 107 (60.1 %) control group reported mild pain
whereas in the post-test 116 (64.4 %) in the study group and
74 (41.6 %) in the control group reported mild pain and
majority of the samples, 58 (32.2 %) shifted to no pain in the
study group whereas in control only 13 (7.3 %) had a change.
On day 5, 92 (51.1 %) of the study group during pre-test, and the control group 59 (33.1 %) were reported no pain and 88 (48.9 %) in the study and 77 (43.1 %) in the control had mild pain. During post-test in study group 146 (81.1 %) had no pain and 30 (16.6 %) were in mild pain whereas in the control group 32 (17.8 %) were with moderate and 65 (36.11 %) reported mild pain.
The study findings conclude that patients who received foot reflex therapy in the post-operative period showed better pain recovery than patients who did not receive the therapy. [(Mean: 1.27 with SD: 1.12) (Mean: 0.03 with SD: 0.32) at p < 0.001].
DI SCU S SI ON
Both by patient and physician, pain is the most undesired
symptom in the post-operative period.4 Poorly controlled
post-operative pain may affect the patient’s psychological,
social and mental health. It also mainly reduces the quality of
life during and after the surgery. This can lead to other
physiological disturbances like impaired respiration, sleep
disturbances and loss of appetite. The discharge of the patient
37.44
30.55
16.66
5.56
9.46
40
33.33
19.46
1.665.55
05
1015202530354045
Pe
rce
nta
ge
Study Group Control Group
Jemds.com Original Research Article
J Evolution Med Dent Sci / eISSN - 2278-4802, pISSN - 2278-4748 / Vol. 9 / Issue 44 / Nov. 02, 2020 Page 3313
is delayed when the pain is not controlled on time after the
surgery, which in turn impacts the cost of the healthcare,
alleviation of negative pain and loss of productivity of results.
This has become a big challenge for healthcare providers
which is one of the important roles in controlling the
postoperative pain by managing both pharmacological and
non-pharmacological pain-relieving interventions.
Uncontrolled pain can lead to other serious health problems
like cardiac dysrhythmias, atelectasis, pneumonia and
sometimes sensory abnormalities also.14 This leads to the need
for the development of complementary therapy in alleviating
post-operative pain.
Several studies on complementary therapies have proven
to improve the medical treatment which augment the comfort
of the patient. Soothing music, relaxing on own by different
methods, touch therapy, reflexology therapies, plant based
medications and yoga are other alternative treatment.15 Foot
reflexology was chosen as an alternative nursing intervention
in this study. Earlier studies were performed to investigate the
effect of reflexes on postoperative pain in cancer patients and
none of the studies were on patients undergoing major
abdominal surgery for benign conditions / diseases.
The Gate theory, serotonin hypothesis and the restorative-
sleep hypothesis16 are evident of the analgesic effects of
reflexology on post-operative pain. Current study also
revealed that a high percentage of severe pain was observed
during the 3rd and 4th post-operative days. It was also noticed
that the level of knowledge on usage of complementary
medical practise and alternative treatment among the patients
and care givers is low and 67 % of them were unaware about
complementary and alternative medicine use to control post-
operative pain. The outcome of the present study concluded
that postoperative pain is very common in post-surgical
condition and available managements are difficult to be
continued owing to the drug side effects.
Another study evaluated the benefit of massage therapy in
improving peri-operative patient related outcomes, it revealed
significant reduction of VAS scores for pain from 5.3 to 2.9 (n
= 79, p < 0.0001) and also an improved well-being from 5.2 to
6.7 (n = 69, p < 0.0001).17 One of the study examined the
effectiveness of massage of hand in relation to pain, feeling and
providing nursing care among 45 post-operative patients at
surgical ward. Pain was assessed through visual analogue
scale. The nursing support and measurement of physiological
conditions was evaluated. The study findings showed a
significant pain relief (t = 4.04, p = 0.0001), improvement in
feeling and an increase in skin temperature.18
The study was conducted to evaluate the
neurophysiological effect on different types of body massage
in healthy adults in support to functional magnetic resonance
imaging methods. The outcome showed that the massage
treatment activates the subgenual and posterior cingulate
cortices which in turn increases the oxygen level of blood
during the cognitive task performances. The results showed
light on applying these new interventions might improve to
plan new targets for managing pain among healthy
individuals.19 Another study conducted to review the effect of
reflexology on pain and outcomes of the labour in 88 primi
paras mothers. In the reflexology group, there was a significant
difference between the Pain Rating Index (PRI) before and
after the 4 stages of intervention (p < 0.001). Thus, the study
concluded reflexology can decrease the labour pain and also it
is a safe technique and it can be replaced as an alternative for
pharmacological methods to control the pain.20 The findings of
this current study also lines with the outcomes of those in the
previous studies. The patients showed a significant change in
the mean pain scores from 4.05 in the 1st post-operative day to
1.27 and 0.03 in the 4th and 5th post-operative days
respectively. The pain intensity also reduced significantly in
the study group in the 4th and 5th post-operative days to mild
or no pain from severe pain in the 1st post-operative day when
compared to the control group following the massage. Hence
foot reflex therapy can be used as an adjuvant therapy to
relieve pain in post-operative patients.
Another study was performed among stomach cancer
patients which investigated the foot reflex treatment and
management as adjuvant therapy to alleviate pain and
reduction of anxiety in patients with cancer and also
supported to the management of postoperative pain in cancer
patients.21 Thus nurses play an important role in improving
the patient’s health and post-operative recovery as they come
in close line of contact with the patients. Foot reflex therapy
can be a very good alternative complementary therapy in this
accord which the nurses can offer to the patients apart from
the administration of regular analgesics and other pain-
relieving medications.
CONC LU S I ON S
Postoperative pain was reduced in patients who underwent
abdominal surgery, upon treatment with foot reflex therapy.
Those who received foot reflex therapy for five days post
operatively and further continued the therapy being given by
patient’s care giver at home have produced a more significant
positive effect on pain. Foot reflex therapy is an effective
therapy to control acute post-operative pain and thereby
improves the quality of life of patients. More specific studies
should be conducted in the future about the effectiveness of
foot reflex therapy in various other parameters and
comparative studies can be done among types of surgery and
anaesthesia.
Data sharing statement provided by the authors is available with the
full text of this article at jemds.com.
Financial or other competing interests: None.
Disclosure forms provided by the authors are available with the full
text of this article at jemds.com.
REF ER ENC E S
[1] Majuta LA, Longo G, Fealk MN, et al. Orthopedic surgery
and bone fracture pain are both significantly attenuated
by sustained blockade of nerve growth factor. Pain
2015;156(1):157-65.
[2] Vander Velpen GC, Shimi SM, Cuschieri A. Outcome after
cholecystectomy for symptomatic gall stone disease and
effect of surgical access: laparoscopic v open approach.
Gut 1993;34(10):1448-51.
[3] McCabe C. Effective pain management in patients in
hospital. Nurs Stand 2017;31(29):42-6.
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J Evolution Med Dent Sci / eISSN - 2278-4802, pISSN - 2278-4748 / Vol. 9 / Issue 44 / Nov. 02, 2020 Page 3314
[4] Chu YF, Sun J, Wu X, et al. Antioxidant and
antiproliferative activities of common vegetables. J Agric
Food Chem 2002;50(23):6910-6.
[5] Turk DC, Dworkin RH. What should be the core outcomes
in chronic pain clinical trials? Arthritis Res Ther
2004;6(4):151-4.
[6] Brennan F, Carr DB, Cousins M. Pain management: a
fundamental human right. Anesth Analg
2007;105(1):205-21.
[7] Power I. Recent advances in postoperative pain therapy.
Br J Anaesth 2005;95(1):43-51.
[8] Apfelbaum JL, Chen C, Mehta SS, et al. Postoperative pain
experience: results from a national survey suggest
postoperative pain continues to be undermanaged.
Anesth Analg 2003;97(2):534-40.
[9] Sommer M, de Rijke JM, van Kleef M, et al. The prevalence
of postoperative pain in a sample of 1490 surgical
inpatients. Eur J Anaesthesiol 2008;25(4):267-74.
[10] Vallano A, Aguilera C, Arnau JM, et al. Management of
postoperative pain in abdominal surgery in Spain. A
multicentre drug utilization study. Br J Clin Pharmacol
1999;47(6):667-73.
[11] Rambod M, Sharif F, Pourali-Mohammadi N, et al.
Evaluation of the effect of Benson's relaxation technique
on pain and quality of life of haemodialysis patients: a
randomized controlled trial. Int J Nurs Stud
2014;51(7):964-73.
[12] Rambod M, Pasyar N, Sharif F, et al. The effect of
relaxation technique on physical activity of hemodialysis
patients. Iran Journal of Nursing 2014;27(90):22-32.
[13] Ali A, Rosenberger L, Weiss TR, et al. Massage therapy and
quality of life in osteoarthritis of the knee: a qualitative
study. Pain Med 2017;18(6):1168-75.
[14] Black JM, Hawks JH. Medical-surgical nursing. Elsevier
Saunders 2005.
[15] Rodgers A, Walker N, Schug S, et al. Reduction of
postoperative mortality and morbidity with epidural or
spinal anaesthesia: results from overview of randomised
trials. BMJ 2000;321(7275):1493.
[16] Smith TL, Litvack JR, Hwang PH, et al. Determinants of
outcomes of sinus surgery: a multi-institutional
prospective cohort study. Otolaryngol Head Neck Surg
2010;142(1):55-63.
[17] Sunshine W, Field TM, Quintino O, et al. Fibromyalgia
benefits from massage therapy and transcutaneous
electrical stimulation. J Clin Rheumatol 1996;2(1):18-22.
[18] Attias S, Schiff E. P02. 38. Effectiveness of reflexology in
improving perioperative patient centered outcomes: a
comparative effectiveness study. BMC Complementary
and Alternative Medicine 2012;12(S1):P94.
[19] Embong NH, Soh YC, Ming LC, et al. Revisiting reflexology:
concept, evidence, current practice, and practitioner
training. J Tradit Complement Med 2015;5(4):197-206.
[20] Sliz D, Smith A, Wiebking C, et al. Neural correlates of a
single-session massage treatment. Brain Imaging Behav
2012;6(1):77-87.
[21] Valiani M, Shiran E, Kianpour M, et al. Reviewing the effect
of reflexology on the pain and certain features and
outcomes of the labor on the primiparous women. Iranian
J Nurs Midwifery Res 2010;15(Suppl 1):302-10.
See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/343930818
Carcinosarcoma of the Breast - A Rare Presentation
Article · August 2020
DOI: 10.18535/jmscr/v8i8.43
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JMSCR Vol||08||Issue||08||Page 250-254||August 2020
Case Report
Carcinosarcoma of the Breast - A Rare Presentation
Authors
Aniruddha Mundhada1, Lawrence DCruze
2, Sandhya Sundaram
3, D. Pratiba
4,
Ramya Ramakrishnan5, Bhawna Dev
6
1Resident, Department of Pathology, Sri Ramachandra Medical College and RI, Porur, Chennai, India-6001162
2,4Professor, Department of Pathology, Sri Ramachandra Medical College and RI, Porur, Chennai, India-6001163
3Associate Professor, Department of Pathology, Sri Ramachandra Medical College and RI, Porur, Chennai, India-
6001164 5Professor, Department of General Surgery, Sri Ramachandra Medical College and RI, Porur, Chennai, India-600116
6Professor, Department of Radiology, Sri Ramachandra Medical College and RI, Porur, Chennai, India-600116
*Corresponding Author
Sandhya Sundaram
Abstract
Metaplastic carcinoma of the breast with mesenchymal differentiation (MCMD), previously known as
carcinosarcoma, has been recently designated as a subtype of metaplastic breast carcinoma. It is a very
rare and aggressive tumor that accounts for 0.08%–0.2% of all breast cancers reported in the literature.
Histologically, MCMD is characterized by a biphasic pattern of malignant epithelial and sarcomatous
components without evidence of a transition zone between the two elements. We herein describe a unique
case of metaplastic carcinoma of the breast in a young lady, which on core biopsy showed features of a
poorly differentiated malignancy. The differential diagnosis was given as poorly differentiated carcinoma
and high-grade lymphoma. IHC was suggested to confirm the lineage. The mass was large and rapidly
growing and showing signs of impending rupture. Patient therefore underwent an elective modified radical
mastectomy with a very close margin confirmed on frozen sections and final diagnosis after extensive
sampling as triple negative MCMD. There was involvement of ipsilateral axillary nodes. These tumors
present with distal metastases, and have earlier local recurrence and poor prognosis compared with
classic invasive breast cancer. Because of the rarity of MBC, the optimal treatment has not been well
defined. Surgery is the main curative treatment modality since MBC has shown a suboptimal response to
standard chemotherapy.
Keywords: metaplastic breast carcinoma, carcinosarcoma, differentiation, mesenchymal.
Introduction
Metaplastic carcinoma of the breast with
mesenchymal differentiation (MCMD) is
exceptionally rare [1]
that has been recently
classified as a subtype of metaplastic breast
carcinoma (MCB) by WHO. The molecular
pathogenesis of MCMD is poorly understood, but it
has not been proven unanimously that both
epithelial and mesenchymal components originate
from a single cell clone [2,14]
. Risk factors for this
pathology are unknown. We herein describe a
unique case of MCMD of the breast in a young
patient who presented with a large boss elated,
rapidly growing mass and signs of impending
rupture.
http://jmscr.igmpublication.org/home/
ISSN (e)-2347-176x ISSN (p) 2455-0450
DOI: https://dx.doi.org/10.18535/jmscr/v8i8.43
Aniruddha Mundhada et al JMSCR Volume 08 Issue 08 August 2020 Page 251
JMSCR Vol||08||Issue||08||Page 250-254||August 2020
Case Presentation
A 35-year-old woman presented with chief
complaint of a large rapidly growing bosselated left
breast mass since six-months. She revealed that she
had first noticed a small lump one year ago which
for the last 6 months has rapidly increased in size.
Physical examination revealed a giant bosselated
left breast mass measuring approximately 20x18
cms (Fig. 1). There were 3x2cm firm palpable
ipsilateral axillary, supraclavicular
lymphadenopathy on palpation. Nipple areolar
complex appears stretched with no peau d’orange”.
Overlying skin was pinchable, lump was mobile and
not attached to the chest wall. Right breast and
axilla were normal. BIRADS score was 4B by sono-
mammogram. Clinically, the tumor was diagnosed
as malignant phyllodes. Contralateral breast and
axilla were normal. Her past medical history was
unremarkable and she had no family history of
breast or ovarian cancer. A tru-cut needle biopsy
showed features of a poorly differentiated
malignancy and immunohistochemistry was
suggested for confirmation. As the mass was rapidly
increasing with signs of impending rupture, a left
modified radical mastectomy with axillary node
dissection was performed after a thorough
preoperative evaluation. Mediastinal and hilar
thoracic lymph nodes were negative by preoperative
PET–CT. Gross examination revealed a grey white
solid irregular mass with fleshy areas. The surgical
margin was very close (0.2cm) from the tumor (Fig.
2). Ipsilateral axillary lymph nodes were involved
by tumor. Histological examination was suggestive
of metaplastic breast carcinoma with mesenchymal
and high-grade epithelial components. There was
moderate cytologic atypia and brisk mitosis.
Interspersed areas of necrosis and hemorrhage were
noted (Fig. 3). Surgical margins very close to the
tumor. Extensive sampling was done to represent
the entire tumor to rule out malignant phyllodes.
However, glandular components entrapped within
the stromal elements were not seen and there was a
high proliferative index. Also, the clinical history of
rapid increase in mass was against the diagnosis of
phyllodes tumor. This ruled out phyllodes tumor
which was thought of as a differential initially. The
tumor conferred to pT3 pN2aM0. Tumor cells were
triple negative (ER, PR and HER-2(Fig. 5).
Vimentin, EGFR was positive and Ki67 LI was
approximately 60%. PAN CK was positive in the
epithelial component and P63 was negative. IHC for
AR, GATA3 were negative. The patient received
adjuvant chemotherapy consisting of four cycles of
Doxorubicin/cyclophosphamide followed by four
cycles of Docetaxel plus trastuzumab and
radiotherapy to the chest wall and the axilla. She is
asymptomatic and free of disease, five months after
surgery with follow-ups scheduled every 6 months.
Fig 1- Left Breast lump of size 20x18cm occupying
the whole of left breast with stretched out skin and
slight boss elated surface
.
Fig 2- Sonographic features show a large
heterogeneous cystic-solid lesion
Aniruddha Mundhada et al JMSCR Volume 08 Issue 08 August 2020 Page 252
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Fig 3- Gross appearance of specimen showing large
variegated mass
Fig 4 - Microscopic examination showing poorly
differentiated carcinoma with sarcomatoid
differentiation
Fig 5. Immunohistochemistry: (a)High Ki67
labelling index (b)Pan-Ck Positive
Discussion
According to epidemiologists from the American
Cancer Society, 279100 new cases of breast cancer
will occur in 2020 in the USA.[1]
MBC is rare,
accounting for 0.25%–1% of breast cancers
diagnosed annually, or approximately 700–2790
new cases.[2,3]
Meta-plastic breast cancer is
classified as a distinct pathologic entity by the WHO
and characterized by mixed epithelial and
sarcomatoid histology.[4]
In our institute, 356 cases of Invasive Mammary
carcinomas have been reported in SRMC & RI, with
only 2 cases of Metaplastic Carcinoma, in the last
year. Carcinosarcoma / metaplastic breast carcinoma
is a sarcomatoid metaplasia of malignant epithelial
cells. It is a rare, locally aggressive disease
comprising only 0.08-0.2% of all malignant breast
lesions.[5]
The cell of origin is unknown, but the hypothesis is
that myoepithelial cells originate from a single stem
cell like spindle-cells. The carcinomas have been
reported to develop from existing cystosarcoma
phyllodes, fibroadenoma and cystic backgrounds. A
rapidly growing breast mass is the most common
manifestation. [2,14]
Accurate diagnosis can be clinched from the
histopathology images. These entities are usually
triple negative and lymph node involvement is
less.[6,8,13]
Histology demonstrates Sarcomatous
component which resembles fibromatosis; the
epithelial component can reveal osteoclast-like giant
cells too. The tumors are often cystic structures with
lining composed of squamous cell carcinoma.
Different imaging methods can be used to diagnose
MBC. Magnetic resonance imaging (MRI) features
show a T2 hyperintense, irregular mass that may
show spiculated margins. The mass is irregular
and/or spiculated margins on mammograms.
Sonographically a heterogeneous mass with both
solid and cystic components present with complex
echogenicity is appreciated. [5,9]
Treatment in many reported cases was usually
surgical resection with sentinel lymph node biopsy
or axillary node dissection, followed by
postoperative chemotherapy and radiation therapy.
The treatment protocol is not standardized due to
low incidence and variability in presentation.[6]
Main modalities are surgery and chemotherapy with
radiation; however, traditional treatment regimens
used for IDC have shown variable responses in
MBC.[7,10,11]
Mastectomy is usually required due to
the large size of tumor at presentation, but breast
Aniruddha Mundhada et al JMSCR Volume 08 Issue 08 August 2020 Page 253
JMSCR Vol||08||Issue||08||Page 250-254||August 2020
conservation therapy shows no significant change in
disease free survival when compared with
mastectomy.[10]
The tumor has been shown to be
resistant to conventional breast cancer therapy. The
most common sites of metastatic disease are the
lungs and pleura[15]
, whereas brain, hepatic and
skeletal metastases are uncommon.[16]
Due to the
nature of MBCs, a multidisciplinary approach
should always be considered. Participation of
patients in clinical trials incorporating agents
targeting PI3K and EMT pathways should be
considered.[12,17]
Intensive follow-up of patients
with MBC is mandatory due to the aggressive
clinical course of the tumor.
Conclusions
Because of the rarity of the tumor, there are not
enough data and standard guidelines for the optimal
treatment and information about management and
prognosis is based on small retrospective studies
rather than randomized trials. Surgery is the main
curative approach. An intensive follow-up is
required for the detection of an early recurrence of
the disease.
Declaration of Conflicting interests- Authors
report no conflicting interests
Ethical Approval- Not required from the institution
Funding- None
Consent for Publication- All authors hereby
consent for publication of this case report.
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Entity. Nepalese Journal of Cancer, 3(1),
pp.57-59.
14. Ilhan, E., Vardar, E., Ozkok, G., Sezgin, A.,
Sahin, S., Teker, K., Postaci, H. and
Yildirim, M., 2010. A rare tumour of the
breast: carcinosarcoma. Journal of clinical
medicine research, 2(2), pp.96-98.
15. Esbah, O., Turkoz, F.P., Turker, I., Durnali,
A., Ekinci, A.S., Bal, O., Sonmez, O.U.,
Budakoglu, B., Arslan, U.Y. and Oksuzoglu,
B., 2012. Metaplastic breast carcinoma: case
series and review of the literature. Asian
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pp.4645-4649.
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Kuo, Y.L., 2015. Metaplastic breast
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A case report. Medicine, 94(17).
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Helgason, T., Karp, D.D., Meric-Bernstam,
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List of Abbreviations
MBC- Metaplastic breast carcinoma, MCMD-
Metaplastic carcinoma of the breast with
mesenchymal differentiation, MRI- Magnetic
resonance imaging, IDC- Invasive ductal carcinoma,
ER- Estrogen receptor, PR- Progesterone receptor,
WHO- World Health Organisation
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Saudi J Kidney Dis Transpl 2020;31(1):100-108© 2020 Saudi Center for Organ Transplantation
Original Article
Effects of Graded Exercise Training on Functional Capacity, MuscleStrength, and Fatigue after Renal Transplantation: A Randomized
Controlled Trial
ThillaiGovindarajan SenthilKumar1, Periyasamy Soundararajan2, Arun G. Maiya3, Annamalai Ravi4
1Faculty of Physiotherapy, Sri Ramachandra Institute of Higher Education and Research (Deemedto be University), 2Department of Nephrology, Saveetha Medical College and Hospital, Chennai,Tamil Nadu, 3Department of Physiotherapy, School of Allied Health Sciences, Manipal Academyof Higher Education, Manipal, Karnataka, 4Department of General Surgery, Sri Ramachandra Institute
of Higher Education and Research (Deemed to be University), Chennai, Tamil Nadu, India
ABSTRACT. Successful renal transplantation (RT) recipients suffer residual muscle weakness,fatigue, and low functional capacity. A safe, feasible, structured, early graded exercise training toimprove functional capacity, muscle strength, and fatigue is the need of the hour. The aim of thestudy is to assess the effectiveness of graded exercise training on the functional capacity, musclestrength, and fatigue after RT. It is a randomized controlled trial conducted at a tertiary carehospital from January 2012 to December 2016. This trial included 104 consented, stable renaltransplant recipients without cardiopulmonary/neuromuscular impairment. They received eitherroutine care (51) or graded exercise training (53) for 12 weeks after randomization. Thefunctional capacity, isometric quadriceps muscle strength, and fatigue score were measured atbaseline, six, and 12 weeks later to induction. The outcomes of the study and control groups wereanalyzed using the t-test, Wilcoxon signed-rank test, ANOVA, and Pearson’s correlation. For allanalyses, P <0.05 was fixed acceptable. The functional capacity improved by 147 and 255 m, themuscle strength by 6.35 and 9.27 kg, and fatigue score by 0.784 and 1.781 in the control and thestudy group (SG), respectively, significantly more in the SG. Functional capacity had a positiveand negative correlation with muscle strength and fatigue, respectively (P <0.05). The gradedexercise training significantly improved the functional capacity, fatigue levels, and musclestrength after RT.
Correspondence to:
Mr. ThillaiGovindarajan SenthilKumar,Faculty of Physiotherapy, Sri RamachandraMedical Institute of Higher Education andResearch (Deemed to be University),Chennai, Tamil Nadu, India.E-mail: senthilkumar.t@sriramachandra.edu.in
Introduction
Renal transplantation (RT) has improvedpatient survival in end-stage renal disease.1
However, even after successful RT patientssuffer from reduced muscle strength, fatigue,and myopathy.2-4 The lowered physical fitness,effort tolerance, and muscle strength with
Saudi Journalof Kidney Diseases
and Transplantation
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fatigue affect the functional capacity. RT reci-pients also are noted to have hypoactivelifestyle, physical fatigue, and impaired peakexercise performance similar to other solidorgan transplants, implicating the need for thestructured rehabilitation program.5-8
Many recommendations support regular phy-sical activity and exercise along with titrationof medications to improve functional abilitiesand to overcome the barriers of rehabili-tation.9-14 The regulation of intensity andprogression of exercises remains a challengedue to the hypertensive, nonlinear responsesand muscle weakness.15,16 The follow-up isgood in the early phase and hence initiatingearly, graded exercise training would be afeasible and effective way to ameliorate thephysical impairments.9,14,17
Subjects and Methods
This randomized controlled trial with blin-ding of outcome measurement was done on104 Post RT recipients [control group (CG) -51 and study group (SG) - 53] during January2012 and December 2016 with institutional
ethics committee (IEC-NI/11/DEC26/83)approval and the retrospective registrationwith CTRI (CTRI/2017/11/010601). RT reci-pients with vitals instability, surgical compli-cations, acute renal rejection, and pre-existingneuromuscular deficits were excluded from thestudy. The patients with age (18–65 years),both genders, willing to participate were allo-cated to either control or SG by restrictedrandom sampling (unequal block randomi-zation, eight to 10 in each block, Figure 1). Allthe participants received standardized medicalcare as per their requirements including induc-tion therapy, immune suppression, and pulsesteroids.
A structured, graded exercise training pro-tocol after RT (SET-adjuvant RT) was framedas per the ACSM guidelines18 and expertopinion. The contents of training protocol werevalidated and found to be clinically safe. TheCG received routine hospital care, includingchest physiotherapy, breathing exercise, incen-tive spirometer training, and graded ambula-tion as per patient tolerance. The SG gottrained in three phases (Table 1). The phase Itraining included graded ambulation, strength
Figure 1. Consort flowchart.
Effects of graded exercise after renal transplantation 101
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training with the use of gravity and own bodyweight. The study group was assessed for 10repetitions maximum (RM) of the musclequadriceps, a key muscle for ambulation.Phases II and III had exercises involvingresistance training (50% to 80% of 10 RM),flexibility exercises and aerobic conditioning(walking/bicycle pedalling) as per rating ofperceived exertion (RPE) on the Borg scale ingraded manner. The exercise intensity wasprogressively increased with RPE (range 6–9)during 1st week to RPE (range 9–13) during10–12 weeks. Resistance was increased ingraded manner at rate of 5% to 10% of theprevious load as per tolerance every weekduring follow-up. The resisted exercise wasavoided in the fistula/cannulated extremity.The SG patients underwent supervised, gradedexercise training twice a week with phone callreminders. The study participants did thetrained exercises at home for two more daysand details were noted in the exercise log. Theexercise log was maintained by the patient/caretaker to improve the adherence to pro-tocol. The outcomes were measured at three-time points (T1-Baseline - before discharge,T2 - at the end of 6 weeks, T3 - at the end of12 weeks after allocation).
Outcome measures The functional capacity was quantified by thedistance walked in the six-minute walk test, asper the American Thoracic Society Guidelines.19
It is a safe, widely used self-paced submaxi-mal exercise with the ability to predict morta-lity and the clinical outcomes after trans-plantation.20 The isometric quadriceps musclestrength (IQMS) was measured with standard-dized dynamometer. The fatigue was measuredwith fatigue severity score, used in manyneuro-musculoskeletal dysfunctions and alsoin RT patients.
Data Analysis
The data were analyzed using the StatisticalPackage for the Social Sciences (SPSS) statis-tical software version 15.1 (SPSS Inc, Chicago,IL, USA) with 0.05 as the level of confidence.The normality of data was verified usingShapiro–Wilk test. The within and between-group comparison of the functional capacitywas analyzed with paired and unpaired t-test,respectively. The IQMS and fatigue levels werecompared between the groups using Mann–Whitney U-test. The test of repeated measuresof ANOVA with Bonferroni correction was
Table 1. Description of exercises in the control and study group.Control group Study group
Phase I (From randomization up to 3 weeks )
Chest physiotherapy, breathing exercises, use ofincentive spirometer, limb movements, ambulationas tolerated by the patient
Also received graded gravitational stress and limbleverage increased for strengthening, RPE basedambulation in progression( 6–11); resistance up to50% of 10 RM
Phase II ( 3 to 6 weeks after training)
Home exercises with self-paced walking; gradualparticipation in ADL
Graded aerobic exercises (Walking/treadmillwalk/bicycle ergometer training); resisted exer-cises - 50–65 of 10 RM% flexibility exercises;RPE-guided progression in exercise volume (RPE:9–14)
Phase III (6-12 weeks after training)
Home-based increase in activities; self-pacedwalking as tolerated by the patient
Progressive, graded aerobic exercises (Walking/treadmill walk/bicycle ergometer training); resis-ted exercises: 65–85 of 10 RM% flexibility exer-cises; RPE-guided progression in exercise volume(RPE: 9–14)
RM: Repetition maximum, RPE: Rating of perceived exertion, ADL: Activities of daily living.
102 SenthilKumar T, Soundararajan P, Maiya AG, et al
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used to compare within the groups for out-comes with repeated measures. Pearson’scorrelation was used to determine the corre-lation between the measured outcomes.
Results
The groups were similar in their baselinecharacteristics and outcomes measured at thestart of trial (Table 2). After the graded training,the functional capacity, IQMS and fatiguescore improved in the SG significantly thanthe CG at six weeks as well 12 weeks, P <0.05
(Table 3). There was a significant improve-ment within the SG on repeated measures offunctional capacity, muscle strength, andfatigue. The mean difference in the improve-ment of the functional capacity, musclestrength was found to be more in the SG frombaseline to six weeks, while fatigue scoreimproved more between six and 12 weeks,even though both the groups had significantchanges at all measurements (Table 4). Themuscle strength (IQMS) had a positiverelationship with the functional capacity at allmeasurements (Figures 2 and 3). The fatigue
Table 2. Demographic and clinical characteristics of the study participants.Characteristics Control group Study group
Age (years) 35.08 (8.78) 36.24 (8.66)Gender Male 48 (78.7) 47 (77) Female 13 (21.3) 14 (22.1)Body Mass Index 22.21 (2.20) 22.59 (1.75)Comorbidities Diabetes 22 (36.1) 16 (31.1) Hypertension 23 (62.3) 21 (65.6)Type of transplantation LRRT 45 (73.8) 47 (77) DDRT 16 (26.2) 14 (23)Renal parameters BUN 20.41 (1.81) 20.21 (1.87) Serum creatinine 2.20 (0.435) 2.23 (0.520) Hemoglobin 10.4 (0.875) 10.2 (0.882)Units in number (percentage), others as mean (SD). LRRT: Live related-renal transplantation; DDRT:Deceased donor renal transplantation, BUN: Blood urea nitrogen; SD: Standard deviation.
Table 3. Comparison of functional capacity, muscle strength, and fatigue between groups.
Measured OutcomesControl group
Mean(SD)Study groupMean(SD)
Mean difference(CI)
P
Functional capacity (SMWD) Baseline (T1) 252 (33.7) 249 (41.33) 13 (10.88, 16.15) 0.7a
Post training (T2) 318 (48.72) 386 (86.91) 68 (42.38, 92.90) 0.001a
Post training (T3) 399 (70.74) 504 (102.17) 105 (73.40, 136.45) 0.001a
Muscle strength (IQMS) Baseline (T1) 2.40(0.305) 2.39 (0.521) 0.007 (0.145, 0.160) 0.922a
Post training (T2) 5.78(0.551) 7.96 (1.029) 2.18 (0.150, 2.481) 0.001a
Post training (T3) 8.75(1.52) 11.66 (1.166) 2.91 (0.244, 3.401) 0.001a
Fatigue (FSS) Baseline (T1) 60.33# 62.33# 0.714b
Post training (T2) 86.93# 36.07# 0.001b
Post training (T3) 83.49# 39.51# 0.001b
#Mean rank; aUnpaired t-test bWilcoxon signed rank test. SMWD: Six-minute walk distance (meters),IQMS: Isometric quadriceps muscle strength (Kilograms), SD: Standard deviation, CI: Confidenceinterval unpaired t-test, FSS: Fatigue severity score.
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score had a significant negative correlationwith functional capacity at the six and 12weeks post-intervention (Figures 4 and 5).
Discussion
The functional capacity in SG improvedsignificantly than the CG. The natural upsurgein energy levels, could have resulted in im-provement in the CG also. The recommendedfunctional capacity of 680 m in healthy parti-cipants was attained by the SG in this trial.The minimal clinically important difference of86 m reported in pulmonary conditions,21 waswell achieved in the present study. The func-tional capacity in post-RT recipients was repor-ted as 318 ± 136 m with a range of 0–750 m.22
In the present study, SMWD has improvedfrom 252 and 249 to 399 and 504 m in thecontrol and SGs, respectively, which is almostequivalent to the previous finding.23 The increasein physical activity participation, increased
appetite, recovery from uremic symptoms, andreduction in psychological symptoms, inclu-ding the need for dialysis, were the possiblereasons for the improvement after RT.Interestingly, this study includes early inter-vention after RT up to three months, whichhave elicited good improvement in functionalcapacity. The early training with follow-upwith graded training has remained a possiblereason for the significant improvement in thefunctional capacity.The muscle strength has remained an important
determinant in physical activity participation.The quadriceps muscle is known for its role ininfluencing the walking ability of an individual.The reduction in muscle strength was describedin post-RT as in chronic kidney diseases.24,25
The relationship between the impaired quadri-ceps muscle strength and gait performance inRT cites the need for muscle strengthening.26
There was a significant improvement in IQMSin the SG, which shows the effectiveness of the
Table 4. Comparison of functional capacity, muscle strength, and fatigue before and after training within thegroups.
Control group (n=61) Study group (n=61) P*Functionalcapacity T1 T2 T3 T1 T2 T3 Time Group
SMWD(m)
251.71(33.71)
318.05(48.73)
399.08(70.74)
249.06(41.33)
385.69(86.91)
504.03(102.18)
F (2,59)=256.29, ηp2=0.897 F (2,59)=253.09, ηp
2=0.896Meandifference
66.34a 81.03b 147.37c 136.62a 118.34b 254.97c<0.001a,b,c <0.001b,c
Control group (n=61) Study group (n=61) P*Musclestrength T1 T2 T3 T1 T2 T3 Time Group
IQMS(Kg)
2.40(.303)
5.78(.551)
8.75(1.51)
2.39(.521)
7.96(1.03)
11.66(1.17)
F (2,59)=256.29, ηp2=0.897 F (2,59)=253.09, ηp
2=0.896Meandifference
3.38a 2.97b 6.35c 5.57a 3.70b 9.27c<0.001a,b,c <0.001b,c
Control group (n=61) Study group (n=61) P*FatigueT1 T2 T3 T1 T2 T3 Time Group
FSS5.66
(.386)5.49
(.222)4.88
(.326)5.68
(.404)4.97
(.403)3.90
(.944)F (2,59)=128.15, ηp
2=0.681 F (2,59)=77.25, ηp2=0.724
Meandifference
0.175a 0.609b 0.784c 0.71a 1.07b 1.781c
<0.001a,b,c <0.001b,c
Data are expressed as mean (SD); T1 Baseline, T2 6 weeks, T3 12 week. *ANOVA Repeated measures withBonferroni corrections, aDifference between baseline and 6 weeks, bDifference between 6th and 12th weeks,cDifference between baseline and 12th week; F Wilks’ Lambda; ηp
2partial Eta squared. SMWD: Six-minute walkdistance, m: meters, IQMS: Isometric quadriceps muscle strength, Kg: Kilograms, FSS: Fatigue severity score,SD: Standard deviation.
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Figure 2. Correlation between functional capacity and muscle strength at baseline after renaltransplantation.
Figure 3. Correlation between functional capacity and muscle strength at 12 weeks after renaltransplantation.
Figure 4. Correlation between Functional capacity and fatigue at 6 weeks after renal transplantation.
Effects of graded exercise after renal transplantation 105
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protocol. The muscle strengthening after RTwas shown as a safe and useful method inimproving physical performance and peakoxygen uptake in post-RT patients.27,28 Therole of resistance training in improving musclenutrition and physical function is known.29
The functional capacity improved with astrong correlation with six-minute walk dis-tance in this study, as noted before.30
Fatigue remains a multifactorial problem withphysical and mental causes and its improve-ment leads to overall wellbeing.31 Fatigueremained as the major outcome of interventionas well to a measure of general wellbeing.32-34
The improvement of fatigue implies theindirect psychological wellness associatedwith better muscle activation, physical perfor-mance, and social participation. The negativerelationship with the functional capacityillustrates its functional impact. The need forexercise training to improve fatigue wasreported before.34 A recent study has shownsuccessful RT recipient still have low QOLwith fatigue,35 which supports the need ofgraded exercise training. The exercise traininghad positive outcomes on the quality andquantity of sleep and lipid profiles, whichwere associated with improvement in fatigue.36
All the participants received standardizedmedications by the renal physicians as pertheir individual needs. The present studyexplores the effects of the early intervention
and hence medication effects need to beexplored by long-term follow-up of theparticipants. Thus, we can conclude that theuse of graded exercise-based rehabilitationwith strength training provides significantclinical benefits at the early and crucial post-operative period after RT.
Presentation at a Meeting
Part of the study presented at InternationalSymposium on Exercise Science Research inFebruary 2015 at Manipal Academy of HigherEducation, Manipal University, Manipal, India.
Conflict of Interest: None declared.
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4. Adams GR, Vaziri ND. Skeletal muscledysfunc-tion in chronic renal failure: Effects ofexercise. Am J Physiol Renal Physiol 2006;
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15. Abraham G, Yuvaraj A, Haridas AP, et al.Prevalence of hypertension in postrenal trans-plant recipients: A retrospective tertiary carestudy. Indian J Transplant 2017;11:194-7.
16. Rogan A, McGregor G, Weston C, et al.Exaggerated blood pressure response todynamic exercise despite chronic refractoryhypotension: Results of a human case study.BMC Nephrol 2015;16:81.
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Cardiorespiratory fitness is related to physicalinactivity, metabolic risk factors, and athero-sclerotic burden in glucose-intolerant renaltransplant recipients. Clin J Am Soc Nephrol2006;1:1275-83.
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Date of manuscript receipt: 10 August 2018.Date of revised copy receipt: 19 October 2018.Date of final acceptance: 21 October 2018.
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*Correspondence to Author: Rekha ASri Ramachandra Medical Col-lege,SRIHER
How to cite this article:Naresh Duthaluri, Adith C, PrabhuP, Rekha A. Evaluation of laboratoryrisk indicator for necrotizing fasciitis(Lrinec) scoring system for diagno-sis of necrotizing fasciitis in patientspresenting with soft tissue infection.International Journal of Case Re-ports, 2020; 4:155.
eSciPub LLC, Houston, TX USA.Website: http://escipub.com/
Naresh Duthaluri et al., IJCR, 2020 4:155
International Journal of Case Reports
(ISSN:2572-8776)
Case Report IJCR (2020) 4:155
Evaluation of laboratory risk indicator for necrotizing fasciitis (Lrinec) scoring system for diagnosis of necrotizing fasciitis in patients presenting with soft tissue infection
Necrotizing soft tissue infection represents a diverse process; the term itself encompasses a con-tinuum ranging from pyoder-ma to life threatening infections (clostridial gas gangrene with my-onecrosis, anaerobic cellulitis, and severe, necrotizing vib-rio infections). These can occur in any anatomical area but the commonest site is the extremities. Necrotizing fasciitis is often underestimated because of the lack of specific clinical findings in the initial stages of the disease. The paucity of specific cu-taneous signs to distinguish necrotizing fasciitis from other soft tissue infections such as cellulitis makes the diagnosis extremely difficult. The first and most important consideration for an accu-rate, prompt diagnosis is to have a high index of suspicion. It has been shown by numerous studies in the past that early recogni-tion and surgical interven-tion at the earliest is the sole factor in preventing the morbidity and mortality in patients with ne-crotis-ing fasciitis [1-3]. So a scoring system which is easy to follow and cost effective with high positive and negative predictive value is required. One such scoring system is the LRINEC scoring system devised by Wong et al [4] in 2005 which claims to have a positive predictive value of 92.0% and negative pre-dictive value of 96.0%. The mortality in necrotizing fasciitis is as high as 34%. [5] We evaluated LRINEC scoring system in patients presenting with symptoms and signs sugges-tive of soft tissue infection that progresses to necrotizing fasciitis in Sri Ramachandra Medical College and Hospital, Porur, Chennai over a period of two years.
Naresh Duthaluri, Adith C, Prabhu P, Rekha A
Sri Ramachandra Medical College,SRIHER
ABSTRACT
IJCR: https://escipub.com/international-journal-of-case-reports/ 1
Naresh Duthaluri et al., IJCR, 2020 4:155
IJCR: https://escipub.com/international-journal-of-case-reports/ 2
MATERIALS AND METHODS
We performed this study on 91 consecutive pa-
tients in the ER over two years with symptoms
suggestive of soft tissue infections atSri Rama-
chandra Medical College.
All the patients presenting with symptoms sug-
gestive of soft tissue infections underwent clini-
cal examinations and the investigations (Hae-
moglobin,total white cell counts ,random blood
sugar,serum creatinine,serum sodium,serum C-
reactive protein and a wound swab).
Information regarding the demographics & co-
variates of soft tissue infections was collected
using a pretested semi- structured profoma cum
observational checklist.
LRINEC scoring system was applied to each of
the study subjects (Table 1)
VARIABLE SCORE
C-reactive protein (mg/dl)
<1.5
>1.5
0
4
Total white cell count (cmm)
<15000
15000-25000
>25000
0
1
2
Haemoglobin (g/dl)
>13.5
11-13.5
<11
0
1
2
Sodium (mmol/l)
>135
<135
0
2
Creatinine (mgs/dl)
<1.4
>1.4
0
2
Glucose (mgs/dl)
<180
>180
0
1
Table 1: The LRINEC (laboratory risk indicator for necrotizing fasciitis) score [4].
LRINEC score of 6 or greater is considered positive for necrotizing fasciitis.
The inclusion criteria included all the patients
presenting to Sri Ramachandra Medical College
and Hospital with symptoms suggestive of soft
tissue infections during the study period.
The exclusion criteria were 1) Patients below 15
yrs or above 90 yrs of age. 2) Patients who have
received antibiotic treatment in the last 48 hours
or a minimum of 3 doses of antibiotic prior to
presentation. 3) Patient who has undergone sur-
gical debridement for present episode of soft tis-
sue infection.
This was a hospital based observational study.
The collected data were statistically analysed
with IBM.SPSS statistics software 23.0 Version.
To describe about the data descriptive statistics
frequency analysis, percentage analysis were
used for categorical variables and the mean &
S.D were used for continuous variables. The
performance of the final model was very good
(Hosmer-Lemeshow goodness of fit test, P=
0.492) and discriminated well between patients
with necrotizing fasciitis and those with other
soft tissue infections. Area under the receiver
operating characteristic curve for the develop-
mental cohort was 0.795 (95% CI, 0.699–0.892)
with Sensitivity, Specificity, NPV and PPV.The
methods of analyses used in this study was mul-
tivariate analyses by backward stepwise (Wald)
logistic regression procedure. In all the above
statistical tools the probability value .05 is con-
sidered as significant level.
RESULTS
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A Total of 91 consecutive patients with soft tis-
sue infections who fulfilled the inclusion criteria
were taken up for the study during a period of
two years [after getting Institutional Research
Ethics Committee clearance (REF: CSP-
MED/15/AUG/24/07)] and LRINEC score was
applied to validate the progression of any soft
tissue infection into necrotizing fasciitis.
When we analyzed the patients with necrotizing
fasciitis, we found that in the age group 41-50
years there were 8(23.5%) patients, 51-60 years
there were 14 (41.1%) and in 61-70 years there
were 7(20.5%) patients (Fig 1 depicts age distri-
bution)
Figure 1: Demographic representation of Age distribution
In our study population of 91 patients the mean
age was 55.59 years (SD±14.368) with a me-
dian of 57 years. With regards to the age distri-
bution, maximum clustering was observed in the
45 to 65 years age group, with 49 patients con-
stituting 53.8% of the group.
When we looked at the gender distribution of the
total number of patients presenting with soft tis-
sue infection we found that 76 patients were
males which is 83.5% while 15were females
(16.5%).
A diagnosis of necrotizing fasciitis was made if
patients presented with the following characteri-
stics: acute pain, extensive fascial necrosis
sparing the muscles, foul smelling fluid and
signs of systemic toxicity.
57 out of the 91(62.6%) patients had soft tissue
infection. Out of the 34 patients (37.4%) diag-
nosed with necrotizing fasciitis majority of them
were males accounting to 91.2%.
C- REACTIVE PROTEIN
C- Reactive Protein is a nonspecific parameter
for any inflammatory process. In our study, the
patients were divided into two groups lesser
than 1.5mg/dl and greater than 1.5mg/dlas seen
in Table 2
Necrotizing fasciitis (n/%) Soft tissue infection (n/%)
> 1.5 20 (58.8%) 8 (14.0%)
<1.5 14 (41.1%) 49 (85.9%)
Table2: CRP in total population (mgs/dl)
Among 34 patients with necrotizing fasciitis, 20
patients had CRP greater than 1.5mgs/dl and 14
patients had CRP less than 1.5mgs/dl. Whereas
in soft tissue infection group, 8 patients had
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CRP greater than 1.5mg/dl and 49 less than
1.5mgs/dl.
Mean C- reactive protein of the total population
was 1.315mg/dl (SD±0.6931). In the necrotizing
fasciitis group mean C- reactive protein was
1.80mg/dl as compared to soft tissue infection
group which was 1.026mg/dl. This was statisti-
cally significant (p value 0.001) as seen in table
3.
Group Number of Patients Mean Std. Deviation
CRP
Soft tissue infection 57 1.026 0.6143
Necrotizing fasciitis 34 1.80 0.5326
Table 3: Mean of the total population of CRP (mg/dl)
WHITE BLOOD CELL COUNTS
Increased white blood cell count is a direct con-
tribution to the under lying infection. The
patients were categorized into three groups
(<15,000cmm, 15000cmm to 25,000cmm and >
25000cmm) as seen in table 4
Necrotizing
fasciitis (n/%) Soft tissue infection (n/%)
< 15000 16 (47%) 35 (61.4)
15000-25000 13 (38.2%) 19 (33.3%)
>25000 5 (14.7%) 3 (5.2%)
Table 4: WBC in the total population (cmm)
Among 34 patients with necrotizing fasciitis, 16
patients had WBC less than 15000cmm, 5 pa-
tients had WBC greater than 25000cmm range
and 13 patients had WBC ranging from
15000cmm to 25000cmm. Where in soft tissue
infection group, 35 patients had WBC less than
15000cmm, 3 patients had WBC greater than
25,000cmm and 19 patients had WBC ranging
from 15000cmm to 25000cmm.
In the total population white blood cell count
mean was 14837.36cmm (SD ± 7275.219). The
mean white blood cell count in soft tissue infec-
tion group was 13668.42cmm as compared to
necrotizing fasciitis group which was 16797.06
cmm as seen in table 5. This was significant sta-
tistically with p value of 0.047.
Group Number of Patients Mean Std. Deviation
WBC Soft tissue infection 57 13668.42 6518.851
Necrotizing fasciitis 34 16797.06 8119.169
Table 5: Mean of white blood cell count (cmm)
HEMOGLOBIN
The level of hemoglobin was categorized into,
less than 11gm/dl, 11gm/dl to 13.5gm/dl and
greater than 13.5gm/dl and the whole group was
divided accordingly. Among 34 patients with ne-
crotizing fasciitis, 14 patients had hemoglobin
less than 11gm/dl, 2 patients had hemoglobin
greater than 13.5gm/dl and 18 patients had he-
moglobin ranging between 11gm/dl to
13.5gm/dl. Wherein soft tissue infection group
23 patients had hemoglobin less than 11gm/dl,
9 patients had hemoglobin greater than
13.5gm/dl and 25 patients had hemoglobin be-
tween 11gm/dl to 13.5gm/dl. Mean hemoglobin
in the total population was 11.481gm/dl (SD ±
1.96). The mean hemoglobin in necrotizing
fasciitis group was 11.6gm/dl while in soft tissue
infection group it was 11.8gm/dl. However, this
was not statistically significant (p value - 0.265)
SODIUM
Sodium range was categorized into greater than
135mmol/l and lesser than 135mmol/l, the whole
group was divided accordingly.
Among 34 patients with necrotizing fasciitis, 17
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patients had sodium greater than 135mmol/l and
17 patients had sodium less than 135mmol/l.
Whereas in the soft tissue infection group, 40
patients had sodium greater than 135mmol/l and
17 less than 135mmol/l. Mean sodium in the to-
tal group was 135.45mmol/l (SD ± 4.65). The
mean sodium in necrotizing fasciitis group was
134.74mmol/l as compared to soft tissue infec-
tion group which was 135.8mmol/l. However,
this was not statistically significant (p value
0.260)
CREATININE
Creatinine range was categorized into greater
than 1.4mgs/dl and lesser than 1.4mgs/dl, the
whole group was divided accordingly. Among 34
patients with necrotizing fasciitis, 10 patients
had creatinine greater than 1.4mgs/dl and 24
patients had creatinine less than 1.4mgdl.
Wherein soft tissue infection group, 12 patients
had creatinine greater than 1.4mgs/dl and 45
patients had creatinine less than 1.4mgs/dl.
Mean creatinine in the total population was
1.24mgs/dl (SD ± 1.01). The mean sodium in
necrotizing fasciitis group was 1.23mgs/dl as
compared to soft tissue infection group which
was 1.26mgs/dl. However, this was not statisti-
cally significant (p value - 0.902).
RANDOM BLOOD SUGAR
Random blood sugar range was categorized
into greater than 180mgs/dl and lesser than
180mgs/dl, the whole group was divided accord-
ingly.
Among 34 patients with necrotizing fasciitis, 22
patients (64.7%) had random blood sugar
greater than 180mgs/dl and 12 patients (35.3%)
had random blood sugar less than 180mgs/dl.
Wherein soft tissue infection group, 15 patients
(24.6%) had random blood sugar greater than
180mgs/dl and 42 patients (75.4%) had random
blood sugar less than 180mgs/dl
Mean random blood sugar in the total group was
159.35mgs/dl (SD ± 94.77). The mean random
blood sugar in necrotizing fasciitis group was
154.86mgs/dl as compared to soft tissue infec-
tion group which was 166.88mgs/dl. However,
this was not statistically significant (p value -
0.561)
Of the total 91 patients, fourteen patients with
necrotizing fasciitis had a LRINEC score greater
than 8, seven patients had a score less than 5
and thirteen patients were within the range of 6-
7. In soft tissue infection group there were six
patients with a score greater than 8, forty three
patients had a score less than 5 and eight pa-
tients were within the range of 6-7. Fig 2 depicts
LRINEC score distribution.
Figure 2: Distribution for LRINEC SCORE
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CO-MORBIDITIES IN THE STUDY POPULA-
TION
DIABETES MELLITUS:
Out of the 91 patients in my study 39 patients
(42.9%) had previous history of diabetes melli-
tus and 52 of them (57.1%) did not have previ-
ous history of diabetes mellitus.
SYSTEMIC HYPERTENSION
Out of the 91 patients in my study 13 patients
(14.3%) had previous history of hypertension
and 78 of them (85.7%) were not hypertensive.
When analyzing 34 patients with necrotizing
fasciitis 15 patients were diabetic (44.1%) and 2
patients were hypertensive (5.9%).
Kidney injury was defined as patient on admis-
sion had signs of decreased urine output of
lesser than 300ml and creatinine of greater than
1.6mg/dl. In our study of the total population
27.5% (25 patients) were diagnosed with kidney
injury.
Multi organ failure was defined as patient who
had presented with one or more of systemic dis-
eases such as diabetes mellitus/ systemic hy-
pertension/ liver disease/ kidney injury.
Of the 34 patients with necrotizing fasciitis, 11
patients had kidney injury and 7 patients had
multi organ failure.
MICROBIOLOGY
In our study we had analyzed the organism
grown in the culture as single organism growth
or poly microbial. Of the 91 patients 68 patients
(74.7%) had single organisms in the culture,
wherein 23 patients (25.2%) had poly microbial
organism in the culture.
In my 34 patients with necrotizing fasciitis 24 pa-
tients (70.6%) had single organism growth in the
culture wherein 10 patients (29.4%) had poly mi-
crobial organisms in the culture
MORTALITY
5 patients of the 91 patients (5.5%) in the study
population succumbed to their illness. In the ne-
crotizing fasciitis group, 5 out of 34 patients
(14.7%) died and all these patients had a
LRINEC score of greater than 8.
In the subgroup of patients with LRINEC greater
than 8, nine patients with necrotizing fasciitis
survived their infection. Table 6 shows the
LRINEC score in both groups
Groups
Total
Necrotizing Fasciitis Soft tissue Infection
Score
range
>6 27 14 41
< 6 7 43 50
Total 34 57 91
Table 6 shows the the LRINEC score in both groups.
Odd’s Ratio: 0.375
True Positive False Positive False Negative True Negative Total P value of score
Observation 27 14 7 43 91 <0.001
Sensitivity Specificity PPV NPV Accuracy
Evaluation (%) 79.4 75.4 65.9 86.0 76.9
Table 7 showing the summation of accuracy.
Sensitivity of the LRINEC score was 79.4%, its
specificity was 75.4%, positive predictive value
was 65.9% and negative predictive value 86%.
This is statistically significant with p value of
0.001as seen in table 7.
According to our study, LRINEC score of greater
than 6 had a 4.3 times greater risk (Relative risk
Ratio) of progression into necrotizing fasciitis.
ROC allows to create complete sensitivity/spec-
ificity report. The ROC is fundamental tool for di-
agnostic test evolution. In a ROC the true posi-
tivity rate (sensitivity) is plotted in function of the
false positive rate (1-Specificity) for different cut
off points of a parameter. Each point on the ROC
represents a sensitivity/specificity pair corre-
sponding to a particular decision threshold. The
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area under the ROC curve (AUC) is a measure
of how well a parameter can distinguish be-
tween two diagnostic groups (disease/ normal).
In my study the state of necrotizing fasciitis is
assessed applying the LRINEC score as seen in
fig 3.
Fig 3ROC
Clinical variables P value
SOFT TISSUE INFECTION
(n=57)
NECROTIZING FASCIITIS
(n=34)
Age in years
<45 years 5 (14.7%) 13 (22.8%) 0.878
45-65 years 24 (70.5%) 25 (43.8%)
>65 years 5 (14.7%) 19 (33.3%)
Gender
Male 31 (91.2%) 45 (78.9%) 0.452
Female 3 (8.8%) 12 (21.1%)
Hemoglobin
<11.0 14 (14.1%) 23 (40.3%) 0.265
11.0-13.5 18 (52.9%) 25 (43.8%)
>13.5 2 (5.8%) 9 (15.7%)
Total count
<15000 16 (47%) 35 (61.4%) 0.047
15000-25000 13 (38.2%) 19 (33.3%)
>25000 5 (14.7%) 3 (5.2%)
RBS
<=180 12 (35.2%) 15 (24.6%) 0.561
>180 22 (64.7%) 42 (75.4%)
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Serum creatinine
<=1.4 24 (70.5%) 45 (78.9%) 0.902
>1.4 10 (29.5%) 12 (21.1%)
Sodium
<135 17 (50%) 17 (29.9%) 0.260
>135 17 (50%) 40 (70.1%)
CRP
<150 14 (41.1%) 49 (85.9%) 0.001
>150 20 (58.8%) 8 (14%)
LRINEC SCORE
>6 27(79.4%) 14 (24.55%) 0.001
<6 7 (20.5%) 43 (75.4%)
Table 8 showing the consolidated values.
DISCUSSION
LRINEC score was applied on admission to the
91 patients presenting to ER with soft tissue in-
fections and they were observed clinically after
48 hours to see if these patients progressed to
necrotizing fasciitis. Validation of the score
would help prognosticate patients (at admission)
who are likely to progress to necrotizing fasciitis.
A review of literature states that there is no age
or gender prediction for necrotizing fasciitis.
Most common age group was between 45-65
years, accounting for 70% of the necrotizing
fasciitis group. While mean age group was
55.59±14.36 years in the present study, it was
51.5, 54 and 50.8±15.4 in David.et.al [5], Pau-
lin.et.al [6], and N. Shahik.et.al [7], respectively. In
our study, 91.2% of the patients were males
whereas it was 27.4%, and 69% in David.et.al [5], and Paulin.et.al [6] respectively.In the ne-
crotizing fasciitis group, the mean of CRP was
1.80mg/dl, where as in a similar study done by
Wong.et.al [4] it was 2.54mg/dl. The mean CRP
value in our study was significantly higher in the
necrotising fasciitis group compared to that of
soft tissue infection group.
In the necrotizing fasciitis group, the mean of
white blood cell count was 16797.06cmm,
where as in similar studies done by Wong.et.al
[4] and N. Shaik.et.al [7] it was 16232.1cmm and
20720.7cmm respectively. The mean white
blood cell count was higher in the necrotizing
fasciitis group as compared to that of soft tissue
infection group.
In the necrotizing fasciitis group, the mean of so-
dium was 134.74mmol/l, where as in similar
studies done by Wong.et.al [4] and N. Shaik.et.al
[7] it was 133.5mmol/l and 129.3mmol/l respec-
tively. The mean sodium was higher in the ne-
crotizing fasciitis group as compared to that of
soft tissue infection group.
In the necrotizing fasciitis group, the mean of
creatinine was 1.23mg/dl, where as in similar
studies done by Wong.et.al [4] and N. Shaik.et.al [7] it was 1.09mg/dl and 1.5mg/dl respectively.
The mean creatinine was higher in the necrotiz-
ing fasciitis group as compared to that of soft tis-
sue infection group.
In the necrotizing fasciitis group, the mean of
random blood sugar was 166.8mg/dl, where as
in similar studies done by Wong.et.al [4] and N.
Shaik.et.al [7] it was 225.18mg/dl and 281mg/dl
respectively. The mean random blood sugar
was higher in the necrotizing fasciitis group as
compared to that of soft tissue infection group.
In our study, out of the total 91 patients, 34 pa-
tients (37.4%) progressed to necrotizing
fasciitis. Out of the 34 patients, 27 (79.4%) of
them had a LRINEC score of more than 6 and
was statistically significant (P value < 0.001).
There was great variation in the results ob-
served in various studies. In our study the sen-
sitivity was 79.4% and specificity was 75.4% in
Naresh Duthaluri et al., IJCR, 2020 4:155
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comparison with similar studies done by Liao.
et.al [8] and Wong.et.al. [4] it was 59.2% and
83.8%, 89.9% and and 96.9% respectively.
The positive predictive value of LRINEC score >
6 was 65.9% as compared to 92% and 37.9% in
similar studies done by Wong.et.al. [4] and
Liao.et.al [8] respectively. The negative predic-
tive value of LRINEC in our studies was 86.0%
as compared to 96 % and 92.5% in studies done
by Wong.et.al. [4] and Liao.et.al. [8] as seen in Fig
4
Fig 4: LRINEC SCORE in different studies.
The paucity of studies with LRINEC score re-
mains a stumbling block for greater analysis.
LRINEC is useful in distinguishing necrotizing
fasciitis from other soft tissue infections. How-
ever the small sample size is one of the limita-
tions of this prospective study. Meta analysis of
data will be needed for a greater validation.
CONCLUSIONS
In our prospective study of 91 patients present-
ing with soft tissue infection, 34 patients (37.4%)
progressed to necrotizing fasciitis whereas 57
patients (62.6%) did not.
Of the 41 patients who had a Laboratory Risk
Indicator for Necrotizing Fasciitis (LRINEC)
score of greater than 6, twenty seven patients
progressed to necrotizing fasciitis and of 50 pa-
tients with score lesser than 6, seven patients
progressed to necrotizing fasciitis.
Various variables of the LRINEC score such as
C-Reactive protein, white blood cell count, he-
moglobin, random blood sugar, creatinine and
sodium were analyzed individually. Laboratory
parameters such as C- Reactive protein and
white blood cell count were also statistically sig-
nificant with p-value of 0.001 and 0.047 respec-
tively as seen in Table8.
We found that LRINEC had a sensitivity of
79.4% and positive predictive value of 65.5%.
LRINEC score is a useful tool to prognosticate
patients at initial assessment and can serve as
a predictor of patients who present with soft tis-
sue infection and progress to necrotizing
fasciitis
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nants of mortality. J Bone Joint Surg Am 2003;
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[3] McHenry CR, Piotrowski JJ, Petrinic D, et al.
Determinants of mortality for necrotizing soft-
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[4] Wong CH, Khin LW. The LRINEC (Laboratory
Positive Predictive value
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risk indicator for necrotizing fasciitis) score: A
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[6] Pauline Kha, Julien Colot, Shirley Gervolino,
Gilles Guerrier, Necrotizing soft-tissue infec-
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[7] N. Shaikh, Ayman El-Menyar, Insolvisagan N-
atesa Mudali, Hassan Al-Thani, Clinical Pre-
sentations and outcomes of necrotizing fascii-
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years Annals of Medicine and Surgery 4
(2015) 355e360.
[8] Chun-I Liao, Yi-Kung Lee, Yung-Cheng Su,
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1Paramasivam S, et al. BMJ Case Rep 2020;13:e235195. doi:10.1136/bcr-2020-235195
Case report
Obstructed ileocaecal tuberculosis with splenic tuberculosis and solid pseudopapillary tumour of tail of pancreas in an immunocompetent womanSurendran Paramasivam, Magesh Murali, Parimuthukumar Rajappa
Rare disease
To cite: Paramasivam S, Murali M, Rajappa P. BMJ Case Rep 2020;13:e235195. doi:10.1136/bcr-2020-235195
General Surgery, Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India
Correspondence toDr Magesh Murali; mageshpsg1147@ gmail. com
Accepted 14 July 2020
© BMJ Publishing Group Limited 2020. No commercial re- use. See rights and permissions. Published by BMJ.
SUMMARYA 22- year- old young woman presented with fever, lower abdominal pain and vomiting for 20 days. She had persistent fever and abdominal pain. Fever panel was negative. Clinical features were suggestive of subacute small bowel obstruction. Contrast- enhanced CT abdomen showed thickening of distal ileum, ileocaecal junction and caecum with conglomerate necrotic nodal mass in the ileocolic mesentry along with a lesion in the tail of pancreas. Patient was discussed with multidisciplinary team and decided to undergo a single- stage procedure after adequate nutritional optimisation. During optimisation, she underwent acute obstruction and hence taken up for emergency laparotomy proceeded to right haemicolectomy with distal pancreatectomy and splenectomy 4 weeks after the time of admission. Histopathology showed ileocaecal tuberculosis and solid pseudopapillary tumour with margins free of tumour. Approach of obstructed ileocaecal tuberculosis in the setting of incidental diagnosis of solid pseudopapillary tumour of pancreas in a moribund patient was challenging.
BACKGROUNDAbdominal tuberculosis (TB) is on increasing trend and poses diagnostic challenge due to non- specific features of the disease. Ileocaecal region is the most common site of abdominal TB probably due to physiological stasis, abundant lymphoid tissue, increased rate of absorption and closer contact of the bacilli with mucosa. Majority of the patients present with obstructive features. It is diagnosed only after tissue pathology via biopsy or explor-atory laparotomy. Almost all cases of ileocaecal TB are effective to antituberculous therapy. Involve-ment of spleen in abdominal TB is rare. Combined involvement of spleen along with ileocaecal region is extremely rare.
Solid pseudopapillary neoplasm of the pancreas is a rare entity with low malignant potential and excellent overall prognosis. It has non- specific clinical presentation such as abdominal pain and nausea, with vague radiological features. Histolog-ical features of this neoplasm are usually specific. Immunostains helps to differentiate this tumour from other circumscribed tumours of the pancreas. The definitive treatment is surgical resection.
Here, we present a rare case of obstructed ileo-caecal TB with splenic TB in the setting of solid
pseudopapillary tumour of tail of pancreas which is not mentioned or published in any historical liter-ature till now.
CASE PRESENTATIONThe patient was a 22- year- old young woman presented with fever, lower abdominal pain and vomiting for 20 days with significant loss of weight. She had a cousin diagnosed to have spine TB and on antitubercular therapy (ATT) for 1 year and was declared cured for the same. On general examina-tion, she was emaciated with body mass index of 16.5. She was pale and showed signs of dehydra-tion. Temperature was 1010F, pulse rate 100/min and blood pressure 110/70 mm Hg. Per abdominal examination showed a palpable single mass size of about 7×5 cm present in the right iliac fossa which is irregular in shape, nodular surface, varying consistency, non- tender, not mobile with extent superiorly 4 cm below transtubercular plane infe-riorly 2 cm above inguinal ligament laterally along the anterior axillary line and medially 2 cm above and lateral to right pubic tubercle with no hepato-megaly or splenomegaly.
INVESTIGATIONSOn laboratory investigations, haemoglobin was 96 g/L, total white cell counts 15.6×109/L and erythrocyte sedimentation rate (ESR) 42 mm/hour. Liver function test, renal function test and serum electrolytes were within normal limits. Ultrasound abdomen showed thickened ileocaecal junction and caecum with enlarged hypoechoic nodes in a thick-ened hyperechoic mesentery.
She had persistent fever and abdominal pain. Sputum for gram stain and acid fast bacilli (AFB) was negative. Mantoux negative. Chest X- ray was normal (figure 1). Tests for fever were negative. Contrast- enhanced CT abdomen showed diffuse circumferential thickening of distal ileum, ileocaecal junction and caecum with conglomerate necrotic nodal mass in the ileocolic mesentry of 5×5.8×4.6 cm (figure 2). Another lesion of 5.7×4.6×4.1 cm noted in the tail of pancreas with broad zone of contact with spleen and left kidney which was heterogenous, predominantly hypodense with irregular peripheral hyperdense lesion (figure 3). Serum CA 19-9 (cancer antigen 19-9) was 15 and serum carcinoembryonic antigen (CEA) was 1.9.
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on January 12, 2021 at Sri R
amachandra U
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CT thorax showed no evidence of acute pulmonary or pleural infective process.
TREATMENTPatient was diagnosed to have subacute small bowel obstruction secondary to ileocaecal TB and a lesion in the tail of pancreas during midsummer. Patient was discussed with multidisciplinary team and decided to undergo a single- stage procedure after adequate nutritional optimisation.
For patients undergoing elective splenectomy, vaccination should ideally be started approximately 10–12 weeks prior to surgery so that the recommended vaccine series can be completed at least 14 days prior to splenectomy. If all recommended vaccine series cannot be completed in this time period, vaccine series can be resumed 14 days after splenectomy. For patients undergoing emergency splenectomy, vaccination should ideally be started 14 days after splenectomy. In both cases, 14 days is the minimum time period to develop antibodies following vaccination. In our case, since patient was planned for elective surgery, vaccine series was started 4 weeks prior to surgery in view of possibility of splenectomy.
She was well optimised using both enteral and parenteral nutrition as per nutritionist advice. During optimisation, she
underwent acute obstruction and hence taken up for emer-gency laparotomy proceeded to right haemicolectomy with distal pancreatectomy and splenectomy 4 weeks after the time of admission.
It is a challenge to plan for surgery in the setting of coex-isting lesion in the tail of pancreas which is a highly moribund procedure in an emaciated patient. Preparation of the patient for surgery is a great challenge.
There was an extensive cocoon involving the distal ileum and caecum with large necrotic nodes in the mesentery and a mass lesion noted in the tail of pancreas encasing the splenic vessels and hilum with nodules over the spleen.
Hence, emergency laparotomy proceeded to right haemicol-ectomy (figure 4) with distal pancreatectomy and splenectomy (figure 5).
At gross examination of resected right haemicolectomy spec-imen, lesion at ileocaecal junction was grey- white colour with size of about 9.5×6.2 × 4 cm extending into the serosa. Histo-logically, it showed numerous well- defined epithelioid gran-ulomas, Langhans’ giant cells and extensive areas of necrosis (figure 6). Appendix and lymph node showed necrotising granu-lomatous inflammation.
Figure 1 Chest X- ray shows no tuberculosis signs.
Figure 2 Ileocaecal tuberculosis. (A) Axial contrast- enhanced CT shows thickening of distal ileum, ileocaecal junction and caecum (blue arrows). (B) Coronal contrast- enhanced CT shows thickening of distal ileum and caecum with extensive conglomerate necrotic nodal mass (blue arrows).
Figure 3 Solid pseudopapillary tumour of tail of pancreas. (A) Axial contrast- enhanced CT shows mass arising from tail of pancreas with haemorrhagic content (red arrows). (B) Coronal contrast- enhanced CT shows mass arising from tail of pancreas in close relation to spleen (red arrows).
Figure 4 Resected right haemicolectomy specimen.
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On gross examination of resected cystic neoplasm of tail of pancreas and spleen altogether weighing 331 g, spleen measures 11.5×6× 2.5 cm; tail of pancreas measures 4.5×3.8×2.5 cm (figure 7A). Cut surface of spleen on gross examination showed grey- brown, no grey white or friable areas (figure 7B). Histolog-ically, spleen showed areas of congestion, well- defined epithe-lioid granulomas and Langhan type of giant cells and necrosis with positive AFB stain using the Ziehl- Neelsen technique (figure 7C).
Cut surface of tail of pancreas showed solid tumour size of about 4.2×3.2 × 2 cm confined to it with adjacent rim of normal pancreatic parenchyma measuring 1.5×1 cm (figure 8A). Histologically, it showed fibrous septations and areas of degen-eration forming white clefts giving the tumour pseudopapil-lary appearance (figure 8B–E). Immunohistochemistry report showed negative for beta catenin and positive for vimentin and CD10 (figure 9). Histopathology of distal pancreatectomy spec-imen showed pT3 pNx solid pseudopapillary neoplasm with margins free of tumour.
Postoperatively, she tolerated feeds well and symptomatically improved. She was started on ATT and also advised to take high protein diet.
OUTCOME AND FOLLOW-UPAfter 4 weeks of starting ATT, she gained weight of about 45 kg from 42 kg. Her surgical scar healed well by primary intention. She gained weight of about 51 kg from initial weight of 42 kg after 6 months of starting ATT. Contrast- enhanced CT abdomen showed no lesion at the pancreas. Booster dose vaccination was given. She was advised to continue ATT for three more months. Regular follow- up was advised. Approach of obstructed ileo-caecal TB in the setting of incidental diagnosis of solid pseudo-papillary tumour of tail of pancreas in a moribund patient was challenging.
DISCUSSIONTB is caused by an acid fast rod- shaped bacilli named myco-bacterium TB. India is worlds’s TB capital. All forms of TB are
Figure 5 Resected cystic neoplasm of tail of pancreas (white arrow) with splenectomy.
Figure 6 Ileocaecal tuberculosis. (A) Gross specimen. (B–D) Histological examination (B) 4×, (C) 10×, (D) 40× shows numerous well- defined epithelioid granulomas, Langhans’ giant cells and extensive areas of necrosis.
Figure 7 (A) Gross specimen of cystic neoplasm of tail of pancreas with spleen. (B) Cut surface of spleen showing gray- brown areas. (C) Histopathological examination of splenic tissue showing positive AFB stain using the Ziehl- Neelsen technique.
Figure 8 Solid pseudopapillary tumour of tail of pancreas. (A) Cut surface of solid pseudopapillary tumour of tail of pancreas. (B–E) Histological examination. (B) Solid pseudopapillary tumour of pancreas with adjacent normal pancreas (C) 4×, (D) 10×, (E) 40×.
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continuing to increase in all regions1 possibly due to increased cases of HIV, expanded use of immunosuppressant therapy, globalisation of the world population and increased transmission in environments such as prisons, homeless shelters and other reasons like evolutionary changes in the biology of the bacte-rium, drug resistance and so on.2
Globally, around 10 million people3 fell ill with TB and 1.3 million died from the disease in the year 2018. Extrapulmo-nary TB occurs in about 20% of TB4 while abdominal TB consti-tutes about 10% of extrapulmonary TB.5
Abdominal TB can affect any age group. It can occur in any of the following four forms in isolation or in combination namely tubercular lymphadenopathy, peritoneal TB, gastrointestinal (GI) TB and visceral TB involving solid organs like liver, spleen, pancreas and kidney. It affects abdomen through ingestion of infected milk, food or sputum, haematogenous spread from distant tubercular focus, direct spread to the peritoneum from infected adjacent focus and lastly through the lymphatic chan-nels from infected nodes.6 7 Patient usually present with colicky abdominal pain, borborygmi and vomiting.8 Any segment of the GI tract can be involved by TB, but the ileocaecal region is the most commonly involved part of the tract, noted in up to 90% of cases with intestinal TB.9 The mucosal layer of the GI tract can be infected with the bacilli with formation of epithelioid tuber-cles in the lymphoid tissue of the submucosa as the initial patho-logical process. Within 2–4 week, it undergoes caseous necrosis, which leads to sloughing of the overlying mucosa and the devel-opment of an ulcer. Later, it spread into the deeper layers and into the adjacent mesenteric lymph nodes and into peritoneum. Indeed, extensive involvement of the adjacent regional nodes is a well- recognised pathological feature.9 The caecal wall is thick-ened and the surrounding nodes are matted and adhere to the wall of caecum and terminal ileum, forming an inflammatory mass.
Splenic TB can occur in two forms: one is as a part of dissem-inated disease and second is as an isolated form. Spleen is the third most common organ (lung 100%, liver 82%, spleen 75%, lymph nodes 55% and bone marrow 41%)10 involved in miliary TB. It is also seen in patients infected with HIV11 12; yet isolated involvement is also reported.13–15 Most of the times, splenic TB presents as fever of unknown origin.16 There are five types of finding on ultrasound of splenic TB according to
pathomorphological classification: miliary, nodular, tubercular splenic abscess, calcific and mixed type. On sonography, multiple hypoechoic intrasplenic lesions may also be seen in other condi-tions including myeloproliferative disorder such as leukaemia, lymphoma, Hodgkin’s disease and metastasis.17 Similar sono-graphic pattern is also being reported in AIDS- related lympho-matous involvement of spleen.18Histopathological and/or microbiological evidence is essential to diagnose splenic TB. ATT is the initial modality in treating splenic TB. Surgery is indi-cated in case of treatment failure or complications of splenic TB like splenic abscess/rupture.
Solid pseudopapillary neoplasm (SPN) of the pancreas represents only about 1% of all pancreatic tumours. Head of pancreas or its tail is the most frequently involved site.19 SPN most commonly affects young women between second and third decades of life.20 Most patients present with abdominal pain and few with asymptomatic abdominal mass.21 Serum tumour markers for pancreas are usually not elevated. CT abdomen shows a well- defined, encapsulated mass with a mean size of more than 5 cm and a thick, enhancing capsule. Following contrast admin-istration, enhancing solid components are typically identified at the periphery with centrally located cystic areas.19 Histological features of this neoplasm are usually specific. Immunostains such as beta catenin, CD10 and E- cadherin help to differentiate this tumour from other circumscribed pancreatic tumours.22 Tumour cells showed positive for CD10 in our case. SPN has a low- grade malignant potential despite the nature of local aggressiveness.
Figure 9 Solid pseudopapillary tumour of pancreas—immunohistochemistry stains. (A) Beta catenin negative. (B) Vimentin positive. (C) CD 10 positive. (D) CD 10 positive in high power field.
Patient’s perspective
I came with 20 days of fever, abdominal pain and vomiting. They took test and CT scan in that they diagnosed ileocaecal tuberculosis with a tumor in the tail of pancreas. Chief doctor explained about the need of removal of part of my bowel and part of pancreas. The possibility of removal of spleen has also been explained and they vaccinated me to prevent infection. Doctor told me the complications of surgery. I had severe abdominal pain and they did emergency surgery. After surgery, my fever, abdominal pain and vomiting got subsided. Doctor explained the biopsy report and he told me to take anti tuberculous treatment. I gained weight and I’m going to college now. I am thankful for the chief surgeon and his team.
Learning points
► Challenge that encountered while managing solid pseudopapillary tumour of tail of pancreas in the setting of obstructed ileocaecal tuberculosis.
► Approach of pseudopapillary tumour of tail of pancreas in the emergency setting that encasing the splenic vessels and hilum was very much challenging.
► Examination of all visceral organs, peritoneum, lymph node and bowel should be done to rule out disseminated abdominal tuberculosis even in isolated tuberculous presentation of any abdominal organs during laparoscopy or laparotomy.
► Surgery is the treatment of choice for solid pseudopapillary tumour of pancreas even in the case of distant metastasis or local recurrence
► Knowledge of about vaccination against capsulated organism to prevent overwhelming post splenectomy infection.
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It has excellent prognosis.23 Surgery is the treatment of choice, even in the presence of distant hepatic metastasis or local recurrence.24
Contributors MM: a post graduate assistant and followed up the case. SP and PR are primary surgeons.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not- for- profit sectors.
Competing interests None declared.
Patient consent for publication Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
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