SYLVESTER O'HALLORAN SURGICAL SCIENTIFIC MEETING Proceedings of meeting held 6th & 7th March 1998 in the Foundation Building, University of Limerick.

SESSION 1 CLINICAL VALUES OF CA15.3 IN BREAST CANCER

PATIENTS WITH BONE METASTASES ALONE

N. Relihan, G. McGreal, M. Murray, E. W. McDermott, N. J. O'Higgins, M. J. Duffy.

Departments of Surgery and Nuclear Medicine, St. Vincent's Hospital, Elm Park, Dublin 4.

Breast cancer patients who develop bone metastases have an unpredictable clinical course. Numerous studies have shown that CA15.3 is elevated in the presence of multiple metastatic sites, including bone. However, little is known about CA15.3 levels in patients with only bone metastases. The aim of this investigation was therefore to study CA 15.3 levels in this group of patients and relate levels to the extent of bone disease and to subsequent survival. CA15.3 levels were measured by ELISA (Boehringer Mannheim) in 45 patients with metastases confined specifically to bone. Patients were initially divided into those with _<2 bone metastases (n=26) and those with >2 bone metastases (n=19). Patients with bone metastases, irrespective of the number of sites had significantly higher CA15.3 levels (mean >2=122.66 u/ml, mean _<2=44.34 u/ml) than levels at the time of diagnosis of the primary tumour (mean >2=4.18 u/ml, mean <2=23.74 u/ml, p<0.05). Although patients with greater than 2 metastases sites tended to have higher CA15.3 levels values at recurrence (mean = 122.6 u/ml) than those with 2 or less (mean = 44.34 u/ml), this difference was not significant. Patients with CA15.3 > 30 u/ml at the time of recurrence had a significantly shorter survival (mean = 18.6 months) than those with marker levels <30 u/ml (mean = 31.5 months, p<0.05). Thirteen of 37 patients had rising CA15.3 prior to diagnosis with a mean lead time of 10.26 months. This is one of the first studies to concentrate solely on patients who have bone secondaries only. It demonstrates that CA15.3 is a reliable turnout marker in detecting the presence of bone recurrence but not in determining the extent of disease. CA15.3 levels >30 u/ ml at diagnosis of bone recurrence signified shorter survival.

TAMOXIFEN IS ANTI-ANGIOGENIC I N V I T R O AND ATTENUATES VEGF-MEDIATED ANGIOGENESIS IN VIVO

D. A. McNamara, J. Harmey, J. H. Wang, D. Donovan, E. Kay*, T. N. Walsh, D. J. Bouchier-Hayes.

RCSI Departments of Surgery and Pathology*, Beaumont Hospital, Dublin.

The pivotal role of angiogenesis in tumour growth is now established. Turnouts secrete a number of pro- and anti- angiogenic factors including vascular endothelial growth factor (VEGF), the most potent pro-angiogenic cytokine identified to date. Having previously demonstrated that tamoxifen reduces serum levels of VEGF in cancer patients, we hypothesised that it inhibits VEGF-mediated angiogenesis. Our aim was to evaluate tamoxifen in 2 models of angiogenesis: human macro- and microvessel endothelial cell proliferation and in an in vivo model of VEGF-induced angiogenesis.

Human microvessel endothelial cells and human umbilical vein endothelial cells were cultured in vitro and treated with tamoxifen in DMSO (100 ng/ml - 2.5 I.tg/ml) or DMSO alone.

Endothelial cell proliferation at 24 and 48 h was quantified using 5-bromo-2'-deoxyuridine labelling. Adult male Sprague-Dawley rats were pre-treated with tamoxifen or placebo for 3 days. They were injected with Matrigel, a tumour-derived basement membrane complex which forms a gel at 37 ~ containing VEGF to elicit neovascularisation. Tamoxifen or placebo was continued for 5 further days. Gels were excised, paraffin mounted, stained with haematoxylin and eosin and microvessel density was quantified.

Human microvessel , but not human umbi l ica l vein, endothelial cell proliferation was inhibited by tamoxifen in vitro at a dose of 2.5 gg/ml when compared to controls (p=0.001). In vivo, tamoxifen reduced angiogenesis elicited by VEGF. The mean microvessel count in tamoxifen-treated VEGF gels was 52.6 per high powered field (hpf) versus 63.3 per hpf in VEGF controls (p<0.05).

We have confirmed that tamoxifen is anti-angiogenic in vivo and in vitro. Furthermore, we have shown that tamoxifen can inhibit VEGF-mediated angiogenesis. This effect merits further evaluation to assess the potential role of tamoxifen in the induction of dormancy in micrometastases.

FAILURE OF APOPTOTIC CELL DEATH IS ASSOCIATED WITH BCL-2 AND BAX PROTEIN CHANGES IN AN EX

VIVO MODEL OF BLADDER CANCER

J. D. Kelly*, K. E. Williamson, R W. Hamilton, D. McManus, H. P. Weir*, P. F. Keane*, S. R. Johnston*.

*Department of Urology, Belfast City Hospital. Department of Pathology, The Queen's University of Belfast.

Effective anticancer agents induce apoptosis in susceptible cells and expression of bcl-2 and related genes alter drug resistance in vitro. The aim of this study was to quantitate Bcl- 2 and Bax in superficial bladder turnouts before and after mi tomycin C (MMC) therapy to de termine whether susceptibility to undergo apoptosis was related to cell phenotype.

Sixteen samples from pTa or pT1 GI-III TCC tumours obtained at resection were divided into time zero, control and treatment samples. Treatment samples were exposed to MMC for 1 h before incubation with controls in an ex vivo environment. Changes in Bcl-2 and Bax protein expression were determined by the difference in percentage of positively staining cells between treated and time zero samples determined by flow cytometry. Results were related to a morphologically derived apoptotic index (AI). Seven turnouts had AI>I0 (mean SD = 15.6 + 3.7) and 9 AI<10 (mean SD = 3.5 + 3.2). There was a significant positive correlation (Pearson correlation: p<0.05) between AI and the MMC induced change in Bax and a clear trend for tumours having AI>I0 to show reduced Bcl-2 after exposure to MMC (Chi squared test: p=0.091). Correlation was shown between increased Bax expression and reduced Bcl-2 expression in tumours with AI> 10 (Pearson correlation: p<0.05).

Down-regulation of Bcl-2 and up regulation of Bax are associated with induction of apoptosis following MMC treatment in superficial bladder tumours. The results suggest that in tumours which fail to under go apoptosis, there is dysregulation of Bcl-2 and Bax indicating a possible mechanism of treatment failure.

2 Sylvester O'Halloran

FREQUENT EXPRESSION OF CD44 VARIANT mRNA IN NORMAL AS WELL AS TUMOUR COLORECTAL TISSUE

M. Morrin, P. V. Delaney. Colorectal Research Unit, Limerick Regional Hospital and

University of Limerick.

The CD44 adhesion molecule was originally recognised as being involved in lymphocyte migration, but is now known to be expressed on many tissue types. Multiple isoforms of the protein can be generated by mRNA splicing. Some of these variants have been implicated in tumour metastasis formation, primarily CD44v6, but a lack of consensus has emerged in the more recent literature regarding the prognostic significance of CD44 variant expression. We did not find CD44v6 protein expression to be of prognostic significance when analysed previously. In this study the expression of CD44 variants at the mRNA level using RT-PCR was investigated in order to gain greater understanding of their role in metastasis.

Total RNA was isolated from a series of normal/tumour tissue pairs, reverse transcribed and PCR amplified using primers from the constant region of the CD44 gene. This was then used as template for a series of "exon-specific" PCR reactions to analyse CD44 variant expression patterns. The PCR products were further investigated by Southern blotting and hybridisation with digoxigenin-labelled, variant-specific probes.

A complex and diverse array of CD44 mRNA transcripts was observed. Eighty per cent of the tumour /normal pairs demonstrated variant expression, although in many cases the transcripts were not as strongly expressed in the normal tissue. After hybridisation with variant-specific probes it was observed that the transcripts were generally composed of combinations of variants, with the v8-9-10 transcript most frequently expressed. No increase in CD44v6 mRNA expression was observed, contrary to what has been reported at the protein level. The frequent expression of multiple CD44 mRNA transcripts in normal colorectal tissue suggests either a difference in translational mechanisms of these transcripts between normal and tumour tissue or alternatively a lack of significance in tumour development.

DIRECT ACIDIFICATION OF COLONIC MUCOSA BY DOPAMINE - EPITAPH FOR TONOMETRY?

D. C. Winter, B. J. Harvey, J .P. Geibel, G .C. O'Sullivan. Departments of Surgery & Cellular Physiology, Mercy Hospital and U.C.C. and Department of Surgery, Yale

University, Connecticut, U.S.A.

Tonometric measurements of colonic and gastric mucosa pH are used to determine splanchnic perfusion. Acidification has been assumed to signify poor circulatory responses to inotropes (e.g. dopamine). We examined the direct effects (independent of oxygenation) of low-dose dopamine on the cellular pH of intestinal mucosa in-vitro.

Cellular pH was recorded using confocal laser imaging of isolated crypts (from the distal colon of adult Sprague-Dawley rats) loaded with a pH-sensitive, fluorescent probe (BCECF). Fluorescent emission intensity is expressed as percentage of basal (mean + S.E.M.) at a dose of 250 nM dopamine for n=144 (n=number of cells measured per crypt x number of crypts x number of animals). A t-test was employed for statistical analysis.

Dopamine produced a cytosolic acidification within 2+0.35 min (47.1 + 12 per cent). This was unaffected by (i) the nominal

Vol. 167 Supplement No. 5

absence of bicarbonate (lmM acetazolamide and CO2-free HEPES perfusate, 45.9+6 per cent) or (ii) ct/B-adrenergic receptor blockade (prazosin ~ind propanolol respectively, 48.4+14 per cent) - all P>0.8. No effect of dopamine occurred following (a) inhibition of sodium-hydrogen exchange with ethyl-isopropylamiloride or (h) generating adenosine 3',5'-cyclic monophosphate with forskolin - both P<0.001.

Ligation of dopamine receptors acidifies mucosal crypt cells in a bicarbonate-independent mechanism that may involve an inhibition of sodium-hydrogen exchange.

This explains the observed mucosal acidification during dopamine infusion despite an improved splanchnic perfusion. Direct effects of pharmacological agents on mucosal tissue must he considered when evaluating perfusion parameters based on tonometric data.

GELATIN SUBSTRATE AND HEPATOCYTE GROWTH FACTOR IMPROVE ANTIGEN PRESENTING

CAPABILITIES OF CULTURED HUMAN DENDRITIC CELLS

C. P. Delaney, R. Coffey, T. E Gorey, J. M. Fitzpatrick. Department of Surgery, Mater Misericordiae Hospital,

Dublin 7.

Dendritic cells (DC) are the most potent initiators of T-cell responses. Clinical immunotherapeutic trials using DC are impeded by difficulties isolating large numbers of DC, and a relative lack of knowledge about maximising their ability to present antigen in vivo. Hepatocyte growth factor (HGF) is a cytokine which has powerful mitogenic, motogenic and morphogenic activities on a wide variety of cell types. This study was designed to improve the yield and antigen-presenting capabilities of human blood-derived cultured DC.

PBMC were isolated from peripheral blood by density gradient and depleted of plastic-adherent contaminating non- precursor cells. Precursors were cultured in specific medium supplemented with optimal concentrations of GM-CSF and IL- 4 as determined in preliminary experiments. Cultures were maintained for 14d before harvest of floating mature DC for morphological and immunophenotypic analysis. The effect of culturing on a 1% per cent gelatin substrate, and supplementation with recombinant HGF were determined. All experiments were performed in triplicate. Stimulatory ability was assessed using the mixed leukocyte reaction with stimulator:responder ratios from 1:3 to 1:27 pulsed with 0.5 gCi 3H-thymidine.

Responder Gelatin Gelatin HGF HGF HGF HGF HGF cell type substrate absent 0ng/ml lng/ml 5ng/ml 10ng/ml 15ng/ml None 1143 802 915 850 823 1083 936 Syngeneic 2672 1768 3334 2824 3 3 3 8 2838 1593 Allogeneic 12275* 5736 8733 12218* 9512 3949 5470

Results in c.p.m, for 1:27 stim:responder ratios. *=p<0.01 vs gelatin absent or HGF 0ng/ml, respectively.

Culture of DC precursors on a 1 per cent gelatin substrate increased the ability of mature DC to present syngeneic and allogeneic antigens by 80 per cent (p<0.001). Analysis of a concentration curve for HGF showed optimal enhancement of stimulatory ability to be achieved at lng/ml, which increased syngeneic and allogeneic antigen-presenting ability by 55 per cent (p<0.01).

Gelatin substrate significantly increases the stimulatory ability of cultured blood-derived human DC. This effect is further increased by up to 50 per cent using HGF. These

t.1.Ms. Sylvester O'Halloran 3 April, May, June, 1998

modifications may improve the ability of DC to present turnout antigen in clinical immunotherapeutic trials.

INHIBITION OF POLYMORPHONUCLEAR NEUTROPHIL APOPTOSIS IN THE PERIOPERATIVE PERIOD

N. E Fanning z, T. Cotter 2, D. Bouchier-Hayes ~, W. Kirwan ~, H. P Redmond.

Cork University HospitaP, Department of Biochemistry UCC 2, Beaumont Hospital 3, Department of Surgery, National University

of Ireland (Cork), Cork University Hospital, Wilton, Cork.

The neutrophil remains the key pro-inflammatory cell activated in the initial response to surgical trauma which induces both a local and systemic neutrophilia. Resolution of the acute inflammatory response is dependent upon neutrophil apoptosis and subsequent ingestion by macrophages. The aim of this study was to evaluate the effect anaesthesia and elective surgery has on neutrophil apoptosis.

Non septic patients undergoing elective transabdominal surgery had whole venous blood harvested immediately preinduction of anaesthesia, postinduction but prior to surgical intervention, and post surgery. Platelet poor plasma (PPP) and neutrophils were isolated by dextran sedimentation and ficoll gradient centrifugation. Neutrophils were suspended in RPMI ~ supplemented with 10 per cent autologous, preoperative or postoperative PPP. Neutrophil apoptisis was quantified by immunofluorescence flow cytometry of annexin-V binding to phosphotidyl serine residues on apoptotic cells and apoptosis was confirmed by morphology. Indirect immunofluorescent flow cytometry was utilised to quantify cell surface expression of the death receptor Fas, and its ligand (FasL)

1 hour 12 hours 24 hours Fas FasL culture cul ture culture

% apoptosis % apoptosis % apoptosis % expression % expression Preinduction 5.0-2_1.1 55.0-+-_10.8 77.8_+3.9 57.3+4.8 17.5+1.5 Postinduction 3.8-+0.9 33.7_+12.9" 59.8_+7.6* 66.7_+7.2 18.5_+8.5 Postsurgery 4.3_+1.3 26.5_+11~6" 51.8_+11.3" 61.0+_.5.8 12.5_+3.5 Data = % neutrophil apoptosis _+ S.E.M. Statistics via paired students t test (*=p<0.05)

Following anaesthesia and surgery neutrophil apoptosis is significantly inhibited. This appears to be a cell intrinsic mechanism as culture of pre induct ion neutrophils with postinduction and postsurgery PPP failed to inhibit neutrophil apoptosis. Interestingly, there was no difference in cell surface expression of Fas and FasL.

These results show for the first time that following anaesthesia and surgery neutrophil apoptosis is significantly inhibited. This appears to be mediated through a cell intrinsic mechanism and functions downstream of the Fas/FasL death complex. Alteration in proinflammatory cell kinetics following surgery has important implications in the normal resolution of the acute inflammatory response following surgical intervention.

OF MICE OR OF MEN? THE EFFECT OF ENDOTOXIN ON THE MACROPHAGE.

D. A. McNamara, G. Pidgeon, J. Harmey, T. N. Walsh, H. P. Redmond*, D. J. Bouchier-Hayes.

RCSI Department of Surgery, Beaumont Hospital, Beaumont Road, Dublin 9 and *Department of Surgery, University

College Hospital, Cork.

Angiogenesis is an important determinant of tumour

proliferation and vascular endothelial growth factor (VEGF) is the most potent angiogenic factor known. We have previously shown that exposure to airborne endotoxin (lipopolysaccharide, LPS) during surgery results in increased serum VEGF levels in a tumour-bearing murine model. The macrophage is one possible source as it is known to be activated by LPS to produce a number of cytokines, notably tumour necrosis factor alpha, and such activation is augmented by the presence of a tumour. Our aim in this study was to determine whether LPS could stimulate macrophages to produce VEGF and to assess whether there is any difference between the human and the murine macrophage in this regard.

Peritoneal macrophages isolated from LPS sensitive (HEN) and LPS resistant (HEJ) mice were adhered and stimulated in vitro with LPS (lng to 100ng) for 24 h.

Human monocytes were isolated, matured to macrophages in vitro and activated. They were incubated with LPS (1-100 ng) for 24 h. VEGF mRNA expression was determined semi- quantitatively by rt-PCR (reverse transcriptase polymerase chain reaction) and VEGF protein levels were determined by ELISA.

VEGF mRNA and protein expression were not significantly altered in LPS-stimulated peritoneal macrophages isolated from LPS sensitive or LPS resistant mice. In human macrophages, however, VEGF mRNA expression is increased in response to LPS in a dose-dependent manner.

Conclusion: In the murine model, LPS fails to elicit VEGF production by macrophages. In contrast, human macrophages increase VEGF production following LPS exposure. This finding emphasises further fundamental differences between routine and human macrophages which are not, as yet, fully explained.

SMOKING AND SHEAR STRESS INDUCED ENDOTHELIAL CELL ANOIKIS MAY BE PREVENTED

BT THE AMINO ACID TAURINE

F. Fennessy, J. H. Wang, C. Kelly, D. Bouchier-Hayes. Royal College of Surgeons in Ireland, Beaumont Hospital,

Dublin.

Vascular endothelial cells (ECs) require attachment to the extracellular matrix (ECM) for growth and survival, and loss of this anchorage dependence, required for normal functioning of the endothelial cell, by disruption of the ECM results in anoikis, or apoptosis resulting from lack of anchorage. Anoikis may be the result of either mechanical or chemical stresses. Cigarette smoking increases shear stress (SS) and oxidant-mediated EC damage. We have previously demonstrated that the amino acid taurine can reverse the abnormal function of Ecs in smokers and can prevent oxidant-mediated EC apoptosis in vitro. We hypothesise that 1) increases in SS in vivo results in increased endothelial cell death by apoptosis and that 2) taurine treatment of young smokers can prevent the increase in apoptosis induced by cigarette smoking.

We studied 7 healthy smokers with a self-reported smoking history of 2-pack yr; and 11 control non-smoking subjects. Using the methodology described by Hladovec and Rossrnann t, circulating endothelial cells were isolated from a peripheral blood sample and counted. On 2 occasions fluorescein-labelled anti-human factor VIII related antigen mAb was used to confirm the identity of the endothelial cells. Apoptosis of these cells was confirmed with the terminal deoxynucleotidyl transferase- mediated dUTP nick end labelling (TUNEL) technique u~m~ the in situ cell death detection kit (Boehringer Mannheim~.

4 Sylvester O'Halloran Vol. 167 Supplement No. 5

Samples for estimation of EC desquamation were taken before and after inflat ion and subsequent deflat ion of a cuff to 200mmHg for 2 min (n=8), and before and after treatment of smokers with taurine, 1.5 gms/day/5 days (n=7).

No. of apoptotic cells/0.9gl chamber Non-smo Smokers Taurine Rx. smokers Baseline IncreaseSS 0.93:s 3.29+1.43" 1. I 1i-0.59"* 1.06:s 2.4i-0.77"** (*p=0.02 vs.non-smo; **p=0.006 vs. smo; ***p--0.002 vs. baseline) Stats: 2 sample t-test

This study reveals that increases in SS acutely, and cigarette smoking chronically induce anoikis. The amino acid taurine has the capability to prevent EC apoptosis and may play an important role in endothelial cell functioning and survival.

Reference I. Hladovec, J., Rossmann, P. Circulating endothelial cells isolated together with platelets and the experimental modification of their counts in rats. Thromb. Res. 1973; 3: 665-674.

MODULATION OF AMINO ACID CONCENTRATION IMPROVES IN VITRO LYMPHOCYTE FUNCTION FROM

SEPTIC PATIENTS

C. E Delaney, R. Flavin, R. Coffey, T. E Gorey, J. M. Fitzpatrick.

Department of Surgery, Mater Misericordiae Hospital, Dublin 7.

The benefit of adequate nutrition for septic patients has been particularly appreciated in recent years. Although certain amino acids (AA) become conditionally essential in times of operative and oncological stress, the effects of AA on lymphocyte proliferative responses from septic patients are unknown. This study examines the effect of altering AA concentration on in vitro lymphocyte responses using select ive deplet ion or supplementation of single or combined AA, and determines whether supranormal concentrat ions of AA might have a beneficial clinical role.

Consenting patients in the ICU with positive SIRS criteria and sepsis were recruited. Lymphocytes were separated and cultured in RPMI at 37~ in humidif ied 5 per cent CO v Depletion plates were prepared with wells in triplicate containing all essential AA except 1 per triplicate. Supplementation plates were prepared with wells in triplicate containing all AA with selective addition of arginine, glutamine, taurine and other essential AA at 2x and 4x physiological concentration. Plates were incubated with and without mitogen for 72 h, before pulsing with 3H-thymidine to assess DNA synthesis.

Eight patients have been recruited for in vitro assessment to date. A significantly reduced proliferative ability was seen for lymph0cytes in wells depleted of arg (36.6 per cent reduction, p<0.01), glu (27.6 per cent, p<0.001), met (I 8.7 per cent, p<0.05) and trp (25.2 per cent, p<0.05). No reduction was seen after depletion of lys, phe, asp, pro, cys, set, gly, thr, his, iso, tyr, leu or val. Supp lemen ta t ion with 2x and 4x phys io log ica l concentration of arginine increased proliferative ability by 11.8 per cent (p=0.2) and 19.2 per cent (p<0.05) respectively, and with 2x and 4x glutamine by 21.4 per cent (p<0.05) and 51.2 per cent (p=0.001) respectively. Combinations of arg and glu, and supplementation with taurine, cys, met, gly, phe, his, tyr, leu, trp had no beneficial effect.

Dep le t ion s tudies sugges t that a rg in ine , g lu tamine , methionine and tryptophan play significant roles in maintaining

p ro l i f e ra t ion o f ' l ymphocy te s from sep t ic pat ients . Supplementa t ion with 2x and. 4x normal phys io log ica l concentrations of glutamine or arginine significantly improves the ability of lymphocytes to respond to a proliferative stimulus. Increased amounts of arginine and glutamine supplementation may be a method of enhancing T-cell responses in septic patients.

S E S S I O N 2

ENDOTHELIAL CELL DYSFUNCTION AS A PUTATIVE MECHANISM OF CELL HOMOCYSTEINE'S

ATHEROGENICITY

A. M. Rasheed, J. H. Wang, C. Kelly, D. J. Bouchier-Hayes, A. Leahy.

Royal College of Surgeons in Ireland, Department of Surgery, Beaumont Hospital, Dublin.

Despite recognition of homocysteine as an independent risk factor for atherosclerosis, the mechanism of its atherogenicity remains unclear. This study assessed homocysteine 's (Hcy) effect on endothelial cell (EC) reparative capacity by measuring EC's proliferation and apoptosis. Endothelial cell function was also assessed by measuring nitric oxide (NO) and endothelin-1 (ET- 1) concentrations.

Human umbilical vein endothelial cells (HUVECs) at passage 2-3 were treated with d,l-Hcy at concentrations of 0.00 mM, 0.01mM, 0.1 mM, 1.0 mM, 2.5 mM for 24 h. EC proliferation was assessed using 5-bromo-2 'deoxy-uridine labelling and detection kit. Apoptosis was assessed using cell death detection ELISA kit. Nitric oxide concentration in the supernatant was measured using the Griess reaction after 24 and 48 h. ET- 1 concentration was measured in the supernatant at 24 and 48 h using human ET-1 ELISA kit. Constitutive NOS expression was assessed by Western blott ing using ant i -human EC-NOS antibody. Statistical analysis was performed using ANOVA and student's t test.

Hey inhibited HUVECs proliferation, induced apoptosis and decreased NO concentrations independent of ecNOS expression. It increased ET- 1 concentrations up to 1 mM Hey concentrations and declined thereafter suggesting EC toxicity.

Impairment of EC reparative capacity and induction of endothelial cell dysfunction are recognised early events in atherosclerosis. These events are seen secondary to exposure to homocysteine and may therefore provide a mechanism for its atherogenecity.

LAPAROSCOPIC FUNDOPLICATION: COMPLETE OR PARTIAL WRAP?

E. E. Lang, M. T. E Caldwell, W. A. Tanner, Department of Surgery, Meath and Adelaide Hospitals,

Dublin 8.

Laparoscopic anti-reflux surgery has become a viable alternative to long-term medical treatment of gastro-oesophageal reflux disease. The Rosetti-Hell operation has been the gold standard for some time, however it has been suggested that the post-operative symptoms of dysphagia and gas-bloat may be reduced by performing a partial fundoplication.

We looked at the ou tcome of pa t ien ts undergo ing laparoscopic fundoplication in the Meath and Adelaide hospitals since the introduction of a modified Toupet operation (270

LJ.M.S. Sylvester O'Halloran 5 April, May, June, 1998

degree wrap) for selected patients. Twenty-eight patients, 14 undergoing a Toupet procedure and 14 having a Rosetti-Hell procedure, were interviewed pre and post-operatively. Forty- three per cent of patients undergoing Toupet procedure had proven manometric abnormality.

Results: Outcome Toupet procedure Rosetti-Hell procedure Dysphagia 6 (43%) 6 (43%) Gas-bloating 2 (14%) 6 (43%) Required oesophageal dilatation 1 (7%) 2 (14%)

Gas-bloat was a greater problem in patients who had a Rosetti-Hell procedure than in those having a modified Toupet procedure. Although dysphagia occurred in equal numbers in both groups, those in the Rosetti-Hell group reported more severe symptoms of greater duration. Of these patients, 4 required further endoscopic investigation and 2 proceeded to oesophageal dilatation. One patient in the Toupet group required oesophageal dilatation. All post operative symptoms were transient. In total 89 per cent patients reported relief from their initial symptoms.

We conclude that transient gas bloat and dysphagia are a problem following laparoscopic fundoplication. These may be reduced with a partial fundoplication. A randomised trial comparing the 2 procedures is now indicated.

INFANTILE HYPERTROPHIC PYLORIC STENOSIS - HOME OR AWAY?

P. D. Kiely, M. O'Reilly, S. Tierney, M. Barry, P. V. Delaney, J. Drumm, P. A. Grace.

Department of Surgery, University of Limerick and Limerick Regional General Hospital, Limerick.

A multidisciplinary approach is essential for the efficient management of infantile hypertrophic pyloric stenosis (IHPS). In this study we evaluated our philosophy that the majority of patients may be managed in a well equipped regional centre with transfer to specialist centres reserved for complex cases.

Using the HIPE database, 64 infants treated for IHPS between January 1991 and December 1996 with a home address within the Mid Western health board region were identif ied. Demographic and clinical details were obtained by chart review. Sixty-one (95 per cent) of the infants were born within the region and initially assessed in Limerick regional general hospital (LRGH) and 3 were born and treated elsewhere. Four of the 61 patients initially assessed in LRGH were referred to a specialist paediatric centre for surgery because of prematurity (n=l), low birth weight (n=l), capillary haemangioma (n=l), and severe metabolic derangement (n=l).

Among the 64 infants, 54 (84 per cent) were male, 21 (33 per cent) were first born and only 7 (11 per cent) had a positive family history. Fifty-two (81 per cent) were born by spontaneous vaginal delivery, 8 (12 per cent) by caesarean section and 4 (6 per cent) were forceps assisted. Median age was 39.6 days (range 13-114) and all infants had electrolyte abnormalities. The diagnosis was made clinically by test feed in 45 infants, and by barium meal and ultrasound in 12 and 7 infants respectively.

Fifty-seven (89 per cent of all cases occurring in the region) infants underwent Ramstedt 's pyloromyotomy in LRGH. Surgery was performed on the next available elective operating list following correction of the electrolyte abnormalities using intravenous fluids. Enteral intake was resumed after 24 h. There

were no negative laparotomies or perioperative deaths and mean postoperative stay was 6.4 days. Persistent vomiting occurred in 6 patients but resolved with conservative management in 5 infants. One infant was transferred to a specialist paediatric centre for redo-pyloromyotomy. There were 4 wound infections (7 per cent) and one wound dehiscence. Twenty-four (38 per cent) had other significant co-exisiting conditions.

These data show that 87 per cent of patients were successfully treated exclusively within the region. We conclude that the majority of infants with IHPS may be safely managed in a regional centre and transfer to specialist paediatric centres should be reserved for "high risk" cases.

OPEN CHOLECYSTECTOMY IN THE LAPAROSCOPIC ERA; IMPLICATIONS FOR SURGICAL TRAINING

C. M. Gallagher, D. C. Grant, P. Connell, M. K. Barry, O. Traynor, J. M. P. Hyland.

Department of Surgery, St. Vincent's Hospital, Elm Park, Dublin 4.

The aim of this study was to review our experience of open cholecystectomy in the laparoscopic era. Since July 1990 a total of 927 cholecystectomies have been performed in our unit. All patients who underwent open cholecystectomy were reviewed. These included 66 of 801 laparoscopic cholecystectomies converted to an open procedure (8.2 per cent) and 126 open cholecystectomies. Of the combined total of 192 patients treated by open cholecystectomy, there were 127 females and 65 males. Forty-one patients had elective open cholecystectomy during the transition year after the introduction of laparoscopic surgery. Thereafter the most common indications for open operation were, previous abdominal surgery (n=21), suspected malignancy (n=10) and empyema / mucocele (n=10). Indications for conversion in the 66 patients included anatomical uncertainty (n=42), empyema (n= 11), bleeding (n=4) and technical problems (n=4). Two patients died post operatively (1 per cent). The overall compl ica t ion rate was 23 per cent (n=44), cardiorespiratory (n---22), retained common bile duct stone (n=3), deep venous thrombosis (n=2), sub phrenic abscess (n=2), bile duct injury (n=2), wound infections (n=2), post op haemorrhage (n=2) and miscellaneous (n=9). Even in the laparoscopic era open cholecystectomy is required in a percentage of patients, many of whom present with complicated biliary tract disease and associated morbidity. These patients require experienced surgical management which has major implications for surgical training.

GALLSTONES AND LAPAROSCOPIC CHOLECYSTECTOMY IN HEPATITIS C PATIENTS

M. J. O'Sullivan, D. Evoy, B. Cannon*, L. Kenny-Walshe*, M. J. Whelton*, H. E Redmond, W. O. Kirwan.

Departments of Surgery and Hepatology*, Cork University Hospital, Wilton, Cork.

Hepatitis C virus (HCV) was first identified in 1989 and is the commonest cause of non-A, non-B hepatitis worldwide. In Ireland, a large percentage of cases are associated with ant~-D immunoglobulin. The association between HCV and gallstones is unclear. We examined the incidence of gallstones in a cohort of female patients who received contaminated anti-D in 1977. and reviewed laparoscopic cholecystectomy in these patients.

6 Svlvester O'Halloran Vol. 167 - Supplement No. 5

Of the 201 women studied, who were infected with HCV from anti-D in 1977, 35 (17.4 per cent) had developed gallstones by 1997. Twenty-seven of these were discovered by screening ultra-sonography and 8 had undergone cholecystectomy prior to being diagnosed with HCV. This incidence is equivalent to that found in the population at large 1. We perform laparoscopic cholecystectomy and bi-lobar liver biopsy, if requested, on all consenting HCV patients, even if asymptomatic. Of the 25 women who underwent laparoscopic cholecystectomy, only 8 had a positive family history, in a first degree relative. Ten of the patients were entirely asymptomatic and 15 complained of chronic biliary symptoms when questioned. The patients had their surgery between February 1995 and July 1997 The operation was routine in all cases and no patient suffered any peri- or post-operative complication. Histological examination of the gall-bladder revealed chronic Cholecystitis in all cases with seven also having cholesterolosis. In conclusion, the incidence of gallstones at twenty years in this cohort of patients was that which could be expected in the general population. Laparoscopic cholecystectomy is a very safe procedure in patients with mild chronic liver disease.

R e f e r e n c e

1. Williams, C. N., Johnston, J. L. The prevalence of gallstones and risk factors in Caucasian women in a rural Canadian community. Canadian Med. Assoc. J. 1980; 122: 664-668.

IMPACT OF DIAGNOSTIC LAPAROSCOPY IN THE MANAGEMENT OF ACUTE ABDOMINAL PAIN IN

YOUNG WOMEN

H. O'Grady, S. O'Neill, D. C. Grant, M. K. Barry, O. Traynor, J. M. Hyland.

Department of Surgery, St. Vincent's Hospital, Elm Park, Dublin 4.

Acute appendicitis accounts for less than 40 per cent 1 of presentations of acute abdominal pain in young women. Non- invasive studies are frequently employed to determine other causes of acute abdom!nal pain in patients treated conservatively. The aim of this study is to evaluate the impact of diagnostic laparoscopy in the management of acute abdominal pain in women less than 30 yr of age.

A total cohort of 130 patients (1991-1997) were included in the study with a mean age of 21.5 yr. At laparoscopy, the diagnosis of acute appendicitis was made in 62 patients (48 per cent). Histology confirmed this diagnosis in 58 (94 per cent). An additional 16 visually normal appendices were removed, 6 of which contained histologic abnormalities (4 acutely inflamed, 2 fibrosis/obliterated lumen).

Gynaecological causes of pain were found in 37 patients (28 per cent). These included 33 cases of ovarian cysts, 1 infarcted ovary, 1 case of endometr ios i s and 2 cases of pelvic inflammatory disease. Seven patients had miscellaneous diagnoses and no cause was found in the remaining 8 patients.

Diagnostic laparoscopy is a useful modality in the evaluation of acute abdominal pain in young women. Positive findings may be expected in the majority of patients. Our findings suggest that negative appendicectomies may be reduced using this method.

R e f e r e n c e

1. Irvin, T. T. Abdominal pain: a surgical audit of 1190 emergency admissions. Br. J. Surg. 1989; 76: 1121-1125.

SHOULD THE NORMAL APPENDIX BE REMOVED AT DIAGNOSTIC LAPAROSCOPY FOR ACUTE RIF PAIN?

S. H. Teh, S. O'Ceallaigh, M. K. O'Donohoe, W. A. Tanner, F. B. Keane.

Department of Surgery, Meath & Adelaide Hospitals, Dublin 8.

The increased use of laparoscopy in the diagnosis of acute appendicitis has significantly reduced the number of unnecessary appendicectomies. However, the dilemma still exists as to whether an appendix which is visually normal at laparoscopy for acute RIF pain, should be removed, or if it is not removed, is there a risk of missed appendicitis?

The outcome of patients with a normal laparoscopy for acute RIF pain in whom the appendix was not removed is reviewed in this study.

The records of all patients who had laparoscopy for acute RIF pain were analysed and the relevant data extracted. Patients who had a negative laparoscopy and no procedure performed were subsequent ly fol lowed-up ei ther by te lephone questionnaire or through their GP.

Of the 171 patients who had emergency laparoscopy in the Meath Hospital between January 1990 and July 1994, 41 had no abnormality detected. The mean age of these patients was 22.7 yr (range 15-38). There were 36 females (88 per cent) and 5 males (12 per cent). Full follow-up is available on 35 patients (85 per cent). The median follow-up is 58 months (range 3-87). Twenty-one patients have remained entirely asymptomatic. Of the 14 patients who had recurrent symptoms, 2 subsequently had a histologically normal appendix removed, yet remained symptomatic, 2 had a second negative laparoscopy, 5 had ultrasound and 4 had colonoscopy or barium enema.

The results of this study suggest that removal of a normal appendix at emergency laparoscopy is unjustified.

DEFUNCTIONING LOOP ILEOSTOMY - ASSESSMENT OF PROCEDURE RELATED MORBIDITY

G. C. O'Toole, D. C. Grant, M. K. Barry, J. M. P. Hyland. Coloproctology Unit, St. Vincent's Hospital, Elm Park,

Dublin 4.

Reported complication rates for loop ileostomy construction (5-41 per cent) or reversal (10-36 per cent) indicate that their method of faecal diversion may be associated with considerable morbidity. The aim of this study was to determine the morbidity associated with both construct ion and reversal of loop ileostomies in our unit.

An analysis was performed of all patients undergoing loop ileostomy construction or reversal between 1990-1997. One hundred and two patients, (43 male, 59 female) with a mean age of 38 (range 13-81 ) yr had a loop ileostomy constructed. Indication for ileostomy construction included inflammatory bowel disease (76 patients), low anterior resection for carcinoma (16 patients) or miscellaneous reasons (10 patients). Nine patients (9 per cent) had complications arising from ileostomy construction including 4 parastomal infections, 3 high output ileostomies, 1 small bowel obstruction and 1 ileostomy stenosis in the early post operative period. Only the stricture required surgical intervention. All other complications settled on conservative management. Mean time to ileostomy reversal was 16 weeks. Three patients (4 per cent) had complications associated with reversal. All of these complications required

I.J.M.S. Sylvester O'Halloran 7 April, May, June, 1998

surgical intervention, 2 for small bowel obstruction, 1 for small bowel perforation. Currently 81 patients have had their ileostomy reversed, and 16 patients have had their loop ileostomy converted to a permanent stoma for reasons not related to the loop ileostomy itself.

Loop ileostomy construction and reversal is associated with acceptable morbidity rates. We recommend a defunctioning ileostomy as the procedure of choice for temporary faecal diversion.

CANCER OF THE LARGE BOWEL IN A RURAL IRISH SETTING

J. Calleary, L. Basso, S. B. Amjad, Z. Khan, L. McMullin, W. P. Joyce.

Department of Surgery, Cavan/Monaghan General Hospitals.

Cavan/Monaghan has one of the highest incidences of sigmoid and rectal carcinoma according to latest figures from the cancer registry. Accordingly we looked at survival of those operated on within our unit between January 1994 and December of 1995 to ascertain what if any impact this had clinically.

A total of 57 patients (M:F = 37:20) with a mean age of 68.3 (range 25-86) yr were operated on. 89.5 per centof these were elective procedures. The mean time to presentation was 3.7 months. In descending order the sites were: rectum (23), sigmoid (19), caecum (4), ascending (3), transverse (2) and others (6). The operative procedures were as follows: anterior resection (26), abdomino-perineal (10), right hemicolectomy (8), left hemicolectomy (7) and others (6). There were no peri-operative deaths with a mean stay of 14.9 days. Pathological analysis showed 9 Dukes A, 25 Dukes B, 12 Dukes C and 7 Dukes D lesions.

At 24 month follow up 48 (84.2 per cent) were available for analysis. Of these 41 (85.4 per cent) were alive and well. Three were alive but with recurrent disease and 4 (8.3 per cent were dead. Two of those who died were Dukes C and 2 Dukes D. There was 1 each from Dukes B, C and D amongst those with recurrence. In conclusion, whilst our figures are early, our survival figures are comparable to previously published results and do not appear to be influenced by the high incidence of colo rectal carcinoma within the region.

PILONIDAL SINUS EXCISION - THE CASE FOR DAY SURGERY

P. J. Balfe, M. T. Caldwell, F. B. Keane, W. A. Tanner. Department of Surgery, Meath & Adelaide Hospital, Dublin 8.

Pilonidal sinus is a relatively common surgical presentation and traditionally has been a major drain on inpatient bed days. Opinions vary in the elective setting on whether excision or exteriorisation is best. In our unit, most are dealt with by excision and primary closure and an increasing number are being carried out as day case procedures.

This study reviews the last 18 months experience at the Meath Hospital to assess if the increasing trend towards day case procedures compromised the cure rate. Forty-six (29 M, 27 F) patients undergoing pilonidal sinus excision over that period were reviewed. Thirty were carried out as inpatients and 16 as day cases. Of the 30 inpatients, 6 (20 per cent) experienced failed healing compared to 3 (19 per cent) in the day case group. Two of the 16 day cases required overnight admission.

Failed Healing Hospital Stay Day Case 3/16 (19%) In-patient 6/30 (20%) Median = 3, Range = 3-8

Day case pilonidal excision is feasible in a significant number of patients and does not appear to compromise healing.

SESSION 3

TAURINE EXACERBATES ISCHAEMIA INDUCED RENAL FAILURE

S. Teahan, K. A1-Brekeit. S. Tierney, A. Rasheed, D. Bouchier-Hayes, A. Leahy.

Department of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9.

Acute renal failure frequently occurs following hypovolaemic or septic shock, major surgery and other conditions characterised by renal ischaemia-reperfusion injury. Recent work indicates that the administration of taurine helps protect against ischaemia- reperfusion injury (I.R.I.) in both the heart and liver. The aim of this study was to determine if taurine also protects the kidney from I.R.I.

Three days preoperatively, animals were randomised into 1 of 3 groups; control (n=16), homocysteine (n=15), taurine (n=l 5). The control group were allowed normal drinking water with no additives and the other groups were given homocysteine and taurine respectively in their drinking water for the duration of the experiment. Under general anaesthesia, fol lowing administration of heparin, a left nephrectomy was performed, then the right renal pedicle was clamped for 45 rain. Blood samples were taken preoperatively and on days 1, 2, 3 and 5. Organ oedema was assessed by measuring the wet to dry ratio.

Results: < Mean Creatinine > < Mean Urea > Control Homo- Taurine P value Control Homo- Tanrine P value

cysteine cysteine Preop 45 15 47 6 8 18 Day 1 249 263 347 37 41 63 Day 2 225 241 335 41 35 83 Day 3 161 132 554 <0.001 31 29 80 <0.01 Day 5 89 84 847 <0.001 18 18 251 <0.001

*P value compared mean urea + creatinine in the taurine group to the mean values in the control + homocysteine groups.

Conclusions: Although taurine appears to protect against organ specific damage in IRA., systemic administration of taurine is unlikely to be of benefit in ischaemia reperfusion injury because of its deleterious effects on renal function.

EFFECTS OF NITRIC OXIDE SYNTHETASE INHIBITION ON SODIUM TAUROCHOLATE-INDUCED

EXPERIMENTAL PANCREATITIS

S. O'Neill, C. P. Delaney, A. Cullen*, C. O'Keane*, T. F. Gorey, J. M. Fitzpatrick.

Departments of Surgery and Pathology*, Mater Misericordiae Hospital, Dublin 7.

The role of nitric oxide (NO) in acute pancreatitis is controversial. Some authors suggest that NO blockade improves outcome, while others maintain that exogenous NO reduces systemic complications of the disease. Using an experimental pancreatitis induced by l-arginine (the precursor for NO), we have shown that NO synthetase (NOS) inhibition protects from

8 Sylvester O'Halloran

the mortality, hyperamylasaemia and histological injury seen in this model. In this study we examine the role of NOS blockade in sodium taurocholate induced haemorrhagic pancreatitis.

Thirty male Wistar rats (300-350g) were used (n=6 per group). Group 1 underwent laparotomy only; groups 2 and 3 received a retrograde pancreatic ductal infusion of 0.2ml of 0.9 per cent NaC1 or 5 per cent Na taurocholate respectively; groups 4 and 5 were given 20 mg/kg I-NMMA or 20 mg/kg 1-canavanine respectively prior to receiving Na taurocholate. Amylase, calcium and glucose were monitored. Histology was scored with a standardised blinded system. Expression of iNOS, ecNOS and endothelin were assessed blindly using immunohistochemistry to confirm adequate blockade of NOS expression.

Group Intervention Amylase Calcium Glucose Histology I laparotomyonly 5138+926 3.10-20.04 11.35:1.1 normal 2 normal s a l i n e 7742~.1123 3.11_-/-0.07 12.7+1.9 normal 3 Na taurocholate 11738+__2745* 3.035:0.10 7.45:.5.3 ++ 4 Nataur.+l-NMMA 12280+_.2131" 3.115:0.06 9.4_+0.8 +++ 5 Nataur.+l-canavanine 12043+_.3554* 3.09-20.07 8.65:0.9 +++

* = p<0.05 versus group 2 animals.

The results suggest that blockade of NO may exacerbate Na taurocholate pancreatitis. This effect is seen with blockade of ec and iNOS (1-NMMA) and selective iNOS blockade (l- canavanine). In conjunction with previous results showing an improvement in arginine induced pancreatitis with NOS blockade, these data may indicate that NO modulation may simply reduce the hypotension seen in arginine pancreatitis, but contributes to disease progression in biliary-induced pancreatitis.

TAURINE RESTORES ENDOTHELIAL DEPENDENT BUT NOT INDEPENDENT DYSFUNCTION IN YOUNG

CIGARETTE SMOKERS

F. Fennessy, C. Kelly, D. Bouchier-Hayes. Royal College of Surgeons in Ireland, Beaumont Hospital,

Dublin.

Abnormal vasoactivity, manifesting as reduced vasodilatation or paradoxical vasoconstriction in response to physiological stresses, is a feature of established vascular diseases. Flow- dependent dilatation is a feature known to be dependent on intact endothelial function. Cold pressor vasoactivity is thought to depend in part on endothelial vasodilator function and also on adrenergic stimulation. Using a non-invasive technique of measuring brachial artery diameter, we compared the effect of cigarette smoking on both flow-mediated and cold pressor- induced arterial diameter changes. We postulate that cigarette smoking impairs endothel ial-dependent and independent functions. We also investigated the effects of taurine, an anti- oxidant which has also recently been shown to upregulate constitutive nitric oxide production, on flow-mediated and cold pressor induced arterial changes in smokers.

We studied 8 healthy smokers and 11 non-smoking controls. Right brachial artery diameter changes were measured using ultrasonography at base-l ine conditions, during reactive hyperaemia, and at 1 min intervals for 10 min post immersion of the left hand in ice. Flow-mediated and cold pressor responses were re-assessed in smokers post taurine supplementation of 1.5 gms/day/5 days.

Flow-mediated dilatation was observed in all control subjects, but was significantly impaired in smokers (*p<0.005). Oral supplementation of taurine markedly improved dilatation (**p=0.005), returning diameters back to those of controls. Cold

Vol. 167 Supplement No. 5

pressor-induced vasodilation was present at 1 min in controls, in contrast to smokers in whom a vasoconstriction was induced at this time point (***P=0.02). After taurine supplementation cold pressor induced vasocons t r ic t ion was reduced (****P=0.05), but vasoactivity was not restored to that of controls.

Flow Dependent Dilatation (mm) non-smo smokers* smo tx. taurine** 0.37+0.09 0.025+0.01 0.365:0.04

Cold pressor induced vasoactivity non-smo smokers*** smo tx. tanrine**** 4.22%+5.04% 4.04%5:1.34% 0.5%5:1.9% (dilatation) (constriction) (constriction)

These data confirm the presence of endothelial dependent and independent abnormal vasoactivity in otherwise healthy young smokers. Treatment of smokers endothelium does not normalize the response of the blood vessel to stress. The failure to completely restore normal haemodyn~tmics with taurine underscores the need to eschew cigarette smoking.

SMOKERS MONOCYTE-CONDITIONED MEDIUM DOWNREGULATES NITRIC OXIDE AND UPREGULATES ENDOTHELIN-1 PRODUCTION, BOTH OF WHICH MAY

BE REVERSED BY THE AMINO ACID TAURINE

F. Fennessy, J. H. Wang, C. Kelly, D. J. Bouchier-Hayes. Beaumont Hospital, Royal College of Surgeons in Ireland,

Dublin.

Cigarette smoking is a major risk factor for atherogenesis and is present in young healthy cigarette smokers, and increased monocyte-endothelial cell interactions are potentiated in smokers and implicated in the pathogenesis of atherogenesis. We investigated the effect of monocyte-conditioned medium (MCM) of young smokers on endothelial nitric oxide (NO) and endothelin-1 (ET-1) production, and compared them to those of non-smoking controls. As wehave previously demonstrated that flow-mediated endothelial dependent dilatation can be restored to normal in smokers treated with the amino acid taurine, we investigated if MCM of taurine-treated smokers would have a beneficial effect on NO and ET-1 product ion from the endothelium.

Peripheral blood mononuclear cells were isolated from healthy volunteer cigarette smokers and non-smoking controls. Medium was condi t ioned in a time (24 and 48 h)- and concentration 2x106 monocytes dependent manner. Confluent monolayers of HUVEC were co-cultured with MCM, again in time (24 and 48 h)- and concentration (24 and 48 h conditioned medium)- dependent manner. ET-I and NO production were measured and the experiment was repeated post-supplementation of smokers with 1.5g taurine/day/5 days.

1. Endothelin-I production (pg/ml supernatant) Groups 24 h incubation 48 h incubation Smoker (n=8) 74.87+8.6 66.77+ 13 Non-smoker (n=8) 32.9+3.9* 37.25+5.5* Taurine treated smoker ( n = 8 ) 31.5_+6.9* 33.40-29.5* 2. Plasma Nitrite production (laM nitrite/ml supernatant) Groups 24 h incubation Smoker 24 h MCM (n=8) Smoker 48 h MCM (n=8) Non-smoker 24 h. MCM (n=5) Non-smoker 48 h MCM (n=5) Taurine tx'd smo 24 h MCM (n=8) Taurine tx'd smo 48 h MCM (n=8)

(stats 2 sample t-test)

0.17:!:0.16 0.39_-/-0.35 1.4+0.24* 1.3+0.47* 1.895:0.31" 1.66+0.39*

*P<0.001 vs. smo

48 h incubation 0.38_+0.18 0.39_+0.42 1.9_+0.42* 2.5_+0.69* 3.8_+0.8* 4.17+0.75"

I.J.M.S. April, May, June, 1998

Sylvester O'Halloran 9

Conditioned medium of monocytes from young healthy cigarette smokers significantly attenuates NO release and upregulates ET-1 release from normal endothelium, providing evidence that monocyte functioning and its interaction with endothelium is abnormal in smokers. These data suggest that soluble factors may mediate the effects of monocytes, and may provide evidence for a contributory role of the moaaocyte in diminished endothel ia l -dependent relaxation in smokers. Monocytes of smokers treated with taurine can restore NO and ET-1 released from endothelium to control non-smoking levels, suggesting that modification of monocyte as well as endothelial functioning is important in the prevention and management of atherogenesis.

MODULATION OF MUCOSAL BARRIER FUNCTION DURING INTESTINAL ISCHAEMIA BY ENDOGENOUS

RELEASE OF ADENOSINE

D. C. Winter, J. MacFarlane, B. J. Harvey, G. C. O'Sullivan. Departments of Surgery and Cellular Physiology, Mercy

Hospital and University College Cork.

Loss of intestinal barrier function during periods of mucosal ischaemia leads to bacterial translocation and endotoxaemia. Multiple organ dysfunction syndrome may develop if the insult is severe or prolonged. We examined the effect of experimentally- induced ischaemia on the mucosal barrier of human colon in- vitro.

Normal mucosa, microdissected from fresh colectomy specimens, was mounted in Ussing chambers and oxygenated in a Ringers solution. ' Ischaemia' was induced by inhibiting glycolysis and oxidative phosporylation with 2-deoxyglucose (a non-hydrolysable substrate) and oligomycin A respectively. Barrier integrity was assessed by recording transepithelial resistance (ohm/cm2). Values represent mean + S.E.M. for n=6 (t-test for statistical analysis).

Controls exhibited stable transepithelial resistance (146+12.9 ohm/cm 2) indicating normal barrier function. Ischaemia produced a biphasic fall in resistance - an early transient trough (correlating with chloride secretion) (63.7+9.2 ohm/cm 2) was followed by a progressive loss or barrier integrity (26.6 per cent at 40 min) (P<0.01). Aspirated luminal bath fluid from ischaemic colon (at I0 rain) induced a similarly transient secretion when added to controls. Secretion was inhibited by an adenosine receptor antagonist (8-phenyltheophylline) in both groups (P<0.01). Prior exposure of mucosa to adenosine ameliorated barrier function during subsequent ischaemia (64.7 per cent at 40 min P<0.01).

Ischaemic colonic mucosa generates secretion through release of adenosine in an auto/paracrine manner. This may indicate a defence mechanism to protect mucosal barrier integrity. The mechanism by which adenosine confers protection is a potential therapeutic target in the management of critically ill patients with impaired splanchnic perfusion.

THE ROLE OF BLOOD FLOW CHARACTERISTICS IN THE FORMATION AND RATE OF PROLIFERATION OF

ARTERIAL DISEASE ON THE BED OF DISTAL ANASTOMOSES OF VASCULAR BYPASS GRAFTS

M. Walsh t, T. McGloughlin t, P. Grace 2, D. Colgan 3. mUniversity of Limerick, Plassey Technological Park, Limerick,

2Limerick Regional Hospital, Raheen, Limerick, 3Boston Scientific Ireland Ltd., Ballybrit Business Park, Galway.

After grafting the arterial disease initiation process has been

shown to involve the presence of abnormal wall shear stresses acting on the endothelium (Lei)k These abnormal shear stresses cause "stretching" of the endothelium, which causes the cell- cell gaps to widen. This results in particles passing through the endothelium, while in normal flow, the particles would be too large to pass through. This causes disease formation.

Numerical simulations of the blood flow have been performed using a computational fluid dynamics (CFD) package (FLUENT, (Fluent Europe)). The veloci ty of blood flow changes periodically due to the rhythmic pumping of the heart. The initial pulsatile studies, using steady flow velocities from a velocity profile of a resting heart pulse, show that the floor stagnation point moves within the artery over a path repeated for every pulse. This movement contributes to the rate of proliferation of arterial disease.

The significance of the non-Newtonian nature of blood was also investigated. Blood displays both Newtonian and non- Newtonian behaviour in the arterial system (Cho2). However, blood displays its non~ characteristics specifically in small diameter vessels and in regions of complex flow. Initial results show that the non-Newtonian nature of blood contributes to the abnormal wall shear stress distribution present at the distal anastomosis. Thus the non-Newtonian nature of blood increases the shearing forces acting on the endothelium and therefore increases the rate of proliferation of the disease also. References 1. Lei, M. Computational fluid dynamics analyses and optimal design of bifurcating blood vessels. PhD. Thesis, North Carolina State University 1995. 2. Cho, Y. I., Kensey, K. R. Effects of the non-Newtonian viscosity of blood on flows in a diseased arterial vessel�9 Part 1 - Steady Flows, Biorheology 1991 ; 28: 241-262.

A CRITICAL REAPPRAISAL OF THROMBOLYS1S 1N A SPECIALIST VASCULAR SURGICAL UNIT

P. Madhavan, S. Sultan, M. P. Colgan, N. McEniff*, M. Molloy*, D. Moore, G. Shanik.

Departments of Radiology* and Vascular Surgery, St. James's �9 Hospital, Dublin 8.

The widespread use of intra-arterial thrombolytic therapy has been based on perceived benefits over operative treatment and the downgrading of the magnitude of subsequent surgery. We retrospectively analysed 33 patients who had thrombolysis for peripheral artery occlusion in St. James's Hospital from 1991- 1997.

One patient received streptokinase rather than tissue thromboplastin activator (TPA) unsuccessfully and was not included. Five other patients' records were inadequate for analysis leaving 27 cases for consideration. Patients' notes were analysed for risk, duration of occlusion, conduits thrombolysed, duration of treatment and dosage of TPA.

There were 15 males and 12 females. The mean age was 62 yr (range 20-87). Fourteen were current or reformed smokers. Five were diabetic. Indications for treatment included acute graft occlusion, embolus and arterial thrombosis. Duration of occlusion was <24 h in 7, 1-7 days in 10 and >7 days in 10 patients.

Twelve of 27 (44 per cent) patients had complete clot lysis. No major amputations occurred in this group but 11/12 required revisional surgery to maintain graft patency. Four of the 12 had significant complications (2 false aneurysms and 2 haematomas requiring transfusion). Fifteen patients (56 per cent) had either

10 Sylvester O'Halloran Vol. 167 Supplement No. 5

no clearance or partial lysis. There were 5 amputations in this group and 1 death. Analysis of these failures did not show that time before presentation (more than or less than 24 h), type of conduit occluded, gender, aetiology or smoking history had any s igni f icant bear ing on outcome. TPA was un iversa l ly unsuccessful in diabetic patients. Total dose of TPA appeared to be inversely related to success and increased duration of infusion did not improve outcome.

Conclusion: We question the benefits of such therapy and suggest that primary surgical, treatment may in fact be more appropriate.

A RENAL DIALYSIS UNIT: ITS IMPACT ON VASCULAR SURGICAL WORKLOAD

E. Eguare, R Maher*, M. Creamer*, C. Fiuza, P. Grace, C. J. Cronin*, P. Burke.

Department of Surgery & The Haemodialysis Unit*, Regional General Hospital, Dooradoyle, Limerick.

The development of regional dialysis units has lead to an increased demand for vascular access surgery. Between January 1995 and October 1997, 34 patients entered the long-term dialysis programme in the Mid-Western region (population = 320,000). There were 24 (70.6 per cent) males and 10 (29.4 per cent) females - median age 65 yr (range 20-83 yr). Eighty-four procedures relating to vascular access were performed in the 34 patients (an average of 2.4 procedures per patient), 62 (73.5 per cent) procedures were to create access, and 22 related to catheter removal, fistula closure or complications of access surgery. Only 9 patients commenced dialysis using an arteriovenous fistula; in 19 patients the first access procedure was a Quinton wide- bore intravenous catheter and 6 had a temporary intravenous catheter. Twenty-two patients had arteriovenous fistulae formed (19 autogenous and 3 Gortex), 5 required revision of their fistulae and 3 subsequently had new fistulae created. A total of 10 patients (29 per cent) developed complications after access surgery. Twenty of the 34 patients are alive and well-on dialysis, 8 had renal transplant, 1 patient spontaneously recovered and 5 patients have died.

Vascular access procedures accounted for 10 per cent of the vascular surgical workload in the 33 month period and much of these related to surgical complications. Planned creation of an arteriovenous fistula will help to reduce the need for repeated catheter placements and may help to reduce the morbidity associated with vascular access. Vascular access is an important part of the renal dialysis services and surgical expertise should be available at a regional level to cope with likely demand.

TOWARDS BETTER DETECTION OF OCCULT DIABETES IN VASCULAR PATIENTS

H. H. Sigurdsso ~, J. A. M. Shaw ~, W. Kim ~, G. Linklater ", W. G. Simpson h, D. W. M. Pearson ~, K. S. Cross ~.

Departments of Vascular Surgery ~, Clinical Biochemistry b and DiabetesL Aberdeen Royal Infirmary.

Postal Address: Dept. of Vascular Surgery, Ward 36, Aberdeen Royal Infirmary.

Audit of 100 admissions to a regional vascular centre revealed inadequate screening for diabetes mellitusL A prospective study

was undertaken to determine the incidence of diabetes and impaired glucose tolerance (IGT) in admissions with peripheral vascular disease and to compare ~,arious screening tests.

Consecutive admissions to the vascular unit with chronic lower limb ischaemia were recruited by informed written consent. Incidence of known diabetes was recorded with any history of primary osmotic symptoms or family history of diabetes. Random plasma glucose (RPG) was assayed on admission with fasting plasma glucose (FPG) and glycosylated haemoglobin (HbA1C) the following morning. Interval 75g oral glucose tolerance test (OGTT) was performed in those without known diabetes as a 'gold standard' measure of glucose tolerance.

Two hundred and 14 patients were recruited. Fifty-two (24 per cent) bad previously diagnosed diabetes. Seventy-four of the remainder have undergone OGTT to date with 9 (12 per cent) new diagnoses of diabetes and 14 (19 per cent) of IGT. HbA1C correlated best with diagnostic 2 h OGTT value (r=0.53; p<0.001) compared with RPG (r=0.3; p=0.0 I) and FPG (r=0.18; p=0.16). HbAlc was the most sensitive screening test for diabetes given adequate specificity (HbA1C>6 per cent: sensitivity 88 per cent; specificity 77 per cent V8 RPG>7.8mmol/1 : sensitivity 44 per cent; specificity 94 per cent vs EPG>7mmol/l: sensitivity 63 per cent; specificity 93 per cent).

Conclusion: There is a high incidence of previously diagnosed diabetes in admissions with peripheral vascular disease. Moreover, occult abnormal glucose tolerance is present in 31 per cent of the remainder. Random plasma glucose is a poor screening test and it may be that HbA1C proves to be the best screening tool in this high risk population.

Following completion of outstanding OGTT's and further data analysis, a revised protocol for diabetic screening will be implemented and audited to complete the loop.

Reference 1. Stuart, W. P., Wolf, B., Macaulay, E. M., Cross, K. S. Screening for diabetes on a vascular ward: lessons from an audit. J. R. Coll. Surg. Edin. 1998; in press.

DON'T JUST SIT THERE - WIGGLE YOUR TOES!

P. Fitzgerald, P. Quinn, S. Tierney, D. Bouchier-Hayes. Department of Surgery, Beaumont Hospital & Royal College

of Surgeons in Ireland, Dublin 9.

Leg swelling commonly occurs in those seated for long periods, such as during long haul airline flights, even in the absence of deep venous thrombosis. Prevention of swelling by repeated flexion and extension of the ankle joint is often recommended but the efficiency of this manoeuvre is unknown. This study was designed to compare the effects of ankle movements against resistance on the efficiency of venous pumping in the seated and erect position.

The air plethysmograph was used to determine venous pump efficiency in erect and seated positions in a single limb of 10 healthy adult volunteers. Functional venous volume is the difference in limb volume between supine and erect or seated positions. Ejection volume is the volume of blood ejected by a single contraction of calf muscles by standing once on tiptoe (erect) or by pressing once on a custom designed foot pump (seated). Residual volume is that remaining after 10 maximal calf contractions in either erect or seated positions. These are expressed as fractions (percentage) of the functional venous

I.J.M.S. April, May, June, 1998

volume as the ejection volume fraction (EVF) and the residual volume fraction (RVF). EVF and RVF are indicators of calf pump efficiency and RVF correlates accurately with ambulatory venous pressures. Results (Means+standard deviation) were:

Venous Ejection Ejection volume Residual Residual Volume volume (ml) volume (ml) Fraction (%) Volume (ml) Fraction (%)

Erect 88+20 51+_20 58+17 24+5 27+6 Seated 76+18" 45+16 60-+14 21_+7 27-+6

r ~ 0.84 0.90 0.65 0.68 0.11 p <0.05 vs Erect (Paired Student's t test), r 2 Pearson Correlation coefficient (Erect vs seated).

Although functional venous volume was significantly less in the seated position, EVF and RVF were similar in both groups indicating similar venous pump efficiency in the erect and seated position. We conclude that repeated plantar flexion of the ankle while seated, by effectively operating the calf venous pump, may prevent limb swelling during prolonged sitting.

SESSION 4

THE INFLUENCE OF SLING TENSION ON THE OUTCOME OF PUBOVAGINAL SLING SURGERY FOR

STRESS URINARY INCONTINENCE.

C. M. Brady, S. M. A. Shah, M. Ehtisham, M. S. Khan, H. D. Flood.

Department of Urology, The Regional Hospital, Dooradoyle, Limerick.

Pubovaginal sling (PVS) has been criticised because of the frequent need for intermittent catheterisation (IC) postop. However, some investigators have suggested that reducing sling tension may reduce voiding dysfunction without compromising treatment efficacy. Therefore, we compared early voiding dysfunction and efficacy in 2 groups of patients after PVS where the only variable was sling tension.

Sixty consecutive patients underwent PVS by the same urologist from January 1996 to August 1997. Both groups were well matched. In the first 30 (Group 1), the sling suture was tied very loosely (2-3 fingers, no tension) and in the second 30 (Group 2) tighter (1-2 fingers, some tension). Two days postoperatively, voiding efficiency (VE) was measured. Residual volume was measured by IC. When voiding efficiency was >75 per cent IC was stopped. If a patient had clinical and urodynamic evidence of stress incontinence PVS was considered a failure.

VE was significantly better in Group 1 than Group 2 for the 1 st 3 voids 48 per cent, 63 per cent, 69 per cent v 23 per cent, 30 v 38 per cent, respectively. In addition, although 8/30 (27 per cent) patients in Group 1 and 17/30 (57 per cent) patients in Group 2 needed to continue ISC after the 1st 3 voids (X2=5,55, p < 0.025) the mean duration of catheterisation was not significantly different (13 v. 20 days; t test, p=0.5, N.S.). On the other hand, the early failure rate (<3 mths) for Group 1 was significantly higher than in. Group 2 [6/30 (20 per cent) v 1/30 (3 per cent); )~z =4.04, p<0.05)].

As practised by these investigators there is a degree of sling tension which when used will result in a very high early success rate with a very small penalty of early voiding dysfunction. Advocates of PVS need to avoid tying the sling too loosely. What is "loose" needs to be determined by the individual operator over a large number of cases as accurate standardisation between operators is probably impossible.

Sylvester O'Halloran 11

THE VALUE OF MEDIASTINOSCOPY AND LYMPH NODE BIOPSY IN PREOPERATIVE STAGING OF LUNG

TUMOURS

M. Loubani, K. Sweeney, B. Lenehan, V. Lynch. Thoracic Surgery Unit, St. Vincent's Hospital, Elm Park,

Dublin 4.

Mediastinoscopy and lymph node biopsy in pre operative staging of lung turnouts is not universally accepted. The aim of this study was to determine the sensitivity of mediastinal node biopsies obtained at mediastinoscopy.

There were 324 mediastinoscopies carried out in the period 1996-1997.

One hundred and 93 of these were for staging of lung tumours. Mediastinoscopy is normally carried out after rigid bronchoscopy at the same setting. We routinely take 10 biopsies from the lymph nodes of the suspected hilum. There were no complications reported.

Eighty-seven (47 per cent) patients had mediastinal lymph nodes positive for tumour. One hundred and 6 (53 per cent) had lymph nodes negative for tumour. Fifty-six of these patients were not considered suitable candidates for surgery. Fifty patients progressed to thoracotomy for resection of tumour with curative intent. We reviewed the charts of the 50 consecutive patients who had surgery. There were 30 males and 20 females with a mean age of 66 (range 43-85).

The final pathology on these 50 patients included squamous cell carcinoma (20), adenocarcinoma (18), large cell carcinoma (11) and clear cell carcinoma (1). On review of the final pathology reports 6 out of the 50 patients had positive hilar lymph nodes.

The findings at mediastinoscopy as compared with the final pathology show that it has a sensitivity of 96 per cent (87/87+6). This combined with a specificity of 100 per cent and no complications leads us to recommend the routine use of mediastinoscopy.

POLYESTER IS A SAFE ALTERNATIVE TO STAINLESS STEEL WIRE IN TENSIONS BAND FIXATION OF

PATELLAR FRACTURES

A. Joy, G. McGreal, D. Reidy, K. Mahalingam, W. Cashman. Department of Orthopaedics, Cork University Hospital,

Wilton, Cork.

Because wire is difficult to handle, and often requires removal, we use a braided polyester suture in place of stainless steel wire in tension band fixations. The objective of this study was to test the biomechanical properties of this technique. Sixteen cadaveric patellae were fractured and then repaired by the modified tension band technique, as described by the AO group. Eight were fixed using 18 gauge stainless steel wire as a tension band and 8 using braided polyester (no. 5 Ticron) instead of wire. All specimens were subjected to tensile testing on a Lloyd's T5K tensile testing machine, to the point of failure of fixation. Polyester was 75 per cent as strong as steel.

For dynamic testing, the patellae of 7 cadaveric knees were fractured and then repaired with polyester tension bands. The specimens were mounted in a specially constructed device which held the femur horizontally, allowing the tibia to swing freely before a scale calibrated in degrees. A weight of 11.8 kg was attached to each tibia, 12.7 cm below the knee joint, to simulate twice the weight of an average leg. The quadriceps tendon was grasped in a clamp and pulled in the direction of the femur

12 Sylvester O'Halloran Vol. 167 Supplement No. 5

causing the knee to extend. Fracture separation was measured every 10 ~ from 90 ~ to neutral, giving a mean of 0.08 mm.

Three specimens fixed using wire tension bands were compared with 3 fixed using polyester over 2000 cycles of flexion and extension, against an applied weight of 5.9 kg. There was no significant difference in the resulting fracture gaps (Mann Whitney). We conclude that polyester is a safe alternative to wire in tension band fixation.

ADJUNCTIVE CHEMORADIOTHERAPY IN OESOPHAGEAL CARCINOMA DOES NOT INCREASE

POST-OPERATIVE MORBIDITY OR MORTALITY

E. D. Mulligan, T. Purcell, B. Dunne, M. Griffin, N. Noonan, D. Hollywood, N. Keeling; J. V. Reynolds, T. P. J. Hennessy. Department of Surgery, Pathology and Gastroenterology, St.

James' Hospital, Dublin.

The oncological benefit of multimodal therapy (preoperative chemo- and radiotherapy followed by surgery) in oesophageal cancer compared with surgery alone has been established, with improved disease-free and overall survival reported. Assurances that this benefit is not at the cost of increased perioperative wound and septic complications as a result of the neoadjuvant therapies is required. We performed a detailed analysis of morbidity and mortality associated with these factors in randomised clinical trials of patients with oesophageal cancer receiving either neoadjuvant therapy (2 cycles of fluorouracil and cisplatin and 40Gy of external beam radiation) prior to surgery or surgery alone.

All complications that may be influenced by abnormal wound heal ing or immune func t ion were recorded, inc lud ing anastomotic leaks, organ failure, septicaemia and multiple organ failure (MOF). The results were as follows:

multimodal surgery only n=104 n--lOg

30 day mortality 11 (11%) II (10%) Major complications 38 (37%) 44 (41%) Number of complications 56 73 pneumonia 22 (21%) 29 (27%) anastamoticleaks 10 (10%) 8 (7%) sepsis/MOF 4 (4%) 9 (8%) organ failure 9 (9%) 5 (5%) abdominal/thoracicabscess 6 (6%) 2 (2%)

There was no significant difference between groups in complications that may relate to preoperative wound healing and immune competence. Fears that a price may be paid in the perioperative period for the oncological efficacy of multimodal therapy were thus unfounded in these randomised studies.

FORTY SEVEN YEARS OF PHAEOCHROMOCYTOMAS

D. O'Halloran, G. McGreal, E. W. McDermott, N. J. O'Higgins.

Department of Surgery, St. Vincent's Hospital, Elm Park Dublin 4.

Thirty patients with phaeochromocytomas had surgery in St. Vincent's Hospital between 1950 and 1997. The age of patients at operation ranged from 17 to 74 yr. Twenty-two of the patients were female and eight male. Twenty-six patients had sporadic tumours and 4 had multiple endocrine neoplasia syndrome (MEN

2). None of the patients were related. All but one of the patients had hypertension, 20 had exc.essive sweating and 22 had palpitations, all having at least 1 of these cardinal symptoms. Other symptoms included syncope, pallor, lethargy, blurred vision, chest pain and abdominal pain. Diagnostic tests changed over this period. The diagnosis was confirmed biochemically in 25 patients, in the early cases by the phentolamine test and later by measurement of urinary VMA and catecholamines. IVP was used to locate the tumour in 10 of the 17 patients that presented before 1967. CT, ultrasound or MIBG scanning were used to locate the tumours in 11 of the 13 cases since 1967. Fourteen of the tumours were left sided, 11 were right sided, 3 were bilateral and 2 were extra-adrenal. In 2 patients, the diagnosis was made at laparotomy. Before 1967, 3 of 17 patients died peri- operatively, 2 of these from strokes and 1 from suspected pulmonary embolism. Since then, all patients have survived surgery. Four of the women had phaeochromocytoma diagnosed during pregnancy. Of these, one had surgery while pregnant and the others had surgery in the post-partum period. All 4 women and their offspring survived, Two of the tumours were malignant, the remainder being benign. One patient has died from metastatic disease. This series illustrates the changing trends in the surgical management of phaeochromocytomas.

FLEXIBILITY: ITS IMPORTANCE IN RAPID DIAGNOSTIC BREAST CLINIC PROTOCOLS

P. Neary, D. Hamilton, N. Haider, N. Aherne, D. Walsh*, M. Murphy +, R. G. K. Watson #.

Departments of Surgery ~, Radiology* and Pathology +, Waterford Regional Hospital.

Rapidity of diagnosis is thought to alleviate anxiety in symptomatic breast disease. A rapid diagnostic breast clinic (RDBC) was establ ished in September 1996. General practitioners were instructed to refer only patients of 35 yr or over who had a palpable breast lump, breast pain, or nipple distortion and/or discharge. On the morning of the clinic patients underwent examination, mammography, ultrasonography, and fine needle aspiration cytology (FNAC). A scoring system between 1 and 5 was devised to assess malignant status with 1 being considered benign and 5 definitely malignant for each diagnosis modality. Following diagnosis the patients were counselled as to their proposed management.

In total 160 patients were seen over a 12 month period of which 13 per cent had an inappropriate referral. Over 80 per cent had a breast lump and 26 per cent had a family history of breast carcinoma. Interestingly, only 13 per cent of patients with malignancy had a positive family history. Fifty-three per cent were post-menopausal. There were 39 cancers indicating a cancer referral rate of 1 in 4. A score of 5 on cytology or a total score of 16 or above was indicative of malignant disease. Only 6 per cent required open or Tru-cut biopsy. In all patients requiring surgery this was undertaken within 2 weeks of their original clinic appointment. Of note, one patient (26 yr) deemed an inappropriate referral, had a resectable carcinoma detected.

The guidelines proposed adequately cover referrals for the diagnosis of malignant breast disease. This resulis in a reduction in the benign disease work-load of a specialist breast clinic. Although RDBC guidelines are well established, a degree of flexibility is required to ensure all patients with cancer are included.

I.J.M.S. April, May, June, 1998

LAPAROSCOPIC OOPHRECTOMY AS AN ADJUVANT THERAPY IN WOMEN WITH BREAST CARCINOMA

"THE GALWAY EXPERIENCE"

M. Joyce*, S. Johnston, O. Clinton, H. E Given. National Breast Cancer Research Institute and Department of

Surgery National University of Ireland, Galway.

In Univers i ty College Hospital Galway, laparoscopic oophorectomy (Lap) is offered as an adjuvant therapy to pre- menopausal women with breast carcinoma. Our study involved 100 consecutive women who had a bilateral oophorectomy in the period from 1993 to 1997. This group was compared for overall survival and disease free survival against an age staged matched group (Con=91).

The results are

Con Lap Con Con Lap Lap overall ER<20 ER>20 ER<20 ER>20

% Recurrence 28% 19% 33% 29% 33% 18% % Deaths 15% 10% 14% 21% 22% 5% % Disease free 73% 81% 67% 71% 67% 82%

These data suggest that; 1) there is a clinically significant improvement in overall survival and disease free survival for those patients who had bilateral oophorectomy, against controls who were matched for both age and stage. 2) the greatest benefit was seen in those pre-menopausal women deemed to be oestrogen receptor rich. 3) this benefit was demonstrated through all stages of disease. In conclusion, this initial Galway analysis, suggests that surgical ablation of functioning ovaries prolongs disease free interval and overall survival without significant morbidity.

LONG TERM RESULTS OF COMBINED AORTIC AND RENAL ARTERY RECONSTRUCTION

A. Brannigan, M. O'Donohoe, J. Donohoe, T. Corrigan. Mater Misericordiae Hospital, Dublin.

The role of surgery in the management of renovascular hypertension is established. However, combined aortic and renal disease still presents a major challenge to the vascular surgeon.

The results of surgery for combined renal and aortic disease in 16 patients with 23 renal artery stenosis or occlusions are reviewed. The mean age was 58 yr and male:female ratio 10:6. Six patients had aneurysmal disease and 10 aorto-iliac occlusive disease. In addition to severe hypertension, 9 patients had evidence of renal failure pre-operatively, 1 of whom was dialysis dependent. There were 4 unilateral and 1 bilateral renal artery occlusion. Surgical procedures performed included aortic tube grafts, aorto-iliac and aorto femoral bypasses with combined aortic graft - renal artery bypass. Autogenous saphenous vein was used for 12 of the renal bypasses. The mean follow-up is 75 months (range 12-156). There was 1 post-operative death (6.2 per cent). Ten patients are still alive and of the 5 who died during follow-up, none died from renal arterial disease. Mean arterial blood pressure fell from-a pre-operative level of 180/ 107 mm Hg, on therapy, to a current level of 139/80 mm Hg (p<0.05). In patients with renal failure, mean serum creatinine fell from 238 Ixmol/l pre-operatively to 148 I.tmol/1 currently (p<0.05). Medication fell in both dosage and number of agents from a mean of 2.3 agents pre-op to a current level of 1.3.

It is conc luded that combined aortic renal artery reconstruction is a viable therapeutic option in patients with combined aortic and renal arterial disease.

Sylvester O'Halloran 13

THE MAJORITY OF RECURRENT VARICOSE VEINS OF THE LONG SAPHENOUS SYSTEM CAN BE PREVENTED

M. Bresnihan, M. K. O'Donohoe, T. M. Feeley. Department of Surgery, Meath & Adelaide Hospitals,

Dublin 8.

Recurrence of varicose veins after surgery is a significant problem accounting for up to 20 per cent of all varicose vein surgery. The aim of this study was to identify the anatomical failures of primary surgery and determine if these failures could be avoided. All patients undergoing varicose vein surgery under a single vascular surgeon underwent clinical assessment, duplex scanning and recording of intraoperative anatomical cause of recurrence. In a series of 900 operations for varicose veins, 101 operations (11.2 per cent) in 91 patients were for recurrence. The mean age was 53.3 yr and the female:male ratio 3:1. The surgical approach was based on the duplex findings.

The anatomical causes of recurrence identified were:- + Sapheno Popllteal

Incompetence Intact sapheno-feraoral junction and long saphenous complex 19 6 Residual long saphenous stump with tributaries 17 2 Residual long saphenoas stump, tributaries and thigh saphenous 20 0

I n c o ~ t residual thigh saphenous 18 4 Neovasculatisation 6 0 De novo sapheno popliteal incompetence 21

Therefore, failure to adequately ligate the sapheno-femoral junction and its tributaries was the cause of recurrence in 56 per cent, while 18 per cent were due to a residual intact thigh saphenous vein. Thus 74 per cent of recurrences are potentially avoidable by careful sapheno-femoral surgery. A further 21 per cent of recurrences are due to either new onset or unrecognised sapheno-popliteal incompetence, many of which could have been avoided by pre-operative duplex scanning.

It is concluded that the key to successful primary varicose veins surgery is to accurately identify and ligate the sapheno- femoral junction and its tributaries and strip the thigh saphenous vein. Duplex scanning is useful in both the diagnosis of recurrence and unrecognised short saphenous incompetence.

TRANSFEMORAL ENDOLUMINAL AORTIC MANAGEMENT; A MINIMALLY INVASIVE OPTION IN

AORTIC INTERVENTION

S. Sultan, P. Madhavan, M. P. Colgan, D. Moore, G. Shanik. Vascular Surgery Department, St. James's Hospital, Dublin 8.

Transfemoral endoluminal aortic management [TEAM] offers a minimally invasive option in selected patients requiring aortic surgery. We report 8 cases with a cumulative primary patency rate of 100 per cent at 24 months. The indication for TEAM included aortic aneurysms in high risk patients (n=3), embolic disease from saccular aortic aneurysms (n=2), aorto-iliac disease with blue toes (n--2) and aorto-renal vein fistula (n=l). There were 3 males and 4 females with mean age 68.5 yr. TEAM was chosen because of high surgical risk with conventional surgery. All patients had segmental pressures, colour-coded ultrasound, arteriography, and contrast enhanced computed tomography preoperatively. The procedures were performed in the operating theatre under epidural anaesthesia. The procedure was considered successful if there was complete exclusion of the

14 Sylvester O'Halloran

lesion and restoration of normal blood flow documented by completion angiogram. The average duration of surgery was 2.1 hr. Patients were discharged after a mean hospital stay of 4 days. Physical examination and non-invasive testing were performed prior to discharge, at 6 weeks, 6 months, 1 yr and annually thereafter. There were no operative deaths, no peri-operative blood transfusions and no intensive care unit beds were needed. Mean follow up is 13 months and all grafts remained patent without complications. Our initial results suggest TEAM can be used successfully in selected patients with aorta-iliac disease. Long-term follow up is required to ensure the durability of these devices as vascular surgeons now appreciate the potential of internal bypass.

POSTER SESSION

. THE ACCURACY OF DOPPLER ULTRASOUND IN THE DIAGNOSIS OF TESTICULAR TORSION

M. P. McMonagle, D. Quinlan, D. Kelly. St. Vincent's Hospital, Elm Park, Dublin 4.

This retrospective analysis looked at 17 patients aged 30 yr or less who presented to the accident and emergency department, with acute testicular pain, within the past 12 months. The age range was 16-30 yr inclusive with a mean age of 19.6 yr. All patients were explored within 3 h of presentation and obtaining Doppler ultrasound of testes did not delay transfer to theatre. Patients were divided into 2 groups. Group A consisted of those patients who had an ultrasound and subsequent exploration and Group B those patients who had exploration alone. Group B consisted of 8 patients; 7 had testicular torsion, 1 had torsion of cyst of Morgagni. Group A consisted of 9 patients. In 6 of these cases the ultrasound and intra-operative findings correlated well for testicutar torsion. In 3 cases, the ultrasound and intra- operative findings did not correlate. One case was radiologically consistent with torsion, but was completely normal at surgical exploration. Two cases were radiologically inconsistent with torsion but were torted at exploration. Therefore the false positive rate for Doppler ultrasound in the management of testicular torsion was 12.5 per cent (1/8), and the false negative rate was 25 per cent (2/8).

In conclusion, the use of Doppler ultrasound in the diagnosis of testicular torsion is not reliable.

PATIENT KNOWLEDGE OF RISKS AND PROPHYLAXIS POST-SPLENECTOMY

P. K. Hegarty, B. Tan, C. Cronin, M. P. Brady. Department of Surgery, Cork University Hospital, Wilton,

Cork.

The asplenic patient has a deficient immune response particularly to diplococci. Certain immunisation and prophylaxis is required. Patients must be aware of these measures and take an active role in their health management.

A telephone survey was carried out of 50 patients who had a total splenectomy between 1989 and 1997. This evaluated their knowledge of the risks of asplenism and means of limiting these risks. The results of this and its implications for current practice are discussed.

Vol. 167 Supplement No. 5

CODING FOR AUDIT IN IRELAND

M. Zeeshan, D. J. McAvinchey. General Hospital, Nenagh, Co. Tipperary.

Hospital inpatient enquiry (HIPE) is funded from central sources to return reports on hospital activity in Ireland. Dedicated coding staff are employed and trained in data ga ther ing and coding. The HIPE remit has no role in implementation of audit nor in facilitation of audit activity other than as defined by the ESRI and Department of Health.

In order to assess the accuracy of coding practice, the clinical description from the discharge letter database was compared to the ICD-9 and OPCS description from the HIPE database. A high level of accuracy was found; 6 per cent wrong code for diagnosis and 4 per cent wrong code for procedures. (See table).

TOTAL NO. OF PATIENTS SURVEYED = 530 Accuracy of Diagnosis Codes

Missing data Accurate Inaccul'ate Wrong Discharges HIPE

87 18 356 62 25 88.76% 14.58% 5.88%

Accuracy of Procedure Codes Total Procedures Accurate ~naccurate Wrong

161 145 10 6 90.06% 6.21% 3.72%

Conclusions: This high degree of accuracy is due in part to the careful provision of a principle diagnosis and procedure from the clinical setting. This could be improved by including the coding process within the discharge letter database and regular validation reports to check for accuracy. There is no necessity, in Irish hospitals, for doctors to do their own coding. Co- operation between HIPE coding and clinical audit projects would be beneficial to both parties.

ELECTIVE THYROID SURGERY IN THE 1990s: HAVE WE PROGRESSED?

N. Aherne, C. Mooney, D. Coyle, N. Haider, D. Hamilton, P. Neary, R. G. K. Watson.

Department of General Surgery, Ardkeen, Waterford Regional Hospital.

Thyroid surgery still remains both a common and challenging operation for the general surgeon. We retrospectively examined our own experience in elective thyroid surgery in the late 1980s (1984-9) and compared this to our results for cases performed in the 1990s (1990-7). This study comprises a 13 yr period covering 169 cases and examines the patient demographics, operative course, histological profile and postoperative outcome of both time periods.

Between 1984-9 76 patients underwent elective thyroid surgery; from 1990 we have operated on 93 further patients. Female patients still predominate with the male:female ratios remaining similar during both intervals (1:6, 1980s), (1 : 1.75, 1990s). The mean age of the patients has increased in recent times with an older case population presenting in recent yrs. (1980s mean age 40 yr, 1990s mean age 61 yr). The mean length of stay has decreased from 7.3 days (range 4-20) to 5 days (range 4-13). Mul t inodular goi tre remains the most common presentation representing 54 per cent cases in 1980s and 65 per cent cases recently. There has been an increase in the number of adenomas 18 per cent (vs 10 per cent) and carcinomas 9 per cent (vs 4 per cent) operated upon. The postoperative morbidity

I.JM.S. Sylvester O'Halloran 15 April, May, June, 1998

has decreased also. In our original series there were 4 per cent haematomas, 6 per cent wound infections and 2 recurrent goitres. These problems have not arisen in the latter series of patients. We have had no peroperative mortalities.

Our retrospective analysis covering 13 yr and 169 patients revealed that despite an increasing age profile and a higher incidence of carcinoma based surgery, the mean length of stay for our patients has decreased. This may be secondary to the improvement in preoperative assessment and imaging (7 per cent of cases underwent CT or MRI), combined with increasing re f inement of modern surgical techniques . These data characterise our own experience in elective thyroid surgery and augurs well for cost based analysis of this surgery in nonspecialised units

POSSIBLE PREVENTATIVE STRATEGIES FOR FEMORAL NECK FRACTURES

G. Khayyat, E. Masterson. Croom Orthopaedic Hospital, Croom.

Approximately 300 fractures of the femoral neck are referred to our unit annually for management, This usually entails either internal fixation or replacement of the femoral head with a prosthesis. The increasing age of our population will make this an ever increasing problem in the yrs to come.

The majority of such fractures occur in patients over the age of 70 yr and many are over 80 yr. The mechanism of injury is usually a low ve loc i ty fall occur r ing within the home environment or within a nursing institution.

We have prospectively evaluated the precise mechanism of injury in a group of 100 fractures to determine whether any preventative strategies might be usefully employed in the domestic environment.

Nearly all fractures occurred either in the home or within its immediate vicinity. Most injuries occurred following a simple fall. Common contributory factors included stairs or steps, loose carpets or floor coverings, and attempts to perform strenuous domestic tasks. Other factors included difficulty in accessing bathroom facilities, simple falls from high beds, medications and co-existent diseases.

We feel that many of these injuries are potentially preventable and that visits to the home environment by occupational therapists and social services would prove cost effective in this regard.

COMPARISON OF FIVE YEAR FOLLOW-UP OF PATIENTS WITH MAMMOGRAPHICALLY DETECTED

VS CLINICALLY DETECTED BREAST CANCER.

T. Thambi-Pillai, K. Farah, C. P. Delaney, M. B. Codd*, J. M. Fitzpatrick, T. F. Gorey.

Departments of Surgery and Epidemiology*, Mater Misericordiae Hospital, Dublin 7.

Mammographic imaging of the breast has made the detection of preclinical breast cancer possible. The technique is thought to confer a survival advantage of up to 25 per cent to the patient, and also increases the feasibility of performing conservative breast surgery. The ECCLES breast screening program was initiated in 1989 to evaluate the benefit of mammographic screening for an Irish cohort of patients. This study was designed to determine any benefit of screening for these patients by

comparing their 5 yr follow-up with a group of patients who presented over the same time period with symptomatic turnouts.

Patients who underwent their initial treatment between November 1989 and December 1992 were included. Records were examined to determine patient, turnout and treatment characteristics. Patients were reviewed in the clinic and evaluated for disease-free status, loco-regional recurrence and distant metastatic disease. Univariate and multivariate analysis were performed using SPSS and surv iva l curves were constructed and compared.

n Follow- TI T2 NO N1 Mastec- ChemoRx 5 year up (mths) (%) (%) (%) (%) tomy (%) (%) mort.

Screened 44 65.1 47.7* 45.4 75.0* 18.2 86.4 6.8** 2.3 Symptomatic 82 62.8 29.3 52.4 56.1 34.1 80.2 33.0 8.5 * p=0.05 vs. symptomatic patients. ** p<0.05 vs. symptomatic patients.

Forty-four tumours were diagnosed by screening (57.6-+7.6 yr), while 82 were symptomatic (55.9+14,2 yr. Mean follow-up was over 5 yr both groups. Tumours in screened patients were smaller and less l ikely to have involved nodes than in symptomatic patients. Mastectomy rates were similar in both groups, however screened patients were significantly more likely to require chemotherapy. Although there was a trend towards reduced 5 yr mortality in screened patients, this did not reach significance.

Mammography detects earlier stage breast cancer in an Irish cohort of women, permitting the option of conservative surgery to be considered in more patients. Early indications suggest that a survival advantage may develop for this cohort of patients.

PANCREAS REGENERATION AFTER PARTIAL RESECTION: DOES IT OCCUR IN MAN?

M. K. Barry, G. G. Tsiotos, C. D. Johnson*, M. G. Sarr. Departments of Surgery and *Radiology, Mayo Clinic,

Rochester, MN55905, U.S.A.

Although pancreatic regeneration after partial resection or pancreatic injury has been demonstrated experimentally in animal models , no reports indicate whether a s imilar phenomenon occurs in the human pancreas. Our aim was to determine reliably for the first time whether the human pancreas regenerates after resection.

We reviewed the pre- and postoperative computerised tomograms (CT's) of 21 patients after curative anatomic proximal pancreatectomy (estimated 50 per cent resection) for malignancy (1993-96) who had no recurrent disease during fo l low-up. Patients with di lated pancrea t ic ducts and parenchymal abnormalities were excluded. Three measurements (pancreatic body width, tail width, and length) were recorded for each patient. These segments of pancreas on preop CT were compared with the same region of the pancreatic remnant on postop CT at 2 different time points postop: mean of 10 months (range: 4-23 months) for 21 pts, and mean of 21 months (range: 9-41 months) for 9 pts. Data are expressed as mean + SEM and compared using paired t-test. The 21 patients (8M, 13F) had a mean age of 66 yr (range: 37-83 yr). Resection was for pancreatic, ampullary, and duodenal cancer in 9, 9, and 3 patients. Measurements before and 10 months after resection (n=21) were no different for body width (2.0_+0.1 vs 1.8+0.1 cm, p=0.4), tail width (2.2+0.2 vs 1.8+0.2cm, p=0.1) or length (8.2+0.3 vs 7.4+_0.4cm, p=l). All patients were alive with no evidence of disease at a follow-up of 20 months (range: 6-41 mos). Measurements before and 21 months after resection (n=9)

16 Sylvester O'Halloran Vol. 167 Supplement No. 5

were: body width 2.2+0.2 vs 1.5_+0.2cm, p=0.006, tail width 2.2_+0.1 vs 1.5+0.2cm, p=0.0 1, and length 8.1+0.4 vs 8. l_+0.4cm, p=0.9.

This study provides no evidence that the human pancreas regenerates after partial anatomic (50 per cent) resection.

A STUDY OF HELICOBACTER PYLORI AS A POSSIBLE PATHOGEN IN ACUTE APPENDICITIS

M. R. Kell, M. Lynch, D. Ryan, A. O'Donovan, D. C. Winter, H. P. Redmond.

Department of Surgery Cork Regional Hospital and University College, Cork.

Helicobacter pylori has been identified as a pathogen in peptic ulcer disease and non-ulcer dyspepsia. A direct link with gastric cancer has led the WHO to recently classify H. pyl.ori as a grade 1 (definite) carcinogen. H. pylori has also been directly linked to primary B-cell mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach, salivary glands, duodenum, small intestine and rectum with complete remission reported following H. pylori eradication ~. It is possible that Helicobacter pylori could grow in the appendix or that appendicular MALTomas could arise due to proximal H. pylori infestation. We tested the hypothesis that these factors contribute to the initiation of appendicitis.

We performed histological and microbiological analysis of the appendices from 25 consecutive patients undergoing open appendectomy. Once excised, appendix samples were sent for histological and microbiological examination. Serology was performed in all cases on admission.

The mean age of the sample group was 23.68 yr (8-44 yr). Eighty-four per cent had a histological confirmed appendicitis. Serology was positive in 60 per cent. No appendix specimens demonstrated positive urease activity and culture was negative for all. Similarly, no histological evidence of H. pylori was observed in the 25 specimens.

It is evident that H. pylori has effects on the host that extend far beyond the stomach. Moreover, H. pylori may live outside the upper gastrointestinal tract 2. However, in this study of 25 patients H. pylori was neither isolated nor visualised from appendix specimens. Furthermore, we were unable to link positive serology and acute appendicitis.

Conclusion: We were unable to find any direct or indirect evidence for an association between H. pylori and appendicitis.

References: 1. Matsumoto, T., Lida, M., Shimizu, M. Regression of mucosa- associated lymphoid-tissue lymphoma of rectum after eradication of HelicobacterPylori. Lancet. 1997; 350:115-6. 2. Thomas, J. E., Gibson, G. R., Darhoe, M. K. et al. Isolation of Helicobacterpylori from human faeces. Lancet. 1992; 340:1194-1195.

OPERATIVE REPAIR IMPROVES CONTINENCE IN PATENTS WITH ANAL SPHINCTER INJURY.

C. P. Delaney, M. Cassidy, M. Doyle, G. Fulton, P. R. O'Connell.

Department of Surgery, Mater Misericordiae Hospital, Dublin 7.

Faecal incontinence is a profoundly distressing condition. Symptoms are adequately controlled in most patients using dietary and pharmacological means. A minority of patients

continue to have incapacitating symptoms and require surgical intervention. This study assesses 22 such female patients (mean age 44 yr) who underwent Parks' overlapping anal sphincter repair for anatomical sphincter injury between 1990 and 1996.

Patients were re-assessed and scored for faecal incontinence (0-20 Pescatori score), faecal urgency, urinary incontinence and perineal pain before consenting to trans-anal ultrasound and anal manometry to determine anatomical and physiological outcome. All patients had sphincter injury secondary to traumatic vaginal delivery.

Pescatori score Max. restin~ pressure Max. saueeze incr. pre post p pre post p pre post p

Park's repair 14.5 9.1 0.005 30.0 27.9 0.71 31.1 44.0 0.12

Although sphincter repair produced little change in anal manometry, patients after surgical repair had significantly improved Pescatori scores for faecal incontinence. There was no change in the degree of faecal urgency, perineal pain or urinary incontinence. Postoperative trans-anal ultrasound of the anal sphincters was performed in 11 patients and revealed thinning of the internal sphincter. The external sphincter was scarred but grossly intact in all cases. Nine patients had a minor defect in the superficial component of the external anal sphincter. This did not correlate with clinical outcome.

The Parks' overlapping anal sphincter repair improves faecal continence in patients with anatomical anal sphincter injury who respond inadequately to conservative measures.

EVIDENCE BASED SURGERY, FACT OR FICTION?

R. Kingston, M. Dillon, M. Barry, S. Tierney, P. A. Grace. Department of Surgery, Limerick Regional General Hospital

& University of Limerick, Limerick, Ireland.

Increasing pressure to reduce costs and increase efficiency within the health service demands that treatment be supported by scientific evidence of its effectiveness. The aim of this study was to evaluate the proportion of evidence based therapy during one month in a Regional hospital. All 206 general surgical and urology patients (elective and emergency) admitted during a single month (November 1996) were identified retrospectively using the Hospital inpatient enquiry (HIPE) database. From patients charts, the primary diagnosis, comorbidity and treatment given were determined. Two computerised databases (Medline, Cochrane) were searched over the previous 5 yr for evidence supporting the treatment administered. Treatment was classified as (A) supported by randomised clinical trial (RCT), (B) supported by case studies, or (C) unsupported by any objective evidence. The results were:

Diagnosis RCT Case studies Unsupported Total General/Gl 53 (32%) 106 (63%) 7 (4%) 166 Urological 8 (31%) 17 (65%) 1 (4%) 26 Vascular 8 (57%) 6 (43%) 0 14 Total 69 (33%) 129 (63%) 8 (4%) 206

Treatments unsupported by evidence included: amoxycillin/ clavulanic acid for tonsillitis (n=2); left hemicolectomy for bleeding polyp (n=l); biopsy of cervical lymph node (n=l); biopsy of mastectomy scar nddule (n=l); suturing of facial laceration under general anaesthesia (n= 1); alginate suspension for recurrent vomiting in a 5 yo child (n=l); and radical cystectomy for transitional cell carcinoma of the bladder (n= 1).

We found that treatment in 96 per cent of our patients was evidence based, but was based on randomised controlled trials

in only 33 per cent. Treatment in 63 per cent was validated by published case reports or large case series and only 4 per cent of treatments were entirely unsupported by the recent literature. These data reflect the difficulties in organising large randomised clinical trials but demonstrate that, in our unit, modern surgical practice is predominantly evidence based.

excision but the differences were not significant. When the 26 original surgical specimens were cut, 6 showed turnout grossly involving some margin, while 3 tumours extended close to a margin. No comment was made about the others. If this was known at the time of surgery, wider excision of the margin in question could have been performed during the initial operation. Perhaps up to 9 re-excisions may have thus been avmded.

WHAT DETERMINES OUR RE-EXCISION RATE FOLLOWING BREAST CONSERVING SURGERY FOR

CARCINOMA?

G. McGreal, B. Lenehan, M. Murray, E. McDermott, N. O'Higgins .

Department of Surgery, St. Vincent's Hospital, Elm Park, Dublin.

Breast conserving surgery is an established treatment for selected patients with breast carcinoma, with overall survival e q u i v a l e n t to that f o l l o w i n g mas t ec tomy . Pat ients with histologically positive resection margins have a local recurrence rate of 20 per cent , even with radiotherapy. This falls to 8 per cent when resection margins are free of tumour. For this reason, we perform further surgery in patients with involved margins fo l lowing ini t ial breast conse rv ing surgery. Patients with involvement of deep margins, and other margins where the initial excision has been as complete as possible, do not have re- excisions. Our aims were to establish our rate of re-excision and to identify factors that may predict the need for same. Between 1/8/95 and 31/7/97, a total of 232 patients had surgery for breast carcinoma, 89 (41 per cent) having conserving surgery initially. Twenty-six (28 per cent) of these had further excision for i n v o l v e d margins , of which 10 had modi f ied radical mastec tomy and 16 had wider local excision. Of these 16 patients, 6 had a third procedure, comprising 5 mastectomies and 1 further local excision. This meant, that of 89 patients, 121 opera t ions were per formed and 64 finally had breast conserva t ion . Factors relat ing to the first operat ion were analysed (Mann Whitney) in the group of patients who required re-excision and those who did not. There was no significant difference in turnout size, grade, his tological type, site, or surgeons ' exper ience . An ex tens ive in-situ component and lymphovascula r invas ion were associated with re-excis ion (p=0.04 and 0.03 respectively). Positive lymph nodes and lobular cancerisat ion were more common in patients requiring re-

BILATERAL GRAFT FAILURE CAUSING FALSE ANEURYSMS AT 13 YEARS

M. R. Kell, R. G. O'Sul l ivan, B. Tan, J. A. O'Donnel l . Department of Surgery, Cork Regional Hospital and

University College, Cork.

A 70 yr old men presented with painless bilateral groin swel l ings of 4 weeks duration. He had undergone aorto- bifemoral reconstruct ion 13 years previously for occlusive disease. His only medical history was of essential hypertension and stable angina. On examination he was found to have b~Iateral pulsatile swellings symmetrically in the region of his femoral triangles. He was admitted for bed rest and imaging which revealed bilateral 4 cm aneurysms in both femoral limbs of the 13 yr old graft. At surgery false aneurysms were found in both graft limbs, these did not involve the anastomotic sites which were patent.

This patient exhibits a primary graft failure rather than the delayed anastomotic failure ~ which was initially suspected. At the initial surgery a woven Dacron trouser graft was inserted and vascular control was achieved by clamping both limbs with a "DeBakey" type clamp while the distal anastomoses were fashioned. We postulate that these clamps caused sufficient damage to the graft to result in delayed failure 13 yr later; this would also explain why these aneurysms were symmetrical. This is an exceptionally rare cause of vascular prosthesis failure and we have found only one other described 2.

References 1. White, R. A., Donayre, C. E., Walot, I., Wilson, E., Jackson, G., Kopchok, G. Endoluminal graft exclusion of a proximal para- anastomotic pseudoaneurysm following aortobifemoral bypass. J. Endovasc. Surg. 1997; 4: 88-94. 2. Orri, M., Shirasugi, N., Yamazaki, M., Akiyama, Y. Pseudoaneurysln caused by disruption of an externally supported knitted Dacron graft for femoropopliteal bypass. Tokai J. Exp. Clin. Med. 1995; 20:241-4