Gut, 1963, 4, 158

The management of primary adenocarcinoma of thevermiform appendix

K. T. HESKETH1From the Department of Surgery, Hammersmith Hospital and Postgraduate

Medical School, London

EDITORIAL SYNOPSIS Primary adenocarcinoma of the appendix is not of low grade malignancy ashas been previously supposed and a right hemicolectomy is the proper procedure, offering a muchbetter prognosis than simple appendicectomy.

Primary adenocarcinoma of the appendix is rare andlikely to pass unrecognized. The diagnosis is usuallymade by a histologist, unless at operation the diseaseis so advanced that its nature is unquestioned. It isthe purpose of this paper to describe several newcases and to examine past experiences of this tumouras a guide to treatment and prognosis.Tumours of the appendix constitute only 0.3 to

0.4% of all intestinal growths and during the lastcentury were regarded as metastases although Mer-ling (1838) and Rokitansky (1867) both describedprimary tumours of the appendix. Kelly and Hurdon(1905) in their large text on the appendix offered aclassification of these tumours. Their illustrationsshow three typical argentaffin tumours, one adeno-carcinoma, and one probable sarcoma. Collins (1955)surveyed 50,000 human appendices mostly removedfor appendicitis. His series embraces almost 100disease classifications including 18 malignant condi-tions.Many estimates of the incidence of this carcinoma

are found in the literature, varying from 0.5% to3.0% of appendicectomies. None of these estimatesis based on large series and they must vary with localhistological classification. Two extensive series areavailable, both from the United States. Norment(1932) in a survey of 45,000 appendices reported 67'carcinomas'. Two of these are grouped apart as'atypical' columnar-celled growths and were prob-ably adenocarcinomas. The histological description ofthe remaining 65 leaves little doubt that they wereargentaffin tumours. Collins (1955) found 0.08% in50,000 cases; this possibly represents the incidence.

In 1955 in England and Wales it is estimated that117,000 persons had their appendix removed and ifthe figures in Hammersmith Hospital are any guide'Present address: c/o British Military Hospital, Singapore

TABLE INUMBER OF APPENDICECTOMIES PERFORMED DURING 10

YEARS IN DEPARTMENT OF SURGERY, HAMMERSMITHHOSPITAL

Year 'Primary' 'Incidental' TotalOperations Operations

1949195019511952195319541955195619571958

Total

280260240230255310240220270220

2,525

27404030202110438665

382

307300280260275331250263356285

2,907

(Table I) this number is fairly constant each year.In the United Kingdom only 12 cases of adenocarci-noma of the appendix which fulfil strict criteria havebeen reported in the 30 years before this paper. Inthis department over the past ten years 2,525 'prim-ary' appendicectomies have been performed and tothese must be added 382 'incidental' operations doneduring the course of gynaecological or other abdomi-nal procedures. During this period one case ofadeno-carcinoma has arisen (case 1).

Previous writers have commented on the confusedstate of the literature concerning this tumour. In 1906Rolleston and Jones produced the first extensive ac-count and collected a series of cases including that ofBeyer (1882) who described what has come to beregarded as the first authentic case. They also inclu-ded cases by men famous in the history of the appen-dix-Battle and McBurney. However, no clearhistological classification emerges from this and noneof these cases is included here partly due to lack ofhistological evidence, and also because the treatment

158

The management ofprimary adenocarcinoma of the vermiform appendix

and prognosis of acute, uncomplicated appendicitishas altered so much in the past balf century as tominimize the value of these early cases.

Frauenthal and Grausman (1933), describing a

case, mentioned 360 previous accounts, a figure farin excess of anything subsequently accepted. At theother extreme, Young and Wyman (1942) questionedall but four earlier reports, two from the UnitedStates and two from Germany. In 1943 Uihleinand McDonald re-assessed histologically 144 casesseen over a 30-year period at the Mayo Clinic,confirming only five.The earliest case report quoted here is 1929 but

most of the others have been in the last five years.The older accounts are less easy to evaluate properlyand follow-up reports impossible to obtain.

Notwithstanding the publications that haveappeared, as recently as 1953 Clarke and Simondscommented that little was known regarding thefrequency, route, and extent of metastases, or of theprognosis of carcinoma of the appendix and thebest surgical procedures for dealing with it.

HISTOLOGICAL CLASSIFICATION

Difficulty arises with the histology of the adenocar-cinoma and the confusion with the argentaffin carci-noma commonly known as the 'carcinoid'. In theirpaper of 1943 Uihlein and McDonald produced thefollowing classification which has provided a stand-ard for several subsequent authors: 1 Carcinoid type,2 cystic type, and 3 colonic type.

I CARCINOID TYPE Willis (1948) prefers to callthese argentaffin carcinomas 'lest we disguisetheir inherent malignant nature'. They were shownin 1914 to have the property of reducing ammoniacalsilver salts to silver and are now well recognizedas a distinct entity. Masson (1928) gave a classicaldescription of these tumours. Their golden-yellowcolour is almost constant and they tend to bemulticentric in origin. The cells may be biochemicallyactive, secreting 5-hydroxytryptamine and causinga clearly defined syndrome.

2 CYSTIC TYPE Cystic type or mucocele of theappendix was first recognized by Rokitansky in1842. Although included in their classification byUihlein and McDonald, it is not clear that this is a

distinct entity and there is certainly no evidence thatit is always of a malignant nature. Willis says that toproduce a mucocele one does not require a neo-

plastic process and Aird does not regard the muco-

cele as necessarily malignant.Woodruff and McDonald (1940) had discussed

this. From 43,000 appendices removed over a 24-6

year period at the Mayo Clinic they abstracted 146cases of mucocele: 136 of these were simple and in10 were due to early neoplastic hyperplasia of themucosa similar to that seen in McCollum's cases(V.1.). It could be suggested that in these cases theovergrowth of the mucosa provides a mechanicalfactor which leads to the production of a mucocele.The condition may be produced experimentally bymechanical means.

3 COLONIC TYPES The colonic type or adenocarci-noma behaves similarly to other colonic carcinomasbeing either polypoid or ulcerative.

Attempts have been made to subdivide the adeno-carcinomas into several grades; this is unrealistic insmall series and produces statistically insignificantfigures.

It has been written that the site of the lesion gives aclue to its nature: that the adenocarcinoma is to befound in the proximal third and that the distal thirdsare the province of the argentaffin tumour. In a highproportion of reports here the site of the tumour isnot reported. This prevents any conclusion but 22(23 %) cases of adenocarcinoma are recorded in theproximal third and 38 (34%) in the distal thirds.Thirty-five (37 %) were not recorded. When thetumour is found at the proximal extreme of theappendix it is a matter of opinion whether it arisesin the appendix or the caecum: one or two doubtfulcases of this category have been discarded.There are certain anatomical features of the appen-

dix which affect the progress of the disease. Thenarrow lumen is soon occluded by even a smallgrowth, which may precipitate an acute obstructiveappendicitis. This is the usual picture and may causea number of carcinomas to be removed at an earlystage, and to go unnoticed. The appendix is alsocovered by peritoneum and extensive soiling of theperitoneal cavity easily occurs if the appendix perfor-ates; this is the commonest site for metastases.The material for this series has been collected from

the reports mostly in the British, Canadian, andUnited States literature with the addition of a fewothers. A total of 95 cases has been selected foranalysis (Table II). Many, especially those describedin the earlier papers, have been discarded as notfulfilling the conditions of the present enquiry whichhas been limited to invasive tumours, reasonablybelieved to be adenocarcinomata and penetratingbeyond the submucosa. To these have been addedthe new cases described. There are several reports ofthe tumour confined to the mucosa but it is difficultto draw a line between a simple hyperplasia and thisvery early form of malignancy when reading someof the reports.Those workers who had not already recorded the

159

Age Sex Presentation

TABLE IIDETAILS OF INDIVIDUAL CASES

Initial Operation Which Later Right How Site ofKnownThird of Hemicolectomy Long SecondaryAppendix After- Deposits

wards

Known RemarksSurvival

73 F Secondary deposits

73 F Cholelithiasis (inci-dental operation)

72 M Appendix abscess55 M Acute appendicitis34 F Acute appendicitis43 F Appendix abscess48 F Appendix abscess83 F Appendix abscess89 F Appendix abscess? F Acute appendicitis

36 F Acute appendicitis

69 F Pain and mass in R.lower quadrant

48 M Acute appendicitis80 F Acute appendicitis

56 M Acute appendicitis

71 M Acute appendicitis

49 F Secondary ovariandeposits

53 M Acute appendicitis62 M Acute appendicitis

55 F41 M

72 M43 M57 M53 M70 M

60 F64 F53 M52 F51 F55 F

34 M54 F

52 F

62 M

36 F

60 M

50 F

65 M46 M

36 M40 M22 F

65 M58 F

60 M

_ D

Appendectomy D

Appendectomy PAppendectomy DAppendectomy DDrainage onlyAppendectomy PR. hemicolectomy -R. hemicolectomy PAppendectomy DAppendectomy All

Appendectomy P

AppendectomyAppendectomy M

Appendectomy -

Appendectomy D

Appendectomy, DpanhysterectomyAppendectomy DAppendectomy

Acute appendicitis AppendectomyAcute appendicitis Appendectomy

Appendix abscess Appendectomy DAcute appendicitis Appendectomy PAcute appendicitis Appendectomy PAcute appendicitis Appendectomy DAcute appendicitis Appendectomy P

Carcinoma caecum R. hemicolectomy -Acute appendicitis Appendectomy DAcute appendicitis AppendectomyChronic appendizitis Appendectomy? Acute cholecystitis Appendectomy DGynaecological case Appendectomy M(incidental operation)Acute appendicitis Appendectomy DCholelithiasis (inci- Appendectomydental operation)Gynaecological Appendectomy(incidental operation)Strangulated right Appendectomy Dfemoral herniaPain in right lower Appendectomy Mquadrant 6 months'Chronic appendicitis' Ileo-transverse P

colostomyCholelithiasis Appendectomy D(incidental operation)Acute appendicitis R. hemicolectomy PDuodenal ulcer Appendectomy M(incidental operation)Acute appendicitis Appendectomy D'Chronic appendicitis' Appendectomy MGynaecological case Appendectomy M(incidental operation)Acute appendicitis Appendectomy PAppendix abscess Appendectomy M

Acute appendicitis Appendectomy D

- - Peritoneum Died soonafter

No - - 5 years Still alive and well

Yes 2 weeks - - No available follow-upNo - No (14 years)1 Alive and well at that tinieNo - No No known follow-upYes 3 weeks Ovary 5 years Died of metastasesNo - - - No available follow-up- - - - No available follow-up- - Locally - No available follow-upYes 3 years Locally - No available follow-upYes 2 weeks - (3 years) Still alive and well then

No available follow-upNo - No (9 months) Still alive and well then

No available follow-upYes 2 weeks - 6 years Still alive and wellRefused - Locally peritoneum, 1 year No available follow-up,

abdominal wall probably died soon after-wards

Refused - - (1 year) Alive and well at that time.no further availablefollow-up

Yes 2 weeks Local node, 5 years Died of metastasesperitoneum wound

No - Ovary and No available follow-up, presumedperitoneum dead shortly afterwards

Refused - - No available follow-upNo - - (21 years) Alive and well at that time,

no further availablefollow-up

Refused - - 6 months DiedAdvised - - Did not return for hemicolectomy. No

further traceNo - - 2 years DiedYes 2 weeks - 5 years Still alive and wellYes Not known- - Still alive and wellYes Not known- 94 years Still alive and wellNo - (4 years) Still alive and well 1951

at age 74- - - 9 years Still alive and wellNo - - 84 years Still alive and well- - Locally 4 years DiedNo - Peritoneum 24 years Died of metastasesNo, poor heart - - 5X years Still alive and wellInoperable at 4 weeks Peritoneum - No available follow-up,

presumed dead soonafterwards

Yes 3 months - 7 years Still alive and wellYes 4 weeks - 3 years Still alive and well

Yes 3 weeks - 8 years Still alive and well

Refused - - 13 years Died of heart disease

No - No (10 years) Still alive and well then,no available follow-up

Yes 3 weeks No (34 years) Still alive and well then,no available follow-up

No - No (4 years) Still alive and well then,no available follow-up

- - - 5 years Still alive and wellNo - No (I year) Still alive and well then,

no available follow-upYes 3 weeks No 19 years Still alive and wellNo - - - No available follow-upNo - - - No available follow-up

Yes 3 weeks - - No available follow-upNo - Wound locally (24 years) Still alive then, no avail-

1 year able follow-upRefused - - (8 months) Still alive then, no avail-

able follow-up

'Survival times shown in parentheses are those patients known to have lived for that period but are not up to date (1959

TABLE I I continuedDETAILS OF INDIVIDUAL CASES

Age Sex Presentation Initial Operation Which Later RightThird of HemicolectomyAppendix

How Site of KnownLong SecondaryAfter- Depositswards

Known RemarksSurvival

Appendix abscess Appendectomy P

Gynaecological case Appendectomy P

(incidental appendectomy)Appendix abscess R. hemicolectomy1I years pain in right Appendectomy P

lower quadrantSecondary deposits - P

Carcinoma caecum R. hemicolectomy DIntestinal obstruction R. hemicolectomy D

Gynaecological case Appendectomy(incidental operation)Acute appendicitis Appendectomy D

Acute appendicitis Appendectomy P

Acute appendicitis Appendectomy M

Acute appendicitis R. hemicolectomy MGynaecological case Appendectomy D(incidental operation)Secondary deposits

Acute appendicitis Appendectomy M

Acute appendicitis AppendectomyIntestinal obstruction Appendectomy D

Secondary depositsAcute appendicitis Appendectomy DAcute appendicitis Appendectomy D

Carcinoma of caecum R. hemicolectomy P

Acute appendicitis Appendectomy P

Mass in right lower R. hemicolectomy PquadrantCholelithiasis Appendectomy D(incidental operation)Acute appendicitis Appendectomy All thirds

Acute appendicitis Appendectomy M

Right lower quadrant Appendectomy P

pain for 6 monthsAcute appendicitis Appendectomy

Right lower quadrant Appendectomy Dpain for 3 weeksAcute appendicitis AppendectomyAcute appendicitis AppendectomyAcute appendicitis Appendectomy DAcute appendicitis AppendectomyAppendix abscess Appendectomy

Acute appendicitis Appendectomy

Secondary deposits

Appendix abscess R. hemicolectomyAcute appendicitis AppendectomyAcute appendicitis Appendectomy D

Acute appendicitis AppendectomyAcute appendicitis Appendectomy

Mass in right iliac fossa R. hemicolectomy PSix months pain in Appendectomy Dright iliac fossaSecondary ovarian BiopsydepositsPain in right iliac AppendectomyfossaAppendix abscess R. hemicolectomyAcute appendicitis Appendectomy

Acute appendicitis R. hemicolectomy

YesYes

No

No

No

No

No

Yes

No

Refused

No

Yes

No

No

No

NoNo

Yes

NoNoYesNoInoperable

Yes

NoNo

NoYes

Yes

Yes

No, due to poorcondition

5 weeks Wound at 3 years 4 years Died8 weeks - 7.L years Still alive and well

- Peritoneum 2 years Died- Ovaries 21 years Died

- Peritoneum - Died shortly afterwards- Peritoneum 3 years Died- Local nodes 8 years Still alive and well

(excised)- Ovary 10 months Died

- Wound and 1P years Believed deadperitoneum

- - 7 weeks Died from abdominalabscess

8 weeks - 84 years Still alive and well- - 8 years Still alive and well- - 25 years Still alive and well

- Glands, lungs - Died soon afterpleura, and peritoneum

- - 2 years Died of C.V.A.- - 3 days Died ? renal failure- Glands and 6 months Died

peritoneum- Peritoneum - Died soon after- - - No available follow-upNot Glands, colon, No available follow-upstated wound- Nodes, lungs, liver, 10 months Died

peritoneum- Peritoneum 4 months Died- Peritoneum 6 months Died

- - 7 months Died despite deep x-raytherapy

- Omentum, 3 months Diedperitoneum

- Peritoneum 10 months DiedNo 24 months Died other causes

- - 6 weeks Died after laparotomy ?no obvious cause

10 days - 6 years Still alive and well

- - 3 days Died peritonitis- Generalized 2 years Died4 weeks No 2 years Still alive and well- - - Died of peritonitis4 weeks Peritoneum 3 months Died

2 weeks Local nodes 2 weeks Died C.V.A.(excised)

- Glands and Died soon afterwardsperitoneum

- 'Generalizeddeposits'

9 weekslater

8 weekslater- Ovary and

peritoneum2 weeks Locally,later peritoneum

r- Locally

- Locally

5 years DiedNo available follow-up

1X years Died

- No available follow-up5 years Still alive and well

10 years Still alive and well- Still alive and well

- Died shortly afterwards

6 months Died despite deep x-raytherapy

8 years Still alive and well8 months Died suddenly ? coronary

3 years Died ofsecondary deposits'Survival times shown in parentheses are those patients known to have lived for that period but are not up to date (1959).

56 M42 F

54 F41 F

51 M57 M40 F

49 F

64 M

72 M

26 F67 F43 F

61 M

79 M51 F56 F

46 M72 F

42 M

46 M47 M

59 M

63 M

65 M65 M

58 M

51 F

44 F49 F61 F67 F43 M

61 F

68 F

47 F41 M60 M

39 M51 M

51 F17 F

63 F

42 M

72 F? F

54 F

K. T. Hesketh

death of a patient have all been circularized to bringthe follow-up figures up to date.

DIAGNOSIS

The diagnosis has never been established beforeoperation and it will be seen that this condition mostcommonly presents as an acute obstructive appendi-citis. Forty-two (44%) of the cases here presented asacute appendicitis, a further 13 (14%) as appendixabscesses, and 8 (11 %) as 'chronic appendicitis'.These together comprise 66% of all cases. Eightcases (11 %) presented in a terminal phase withwidespread metatases.As many as 13 (14%) patients had an 'incidental'

appendicectomy with subsequent histological dis-covery of an adenocarcinoma. A pre-operative diag-nosis of cholelithiasis or a gynaecological disorderhad without exception been made and sustained atoperation. No attempt has been made to classifythese cases separately.

AGE AND SEX INCIDENCE

The age incidence and range is shown graphically(Fig. 1). The youngest subject is 17 years old. Theage group 40-65 years is most commonly affectedbut no age group appears immune.There is no sex predominance of any significance,

there being 49 female patients and 45 males.

TREATMENT

When we come to treatment, we found in this Unit

17-Ia15-14-13-12-

I09-

7-6-

4-3-2

that no one had first-hand experience of this diseaseand faced with such a growth found by appendi-cectomy (case 1) the decision to do a formal righthemicolectomy was originally founded on basicprinciples. A brief survey of some of the literature atthat time did little to help. Authors were divided asto the proper measures to adopt. This more extensiveanalysis has attempted to show that the proportionof cases in which a hemicolectomy has been donehas risen appreciably in the last few years. One couldinfer from this that the more radical operation is be-coming accepted as a proper form of treatment.There still remains the problem of direct 'seeding' ofthe peritoneal cavity but it would seem that this isunavoidable.The treatment at the moment is essentially surgical.

Only two patients were given radiotherapy, one inthe United States and case 2 reported in the UnitedKingdom. The first was dead of the disease in sevenmonths and in the other instance only a short pal-liative course was given because of intestinal ob-struction and rapid deterioration. Deep x-raytherapy has probably no more obvious application incases of adenocarcinoma of the appendix than incarcinomas of the colon.From the point of view of treatment let us consider

a total of 87 cases, omitting those eight presentingin a terminal stage.Of these 87, 15 (17%) bad a right hemicolectomy

as a primary procedure when the nature of thedisease was recognized at the initial operation.Twenty-five (28 %) had a hemicolectomy as asecondary procedure a week or so after. This wouldallow proper preparation of the patient. For 12patients (14%) a further resection was proposed butwas not carried out either because of the patient'scondition or because consent to operation wasrefused. Radical surgery was thus proposed in 60%of the cases and carried out in 46 %. Those remaininghad an appendicectomy only. Two of these also hada local resection of the caecum.McCollum et al. (1957), in considering those

tumours confined entirely to the mucosa (V.S.), wereof the opinion that appendicectomy would suffice.Growths of this type have not been considered herebut the anatomical structure of the organ raisesgrave doubts whether a distinction can be drawn intheir treatment. The muscular layers of the appendixare often deficient at several points where the sub-mucosa becomes adjacent to the serosa.Adenocarcinoma of the appendix has bzen referred

to previously as one of low-grade malignancy but thecases reviewed suggest that it behaves as aggressivelyas any other colonic cancer although it differs insome respects. Transcoelomic spread occurs readilyand produces peritoneal and ovarian secondary de-

o '0 -n o-u o on-' i o '0 -o

0 N '4Nt 'M usuT o 'on Z :0 .r,S

FIG.O._ i o age inc id 0n 0 n ran

FIG. 1. HiStogranl of age incidence and range.

162

The management ofprimary adenocar-cinoma of the vermniiform appendix

posits. By their nature these multiply rapidly andappear to be lethal before extensive hepatic metasta-ses are established. Few references are found tosecondary deposits in the liver. Adjacent lymphnodes are commonly involved and serve as a strongmotive for radical surgery. Local recurrence is alsoquite common both intraperitoneally and in thewound. This has occurred despite hemicolectomyand sometimes several years after operation.

PROGNOSIS

In assessing the prognosis, the 18 patients known tohave died of intercurrent disease, and those presentingwith secondary deposits or dying within three monthsof operation have been excluded. The remainder ofthe patients has been divided into two groups, thosein whom a simple appendicectomy was performedand those who had a right hemicolectomy. Twoexpressions of the prognosis have been used. First,5 and 10-year survivals for each group are given, and

757

secondly the 'median survival time' is given for eachgroup, i.e., the time at which 50% of the patientsremain alive; these are plotted with the times atwhich 750% and 250% remain alive, and give a muchbetter idea of the pattern of survival and enablebetter comparison of techniques (Fig. 2).From Fig. 2 it will be seen that the survival

curve for the cases submitted to more radical surgeryis shifted well to the right and is much less steep. Itshould be remembered also that this improvedprognosis is underemphasized by this graph as two-thirds of the patients are still alive. Nineteen caseswhere only appendicectomy was performed havebeen followed up to date (Fig. 3); of these 14 (75 %)died of the disease. There are four survivors (200%)reaching or exceeding five years. The other groupcomprises 31 cases in which right hemicolectomy wasundertaken and for which current follow-up reportsare available (Fig. 4). Ten deaths (33 %) are reported.Nineteen (63 %) patients survived for five years or

* Author's cases

5 10

a0 .

1 2 3 4 5 6 7 8 9

Time in years 0

0

5 10

'<MM I~~~~~~~~~~~~~~~~~~~0

I i , ' i i F ~

2 3 4 5 6 7 8 9

Survival Time in Years

FIG. 4.

FIG. 2. Survival times for patients subjected toappendicectomy and to right hemicolectoiny.

FIGS. 3 and 4. Survival times offive years and over forboth groups followed up to date.

In

>

L.

0.

50-

2 5 -

FIG. 2.

801

*72* 1 7*42S lS l477265 1474267264057544256433465605343736485254

*54

6046566473

o S I

o 52

o 7265 _

0' 49i6559434941

FIG. 3.

I * I I

1 2 3 4 5 6 7 8 9Survival Time in Years

10 11 12

I TI a210 12. , . . . . . .~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

163

IIII

1 --25

--19

K. T. Hesketh

more including two (8%) exceeding 10 years. Inboth groups all but one of the deaths which haveoccurred have been in the first five-year period.

CASE REPORTS

CASE 1 This girl, aged 17, was first seen as an out-patient on 10 December 1958, complaining of abdominalpain. She stated that she had been quite well until sixmonths previously when she began to have attacks ofsharp, central abdominal pain, often radiating to theright lower quadrant, and lasting perhaps half an hour ata time. Until recently she had had approximately twoattacks a week but for the past eight weeks she had hadpain almost every day. During these last weeks also shehad periods of diarrhoea every two or three days whenshe passed three or four loose stools a day with no bloodor mucus. There was nothing untoward in her previous orfamily history, and clinical examination produced no ab-normal physical signs (pulse 80, blood pressure 150/75mm. Hg). A contrast enema at this time showed a freeflow of barium around the colon, the terminal ileum alsofilled: no abnormality was shown. The urine was normal.On 21 January 1959 she was admitted and the next day

a normal-looking appendix was removed through a rightILanz incision. Nothing else was found at the time in the

FIG. 5. Case 1: A section showing invasion ofthe muscularlayers of the appendix wall by the tumour (x 240).

abdomen to account for her symptoms. A sigmoidoscopywas also done but nothing abnormal was seen. She madean uneventful recovery.

Histology 'An externally normal appendix 4-5 cm.long x O 5 cm. diameter shows no evidence of acute orchronic inflammation. In the tip of the appendix is atumour composed of columnar cells in well-formedtubules separated by a fibrous stroma, forming a nodule2 mm. in diameter. Strands of tumour are invading themuscular coat. Occasional Paneth cells were seen in thetumour near the mucosa. Having failed to demonstratethe presence of argentaffin granules by either the silveror Diazo techniques and in the presence of many tubularacini, a diagnosis of an adenocarcinoma was made'(Fig. 5).

It was agreed that more radical surgery was necessary.At this stage it was difficult to correlate her marked symp-toms with such a relatively small lesion but followingappendicectomy they had all resolved.On 24 March 1959, through a right Rutherford Morison

incision, the ascending colon was found to be freelymobile. There were a number of enlarged, soft nodes inthe mesocolon. No obvious secondary deposits werefound. The right colon was mobilized and removed to-gether with the proximal third of the transverse colon anddistal six inches of the ileum. An end-to-end anastomosiswas performed between ileum and transverse colon andthe mesenteric defect repaired. The wound was closedwithout drainage.

Histological examination of the excised bowel, includ-ing 17 lymph nodes, disclosed no tumour. She made anuneventful recovery and when last seen in the follow-upclinic was quite well.

CASE 2 This man, aged 42, gave a history of three attacksof pain during the previous six years which had beendiagnosed as appendicitis but treated conservatively.Following the last attack he was advised to have hisappendix removed and this was done on 5 December1955. Histological examination showed the epithelium tobe replaced by a well-differentiated adenocarcinoma andthe wall was extensively invaded through to the serosa bymuch less differentiated adenocarcinoma (Figs. 6 and 7).On 16 December 1955 a right hemicolectomy was per-formed and this specimen when submitted to sectionshowed poorly differentiated adenocarcinoma withnumerous mitoses situated in the muscular layers of thecaecum with an intact mucosa over it (Fig. 8). A lymphnode also showed secondary deposits of adenocarcinoma(Fig. 9.)Two months later he was found to have a local recur-

rence of the tumour. He was referred for radiotherapy buthad had only one treatment when he developed intestinalobstruction. At laparotomy a large carcinomatous masswas found, some 12 cm. across, in the right lower quad-rant, with small masses scattered throughout the periton-eal cavity; one of these was involving and obstructing thesmall bowel. Masses were also found in the liver. Afteroperation he was given a short palliative dose of irradia-tion with little change in the size of the mass. On hisreturn home he died three weeks later-only sevenmonths after the appendicectomy.

164

The managenment of primary adeniocarcinonma of the vermiform appendix

FIG. 6. Case 2: The typical appearance of the adenocarcinoma seen here in a section from the wall of the appendix.This section shows marked glandular formation, numerous mitoses, reduplication of the 'mucosal' layers, and an overallirregular pattern ( x 160).

FIG 7. Case 2: Showing the spread of tumour in the mesoappendix (x 80).

165

K. T. Hesketh

FIG. 8. Case 2: Metastatic deposits of adenocarcinoma in the wall of the caecum with intact caecal mucosa. This istaken from the hemicolectomny specimen ( x 60).

FIG. 9. Case 2: Metastatic deposits of adenocarcinoma in a lymph node removed at hemnicolectomy ( x 160).

166

The management ofprimary adenocarcinoma of the vermiform appendix

FIG. 10. Case 3: A section of ovary showing deposits of FIG. 11. Case 3: A high-powered view ofthe ovarian meta-adenocarcinoma (x 80). stasis shown in Fig. 10 (x 1,000).

CASE 3 This woman, aged 64, presented in November1944, complaining of abdominal enlargement and painfor the previous six weeks together with loss of appetiteand loss of weight. She was found to have bilateral, firmabdominal masses arising from the pelvis, and at subse-quent laparotomy one week later these were found to beinoperable ovarian tumours. A biopsy was taken whichwas reported as a secondary deposit of degenerate mucoidcarcinoma (Figs. 10 and 11), probably from a primarycentre in the colon or stomach.A year later she was readmitted in a moribund con-

dition and died two days later. Necropsy revealed aprimary adenocarcinoma of the appendix with massivesecondary deposits in both ovaries and peritoneum.

CASE 4 This woman, aged 72, presented in October 1951,and pre-operatively a diagnosis of chronic appendicitiswith resolving abscess was made. The malignant nature ofher condition was appreciated at operation and a righthemicolectomy was performed as a primary procedure.From this she made an uneventful recovery and she is stillalive and well.

Histological examination of the tumour showed anadenocarcinoma of the appendix.

CASE 5 This woman (age not recorded) presented in1954 with acute appendicitis for which her appendix was

removed; this was shown to contain an adenocarcinoma.No further operation or treatment was instituted in viewof her poor general condition and mental instability, forwhich she had previously had a pre-frontal leucotomysome years before.

This patient survived eight months with a gradually in-creasing mass in the right lower quadrant: she diedsuddenly and it was thought that she had a coronarythrombosis. No necropsy was made.

CASE 6 This woman, aged 54, was operated upon in 1954for acute appendicitis and at operation a carcinoma of theappendix was found. A right hemicolectomy was perfor-med as a primary procedure and she remained well for 18months when her abdomen was re-explored because ofintestinal obstruction. This was found to be due to astenosis of the anastomosis and she appeared quite free oftumour at that time. However, a year later she again hadan obstruction and a palpable mass in the right lowerquadrant; she refused operation and settled after conser-vative treatment. She died six months later. No necropsywas performed.

I am most indebted to the late Professor Ian Aird for hisencouragement in the preparation of this work and toMr. K. P. S. Caldwell of Exeter for cases 4, 5, and 6.A special debt must be acknowledged to all those

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168 K. T. Hesketh

authors who have written previously on this subject andsome of whom have gone to endless trouble to answer mymany letters enquiring after their patients.Thanks are also due to Professor C. V. Harrison and

the Department of Morbid Anatomy, to the Departmentof Medical Illustration for the tables and photomicro-graphs, and to the Royal Society of Medicine for someobscure references and translations.

I must also acknowledge the permission of the MedicalDirector-General of the Royal Navy to publish.

REFERENCES

Aird, 1. (1957). A Companion in Surgical Studies. Livingstone,Edinburgh.

Clarke, R. G.. and Simonds, J. P. (1953). Adenocarcinoma of theappendix: report of two cases. Amer. J. dig. Dis., 20, 47-50.

Collins, D. C. (1955). A study of 50,000 specimens of the humanvermiform appendix. Surg. Gynec. Obstet., 101, 437-445.

Frauenthal, M., and Grausman, R. I. (1933). Primary carcinoma inthe vermiform appendix. Amer. J. Surg., 19, 118-119.

Kelly, H., and Hurdon, E. (1905). The V'ermniforrn Appendix and itsDiseases. Saunders, Philadelphia.

McCollum, M. (1957). Adenocarcinoma of the appendix. Grace Hosp.Bull. (Detroit), 35 (1), 39.

Masson, P. (1928). Carcinoids (argentaffin-cell tumors) and nervehyperplasia of the appendicular mucosa. Amer. J. Path., 4,181-211.

Merling (1838) and Rokitansky (1867) quoted by Weaver, C. H.(1957). Amer. J. Surg., 36, 523.

Norment, W. B. (1932). Tumors of the appendix. Surg. Gynec.Obstet., 55, 590-596.

Public Health Monograph No. 38. U.S. Treasury Dept.Rolleston, H. D., and Jones, L. (1906). Primary malignant disease of

the vermiform appendix. Med. Chir. Trans., 89, 125-156.Registrar-General's Returns. (1959). General Register Office.Uihlein, A., and McDonald, J. R. (1943). Primary carcinoma of the

appendix resembling carcinoma of the colon. Surg. Gynec.Obstet., 76, 71 1-714.

Willis, R. A. (1948). Pathology of Tumours. Butterworth, London.Woodruff, R., and McDonald, J. R. (1940). Benign and malignant

cystic tumors of the appendix. Suirg. Gynec. Obstet., 71,750-755.

Young, E. L., and Wyman, S. (1942). Primary carcinoma of theappendix associated with acute appendicitis. Report of a case.New Engi. J. MVed., 227, 703-705.

The March 1963 Issue

THE MARCH 1963 ISSUE CONTAINS THE FOLLOWING PAPERS

Electron microscopic changes associated with waterabsorption in the jejunum A. WYNN WILLIAMSPost-operative absorption of water from the smallintestine L. F. TINCKLER and w. KULKE

A case of jaundice due to unilateral hepatic duct ob-struction with relief after hepatic lobectomy STEVENMISTILIS and LEON SCHIFF

A comparison of the use of Aldactone and Aldactone Ain the treatment of hepatic ascites STANLEY SHALDON,JILL A. RYDER, and MYRON GARSENSTEIN

Liver disease and ammonia intoxication KENNETH S.WARREN and STEVEN SCHENKER

Torsion of the gall bladder R. K. GREENWOODDuodenal diverticula and haemorrhage M. J. S.LANGMAN

The reliability and reproducibility of the Schilling testin primary malabsorptive disease and after partialgastrectomy J. F. ADAMS and E. JUNE CARTWRIGHT

The influence of diet on the quality of faecal fat inpatients with and without steatorrhoea JOAN P. W. WEBB,A. T. JAMES, and T. D. KELLOCK

Studies in dogs on the biphasic nature of the gastricsecretory response to hypoglycaemia and other stimuliwith special reference to the role of the adrenals w.SIRCUS, C. J. W. HUSTON, R. M. PRESHAW, H. BASSOE, andR. A. HARKNESS

1 The patterin of the biphasic response and the relation togastric innervation and to hypoglycaemia2 The relationship of the gastric secretory response tohypoglycaemia and to changes in the level of plasmacortisol3 The effect of bilateral adrenalectomy4 The interrelationship of the phases of the response andthe role of the antrumThe pancreas and gastric secretion: failure of pan-createctomy to prevent inhibition of gastric secretion bysecretin JOSEPH A. KENNEDY and GEORGE A. HALLENBECK

A 5-hydroxytryptophan-secreting carcinoid tumourA. C. P. CAMPBELL, A. H. GOWENLOCK, D. S. PLATT, andP. J. D. SNOW

Histochemistry of the gastric mucosa J. PINTO CORREIA,M. ISABEL FILIPE, and J. COSTA SANTOS

1 In nornmal mucosa2 In pathological conditions and in changes induced bYhistamineStudies on the effect of vagotomy on small intestinalmotility using the radio-telemetering capsule B. ROSS,B. W. WATSON, and A. W. KAY

Localization of intestinal bleeding using a miniatureGeiger counter B. MCKIBBIN and B. W. WATSONBritish Society of GastroenterologyGastroenterological Society of Australia

Copies are still available and may be obtained from the PUBLISHING MANAGER,BRITISH MEDICAL ASSOCIATION, TAVISTOCK SQUARE, W.C.I., price 18s. 6D.