Primary carcinoma of the gallbladder

‘“”

SCIENTIFIC

Primary

PAPERS :

Carcinoma REPORT

of the Gallbladder*

OF FORTY-SEVEN

B. J. TABET,

M.D.,

CASES

Cleveland, Ohio others contending that the reverse might be true. The frequency with which caIcuIi are present in primary carcinoma of the gaIIbIadder and their known presence prior to the cancer, as we11 as the experimenta production of carcinoma by insertion of foreign bodies into the gaIIbIadder of the experimenta anima1, support the contention than an etioIogic reIationship may exist. In the forty-seven patients of this series, gaIlstones were found in thirty-eight (80 per cent). One patient presented a cholecystoduodenocolic f%tuIa and had no stones in the gaIIbIadder, but one caIcuIus Iess than 1.0 cm. in its greatest dimension was found in the right hepatic duct at autopsy, suggesting that ChoIeIithiasis may have been present and the stones “passed” by the fistuIa. The operative records of two patients made no mention of the presence or absence of stones, but stones were demonstrated on ora choIecystograms. This constitutes an incidence of forty-one gaIlstones in forty-seven patients with cancer (87 per cent). In two of the patients in whom no stones were found, the diffuse carcinomatous growth was hard and CartiIaginous, and palpation did not indicate the presence or absence of stones. One diagnosis was made by SiIverman needIe biopsy, and autopsy was not performed. This patient was jaundiced. In onIy three cases (6.38 per cent) was there definite absence of

ARCINOMA of the gallbIadder is usually a hopeless entity. In the earIy stage of this highly maIignant neopIasm, when extirpative therapy might be of some vaIue, the preoperative diagnosis is inherentIy difFicuIt to establish. According to the U. S. Bureau of Census, more than 10,000 of 150,000 annua1 deaths from cancer are due to cancer of the Iiver and biIiary passages. Cancer of the gaIIbIadder accounts for about two-thirds of these, or 6,500 deaths yearIy. This communication reports forty-seven new cases of this condition seen at St. AIexis HospitaI, CIeveIand, Ohio, between 1945 and 1957, and correIates data derived from other hospitals in the city of CIeveIand during the same period. These cases are compared with those previousIy reported in the Iiterature. A comprehensive picture of the morbid anatomic and cIinica1 aspects of the disease is discussed. The clinica and operative records, necropsy protocoIs, histologic sections and photographs of these cases were carefuIIy reviewed.

C surgicalIy

ETIOLOGY Much attention in the Iiterature has been focused upon the frequent simuItaneous occurrence of carcinoma of the gaIIbIadder and gaIIstones. Many investigators beIieve that an etioIogic basis in this association exists, some hording that the cakuli predispose to the carcinomatous condition in the gaIIbIadder, *This

’

articIe is an abridgment of the thesis presented at the compIetion of a general surgica1 residency at St. AI&s HospitaI, CIeveIand, Ohio. 365

American

Journal

of Surgery,

Volume

IOO, September

1960

Tabet TABLE I CALCULI, PRECURSORS OF CANCER T

Age hr.

and Sex

Time of ChoIecystostomy

Time of ChoIecystography

results followed in both groups. A thickening of the wall of the gallbladder was found with pronounced hyperplasia of the glandular elements which formed cysts and tended to invade the liver. In two of these animals, the appearance was suggestive of cancer. In 1947, Petrov and Krotkina [28] also found the development of malignant growth after introduction of hard foreign bodies into the gallbladder of guinea pigs. More recently, Fortner [ 151 introduced methylcholanthrene fashioned into pressure pellets into the gallbladder of fourteen young cats after aspiration of bile and ligation of the cystic duct to prevent dissolution of the pellets. Eight cats died within ten months from respiratory infections. Five of the remaining six cats exposed for twenty-three months or more were found to have primary carcinoma of the gallbladder. Methylcholanthrene and cholanthrene are highlypotentcarcinogenic hydrocarbons. Chemically, they are closely related to the bile acids from which they can be prepared by simple Future research may well chemical steps. ascertain whether or not gallstones or the contents of the bile from subjects of carcinoma of the biliary tract contain methyIcholanthrene or any related carcinogenic substance. The association of carcinoma of the gallbIadder with gallstones almost certainly has etiologic significance for there is strong evidence that the stones commonly precede the cancer and do not mereIy result from its presence. The mechanical irritation of calculi, the relation to a peculiar form of lipoid metabolism, and the irritative and digestive action of bile may combine to produce the remarkable susceptibility of this mucous membrane to cancer. The statistics and experimental data are convincing enough to suggest that cholelithiasis is a common predisposing factor and precursor of carcinoma in the gallbladder. For this reason, cholecystectomy is advised for those patients after the age of forty with symptoms and non-visualization of the gahbladder on double-dose oral cholecystograms.

-

DeveIopment of Cancer

Time I ntervaI (yr.1

s/W55

II

4/w53 1 I /7/55 8/16/55 I l/23/56

32 I 5

-_ 65, F 55. 61, 63, 66,

I944 I923

F

F F

M

-

9

-

gallstones on roentgenographic examination and at exploration. The marked predilection of cancer of the gallbladder in women has been attributed to the preponderate incidence of cholelithiasis in the female. Five patients in our series were known to have gallstones for varying periods of time before the cancer developed in the gallbladder. Table I indicates the time interval between discovery of the gallstones by cholecystogram or cholecystostomy and the development of the cancer and associated cholelithiasis. EXPERIMENTAL OF

PRODUCTION THE

OF

CARCINOMA

GALLBLADDER

Many investigators have endeavored to produce tumors of the gallbladder in animals by introducing foreign bodies such as pebbles, suture materials, lanolin, paraRm, pitch, tar, cement, tile, fragments and gallstones with or without radium. Both calculi and cancer may be developed in response to a common agency. Such an occurrence has been known to occur in the kidney. Daels and Biltris [IO,II] inserted a strip of collodion impregnated with radium sulfate into the kidney of a guinea pig which twenty-two months later was found to have lithiasis and sarcoma of that kidney. Kazama [20] introduced a foreign body into the gallbladder of ninety-eight guinea pigs and produced cancer in twenty-six, nine with metastases. Leitch [23], in 1924, undertook a repetition of Kazama’s experiments and reported that he produced malignant lesions in the gallbladder of guinea pigs by introducing human galIstones. Delbet and Godard [r3] inserted gallstones from cancerous patients into the gallbladder of six guinea pigs and from noncancerous patients into ten guinea pigs. Similar

DATA

__ 366

During the twelve-year period Incidence. from 1945 to 1957 there were forty-seven cases in which a microscopic diagnosis of primary carcinoma of the gallbladder was recorded at St. Alexis Hospital. This series includes two

Primary Carcinoma of GaIIbIadder TABLE II

autopsy findings and forty-five operative specimens. There were tweIve men and thirty-five women, a ratio of I man to 3 women. The distribution of the patients according to age and sex is shown in TabIe II. It is of interest to note that 25 per cent of the patients were in the fifth decade, 52 per cent of the patients were in the sixth decade, and 71 per cent of the patients were over sixty years old. Ninety-six per cent of the patients with this condition are over the age of fifty. The average age for men in the group was sixty-one years, for women in the group sixty-four, and for the entire group sixty-three. The youngest patient in the group of men was forty years of age, the oIdest seventy-nine. In the group of women the youngest was fifty and the oldest seventy-eight. Women in the sixth decade numbered twenty-one, or 45 per cent. A comparative study was made from hospitals in the CIeveIand area of carcinoma of the galIbIadder in reIation to the number of admissions and choIecystectomies performed. TabIe III represents a correIation of these figures. It wiI1 be noted that our percentage of carcinoma of the gahbladder was the highest. Pathology. Carcinoma of the gaIIbIadder starts anywhere in the organ and infiltrates the viscus IocaIIy, causing thickening and stiffening of the wail at the site of invoIvement. Some growths protrude into the Iumen as irreguIar, smaI1 or buIky, firm or soft masses. More frequentIy the growth infiItrates the entire viscus and by direct extension upward involves the liver or downward, the porta hepatis and the

AGE

I

40-49 50-59 60-69 70-79

HospitaIs

Huron Road Hospital. Marymount Hospital. Lutheran HospitaI. . St. Vincent Charity Hospital, CIeveland CIinic Hospital. . St. John’s HospitaI.. St. AIexis HospitaI. TotaI

..

419 229 189 364 493 3’6 326 2,336

DISTRIBUTION

I

I

2

4 3 3

--__

I2 61

2

__-__

8 21 6

I2 24 9

35 64

::

-___

4 25 52 r9

common biIe duct as we11 as the pancreas and duodenum. Microscopicahy, the majority of carcinomas of the gaIIbIadder are coIumnar ceIIs of varying heights, mounted on delicate connective tissue staIks, or that form acinar tubuIar structures in a scanty or more abundant, Ioose or dense fibrous connective tissue stroma. OccasionaIly the coIumnar ceIIs produce mucin in abundance. In other instances, a squamous ceII carcinoma is encountered in the gaIIbIadder secondary to metapIasia. In the forty-seven cases of our series, there were forty-three adenocarcinomas (gr .4g per cent), three squamous ceII carcinomas (6.38 per cent) and one sarcoma (2.13 per cent). Symptomatology. The major symptoms reIative to the present ihness which the forty-seven patients presented at the time of admission were as foIIows : Thirty-six patients compIained of duI1, aching pain in the right upper quadrant of the abdomen which required their taking occasional III

IN CLEVELAND

Bed Capacity

SEX

I

Total Average

TABLE DATA FROM HOSPITALS

AND

No. of Admissions

ML229

(1945

TO TIME OF WRITING)

ChoIecystectomies Performed

Cases of Carcinoma of GaIIbIadder

Per cent

107,218

2,064 683 1,432

112,255

1,706

136,106 100,000

1,722: 1,870

,“:* 47

148,689

1,717

47

2.73 ___~__

233

2.08

61,121

843,618

* The records of 1957 are incompkte.

367

I IPI

30 9 29

r .45 1.31 2.02

2.w 2.51

2.05

Tabet TABLE SYMPTOMS

ADMISSION

NO. Symptom

secondary to the obstruction of the Ieft externa1 iIiac artery. Physical Signs. A mass in the right upper quadrant thought to be the liver or gallbIadder was the most important physica finding. Ascites was present in seven patients, and at paracentesis the Iiquid removed varied from a cIear, cloudy amber fIuid, bIood-stained peritonea1 effusion to a pure hemoperitoneum ranging in amount from 800 to 4,000 cc. The mechanism of ascites in these cases is not always cIear-cut and may be due to such factors as carcinomatosis of the peritoneum or mesentery, obstruction of the portal vein by a neopIasm, thrombosis of the porta or hepatic veins, or cirrhosis of the liver with hypoproteinemia. Jaundice was present in fourteen patients on admission but was subsequentIy noted in twenty-six patients during the cIinica1 course. In the majority of cases, the jaundice was persistent, painIess, afebriIe and progressive; in eighteen patients it was associated with dark urine and cIay-coIored stooIs. Radiographic Findings. Twenty-seven patients had radiographic examinations at a date varying from a few days to eIeven years prior to the proved diagnosis of carcinoma of the gaIlbIadder. OraI choIecystography reveaIed visuaIization of the gal1bIadder with stones in two patients, non-visuaIization of the gallbladder with stones in thirteen, and non-visuaIization of the gaIIbIadder in eleven. In one patient, an upper gastrointestina1 series reveaIed a choIecystoduodenocoIic l%tuIa which at autopsy proved to be a squamous ceI1 carcinoma of the gaIIbIadder. Preoperative Diagnosis and Location of Carcinoma. In the forty-seven cases, there were 0nIy four instances in which the surgeon considered the diagnosis of primary carcinoma of the gaIIbIadder as the first impression. TabIe v Iists the different clinica diagnoses made prior to surgery. Not only is the cIinica1 diagnosis diffrcuIt, but accurate Iocation of the primary Iesion even at the time of Iaparotomy is often fraught with considerabIe difficulty. TabIe VI summarizes the Iocation of the primary tumor according to the operative records. Operative Procedures. At the time of surgery the usua1 extent of the disease, the common invoIvement of the liver and perihepatic or ceIiac Iymph nodes suggested that any attempt at radica1 surgery was unjustifiabIe and that a

IV

ON

of GS‘ZS

Per cent

Minimum

Maximum

-l-lIntolerance

to fatty

foods..

38

81

6 mo.

Severa ye&US

upper

quadrant.

36

76

2 days

23

49

IO lb. in 6 mo.

Several years 70 lb. in 3 mo.

18 I, 14

38 36 30 19 15

3 z 3 3 z

I 4 a 6 I

Pain

in right

Loss

of weight.

_.

Dark urine, clay-colored stools.. Weakness.. . Jaundice.. Anorexia.. Nausea, vomiting.

.

9

7

I

days wk. days mo. days

wk. mo. mo. mo. wk.

I

narcotics for alleviation. The pain was usually in the right upper quadrant; less frequently it referred to the epigastrium and least frequently to the right lower quadrant. In thirty-eight of our forty-seven cases, there was a history suggestive of gallbladder disease with intolerance to fatty foods of several years’ duration. Our hospital patients are mainly of Polish, Bohemian and Slovenian ancestry who are known for their consumption of high fatty diets comprised of pork, sauerkraut, pigs-in-the-blanket and koIbasa. Other symptoms such as weakness, Ioss of weight and anorexia completed the cIinica1 picture and were occasionahy suggestive of mahgnancy. Table IV summarizes the symptoms present in the forty-seven cases. Attention is directed to three cases of carcinoma of the gaIIbIadder which were silent, without symptoms, and noted as incidenta findings. Routine roentgenographic examination in one patient discIosed a herniation of the entire stomach and part of the transverse coIon through the diaphragm behind the heart. A barium swaIIow test reveaIed a cholecystoduodenocoIic tistuIa. Autopsy reveaIed a squamous cc11 carcinoma of the gaIIbIadder. Another patient who underwent peIvic Iaparotomy was found to have 800 cc. of bIoodstained peritonea1 effusion, and the peritoneum was studded with hard metastatic noduIes from a primary carcinoma of the gaIIbIadder. In a third patient, autopsy discIosed a nonsuspected adenocarcinoma of the gaIIbIadder associated with an acute suppurative pancreatitis. CIinicalIy, the patient was admitted for an ischemic necrosis of the left Iower extremity 368

Primary

Carcinoma

of GaIIbIadder TABLE VI SITE OF CARCINOMA

TABLE v PREOPERATIVE DIAGNOSIS

No. of

Diagnosis

Acute choIecystitis.. Chronic ChoIecystitis with Iithiasis. Obstructive jaundice.. Obstructive jaundice (stone). Obstructive jaundice (tumor). Carcinoma of pancreas with metastases to liver. Carcinoma of liver..

Indeterminate

.

8 8 I

3 IO

5 5

3 4

Carcinoma of the gaIIbIadder..

paIliative procedure was indicated. Whenever possibIe, of course, choIecystectomy was performed. In one patient, carcinoma of the gaIIbIadder with direct extension to the immediate surrounding Iiver parenchyma was successfully treated by cholecystectomy and associated wedge resection of the Iiver. The operative procedures performed in this series are Iisted in TabIe VII. In one patient, the pathoIogy was mistaken for acute cholecystitis and choIecystostomy was performed. ProgressiveIy increasing jaundice deveIoped postoperatively and the patient required re-expIoration, at which time a biopsy proved theildiagnosis of carcinoma of the gaIIbIadder. Prognosis and Survival. The disease was rapidIy fata1, Ieading to death in the first postoperative month in sixteen cases (34 per cent). TABLE VII TYPE OF OPERATIONS PERFORMED

-

Operation

ChoIecystectomy......................... ChoIecystectomy and wedge resection of Iiver ChoIecystostomy ......................... Cholecystostomy and biopsy of gaIlbladder. Biopsy of gaIIbIadder. .................... Biopsy of Iiver ........................... Biopsyofomentum ....................... Biopsy of liver and omentum. ............. Biopsy of liver and gaIIbIadder. ............ Cholecystostomy, biopsy of Iiver and galI-

bIadder................................ Silverman needle biopsy. .................. Not operated, autopsied ...................

Ivo. of Cases

No. of

Site of Primary Tumor

Cases

Cases

Diffuse growth in gaIIbIadder with extension to liver, biIe ducts, nodes (omentum, retroperitoneal space) (periaortic and perihepatic) GaIIbIadder fundus with direct extension to liver................................... GaIIbIadder fundus alone.. Lower haIf of gaIIbIadder with liver invoIvement . Cystic duct onIy.. . Not operated. ..

28 6 2 8 I

2

Thirty-two patients (68 per cent) died in the first three months foIIowing surgery. Over 83 per cent died in the first six months. (TabIevIII.) Three patients Iived 349, 394 and 533 days, respectively, whiIe one patient with a fifteenyear surviva1 was not incIuded because the microscopic sections were unavaiIabIe. The patient surviving 533 days had carcinoma of the fundus of the gaIIbIadder with gross extension to the immediate surrounding liver parenchyma which required choIecystectomy and wedge resection of the liver. Four patients (8.5 per cent) with carcinoma of the gaIIbIadder in our series are aIive and we11today. (TabIe IX.) These four were treated by choIecystectomy onIy. In two, the microscopic sections reveaIed carcinoma of the fundus of the gaIlbladder with extension to serosa, and they have survived one and a haIf years and two years, eight months, respectively. One patient with grossIy chronic choIecystitis was reported as having part.iaIIy differentiated adenocarcinoma with ChoIeIithiasis; the patient, TABLE VIII POSTOPERATIVESURVIVAL

II I I

Time of Death

15 6 I 2 2 2

Day of operation.. I to IO days postoperatively. I I to 30 days postoperativeIy.. I mo. to 3 mo. postoperativeIy . 3 mo. to 6 mo. postoperativeIy. Autopsy findings.. . .

3 I 2

TotaI.........................

369

No. of Cases

I 5 10 16 5 2 39

Per cent

2.12 10.63 21.27 34.04 10.63 4.25 83

Tabet

-

Age (yr.) and Sex

association between gaIIstones and primary carcinoma of the gaIIbIadder. Brit. J. Surg., 20: 607,

TABLE IX OPERATED AND STILL ALIVE

-

-

Date of Operation

Operation Performed

11/19/52 9/21/5o

ChoIecystectomy ChoIecystectomy ChoIecystectomy Cholecystectomy

1933. 7. BORROWS, H. GaIlstones and cancer. Brit. J. Surg., 27: 166, 1939. 8. Carcinoma of the major intra-hepatic and extrahepatic biIe ducts excIusive of the papiIIa of Vater. Rochester, Minnesota, March 1957. g. COATES, H. W. Carcinoma of the gaIIbIadder seven years after remova of a stone. Clin. J., 58: 54,

Alive

-. 70. 62, 67. 63,

M M F F

11/7/56 8116155

5% yr. 7% yr. 1% yr. 2 yr., 8 mo.

1929. 10. DAELS, F. and BILTRIS, R. Production de carcinome gIanduIaire au moyen du radium. Bull. Assoc. fray. ktude cancer, 16: 772, 1927. I I. DAELS, F. and BILTRIS, R. Contribution a I’etude de de tumeurs malignes experiIa provocation mentales au moyen de substances radio-actives. Bull. Assoc. franc. btude cancer, 20: 32, 1931. 12. DELANNOY, E., LAGACHE, G., DEVAMBEZ, J. and GODEFROY-VENDEVILLE, Y. Cancers de Ia v&sicuIe r&v&s par I’anatomie pathologique aprPs choI&cystectomie pour Iithiase. Lyon cbir., 51: 421, 1956. 13. DELBET, P. and GODARD, H. Inclusion de caIcuIs biliares humains dans Ia vesicule chez Ie cobaye. Bull. Assoc. franq. Etude cancer, 17: 347, 1928. 14. DESFORGES,G., DESFORGES,J. and ROBBINS, S. L. Carcinoma of the gaIIbIadder; an attempt at experimenta production. Cancer, 3: 1088, 1950, 15, FORTNER, J. G. Experimenta induction of primary carcinoma of the gaIIbIadder. Cancer, 8: 689,

-

-

then a seventy year oId white woman, represents a five and a haIf-year cure. In the fourth patient, who had carcinoma of the cystic duct and underwent choIecystectomy on September 2 I, 1950, jaundice deveIoped in 1957 and resection of a segment of the common biIe duct was performed for an obstructive maIignant Iesion. The patient is symptom-free at present. SUMMARY

Forty-seven cases of primary carcinoma of the gallbladder are reported, forty-five of which included operative specimens. The sex incidence was one man to three women; the youngest patient was forty years of age, the oIdest seventy-nine. Three cases of cIinicaIIy siIent, symptom-free carcinoma of the gaIIbIadder are reported. The diagnosis of carcinoma of the gaIIbIadder preoperatively is difIicuIt and rare. The etiologic roIe of choIeIithiasis predisposing to the carcinomatous condition is discussed and supported by clinica and experimental data. SurgicaI therapy in carcinoma of the galIbladder is usuaIIy paIIiative and the life expectancy is poor. Four patients aIive for varying intervaIs foIlowing surgery are presented; one is surviving five and a haIf years postoperativeIy; the other, seven and a half years.

1955. 16. FINNEY, J. M. R. Primary carcinoma of the gaIIbladder. Ann. Surg., 121: 425, 1945. 17. HALLE, J. N. Histore de Ia societe de medicin. Paris, I 786. 18. JONES, C. Carcinoma of the gaIIbIadder. Ann. Surg., 132: 110, 1950. 19. JONES, H. W. and WALKER, J. H. Correlations of the pathoIogic and radiologic findings in tumors and pseudo-tumors of the gaIIbIadder. Surg., Oh-t. @ CyneC., 105: 599, 1957. 20. KAZAMA, Y. Studies on artificia1 production of tumors in viscera. Japan M. World, 2: 309, 1922. 21. KAZMIERSKI, R. Primary adenocarcinoma of galIbladder with intramura1 caIcification. Am. J. Surg., 82: 248, 1951. 22. LAHEY, F. Earlier operations in ChoIeIithiasis. S. Clin. North America, 17: 725, 1937. 23. LEITCH, A. GaIIstones and cancer of the gaIIbladder: an experimenta study. Brit. M. J., 2: 451, 1924. 24. LICHTENSTEIN,G. and TANNEBAUM, W. Carcinoma of the gaIIbIadder: a study of 75 cases. Ann. Surg., 111: 411, 1940. 25. MASSE, L. and DUGOURT, G.: La choIecystohepatectomie dans Ie cancers de Ia vesicuIe. Arch. mal. app. digestif., 39: 261, 1950. 26. MUSSER, J. H. Primary cancer of the gaIIbIadder and biIe ducts. Boston M. ti S. J., 71: 525, 1889. 27. PACK, G. T., MILLER, T. and BRASFIELD, R. TotaI right hepatic Iobectomy for cancer of gaIIbIadder; report of 3 cases. Ann. Surg., 142: 6, 1955. 28. PETROY, N. N. and DROTKINA, N. A. Experimenta carcinoma of gaIIbIadder; suppIementary data. Ann. SUrg., 125: 241. 1947.

REFERENCES I. ARMINISKI, T. C. Primary carcinoma of the gaIIbladder. Cancer, 2: 379, 1949. 2. BENJAMIN, E. Carcinoma of the gaIIbIadder. Minnesota Med., 31: 537, 1948. 3. BERGHAUSEN, 0. Primary carcinoma of the gaIIbIadder. Ohio M. J., 38: 125, 1942. 4. BOOKER, R. J. and PACK, G. T. Carcinoma of the gaIIbIadder. Am. J. Surg., 78: 175, 1949. 5. BOSSE, M. D. Carcinoid tumor of the gallbladder. Arch. Patb., 35: 898, 1943. 6. BORROWS, H. An experimentaI inquiry into the

370

Primary

Carcinoma

of GaIIbIadder

J. and MASSENHOUEF,A. Un cas d’hemochoIecyste, caIcuIeux et cancereux. Presse mtd., 49: 462, 1941. 30. RIVKIN, L. M. Fifty-two operative cases and review of literature. A&. Surg., 7: 128, 1955. 31. RUSSELL, P. W. and BROWN, C. H. Primarv carcinoma of the gahbladder. Ann. Szrrg., 132: - 121,

hepatectomy for carcinoma of the gaIIbIadder with IocaI Iiver extension. Surgery, 22: 48, 1947. 35. STEWART, H. L., LIEBER, M. M. and MORGAN, D. R. Carcinoma of extrahepatic biIe ducts. Arch. Surg., 41: 662, 1940. 36. THOREK, M. PartiaI hepatectomy in cancer of the gaIIbIadder. J. Internot. Cell. Surgeons, IO: 369,

1950. 32. SAINBURG, F. and GARLOCK, J. Carcinoma of the gaIIbaIdder. Surgery, 23: 210, 1948. 33. SAWYER, C. D. and MINNIS, J. F., JR. Primary carcinoma of the gaIIbIadder. Am. J. Surg., 91: gg. 1956. 34. SHEINFELD, W. ChoIecystectomy and partia1

1947. 37, VADHEIM, J. L., GRAY, H. K. and DOCKERSY, M. B. Carcinoma of the gaIIbIadder. Am. J. Surg.,

29.

QUENU,

63: 173, 1944. 38. WARREN, R. and BALCH, F. G. Carcinoma of the gaIIbIadder: the etioIogica1 roIe of gaIlstones. Surgery, 7: 657, 1940.

371