Carcinoma of the extrahepatic bile ducts

Carcinoma

of the Extrahepatic A Clinicopathologic

Study

JONATHANA. VAN HEERDEN,M.B., CH.B., EDWARDS. JUDD,M.D., Rochester, Minnesota

From the Sections of Surgery (Dr. Judd) and Surgical Pathology (Dr. Dockerty), Mayo Clinic and Mayo Foundation, and Mayo Graduate School of Medicine ( University of Minnesota) (Dr. Van Heerden), Rochester, Minnesota.

Bile Ducts*

ANDMALCOLMB. DOCKERTY,M.U.

operative incidence has been reported as 0.5 [7] to 1.4 per cent [P] of all operations on the biliary tree. Of the most common manifestations, jaundice has been noted in 87 [12] to 100 per cent [Z] of some series, loss of weight in 78 [7] to 95 per cent [8], and pain in 20 [6] to 60 per cent [7]. In reported series the majority of patients were between fifty and seventy years of age with the limits being seventeen and eighty-two years. Gray [6] recorded an average age incidence of 59.2 years, and Permen and McCollum [II] 62.7 years. Distribution between the sexes varies somrwhat although most reports have indicated a slight predominance in men; for example, the incidence was 51 per cent in Judd and Gray’s [P] series and 61 per cent in Gray’s [6]. Brown and associates [Y] from England reported a reversal of this ratio: three male to four female patients. Certain biochemical findings are indicative of obstructive jaundice. There is great variation in the serum bilirubin levels, a fact re-emphasized in the present series. Ham and Mackenzie [Z] discussed the so-called dissociation between the serum bilirubin and serum alkaline phosphatase levels, in which high levels of alkaline phosphatase were found with little or no rise in bilirubin levels. When this phenomenon occurs, neoplastic obstruction of the biliary tree should be strongly suspected. Clinical examination is not generally thought to have much diagnostic value, icterus and hepatomegaly being nonspecific although very

HIS STUDY is concerned with malignant of the extrahepatic bile ducts, exclusive of the papilla of Vater. Renshaw [1] in 1922 wrote, “Surgical treatment of malignant conditions of the biliary tract has not advanced proportionately with that of other parts of the upper abdomen.” Today, almost forty-five years later, the same could well be said. The diagnosis of carcinoma of the extrahepatic bile ducts is still, unfortunately, a delayed diagnosis; radical, curative surgery is the exception rather than the rule; and five year survival after surgery is extremely rare. Despite its infrequency, the disease accounts for about 13 per cent of deaths from carcinoma in the United States [Z]. Waugh [3] stated that if jaundice is present, cure by surgery is most unlikely. Therefore, great strides will have to be made in earlier diagnosis and treatment if any improvement in results is to be forthcoming.

T tumors

BACKGROUND INFORMATION Several reviews of carcinoma of the extrahepatic bile ducts have come from the Mayo Clinic in the last four decades [1,4-S], and reports from other centers appear with increasing frequency [2,9,10]. The incidence of this disease at autopsy is given as 0.26 [8] to 0.54 per cent [11] while the

* Presented at the Seventh Annual Meeting of the Society for Surgery of the iZlirncntary Tract, Chicago, Illinois, June 25 and 26, 1966. Vol. 113, January

1967

49

Van Heerden, Judd, and Dockerty common. A palpable gallbladder is a rare finding. The most frequent primary site for these tumors is the common hepatic or common bile duct, the incidence in these locations being about equal. Carcinoma of the cystic duct is rare. In almost all reported series every lesion was an adenocarcinoma, either papillary, nodular, or diffuse, although in Brown and associates’ [9] series 35 per cent were classified as infiltrating scirrhous carcinoma and 5 per cent as anaplastic. Associated lithiasis has been reported in 34 [9] to 65 per cent [P] of cases. Its etiologic significance is debatable. Metastasis at operation is common, having been noted in 50 [13] to 71 per cent [8] of cases. The interval from onset of symptoms to treatment has varied, averaging two weeks in Marais and Dreyer’s [la] series and 3.6 months in that of Pallette and associates [SLY].The average postoperative survival time has been reported as four months [7] to one year [IP]. We could find no report of any five year survival. PRESENT

STUDY

All seventy-eight cases of malignant tumor of the extrahepatic bile ducts (excluding the papilla of Vater) seen at the Mayo Clinic from 1954 to 1963 inclusive have been reviewed. Histologic sections from each were examined by one of us (M. B. D.), but in nine cases the available tissue was not from the primary site. In these the diagnosis was verified by review of histologic sections of the liver, involved lymphatics, or peritoneal implants as well as the surgical notes from the original operation at which it was suspected that the bile ducts were the site of the primary tumor. Seventy-three of the seventy-eight patients underwent surgery, and carcinoma of the extrahepatic bile ducts was demonstrated in seventyone. In the remaining two, other diagnoses made at operation were corrected at autopsy; in five additional instances the first diagnosis was made at autopsy. From 1954 to 1963 inclusive, 6,900 autopsies were performed at the Mayo Clinic. Fifteen of our cases were included, making the incidence at autopsy 0.22 per cent. Of these fifteen patients, eight had had exploratory operations recently for carcinoma of the bile ducts.

The age of our patients varied from twcntyeight to eighty-five years, averaging sixty. Forty-nine patients were men and twenty-nine women. This preponderance of male patients (63 per cent) agrees with the reports of most other series [4,6]. Significant associated disease was present in seventeen patients (22 per cent) as follows: diabetes mellitus, eight patients; chronic ulcerative colitis, two; myxedema, one; carcinoma of breast (twenty-six years before) in addition to diabetes mellitus for ten years before diagnosis of carcinoma, one; carcinoma of cervix (thirteen years before), one; pernicious anemia, one; chronic duodenal ulcer, one; achondroplasia, one; pulmonary tuberculosis, one. The two patients with chronic ulcerative colitis had had the colonic disease for fifteen and seventeen years. They were thirty-three and thirty-four years of age, respectively, when carcinoma of the bile ducts was diagnosed, and that is well below the average age for onset of this disease. The relationship between the pericholangitis of chronic ulcerative colitis and the development of malignancy of the extrahepatic bile ducts continues to be of great clinical interest. There was a surprisingly high association with diabetes mellitus. Eight patients (10 per cent) had had diabetes for six months to fifteen years before the discovery of malignancy of the bile duct. The prevalence of diabetes mellitus in the general population has been estimated at 1.7 per cent [16]. This association has not been reported from other institutions and its significance is not known at this time. CLINICAL

FEATURES

Symptoms. Jaundice was the most common symptom, being present in forty-eight patients. The interval between its onset and definitive treatment varied from two weeks to twenty-two months, averaging 16.1 weeks. Pain was a presenting symptom and prominent feature in forty-five cases (fifty-eight per cent). Most commonly it occurred in the epigastrium and right upper quadrant and was dull and aching, colicky pain being the exception. It was often aggravated by eating although vomiting was rare. Pain usually anteceded the jaundice, and alleviation of the pain with the onset of jaundice was not observed. American

Jouvnal

of Surgery

Carcinoma

of Extrahepatic

Loss of weight \vas recorded in fifty-three cases (OS per cent) and varied to a maximum of 65 pounds. averaging 13.6 pounds. The other symptoms included recurrent chills and fever in four patients, constipation in two, ljruritis in two, nausea and vomiting in one, malaise and loss of appetite in one, nausea and chills in one, and postoperative hiliary fistula in one. Physical Signs. Clinical examination contributed little of significance in most cases. It is interesting that obvious clinical jaundice was not present in fifteen cases (19 per cent). Hepatomegaly was present in fifty-five (71 per cent), and the gallbladder was palpable in fourteen (IS per cent). A “second look” was the occasion of discovering carcinoma in one patient. LABORhTORY

FINDINGS

The values for total serum bilirubin in most cases agreed with the typical findings in obstructive jaundice. Their range was from 0.5 to 36.8 mg. per cent, averaging 11.2 mg. per cent. The hemoglobin amounted to less than 10 gm. per cent in only four cases, and this determination was judged to be of little diagnostic value. The serum alkaline phosphatase, measured in seventy-one cases, ranged from 14.4 to Z-49 King-Armstrong (K-A) units per 100 ml. and averaged 77.4 units. In thirty-nine cases the serum bilirubin figures were less than 10 mg. per cent while in forty-four cases the serum alkaline phosphatase values were more than 50 K-A units. Similarly, twenty-four patients had bilirubin levels of less than 5 mg. per cent while twenty-one cases had phosphatase levels of more than 100 K--A units. A closer analysis of these results is shown in Figure 1. Despite the trends of the aforementioned groups, the dissociation (discussed by others [Z]) in individual cases was too random to be significant. The prothrombin time, determined in seventy-five cases, varied from seventeen to thirty-five seconds with an average of twenty seconds. This investigation proved to be of no diagnostic value. The serum glutamic oxalacetic transaminase, recorded in thirty-eight cases, ranged from 1.16 to 15.1ti PM/hr./ml., averaging 6.03. This is considerably above the accepted upper limit of normal (1 .Xi) but was not of much diagnostic aid.

f ;8

Bile Ducts

36.

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Serumdkoh vwsphoto~e, ~~nq-armr~ngunite1 momi. FIG. 1. Relationshipof serun~ bilirubin and,serum line phosphatasc l~rls in carcinoma of cstrahrpatic &a-

bile ducts.

Duodenal contents were aspirated and examined in eighteen cases. Blood was present in two and clear bile in eight. The presence of bile in eight of eighteen cases of carcinoma of the extrahepatic bile ducts tends to negate any value that this test might seem to have. The analysis of duodenal contents for malignant cells may have some diagnostic usefulness but has not been evaluated as yet. SURGICAL

EXPERIENCE

Prior Explomtion and Intervention. In twenty-three cases (29 per cent), twenty-seven surgical procedures of various kinds had been performed on the biliary tree two weeks to twenty years before the patients came to the Mayo Clinic. These included negative exploration, eight patients (seven in three cases); cholecystectomy, seven; positive exploration and biopsy, four; cholecystectomy and T tube choledochostomy, two; common duct exploration and T tube choledochostomy, two; liver biopsy , two; choledochojejunostomy, two ; choledochoduodenostomy, one. Eighteen of these twenty-seven interventions had failed to establish a diagnosis of malignancy, and in three cases the negative explorations had been multiple.

Dejinitive Therapeutic or Dicqnostic Procedure. It is evident from the records that in forty-three cases (59 per cent of the seventythree surgical cases), the operations performed at this institution were only exploratory or palliative. The fact that in nineteen cases

(24 per cent) the procedure consisted only of biopsy of an inoperable lesion truly reflects

Van Heerden, TABLE RESULTS

OF RADICAL

PATIENTS

WITH

and Dockerty

I

PANCREATODUODENECTOMY

CARCINOMA

Judd,

IN SIX

OF EXTRAHEPATIC

BILE

DUCTS

Case I II III IV V VI

Lesions (All Limited to Common Bile Duct) Adenocarcinoma, grade 3 Papillary mucoid adenocarcinoma, grade 2 Papillary adenocarcinoma, grade 2 Scirrhous adenocarcinoma, grade 2 Scirrhous adenocarcinoma, grade 2 Adenocarcinoma, grade 3

Survival

37 mo. 2 wk.*

4

U( ___-_13

1’

distriFIG. 2. hdtOrIIic bution of carcinoma of extrahepatic bile ducts in seventy-eight cases.

‘!

-___-_24 d

3 wk.* 57 mo.

* Hospital death.

the difficulty of obtaining good surgical results this disease. The definitive operative procedures in the seventy-three patients included : biopsy only, nineteen patients; T tube choledochostomy, eighteen; hepatoduodenostomy, seven ; pancreatoduodenectomy, six ; choledochoduodenostomy, five; hepaticojejunostomy, three; cholecystectomy, three; insertion of vitallium tube, three; choledochoduodenostomy over vitallium tube, two ; choledochojejunostotny over vitallium tube, two; cholein

,”

3 days* Not traced

:,s

dochoduodenostomy with gastroenterostomy, one; cholecystojejunostomy, one; hepaticogastrostomy with T tube, one; hepaticojejunostomy with T tube, one; incision of liver lobe, one. Pancreutoduodeneclomy. The Whipple operation was performed in six cases, which are summarized briefly in Table I. Although the group was small and only five patients were traced, it is noteworthy that the two of these who were able to leave the hospital postoperatively survived much longer than the mean period for the series as a whole, and indeed gave the group a relatively good average.

FIG. 3. A, mucoid adenocarcinoma, grade 1, primary in common hepatic duct. (Hematoxylin and eosin stain; original magnification X 100.) B, mucoid adenocarcinoma, grade 2, of common bile duct, showing pools of mucus and fair degrees of cellular pleomorphism. (Hematoxylin and eosin stain; original magnification X 150.)

Carcinoma

of Extrahepatic

Bile Ducts

,Tl: ;

HISrOLOGIC

TYPE AND GRADE OF CARCINOMA OF I:XTRAHEPA'rIC RILE DUCTS IN SEVENTY-EIGHT PATIENTS

Histologic

Type

Adenocarcinoma Papillary Scirrhous Mucoid Medullary Adenoacanthoma Total

PATHOLOGIC

_----Grade------. 1 2 0 5 5 0 1 0 11

0 9 23 6 5 1 41

3

4

0 2 1” 0 ;? 19

0 0 x 0 1 0 4

FEATURES

Exact determination of the origin of the tumor was often difficult, especially when it occurred near the junction of the right and left hepatic ducts with the common hepatic duct. In deciding, we placed major emphasis on the surgical findings. Care was taken to exclude any tumor arising from the papilla of Vater as well as any which had arisen in the gallbladder and invaded the cystic duct secondarily. The anatomic distribution of accepted lesions is shown in Figure 2. The cell types and the estimates of degrees of anaplasia (Rroders’ method) are presented in

Table II, and typical pictures are shown in Figure 3. At the time of definitive surgical treatment or exploration (including autopsy) the tumor had spread beyond the bile duct in fifty-five cases (71 per cent). This severely restricted aggressiveness in surgery. The structures most corrmonly involved were the liver (Fig:. 4). the

FIG. 3. C, papillary adenocarcinoma, grade 1, of common bile duct, with some production of mucus likewise evident. (Hematoxylin and eosin stain; original magnification X 150.) II, stenosing carcinoma of common hepatic duct with scirrhous reaction. /Hematoxvlin and eosin stain; original magnification X 150.) Vol. 113, Januavy

1967

Van Heerden,

Judd, and Dockerty TABLE

PRIMARY

AND

POSTOPERATIVE

ANCILLARY

TREATMENT

AND

HEPATIC

Primary Operation

Case

Affected Common Duct

BILE

Pancreatoduodenectomy

Bile

24

VII

Choledochoduodenostomy

Bile

VIII

T tube choledochostomy

Hepatic

3 13 4

IX

T tube choledochostomy

Bile

X

Hepaticojejunostomy

Hepatic

12 18

XI

Hepaticoduodenostomy

Bile

29

1

vessels associated with the portal

vein and hepatic artery, the retroperitoneal lymphatics, the gastrohepatic omentum, the peritoneum, and the adjacent pancreas. In one patient who presented with severe backache, the lumbar vertebrae were involved by metastasis from a primary carcinoma of the common hepatic duct. Perineural involvement by tumor was sought and found in nineteen instances (24 per cent). Associated lithiasis was present in only fourteen cases (18 per cent), which is far below the incidence reported in most other etiologic relationship is series [4,9]. The questionable. COURSE TREATMENT

AFTER OR

DEFINITIVE EXPLORATION

Immediate Postoperative Period.

Among the seventy-three surgical cases in this series there were eight hospital deaths (two days to four weeks postoperative), making the surgical mortality 10.2 per cent. Wound infection and dehiscence occurred in seven patients; fistulas (biliary, duodenocutaneous, or both) in three; unexplained fever in two ; and subphrenic abscess, pelvic abscess, and gastrointestinal hemorrhage in one each. It is noteworthy, however, that fifty patients had a completely uneventful immediate postoperative course. Six patients received either delayed chemotherapy (5-fluorouracil, streptonigrin, or both),

IN

SIX

PATIESTS

\YITH

CARCINOMA

UF

ESIRA-

DUCTS

Y--Ancillary Months Postoperative

VI

lymphatic

III RESULTS

Treatment----Modality

or Particulars

Hepaticojejunostomy and chemotherapy 5-Fluorouracil Streptonigrin Roentgen ray and 5-fluorouracil Roentgen ray and 5-Auorouracil Vitallium tube inserted Gastrojejunostomy (for obstruction) and chemotherapy Vitallium tube inserted at operative site (for recurrence)

delayed deep roentgenologic surgery. A brief summary given in Table III.

--Results-status

Months Postoperative

Dead

57

Dead

13.5

Dead

5

Dead

24

Alive

37

Dead

41.5

therapy, or further of these cases is

Later Follow- up Study. Complete follow-up information was obtained in sixty-seven patients (86 per cent). From among the sixty-two traced surgical cases, one patient is alive at the time of writing, being thirty-seven months postoperative. She presently has gross ascites and marked nodular hepatomegaly. Survival after surgery ranged from two days to sixty-five months, averaging 11.4 months. This is far above the reported averages of four to six months. Five patients (8.1 per cent) survived three years postoperatively and one (1.6 per cent) survived five years. CASES FIRST DIAGNOSED

AT AUTOPSY

Cuse 12. At operation on a sixty-seven year old woman, the liver was found to be grossly infiltrated and biopsy revealed undifferentiated grade -1 carcinoma. Severe hypotension led to death two days postoperatively. Advanced primary carcinoma of the cystic duct was found at autopsy. Case 13. A sixty-two year old woman was admitted because of severe backache, and hepatic coma soon developed. She died two weeks after admission. Adenocarcinoma of the common hepatic duct was revealed by postmortem study. Case 14. A seventy-seven year old man was admitted in hepatic coma and died one week later. Adenocarcinoma at autopsy.

of the common

bile duct was found

Carcinoma

of Hxtrahepatic

Ctrsp1 i. A seventy-two year old man underwent ~hc)lcdochoduodenost(~rny for penetrating duodenal ulcer obstructing the common bile duct. Death occurred two days postoperatively after severe hy1Jotension. Adenocarcinnma of the commnn bile duct was found. (?Ls(’ 16. A seventv-seven year old man was treated by cholecysto;ejunostomy for supposedly Ilenign obstruction of the common bile duct. Death occurred three weeks postoperatively after wound disruption and coma. Adenocarcinoma of the common hepatic duct was found. (‘(zsf’ 17. .4 fifty-fi\-e year old man was admitted with severe hematemesis and jaundice and died one week later. Adenocarcinoma of the common bile duct was discovertrd. CflSfJ 18. A sixty-fi\-e year old man presented with hepatorenal failure and died two weeks later. Adenocarcinoma of the common hepatic duct was demonstrated at au topsy.

REFERENCES 1. RENSHAIV, K. Malignant neoplasms of the extrahcnatic bile ducts. Ann. SUYP.. X5: 205, 1922. 2. HAM, J. M. and MACKENZIE, 6: C. Primary carci-

noma of the extrahepatic bile ducts. Surg. Gynec. & Obst., 118: 977, 1964.

3. WAUGH, J. M. Cited by Mar&,

J. S. and Dreyer, B. j. VAN R. [Id]. 4. JUDD, E. S. and GRAY, H. K. Carcinoma of the gallbladder and bile ducts. I’roc. Internat. Assemb. Inter-State Post-arod. 111. A. North America, ‘7: 312, 1931. 5. JIJDD,E. S. and GRAI. H. I;. Carcinoma of the gall-

.-,,-J

(i. GRAY, II. Ii.

7.

8.

9.

10. 11.

12.

SIJMMARY

Seventy-eight cases of carcinoma of the extrahepatic bile ducts were reviewed, including seven diagnosed at autopsy. Diabetes mellitus was associated in 10 per cent. Jaundice and pain were presenting complaints in 62 and 58 per cent, respectively. The serum bilirubin value was generally in accord with obstructive jaundice, and usually the serum alkaline phosphatase value had the same trend. Seventy-three patients underwent surgery at the Mayo Clinic, but in 59 per cent it was only exploratory or palliative. At operation, involvement had reached beyond the primary site in il per cent. Lithiasis was associated in only 1S per cent. Radical pancreatoduodenectomy in five traced cases resulted in two relatively long survi\-als. Complete followup information was obtained in sixty-seven cases, of which sixty-two were Surgical. Average survival after surgery was 11.1 months. Three year survival was S. 1 per cent, and five year survival 1.O per cent.

Bile Ducts

13.

14.

15.

16.

Carcinoma of the gnllbladdcr, c\tr:ihcpatic bile ducts and the mxjor duoden: papilla. S. C/in. North Amvica, 21 : 11 Ii. 1911. K~mI,I.vc, H. i\., DOCKERTY. h’I. B., and WAUGH, 1. M. Carcinoma of the estrahepatic bile ductb. .>“urg.Gqwec. & Obst., 89: 429, 1919. KVKAYTI, K., BAGGENSTOSS, .I. H.. STACFFEK, M. H., and PRIESTLEV, J. T. Carcinoma of the major intrahepatic and the cxtrahepatic bill, ducts esclusive of the papilla of \‘atcr. .$2lr1: (;ynec & Obst., 101: 357, 19.57. BROIVN, I). B., STRANG, R., GORUON. J,, anti HENDRV, E. B. Primary wrcinoma of thv extrahepatic bile-ducts. Brit. J. Surg., 49: 22, 1961. DENBESTIN, L. and LIECHTY, R. 1~).Cancer of the, biliary tree. Am. .r. Surg., 109: 587, 1965. PERMEN, L. E. and MCCOLLUM. E. B. I’rirnaq carcinoma of the extrahcpatic biliary ducts. Ilenry Ford Hosp. 121. Bull.. 11: 167. 1963. WAUG~. J. M. Carcinoma of the cxtrahcpatic bile ducts. In: Treatment of Cancer and .%llied Diseases. 2nd cd., vol. 5. Tumors of thr %strointestinal Tract, Pancreas, Biliary Systcrn. and Liver. p. 364-369. Edited by Pack, C,. T. and i2ricl. I. M. New I’ork, 1962. Paul B. Hoebcr, Inc STROHL, E. L., REED, W. H., DIFFENRA’IJ(:H, W. (3.. and ~.NUERSON, R. E. Carcinoma of the bile ducts. ilrrh. Surf., 87: 567, 1903. MARAIS. J, S. and DREYER, B. J. VAN R. Karsinoon7 van die ekstrahcpatirsc galhuiTc. South Afric.an 111. J., 36: 979, 1962. PAI.LETTE, E. M., HARRINGTON, R. W., and PAl.LETTE, E. C. Carcinomas of thv estrahcp&ic biliary system. Am. .‘;urgeon, 29: il9). 1963. RE~LEIN, Q. R. A current estimate of the prcvalrncc of diabetes mellitus in the United States. ;Inn. 1Yew Jnrk Armd. .71-i., 82: 229, 1959. DISCUSSION

E. S. R. HUGHES (Melbourne, hustralia) :We have had much the same experience in Melbourne. In Australia the incidence of carcinoma of the stomach has decreased 50 per cent over the last two decades, but the incidence of extrahepatic carcinoma of the bile duct has not shown any decline. I should like to ask Dr. Van Heerden if he has noted any incidence or increased incidence of this carcinoma in patients with ulcerative colitis. I have had two patients with ulcerative colitis who died many years after colectomy from extrahepatic car&no& of the bowel. There is a real delay in diagnosis because of the tendency to keep repeating liver function tests until some conclusion is reached, and every day the patient has jaundice makes the surgical problem more and more complicated. I have learned from bitter experience not to hand over these patients to a junior surgeon, because interpretation of some of these carcinomas, which can be minute in size, is often a little beyond the scope of the junior surgeon.

Van Heerden, Judd, and Dockerty KENNETH WARREN (Boston, Mass.) : I want to reemphasize that morbidity, mortality, and salvage rate depend largely on the location of the tumor. We have performed resection in twenty-five patients with typical sclerosing carcinoma involving the intrapancreatic portion of the common duct. Three patients died, and 36 per cent have lived five years or longer. This percentage should not be confused with those which include all carcinomas of the common duct, because as we move more proximally, practically none of these tumors is curable. After evaluating the tumor at laparotomy we design the procedure which will produce the maximal degree of improvement in each patient. Palliation may be increased with the use of either a Y or T tube with one limb traversing the tumor. One may also be able to get in above the tumor and anastomose the duct proximal to the tumor to a limb of the jejunum. Mr. Rodney Smith has recommended mobilizing the gallbladder partially, preserving the blood supply, and finding a duct behind the gallbladder and anastomosing this to the gallbladder. Delay in making the diagnosis leads to tragic results as does failure to distinguish between carcinoma of the distal common duct and carcinoma of the head of the pancreas. JOHN MANN BEAL (Chicago, Ill.) : These really are not terribly common problems when one realizes that seventy-eight cases were encountered at the Mayo Clinic in ten years. The diagnosis is occasionally overlooked at operation. I was interested in noting the number of patients who had been operated on elsewhere before being operated on at the Mayo Clinic, and this, I am sure, is familiar to all. One method of obtaining earlier diagnosis is percutaneous transhepatic cholangiograms, and these patients are excellent candidates for this procedure. This procedure is safe if used immediately before operation. We have had experience with approximately thirty-five percutaneous transhepatic cholangiograms. Use of an image intensifier, image amplifier, and television monitor makes the technic relatively simple and safe. The procedure locates the side and strongly suggests the type of obstruction present. This is useful in patients who have jaundice; moreover, it can facilitate in getting the operation performed earlier. BENTLEY P. COLCOCK (Boston, Mass.) : I am interested in the relation between sclerosing cholangitis and ulcerative colitis, Whenever anyone asks my advice about a patient with sclerosing cholangitis, I immediately ask if they have ulcerative colitis. If they do not, I am much more pessimistic about being able to give them any helpful advice. EDWARD S. JUDD (closing) : Mr. Hughes raised the question aborrt the change in the incidence of malignant tumors. I am sure he is aware that in this

country, too, we are fascinated by the marked decrease in the incidence of cancer of the stomach. We have an impression that pancreatic malignancy may be increasing; however, as Dr. Beal mentioned, the tumor we have been discussing is still rather rare. Mr. Hughes also comment.ed on the problem of chronic ulcerative colitis. We have been struck by this also, and the association with jaundice is a matter of note. Dr. Van Heerden mentioned the two patients included in this series who, indeed, did have chronic ulcerative colitis. Many will recall Dr. VVarren’s paper presented last year in New York before this Society which dealt with sclerosing cholangitis. We, too, have been intrigued by this coincidental problem, and do not know the answer. However, as Dr. Colcock mentioned, we are alerted to the possibility because this is a serious complication, indeed. Mr. Hughes mentioned the delay in diagnosis as being extremely serious, and I think Dr. Beal has hit upon one adjunct which will be tremendously helpful. Recently, my colleague, Dr. Don McIrath. had two patients who had been explored previously. The diagnosis had not been made. LVith percutaneous cholangiography, he was able to determine that both had this type of tumor. Unfortunatelv, one had been thought to have sclerosing cholangitis for over two years and had had a massive course of steroids to the point of osteoporosis; of course. nothing can be done now. Dr. Warren mentioned the splinting tube at operation, and we certainly are all in favor of this. We have used this tube and think it will reduce mortality if properly applied. He mentioned especially the difficulty with inaccessible lesions; of course, more may be located with percutaneous cholangiography but may be so high that thev are impossible to remove. The question is what can be done about them surgically. Dr. Beal has stressed the overlooked diagnosis. Many of our patients were explored before coming to us. We must confess that in several patients the diagnosis was missed by our surgeons also at the first operation; however, with percutaneous cholangiography properly performed in the operating room, these tumors may be detected. Dr. Colcock also mentioned chronic ulcerative colitis, and we hope to have some information soon. In summary, the situation is dismal. The coincidence of a high level of alkaline phosphatase and a relatively low level of serum bilirubin apparently is not significant. Although it is obvious that radical surgery is often not feasible and at least in our experience has a high mortality, if we persist, we will be able occasionally to find a case that can be treated in a radical fashion, and occasionally we will have a long-term survival.

American

Journal

of Surgery