Early carcinoma of the extrahepatic bile duct

Early Carcinoma of the Extrahepatic Bile Duct

Tsukasa TSUNODA, Toshifumi ETO, Masataka KOGA, Tsutomu TOMIOKA, Koichi MOTOSHIMA, Takashi Y.~Xt~GOCHI, Kunihide IZAWA and

Ryoichi TSUCHIYA

ABSTRACT: This study attempts to define early carcinoma o f the extrahepatic bile duct through a study o f 11 patients whose carcinomatous invasion did not extend to the outer layer of the bile duct. The patients were divided into the following 3 groups, namely; a mucosa group comprised of 3 patients, a fibromuscular layer group comprised of 5 patients, and an adventitia group comprised of 3 patients. None o f the patients had any lymphnode metastases. Histological characteristics were determined according to infiltrative growth (INFa, t , y), lymphatic invasion (ly), venous invasion (v) and perineural invasion (pn). In the mucosa group, INFa was observed in 2 patients, while ly, v, and pn factors were all negative. In the fibromuscular layer group, INFfl was seen in 3 patients, ly was positive in 2 patients, while v, and pn factors were negative in all patients. In the adventitia group, INFy was found in 2 patients, and ly, v, and pn factors were positive in all patients except for 1 in whom v was negative. Death from recurrence occurred in all the adventitia group patients and in 1 other patient. Early carcinoma of the extrahepatic bile duct could therefore be defined at present, as being carcinoma confined to within the mucosa and fibromuscular layer.

KEY WORDS: early carcinoma, bile duct carcinoma, histopathological analysis

INTRODUCTION

T h e r e has been an increasing interest re- cently in early carcinoma of the extrahepatic bile duct, however, its definition is still con- troversial. Can early carcinoma be judged by histological carcinomatous invasion into the bile duct wall as in hollow organs such as the stomach and colon? If so, what depth of

The Second Department of Surgery, Nagasaki Uni- versity School of Medicine, Nagasaki, Japan

Reprint requests to: Tsukasa Tsunoda, MD, The Second Department of Surgery, Nagasaki University School of Medicine, 7-1 Sakamoto, Nagasaki 852, Japan

carcinomatous invasion should be defined as early carcinoma of the extrahepatic bile duct?

This study was carried out in an attempt to define early carcinoma of the extrahepatic bile duct histopathologically, on the basis of our experience of treating bile duct cancer over the past eighteen and a half years.

MATERIALS AND METHODS'

A total of 146 patients with primary carcinoma of the extrahepatic bile duct treated in the Second Department of Surgery, Naga- saki University Hospital f rom September 1969 to March 1988 were reviewed. In 11 of

JaPAnESE JOVgYAL OF SURGERY, VOL. 19, No. 6 pp. 691-698, 1989

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Volume 19 Number 6 Early carcinoma of the bile duct 693

these 146 patients (7.5 per cent), the carcinomatous invasion did not extend to the outer layer of the extrahepatic bile duct. As the carcinomatous invasion in the remaining cases extended beyond the outer layer of the bile duct, this was considered to be advanced carcinoma and they were therefore excluded from the present study.

AS the bile duct wall consists of 3 layers; the mucosa, the fibromuscular layer, and the adventitia, the patients analyzed in this study were divided into 3 groups according to the depth of carcinomatous invasion into the bile duct wall. Three patients belonged to the mucosa group, 5 to the fibromuscular layer group, and 3 to the adventitia group.

The macroscopic tumor type, tumor size, histological findings and postoperative survival period were examined in all 11 patients. For the histological study, total resected specimens embedded in paraffin were cut serially at 3 to 4 mm intervals and then stained with hematoxylin and eosin, Masson trichrome and elastica Van Gieson to obtain precise findings. Histological findings were described according to the "General Rules of Surgical and Pathological Studies on Cancer o f the Biliary Trac t ''1 p r o p o s e d by the Japanese Society of Biliary Surgery. The histological characteristics were determined according to the following four factors: infiltrative growth, lymphatic invasion, venous invasion, and perineural invasion of the carcinoma. In the infiltrative growth (INF) category, a meant a state in which the tumor tissue was clearly distinguished from the peripheral tissues, showing only the slightest infiltrative growth. INF), indicated that the tumor tissue showed infiltrative tendencies and that the border between the tumor and pe r iphe ra l tissue was unclear ; in o the r words, that infiltrative growth of the tumor was prominent. INF/3 was an intermediate state between INFa and INF),. Gradings of lymphatic invasion (ly) consisted o f ly 0 for negative, ly I for slightly positive, ly 2 for moderate involvement, and ly3 for prominent involvement. Gradings of venous inva-

sion (v 0, v 1, v 2, and v3) and gradings of perineural invasion (pn0, pnl, pn2, and pn3) were represented in the same way as those of lymphatic invasion.

Additionally, the thickness of the bile duct wall and the distance from the bile duct to the surrounding structures were measured at three points (upper, middle and lower) in the hepatoduodenal l igament of an autopsy case without hepatic, biliary or pancreatic disease.

RESULTS

Macroscopic and microscopic findings in each group (Table 1) 1. Mucosa group: In the mucosa group

(Cases No. 1, 2, 3), the gross shape included a pedunculated polyp in 1 patient, a sessile polypoid lesion in 1, and a pedunculated polyp with a sessile polypoid lesion in 1. The mean tumor size was 1.2 X 0.7 cm, which was smaller than that o f ei ther the fibromuscular layer group or the adventitia group. The microscopic findings in this group revealed papillary adenocarcinoma in 2 patients and poorly differentiated adenocarcinoma in 1. There were no lymphnode metastases and the category of INF was INF0t i n 2 patients and INFfl in l. No lymphatic, venous, or perineural invasions were observed. The following is a description o f a representative case in the mucosa group (No. 2).

This patient was a 68 year old Japanese man whose chief complaint was right upper quadran t pain with fluctuating jaundice . Endoscopic re t rograde cho lang iog raphy (ERC) revealed a 1.0 X 1.0 cm filling defect in the common hepatic duct (Fig. 1). Resection of the extrahepatic duct and anastomosis of the right and left hepatic ducts to the non functional jejunal loop (Roux-Y) was performed. The gross appearance o f the tumor revealed a sessile polypoid lesion of 1.0 X 0.4 cm (Fig. 2). Microscopy revealed papillary a d e n o c a r c i n o m a l imi ted to wi th in the mucosa (Fig. 3) with no lymphnode metastases. The four factors were graded as INFol, ly0, v0, and pn 0. He died o f liver metastasis 8.8

694 Tsunoda et al. ~ Jpn, J. Surg. November 1989

Fig. 3. High power histological picture showing papillary adenocarcinoma limited to the mucosa in Case No. 2. (HE XlO0)

Fig. 1. ERC of Case No. 2 showing a filling defect (arrow) in the common bile duct.

Fig. 4. ERC of Case No. 5 demonstrating a filling defect (arrow) in the intrapancreatic bile duct.

Fig. 2. Low power view of a cross section showing the sessile polypoid lesion of Case No. 2 between the two arrows. (HE X13)

years after the operation. 2. F ib romuscu la r layer group: In the

fibromuscular layer group (Cases No. 4, 5, 6, 7, 8), the gross appearance of the tumor was a peduncutated polyp in 2 patients, a pedunculated polyp with sessile polypoid lesion in 1, a sessile polypoid lesion in 1, and a flat lesion in 1. The m e a n size of the tumors was 2.6 X 1.2 cm, which was larger than that o f the mucosa group but smaller than that o f

the adventitia group. Microscopic findings in this group revealed a high degree of differ- entiation in all patients but no lymphnode metastases. The category o f INF was INF/? in 3 patients, and INFa in 2. The gradings of venous and per ineural invasion were v 0 and pn 0 in all patients, but lymphatic invasion (ly 1) was seen in 2 of the 5 patients. The following is a description of a representative case in the fibromuscular layer group (No. 5).

The pat ient was a 67 year old Japanese man whose chief complaint was upper ab- dominal pain with fluctuating jaundice. ERC revealed a 2.0 X 1.0 cm filling defect in the intrapancreatic bile duct (Fig. 4) and a pan- creatoduodenectomy with reconstruction by

Volume 19 Early carcinoma of the bile duct 695 Number 6

Fig. 5. A pedunculated polyp (arrow) was comprised of papillary adenocarcinoma confined to the fibromuscular layer in Case No. 5.

a modified version of Child's method was performed. Macroscopically, the tumor type was a pedunculated polyp of 2.4 X 1.0 cm and microscopy showed papillary adenocar- c inoma confined to within the fibromuscular layer (Fig. 5) with no lymphnode metastases. Histopathological gradings of the four factors were INF/3, ly 0, v 0, and pn 0. He died of unrelated colon cancer, 2 years after the operation and an autopsy revealed no recurrence of carcinoma of the common bile duct.

3. Adventitia group: In the adventitia group (Cases No. 9, 10, 11), the gross shape was an infiltrating type in 2 patients and a pedunculated polyp with sessile polypoid lesion in 1. The mean tumor size was 4.3 X 2.1 cm, this be ing the largest a m o n g the 3 groups. Microscopic examination revealed papillary adenocarcinoma, well differenti- a ted a d e n o c a r c i n o m a , a n d m o d e r a t e l y differentiated adenocarcinoma, respectively, but no lymphnode metastases. The category of INF was INFy in 2 patients and INF/~ in 1. As for the histological gradings, ly, and pn, were seen in all 3 patients, and v 1 in 2. The following is a description of a representative case in the adventitia group (No. 10).

The pat ient was a 53 year old Japanese man whose chief complaint was jaundice. He had undergone a hemigastrectomy and reconstruction with a gastrojejunostomy for a

Fig. 6 ~. PTC of Case No. 10 showing a "rat- tail" constricting lesion (arrow) of the common hepatic duct.

gastric ulcer 2 years earlier. Percutaneous transhepatic cholangiography (PTC) revealed a "rat-tail" constricting lesion of the common hepatic duct (Fig. 6). A curative resection of the extrahepatic duct was done, but it was necessary to per form additional resections twice on both the left hepatic duct and the i n t r a p a n c r e a t i c duct, to ob ta in microscopically tumor-free resected margins at the time of the operation. Intestinal con- tinuity was achieved by anastomosing the right hepatic duct to the duodenum in association with ligation of the left hepatic duct. The gross shape of the tumor revealed an infiltrating type tumor, 5.2 X 1.4 cm in size (Fig. 7a, b) extending f rom the left hepatic duct to the common bile duct. Microscopic examination of the resected specimen revealed well-differentiated tubular adenocar- c inoma (Fig. 8) limited to the adventitia without any sign of invasion to the subserosa in all sections. No lymphnode metastases were observed and gradings of the four factors were INFy, ly 1, vl, and pn v He died of recurrent cancer at the anastomotic site 7.2 years after the operation.

696 Tsunoda et al. Jpn. J. Surg. November 1989

b Fig. 7. a. Resected specimen of Case No.

10 showing the infiltrating type of tumor with superficial spread, b. An illustration of the resected specimen of a. Dotted lines show the spread of carcinomatous invasion.

Prognosis All 11 patients underwent tumor resection,

but 2 of the patients in the adventitia group (Cases No. 9, 11) had a residual tumor at the resected stump on the duodenal side due to diffuse spreading of cancer cells along the bile duct. Although the follow-up periods ranged from between 2 months to 10.3 years, excluding 1 operative death, death from recurrence occurred in 1 patient from the mucosa group, and in all the adventitia group patients. Death from recurrence was not seen in any of the 5 patients in the fibromuscular layer group.

Fig. 8. Well-differentiated tubular adenocarcinoma in Case No. 10 widely involves the wall of the bile duct but does not extend to the outer layer. Arrows show the layer of advenfitia. (HE X40)

Thickness of the bile duct wall and distance from the bile duct to the surrounding structures (Fig. 9a, b, c) The thickness of the bile duct wall was less

than 1 mm along the efitire extrahepatic bile duct. The distance from the bile duct wall to the anterior peritoneum was 1.0-1.3 mm, to the posterior peritoneum, 0.2-1.6 cm, to the portal vein, 0.2-0.5 cm, and to the hepatic artery, 0.2-1.0 cm.

DISCUSSION

When a carcinoma develops in the par- enchymal organs such as the pancreas and liver, it seems that the smaller the size of the tumor, the earlier the disease, ~ and when a carcinoma develops in the hollow organs such as the stomach and colon, early carcinoma has been defined as a lesion confined to the mucosa or submucosa? How- ever, little is known about early carcinoma of the extrahepatic bile duct.

Kasai et al. 4 collected 109 cases of "early carcinoma" of the bile duct from the 48

Volume 19 Number 6 Early carcinoma of the bile duct 697

C

Fig. 9. Low power view of a cross section at the three different sites (a, upper; b, middle; c, lower sites) of the hepatoduodenal ligament. GB, Gallbladder; CD, Cystic duct; BD, Bile duct; HA, Hepatic artery; PV, Portal vein; GDA, Gastroduodenal artery; LN, Lymphnode; N, Nerve

medical institutions present at the 19th annual meet ing of J apan Biliary Association in 1983. In the proceedings of the meeting, 25 of these 48 institutions described their definitions of "early carcinoma" and differ- ing opinions on the definition of early

carcinoma of the bile duct were found. The various definitions included carc inoma limited to the mucosa or fibromuscular layer in 10 institutions, carcinoma confined to the wall of the bile duct in 6, carc inoma of Stage I in 4, carc inoma with a long survival per iod in 3, and carcinoma without jaundice in 2. The criteria used in 16 of the 25 institutions (64 per cent) therefore depended on the depth of carcinomatous invasion into the wall of the bile duct. No institutions used tumor size in the judgement of early carcinoma.

We analyzed 11 cases in which carcinomatous invasion was conf ined to the wall of the bile duct. Interestingly enough, the inci- dence of INF,, lymphatic, venous, and perineural invasions were frequently demon- strated when the tumor extended beyond the fibromuscular layer, al though there were no lymphnode metastases in any of the groups. Furthermore, death f rom recurrence was seen in only 1 of the 8 patients f rom the mucosa and fibromuscular layer groups but in all 3 patients from the adventitia group and the recurrences in the adventitia group all occurred at the resected stumps. Thus, careful attention should be paid to the longi- tudinal superficial spreading of cancer cells in the bile duct wall even when there is no apparent invasion of the outer layer of the bile duct.

We examined the rate of death from recurrence among 20 mucosa and 32 fibromuscular layer cancer patients who had undergone curative resections, collected by Kasai et al. at 19th annual meeting of the J apan Biliary Association in 1983. 4 Although the follow-up periods ranged f rom between 1 month to 6.4 years, no death f rom recurrence was seen among the 20 mucosa cancer cases and only 5 were seen among the 32 fibromuscular layer cases (15.6 per cent).

Therefore , on the basis o f histopathological findings and review of prognosis, early carcinoma of the extrahepatic bile duct could be defined as carc inoma confined to within the mucosa and fibromuscular layer.

With regard to the gross shape of the

698 Tsunoda et al. Jpn. J. Surg. November 1989

t u m o r in the mucosa a n d f i b romuscu l a r l ayer groups , it was ma in ly t he p e d u n c u l a t e d type o r sessile p o l y p o i d type p r o t r u d i n g in to the l umen . However , at this stage, it is diff icult to d e t e r m i n e w h e t h e r o r n o t m o s t ea r ly car- c i n o m a s a re o f the p r o t r u d i n g typep b e c a u s e the gross shape o f mos t a d v a n c e d cance r s is o f the inf i l t ra t ing type?

T h e i n c i d e n c e o f ea r ly c a r c i n o m a o f the ex t r ahepa t i c bi le duct was very low, b e i n g on ly 5.5 p e r cen t in o u r ser ies a c c o r d i n g to the a b o v e - m e n t i o n e d cr i ter ia . I t is sugges ted tha t c a n c e r cells a r i s ing f rom t h e m u c o s a o f the b i l e duct can easi ly e x t e n d to the ou te r layer o f the bi le duct a n d t h e n invade di rec t ly in to the por ta l vein, hepa t i c ar tery, n e u r a l t issues a n d soft fatty tissues. However , ongo- ing inves t iga t ions are n e c e s s a r y in o r d e r to fu r the r c lar i fy ear ly c a r c i n o m a o f the extra- hepa t i c bi le duct.

ACKNOWLEDGEMENT

This work was s u p p o r t e d in p a r t by a G r a n t in A id for C a n c e r R e s e a r c h (62-22) f r o m the Minis t ry o f H e a l t h a n d W e l f a r e o f the J a p a -

nese G o v e r n m e n t .

(Received for p u b l i c a t i o n o n Nov. 29, 1988)

REFERENCES

1. Japanese Society of Biliary Surgery. General rules for surgical and pathological studies on cancer of biliary tract. 2nd ed. Tokyo: Kanehara Publishing, 1986; 47-54. (in Japanese)

2. Tsuchiya R, Noda T, Harada N, Miyamoto T, Tomioka T, Yamamoto K, Izawa K, Tsunoda T, Yoshino R, Eto T. Collective review of small carcinomas of the pancreas. Ann Surg 1986; 203; 77-81.

3. Japanese Research Society for Gastric Cancer. The general rules for the gastric cancer study in surgery and pathology. Part. Clinical classification. Jpn J Surg 1981; 11: 127-139.

4. 19th Japan Biliary Association Proceedings. Early carcinoma of extrahepatic bile duct. In Kasai Y, ed. 1983; 258-355. (in Japanese)

5. Kozuka S, Tsubone M, Hachisuka K. Evolution of carcinoma in the extrahepatic bile ducts. Cancer 1984; 54: 65-72.

6. Tsunoda T, Tsuchiya R, Harada N, Noda T, Yama- moto K. Surgical treatment for carcinoma of the extrahepatic bile duct. Jpn J Surg 1985; 15: 123-129.

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Early carcinoma of the extrahepatic bile duct