Surgical treatment for carcinoma of the extrahepatic bile duct

Surgical Treatment for Carcinoma of the Extrahepatic Bile Duct

Tsukasa TSUNODA, Ryoichi TSUCHIYA, Noboru HARADA, Takatoshi NODA and Kensuke YAMAMOTO

ABSTRACT: Eighty-six patients with primary extrahepatic bile duct carcinoma operated on in the Second Department of Surgery at Nagasaki Uni- versity Hospital during a recent 13.5-year period were reviewed. The patients were divided into five groups depending upon the site of the tumor. The operative mortality, resectability, postoperative survival period, and five-year survival rate in each group were studied. The lower third group had the highest resectability, lowest operative mortality and longest post operative survival period. The hepatic duct, the upper third and the extended groups, however, showed extremely poor results. The pathological features of these three groups are discussed here and an operative procedure for resection of the tumor is proposed. We emphasize that the development of methods of early diagnosis is necessary, and recommend aggressive surgical treatment for tumors of the hepatic duct, upper third, and extended groups.

KEY WORDS: carcinoma of the extrahepatic bile duct, hepatic resection, hepaticojejunostomy

INTRODUCTION MATERIALS AND METHODS

The incidence of carcinoma of the extrahepatic bile duct in Japan increased from 0.63 percent of autopsied cases in 1964 to 1.12 percent in 1973, but since 1974 it has re- mained at almost the same level as 1973 and still ranks 4th among all gastroenterological carcinomas in this country. 1

The present report summarizes our results and emphasizes the importance of early diagnosis and extended radical resection. Patients with carcinoma of the gallbladder and carcinoma of the papilla of Vater were excluded from the study.

The Second Department of Surgery, Nagasaki University School of Medicine, Nagasaki, Japan

Reprint requests to: Tsukasa Tsunoda, The Second Department of Surgery, Nagasaki Univer- sity School of Medicine, Nagasaki 852,Japan

Eighty-six patients with primary carcinoma of the extrahepatic bile duct were treated in the Second Department of Surgery, Nagasaki University Hospital during the 13.5-year period from September 1969 to March 1983. The age at operation ranged from five to 83, with an average of 61.8 years. The male:female ratio was 2.3:1. The predomi- nant symptoms at the time of admission were jaundice and pain. About 93 percent of the patients had jaundice, and 7 percent had pain without jaundice.

The preoperative diagnosis was established in 73 patients, or 84.9 percent. Of the 73, 66 were diagnosed by means of percutaneous transhepatic cholangiogram (PTC), 4 by endoscopic retrograde cholangiopancreatico- gram (ERCP) and 3 by selective celiac anglo-

JAPANESE JOURNAL OF SURGERY, VOL 15, No. 2 pp. 123-129, 1985

124 Tsunoda et al. Jpn. J. Surg. March 1985

gram (SCAG). Among the 13 cases which were not diagnosed prior to the operation, seven were confirmed operatively and six by postoperative histology or autopsy. Cytologi- cal examinations of the bile obta ined by PTC were done on 58 patients and 37 revealed positive findings. The diagnostic sensitivity was 63.8 percent. Gallstones were found in nine out of the 86 cases, or 10.5 percent. Three patients had stones in the gallbladder, four in the common bile duct and two in the intrahepatic duct. Seventeen patients out of 50 or 34 percent showed positive findings for infected bile on the basis of bile specimens taken before or during operat ion and then cultured.

The patients were divided into five groups depending upon the location of the tumor, in accordance with the General Rules for Car- c inoma of the Biliary Tract proposed by the Japanese Biliary Surgical Society; ~

Hepat ic Duct Group: tumor arising in the right or left hepatic duct

Upper Third Group: T u m o r occurr ing in the upper half of the c o m m o n bile duct between the confluence of the hepatic ducts and the site at the superior border of the pancreas

Middle Thi rd Group: tumor arising in the lower hal f of the common bile duct

Lower Third Group: tumor arising in the intrapancreat ic port ion of the c o m m o n bile duct

Extended Group: tumor developing in three or more locations

Eleven patients or 12.8 percent in this series belonged to the hepatic duct group, 33 or 38.4 percent to the upper third, 17 or 19.8

percent to the middle third, 17 or 19.8 percent to the lower third and eight or 9.3 percent to the extended group.

Males ou tnumbered females in all five groups. Concerning the liver function tests performed at the time of admission, there was no significant difference among these groups. The durat ion of symptoms prior to definitive operations among these groups was not significantly different either.

The Student 's t test and chi-square analysis were empolyed for the statistical analysis in this study.

RESULTS

Resection of the tumor with bilioenteric anastomosis was performed on 43 patients or 50 percent. As a palliative procedure, either external biliary drainage or the bilioenteric bypass procedure was carried out on 42 patients, and an exploratory laparotomy was done on one (Table 1).

The average operative mortal i ty for all of the patients in this series was 24.4 percent (21 out of 86). The number of mortalities in the hepatic duct and extended groups was higher than the average. The ,opera t ive mortali ty rate in the patients who underwent resection was 7 out of 43 patients, or 16.3 percent, whereas, in the palliatively operated patients, it was 14 out of 43 patients, or 32.6 percent.

As a definitive operat ion for the 11 patients in the hepatic duct group, external transhepatic biliary drainage or intubat ion of the bile duct th rough the blockage was performed in four, anastomosis of the intrahepatic bile

Table 1. Operative Mortality and Resectability

Location of Excisional Op. Palliative Op. Overall Resectability Tumor Mortality Rate Mortality Rate Mortality Rate Rate

Hepatic Duct 40.0% (2/5) 16.7% (1/6) 27.3% 45.5% (5/11) UpperThird 9.1% (1/11) 31.8% (7/22) 24.2% 33.3% (11/33) Middle Third 25.0% (3/12) 20.0% (1/5) 23.5% 70.6% (12/17) LowerThird 7.7% (1/13) 25.0% (1/4) 11.7% 76.5% (13/17) Extended 0% (0/2) 66.7% (4/6) 50.0% 25.0% (2/8)

Total 16.3% (7/43) 32.6% (14/43) 24.4% 50.0% (43/86) ( ): No. of patients

Volume 15 Carcinoma of the Number 2 extrahepatic bile duct 125

duct to the je junum in two, and excision of the tumor with some type of bilioenteric anastomosis in five, i.e. 45.5 percent.

With regard to resection cases in this group, left hepatic lobectomy was performed in four out of the five patients and resection of the right b ranch of the portal vein in the other. Intestinal continuity was reconstructed in three patients with anastomosis of the right hepatic duct to the defunctionalized jejunum, in one pat ient with anastomosis of the right hepatic duct to the duodenum, interposed by the je junum, and in one of the left hepatic duct to the defunctionalized je junum.

The operative mortali ty rate for the excisional operat ion was 40 percent (two out of five patients), whereas it was 16.7 percent (one out of six patients) for the palliative procedure.

Eleven out of 33 patients, or 33.3 percent of the upper third group, underwent an excisional operation. After resection of the tumor, the common hepatic duct was anastomosed to the defunctionalized je junum in four cases, and to the common bile duct in one, while both the right and left hepatic ducts were anastomosed to the je junum in four cases, and the left hepatic duct asso- ciated with ligation of the right hepatic duct was anastomosed to the duodenum in one, and to the je junum in one. Hepat ic resection was not necessary in this group. As a palliative procedure, the intrahepatic duct was anastomosed to the je junum in five patients, intubation or transhepatic external drainage was done in 16 patients and laparotomy in one. The operative mortali ty rate for the excisional operat ion was 9.1 percent (one out of 11 patients) but for the palliative surgery it was seven out of 22 patients, or 31.8 percent.

In the middle third group after resection of the tumor, the common hepatic duct was anastomosed to the duodenum in four patients, including one case in which the jejunum was interposed between the common hepatic duct and the duodenum. The common hepatic duct was anastomosed to the je junum in one. Pancrea toduodenectomy was

performed in seven patients with three operative deaths. As a palliative procedure, common hepatic duct drainage was done in three patients with one operative death, and cholecystostomy was performed in two patients.

As a palliative procedure in the lower third group, cholecystojejunostomy was performed in 2 patients and external cholecystostomy in two others with one operative death. Pan- crea toduodenectomy was performed in 13 patients, or 76.5 percent o f the group, with one operative death. The operative mortal i ty for the excisional operat ion was 7.7 percent, whereas for the palliative surgery it was 25 percent.

In the extended lesion group, an excisional operat ion was done in two out of eight patients, with resection of most of the common bile duct, c o m m o n hepatic duct and bilateral hepatic ducts. Intestinal continuity was reconstructed in one patient with anastomosis of the right and left hepatic ducts to the defunctionalized je junum, and in another patient the right hepatic duct was anastomosed to the duodenum and the left hepatic duct was ligated. As definitive palliative pro- cedures, intubation, transhepatic drainage, or anastomosis of the intrahepatic bile duct to the je junum was performed in six patients with four operative deaths.

As a result, overall operative mortal i ty for the patients who underwent the excisional operat ion was 16.3 percent, whereas tha t for the patients subjected to the palliative procedure was 32.6 percent.

Resectability rates were 45.5 percent for the hepatic duct, 33.3 percent for the upper third, 70.6 percent for the middle third, 76.5 percent for the lower third, and 25 percent for the extended group, respectively. Resect- ability rates in the hepatic duct, the upper third and the extended group were less than the average rate of 50 percent. Therefore, in these three groups, operative mortal i ty was high and resectability low.

For patients who underwent the excisional operation, the cumulative three- and five-year survival rates were 36.4 percent and 32.8 per-


cent respectively. T h e cumula t ive five-year survival ra te in each group was 0 for the hepa t ic duct , 27.3 percen t for the u p p e r th i rd , 15.6 percent for the midd l e th i rd , 49.4 percen t for the lower th i rd a n d 100 percen t for the ex tended group respectively.

As of May 1, 1983, the average pos topera- tive survival pe r iod af ter the excisional opera- t ion in each group, excluding opera t ive deaths, was 20.0 months for the hepat ic duct , 30.6 months for the u p p e r th i rd , 25.9 months for the midd le third, 36.3 months for the

lower th i rd a n d 41.0 months for the ex tended group respectively. The overall survival per iod for pa t ien ts who underwent resection was 31.0 months . On the o ther hand, the average survival pe r iod for those who underwent pa l l ia t ive surgery was significantly shorter at only 6.8 months (Tab le 2).

Recently, the Japanese Bil iary Surgical Society proposed "General Rules for Car- c inoma of the Ext rahepa t ic Bi l iary T r a c t , " in which factors re la ted to resectabi l i ty and prognosis were chosen and symbolized as

Table 2. Operative Survival Rate and Postoperative Period (May, 1983)

Excisional Op. Palliative Op. Location of Cumulative 3 yr. Cumulative 5 yr. Post op. period Post op. period Tumor survival rate survival rate Average mo. Average mo.

(Mean-+S.E.) (Mean_+S.E.) (Mean_+S.E.) (Mean_+S.E.)

Hepatic Duct 20.0+17.9% 0% 20.0+15.7 (3) 10,5+11.8 (5) UpperThird 27.3+13.4% 27.3+13.4% 30.6+33~1 (10) 6.2_+5.2 (15) Middle Third 31.2+14.0% 15.6+13.1% 25.9-+27.2 (9) 3.8-+2.4 (4) Lower Third 49.4+14.8% 49.4_+14.8% 36.3_+34.4 (12) 10,3_+7.4 (3) Extended 100.0% 100.0% 41.0_+50.9 (2) 3,2-+0.2 (2)

Total 36.4+7.6% 3 2 . 8 _ _ _ 7 . 9 % 31.0+30.7 (36)* 6.8___6.6 (29)*

Survival rate was calculated by Kaplan-Meier's method ( ): No. of patients * P<0.01

Table 3a. Factors, Related to Resectability and Prognosis, Proposed by the Japanese Biliary Surgical Society

Metastasis to the Regional Lymph Node Invasion to the Serosa of the Bile Duct Invasion to the Liver (Hepatic Infiltration) Invasion to the Pancreas (Pancreatic Infiltration) Invasion to the Wall of the Duodenum Invasion to the Portal Vein & Hepatic Artery Invasion to the Gallbladder Peritoneal Dissemination Hepatic Metastasis

(N) (s)

(Hinf.) (PanG.)

(D) (V) (C) (P) (H)

Table 3b. Macroscopic Stage-Grouping

or N S Hinf. Panc. D V G

I N ( - ) So Hinf.o Panc.o Do Vo Go II N1 (+) $I Hinf. ~ Panc. 1 D1 V0 G1

III Nz(+),N3(+) $2 Hinf.2 Panc. 2 D2 V1 G2 IV N4 (+) $3 Hinf. 3 Panc.s Ds VI,Va Ga

P1-3, H1.3--Stage IV

Volume 15 Carcinoma of the extrahepatic bile duct 127 Number 2

shown in Tab le 3a. Stage classification was also p roposed (Table 3b).

Eighty-six pat ients were d iv ided into stages accord ing to the above, a l though six could not be classified due to incomple te descr ipt ion (Tab le 4). I t should be no ted tha t near ly ha l f of the pat ients be longed to s tage IV. The combined n u m b e r of pat ients in stages I and II was 19 or 22.1 percent of the total , and they had a resectabi l i ty ra te of 100 percent . The combined n u m b e r of pa t ien ts in the hepa t ic duct , uppe r th i rd a n d ex tended groups, in which the operat ive mor ta l i ty ra te was h igher and the resectabi l i ty ra te lower than average, was 52, that is, four pat ients or 7.7 percen t of the 52 in stage I, two or 3.8 percen t in stage II, 9 or 17.3 pe rcen t in stage I I I , and 33 or 63.5 in stage IV. T h e major i ty of pat ients in those groups, therefore , suffered f rom lesions of the advanced stage.

T h e re la t ionship between stages and operative mor t a l i t y rates was s tudied (Tab le 5). Al- though a h igher ra te was seen in stages I I I and IV in bo th the excisional and the pal l ia- tive operat ions , the opera t ive mor ta l i t y rates of the former were not significantly h igher

than those of the lat ter . Cumula t ive three-year and five-year sur-

vival rates were ca lcu la ted in each stage. Both the three- and five-year survival rates in stages I and II were significantly h igher t han those in stages I I I and IV (Fig. 1). We can see, therefore, the necessity for the deve lopment of methods of ear ly diagnosis, tha t is, stages I and II.

DISCUSSION

Pr imary bile duct ca rc inoma has been one of the most difficult mal ignancies to diagnose and t reat successfully. Local invasion to the hepat ic ar tery a n d por ta l vein and the pres- ence of dis tant metastases make rad ica l surgery difficult. However, surgery is the only way to offer a cure to pat ients with extra- hepa t ic bi le duct ca rc inoma.

A m o n g 5 groups, the lower th i rd g roup revealed the lowest opera t ive mor ta l i ty ra te , the highest resectabi l i ty rate and the longest post- operat ive survival per iod. The reason for this is as follows. Even if invasion or metastasis of the ca rc inoma to the pancreas or regional

Table 4. Stage and Location of Tumor

Stage Location ~ I II III IV Unknown Total

of Tumor ~'-

Hepatic Duct 0 1 (1) 0 9 (4) 1 1l (5) UpperThird 3 (3) 1 (1) 8 (5) 19 (2) 2 33 (11) Middle Third 5 (5) 2 (2) 4 (4) 6 (1) 17 (12) Lower Third 2 (2) 4 (4) 6 (6) 3 (1) 2 17 (13) Extended 1 (1) 1 (1) 5 1 8 (2)

Total 11 (11) 8 (8) 19 (16) 42 (8) 6 86 (43)

( ): No. of Resection

Table 5. Operative Mortality and Stage

Overall Stage Excisional Op. Rate (%) Palliative Op. Rate (%) Mortality (%)

I 1/11 9.1 9.1 II 0/8 0 0

III 4/16 25.0 2/3 66.7 31.6 IV 2/8 25.0 8/34 23.5 23.8

Unknown 4/6 66.7 66.7

Total 7/43 16.3 14/43 32.6 24.4


% 100 _ 9011 i--I 80 ! -

IL$-_.b L, 1' /~

7o Jl i / t i , P + l . 9 6 S . E .

Lg-- ( . . . . . . . . . . . t i I ,I 60 j j

I , I

so q l ' . . . . . . . . . . . . -P . . . . . . . . ~ - l I J'~l t I

40 I L, ! I " - I P - - 1 . 9 6 S . E . / . . . . t _ . . a

3 0 I : ' L . . . . . Y T L 7 l ,

f I 2 0 I L _ . . . . . --~.1 . . . . . . . . . . . . . ' . . . . . .3

i ' , , - 7 I [ I j I . . . . . . . . . . . -11- ,

lo i', • I

IA_ I I i

Fig. 1. Cumulative survival rate following resection for carcinoma of extrahepatic bile duct and stage. - - Stage I (11 cases), - - - Stage II (8 cases), - . . . . Stage III (16 cases), -~ Stage IV (8 cases)

lymphnodes is confirmed in this group, curative t reatment by pancrea toduodenec tomy is possible. On the other hand, the hepatic duct, upper third and extended groups had higher operative mortali ty rates, lower resectability rates, and poor prognosis. The poor results in those three groups is probably due to factors such as the character of the tumor itself, the advanced stage at the time of operation, and the technical difficulty of the procedure. In these three groups, most of the tumors were of the macroscopically infiltrating type. The survival periods of the patients whose resected tumor was of the localized type are significantly longer than those of the patients with tumors of the infiltrating type. ~,4 It is clear, therefore, that early diagnosis and curative resection in these three groups is the key to an improvement of results in the treatment of pr imary bile duct carcinoma. In order to raise the resectability rate, recon- struction of the blood supply in cases where the tumor has invaded the hepatic artery or

portal vein is necessary, along with a redical hepatectomy that eliminates the possibility of residual carc inoma in the ~resected s tump on the hepatic side.

Early symptoms are very vague, but nearly all patients reveal the signs and symptoms of obstructive jaundice. 5 Recently, ultrasono- graphic investigation in patients with sus- pected obstructive jaundice or upper abdomi- nal pain has become the preferred examina- tion. Following confirmation of the dilated duct by ultrasonography, PTC or ERCP can be carried out. 6,7 Furthermore, in order to detect tumors in earlier stages, development of reliable serological screening tests are being at tempted. It has been suggested that deter- minat ion of serum carbohydrate antigen 19-9 (CA 19-9) 8 or serum aa-antitrypsin 9 may be effective in the diagnosis and managemen t of the patient with biliary carcinoma.

The five-year survival rates and average postoperative period after excisional surgery have been encouraging. An aggressive at-

Volume 15 Carcinoma of the extrahepatic bile duct 129 Number 2

t i t u d e is r e c o m m e n d e d even fo r cases in t h e

h e p a t i c d u c t , u p p e r t h i r d a n d e x t e n d e d groups.SA0-14

As r a d i c a l r e sec t i on fo r t h e h e p a t i c d u c t

g r o u p , r i g h t o r lef t h e p a t i c l o b e c t o m y is

m a n d a t o r y . I n t he p r e s e n t series, lef t h e p a t i c

r e s e c t i o n was p e r f o r m e d in f o u r cases.

H e p a t i c l o b e c t o m y is r e c o m m e n d e d fo r t h e

u p p e r t h i r d or t h e e x t e n d e d g r o u p , b e c a u s e

t h e i n f i l t r a t i n g t ype o f t u m o r f r e q u e n t l y

i n v a d e s t h e i n t r a h e p a t i c duc t s . W h e n h e p a t i c

r e s e c t i o n is c o n t r a i n d i c a t e d in t h e u p p e r t h i r d

a n d e x t e n d e d g r o u p s b e c a u s e o f d i s t u r b e d

l iver f u n c t i o n , t h e i n f i l t r a t e d h e p a t i c d u c t

s h o u l d b e r e m o v e d to as h i g h a n e x t e n t as

poss ib le , i n c l u d i n g t h e s e g m e n t a l d u c t . T h i s

o p e r a t i o n r e q u i r e s a h e p a t i c o j e j u n o s t o m y be-

t w e e n t h e severa l d i v i d e d i n t r a h e p a t i c duc t s

at t h e p o r t a h e p a t i s a n d t h e j e j u n a l loop.

W h e n e i t h e r t h e r i g h t o r le f t p o r t a l ve in

b r a n c h is i n v o l v e d b y t h e t u m o r i t c a n b e

r e m o v e d i f t h e h e p a t i c a r t e r i a l s u p p l y is n o t

d i s t u r b e d . A n a s t o m o s i s o f t h e h e p a t i c d u c t ,

i n o n e l obe possess ing p o r t a l ve in supp ly , to a

d e f u n c t i o n a l i z e d j e j u n u m seems to b e suffi-

c i e n t to re l i eve j a u n d i c e , is

( R e c e i v e d fo r p u b l i c a t i o n o n A p r . 12, 1984)

R e f e r e n c e s

1. Annual report of pathological autopsy cases in Japan. Edited by the Japanese Pathological Society. Vol 7-16. 1965 1974. (in Japanese)

2. General rules for surgical studies on cancer of biliary tract. Edited by the Japanese Biliary Surgical Society. Vol. 1. 1981. (in Japanese)

3. Todoroki T, Okamura T, Fukao K, Nishimura A, Otsu H, Sato H, Iwasaki Y. Gross appearance of

carcinoma of the main hepatic duct and its prognosis. Surg Gynecol Obstet 1980; 150: 33-40.

4. Takasan H, Kim CI1, Arii S, Takahashi S, Uozumi T, Tobe T, Honjo I. Clinicopathologic study of seventy patients with carcinoma of the biliary tract. Surg Gynecol Obstet 1980; 150: 721-726.

5. Longmire WP Jr. McArthur MS, Bastounis EA, Hiatt J. Carcinoma of the extrahepatic biliary tract. Ann Surg 1973; 178: 333-345.

6. Voyles CR, Bowley NJ, Benjamin IS, Blumgart LH. Carcinoma of the proximal extrahepatic biliary tree; Radiologic assessment and therapeutic alter- natives. AnnSurg 1983; 197:188 194.

7. Goodnight JE Jr. Bile duct carcinoma. Surgical Clinics of North America 1981 ; 61 : 981-986.

8. Suzuki T, Miyashita T, Naitoh A, Tani T, Tobe T. Differential diagnosis between pancreatic cancer and tumor-forming type of chronic pancreatitis. lgaku No Ayumi 1983; 27: 8-15, (in Japanese)

9. Miyamoto T. Studies on serum ctl-antitrypsin for screening test of carcinoma of the pancreas and the biliary tract. J Jpn Surg Soc 1982; 83: 572-58I. (in Japanese)

10. Evander A, Fredlund P, HoevelsJ, Ihse I, Bengmark S. Evaluation of aggressive surgery for carcinoma of the extrahepatic bile ducts. Ann Surg 1980; 191: 23-29.

11. Launois B, CampionJP, Brissot P, Gosselin M. Car- cinoma of the hepatic hilus; Surgical management and the case for resection. Ann Surg 1979; 190: 151-157.

12. Tsuzuki T, Uekusa M. Carcinoma of the proximal bile ducts. Surg Gynecol Ohstet 1978; 146: 933-943.

13. FortnerJG, Kallum BO, Kim DK. Surgical management of carcinoma of the junction of the main hepatic ducts. Ann Surg 1976; 184: 68-73.

lwasaki Y, Ohto M, Todoroki T, Okamura T, Nishi- mura A, Sato H. Treatment of carcinoma of the biliary system. Surg Gynecol Obstet 1977; 144: 219-224.

Longmire WP Jr, Tompkins RK. Lesion of the seg- mental and lobar hepatic ducts. Ann Surg 1975; 182: 478-495.

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Surgical treatment for carcinoma of the extrahepatic bile duct