Nonsurgical management of primary cholangiocarcinoma

Digestive Diseases and Sciences, Vol. 40, No. 3 (March 1995), pp. 701-705

Nonsurgical Management of Primary Cholangiocarcinoma

Retrospective Analysis of 40 Cases

BHASKAR BANERJEE, MD and STEPHEN K. TEPLICK, MD

Forty patients with cholangiocarcinoma (23 men, 17 women) underwent nonsurgical palliative biliary drainage over a period of 12 years. All were surgically unfit or had unresectable disease. All were jaundiced at presentation with a mean serum bilirubin of 11.5 - 1.9 mg/dl. Thirty patients (75%) had hilar obstruction. Twenty-eight were drained percutaneously, three endoscopically and nine by a combined endoscopic and percutaneous procedure. Technical success was 97.5%. Final mean bilirubin was 1.5 __+ 0.4 mg/dl. Minor complications occurred in 10 (25%) patients, and major complications in four (10%). Procedure-related mortality was 2,5% with a 30-day mortality of 7.5%. Mean survival was 8.2 -2-- 0.5 months. Stent changes were required in eight patients. In patients with inoperable or unresectable cholangiocarcinoma, percutaneous or endoscopic biliary drainage offers effective palliation.

KEY WORDS: cholangiocarcinoma; endoscopic; percutaneous; endoprosthesis; stent.

Primary bile duct adenocarcinoma is an uncommon malignancy with a poor prognosis. It represents 2% of all cancers found at autopsy and 10-20% of all hepatic malignancies (1). Of these, 15-53% are hilar (Klatskin) tumors (2). Cholangiocarcinoma is a rare disorder, reported to be present in 0.12% of 129,571 cases at autopsy (3). Its etiology is unclear, but it may develop in the setting of chronic inflammatory disor- ders of the biliary tree such as sclerosing cholangitis, infestations with flukes, hepatolithiasis, and typhoid carrier state (4-8). It is related to ulcerative colitis, congenital fibropolycystic disease, choledochal cysts, and may occur in association with hepatocellular carcinoma (4, 9, 10). It commonly presents with obstructive jaundice, malaise, weight loss, and hepatomegaly. Laboratory investigations usually show obstructive

Manuscript received March 3, 1994; accepted September 20, 1994.

From the Division of Gastroenterology, Department of Medi- cine and Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205.

Address for reprint requests: Dr. Bhaskar Banerjee, Division of Gastroenterology, Winthrop-University Hospital, 222 Station Plaza North, Suite 429, Mineola, New York 11501.

cholestasis. Percutaneous or endoscopic retrograde cholangiography helps establish the diagnosis. Al- though curative resection would be the ideal management, the majority of patients are not surgical candi- dates at presentation. Other than being unfit, patients are excluded from surgery if metastases involve the hepatic artery or portal vein or if local spread limits surgical anastomosis. Curative resection in 83 patients with hilar cholangiocarcinoma has produced a mean survival of 17-42 months with a 30-day mortality of 7-16.5% (11-14). However, detailed histologic examination was able to confirm complete resection in only two of 26 (7.6%) cases; the tumor tends to metastasize by growing into perineural tissue (15). With palliative resection in 39 cases, mean survival was six months, but with a high 30-day mortality of 30% (13, 14). Surgical bypass in 480 patients produced a mean survival of 7.8 months with 30-day mortality of 25% (11-15, 17). Percutaneous stent placement (49 patients) achieved a mean survival of 6.8 months with a 30-day mortality of 6.3% (18). Endoscopic palliation in 193 patients gave a mean

701 Digestive Diseases and Sciences, VoL 40, No. 3 (March 1995) 0163-2116/95/0300-o701507.50RI ,~.'~ 1995 Plenum Publishing Corporation

BANERJEE AND TEPLICK

survival of 6.3 months (2) and a median survival of 10.5 months with stent placement and intraductal irridium therapy (19). Use of percutaneously placed expandable metal stents (33 patients) has produced a mean survival of 6.3 months with a 30-day mortality of 4.4% (20). Radiation therapy following surgery may appear to improve survival (21), but in a review of the literature, the difference was not considered significant (17). Chemotherapy does not appear to improve survival (22),

Although much has been written about the surgical management of cholangiocarcinoma, very" little has been reported about the nonsurgical palliation of this disease. We reviewed the case records of 40 patients with obstructive jaundice from cholangiocarcinoma who had undergone nonsurgical (percutaneous, endoscopic, or combined percutaneous and endoscopic) biliary drainage, to assess efficacy and associated morbidity and mortality.

MATERIALS AND METHODS

The 40 patients described here were managed over a period of 12 years, from 1981 to 1993, Percutaneous drainage was the only option available until 1989, after which endoscopic drainage was attempted first in the majority of patients, but some were still treated by percutaneous means alone. Percutaneous or combined percutaneous and endoscopic procedure (CP) was performed if endoscopic drainage was unsuccessful, The diagnosis of cholangiocarcinoma was made from: suggestive cholangiographic appearance, positive biopsy or brushings, and absence of other primary cancer. Admittedly, it is often difficult to prove the diagnosis of cholangiocarcinoma. Only patients with extrahepatic cholangiocarcinoma were included. Where reasonable doubt existed, cases were excluded from this review. Pa- tients with extensive intrahepatie cholangiocareinoma, carcinoma of the ampulla of Vater, and gallbladder cancer were excluded, as were cases suggestive of pancreatic cancer and other gastrointestinal malignancies with metastases to the bile duct. Lesions were classified (as upper-, middle-, or lower-third tumors) according to the American Joint Committee on Cancer (23); hilar or upper-third lesions were further classified as type I (tumor not obstructing the primary confluence), type II (obstruction of primary confluence only without extending to secondary bifurcations), or type III (obstruction of primary confluence with stricture extending to left or right secondary confluence) (24). All patients were jaundiced, and almost all were anorectic; other presenting features included weight loss (45%), ab- dominal pain (35%), pruritus (20%), fever (15%), and ascites (5%). All patients were declared unfit for surgery or had unresectable lesions. Irridium-192 seeds were inserted through percutaneous catheters to treat three patients.

RESULTS

Forty patients (23 males, 17 females with a mean age of 67.9 SE + 2.8 and 68.8 sE -+ 3.9 years, respec- tively) were treated with nonsurgical drainage over a period of 12 years. Thirty-one patients (78%) had upper-third lesions, of which 12 had type I, 11 had type II, and 8 had type III strictures. Seven had mid-third lesions, and two had lower third lesions (Table 1). Percutaneous drainage was attempted in 28 patients and was successful in all except one patient who underwent surgical bypass, In one patient surgical exploration was attempted following percutaneous drainage to see if the lesion was resectable. The tumor was unresectable, surgical bypass was performed, and the patient died five weeks later of causes unrelated to any complication of the procedures. In nine patients, a combined percutaneous and endoscopic procedure was performed for stent placement; in all cases the common bile duct was cannu- lated at ERCP, but a guidewire could not be inserted. Three patients had endoprostheses placed endoscopically. All stents placed at endoscopy or at CP were 10 or 11.5 F Amsterdam stents (Wiltek Medical Inc., Winston Salem, North Carolina). In the percutaneous group, single-mushroom, double-mushroom, and pig- tail endoprostheses, as well as expandable metal stents (Wallstent, Schneider Inc., Plymouth, Minne- sota) were utilized. Two patients had external percutaneous drainage only; one developed a fistula. Over- all technical success rate was 97.5%.

All patients were jaundiced at presentation with mean serum bilirubin of 11.5 mg/dl, sE +- 1.9 (normal < 2.0 mg/dl), Available follow-up data in 11 patients showed a final mean bilirubin of 1.5 mg/dl, sE -+ 0.4; P = 0.003. Symptomatic improvement was noted in all of these patients. Five of 19 patients with type II or III obstruction had multiple (two or three) stents

TABLE ]. SUMMARY OF PROCEDURES AND OUTCOME

Mean Complications Site of age Method of

obstl~tction N (yr) drainage* Minor Major

Upper third Type I: 12 67 2P, 3E, 6C, 1S Type II: 11 68.6 9P, 2C 4 1 Type IlI: 8 68.2 7P, IC 3 1

Middle third 7 66.5 7P 2 l Lower third 2 74 2P i 1 Total 40 68 27P, 9C, 3E. IS 10 4

*P - percutaneous transhepatic biliary drainage; E = endoscopic stent placement; C = combined percutaneous and endoscopic procedure for stent placement; S = surgical bypass following failed percutaneous drainage.

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CHOLANGIOCARCINOMA

placed, but satisfactory biliary drainage was achieved in the other I3 patients with a single stent. Minor complications occurred in 10 (25%) patients (three had fever, three had minor hemobilia which did not require blood transfusion, two had bile leaks, one had transient hypothermia, and one had persistent pain at the percutaneous catheter site). Major complications occurred in four (1(]%) patients (two had bacteremia and/or cholangitis; one developed a subphrenic ab- scess with septic shock, which was fatal; and one developed a percutaneous-venous fistula), Of the I4 complications, nine occurred in cases with upper- third lesions, three in mid-third ductal obstructions, and two in the distal-third region (P = 0.35). Proce- dure-related mortality was 2.5% (one patient developed septic shock and died). Thirty-day mortality was 7.5% (three patients). All complications were in the percutaneous group, but were restricted to the plastic stents, mostly the 14 French prostheses. There were no complications in the three patients who received a total of five percutaneously inserted expandable metal stents. There was no morbidity following the endoscopic or combined percutaneous and endoscopic procedures. In the percutaneous group, seven patients required 10 stent changes for blockage, with each stent lasting an average of 6.2 months (sE +_ 1.4). One stent migrated in the combined procedure group after three months and was replaced endoscopically. No stent changes were required in the other 32 cases. Mean survival was 8.2 months (SE --+ 2.5), with a range of 0.25-35.3 months. Of those remaining alive (three patients) mean survival has been eight months (SF + 4.1). Mean survival in the three patients who received intraluminal radiation with irridium-192 was 9.3 _+ 5.4 months; the difference was not significant (P = 0.83).

DISCUSSION

When comparing survival figures, it is important to recognize the severity, of disease and the overall health of the patient. The patients in this report were generally elderly, unfit, and/or had unresectable tumor. In one patient, resection was attempted following PTBD but was found to be unresectable at surgery. The aim in such a patient group is to eliminate jaundice, relieve pruritus, reduce or terminate pain, prevent the complications of cholestasis, and improve overall comfort. Significant reduction in bilirubin was achieved in our patients. Although quality of life could not be assessed objectively in this retrospective study, biliary stenting in obstructive jaundice has been shown, in a prospective study, to reduce anorexia,

improve appetite, and enhance the quality of life (25). Furthermore, stenting has been associated with a shorter hospital stay and fewer complications than surgical bypass (26, 27), although these were in patients with malignant distal bile duct obstruction of any cause.

Technical success rate (97.5%) was very high, par- ticularly with upper-third bile duct obstruction in 78% of cases. The mean survival of 8.2 months and a 30-day mortality of 7.5% in this series compares fa- vorably with mean survival of six months and 30-day mortality of 30% in palliative resection (13, 14). Pal- liative surgery can include major liver resection as well as simple bypass surgery. It would thus be more appropriate to compare our results to bypass surgery. alone. Our results were superior to the mean survival of 7.8 months and 30-day mortality of 25% in bypass surgery (11-15, 17). In a survey of 552 cholangiocar- cinomas, only palliative treatment could be offered to 66% of patients with upper-third bite duct lesions (17). Surgical palliation in the form of transtumoral intubation and biliary-jejunal anastomosis gave simi- lar results, with a 30-day mortality rate of 27% and median survival of nine months; the authors con- cluded that in cases of unresectability, percutaneous or endoscopic biliary endoprosthesis insertion may be preferable to surgery (17). The determination of re- sectability is not simple and sometimes requires surgical exploration. With the advent of endoscopic en- doluminal ultrasound for staging and needle biopsy (28), it may be possible to better define this disease and assign appropriate treatment by nonsurgical means. More work is needed in this area.

Most of the percutaneous procedures were done in the early stages of this series, when both technique and equipment were being refined, and this may explain the associated high morbidity. There was no complication in the nine patients who were treated in the last four years by CP. In these cases, an 8 French catheter was inserted into the duodenum by the percutaneous transhepatic route, prior to internal stent placement at CP. In earlier cases, 14 French catheters were inserted with a higher complication rate. Percu- taneously inserted expandable metal stents use a much smaller (7 F) insertion catheter and have a lower complication rate (20). In our study, there were no complications from the placement of five expandable metal stents in three patients. In fact, it is our current practice to percutaneously place wall stents and not perform the combined procedure, if endoscopic drainage fails. In patients with high-grade hilar obstruction, there appeared to be no advantage

Digestive Diseases amt Sciences, Vol. 40, No. 3 (Marck 1995) 703

gained by inserting multiple endoprostheses. We sug- gest that a single prosthesis provides adequate biliary drainage in hilar lesions and is probably safer than inserting multiple stents.

Although radiation therapy following bypass may be desirable, in a review of the literature (23 reports, 315 patients) mean survival was 10 months with biliary drainage alone and 12.5 months with biliary drainage and radiation (17). Whether external and, in particular, intraductal radiation would improve survival in nonsurgically drained cholangiocarcinoma needs to be assessed in prospective randomized stud- ies. A median survival of 10.5 months in 14 endoscopically drained patients treated with intraductal radiation is encouraging (19). Mean survival in similarly treated patients in our series was 1.1 months longer than the entire group, but the patient numbers were too small to reach statistical significance.

Nonsurgical drainage produces effective palliation in inoperable patients with cholangiocarcinoma. In patients with unresectable hilar lesions, nonsurgical drainage is effective and safer than bypass surgery and should be the preferred approach to palliation. Sur- gical therapy is associated with a longer hospital stay (27) and tends to be more expensive than nonsurgical drainage. Endoscopic stenting should be tried first, since it has been shown to be safer (29). Since endoscopic drainage of hilar obstruction carries a high (30c~) failure rate (30), percutaneous drainage should be required in many of these patients. With the use of percutaneously introduced expandable metal stents, there would be little need to perform combined percutaneous and endoscopic procedures. Out" experience shows that over 95% of patients with inoperable or unresectable cholangiocarcinoma can be effectively drained nonsurgically.

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Nonsurgical management of primary cholangiocarcinoma