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Prognostic Factors After Pancreatoduodenectomy with Extended Lymphadenectomy for Distal Bile Duct Cancer

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Prognostic Factors After Pancreatoduodenectomy with Extended Lymphadenectomy for Distal Bile Duct Cancer ORIGINAL ARTICLE Prognostic Factors After Pancreatoduodenectomy With Extended Lymphadenectomy for Distal Bile Duct Cancer Takanori Yoshida, MD; Toshifumi Matsumoto, MD; Atsushi Sasaki, MD; Yuji Morii, MD; Masanori Aramaki, MD; Seigo Kitano, MD Background: Since 1995, we have been performing pan- Main Outcome Measures: Clinicopathologic char- creatoduodenectomy with regional and para-aortic lymph acteristics and long-term results. node dissection for patients with distal bile duct cancer. Prognostic indicators after extended lymphadenectomy Results: In 6 patients (22%) major surgical complica- have not been fully understood. tions occurred including 1 in-hospital death (3.7%). For 26 patients, the survival rates were 65% for 1 year and Hypothesis: Pancreatoduodenectomy with extended 37% for 3 and 5 years. Univariate analysis found that the lymphadenectomy and adjuvant chemotherapy is the treat- absence of lymph node metastasis, no more than 2 in- ment of choice for patients with distal bile duct cancer. volved nodes, and negative resection margins were pre- dictors of survival. Multivariate analysis with a Cox pro- Design: In a retrospective study, univariate and multi- portional hazards regression model revealed that favorable variate models were used to analyze the effect of patient factors for survival included up to 2 positive nodes, nega- demographics, tumor characteristics, and treatment fac- tive resection margins, and the use of postoperative ad- tors on long-term survival. juvant chemotherapy. Setting: Oita Medical University and its affiliated hos- Conclusions: Patients with up to 2 positive lymph pitals in Japan. nodes had a more favorable prognosis than that of other patients. We recommend pancreatoduodenectomy with Patients: From 1995 to 1999, 27 patients with distal extended lymphadenectomy and adjuvant chemo- bile duct cancer underwent pancreatoduodenectomy with therapy for the treatment of patients with distal bile extended lymphadenectomy. In 9 patients fluorouracil duct cancer. (500 mg/d) was infused continuously for 14 days after surgery as adjuvant chemotherapy. Arch Surg. 2002;137:69-73 N PATIENTS with distal bile duct Results from randomized controlled cancer, lymph node metastasis is trials of patients with adenocarcinoma of the associated significantly with treat- pancreatic head indicated that extended ment outcomes.1-4 The extent of lymphadenectomy and retroperitoneal soft dissection and histological exami- tissue clearance with pancreatoduodenal re- Ination of lymph nodes, however, varies be- section might be accepted as the proce- tween countries, and this variation may re- dure of choice in the treatment of node- sult in erroneous nodal staging and may positive patients with similar morbidity and account for differences in surgical results. mortality to standard dissection.10,11 The use In Japan, some surgeons advocate the com- of postoperative adjuvant chemoradio- plete removal of the primary bile duct can- therapy and intraoperative blood loss are cer with connective tissue clearance, in- considered independent prognostic fac- cluding lymph node and neural plexus tors.12 Because of its rarity, there are a few From the Department of dissection.4-6 Since 1995, we have been per- detailed reports about treatments for distal General Surgery, Nakatsu forming pancreatoduodenectomy with re- bile duct cancer.1-5,13,14 This retrospective Municipal Hospital gional and para-aortic lymph node dissec- study identifies prognostic factors after pan- (Drs Yoshida and Morii), tion for patients with distal bile duct creatoduodenectomy with extended lymph- and the First Department 7-9 of Surgery, Oita Medical cancer. The goal of this radical surgery adenectomy in patients with distal bile duct University (Drs Matsumoto, with extended lymphadenectomy is to pri- cancer, using a series of 27 patients, a suf- Sasaki, Aramaki, and Kitano), marily achieve locoregional control and to ficiently large population to allow for sta- Oita, Japan. secondarily obtain accurate tumor staging. tistical evaluation, and relating to a single (REPRINTED) ARCH SURG/ VOL 137, JAN 2002 WWW.ARCHSURG.COM 69 ©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 PATIENTS AND METHODS was adopted as the differentiation. Lymph nodes were con- sidered positive if any lymph node in the resected specimen contained metastatic foci. The number and location of in- Between January 1, 1995, and December 31, 1999, at the volved nodes were carefully recorded. Lymph nodes were clas- First Department of Surgery, Oita Medical University, Oita, sified according to the General Rules for Surgical and Patho- Japan, and its affiliated hospitals, 100 patients with malig- logical Studies on Cancer of the Biliary Tract15: 5 indicates nant tumors underwent pancreatoduodenectomy with sys- suprapyloric; 6, infrapyloric; 7, left gastric artery; 8, com- tematic lymph node dissection including regional and para- mon hepatic artery; 9, celiac trunk; 11, splenic artery; 12, hepa- aortic nodes. The patient population consisted of 27 patients toduodenal ligament; 13, posterior pancreaticoduodenal; 14, with distal bile duct cancer, 24 with pancreatic head can- superior mesenteric artery; 15, middle colic artery; 16, para- cer, 21 with ampullary cancer, and 28 with other malig- aortic; and 17, anterior pancreaticoduodenal (Figure 1). Re- nancies. Distal bile duct cancer was defined as adenocar- section margins were considered positive if infiltrating ad- cinoma arising from the intrapancreatic bile duct. Pancreatic enocarcinoma was present at the pancreatic neck, proximal head, ampullary, and other adenocarcinomas were ex- bile duct, or periductal soft tissue margins. The lymphatic, cluded from this study. Of the 27 patients with distal bile venous, and perineural permeations were examined rou- duct cancer, 16 were treated by pancreatoduodenectomy tinely with cut sections. with conventional gastrectomy, and 11 underwent a pylorus- Intraoperative blood loss, transfused units of erythro- preserving procedure. Four patients underwent portal vein cytes, and operative time were investigated by reviewing the resection and reconstruction. Para-aortic lymph node dis- medical records. Patients were offered 2 options for post- section extended from the celiac axis to the inferior mes- operative treatment—chemotherapy or no chemotherapy— enteric artery and from the right margin of the inferior vena according to their condition. As adjuvant chemotherapy, fluo- cava to the left margin of the abdominal aorta. One pa- rouracil (500 mg/d) was infused continuously and tient died of an intra-abdominal abscess after the opera- systemically for 14 days after the pancreatoduodenec- tion and was excluded from survival analysis. The remain- tomy.16 ing 26 patients included 16 men and 10 women who had a Follow-up to December 31, 2000, was obtained for all mean age of 63.5 years (age range, 35-80 years). 26 patients and ranged from 12 to 71 months (mean du- The resected specimens with attached choledochal and ration of follow-up, 52.2 months; median duration of follow- peripancreatic lymph nodes were examined by the prepara- up, 54.0 months). Patient demographics, tumor charac- tion of serial tissue sections at 5-mm intervals and were stained teristics, and treatment factors were evaluated using with hematoxylin-eosin. All specimens were reviewed by a univariate and multivariate models to determine their effect single surgical pathologist (A.S.) according to the General Rules on long-term survival. The cumulative survival rate was cal- for Surgical and Pathological Studies on Cancer of the Biliary culated by the Kaplan-Meier method, and the survival curves Tract15 outlined by the Japanese Society of Biliary Surgery. were compared using the Mantel-Haenszel test. Multivar- Local extent of the primary tumor was classified into 2 groups iate analysis was performed using the stepwise forward Cox with the classification based on the presence of pancreatic proportional hazards regression model. Differences were parenchymal invasion.7-9 Predominant histological grading considered statistically significant at PϽ.05. center, to minimize the problem of homogeneity of treat- fied as 12, 13, and/or 17. Seven patients had metastatic ment and follow-up. nodes in group 8 or 14 or both. Para-aortic lymph node involvement was observed in 5 patients. RESULTS There were 12 tumors (46%) without pancreatic in- vasion and 14 (54%) with pancreatic invasion (Table 2). Major surgery-related complications occurred in 6 (22%) Four patients (15%) had positive resection margins (proxi- of 27 patients, including leakage of the pancreaticojeju- mal bile duct in 2 and periductal soft tissue margins in nostomy in 5 (1 death), delayed bleeding in 2, myocar- the other), and 22 (85%) had negative margins. Most car- dial infarction in 1, and obstruction of the efferent loop cinomas either were well differentiated in 15 (58%) or of gastrojejunostomy in 1. One patient, in whom adju- moderately differentiated in 7 (27%). The median intra- vant chemotherapy was not administered, died of intra- operative blood loss was 1000 mL, the median units of abdominal sepsis due to leakage of the pancreaticojeju- erythrocytes transfused was 1, and the median opera- nostomy after 38 postoperative days. The in-hospital death tive time was 7 hours. Nine patients who underwent ad- rate was 3.7%. Two patients with delayed intraperitoneal juvant chemotherapy had no chemotherapy-related com- hemorrhage
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