Brief Article
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World J Gastroenterol. May 21, 2012; 18(19): 2364-2370
Published online May 21, 2012. doi: 10.3748/wjg.v18.i19.2364
Clinical benefit of radiation therapy and metallic stenting for unresectable hilar cholangiocarcinoma
Hiroyuki Isayama, Takeshi Tsujino, Yousuke Nakai, Takashi Sasaki, Keiichi Nakagawa, Hideomi Yamashita, Taku Aoki, Kazuhiko Koike
Hiroyuki Isayama, Takeshi Tsujino, Yousuke Nakai, Takashi Sasaki, Kazuhiko Koike, Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
Keiichi Nakagawa, Hideomi Yamashita, Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
Taku Aoki, Division of Hepato-Biliary-Pancreatic and Transplantation Surgery, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan
Author contributions: Isayama H designed the study concept and worked on the manuscript; Tsujino T worked on the manuscript and performed analysis; Nakagawa K and Yamashita H performed radiation therapy; Nakai Y, Sasaki T and Aoki T corrected the clinical data; Koike K revised the manuscript and over-viewed the study.
Correspondence to: Hiroyuki Isayama, MD, PhD, Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. isayama-tky@umin.ac.jp
Telephone: +81-3-38155411-33056 Fax: +81-3-38140021
Received: February 21, 2011
Revised: March 18, 2011
Accepted: April 12, 2012
Published online: May 21, 2012
Abstract

AIM: To determine the efficacy of external beam radiotherapy (EBRT), with or without intraluminal brachytherapy (ILBT), in patients with non-resected locally advanced hilar cholangiocarcinoma.

METHODS: We analyzed 64 patients with locally advanced hilar cholangiocarcinoma, including 25 who underwent resection (17 curative and 8 non-curative), 28 treated with radiotherapy, and 11 who received best supportive care (BSC). The radiotherapy group received EBRT (50 Gy, 30 fractions), with 11 receiving an additional 24 Gy (4 fractions) ILBT by iridium-192 with remote after loading. ILBT was performed using percutaneous transhepatic biliary drainage (PTBD) route. Uncovered metallic stents (UMS) were inserted into non-resected patients with obstructive jaundice, with the exception of four patients who received percutaneous transhepatic biliary drainage only. UMS were placed endoscopically or percutaneously, depending on the initial drainage procedure. The primary endpoints were patient death or stent occlusion. Survival time of patients in the radiotherapy group was compared with that of patients in the resection and BSC groups. Stent patency was compared in the radiotherapy and BSC groups.

RESULTS: No statistically significant differences in patient characteristics were found among the resection, radiotherapy, and BSC groups. Three patients in the radiotherapy group and one in the BSC group did not receive UMS insertion but received PTBD alone; cholangitis occurred after endoscopic stenting, and patients were treated with PTBD. A total of 16 patients were administered additional systemic chemotherapy (5-fluorouracil-based regimen in 9, S-1 in 6, and gemcitabine in 1). Overall survival varied significantly among groups, with median survival times of 48.7 mo in the surgery group, 22.1 mo in the radiotherapy group, and 5.7 mo in the BSC group. Patients who underwent curative resection survived significantly longer than those who were not candidates for surgery (P = 0.0076). Cumulative survival in the radiotherapy group was significantly longer than in the BSC group (P = 0.0031), but did not differ significantly from those in the non-resection group. Furthermore, the median survival time of patients in the radiotherapy group who were considered for possible resection (excluding the seven patients who were not candidates for surgery due to comorbid disease or age) was 25.9 mo. Stent patency was evaluated only in the 24 patients who received a metallic stent. Stent patency was significantly longer in the radiotherapy than in the BSC group (P = 0.0165). Biliary drainage was not eliminated in any patient. To determine the efficacy of ILBT, we compared survival time and stent patency in the EBRT alone and EBRT plus ILBT groups. However, we found no significant difference in survival time between groups or for stent patencies. Hemorrhagic gastroduodenal ulcers were observed in 5 patients (17.9%), three in the EBRT plus ILBT group and two in the EBRT alone group. Ulcers occurred 5 mo, 7 mo, 8 mo, 16 mo, and 29 mo following radiotherapy. All patients required hospitalization, but blood transfusions were unnecessary. All 5 patients recovered following the administration of anti-ulcer medication.

CONCLUSION: Radiotherapy improved patient prognosis and the patency of uncovered metallic stents in patients with locally advanced hilar cholangiocarcinoma, but ILBT provided no additional benefits.

Keywords: Hilar cholangiocarcinoma, Radiotherapy, Intra-luminal brachytherapy, Biliary metallic stent, Obstructive jaundice