Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2020

01-12-2020 | Metastasis | Research article

Neoadjuvant chemotherapy followed by curative-intent surgery for perihilar cholangiocarcinoma based on its anatomical resectability classification and lymph node status

Authors: Naohisa Kuriyama, Masanobu Usui, Kazuaki Gyoten, Aoi Hayasaki, Takehiro Fujii, Yusuke Iizawa, Hiroyuki Kato, Yasuhiro Murata, Akihiro Tanemura, Masashi Kishiwada, Hiroyuki Sakurai, Shugo Mizuno, Shuji Isaji

Published in: BMC Cancer | Issue 1/2020

Login to get access

Abstract

Background

The prognosis of patients with perihilar cholangiocarcinoma have been unsatisfactory. We established new anatomical resectability classification for patients with localized perihilar cholangiocarcinoma and performed neoadjuvant chemotherapy followed by curative-intent surgery based on its resectability classification and lymph node status to improve prognosis. This study aimed to clarify the long-term outcomes and validation of our strategy.

Methods

Between September 2010 and August 2018, 72 consecutive patients with perihilar cholangiocarcinoma were classified into three groups: Resectable (R = 29), Borderline resectable (BR = 23), and Locally advanced (LA = 20), based on the two factors of tumor vascular and biliary extension. R with clinically lymph node metastasis, BR, and LA patients received neoadjuvant chemotherapy using gemcitabine plus S-1.

Results

Forty-seven patients (65.3%) received neoadjuvant chemotherapy: R in 8, BR in 21, and 18 in LA, respectively. Fifty-nine patients (68.1%) underwent curative-intent surgery: R in 26, BR in 17, and LA in 6. Five-year disease-specific survival was 31.5% (median survival time: 33.0 months): 50.3% (not reached) in R, 30.0% (31.4 months) in BR, and 16.5% (22.5 months) in LA, which were relatively stratified. Among 49 patients with resection, disease-specific survival was 43.8% (57.0 months): 57.6% (not reached) in R, 41.0% (52.4 months) in BR, and 0% (49.4 months) in LA, which were significantly good prognosis compared to 23 patients without resection (17.2 months). Multivariate analysis identified preoperative high carcinoembryonic antigen levels (more than 8.5 ng/ml) and pT4 as independent poor prognostic factor of patients with resection.

Conclusion

Neoadjuvant chemotherapy based on resectability classification and lymph node status was feasible, and was considered efficacious in selected patients.
Literature
1.
Nagino M, Ebata T, Yokoyama Y, Igami T, Sugawara G, Takahashi Y, Nimura Y. Evolution of surgical treatment for perihilar cholangiocarcinoma: a single-center 34-year review of 574 consecutive resections. Ann Surg. 2013;258:129–40.CrossRef
2.
Ebata T, Hirano S, Konishi M, Uesaka K, Tsuchiya Y, Ohtsuka M, Kaneoka Y, Yamamoto M, Ambo Y, Shimizu Y, Ozawa F, Fukutomi A, Ando M, Nimura Y, Nagino M. Bile Duct Cancer Adjuvant Trial (BCAT) study group. Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observation in resected bile ductcancer. Br J Surg. 2018;105:192–202.CrossRef
3.
Edeline J, Benabdelghani M, Bertaut A, Watelet J, Hammel P, Joly JP, Boudjema K, Fartoux L, Bouhier-Leporrier K, Jouve JL, Faroux R, Guerin-Meyer V, Kurtz JE, Assénat E, Seitz JF, Baumgaertner I, Tougeron D, de la Fouchardière C, Lombard-Bohas C, Boucher E, Stanbury T, Louvet C, Malka D, Phelip JM. Gemcitabine and oxaliplatin chemotherapy or surveillance in resected biliary tract cancer (PRODIGE 12-ACCORD 18-UNICANCER GI): a randomized phase iii study. J Clin Oncol. 2019;37:658–67.CrossRef
4.
Primrose JN, Fox RP, Palmer DH, Malik HZ, Prasad R, Mirza D, Anthony A, Corrie P, Falk S, Finch-Jones M, Wasan H, Ross P, Wall L, Wadsley J, Evans JTR, Stocken D, Praseedom R, Ma YT, Davidson B, Neoptolemos JP, Iveson T, Raftery J, Zhu S, Cunningham D, Garden OJ, Stubbs C, Valle JW, Bridgewater J. BILCAP study group. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncol. 2019;20:663–73.CrossRef
5.
Jung JH, Lee HJ, Lee HS, Jo JH, Cho IR, Chung MJ, Park JY, Park SW, Song SY, Bang S. Benefit of neoadjuvant concurrent chemoradiotherapy for locally advanced perihilar cholangiocarcinoma. World J Gastroenterol. 2017;23:3301–8.CrossRef
6.
Le Roy B, Gelli M, Pittau G, Allard MA, Pereira B, Serji B, Vibert E, Castaing D, Adam R, Cherqui D, Sa CA. Neoadjuvant chemotherapy for initially unresectable intrahepatic cholangiocarcinoma. Br J Surg. 2018;105:839–47.CrossRef
7.
Kato A, Shimizu H, Ohtsuka M, Yoshidome H, Yoshitomi H, Furukawa K, Takeuchi D, Takayashiki T, Kimura F, Miyazaki M. Surgical resection after downsizing chemotherapy for initially unresectable locally advanced biliary tract cancer: a retrospective single-center study. Ann Surg Oncol. 2013;20:318–24.CrossRef
8.
Yadav S, Xie H, Bin-Riaz I, Sharma P, Durani U, Goyal G, Borah B, Borad MJ, Smoot RL, Roberts LR, Go RS, McWilliams RR, Mahipal A. Neoadjuvant vs. adjuvant chemotherapy for cholangiocarcinoma: a propensity score matched analysis. Eur J Surg Oncol. 2019;45:1432–8.CrossRef
9.
Kobayashi M, Mizuno S, Murata Y, Kishiwada M, Usui M, Sakurai H, Tabata M, Ii N, Yamakado K, Inoue H, Shiraishi T, Yamada T, Isaji S. Gemcitabine-based chemoradiotherapy followed by surgery for borderline resectable and locally unresectable pancreatic ductal adenocarcinoma: significance of the CA19-9 reduction rate and intratumoral human equilibrative nucleoside transporter 1 expression. Pancreas. 2014;43:350–60.CrossRef
10.
Wolpin BM, Mayer RJ. A step forward in the treatment of advanced biliary tract cancer. N Engl J Med. 2010;362:1335–7.CrossRef
11.
Aloia TA, Charnsangavej C, Faria S, Ribero D, Abdalla EK, Vauthey JN, Curley SA. High-resolution computed tomography accurately predicts resectability in hilar cholangiocarcinoma. Am J Surg. 2007;193:702–6.CrossRef
12.
Japan Pancreas Society. Classification of pancreatic carcinoma, 4th English Edition, Kanehara, Tokyo. 2017.
13.
Morizane C, Okusaka T, Mizusawa J, Takashima A, Ueno M, Ikeda M, Hamamoto Y, Ishii H, Boku N, Furuse J. Randomized phase II study of gemcitabine plus S-1 versus S-1 in advanced biliary tract cancer: a Japan Clinical Oncology Group trial (JCOG 0805). Cancer Sci. 2013;104:1211–6.CrossRef
14.
Sasaki T, Isayama H, Nakai Y, Ito Y, Yasuda I, Toda N, Kogure H, Hanada K, Maguchi H, Sasahira N, Kamada H, Mukai T, Okabe Y, Hasebe O, Maetani I, Koike K. A randomized phase II study of gemcitabine and S-1 combination therapy versus gemcitabine monotherapy for advanced biliary tract cancer. Cancer Chemother Pharmacol. 2013;71:973–9.CrossRef
15.
Ichikawa K, Mizuno S, Hayasaki A, Kishiwada M, Fujii T, Iizawa Y, Kato H, Tanemura A, Murata Y, Azumi Y, Kuriyama N, Usui M, Sakurai H, Isaji S. Prognostic nutritional index after chemoradiotherapy was the strongest prognostic predictor among biological and conditional factors in localized pancreatic ductal adenocarcinoma patients. Cancers. 2019;11:514.CrossRef
16.
Sumiyoshi T, Shima Y, Okabayashi T, Kozuki A, Hata Y, Noda Y, Kouno M, Miyagawa K, Tokorodani R, Saisaka Y, Tokumaru T, Nakamura T, Morita S. Liver function assessment using 99mTc-GSA single-photon emission computed tomography (SPECT)/CT fusion imaging in hilar bile duct cancer: A retrospective study. Surgery. 2016;160:118–26.CrossRef
17.
Yokoyama Y, Nishio H, Ebata T, Igami T, Sugawara G, Nagino M. Value of indocyanine green clearance of the future liver remnant in predicting outcome after resection for biliary cancer. Br J Surg. 2010;97:1260–8.CrossRef
18.
Miyazaki M, Kimura F, Shimizu H, Yoshidome H, Otsuka M, Kato A, Hideyuki Y, Nozawa S, Furukawa K, Mituhashi N, Takeuchi D, Suda K, Takano S. Extensive hilar bile duct resection using a transhepatic approach for patients with hepatic hilar bile duct diseases. Am J Surg. 2008;196:125–9.CrossRef
19.
Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibañes E, Pekolj J, Slankamenac K, Bassi C, Graf R, Vonlanthen R, Padbury R, Cameron JL, Makuuchi M. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250:187–96.CrossRef
20.
Bismuth H, Corlette MB. Intrahepatic cholangioenteric anastomosis in carcinoma of the hilus of the liver. Surg Gynecol Obstet. 1975;140:170–8.PubMed
21.
Bismuth H, Castaing D, Traynor O. Resection or palliation: priority of surgery in the treatment of hilar cancer. World J Surg. 1988;12:39–47.CrossRef
22.
Burke EC, Jarnagin WR, Hochwald SN, Pisters PW, Fong Y, Blumgart LH. Hilar Cholangiocarcinoma: patterns of spread, the importance of hepatic resection for curative operation, and a presurgical clinical staging system. Ann Surg. 1998;228:385–94.CrossRef
23.
Jarnagin WR, Fong Y, DeMatteo RP, Gonen M, Burke EC, Bodniewicz BSJ, Youssef BAM, Klimstra D, Blumgart LH. Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg. 2001;234:507–17.CrossRef
24.
Tempero MA, Malafa MP, Chiorean EG, Czito B, Scaife C, Narang AK, Fountzilas C, Wolpin BM, Al-Hawary M, Asbun H, Behrman SW, Benson AB, Binder E, Cardin DB, Cha C, Chung V, Dillhoff M, Dotan E, Ferrone CR, Fisher G, Hardacre J, Hawkins WG, Ko AH, LoConte N, Lowy AM, Moravek C, Nakakura EK, O’Reilly EM, Obando J, Reddy S, Thayer S, Wolff RA, Burns JL, Zuccarino-Catania G. PancreaticAdenocarcinoma, Version 1. J Natl Compr Cancer Netw. 2019;17:202–10.CrossRef
25.
Ito T, Sugiura T, Okamura Y, Yamamoto Y, Ashida R, Aramaki T, Endo M, Uesaka K. The diagnostic advantage of EOB-MR imaging over CT in the detection of liver metastasis in patients with potentially resectable pancreatic cancer. Pancreatology. 2017;17:451–6.CrossRef
26.
Seo N, Park MS, Han K, Lee KH, Park SH, Choi GH, Choi JY, Chung YE, Kim MJ, Kim HJ, Lee SS, Byun JH, Kim JC, Yu CS, Park SH, Kim AY, Ha HK. Incremental value of liver MR imaging in patients with potentially curable colorectal hepatic metastasis detected at CT: a prospective comparison of diffusion-weighted imaging, gadoxetic acid-enhanced MR imaging, and a combination of both MR techniques. Radiology. 2015;274:712–22.CrossRef
27.
Ikeyama T, Nagino M, Oda K, Ebata T, Nishio H, Nimura Y. Surgical approach to bismuth Type I and II hilar cholangiocarcinomas: audit of 54 consecutive cases. Ann Surg. 2007;246:1052–7.CrossRef
28.
Neuhaus P, Jonas S, Bechstein WO, et al. Extended resections for hilar cholangiocarcinoma. Ann Surg. 1999;230:808–19.CrossRef
29.
Seyama Y, Kubota K, Sano K, et al. Long-term outcome of extended hemihepatectomy for hilar bile duct cancer with no mortality and high survival rate. Ann Surg. 2003;238:73–83.PubMedPubMedCentral
30.
Isaji S, Mizuno S, Windsor JA, Bassi C, Fernández-Del Castillo C, Hackert T, Hayasaki A, Katz MHG, Kim SW, Kishiwada M, Kitagawa H, Michalski CW, Wolfgang CL. International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017. Pancreatology. 2018;18:2–11.CrossRef
31.
Choi ER, Chung YH, Lee JK, Lee KT, Lee KH, Choi DW, Choi SH, Heo JS, Jang KT, Park SM, Lim JH. Preoperative evaluation of the longitudinal extent of borderline resectable hilar cholangiocarcinoma by intraductal ultrasonography. J Gastroenterol Hepatol. 2011;26:1804–10.CrossRef
32.
Matsuyama R, Morioka D, Mori R, Yabushita Y, Hiratani S, Ota Y, Kumamoto T, Endo I. Our rationale of initiating neoadjuvant chemotherapy for hilar cholangiocarcinoma: a proposal of criteria for “borderline resectable” in the field of surgery for hilar cholangiocarcinoma. World J Surg. 2019;43:1094–104.CrossRef
33.
Ito T, Kuriyama N, Kozuka Y, Komatsubara H, Ichikawa K, Noguchi D, Hayasaki A, Fujii T, Iizawa Y, Kato H, Tanemura A, Murata Y, Kishiwada M, Mizuno S, Usui M, Sakurai H, Isaji S. High tumor budding is a strong predictor of poor prognosis in the resected perihilar cholangiocarcinoma patients regardless of neoadjuvant therapy, showing survival similar to those without resection. BMC Cancer. 2020;20:209.CrossRef
34.
Miyata H, Yoshioka A, Yamasaki M, et al. Tumor budding in tumor invasive front predicts prognosis and survival of patients with esophageal squamous cell carcinomas receiving neoadjuvant chemotherapy. Cancer. 2009;115:3324–34.CrossRef
35.
Karamitopoulou E, Zlobec I, Born D, et al. Tumour budding is a strong and independent prognostic factor in pancreatic cancer. Eur J Cancer. 2013;49:1032–9.CrossRef
Metadata
Title
Neoadjuvant chemotherapy followed by curative-intent surgery for perihilar cholangiocarcinoma based on its anatomical resectability classification and lymph node status
Authors
Naohisa Kuriyama
Masanobu Usui
Kazuaki Gyoten
Aoi Hayasaki
Takehiro Fujii
Yusuke Iizawa
Hiroyuki Kato
Yasuhiro Murata
Akihiro Tanemura
Masashi Kishiwada
Hiroyuki Sakurai
Shugo Mizuno
Shuji Isaji
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2020
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-020-06895-1

Other articles of this Issue 1/2020

BMC Cancer 1/2020 Go to the issue

Research article

The role of SRGN in the survival and immune infiltrates of skin cutaneous melanoma (SKCM) and SKCM-metastasis patients

Research article

Clinical significance of peripheral blood and tumor tissue lymphocyte subsets in cervical cancer patients

Research article

Prognosis prediction model based on competing endogenous RNAs for recurrence of colon adenocarcinoma

Correction

Correction to: The efficacy of etanercept as anti-breast cancer treatment is attenuated by residing macrophages

Research article

Assessing how health information needs of individuals with colorectal cancer are met across the care continuum: an international cross-sectional survey

Research article

PD-L1 and CD4 are independent prognostic factors for overall survival in endometrial carcinomas
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits