Abstract
Introduction
Resection for hilar cholangiocarcinoma is the single hope for long-term survival.
Methods
Ninety patients underwent curative intent surgery for hilar cholangiocarcinoma between 1996 and 2012. The potential prognostic factors were assessed by univariate (Kaplan–Meier curves and log-rank test) and multivariate analyses (Cox proportional hazards model).
Results
The median overall and disease-free survivals were 26 and 17 months, respectively. The multivariate analysis identified R0 resection (HR = 0.03, 95 % CI 0–0.19, p < 0.001), caudate lobe invasion (HR = 6.33, 95 % CI 1.31–30.46, p = 0.021), adjuvant gemcitabine-based chemotherapy (HR = 0.38, 95 % CI 0.15–0.94, p = 0.037), and the neutrophil-to-lymphocyte ratio (HR = 0.78, 95 % CI 0.62–0.98, p = 0.036) as independent prognostic factors for disease-free survival. The independent prognostic factors for overall survival were R0 resection (HR = 0.03, 95 % CI 0–0.22, p < 0.001), caudate lobe invasion (HR = 11.75, 95 % CI 1.65–83.33, p = 0.014), and adjuvant gemcitabine-based chemotherapy (HR = 0.19, 95 % CI 0.06–0.56, p = 0.003).
Conclusions
The negative resection margin represents the most important prognostic factor. Adjuvant gemcitabine-based chemotherapy appears to benefit survival. The neutrophil-to-lymphocyte ratio may potentially be used to stratify patients for future clinical trials.
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References
Lafemina J, Jarnagin WR: Surgical management of proximal bile duct cancers. Langenbecks Arch Surg 2012;397:869-879.
DeOliveira ML, Cunningham SC, Cameron JL, Kamangar F, Winter JM, Lillemoe KD, Choti MA, Yeo CJ, Schulick RD: Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg 2007;245:755-762.
Saxena A, Chua TC, Chu FC, Morris DL: Improved outcomes after aggressive surgical resection of hilar cholangiocarcinoma: a critical analysis of recurrence and survival. Am J Surg 2011;202:310-320.
Baton O, Azoulay D, Adam DV, Castaing D: Major hepatectomy for hilar cholangiocarcinoma type 3 and 4: prognostic factors and longterm outcomes. J Am Coll Surg 2007;204:250-260.
Launois B, Reding R, Lebeau G, Buard JL: Surgery for hilar cholangiocarcinoma: French experience in a collective survey of 552 extrahepatic bile duct cancers. J Hepatobiliary Pancreat Surg 2000;7:128-134.
van Gulik TM, Kloek JJ, Ruys AT, Busch OR, van Tienhoven GJ, Lameris JS, Rauws EA, Gouma DJ: Multidisciplinary management of hilar cholangiocarcinoma (Klatskin tumor): extended resection is associated with improved survival. Eur J Surg Oncol 2011;37:65-71.
Nuzzo G, Giuliante F, Ardito F, Giovannini I, Aldrighetti L, Belli G, Bresadola F, Calise F, Dalla VR, D'Amico DF, Gennari L, Giulini SM, Guglielmi A, Jovine E, Pellicci R, Pernthaler H, Pinna AD, Puleo S, Torzilli G, Capussotti L, Cillo U, Ercolani G, Ferrucci M, Mastrangelo L, Portolani N, Pulitano C, Ribero D, Ruzzenente A, Scuderi V, Federico B: Improvement in perioperative and long-term outcome after surgical treatment of hilar cholangiocarcinoma: results of an Italian multicenter analysis of 440 patients. Arch Surg 2012;147:26-34.
Rosen CB, Murad SD, Heimbach JK, Nyberg SL, Nagorney DM, Gores GJ: Neoadjuvant therapy and liver transplantation for hilar cholangiocarcinoma: is pretreatment pathological confirmation of diagnosis necessary? J Am Coll Surg 2012;215:31-38.
Roxburgh CS, McMillan DC: Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol 2010;6:149-163.
Gomez D, Morris-Stiff G, Toogood GJ, Lodge JP, Prasad KR: Impact of systemic inflammation on outcome following resection for intrahepatic cholangiocarcinoma. J Surg Oncol 2008;97:513-518.
Smith RA, Ghaneh P, Sutton R, Raraty M, Campbell F, Neoptolemos JP: Prognosis of resected ampullary adenocarcinoma by preoperative serum CA19-9 levels and platelet–lymphocyte ratio. J Gastrointest Surg 2008;12:1422-1428.
Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A: AJCC Cancer Staging Manual, Seventh Edition. New York, Springer, 2010.
Dindo D, Demartines N, Clavien PA: Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240:205-213.
Rahbari NN, Garden OJ, Padbury R, Brooke-Smith M, Crawford M, Adam R, Koch M, Makuuchi M, Dematteo RP, Christophi C, Banting S, Usatoff V, Nagino M, Maddern G, Hugh TJ, Vauthey JN, Greig P, Rees M, Yokoyama Y, Fan ST, Nimura Y, Figueras J, Capussotti L, Buchler MW, Weitz J: Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery 2011;149:713-724.
Koch M, Garden OJ, Padbury R, Rahbari NN, Adam R, Capussotti L, Fan ST, Yokoyama Y, Crawford M, Makuuchi M, Christophi C, Banting S, Brooke-Smith M, Usatoff V, Nagino M, Maddern G, Hugh TJ, Vauthey JN, Greig P, Rees M, Nimura Y, Figueras J, Dematteo RP, Buchler MW, Weitz J: Bile leakage after hepatobiliary and pancreatic surgery: a definition and grading of severity by the International Study Group of Liver Surgery. Surgery 2011;149:680-688.
Rahbari NN, Garden OJ, Padbury R, Maddern G, Koch M, Hugh TJ, Fan ST, Nimura Y, Figueras J, Vauthey JN, Rees M, Adam R, Dematteo RP, Greig P, Usatoff V, Banting S, Nagino M, Capussotti L, Yokoyama Y, Brooke-Smith M, Crawford M, Christophi C, Makuuchi M, Buchler MW, Weitz J: Post-hepatectomy haemorrhage: a definition and grading by the International Study Group of Liver Surgery (ISGLS). HPB (Oxford) 2011;13:528-535.
Ebata T, Nagino M, Kamiya J, Uesaka K, Nagasaka T, Nimura Y: Hepatectomy with portal vein resection for hilar cholangiocarcinoma: audit of 52 consecutive cases. Ann Surg 2003;238:720-727.
Igami T, Nishio H, Ebata T, Yokoyama Y, Sugawara G, Nimura Y, Nagino M: Surgical treatment of hilar cholangiocarcinoma in the "new era": the Nagoya University experience. J Hepatobiliary Pancreat Sci 2010;17:449-454.
Matsuo K, Rocha FG, Ito K, D'Angelica MI, Allen PJ, Fong Y, Dematteo RP, Gonen M, Endo I, Jarnagin WR: The blumgart preoperative staging system for hilar cholangiocarcinoma: analysis of resectability and outcomes in 380 patients. J Am Coll Surg 2012;215:343-355.
Kondo S, Hirano S, Ambo Y, Tanaka E, Okushiba S, Morikawa T, Katoh H: Forty consecutive resections of hilar cholangiocarcinoma with no postoperative mortality and no positive ductal margins: results of a prospective study. Ann Surg 2004;240:95-101.
Lee SG, Song GW, Hwang S, Ha TY, Moon DB, Jung DH, Kim KH, Ahn CS, Kim MH, Lee SK, Sung KB, Ko GY: Surgical treatment of hilar cholangiocarcinoma in the new era: the Asan experience. J Hepatobiliary Pancreat Sci 2010;17:476-489.
van Gulik TM, Ruys AT, Busch OR, Rauws EA, Gouma DJ: Extent of liver resection for hilar cholangiocarcinoma (Klatskin tumor): how much is enough? Dig Surg 2011;28:141-147.
Dinant S, Gerhards MF, Rauws EA, Busch OR, Gouma DJ, van Gulik TM: Improved outcome of resection of hilar cholangiocarcinoma (Klatskin tumor). Ann Surg Oncol 2006;13:872-880.
Neuhaus P, Jonas S, Settmacher U, Thelen A, Benckert C, Lopez-Hanninen E, Hintze RE: Surgical management of proximal bile duct cancer: extended right lobe resection increases resectability and radicality. Langenbecks Arch Surg 2003;388:194-200.
Neuhaus P, Thelen A, Jonas S, Puhl G, Denecke T, Veltzke-Schlieker W, Seehofer D: Oncological superiority of hilar en bloc resection for the treatment of hilar cholangiocarcinoma. Ann Surg Oncol 2012;19:1602-1608.
de Jong MC, Marques H, Clary BM, Bauer TW, Marsh JW, Ribero D, Majno P, Hatzaras I, Walters DM, Barbas AS, Mega R, Schulick RD, Choti MA, Geller DA, Barroso E, Mentha G, Capussotti L, Pawlik TM: The impact of portal vein resection on outcomes for hilar cholangiocarcinoma: A multi-institutional analysis of 305 cases. Cancer 2012.
Miyazaki M, Kato A, Ito H, Kimura F, Shimizu H, Ohtsuka M, Yoshidome H, Yoshitomi H, Furukawa K, Nozawa S: Combined vascular resection in operative resection for hilar cholangiocarcinoma: does it work or not? Surgery 2007;141:581-588.
Guglielmi A, Ruzzenente A, Campagnaro T, Pachera S, Conci S, Valdegamberi A, Sandri M, Iacono C: Prognostic significance of lymph node ratio after resection of peri-hilar cholangiocarcinoma. HPB (Oxford) 2011;13:240-245.
Hasegawa S, Ikai I, Fujii H, Hatano E, Shimahara Y: Surgical resection of hilar cholangiocarcinoma: analysis of survival and postoperative complications. World J Surg 2007;31:1256-1263.
Jarnagin WR, Bowne W, Klimstra DS, Ben-Porat L, Roggin K, Cymes K, Fong Y, Dematteo RP, D'Angelica M, Koea J, Blumgart LH: Papillary phenotype confers improved survival after resection of hilar cholangiocarcinoma. Ann Surg 2005;241:703-712.
Kow AW, Wook CD, Song SC, Kim WS, Kim MJ, Park HJ, Heo JS, Choi SH: Role of caudate lobectomy in type III A and III B hilar cholangiocarcinoma: a 15-year experience in a tertiary institution. World J Surg 2012;36:1112-1121.
Li H, Qin Y, Cui Y, Chen H, Hao X, Li Q: Analysis of the surgical outcome and prognostic factors for hilar cholangiocarcinoma: a Chinese experience. Dig Surg 2011;28:226-231.
Young AL, Prasad KR, Toogood GJ, Lodge JP: Surgical treatment of hilar cholangiocarcinoma in a new era: comparison among leading Eastern and Western centers, Leeds. J Hepatobiliary Pancreat Sci 2010;17:497-504.
Tsao JI, Nimura Y, Kamiya J, Hayakawa N, Kondo S, Nagino M, Miyachi M, Kanai M, Uesaka K, Oda K, Rossi RL, Braasch JW, Dugan JM: Management of hilar cholangiocarcinoma: comparison of an American and a Japanese experience. Ann Surg 2000;232:166-174.
Wahab MA, Sultan AM, Salah T, Fathy O, Elebidy G, Elshobary M, Shiha O, Rauf AA, Elhemaly M, El-Ghawalby N: Caudate Lobe Resection with Major Hepatectomy for Central Cholangiocarcinoma: Is it of Value? Hepatogastroenterology 2012;59:321-324.
Nimura Y, Hayakawa N, Kamiya J, Kondo S, Shionoya S: Hepatic segmentectomy with caudate lobe resection for bile duct carcinoma of the hepatic hilus. World J Surg 1990;14:535-543.
Hirano S, Kondo S, Tanaka E, Shichinohe T, Tsuchikawa T, Kato K, Matsumoto J, Kawasaki R: Outcome of surgical treatment of hilar cholangiocarcinoma: a special reference to postoperative morbidity and mortality. J Hepatobiliary Pancreat Sci 2010;17:455-462.
Regimbeau JM, Fuks D, Le Treut YP, Bachellier P, Belghiti J, Boudjema K, Baulieux J, Pruvot FR, Cherqui D, Farges O: Surgery for hilar cholangiocarcinoma: a multi-institutional update on practice and outcome by the AFC-HC study group. J Gastrointest Surg 2011;15:480-488.
Nimura Y: Preoperative biliary drainage before resection for cholangiocarcinoma (Pro). HPB (Oxford) 2008;10:130-133.
Kloek JJ, van der Gaag NA, Aziz Y, Rauws EA, van Delden OM, Lameris JS, Busch OR, Gouma DJ, van Gulik TM: Endoscopic and percutaneous preoperative biliary drainage in patients with suspected hilar cholangiocarcinoma. J Gastrointest Surg 2010;14:119-125.
Laurent A, Tayar C, Cherqui D: Cholangiocarcinoma: preoperative biliary drainage (Con). HPB (Oxford) 2008;10:126-129.
Sakata J, Shirai Y, Tsuchiya Y, Wakai T, Nomura T, Hatakeyama K: Preoperative cholangitis independently increases in-hospital mortality after combined major hepatic and bile duct resection for hilar cholangiocarcinoma. Langenbecks Arch Surg 2009;394:1065-1072.
Chauhan A, House MG, Pitt HA, Nakeeb A, Howard TJ, Zyromski NJ, Schmidt CM, Ball CG, Lillemoe KD: Post-operative morbidity results in decreased long-term survival after resection for hilar cholangiocarcinoma. HPB (Oxford) 2011;13:139-147.
Murakami Y, Uemura K, Sudo T, Hayashidani Y, Hashimoto Y, Nakamura H, Nakashima A, Sueda T: Gemcitabine-based adjuvant chemotherapy improves survival after aggressive surgery for hilar cholangiocarcinoma. J Gastrointest Surg 2009;13:1470-1479.
Nagino M, Kamiya J, Arai T, Nishio H, Ebata T, Nimura Y: One hundred consecutive hepatobiliary resections for biliary hilar malignancy: preoperative blood donation, blood loss, transfusion, and outcome. Surgery 2005;137:148-155.
Klempnauer J, Ridder GJ, von WR, Werner M, Weimann A, Pichlmayr R: Resectional surgery of hilar cholangiocarcinoma: a multivariate analysis of prognostic factors. J Clin Oncol 1997;15:947-954.
Ito F, Agni R, Rettammel RJ, Been MJ, Cho CS, Mahvi DM, Rikkers LF, Weber SM: Resection of hilar cholangiocarcinoma: concomitant liver resection decreases hepatic recurrence. Ann Surg 2008;248:273-279.
Kobayashi A, Miwa S, Nakata T, Miyagawa S: Disease recurrence patterns after R0 resection of hilar cholangiocarcinoma. Br J Surg 2010;97:56-64.
Cheng Q, Luo X, Zhang B, Jiang X, Yi B, Wu M: Predictive factors for prognosis of hilar cholangiocarcinoma: postresection radiotherapy improves survival. Eur J Surg Oncol 2007;33:202-207.
Proctor MJ, McMillan DC, Morrison DS, Fletcher CD, Horgan PG, Clarke SJ: A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer. Br J Cancer 2012;107:695-699.
Fava G, Lorenzini I: Molecular pathogenesis of cholangiocarcinoma. Int J Hepatol 2012;2012:630543.
Thanan R, Oikawa S, Yongvanit P, Hiraku Y, Ma N, Pinlaor S, Pairojkul C, Wongkham C, Sripa B, Khuntikeo N, Kawanishi S, Murata M: Inflammation-induced protein carbonylation contributes to poor prognosis for cholangiocarcinoma. Free Radic Biol Med 2012;52:1465-1472.
Johnson C, Han Y, Hughart N, McCarra J, Alpini G, Meng F: Interleukin-6 and its receptor, key players in hepatobiliary inflammation and cancer. Transl Gastrointest Cancer 2012;1:58-70.
Wentz SC, Yip-Schneider MT, Gage EA, Saxena R, Badve S, Schmidt CM: Sulindac prevents carcinogen-induced intrahepatic cholangiocarcinoma formation in vivo. J Surg Res 2009;157:e87-e95.
Gerhardt T, Milz S, Schepke M, Feldmann G, Wolff M, Sauerbruch T, Dumoulin FL: C-reactive protein is a prognostic indicator in patients with perihilar cholangiocarcinoma. World J Gastroenterol 2006;12:5495-5500.
Wang DS, Luo HY, Qiu MZ, Wang ZQ, Zhang DS, Wang FH, Li YH, Xu RH: Comparison of the prognostic values of various inflammation based factors in patients with pancreatic cancer. Med Oncol 2012.
Aliustaoglu M, Bilici A, Seker M, Dane F, Gocun M, Konya V, Ustaalioglu BB, Gumus M: The association of pre-treatment peripheral blood markers with survival in patients with pancreatic cancer. Hepatogastroenterology 2010;57:640-645.
Garcea G, Ladwa N, Neal CP, Metcalfe MS, Dennison AR, Berry DP: Preoperative neutrophil-to-lymphocyte ratio (NLR) is associated with reduced disease-free survival following curative resection of pancreatic adenocarcinoma. World J Surg 2011;35:868-872.
Launois B, Terblanche J, Lakehal M, Catheline JM, Bardaxoglou E, Landen S, Campion JP, Sutherland F, Meunier B: Proximal bile duct cancer: high resectability rate and 5-year survival. Ann Surg 1999;230:266-275.
Acknowledgments
The authors express their gratitude to Cristian Baicus, MD (Carol Davila University of Medicine and Pharmacy) and Raluca Purnichescu-Purtan, PhD (Department of Mathematics, Politehnica University of Bucharest, Romania) for their valuable assistance with the statistical analyses.
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Dumitrascu, T., Chirita, D., Ionescu, M. et al. Resection for Hilar Cholangiocarcinoma: Analysis of Prognostic Factors and the Impact of Systemic Inflammation on Long-term Outcome. J Gastrointest Surg 17, 913–924 (2013). https://doi.org/10.1007/s11605-013-2144-2
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DOI: https://doi.org/10.1007/s11605-013-2144-2