BACKGROUND: The aim of the study was to calculate the short-term and long-term outcomes of curative-intent surgery in distal cholangiocarcinoma (DCC) patients to identify potential prognostic factors. PATIENTS AND METHODS: A retrospective cohort study of 32 consecutive DCC patients treated with pancreaticoduodenectomy between 2009-2017. The clinicopathological and histopathological data were evaluated for prognostic factors using the univariable Cox regression analysis. The Overall Survival (OS) was estimated using the Kaplan-Meier analysis. RESULTS: The study comprised a total of 32 patients, with a mean age of 65.8 (± 9.0) years at the time of surgery. R0 resection was achieved in 25 (86.2%) patients, 19 (65.5%) patients received adjuvant oncological therapy. The OS rates at 1, 3 and 5 years were 62.5%, 37.5% and 21.9%, respectively. The 90-day mortality was 3/32 (9.4%) accounting for one-fourth of the first-year mortality rate. The median OS was 28.5 months. The only statistically significant prognostic factor was vascular resection, which was associated with worse OS in the univariable analysis (HR: 3.644; 95%-CI: 1.179-11.216, P=0.025). An age less than 65 years, ASA grade I/II, hospital stay of fewer than 15 days, R0 resection, lymph node ratio less than 0.2 and adjuvant oncological therapy tended to be associated with better OS but without statistically significant relevance. CONCLUSION: The main factor directly influencing the survival of DCC patients is surgical complications. Surgical mortality comprises a significant group of patients, who die in the first year following pancreaticoduodenectomy. Vascular resection is the most important negative prognostic factor for long-term survival.

Department of Clinical and Molecular Pathology Faculty of Medicine and Dentistry Palacky University Olomouc Czech Republic

Department of Internal Medicine 2 Gastroenterology and Geriatrics Faculty of Medicine and Dentistry Palacky University Olomouc Czech Republic

Department of Oncology University Hospital Olomouc Czech Republic

Department of Surgery 1 Faculty of Medicine and Dentistry Palacky University Olomouc Czech Republic

Department of Surgery 1 University Hospital Olomouc Czech Republic

Zobrazit více v PubMed

Beetz O, Klein M, Schrem H, Gwiasda J, Vondran FWR, Oldhafer F, Camman S, Klempnauer J, Oldhafer KJ, Kleine M. Relevant prognostic factors influencing outcome of patients after surgical resection of distal cholangiocarcinoma. BMC Surgery 2018;18:56. PubMed DOI

Zhou Y, Liu S, Wu L, Wan T. Survival after surgical resection of distal cholanguiocarcinoma: A systematic review and meta-analysis of prognostic factors. Asian J Surg 2017;40:129-38. PubMed DOI

Li X, Lin H, Sun Y, Gong J, Feng H, Tu J. Prognostic significance of the lymph node ratio in surgical patients with distal cholangiocarcinoma. J Surg Res 2019;236:2-11. DOI

Dusek L, Muzik J, Kubasek M, Koptikova J, Zaloudik J, Vyzula R. Epidemiologie zhoubných nádorů v České republice [online]. Masarykova univerzita. 2005 [cited 2021 Jan 17]. Available from: http://www.svod.cz (In Czech)

Kamsa-Ard S, Luvira V, Suwanrungruang K, Kamsa-Ard S, Luvira V, Santong C, Srisuk T, Pugkhem A, Bhudhisawasdi V, Pairojkul CJ. Cholangiocarcinoma Trends, Incidence, and Relative Survival in Khon Kaen, Thailand From 1989 Through 2013: A Population-Based Cancer Registry Study. Epidemiol 2019;29(5):197-204. DOI

Murakami Y, Uemura K, Sudo T, Hashimoto Y, Nakashima A, Kondo N, Sakabe R, Ohge H, Sueda T. Prognostic factors after surgical resection for intrahepatic, hilar, and distal cholangiocarcinoma. Ann Surg Oncol 2011;18(3):651-8. DOI

Kim BH, Kim K, Chie EK, Kwon J, Jang JY, Kim SW, Oh DY, Bang YJ. Long-Term Outcome of Distal Cholangiocarcinoma after Pancreaticoduodenectomy Followed by Adjuvant Chemoradiotherapy: A 15-Year Experience in a Single Institution. Cancer Res Treat 2017;49(2):473-83. DOI

DeOliveira ML, Cunningham SC, Cameron JL, Kamangar F, Winter JM, Lillemoe KD et al. Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg 1999;229:76-83.

Ito K, Sakamoto Y, Isayama H, Nakai Y, Watadani T, Tanaka M, Ushiku T, Akamatsu N, Kaneko J, Arita J, Hasegawa K, Kokudos N. The Impact of MDCT and Endoscopic Transpapillary Mapping Biopsy to Predict Longitudinal Spread of Extrahepatic Cholangiocarcinoma. J Gastrointest Surg 2018;22(9):1528-37. PubMed DOI

Jang JY, Kim SW, Park DJ, Ahn YJ, Yoon YS, Choi MG, Suh KS, Lee KU, Park YH. Actual long-term outcome of extrahepatic bile duct cancer after surgical resection. Ann Surg 2005;241:77-84. DOI

Bahra M, Jacob D, Langrehr JM, Neumann UP, Neuhaus P. Carcinoma of the distal and middle bile duct: surgical results, prognostic factors, and long-term follow-up. J Hepato-Biliary-Pancreat Surg 2008;15:501-7. DOI

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;240:205-13. DOI

Wente MN, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, Izbicki JR, Neoptolemos JP, Padbury RT, Sarr MG, Traverso LW, Yeo CJ, Büchler MW. Delayed gastric emptying (DGE) after pancreatic surgery: A suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 2007;142:761-8. PubMed DOI

Wente MN, Veit JA, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, Izbicki JR, Neoptolemos JP, Padbury RT, Sarr MG, Yeo CJ, Büchler MW. Postpancreatectomy hemorrhage (PPH): An International Study Group of Pancreatic Surgery (ISGPS) definition. Surgery 2007;142:20-5. PubMed DOI

Bassi C, Marchegiani G, Dervenis C, Sarr M, Abu Hilal M, Adham M, Allen P, Andersson R, Asbun HJ, Besselink MG, Conlon K, Del Chiaro M, Falconi M, Fernandez-Cruz L, Fernandez-Del Castillo C, Fingerhut A, Friess H, Gouma DJ, Hackert T, Izbicki J, Lillemoe KD, Neoptolemos JP, Olah A, Schulick R, Shrikhande SV, Takada T, Takaori K, Traverso W, Vollmer CR, Wolfgang CL, Yeo CJ, Salvia R, Buchler M; International Study Group on Pancreatic Surgery (ISGPS). The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After. Surgery 2017;161:584-91. PubMed DOI

Tol JA, Gouma DJ, Bassi C, Dervenis C, Montorsi M, Adham M, Andren-Sandberg A, Asbun HJ, Bockhorn M, Buchler MW, Conclon KC, Fernandes-Cruz L, Fingerhut A, Friess H, Hartwig W, Izbicki JR, Lillemoe KD, Milicevic MN, Neoptolemos JP, Shrikhande SV, Vollmer CM, Yeo CJ, Charnley RM, International Study Group on Pancreatic Surgery. Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: a consensus statement by the International Study Group on Pancreatic Surgery (ISGPS). Surgery 2014;156(3):591-600. PubMed DOI

Chung YJ, Choi DW, Choi SH, Heo JS, Kim DH. Prognostic factors following surgical resection of distal bile duct cancer. J Korean Surg Soc 2013;85:212-18. PubMed DOI

Kiriyama M, Ebata T, Aoba T, Kaneoka Y, Arai T, Shimizu Y, Nagino M; Nagoya Surgical Oncology Group. Prognostic impact of lymph node metastasis in distal cholangiocarcinoma. Br J Surg 2015;102:399-406. PubMed DOI

Ishihara S, Horiguchi A, Miyakawa S, Endo I, Miyazaki M, Takada T. Biliary tract cancer registry in Japan from 2008 to 2013. J Hepatobiliary Pancreat Sci 2016;23:149-57. PubMed

Courtin-Tanguy L, Rayar M, Bergeat D, Merdrignac A, Harnoy Y, Boudjema K, Meunier B, Sulpice L. The true prognosis of resected distal cholangiocarcinoma. J Surg Oncol 2016;113:575-80. PubMed DOI

Tol JA, Brosens LA, van Dieren S, van Gulik TM, Busch OR, Besselink MG, Gouma DJ. Impact of lymph node ratio on survival in patients with pancreatic and periampullary cancer. Br J Surg 2015;102:237-45. PubMed DOI

Ercolani G, Dazzi A, Giovinazzo F, Ruzzenente A, Bassi C, Guglielmi A, Scarpa A, D'Errico A, Pinna AD. Intrahepatic, peri-hilar and distal cholangiocarcinoma: Three different locations of the same tumor or three different tumors? Eur J Surg Oncol 2015;41:1162-9. DOI

Andrianello S, Paiella S, Allegrini V,Ramera M, Pulvirenti A, Malleo G, Salvia R, Bassi C. Pancreaticoduodenectomy for distal cholangiocarcinoma: Surgical results, prognostic factors, and long-term follow-up. Langenbecks Arch Surg 2015;400:623-8. DOI

Gaag NA, Kloek JJ, de Bakker JK, Musters B, Geskus RB, Busch OR, Bosma A, Gouma DJ, van Gulik TM. Survival analysis and prognostic nomogram for patients undergoing resection of extrahepatic cholangiocarcinoma. Ann Oncol 2012;23:264-9. DOI

Ebata T, Nagino M, Nishio H, Igami T, Yokoyama Y, Nimura Y. Pancreatic and duodenal invasion in distal bile duct cancer: paradox in the tumor classification of the American joint committee on Cancer. World J Surg 2007;31:2008-15. PubMed DOI

Nakeeb A, Pitt HA, Sohn TA, Coleman J, Abrams RA, Piantadosi S, Hruban RH, Lillemoe KD, Yeo CJ, Cameron JL. Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors. Ann Surg 1996;224:463-73. DOI

Choi SB, Park SW, Kim KS, Choi JS, Lee WJ. The survival outcome and prognostic factors for middle and distal bile duct cancer following surgical resection. J Surg Oncol 2009;99:335-42. PubMed DOI

Hong SM, Pawlik TM, Cho H, Aggarwal B, Goggins M, Hruban RH, Anders RA. Depth of tumor invasion better predicts prognosis than the current American Joint Committee on Cancer T classification for distal bile duct carcinoma. Surgery 2009;146:250-7. PubMed DOI

Hernandez J, Cowgill SM, Al-Saadi S, Villadolid D, Ross S, Kraemer E, Shapiro M, Mullinax J, Cooper J, Goldin S, Zervos E, Rosemurgy A. An Aggressive Approach To Extrahepatic Cholangiocarcinomas Is Warranted: Margin Status Does Not Impact Survival After Resection. Ann Surg Oncol 2008;15:807-14. DOI

Yoshida T, Matsumoto T, Sasaki A, Morii Y, Aramaki M, Kitano S. Prognostic factors after pancreatoduodenectomy with extended lymphadenectomy for distal bile duct cancer. Arch Surg 2002;137:69-73. PubMed DOI

Bortolasi L, Burgart LJ, Tsiotos GG, Luque-De León E, Sarr MG. Adenocarcinoma of the distal bile duct. A clinicopathologic outcome analysis after curative resection. Dig Surg 2000;17:36-41. PubMed DOI

Kim HJ, Kim CY, Hur YH, Koh YS, Kim JC, Kim HJ, Cho CK. Prognostic factors for survival after curative resection of DCC: perineural invasion and lymphovascular invasion. Surg Today 2014;44:1879-86. PubMed DOI

Yoshida T, Matsumoto T, Sasaki A, Morii Y, Aramaki M, Kitano S. Prognostic factors after pancreatoduodenectomy with extended lymphadenectomy for distal bile duct cancer. Arch Surg 2002;137:69-73. PubMed DOI

Hernandez J, Cowgill SM, Al-Saadi S, Villadolid D, Ross S, Kraemer E, Shapiro M, Mullinax J, Cooper J, Goldin S, Zervos E, Rosemurgy A. An aggressive approach to extrahepatic cholangiocarcinomas is warranted: margin status does not impact survival after resection. Ann Surg Oncol 2008;15:807-14. DOI

Wellner UF, Shen Y, Keck T, Jin W, Xu Z. The survival outcome and prognostic factors for distal cholangiocarcinoma following surgical resection: a meta-analysis for the 5-year survival. Surg Today 2017;47:271-9. PubMed DOI

Petrova E, Ruckert F, Zach S, Shen Y, Weitz J, Grützmann R, Wittel UA, Makowiec F, Hopt UT, Bronsert P, Kühn F, Rau BM, Izrailov RE, Khatkov IE, Lapshyn H, Bolm L, Bausch D, Keck T, Wellner UF, Seifert G. Survival outcome and prognostic factors after pancreatoduodenectomy for distal bile duct carcinoma: a retrospective multicenter study. Langenbeck's Arch Surg 2017;402:831-40. DOI

Urban O, Evinová E, Fojtík P, Loveček M, Kliment M, Zoundjiekpon V, Falt P. Digital cholangioscopy: the diagnostic yield and impact on management of patients with biliary stricture. Scand J Gastroenterol 2018;53(10-11):1364-7. DOI

Shiraki T, Kuroda H, Takada A, Nakazato Y, Kubota K, Imai Y. Intraoperative frozen section diagnosis of bile duct margin for extrahepatic cholangiocarcinoma. World J Gastroenterol 2018;24(12):1332-42. DOI

Hajer J, Havlůj L, Whitley A, Oliverius M, Gürlich R. The role of single-operator cholangioscopy (SpyGlass) in the intraoperative diagnosis of intraductal borders of cholangiocarcinoma proliferation - pilot study. Cas Lek Cesk 2019;158(2):68-72. (In Czech) PubMed

Hong SM, Cho H, Lee OJ, Ro JY. The number of metastatic lymph nodes in extrahepatic bile duct carcinoma as a prognostic factor. Am J Surg Pathol 2005;29:1177-183. DOI

Murakami Y, Uemura K, Hayashidani Y, Sudo T, Hashimoto Y, Ohge H, Sueda T. Prognostic significance of lymph node metastasis and surgical margin status for distal cholangiocarcinoma. J Surg Oncol 2007;95:207-12. PubMed DOI

Murakami Y, Uemura K, Hayashidani Y, Sudo T, Ohge H, Sueda T. Pancreatoduodenectomy for distal cholangiocarcinoma: Prognostic impact of lymph node metastasis. World J Surg 2007;31:337-42. PubMed DOI

Pomianowska E, Westgaard A, Mathisen O, Clausen OP, Gladhaug IP. Prognostic relevance of number and ratio of metastatic lymph nodes in resected pancreatic, ampullary, and distal bile duct carcinomas. Ann Surg Oncol 2013;20:233-41. DOI

Yamashita K, Hosoda K, Ema A, Watanabe M. Lymph node ratio as a novel and simple prognostic factor in advanced gastric cancer. Eur J Surg Oncol 2016;42(9):1253-60. DOI

Ozawa T, Ishihara S, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Hata K, Kawai K, Nozawa H, Kanazawa T, Kazama S, Yamaguchi H, Sunami E, Kitayama J, Watanabe T. Prognostic significance of the lymph node ratio in stage IV colorectal cancer patients who have undergone curative resection. Ann Surg Oncol 2015;22:1513-9. DOI

Zhang MR, Xie TH, Chi JL, Li Y, Yang L, Yu YY, Sun XF, Zhou ZG. Prognostic role of the lymph node ratio in node positive colorectal cancer: a meta-analysis. Oncotarget 2016;7(45):72898-907. PubMed DOI

Fischer LK, Katz MH, Lee SM, Liu L, Wang H, Varadhachary GR, Wolff RA, Lee JE, Maitra A, Roland CL, Fleming JB, Estrella J, Rashid A. The number and ratio of positive lymph nodes affect pancreatic cancer patient survival after neoadjuvant therapy and pancreaticoduodenectomy. Histopathology 2016;68(2):210-20. PubMed DOI

Kawai M, Tani M, Kobayashi Y, Kobayashi Y, Tsuji T, Tabuse K, Horiuchi T, Oka M, Yamaguchi K, Sakata Y, Shimomura T, Yamaue H. The ratio between metastatic and examined lymph nodes is an independent prognostic factor for patients with resectable middle and distal bile duct carcinoma. Am J Surg 2010;199:447-52. PubMed DOI

Oshiro Y, Sasaki R, Kobayashi A, Murata S, Fukunaga K, Kondo T, Oda T, Ohkohchi N. Prognostic relevance of the lymph node ratio in surgical patients with extrahepatic cholangiocarcinoma. Eur J Surg Oncol 2011;37:60-4. DOI

Miura F, Sano K, Amano H, Toyota N, Wada K, Yoshida M, Hayano K, Matsubara H, Takada T. Evaluation of portal vein invasion of distal cholangiocarcinoma as borderline resectability. J Hepatobiliary Pancreat Sci 2015;22:294-300. PubMed DOI

Maeta T, Ebata T, Hayashi E, Kawahara T, Mizuno S, Matsumoto N, Ohta S, Nagino M; Nagoya Surgical Oncology Group. Pancreatoduodenectomy with portal vein resection for distal cholangiocarcinoma. Br J Surg 2017;104:1549-57. PubMed DOI

Byrling J, Andersson R, Sasor A, Lindell G, Ansari D, Nilsson J, Andersson B. Outcome and evaluation of prognostic factors after pancreaticoduodenectomy for distal cholangiocarcinoma. Ann of Gastroenterology 2017;30:571-7. DOI

Lovecek M, Skalicky P, Klos D, Bebarova L, Neoral C, Ehrmann J, Zapletalova J, Svebisova H, Vrba R, Stasek M, Yogeswara T, Havlik R. Long-term survival after resections for pancreatic ductal adenocarcinoma. Single centre study. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016; 160(2):280-6. PubMed DOI

Preoperative nutritional support in patients undergoing pancreatic surgery affects PREPARE score accuracy