The Prognostic Role of True Radical Resection in Perihilar Cholangiocarcinoma After Improved Evaluation of Radial Margin Status

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2022 Dec 23

PMID 36551610

Authors

Mario De Bellis

Maria Gaia Mastrosimini

Simone Conci

Sara Pecori

Tommaso Campagnaro

Claudia Castelli

Paola Capelli

Aldo Scarpa

Alfredo Guglielmi

Andrea Ruzzenente

Affiliations

Soon will be listed here.

Abstract

Background: The evaluation of surgical margins in resected perihilar cholangiocarcinoma (PHCC) remains a challenging issue. Both ductal (DM) and radial margin (RM) should be considered to define true radical resections (R0). Although DM status is routinely described in pathological reports, RM status is often overlooked. Therefore, the frequency of true R0 and its impact on survival might be biased.

Objective: To improve the evaluation of RM status and investigate the impact of true R0 on survival.

Methods: From 2014 to 2020, 90 patients underwent curative surgery for PHCC at Verona University Hospital, Verona, Italy. Both DM (proximal and distal biliary margin) and RM (hepatic, periductal, and vascular margin) status were evaluated by expert hepatobiliary pathologists. Patients with lymph-node metastases or positive surgical margins (R1) were candidates for adjuvant treatment. Clinicopathological and survival data were retrieved from an institutional database.

Results: True R0 were 46% (41) and overall R1 were 54% (49). RM positivity resulted in being higher than DM positivity (48% versus 27%). Overall survival was better in patients with true R0 than in patients with R1 (median survival time: 53 vs. 28 months; = 0.016). Likewise, the best recurrence-free survival was observed in R0 compared with R1 (median survival time: 32 vs. 15 months; = 0.006). Multivariable analysis identified residual disease status as an independent prognostic factor of both OS ( = 0.009, HR = 2.68, 95% CI = 1.27-5.63) and RFS ( = 0.009, HR = 2.14, 95% CI = 1.20-3.83).

Conclusion: Excellent survival was observed in true R0 patients. The improved evaluation of RM status is mandatory to properly stratify prognosis and select patients for adjuvant treatment.

Citing Articles

Current Perspectives in Liver Transplantation for Perihilar Cholangiocarcinoma.

Giovinazzo F, Pascale M, Cardella F, Picarelli M, Molica S, Zotta F Curr Oncol. 2023; 30(3):2942-2953.

PMID: 36975438 PMC: 10047046. DOI: 10.3390/curroncol30030225.

References

Kondo S, Hirano S, Ambo Y, Tanaka E, Okushiba S, Morikawa T . Forty consecutive resections of hilar cholangiocarcinoma with no postoperative mortality and no positive ductal margins: results of a prospective study. Ann Surg. 2004; 240(1):95-101. PMC: 1356380. DOI: 10.1097/01.sla.0000129491.43855.6b. View

Bosma A . Surgical pathology of cholangiocarcinoma of the liver hilus (Klatskin tumor). Semin Liver Dis. 1990; 10(2):85-90. DOI: 10.1055/s-2008-1040460. View

Tang Z, Yang Y, Zhao Z, Wei K, Meng W, Li X . The clinicopathological factors associated with prognosis of patients with resectable perihilar cholangiocarcinoma: A systematic review and meta-analysis. Medicine (Baltimore). 2018; 97(34):e11999. PMC: 6112994. DOI: 10.1097/MD.0000000000011999. View

Chatelain D, Farges O, Fuks D, Trouillet N, Pruvot F, Regimbeau J . Assessment of pathology reports on hilar cholangiocarcinoma: the results of a nationwide, multicenter survey performed by the AFC-HC-2009 study group. J Hepatol. 2012; 56(5):1121-1128. DOI: 10.1016/j.jhep.2011.12.010. View

DeOliveira M, Cunningham S, Cameron J, Kamangar F, Winter J, Lillemoe K . Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg. 2007; 245(5):755-62. PMC: 1877058. DOI: 10.1097/01.sla.0000251366.62632.d3. View

Nuzzo G, Giuliante F, Ardito F, Giovannini I, Aldrighetti L, Belli G . 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(1):26-34. DOI: 10.1001/archsurg.2011.771. View

DAmico F, Mescoli C, Caregari S, Pasquale A, Billato I, Alessandris R . Impact of Positive Radial Margin on Recurrence and Survival in Perihilar Cholangiocarcinoma. Cancers (Basel). 2022; 14(7). PMC: 8996964. DOI: 10.3390/cancers14071680. View

Nassour I, Mokdad A, Porembka M, Choti M, Polanco P, Mansour J . Adjuvant Therapy Is Associated With Improved Survival in Resected Perihilar Cholangiocarcinoma: A Propensity Matched Study. Ann Surg Oncol. 2018; 25(5):1193-1201. DOI: 10.1245/s10434-018-6388-7. View

Rassam F, Roos E, van Lienden K, van Hooft J, Klumpen H, van Tienhoven G . Modern work-up and extended resection in perihilar cholangiocarcinoma: the AMC experience. Langenbecks Arch Surg. 2018; 403(3):289-307. PMC: 5986829. DOI: 10.1007/s00423-018-1649-2. View

10.

Burt A, Alves V, Bedossa P, Clouston A, Guido M, Hubscher S . Data set for the reporting of intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma and hepatocellular carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR). Histopathology. 2018; 73(3):369-385. DOI: 10.1111/his.13520. View

11.

Stremitzer S, Stift J, Laengle J, Schwarz C, Kaczirek K, Jones R . Prognosis and Circumferential Margin in Patients with Resected Hilar Cholangiocarcinoma. Ann Surg Oncol. 2020; 28(3):1493-1498. DOI: 10.1245/s10434-020-09105-1. View

12.

DSouza M, Ahmad Al-Saffar H, Moro C, Shtembari S, Danielsson O, Sparrelid E . Redefining resection margins and dissection planes in perihilar cholangiocarcinoma-radical resection is a rare event. Virchows Arch. 2021; 480(3):557-564. PMC: 8989813. DOI: 10.1007/s00428-021-03231-1. View

13.

Roos E, Franken L, Soer E, van Hooft J, Takkenberg R, Klumpen H . Lost in translation: confusion on resection and dissection planes hampers the interpretation of pathology reports for perihilar cholangiocarcinoma. Virchows Arch. 2019; 475(4):435-443. PMC: 6828829. DOI: 10.1007/s00428-019-02621-w. View

14.

Shinohara K, Ebata T, Shimoyama Y, Mizuno T, Yokoyama Y, Yamaguchi J . A Study on Radial Margin Status in Resected Perihilar Cholangiocarcinoma. Ann Surg. 2019; 273(3):572-578. DOI: 10.1097/SLA.0000000000003305. View

15.

Gerhards M, van Gulik T, Bosma A, Verbeek P, Gonzalez Gonzalez D, de Wit L . Long-term survival after resection of proximal bile duct carcinoma (Klatskin tumors). World J Surg. 1998; 23(1):91-6. DOI: 10.1007/s002689900571. View

16.

Im J, Choi G, Lee W, Han D, Park S, Bang S . Adjuvant radiotherapy and chemotherapy offer a recurrence and survival benefit in patients with resected perihilar cholangiocarcinoma. J Cancer Res Clin Oncol. 2021; 147(8):2435-2445. DOI: 10.1007/s00432-021-03524-7. View

17.

Nagino M, Ebata T, Yokoyama Y, Igami T, Sugawara G, Takahashi Y . Evolution of surgical treatment for perihilar cholangiocarcinoma: a single-center 34-year review of 574 consecutive resections. Ann Surg. 2012; 258(1):129-40. DOI: 10.1097/SLA.0b013e3182708b57. View

18.

Komaya K, Ebata T, Yokoyama Y, Igami T, Sugawara G, Mizuno T . Recurrence after curative-intent resection of perihilar cholangiocarcinoma: analysis of a large cohort with a close postoperative follow-up approach. Surgery. 2018; 163(4):732-738. DOI: 10.1016/j.surg.2017.08.011. View

19.

Castellano-Megias V, Ibarrola-de Andres C, Colina-Ruizdelgado F . Pathological aspects of so called "hilar cholangiocarcinoma". World J Gastrointest Oncol. 2013; 5(7):159-70. PMC: 3731529. DOI: 10.4251/wjgo.v5.i7.159. View

20.

Koerkamp B, Wiggers J, Gonen M, Doussot A, Allen P, Besselink M . Survival after resection of perihilar cholangiocarcinoma-development and external validation of a prognostic nomogram. Ann Oncol. 2015; 26(9):1930-1935. PMC: 4754626. DOI: 10.1093/annonc/mdv279. View