Differences in Prognostic Factors and Recurrence Patterns After Curative-Intent Resection of Perihilar and Distal Cholangiocarcinomas

Abstract

Background: Perihilar cholangiocarcinoma and distal cholangiocarcinoma arise from the same tissue but require different surgical treatment methods. It remains unclear whether these cholangiocarcinoma types have different outcomes, prognostic factors, and/or recurrence patterns. Methods: This retrospective study evaluated patients who underwent curative-intent resection for perihilar cholangiocarcinoma or distal cholangiocarcinoma at a tertiary academic hospital during 2000–2015. Survival and prognostic factors were identified using Kaplan–Meier and Cox regression analyses. Results: The 90-day mortality rates were 0% for perihilar cholangiocarcinoma (36 patients) and 4% for distal cholangiocarcinoma (47 patients). There were no significant differences between perihilar cholangiocarcinoma or distal cholangiocarcinoma in median overall survival (30.9 vs 40.4 months) or median disease-free survival (14.2 vs 21.4 months). Among perihilar cholangiocarcinoma patients, age > 65 years was an independent predictor of poorer overall survival (hazard ratio: 2.45, 95% confidence interval: 1.07–5.64), while requiring bile duct re-resection was an independent predictor of disease-free survival (hazard ratio: 2.76, 95% confidence interval: 1.01–7.51). Among distal cholangiocarcinoma patients, a pN1 category independently predicted poorer overall survival (hazard ratio: 3.40, 95% confidence interval: 1.14–10.11), while preoperative CA19-9 levels >30 U/mL (hazard ratio: 2.51, 95% confidence interval: 1.09–5.79) and pN1 category (hazard ratio: 2.51, 95% confidence interval: 1.09–5.79) predicted a shorter disease-free survival. Local recurrence was more common with perihilar cholangiocarcinoma (50% of recurrences), while multiple synchronous sites were more common for distal cholangiocarcinoma (41% of recurrences). Conclusion: Perihilar cholangiocarcinoma and distal cholangiocarcinoma patients have similar survival outcomes. However, local control appears to be more prognostic for perihilar cholangiocarcinoma patients, while positive lymph nodes are critical prognostic factor for distal cholangiocarcinoma patients.

Distal Bile Duct Cancer: Radical (R0 > 1 mm) Resection Achieves Favorable Survival

“…The 90-day mortality rates reported in the literature range between 3% and 8%, 5 , 9 , 11 , 12 , 14 – 16 which is comparable with our findings. Extended resections, with or without vascular resection, are certainly relevant risk factors for morbidity and mortality but may be necessary to achieve complete tumor removal.…”

“…Firstly, a positive resection margin is an independent risk factor for worse survival, as already shown by previous studies. 3 , 17 , 11 , 14 , 16 The strong impact of a >1mm tumor clearance that was shown by transferring the Leeds protocol for histopathological PDAC workup to DBC underlines the importance of radical surgical approaches in order to achieve this goal. 32 Secondly, intraoperative blood loss showed an even more pronounced effect on OS and should therefore be minimized, especially when extended resections are performed.…”

“…23,32 The independent prognostic factors identified in the present study (i.e., pN+, age ≥70 years, positive resection margin status, intraoperative blood loss ≥1000 mL, and ASA stage > II) are in line with the recent literature identifying positive lymph node status as the most frequently observed negative prognostic factor. 3,4,9,10,[14][15][16][17]19,20 A Japanese multicenter trial showed that not only the presence of positive lymph nodes, but also their number (pN1 vs. pN2), considerably impacts survivalan observation also recently made in PDAC. 15,33 Besides tumorrelated and patient-related parameters, our study shows that surgical parameters significantly influence the oncological outcome.…”

Prognostic factors and patterns of recurrence after curative resection for patients with distal cholangiocarcinoma

“…However, each subtype is now considered to have different tumor biology and prognosis [8]. Beyond that, a 15-year study also demonstrated different patterns of initial recurrence between patients with hilar cholangiocarcinoma and DCCA [21]. Ghiassi-Nejad et al [18] analyzed the recurrence pattern of 145 patients with cholangiocarcinoma, including 102 cases of intrahepatic bile duct cancer and 43 cases of hilar cholangiocarcinoma.…”

The new insight of treatment in Cholangiocarcinoma

“…In a Mayo Clinic cohort of patients, the median OS of DCCA was 22.0 months [25]. In V. Sallinen's study, the OS of DCCA patients was 40.4 months (95% CI: 19.1-61.7 months) [26]. In the study of Zhou WW et al, the median OS of all patients was 45.5 months (95% CI 13.5-77.5 months), and the 1-year, 3-year, and 5-year OS rates after resection were 82.6%, 55.2%, and 47.2%, respectively [27].…”