PD1+ T-cells correlate with Nerve Fiber Density as a prognostic biomarker in patients with resected perihilar cholangiocarcinoma.

Background & Aims: Perihilar cholangiocarcinoma (pCCA) is a hepatobiliary malignancy. Nerve fiber invasion (NFI) shows cancer invading the nerve and is considered an aggressive feature. Nerve fiber density (NFD) consists of small nerve fibers without cancer invasion and is divided into high NFD (high numbers of small nerve fibers) or low NFD (low numbers of small nerve fibers). We aim to explore differences in immune cell populations and survival. Approach & Results: We applied multiplex immunofluorescence (mIF) on 47 pCCA surgically resected patients and investigated immune cell composition in the tumor microenvironment (TME) of nerve fiber phenotypes (NFI, high and low NFD). Group comparison was performed and overall survival (OS) was assessed. The NFI Region of Interest (ROI) was measured with highest CD68+ macrophage levels among 3 ROIs (NFI compared to tumor free p= 0.016 and to tumor p=0.034) and PD1 expression on CD8 and were more abundant in the tumor rather than NFI ROI (p= 0.004 and p= 0.0029 respectively). NFD compared to NFI, demonstrated co-expression of CD8+PD1+ as well as CD68+PD1+ to be significantly higher in high NFD patients (p= 0.027 and p= 0.044, respectively). The high NFD OS was 92 months median OS (95% CI:41-142), for low NFD 20 months ((95% CI: 4-36) and for NFI 19 months (95% CI 7-33). High NFD OS was significantly better compared to low NFD (p= 0.046) and NFI (p= 0.032). Conclusions: PD1+ T-cells correlate with high NFD as a prognostic biomarker, the biological pathway behind this needs to be investigated.

Actual 10-Year Survival after Resection of Perihilar Cholangiocarcinoma: What Factors Preclude a Chance for Cure?

Complete resection of perihilar cholangiocarcinoma (pCCA) is the only potentially curative treatment. Long-term survival data is rare and prognostic analyses are hindered by the rarity of the disease. This study aimed to determine the cure rate and to identify clinicopathological factors that may preclude cure. All consecutive resections for pathologically confirmed pCCA between 2000 and 2009 in 22 centers worldwide were included in a retrospective cohort study. Each center included its retrospective data series. A total of 460 patients were included with a median follow-up of 10 years for patients alive at last follow-up. Median overall survival (OS) was 29.9 months and 10-year OS was 12.8%. Twenty-nine (6%) patients reached 10-year OS. The observed cure rate was 5%. Factors that virtually precluded cure (i.e., below 1%) according to the mixture cure model included age above 70, Bismuth-Corlette type IV tumors, hepatic artery reconstruction, and positive resection margins. Cure was unlikely (i.e., below 3%) in patients with positive lymph nodes or poor tumor differentiation. These factors need to be considered in patient counseling and long-term follow-up after surgery.

Comparison of an Inside Stent and a Fully Covered Self-Expandable Metallic Stent as Preoperative Biliary Drainage for Patients with Resectable Perihilar Cholangiocarcinoma Retrospectively.

BackgroundThere is a need for a more tolerable preoperative biliary drainage (PBD) method for perihilar cholangiocarcinoma (PHCC). In recent years, inside stents (ISs) have attracted attention as a less suffering PBD method. Few studies have compared IS with a fully covered self-expandable metallic stent (FCSEMS) as PBD for resectable PHCC. The aim of this study is to compare them.MethodsThis study involved 87 consecutive patients (IS: 51, FCSEMS: 36). The recurrent biliary obstruction (RBO) rate until undergoing surgery or being diagnosed as unresectable, time to RBO, factors related to RBO, incidence of adverse events related to endoscopic retrograde cholangiography and postoperative complications associated with each stent were evaluated retrospectively.ResultsThere was no significant difference between the two groups in the incidence of adverse events after stent insertion. The mean (s.d.) time to RBO was 40.0 (28.1) days in the IS group and 52.0 (45.5) days in the FCSEMS group, with no significant difference (P=0.384). A total of 7/51 patients in the IS group and 3/36 patients in the FCSEMS group developed RBO. The only risk factor for RBO was bile duct obstruction of the future excisional liver lobe(s) due to stenting (HR 0.033, P=0.006) in the FCSEMS group, but risk factors could not be indicated in the IS group. Regarding postoperative complications, there was no significant difference in the incidence of bile leakage or liver failure. In contrast, pancreatic fistula was significantly more common in the FCSEMS group (13/24 patients) than in the IS group (3/28 patients) (P=0.001), especially in patients who did not undergo pancreatectomy (P=0.001).ConclusionsAs PBD for PHCC, both IS and FCSEMS achieved low RBO rates. In contrast, the incidence of postoperative pancreatic fistula was higher with FCSEMS. Thus, IS, which can be inserted easily, is considered an optimal approach as PBD for resectable PHCC.clinical trial registration number: UMIN000025631