CD8^(+)CD226^(high)T cells in liver metastases dictate the prognosis of colorectal cancer patients treated with chemotherapy and radical surgery

CD226 has been reported to participate in the rescue of CD8^(+)T cell dysfunction.In this study,we aimed to assess the prognostic value of CD226 in tumor-infiltrating lymphocytes(TILs)derived from colorectal cancer(CRC)liver metastases treated with chemotherapy and radical surgery.TILs from 43 metastases were isolated and analyzed ex vivo usingflow cytometry.CD155 and CD3 levels in the tumor microenvironment were assessed by immunohistochemistry.Exploration and validation of biological processes highlighted in this study were performed by bioinformatics analysis of bulk RNA-seq results for 28 CRC liver metastases pretreated with chemotherapy as well as public gene expression datasets.CD226 expression contributes to the definition of the immune context in CRC liver metastases and primary tumors.CD226 on CD8^(+)T cells was not specifically coexpressed with other immune checkpoints,such as PD1,TIGIT,and TIM3,in liver metastases.Multivariate Cox regression analysis revealed CD226 expression on CD8^(+)T cells to be an independent prognostic factor(p=0.003),along with CD3 density at invasion margins(p=0.003)and TIGIT expression on CD4^(+)T cells(p=0.019).CD155 was not associated with the prognostic value of CD226.Gene expression analysis in a validation dataset confirmed the prognostic value of CD226 in CRC liver metastases but not in primary tumors.Downregulation of CD226 on CD8^(+)TILs in the liver microenvironment was restored by IL15 treatment.Overall,CD226 expression on liver metastasis-infiltrating CD8^(+)T cells selectively contributes to immune surveillance of CRC liver metastases and has prognostic value for patients undergoing radical surgery.

Prognostication algorithm for non-cirrhotic non-B non-C hepatocellular carcinoma-a multicenter study under the aegis of the French Association of Hepato-Biliary Surgery and liver Transplantation

Background:Liver resection and local ablation are the only curative treatment for non-cirrhotic hepatocellular carcinoma(HCC).Few data exist concerning the prognosis of patients resected for non-cirrhotic HCC.The objectives of this study were to determine the prognostic factors of recurrence-free survival(RFS)and overall survival(OS)and to develop a prognostication algorithm for non-cirrhotic HCC.Methods:French multicenter retrospective study including HCC patients with non-cirrhotic liver without underlying viral hepatitis:F0,F1 or F2 fibrosis.Results:A total of 467 patients were included in 11 centers from 2010 to 2018.Non-cirrhotic liver had a fibrosis score of F0(n=237,50.7%),F1(n=127,27.2%)or F2(n=103,22.1%).OS and RFS at 5 years were 59.2%and 34.5%,respectively.In multivariate analysis,microvascular invasion and HCC differentiation were prognostic factors of OS and RFS and the number and size were prognostic factors of RFS(P<0.005).Stratification based on RFS provided an algorithm based on size(P=0.013)and number(P<0.001):2 HCC with the largest nodule≤10 cm(n=271,Group 1);2 HCC with a nodule>10 cm(n=176,Group 2);>2 HCC regardless of size Conclusions:We developed a prognostication algorithm based on the number(≤or>2)and size(≤or>10 cm),which could be used as a treatment decision support concerning the need for perioperative therapy.In case of bifocal HCC,surgery should not be a contraindication.

Postoperative pancreatic fistula after distal pancreatectomy: pancreatic thickness and duct size as the only denominators?

We read with great interest the multicenter study from De Pastena and colleagues dealing with the prediction of clinically relevant postoperative pancreatic fistula(CR-POPF)after distal pancreatectomy(DP)(1).The study aimed to develop two scores.One was solely based on preoperative data.The second one relied on both preoperative and intraoperative data.

Improving actual survival after hepatectomy for intrahepatic cholangiocarcinoma—still a long way to go

Complete resection stands as the only potentially curative treatment.Being often late diagnosed,vascular and biliary structures are frequently involved owing to centrally located and/or large lesions at the time of diagnosis.Consequently,complete resection can require complex hepatectomy often on diseased liver,associated with important risks of mortality and morbidity while benefits in terms of prolonged survival remain often uncertain.To date,only one large series investigating actual long-term survival after curative-intent hepatectomy reported an actual 5-year OS of 13%(1).Indeed,around two thirds of patients experience recurrence,mostly to the liver,and eventually die of disease recurrence(2).These observations suggest first that patient selection for resection might be inadequate.Second,surgery alone seems not able to provide sufficient disease control.For instance,recurrence is frequently observed even with early tumours classified AJCC 8th Edition stage IA disease resulting in an estimated 5-year disease specific survival nearing 60%only.

Comment on:local control and survival after induction chemotherapy and ablative radiation versus resection for pancreatic ductal adenocarcinoma with vascular involvement

We read with interest the study from Jolissaint et al.recently issued in the Annals of Surgery(1).In this single center retrospective study,the authors compared oncological outcomes in patients with pancreatic ductal adenocarcinoma(PDAC)and vascular involvement who underwent pancreatectomy(n=105)vs.high dose ablative radiation(A-RT,n=104).All patients received induction chemotherapy first,over a recent study period[2014-2018].While the rationale for submitting patients to pancreatectomy or A-RT was not clearly stated in the Methods section,comparison between the two groups showed that patients allocated to A-RT were frailer with higher Charlson Comorbidity indexes and Eastern Cooperative Oncology Group(ECOG)scores and harbored significantly larger tumors,more often left-sided,with more arterial involvement as compared to patients in the pancreatectomy group.