Management of distal cholangiocarcinoma with arterial involvement: Systematic review and case series on the role of neoadjuvant therapy

BACKGROUND The use of neoadjuvant therapy(NAT)in distal cholangiocarcinoma(dCCA)with regional arterial or extensive venous involvement,is not widely accepted and evidence is sparse.AIM To synthesise evidence on NAT for dCCA and present the experience of a highvolume tertiary-centre managing dCCA with arterial involvement.METHODS A systematic review was performed according to PRISMA guidance to identify all studies reporting outcomes of patients with dCCA who received NAT.All patients from 2017 to 2022 who were referred for NAT for dCCA at our centre were retrospectively collected from a prospectively maintained database.Baseline characteristics,NAT type,progression to surgery and oncological outcomes were collected.RESULTS Twelve studies were included.The definition of“unresectable”locally advanced dCCA was heterogenous.Four studies reported outcomes for 9 patients who received NAT for dCCA with extensive vascular involvement.R0 resection rate ranged between 0 and 100%but without survival benefit in most cases.Remaining studies considered either NAT in resectable dCCA or inclusive with extrahepatic CCA.The presented case series includes 9 patients(median age 67,IQR 56-74 years,male:female 5:4)referred for NAT for borderline resectable or locally advanced disease.Three patients progressed to surgery and 2 were resected.One patient died at 14 months with evidence of recurrence at 6 months and the other died at 51 months following recurrence 6 months postoperatively.CONCLUSION Evidence for benefit of NAT is limited.Consensus on criteria for uniform definition of resectability for dCCA is required.We propose using the established National-Comprehensive-Cancer-Network®criteria for pancreatic ductal adenocarcinoma.

SIMAP500: A novel risk score to identify recipients at higher risk of hepatocellular carcinoma recurrence following liver transplantation

BACKGROUND Recurrence of hepatocellular carcinoma(HCC)following liver transplantation(LT)has a devastating influence on recipients’survival;however,the risk of recur-rence is not routinely stratified.Risk stratification is vital with a long LT waiting time,as that could influence the recurrence despite strict listing criteria.AIM This study aims to identify predictors of recurrence and develop a novel risk pre-diction score to forecast HCC recurrence following LT.METHODS A retrospective review of LT for HCC recipients at University Hospitals Bir-mingham between July 2011 and February 2020.Univariate and multivariate analyses were performed to identify recurrence predictors,based on which the novel SIMAP500(satellite nodules,increase in size,microvascular invasion,AFP>500,poor differentiation)risk score was proposed.RESULTS 234 LTs for HCC were performed with a median follow-up of 5.3 years.Recurrence developed in 25 patients(10.7%).On univariate analyses,RETREAT score>3,α-fetoprotein(AFP)at listing 100-500 and>500,bridging,increased tumour size between imaging at the listing time and explant histology,increase in the size of viable tumour between listing and explant,presence of satellite nodules,micro-and macrovascular invasion on explant and poor differentiation of tumours were significantly associated with recurrence,based on which,the SIMAP500 risk score is proposed.The SIMAP500 demonstrated an excellent predictive ability(c-index=0.803)and outper-formed the RETREAT score(c-index=0.73).SIMAP500 is indicative of the time to disease recurrence.CONCLUSION SIMAP500 risk score identifies the LT recipients at risk of HCC recurrence.Risk stratification allows patient-centric post-transplant surveillance programs.Further validation of the score is recommended.

Para-aortic lymph node involvement should not be a contraindication to resection of pancreatic ductal adenocarcinoma

BACKGROUND Para-aortic lymph nodes(PALN)are found in the aortocaval groove and they are staged as metastatic disease if involved by pancreatic ductal adenocarcinoma(PDAC).The data in the literature is conflicting with some studies having associated PALN involvement with poor prognosis,while others not sharing the same results.PALN resection is not included in the standard lymphadenectomy during pancreatic resections as per the International Study Group for Pancreatic Surgery and there is no consensus on the management of these cases.AIM To investigate the prognostic significance of PALN metastases on the oncological outcomes after resection for PDAC.METHODS This is a retrospective cohort study of data retrieved from a prospectively maintained database on consecutive patients undergoing pancreatectomies for PDAC where PALN was sampled between 2011 and 2020.Statistical comparison of the data between PALN+and PALN-subgroups,survival analysis with the Kaplan-Meier method and risk analysis with univariable and multivariable time to event Cox regression analysis were performed,specifically assessing oncological outcomes such as median overall survival(OS)and disease-free survival(DFS).RESULTS 81 cases had PALN sampling and 17(21%)were positive.Pathological N stage was significantly different between PALN+and PALN-patients(P=0.005),while no difference was observed in any of the other characteristics.Preoperative imaging diagnosed PALN positivity in one case.OS and DFS were comparable between PALN+and PALN-patients with lymph node positive disease(OS:13.2 mo vs 18.8 mo,P=0.161;DFS:13 mo vs 16.4 mo,P=0.179).No difference in OS or DFS was identified between PALN positive and negative patients when they received chemotherapy either in the neoadjuvant or in the adjuvant setting(OS:23.4 mo vs 20.6 mo,P=0.192;DFS:23.9 mo vs 20.5 mo,P=0.718).On the contrary,when patients did not receive chemotherapy,PALN disease had substantially shorter OS(5.5 mo vs 14.2 mo;P=0.015)and DFS(4.4 mo vs 9.8 mo;P<0.001).PALN involvement was not identified as an independent predictor for OS after multivariable analysis,while it was for DFS doubling the risk of recurrence.CONCLUSION PALN involvement does not affect OS when patients complete the indicated treatment pathway for PDAC,surgery and chemotherapy,and should not be considered as a contraindication to resection.

Incidental gallbladder cancer diagnosis confers survival advantage irrespective of tumour stage and characteristics

BACKGROUND Incidental gallbladder cancer(IGBC)represents 50%-60%of gallbladder cancer cases.Data are conflicting on the role of IGBC diagnosis in oncological outcomes.Some studies suggest that IGBC diagnosis does not affect outcomes,while others that overall survival(OS)is longer in these cases compared to non-incidental diagnosis(NIGBC).Furthermore,some studies reported early tumour stages and histopathologic characteristics as possible confounders,while others not.AIM To investigate the role of IGBC diagnosis on patients’overall survival,especially after surgical treatment with curative intent.METHODS Retrospective analysis of all patient referrals with gallbladder cancer between 2008 and 2020 in a tertiary hepatobiliary centre.Statistical comparison of patient and tumour characteristics between IGBC and NIGBC subgroups was performed.Survival analysis for the whole cohort,surgical and non-surgical subgroups was done with the Kaplan-Meier method and the use of log rank test.Risk analysis was performed with univariable and multivariable Cox regression analysis.RESULTS The cohort included 261 patients with gallbladder cancer.65%of cases had NIGBC and 35%had IGBC.A total of 90 patients received surgical treatment(66%of IGBC cases and 19%of NIGBC cases).NIGBC patients had more advanced T stage and required more extensive resections than IGBC ones.OS was longer in patients with IGBC in the whole cohort(29 vs 4 mo,P<0.001),as well as in the non-surgical(14 vs 2 mo,P<0.001)and surgical subgroups(29 vs 16.5 mo,P=0.001).Disease free survival(DFS)after surgery was longer in patients with IGBC(21.5 mo vs 8.5 mo,P=0.007).N stage and resection margin status were identified as independent predictors of OS and DFS.NIGBC diagnosis was identified as an independent predictor of OS.CONCLUSION IGBC diagnosis may confer a survival advantage independently of the pathological stage and tumour characteristics.Prospective studies are required to further investigate this,including detailed pathological analysis and molecular gene expression.