Role of neoadjuvant chemoradiotherapy in liver transplantation for unresectable perihilar cholangiocarcinoma: multicentre, retrospective cohort study.

BACKGROUND: The Mayo protocol for liver transplantation in patients with unresectable perihilar cholangiocarcinoma is based on strict selection and neoadjuvant chemoradiotherapy. The role of neoadjuvant chemoradiotherapy in this scenario remains unclear. The aim of this study was to compare outcomes after transplantation for perihilar cholangiocarcinoma using strict selection criteria, either with or without neoadjuvant chemoradiotherapy. METHODS: This was an international, multicentre, retrospective cohort study of patients who underwent transplantation between 2011 and 2020 for unresectable perihilar cholangiocarcinoma using the Mayo selection criteria and receiving neoadjuvant chemoradiotherapy or not receiving neoadjuvant chemoradiotherapy. Endpoints were post-transplant survival, post-transplant morbidity rate, and time to recurrence. RESULTS: Of 49 patients who underwent liver transplantation for perihilar cholangiocarcinoma, 27 received neoadjuvant chemoradiotherapy and 22 did not. Overall 1-, 3-, and 5-year post-transplantation survival rates were 65 per cent, 51 per cent and 41 per cent respectively in the group receiving neoadjuvant chemoradiotherapy and 91 per cent, 68 per cent and 53 per cent respectively in the group not receiving neoadjuvant chemoradiotherapy (1-year hazards ratio (HR) 4.55 (95 per cent c.i. 0.98 to 21.13), P = 0.053; 3-year HR 2.07 (95 per cent c.i. 0.78 to 5.54), P = 0.146; 5-year HR 1.71 (95 per cent c.i. 0.71 to 4.09), P = 0.229). Hepatic vascular complications were more frequent in the group receiving neoadjuvant chemoradiotherapy compared with the group not receiving neoadjuvant chemoradiotherapy (nine of 27 versus two of 22, P = 0.045). In multivariable analysis, tumour recurrence occurred less frequently in the group receiving neoadjuvant chemoradiotherapy (HR 0.30 (95 per cent c.i. 0.09 to 0.97), P = 0.044). CONCLUSION: In selected patients undergoing liver transplantation for perihilar cholangiocarcinoma, neoadjuvant chemoradiotherapy resulted in a lower risk of tumour recurrence, but was associated with a higher rate of early hepatic vascular complications. Adjustments in neoadjuvant chemoradiotherapy reducing the risk of hepatic vascular complications, such as omitting radiotherapy, may further improve the outcome in patients undergoing liver transplantation for perihilar cholangiocarcinoma.

C-reactive protein identifies patients at low risk of anastomotic leak after esophagectomy.

PURPOSE: Fast-track protocols are increasingly used after digestive surgery. After esophagectomy, the gravity and the fear of anastomotic leak may be an obstacle to generalization of such protocols. C-reactive protein (CRP) might be a reliable tool to identify patients at low risk of anastomotic leak after esophagectomy, so that they can be safely included in a fast-track program. The aim of our retrospective bicentric study is to evaluate the interest of C-reactive protein measurement for the early diagnosis of anastomotic leak after esophagectomy. METHODS: Patients having undergone Ivor-Lewis procedure between January 2009 and September 2017 were included in this bicentric retrospective study. CRP values were recorded between postoperative day 3 (POD 3) and postoperative day 5 (POD 5). All postoperative complications were recorded, and the primary endpoint was anastomotic leak. RESULTS: We included 585 patients. Among them, 241 (41.2%) developed infectious complications and 69 patients (11.8%) developed anastomotic leak. CRP had the best predictive value on POD 5 (AUC = 0.74; 95% CI: 0.67-0.81). On POD 5, a cut-off value of 130 mg/L yielded a sensitivity of 87%, a specificity of 51%, and a negative predictive value of 96% for the detection of anastomotic leak. CONCLUSIONS: CRP may help in identifying patients at very low risk of anastomotic leak after esophagectomy. Patients with CRP values < 130 mg/L on POD 5 can safely undertake an enhanced recovery protocol.

The Role of Cavoportal and Renoportal Hemitransposition in Liver Transplantation.

BACKGROUND Few series of cavoportal (CPA) or renoportal (RPA) anastomosis have been published and their survival rates have never been compared. The objective of this study was to evaluate perioperative and long-term outcomes of CPA and RPA in a nationwide multicentric series and to compare hemitranspositions (HT) to paired orthotopic liver transplantations (OLT). MATERIAL AND METHODS HT performed in France up to April 2019 were analyzed. Endpoints were the incidence of severe (Clavien-Dindo>IIIa) 90-day perioperative complications and long-term patient and graft survival. RESULTS Sixty-four HT (13 CPA, 51 RPA) were performed in 59 patients. The rates of perioperative CD>IIIa complications were 64% and 49% in patients with CPA and RPA, respectively (P=0.59), and the rates of portal thrombosis and ascites were 38.5% and 9.8% (p=0.023) and 53.8% and 21.6% (p=0.049) in patients with CPA and RPA, respectively. The patient and graft perioperative survival rates were 54.4% and 83.3% (HR=3.2; CI 95 [1.1-9.9]; p=0.039) and 54.4% and 77.1% (HR=2.2; CI 95 [0.77-6.4]; P=0.14) in the CPA and RPA groups, respectively. Five-year patient survival was 36.4% and 61.8% in the CPA and RPA groups, respectively (HR=2.5; CI95 [1-6.1]; P=0.039). Compared with OLT grafts, long-term HT graft survival rates were not different (HR=1.7; CI 95 [0.96-3.1]; P=0.066), while patient survival rates were lower in the HT group (HR=4.6; CI 95 [2-11]; P<0.001). CONCLUSIONS Compared to OLT, HT significantly reduces patient survival. Given the poor survival results of CPA, the indication deserves to be limited in the context of organ shortage and RPA should be preferred when HT is needed.

Liver Venous Deprivation or Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy?: A Retrospective Multicentric Study.

OBJECTIVE: To compare 2 techniques of remnant liver hypertrophy in candidates for extended hepatectomy: radiological simultaneous portal vein embolization and hepatic vein embolization (HVE); namely LVD, and ALPPS. BACKGROUND: Recent advances in chemotherapy and surgical techniques have widened indications for extended hepatectomy, before which remnant liver augmentation is mandatory. ALPPS and LVD typically show higher hypertrophy rates than portal vein embolization, but their respective places in patient management remain unclear. METHODS: All consecutive ALPPS and LVD procedures performed in 8 French centers between 2011 and 2020 were included. The main endpoint was the successful resection rate (resection rate without 90-day mortality) analyzed according to an intention-to-treat principle. Secondary endpoints were hypertrophy rates, intra and postoperative outcomes. RESULTS: Among 209 patients, 124 had LVD 37 [13,1015] days before surgery, whereas 85 underwent ALPPS with an inter-stages period of 10 [6, 69] days. ALPPS was mostly-performed for colorectal liver metastases (CRLM), LVD for CRLM and perihilar cholangiocarcinoma. Hypertrophy was faster for ALPPS. Successful resection rates were 72.6% for LVD ± rescue ALPPS (n = 6) versus 90.6% for ALPPS (P < 0.001). Operative duration, blood losses and length-of-stay were lower for LVD, whereas 90-day major complications and mortality were comparable. Results were globally unchanged for CRLM patients, or after excluding the early 2 years of experience (learning-curve effect). CONCLUSIONS: This study is the first 1 comparing LVD versus ALPPS in the largest cohort so far. Despite its retrospective design, it yields original results that may serve as the basis for a prospective study.

Tacrolimus Concentrations Measured in Excreted Bile in Liver Transplant Recipients: The STABILE Study.

PURPOSE: Tacrolimus (TAC) is the main immunosuppressive drug in liver transplantation. Despite intensive therapeutic drug monitoring (TDM) that relies on whole blood trough concentration (TACblood), patients still present with acute cellular rejection or TAC-related toxic effects with concentrations within the therapeutic range. TAC concentration in peripheral blood mononuclear cells (TACPBMC) is considered as an efficient surrogate marker of TAC efficacy. However, it is still not applicable in daily practice. New TDM methods are therefore needed, especially during the early postoperative period. TAC is metabolized in the liver and eliminated through biliary excretion. We therefore hypothesised that TAC concentration measured in excreted bile (TACbileC) could be a relevant surrogate marker of its efficacy. METHODS: The Therapeutic Drug Monitoring of Tacrolimus Biliary Concentrations for Liver-Transplanted Patients (STABILE) study is a prospective monocentric trial. During the 7 first days after TAC therapy initiation, TACbileC was measured. The correlation between TACbileC and TACPBMC as well as between TACblood and TACPBMC was assessed. The correlations between TACbileC and liver graft function parameter or with occurrence of neurologic toxic effects were also evaluated. FINDINGS: Between May 2016 and April 2017, 41 patients were analyzed. TACbileC was significantly correlated with TACPBMC (r = 0.25, P = 0.007). However, a better correlation was found between TACPBMC and TACblood (r = 0.53, P < 0.001) and was confirmed in multivariate analysis. However, only TACbileC was significantly correlated with liver graft function, such as factor V (r = 0.40, P = 0.009) or bilirubin level (r = 0.21, P = 0.01), and significantly lower in patients presenting with neurologic toxic effects (P < 0.001). Receiver operating characteristic curve analysis found that a TACbileC level lower than 0.20 ng/mL on day 2 after TAC therapy initiation was a good predictive marker of occurrence of neurotoxic effects (AUC = 0.81). IMPLICATIONS: TACbileC is not a better surrogate maker of TAC activity than TACblood. However, TACbileC could help predict the occurrence of TAC toxic effects when a T-tube is inserted. ClinicalTrials.gov identifier: NCT02820259.