Laparoscopic versus open extended radical left pancreatectomy for pancreatic ductal adenocarcinoma: an international propensity-score matched study.

BACKGROUND: A radical left pancreatectomy in patients with pancreatic ductal adenocarcinoma (PDAC) may require extended, multivisceral resections. The role of a laparoscopic approach in extended radical left pancreatectomy (ERLP) is unclear since comparative studies are lacking. The aim of this study was to compare outcomes after laparoscopic vs open ERLP in patients with PDAC. METHODS: An international multicenter propensity-score matched study including patients who underwent either laparoscopic or open ERLP (L-ERLP; O-ERLP) for PDAC was performed (2007-2015). The ISGPS definition for extended resection was used. Primary outcomes were overall survival, margin negative rate (R0), and lymph node retrieval. RESULTS: Between 2007 and 2015, 320 patients underwent ERLP in 34 centers from 12 countries (65 L-ERLP vs. 255 O-ERLP). After propensity-score matching, 44 L-ERLP could be matched to 44 O-ERLP. In the matched cohort, the conversion rate in L-ERLP group was 35%. The L-ERLP R0 resection rate (matched cohort) was comparable to O-ERLP (67% vs 48%; P = 0.063) but the lymph node yield was lower for L-ERLP than O-ERLP (median 11 vs 19, P = 0.023). L-ERLP was associated with less delayed gastric emptying (0% vs 16%, P = 0.006) and shorter hospital stay (median 9 vs 13 days, P = 0.005), as compared to O-ERLP. Outcomes were comparable for additional organ resections, vascular resections (besides splenic vessels), Clavien-Dindo grade ≥ III complications, or 90-day mortality (2% vs 2%, P = 0.973). The median overall survival was comparable between both groups (19 vs 20 months, P = 0.571). Conversion did not worsen outcomes in L-ERLP. CONCLUSION: The laparoscopic approach may be used safely in selected patients requiring ERLP for PDAC, since morbidity, mortality, and overall survival seem comparable, as compared to O-ERLP. L-ERLP is associated with a high conversion rate and reduced lymph node yield but also with less delayed gastric emptying and a shorter hospital stay, as compared to O-ERLP.

Factors Associated with Prolonged Recipient Hepatectomy Time During Liver Transplantation: A Single-Centre Experience.

BACKGROUND: Recipient hepatectomy during liver transplantation can be a challenging operation and can increase cold ischaemic time. The aim of this study is to assess factors associated with prolonged recipient hepatectomy. METHODS: From 2005 to 2015, 930 patients were submitted to liver transplantation in our hospital. Prolonged hepatectomy time was defined as operative time >180 min (from knife on skin to total hepatectomy). Patients undergoing early liver retransplantation and living donation were excluded. RESULTS: A total of 715 patients were included in our study. Median age at transplantation was 53 (18-70) years, and median BMI was 26.2 (16-40). Median hepatectomy time was 131 min. Prolonged hepatectomy time occurred in 89 (12.4%) patients. At univariate analysis, previous decompensated cirrhosis with variceal bleeding and/or ascites, higher BMI and previous abdominal surgery were associated with prolonged operating time. Higher surgeon experience and acute liver failure were associated with shorter hepatectomy time. At multivariate analysis, previous episodes of variceal bleeding (p = 0.027, OR 1.78), BMI > 27 (p = 0.01, OR 1.75), previous abdominal surgery (p = 0.04, OR 1.68) and surgeon experience (p = 0.007, OR 2.04) were independently associated with operating time. Prolonged hepatectomy time was significantly associated with cold and total ischaemic time and intraoperative bleeding (p < 0.001, p = 0.002 and p = 0.002, respectively). CONCLUSIONS: Recipient BMI, previous episodes of variceal bleeding, previous abdominal surgery and surgeon experience are independently associated with hepatectomy duration. These factors can be helpful to identify those patients with potentially prolonged hepatectomy time, and therefore, strategies can be put in place to optimize outcomes in this group of patients.

Can we predict recurrence in WHO G1-G2 pancreatic neuroendocrine neoplasms? Results from a multi-institutional Spanish study.

INTRODUCTION: Pancreatic neuroendocrine neoplasms (PNEN) are rare tumours and well differentiated PNEN are associated with relatively indolent physiological behaviour. For this reason, only few studies have investigated those factors associated with recurrence in this group of patients. The aim of this study is to analyse whether it is possible to predict tumour recurrence in World Health Organization (WHO) 2017 G1-G2 PNEN patients. METHODS: This is a retrospective multi-institutional study. Patients submitted to pancreatic resection from 7 Spanish centres were reviewed. Only patients with WHO G1-G2 PNEN were included. Demographic and clinicopathological variables were analysed. RESULTS: Data from 137 patients were reviewed. Median age was 59.2 (25-84) years. Recurrence of disease occurred in 19 (13.9%) patients. Median DFS was 55 months. At multivariate analysis, tumour size >20 mm, lymphnode metastasis and a new tumour grade 2 incorporating Ki-67 labelling index (LI) > 5% and mitotic index (MI) > 2 were independently associated with recurrence. We developed a risk score model with these three factors. High-risk patients had a significantly lower 5-year disease-specific survival compared to low-risk patients (70% vs 100%). CONCLUSION: We propose a novel risk score for recurrence based on lymphnode metastasis, tumour size > 20 mm and a new grade 2 based on Ki-67 LI >5% and MI > 2. If 2 factors are present, patients have a higher risk for recurrence and a significantly poorer DSS, and therefore they should be closely monitored during follow-up. The role of adjuvant chemotherapy in these patients needs to be evaluated in clinical trials.

Liver transplantation for bile duct injury after open and laparoscopic cholecystectomy.

BACKGROUND: Bile duct injury (BDI) after cholecystectomy is a serious complication. In a small subset of patients with BDI, failure of surgical or non-surgical management might lead to acute or chronic liver failure. The aim of this study was to review the indications and outcome of liver transplantation (LT) for BDI after open and laparoscopic cholecystectomy. METHODS: Patients with BDI after cholecystectomy who were on the waiting list for LT between January 1987 and December 2010 were identified from LT centres in Spain. A standardized questionnaire was sent to each unit for extraction of data on diagnosis, previous treatments, indication and outcome of LT for BDI. RESULTS: Some 27 patients with BDI after cholecystectomy in whom surgical and non-surgical management for BDI failed were scheduled for LT over the 24-year interval. Emergency LT for acute liver failure was indicated in seven patients, all after laparoscopic cholecystectomy. Two patients died while on the waiting list and only one patient survived more than 30 days after LT. Elective LT for secondary biliary cirrhosis after a failed hepaticojejunostomy was performed in 13 patients after open and seven after laparoscopic cholecystectomy. One patient from the elective transplantation group died within 30 days of LT. The estimated 5-year overall survival rate was 68 per cent. CONCLUSION: Emergency LT for acute liver failure was more common in patients with BDI after laparoscopic cholecystectomy, and associated with a poor outcome.

Intracellular IFN-γ and IL-2 expression monitoring as surrogate markers of the risk of acute rejection and personal drug response in de novo liver transplant recipients.

Biomarker monitoring is needed in transplantation to reflect individual response to immunosuppressive drugs and graft outcome. We evaluated intracellular expression and soluble production of interferon-(IFN)-γ and interleukin-(IL)-2 as predictive biomarkers of acute rejection (AR) and personal drug response. Pharmacokinetic-pharmacodynamic profiles were determined in 47 de novo liver recipients treated with tacrolimus, mycophenolate mofetil and prednisone. Of the 47 patients, AR occurred in nine. There were no differences in drug concentrations between rejectors and non-rejectors. A pre-transplantation cut-off value of 55.80% for %CD8(+)-IFN-γ(+) identified patients at high risk of AR with a sensitivity of 75% and a specificity of 82%. In the first week post-transplantation, patients with a % inhibition for soluble IFN-γ, %CD8(+)-IFN-γ(+) and %CD8(+)-IL2(+) lower than 40% developed AR, showing low susceptibility to immunosuppressive drugs. Therefore, effector-T-cell response monitoring may help physicians to identify personal response to treatment and patients at high risk of AR.

Role of Adult Living Donor Liver Transplantation in the Treatment of Hepatocellular Carcinoma Within and Beyond Milan Criteria: A Comparative Study.

BACKGROUND AND AIMS: In the context of the shortage of donors, adult living donor liver transplantation (aLDLT) represents a feasible alternative for patients within as well as beyond the Milan criteria. METHODS: From 2001, we performed 42 aLDLTs for hepatocellular carcinoma (HCC). Sixteen of the recipients were within the Milan criteria, whereas 26 fulfilled the Barcelona-Clinic Liver Cancer Group (BCLC) expanded criteria (1 tumor ≤7 cm, 5 tumors ≤3 cm, or tumors 3 ≤5 cm without macrovascular invasion or down-staging to Milan after loco-regional therapies). The objective of the current study was to compare the post-transplantation results of these two groups. RESULTS: Six Milan-in and 16 beyond Milan patients received neo-adjuvant loco-regional therapies. One Milan-in and nine patients from the beyond Milan group presented an explant histological stage beyond Milan. After a median follow-up of 64 months, 5- and 10-year overall survival rates were 60.2% and 51.6% in the Milan-in group and 78% and 65% in the beyond Milan group. Five- and 10-year disease-free survival rates were 64.5% and 55.3% in the Milan-in patients and 67.9% and 56.6% in the beyond Milan patients. Being beyond up-to-seven criteria in the histology of the explant was a significant factor for HCC recurrence. CONCLUSION: The use of aLDLT in patients with HCC within and beyond Milan but within the BCLC expanded criteria offers acceptable survival and recurrence rates. Therefore, we believe that its use in this scenario is justified.