Showing papers by "Philippe Bachellier published in 2017"

Prognostic Value of Resection Margin Involvement After Pancreaticoduodenectomy for Ductal Adenocarcinoma: Updates From a French Prospective Multicenter Study.

Abstract: Objective:The aim of the study was to assess the relevance of resection margin status for survival after resection of pancreatic-head ductal adenocarcinoma.Summary Background Data:The definition and prognostic value of incomplete microscopic resection (R1) remain controversial.Methods:Prognostic fac

Liver transplantation in critically ill patients: Preoperative predictive factors of post-transplant mortality to avoid futility.

Abstract: Background The allocation of liver transplants to patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) with multi-organ failure who are admitted in ICU remains controversial due to their high post-transplant mortality rate and the absence of identified mortality risk factors. Methods We performed a single-center retrospective cohort study to determine the post-transplant mortality rate of patients with ALF and ACLF requiring ICU care prior to liver transplant (LT) and identified pretransplant factors of post-transplant mortality. Results Eighty-four patients (29 with ALF and 55 with ACLF) received a liver transplant while they were hospitalized at the ICU. Their mean model for end-stage liver disease (MELD) score was 41, and their mean sequential organ failure assessment (SOFA) was 15 the day before transplant. The overall 1-year survival rate was 66%. In multivariate analysis, pretransplant lactate level and acute respiratory distress syndrome (ARDS) were the only two independent factors associated with post-transplant mortality. The absence of ARDS and a pretransplant lactate level 80%). Conclusions Low lactatemia lactate level and the absence of ARDS could be useful criteria in selecting those patients in ICU who could be eligible for liver transplant.

Metabolomics approaches in pancreatic adenocarcinoma: tumor metabolism profiling predicts clinical outcome of patients

Abstract: Pancreatic adenocarcinomas (PAs) have very poor prognoses even when surgery is possible. Currently, there are no tissular biomarkers to predict long-term survival in patients with PA. The aims of this study were to (1) describe the metabolome of pancreatic parenchyma (PP) and PA, (2) determine the impact of neoadjuvant chemotherapy on PP and PA, and (3) find tissue metabolic biomarkers associated with long-term survivors, using metabolomics analysis. 1H high-resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy using intact tissues was applied to analyze metabolites in PP tissue samples (n = 17) and intact tumor samples (n = 106), obtained from 106 patients undergoing surgical resection for PA. An orthogonal partial least square-discriminant analysis (OPLS-DA) showed a clear distinction between PP and PA. Higher concentrations of myo-inositol and glycerol were shown in PP, whereas higher levels of glucose, ascorbate, ethanolamine, lactate, and taurine were revealed in PA. Among those metabolites, one of them was particularly obvious in the distinction between long-term and short-term survivors. A high ethanolamine level was associated with worse survival. The impact of neoadjuvant chemotherapy was higher on PA than on PP. This study shows that HRMAS NMR spectroscopy using intact tissue provides important and solid information in the characterization of PA. Metabolomics profiling can also predict long-term survival: the assessment of ethanolamine concentration can be clinically relevant as a single metabolic biomarker. This information can be obtained in 20 min, during surgery, to distinguish long-term from short-term survival.

Laparoscopic Compared to Open Repeat Hepatectomy for Colorectal Liver Metastases: a Multi-institutional Propensity-Matched Analysis of Short- and Long-Term Outcomes

Abstract: While uptake of laparoscopic hepatectomy has improved, evidence on laparoscopic re-hepatectomy (LRH) for colorectal liver metastases (CRLMs) is limited and has never been compared to the open approach. We sought to define outcomes of LRH compared to open re-hepatectomy (ORH). Patients undergoing re-hepatectomy for CRLM at 39 institutions (2006–2013) were identified. Primary outcomes were 30-day post-operative overall morbidity, mortality, and length of stay. Secondary outcomes were recurrence and survival at latest follow-up. LRHs were matched to ORHs (1:3) using a propensity score created by comparing pre-operative clinicopathologic factors (number and size of liver metastases and major hepatectomy). Of 376 re-hepatectomies included, 27 were LRH, including 1 (3.7%) conversion. The propensity-matched cohort included 108 patients. Neither median operative time (252 vs. 230 min; p = 0.82) nor overall 30-day morbidity (48.1 vs. 38.3%; p = 0.37) differed. Non-specific morbidity (including cardiac, respiratory, infectious, and renal events) decreased with LRH (11.1 vs. 30.9%, p = 0.04), while surgical-specific morbidity, including liver insufficiency, was higher (44.4 vs. 22.2%, p = 0.03). One ORH and 0 LRH suffered 30-day mortality. Median length of stay (9 vs. 12 days; p = 0.60) was comparable. At latest follow-up, 26 (96.3%) LRH and 67 (82.7%) ORH patients were alive. Eight (29.6%) LRH and 36 (44.4%) ORH patients were alive without disease. LRH for recurrent CRLM was associated with overall short-term outcomes comparable to ORH, but different morbidity profiles. While it may offer a safe and feasible approach, further insight is necessary to better define patient selection.

Resectable invasive IPMN versus sporadic pancreatic adenocarcinoma of the head of the pancreas: Should these two different diseases receive the same treatment? A matched comparison study of the French Surgical Association (AFC).

Abstract: Purpose To compare survival and impact of adjuvant chemotherapy in patients who underwent pancreaticoduodenectomy (PD) for invasive intraductal papillary mucinous neoplasm (IIPMN) and sporadic pancreatic ductal adenocarcinoma (PDAC). Methods From 2005 to 2012, 240 patients underwent pancreatectomy for IIPMN and 1327 for PDAC. Exclusion criteria included neoadjuvant treatment, pancreatic resection other than PD, vascular resection, carcinoma in situ , or Results There was no difference in patient's characteristics, intraoperative parameters, postoperative outcomes, and histologic parameters. Overall survival and disease-free survival times were comparable between the 2 groups. In each group, overall survival time was significantly poorer in patients who did not achieve adjuvant chemotherapy ( p = 0.03 for the IIPMN group; p = 0.03 for the PDAC group). In lymph-node negative patients of the IIPMN group, adjuvant chemotherapy did not have any significant impact on overall survival time (OR = 0.57; 95% CI [0.24–1.33]). Considering the whole population (i.e. patients with IIPMN and PDAC; n = 246), patients who did not achieve adjuvant chemotherapy had poorer survival ( p Conclusions The courses of IIPMN and PDAC were similar after an optimized stage-to-stage comparison. Adjuvant chemotherapy was efficient in both groups. However, in lymph node negative patients, adjuvant chemotherapy seemed not to have a significant impact.

Evaluation of transcriptomic signature as a valuable tool to study drug-induced cholestasis in primary human hepatocytes

Abstract: Primary human hepatocyte (PHH) sandwich cultures from five different donors were daily exposed to cyclosporine A (CsA), ibuprofen (IBU), chlorpromazine (CPZ), amiodarone (AMI) and paracetamol (APAP) at their respective Cmax (total) for short-term (1–3 days) and long-term treatment (14 days). Whole genome mRNA profiles (34,693 genes in total) were conducted using an Illumina microarray platform. The impact of compound treatments on gene signatures involved in liver differentiation, cholestasis and in bile acid homeostasis was evaluated. Notably, PHH from the five donors showed a highly comparable phenotype of terminally differentiated hepatocytes. As expected, PHH exposed to 100 µM APAP showed no signs of hepatotoxicity both after short- and long-term treatment. CsA at 0.7 µM, IBU at 100 µM, AMI at 2.5 µM and CPZ at 0.1–0.2 µM presented, in line with their cholestatic syndromes reported at therapeutic doses, transcriptomic signatures of cholestasis in PHH cultures; deregulation of genes involved in bile acid homeostasis further confirmed this finding. The strength of the cholestasis signature obtained after treatment with CsA, IBU and AMI could be directly related to the basal expression of the respective drug metabolizing enzymes in the various PHH cultures from different individuals. Our data show that the PHH model system combined with transcriptomics carries the future promise to identify individual gene expression profiles predictive of increased cholestasis risk. As the present work suggests possible correlation between mRNA levels of ADME relevant genes and a transcriptomic signature of cholestasis, particular focus on this research question could be the emphasis of additional data collection.

Liver transplantation for hereditary hemorrhagic telangiectasia: a systematic review

Abstract: Aim To evaluate the indications, timing and results of liver transplantation in patients affected by hereditary hemorrhagic telangiectasia (HHT), by undertaking a systematic review of the current literature. Methods Electronic bibliographical databases were searched on MEDLINE and Pubmed according to the PRISMA criteria. A total of 58 articles were initially found, 11 have been excluded because of single center series later included in the European Liver transplant Registry (ELTR), already reported in this study. Thirty-eight articles have been excluded because they did not report specifically new cases of liver transplantation for hereditary hemorrhagic telangiectasia. Finally 9 articles were included in the analysis. Results A total of 56 patients who underwent liver transplantation for HHT are present in the English literature. One additional patient is presented in this article, for a total of 57 patients worldwide. To date, the most consistent published series is the one of the ELTR, including patients from 15 liver transplantation centers in the period 1985–2003 with a mean follow-up of 69 months. Ten-year patient and graft survival is 82.5% Conclusion Liver transplantation should be considered as a radical but definitive treatment option in patients affected by HHT with liver or cardiac involvement not responsive to medical treatment.

Prediction of hepatocellular carcinoma recurrence after liver transplantation: Comparison of four explant-based prognostic models.

Abstract: Aim Discordance between pre-LT imaging and explanted liver findings have been reported after liver transplantation (LT) for hepatocellular carcinoma (HCC), suggesting the need of reassessing the risk of HCC recurrence post-LT. Our aims were to compare pre-LT imaging and explants features and to test the performances of four explant-based predictive models of recurrence in an external cohort. Methods Staging according to pre-LT imaging and explant features were compared. Four explants-based models were retrospectively tested in a cohort of 372 patients transplanted for HCC in 19 French centres between 2003 and 2005. Accuracies of the scores were compared. Results Pre-LT imaging underestimated tumour burden in 83 (22.7%) patients according to Milan criteria. The highest AUCs for prediction of 5-years recurrence were observed in the "Up to seven" (0.7915 [95% CI: 0.7339-0.849]) and Decaens models (0.747 [95% CI: 0.6877-0.806]), with two levels of risk: low (10%) and high (>50%). Chan and Iwatsuki models identified 3 and 4 levels of risk, but had lower AUCs (0.68 and 0.70) respectively. Accuracy of the "Up to seven" model was superior to the Decaens model (P=.034), which was superior to the Chan model (P=.0041) but not to the Iwatsuki model (P=.17). Conclusion Pre-LT imaging underestimates tumour burden, and prediction of recurrence should be reassessed after LT. The explant-based "Up to seven" and Decaens models provided the best accuracy for prediction of 5-year recurrence, identifying only two levels of risk. New models are needed to further refine the prediction of recurrence after LT.

Assessment of high-priced systemic antifungal prescriptions ☆

Abstract: Objectives To assess compliance with international guidelines for costly antifungal prescriptions and to compare these results with a first study performed in 2007. Methods Retrospective study including all costly antifungal prescriptions made in surgical and medical intensive care units and in a hepatobiliary, pancreatic, and digestive surgery unit. Prescriptions were assessed in terms of indication, dosage, and antifungal de-escalation. Results Seventy-four treatments were analyzed. Treatments were prescribed for prophylactic (1%), empirical (22%), pre-emptive (16%), or targeted therapy (61%). Caspofungin accounted for 68% of prescriptions, followed by voriconazole (20%) and liposomal amphotericin B (12%). Indication was appropriate in 91%, debatable in 1%, and inappropriate in 8%. Dosage was appropriate in 69%, debatable in 8%, and inappropriate in 23%. Prescriptions were inappropriate for the following reasons: lack of dosage adjustment in light of the hepatic function (10 cases), underdosage or excessive dosage by > 25% of the recommended dose in seven cases. De-escalation to fluconazole was implemented in 40% of patients presenting with a fluconazole-susceptible candidiasis. Conclusion The overall incidence of appropriate use was higher in 2012 compared with 2007 (62% and 37% respectively, P = 0.004). Nevertheless, costly antifungal prescriptions need to be optimized in particular for empirical therapy, dosage adjustment, and potential de-escalation to fluconazole.

Sensitizing Surgeons to Their Outcome Has No Measurable Short-term Benefit.

Abstract: OBJECTIVE Investigate if involving surgeons in outcome prediction-research and having them use a dedicated Electronic-Health-Record that provides feedback, improves patients' outcome. BACKGROUND Improvement of clinical outcome mainly relies on the declaration of adverse events, identification of their predictors, self-assessment, and feedback. METHODS Thirteen French Hepato-Pancreato-Biliary-centers made commitment to include all patients undergoing elective hepatectomies in an observational study. Each center was given access to a dedicated website, where perioperative data were prospectively collected. The website provided real-time individual and comparative feedback of outcome and was also intended to perform prognostication studies. The hypothesis was that by using this strategy, the length-of-stay would be reduced by 10%. Power-calculation implied the inclusion of 1720 patients. Secondary endpoints were 90-day mortality, severe morbidity, and the comprehensive-complication index. RESULTS Only 5 of the 13 participating centers were fully compliant in enrolling their patients and the inclusion period was extended by 1-year (October 2012-October 2015) to meet the objective. During this period, the collaborative group published 9 studies based on the study data (median impact factor = 8.327) that identified quantitative clinical variables, qualitative clinical variables, and nonclinical variables influencing outcome. For patients enrolled by the 5 active centers (n = 1752), there was no improvement in length of stay (13.3 vs 12.4 days, P = 0.287), severe complications (23.6 vs 20.5%, P = 0.134), the complication comprehensive index (24.0 vs 24.9, P = 0.448), mortality (4.1 vs 3.9%, P = 0.903), or unplanned readmissions (7.2 vs 8.4%, P = 0.665), even after adjusting for confounders. CONCLUSION Simply sensitizing surgeons to their outcome has no measurable short-term clinical benefit.