Hepatectomy and liver regeneration: from experimental research to clinical application

BACKGROUND: The mechanisms and kinetics of hepatic growth have continuously been investigated. This study concerns liver regeneration in animal and patients who underwent partial hepatectomy evaluated by the hepatic extraction fraction (HEF) calculated through radioisotopic methods. METHODS: Thirty normal Wistar rats were submitted to an 85% hepatectomy, and 95 patients with primary and secondary liver tumours were included. In animal study, the liver regeneration kinetics was assessed by HEF using 99mTc-mebrofenin, the ratio liver/bodyweight and by using bromodeoxyuridine deoxyribonucleic acid incorporation. In patient study, the liver regeneration was evaluated by calculation of HEF before surgery, 5 and 30 days after hepatectomy. RESULTS: In animal, we verified a positive correlation between HEF kinetics and liver/bodyweight ratio or hepatocyte proliferation evaluated by bromodeoxyuridine deoxyribonucleic acid staining after 85% hepatectomy. In the clinical arm, no statistical differences of the HEF before hepatectomy, 5 and 30 days after hepatectomy, were observed. CONCLUSIONS: Our results support the view that human liver regeneration commences early, is fast, non-anatomical and functionally complete 5 days after hepatectomy. The fast functional liver regeneration may have a high clinical impact particularly concerning the post-operative oncological therapeutic approaches.info:eu-repo/semantics/publishedVersio

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

Background: 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. Methods: 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. Results: 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. Conclusions: 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. © 2017 The Author(s)

Liver transplantation for patients with acute-on-chronic liver failure (ACLF) in Europe: Results of the ELITA/EF-CLIF collaborative study (ECLIS)

BACKGROUND AND AIMS: Liver transplantation (LT) has been proposed to be an effective salvage therapy even for the sickest patients with acute-on-chronic liver failure (ACLF). This large collaborative study was designed to address the current clinical practice and outcomes of ACLF patients wait listed (WL) for LT in Europe. METHODS: Retrospective study including 308 consecutive ACLF patients, listed in 20 centres across 8 European countries, from January 2018 to June 2019. RESULTS: 2677 patients received a LT, 1216 (45.4%) for decompensated cirrhosis (DC). Of these, 234 (19.2%) had ACLF at LT: ACLF-1, 58 (4.8%); ACLF-2, 78 (6.4%); and ACLF-3, 98 (8.1%). Wide variations were observed amongst countries: France and Germany had high rates of ACLF-2/3 (27-41%); Italy, Switzerland, Poland and Netherlands had medium rates (9-15%); and United Kingdom and Spain had low rates (3-5%) (p 4 mmol/L (HR 3.14, 95% CI 1.37-7.19), recent infection from multi-drug resistant organisms (HR 3.67, 95% CI 1.63-8.28), and renal replacement therapy (HR 2.74, 95% CI 1.37-5.51) were independent predictors of post-LT mortality. During the same period, 74 patients with ACLF died on the WL. In an intention-to-treat analysis, one-year survival of ACLF patients on the LT WL was 73% for ACLF-1 or -2 and 50% for ACLF-3. CONCLUSION: The results reveal wide variations in listing patients with ACLF in Europe despite favorable post-LT survival. Risk factors for mortality were identified, allowing a more precise prognostic assessment of ACLF patients for potential LT. LAY SUMMARY: Acute on chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation is an effective therapeutic option. This study has demonstrated that in Europe, referral and access to liver transplantation (LT) for patients with ACLF needs to be harmonized to avoid inequities. Post-LT survival for patients with ACLF was >80% after 1 year and some factors have been identified for selecting patients with favorable outcomes

Incidental Gallbladder Carcinoma Discovered after Laparoscopic Cholecystectomy: Identifying Patients Who will Benefit from Reoperation

Background: Despite an early radical reoperation, recurrence and poor survival are observed in up to 40% of patients with an incidentally discovered gallbladder carcinoma (I-GBC) after undergoing a laparoscopic cholecystectomy (LC). This study seeks to identify prognostic factors after re-I-GBC resection. Methods: A retrospective review of a prospectively maintained patient database with patients who were undergoing resection for I-GBC from January 1995 to March 2017 was performed. Prognostic factors for survival were assessed by multivariate Cox analysis. Results: There were 50 consecutive patients (median age 64 years; range 38–82) undergoing reoperation 45 ± 30 days after LC. Re-resection entailed a major hepatectomy in five patients (10%) and lymphadenectomy in all patients. Ninety-day morbidity and mortality were 22 and 2%, respectively. Lymph node (LN) involvement was present in 24 (48%) patients with a mean of 5.79 ± 14.4 LN+. Median overall survival was 40 months with 1-, 3-, 5- and 10-year survival rates of 80, 50, 41 and 36%, respectively. Independent risk factors for overall survival were T3 tumours (HR = 7.58; 95% confidence intervals (CI), 2.41–23.83.) and LN involvement (HR = 3.66; 95% CI, 1.42–9.45). Patients presenting with zero, one and two risk factors had 3-year survival rates of 85, 31 and 0%, respectively, and median overall survival of 80, 22 and 13 months, respectively (p < 0.0001). Conclusions: After I-GBC discovery following an LC, T3 tumours and tumours with LN+ are characterised by poor prognosis. The presence and the identification of these prognostic factors help identify patients in need of alternative perioperative treatments

COVID-19 in liver transplant candidates: wait-list outcomes and post-transplant course

Background: The impact of prior SARS-CoV-2 infection on patients on the waiting list for liver transplantation (LT) and on their post-LT course is presently unknown. Methods: Data from adult LT candidates with laboratory confirmed SARSCoV- 2 infection was collected across Europe and all consecutive patients with symptomatic COVID-19 were included in the analysis. Results: From February 21st to November 20th, 2020, 136 adult cases with laboratory-confirmed SARS-CoV-2 infection from 33 centers in 10 European countries were collected, with 113 having symptomatic COVID-19. Thirtythree (29.2%) were managed as outpatients, 80 (70.8%) required hospitalization including admission to the intensive care unit (28/80, 35%). Thirtyseven (37/113, 32.7%) patients died after a median of 18 (10-30) days, respiratory failure being the major cause (33/37, 89.2%). The 60-day mortality risk did not change between first (35.3%, 95% CI 23.9-50.0) and second wave (26.0%, 95% CI 16.2-40.2). Multivariable Cox regression analysis showed MELD score !15 (MELD15-19:HR 6.09 95%CI 2.01-18.44; MELD ! 20:HR 5.21, 95%CI 1.76-15.45) and dyspnea on presentation (HR:4.1, 95%CI 2.09-8.06) being the two negative independent factors for mortality. Twenty-six patient received a LT after a median time of 78.5 (IQR:44-102) days and 25 are alive after a median follow-up of 118 days (IQR:31-170). Conclusions: Mortality of LT candidates with symptomatic COVID-19 was high (32.7%) peaking at 45% in decompensated cirrhotic with MELD > 15 and did not significantly differ between the 2 waves of the pandemic, respiratory failure being the major cause of death thus supporting high priority for vaccination. Prior SARS-CoV-2 infection did not affect early post-transplant survival (96%).

Republication de: recommandations formalisées d'experts. Prise en charge de la patiente avec une pré-éclampsie sévère–RFE communes Société française d'anesthésie-réanimation (SFAR)–Collège national des gynécologues et obstétriciens français (CGNOF)

International audienceObjective: To provide national guidelines for the management of women with severe preeclampsia. Design: A consensus committee of 26 experts was formed. A formal conflict of interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Methods: The last SFAR and CNGOF guidelines on the management of women with severe preeclampsia was published in 2009. The literature is now sufficient for an update. The aim of this expert panel guidelines is to evaluate the impact of different aspects of the management of women with severe preeclampsia on maternal and neonatal morbidities separately. The experts studied questions within 7 domains. Each question was formulated according to the PICO (Patients Intervention Comparison Outcome) model and the evidence profiles were produced. An extensive literature review and recommendations were carried out and analyzed according to the GRADE® methodology. Results: The SFAR/CNGOF experts panel provided 25 recommendations: 8 have a high level of evidence (GRADE 1±), 9 have a moderate level of evidence (GRADE 2±), and for 7 recommendations, the GRADE method could not be applied, resulting in expert opinions. No recommendation was provided for 3 questions. After one scoring round, strong agreement was reached between the experts for all the recommendations. Conclusions: There was strong agreement among experts who made 25 recommendations to improve practices for the management of women with severe preeclampsia