Publications by authors named "Jean Hardwigsen"

62 Publications

The white test for intraoperative screening of bile leakage: a potential trigger factor for acute pancreatitis after liver resection-a case series.

BMC Surg 2021 Oct 2;21(1):356. Epub 2021 Oct 2.

Department of Digestive Surgery and Liver Transplantation, Hôpital la Timone, 264 rue Saint-Pierre, 13385, Marseille Cedex 05, France.

Background: Acute pancreatitis after liver resection is a rare but serious complication, and few cases have been described in the literature. Extended lymphadenectomy, and long ischemia due to the Pringle maneuver could be responsible of post-liver resection acute pancreatitis, but the exact causes of AP after hepatectomy remain unclear.

Cases Presentation: We report here three cases of AP after hepatectomy and we strongly hypothesize that this is due to the bile leakage white test. 502 hepatectomy were performed at our center and 3 patients (0.6%) experienced acute pancreatitis after LR and all of these three patients underwent the white test at the end of the liver resection. None underwent additionally lymphadenectomy to the liver resection. All patient had a white-test during the liver surgery. We identified distal implantation of the cystic duct in these three patients as a potential cause for acute pancreatitis.

Conclusion: The white test is useful for detection of bile leakage after liver resection, but we do not recommend a systematic use after LR, because severe acute pancreatitis can be lethal for the patient, especially in case of distal cystic implantation which may facilitate reflux in the main pancreatic duct.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12893-021-01354-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487543PMC
October 2021

Peri-operative risk factors of chronic kidney disease after liver transplantation.

J Nephrol 2021 Aug 23. Epub 2021 Aug 23.

Department of Digestive Surgery and Liver Transplantation, Hôpital la Timone, 264 Rue Saint-Pierre, 13385, Marseille Cedex 05, France.

Background: Chronic kidney disease (CKD) is a frequent long-term complication after liver transplantation (LT) and is associated with poor long-term survival. The aim of our study was to identify the risk factors of developing post-transplant CKD at 1 year, during the pre-operative, peri-operative, and post-LT phases.

Methods: All consecutive patients who underwent primary LT between July 2013 and February 2018 were analyzed. To assess the impact of peri- and post-operative factors on renal function at 1 year we performed a propensity score matching on gender, age of the recipient, Model for End-Stage Liver Disease (MELD) score, etiology of the hepatic disease, and estimated Glomerular Filtration Rate (eGFR) at baseline.

Results: Among the 245 patients who underwent LT, 215 had available data at one year (Y1), and 46% of them had CKD. Eighty-three patients in the CKD group and 83 in the normal renal function group were then matched. The median follow-up was 35 months (27-77). Patients with CKD at Y1 had a decreased 5-year survival compared to patients with normal renal function at one year: figures were 62% and 90%, respectively, p = 0.001. The independent predictors of CKD at Y1 were major complications (OR = 2.2, 95% CI [1.2-4.2]), p = 0.015, intensive care unit (ICU) stay > 5 days (OR = 2.2, 95% CI [1.3-5.1]), p = 0.046, ICU serum lactate level at 24 h ≥ 2.5 mmol/L (OR = 3.8 95% CI [1.1-8]), p = 0.034, need for post-LT renal replacement therapy (OR = 6.4 95% CI [1.4-25]), and MELD score ≥ 20 (OR = 2.1 95% CI [1.1-3.9]), p = 0.019.

Conclusions: The peri-operative period has a major impact on CKD incidence. Early recognition of patients at high risk of CKD may be critical for implementation of nephroprotective measures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40620-021-01127-6DOI Listing
August 2021

Oncological relevance of major hepatectomy with inferior vena cava resection for intrahepatic cholangiocarcinoma.

HPB (Oxford) 2021 Sep 24;23(9):1439-1447. Epub 2021 Feb 24.

Department of General Surgery and Liver Transplantation, La Timone Hospital, Aix Marseille University, Marseille, France.

Background: This study aimed to investigate the short- and long-terms outcomes of patients undergoing major hepatectomy (MH) with inferior vena cava (IVC) resection for intrahepatic cholangiocarcinoma (ICC).

Methods: Data from all patients who underwent MH for ICC with or without IVC resection between 2010 and 2018 were analysed retrospectively. Postoperative outcomes, overall survival (OS), and recurrence-free survival (RFS) were compared in the whole population. A propensity score matching (PSM) analysis and an inverse probability weighting analysis (IPW) were performed to assess the influence of IVC resection on short- and long-terms outcomes.

Results: Among the 78 patients who underwent MH, 20 had IVC resection (IVC patients). Overall, the mortality and severe complication rate were 8% and 20%, respectively. IVC patients required more extended hepatectomies (p = 0.001) and had increased rates of transfusions (p = 0.001), however they did not experience increased postoperative morbidity, even after PSM. The 1-, 3- and 5-years OS and DFS were 78%, 45%, and 32% and 48%, 20%, and 16%, respectively. IVC was not associated with decreased OS (p = 0.52) and/or RFS (p = 0.85), even after IPW.

Conclusion: MH with IVC resection for ICC seems to provide acceptable short- and long-term results in a selected population of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hpb.2021.02.007DOI Listing
September 2021

Risk factors of de novo malignancies after liver transplantation: a French national study on 11004 adult patients.

Clin Res Hepatol Gastroenterol 2021 Jul 11;45(4):101514. Epub 2021 Mar 11.

Hôpital Jean Minjoz, Service d'Hépatologie et Soins Intensifs Digestifs, Besançon, France.

Background: After liver transplantation (LT),de novo malignancies are one of the leading causes of late mortality. The aim of the present retrospective study was to identify the risk factors of de novo malignancies in a large cohort of LT recipients in France, using Fine and Gray competing risks regression analysis.

Methods: The study population consisted in 11004 adults transplanted between 2000 and 2013, who had no history of pre-transplant malignancy, except primary liver tumor. A Cox model adapted to the identification of prognostic factors (competitive risks) was used.

Results: From the entire cohort, one (or more)de novo malignancy was reported in 1480 L T recipients (13.45%). The probability to develop a de novo malignancy after LT was 2.07% at 1 year, 13.30% at 5 years, and 28.01% at 10 years. Of the known reported malignancies, the most common malignancies were hematological malignancy (22.36%), non-melanoma skin cancer (19.53%) and lung cancer (12.36%). According to Fine and Gray competing risks regression multivariate analysis, were significant risk factors for post-LT de novo malignancy: recipient age (Subdistribution Hazard Ratio (SHR) = 1.03 95%CI 1.03-1.04), male gender (SHR = 1.45 95%CI 1.27-1.67), non-living donor (SHR = 1.67 95%CI 1.14-2.38), a first LT (SHR = 1.35 95%CI 1.09-1.69) and the type of initial liver disease (alcohol-related liver disease (SHR = 1.63 95%CI 1.22-2.17), primary sclerosing cholangitis (SHR = 1.98 95%CI 1.34-2.91), and primary liver tumor (SHR = 1.88 95%CI 1.41-2.54)). Initial immunosuppressive regimen had no significant impact.

Conclusion: The present study confirms that LT recipient characteristics are associated with the risk ofde novo malignancy and this underlines the need for personalized screening in order to improve survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinre.2020.07.019DOI Listing
July 2021

Long-term abdominal wall benefits of the laparoscopic approach in liver left lateral sectionectomy: a multicenter comparative study.

Surg Endosc 2021 Sep 28;35(9):5034-5042. Epub 2020 Sep 28.

Department of General Surgery and Liver Transplantation, Hôpital de La Croix-Rousse, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, 103 Grande Rue de la Croix-Rousse, 69317, Lyon Cedex 04, France.

Background: Laparoscopy is nowadays considered as the standard approach for hepatic left lateral sectionectomy (LLS), but its value in the prevention of incisional hernia (IH) has not been demonstrated.

Methods: Between 2012 and 2017, patients undergoing laparoscopic (LLLS) or open LLS (OLLS) in 8 centers were compared. Patients undergoing a simultaneous major abdominal procedure were excluded. The incidence of IH was assessed clinically and morphologically on computed tomography (CT) using inverse probability of treatment weighting (IPTW) and multivariable regression analysis.

Results: After IPTW, 84 LLLS were compared to 48 OLLS. Compared to OLLS, LLLS patients had reduced blood loss (100 [IQR: 50-200] ml vs. 150 [IQR: 50-415] ml, p = 0.023) and shorter median hospital stay (5 [IQR: 4-7] days vs. 7 [6-9] days, p < 0.001), but experienced similar rate of postoperative complications (mean comprehensive complication index: 12 ± 19 after OLLS versus 13 ± 20 after LLLS, p = 0.968). Long-term radiological screening was performed with a median follow-up of 27.4 (12.1-44.9) months. There was no difference between the two groups in terms of clinically relevant IH (10.7% [n = 9] after LLLS, 8.3% [n = 4] after OLLS, p = 0.768). The rate of IH detected on computed tomography was lower after LLLS than after OLLS (11.9% [n = 10] versus 29.2% [n = 14], p = 0.013). On multivariable analysis, the laparoscopic approach was the only independent factor influencing the risk of morphological IH (OR = 0.290 [95% CI: 0.094-0.891], p = 0.031). The 2 preferential sites for specimen extraction after LLLS were Pfannenstiel and midline incisions, with rates of IH across the extraction site of 2.3% [n = 1/44] and 23.8% [n = 5/21], respectively (p = 0.011).

Conclusion: The laparoscopic approach for LLS decreases the risk of long-term IH as evidenced on morphological examinations, with limited clinical impact. Pfannenstiel's incision should be preferred to midline incision for specimen extraction after LLLS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00464-020-07985-8DOI Listing
September 2021

Liver transplantation for hepatocellular carcinoma after down staging with sorafenib: a monocentric case-matched series.

J Gastrointestin Liver Dis 2020 03 13;29(1):120-121. Epub 2020 Mar 13.

Aix Marseille University, Department of General Surgery and Liver Transplantation, Hopital la Timone, Marseille, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15403/jgld-748DOI Listing
March 2020

Closed Cyst Resection for Liver Hydatid Disease: a New Standard.

J Gastrointest Surg 2021 02 10;25(2):436-446. Epub 2020 Feb 10.

Department of Surgery and Liver Transplantation, Hôpital de la Timone, Marseille, France.

Background: Although radical resections are recommended for the surgical management of liver hydatid disease (LHD), whether closed (CCR) or opened (OCR) cyst resections should be performed remains unclear. The aim of this study was to compare the postoperative and long-term outcomes of CCR and OCR for primary and recurrent LHD.

Materials And Methods: Medical charts of patients who underwent surgery at a single centre were retrospectively reviewed and compared with respect to major postoperative complications and recurrence rates.

Results: Seventy-nine CCRs and 37 OCRs were included. The major morbidity rates were 19% and 5% in the OCR and CCR groups, respectively (P = 0.036). In multivariate analysis, OCR (P = 0.030, OR = 5.37) and the operative time (P < 0.001, OR = 18.88) were the only independent predictors of major complications. The 5-year and 10-year recurrence rates were both 0% in the CCR group compared to 18% and 27%, respectively, in the OCR group (P < 0.001). The mean time to recurrence was 10.5 (± 8) years.

Discussion: Closed cyst resection for LHD is a safe and effective approach with a low risk of recurrence. Considering that recurrence could appear more than 10 years after surgery, follow-up of patients should be adapted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11605-019-04509-1DOI Listing
February 2021

Early Switch From Tacrolimus to Everolimus After Liver Transplantation: Outcomes at 2 Years.

Liver Transpl 2019 12;25(12):1822-1832

Hôpital Pitié Salpêtrière, AP-HP, Paris, France.

The observational CERTITUDE study follows liver transplant patients who completed the SIMCER trial. SIMCER randomized patients at month 1 after transplant to everolimus (EVR) with stepwise tacrolimus (TAC) withdrawal or to standard TAC, both with basiliximab induction and mycophenolic acid ± steroids. After completing SIMCER at 6 months after transplant, 65 EVR-treated patients and 78 TAC-treated patients entered CERTITUDE. At month 24 after transplant, 34/65 (52.3%) EVR-treated patients remained calcineurin inhibitor (CNI) free. Mean estimated glomerular filtration rate (eGFR) was significantly higher with EVR versus TAC during months 3-12. At month 24, eGFR values were 83.6 versus 75.3 mL/minute/1.73 m , respectively (P = 0.90) and adjusted mean change in eGFR from randomization was -8.0 versus -13.5 mL/minute/1.73 m (P = 0.15). At month 24, 45.9%, 31.1%, and 23.0% of EVR-treated patients had chronic kidney disease stages 1, 2, and 3, respectively, versus 25.7%, 45.7%, and 28.6% of TAC-treated patients (P = 0.05). Treated biopsy-proven acute rejection affected 4 EVR-treated patients and 2 TAC patients during months 6-24. Adverse events led to study discontinuation in 15.4% and 7.7% of EVR-treated and TAC-treated patients, respectively. Grade 3 or 4 hematological events were rare in both groups. A CNI-free EVR-based maintenance regimen appears feasible in approximately half of liver transplant patients. It preserves renal function effectively with good efficacy without compromising safety or hematological tolerance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lt.25664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383505PMC
December 2019

The technique and outcomes of central hepatectomy by the Glissonian suprahilar approach.

Eur J Surg Oncol 2019 Dec 12;45(12):2369-2374. Epub 2019 Sep 12.

Department of General Surgery and Liver Transplantation, Hôpital de la Timone, Marseille, France; Aix-Marseille University, 27 boulevard Jean Moulin, 13385, Marseille, France.

Introduction: Central hepatectomy (CH) is technically challenging and seldom-used to treat centrally located tumors. However, CH is a parenchyma-sparing resection that may decrease the risk of postoperative liver failure. This retrospective study presents our technique of CH and assesses the outcomes.

Methods: All CH performed in our department over two decades (1997-2017) were identified. Indications and short-term outcomes were compared between the two decades. Long-term outcomes were assessed.

Results: Sixty-four patients underwent CH using a suprahilar approach for hepatocellular carcinoma (HCC: n = 30), metastasis (n = 23), intrahepatic cholangiocarcinoma (IHCCA: n = 9) or other diseases (n = 2). CH represented 6% of 1004 major hepatectomies, (7.4% (n = 35) before 2007 vs 5.4% (n = 29) after 2007). The mean operating time was 219 ± 56 min. A perioperative blood transfusion was required in 14 patients (22%). Intraoperative bile duct injuries occurred in 5 patients (8%), and they were repaired. One patient died postoperatively (1,5%). Ten patients (16%) experienced a major complication. Nine patients (14%) suffered from bile leakage, of which 6 healed spontaneously. Only one patient had low grade liver failure. The R0-resection rate was 69%. After 2007, there were no bile duct injuries (0/29 vs 5/35, p < 0.05), and the average hospital stay was shorter but not significantly (11 vs 14 days). Actuarial 5-year survival was 56% for HCC patients and 34% for those with colorectal metastasis CONCLUSIONS: CH is associated with significant biliary morbidity and may increase positive surgical margins. Nevertheless, it should be recommended in selected patients to avoid the risk of postoperative liver failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejso.2019.09.010DOI Listing
December 2019

An ordinal model to predict the risk of symptomatic liver failure in patients with cirrhosis undergoing hepatectomy.

J Hepatol 2019 11 14;71(5):920-929. Epub 2019 Jun 14.

Univ. Lille, CHU Lille, Service de Chirurgie Digestive et Transplantations, Lille, France; CNRS, UMR8161, F-59000 Lille, France. Electronic address:

Background & Aims: Selection criteria for hepatectomy in patients with cirrhosis are controversial. In this study we aimed to build prognostic models of symptomatic post-hepatectomy liver failure (PHLF) in patients with cirrhosis.

Methods: This was a cohort study of patients with histologically proven cirrhosis undergoing hepatectomy in 6 French tertiary care hepato-biliary-pancreatic centres. The primary endpoint was symptomatic (grade B or C) PHLF, according to the International Study Group of Liver Surgery's definition. Twenty-six preoperative and 5 intraoperative variables were considered. An ordered ordinal logistic regression model with proportional odds ratio was used with 3 classes: O/A (No PHLF or grade A PHLF), B (grade B PHLF) and C (grade C PHLF).

Results: Of the 343 patients included, the main indication was hepatocellular carcinoma (88%). Laparoscopic liver resection was performed in 112 patients. Three-month mortality was 5.25%. The observed grades of PHLF were: 0/A: 61%, B: 28%, C: 11%. Based on the results of univariate analyses, 3 preoperative variables (platelet count, liver remnant volume ratio and intent-to-treat laparoscopy) were retained in a preoperative model and 2 intraoperative variables (per protocol laparoscopy and intraoperative blood loss) were added to the latter in a postoperative model. The preoperative model estimated the probabilities of PHLF grades with acceptable discrimination (area under the receiver-operating characteristic curve [AUC] 0.73, B/C vs. 0/A; AUC 0.75, C vs. 0/A/B) and the performance of the postoperative model was even better (AUC 0.77, B/C vs. 0/A; AUC 0.81, C vs. 0/A/B; p <0.001).

Conclusions: By accurately predicting the risk of symptomatic PHLF in patients with cirrhosis, the preoperative model should be useful at the selection stage. Prediction can be adjusted at the end of surgery by also considering blood loss and conversion to laparotomy in a postoperative model, which might influence postoperative management.

Lay Summary: In patients with liver cirrhosis, the risk of a hepatectomy is difficult to appreciate. We propose a statistical tool to estimate this risk, preoperatively and immediately after surgery, using readily available parameters and on online calculator. This model could help to improve the selection of patients with the best risk-benefit profiles for hepatectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2019.06.003DOI Listing
November 2019

High-Dimensional Single-Cell Analysis Identifies Organ-Specific Signatures and Conserved NK Cell Subsets in Humans and Mice.

Immunity 2018 11 6;49(5):971-986.e5. Epub 2018 Nov 6.

Aix Marseille Univ, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Marseille, France; Immunology, Marseille Immunopole, Hôpital de la Timone, Assistance Publique des Hôpitaux de Marseille, France; Innate Pharma Research Laboratories, Innate Pharma, Marseille, France. Electronic address:

Natural killer (NK) cells are innate lymphoid cells (ILCs) involved in antimicrobial and antitumoral responses. Several NK cell subsets have been reported in humans and mice, but their heterogeneity across organs and species remains poorly characterized. We assessed the diversity of human and mouse NK cells by single-cell RNA sequencing on thousands of individual cells isolated from spleen and blood. Unbiased transcriptional clustering revealed two distinct signatures differentiating between splenic and blood NK cells. This analysis at single-cell resolution identified three subpopulations in mouse spleen and four in human spleen, and two subsets each in mouse and human blood. A comparison of transcriptomic profiles within and between species highlighted the similarity of the two major subsets, NK1 and NK2, across organs and species. This unbiased approach provides insight into the biology of NK cells and establishes a rationale for the translation of mouse studies to human physiology and disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.immuni.2018.09.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269138PMC
November 2018

Short-term outcomes after major hepatic resection in patients with cirrhosis: a 75-case unicentric western experience.

HPB (Oxford) 2019 03 16;21(3):352-360. Epub 2018 Aug 16.

Department of Digestive Surgery, Hôpital de la Timone, Marseille, France; Université Aix-Marseille, 27 Boulevard Jean Moulin, 13385, Marseille, France.

Background: The benefit of performing major hepatic resection (MHR) for hepatocellular carcinoma (HCC) in patients with cirrhosis remains controversial because of its high risk of posthepatectomy liver failure (PHLF). This study was conducted to assess the risk of MHR for HCC in patients with cirrhosis.

Methods: Patients with Child-Pugh A or B cirrhosis and HCC who underwent MHR from January 2000 to June 2014 were retrospectively identified. Risk factors for postoperative morbidity and mortality using univariate and multivariate analyses were evaluated.

Results: Seventy patients with Child-Pugh A (93%) and 5 (7%) with Child-Pugh B cirrhosis underwent MHR for HCC. Thirteen (17%) had Barcelona Clinic Liver Cancer (BCLC) stage A, 39 (50%) had BCLC B, and 23 (32%) had BCLC C disease. A perioperative blood transfusion was performed in 18 patients (24%). Ninety-day postoperative mortality was 9% (n=7). Major complications occurred in 16 patients (21%), including PHLF in 9 patients (12%). A multivariate analysis showed that perioperative blood transfusion was the main independent factor associated with mortality (OR= 6.5) and major morbidity (OR=10).

Conclusion: In selected patients with HCC and cirrhosis, MHR is feasible and has acceptable mortality, but careful perioperative management and limiting blood loss are required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hpb.2018.07.020DOI Listing
March 2019

Longterm Risk of Solid Organ De Novo Malignancies After Liver Transplantation: A French National Study on 11,226 Patients.

Liver Transpl 2018 10;24(10):1425-1436

Département d'Hépatologie et Transplantation Hépatique, Centre Hospitalier Universitaire Saint Eloi, Montpellier, France.

De novo malignancies are one of the major late complications and causes of death after liver transplantation (LT). Using extensive data from the French national Agence de la Biomédecine database, the present study aimed to quantify the risk of solid organ de novo malignancies (excluding nonmelanoma skin cancers) after LT. The incidence of de novo malignancies among all LT patients between 1993 and 2012 was compared with that of the French population, standardized on age, sex, and calendar period (standardized incidence ratio; SIR). Among the 11,226 LT patients included in the study, 1200 de novo malignancies were diagnosed (10.7%). The risk of death was approximately 2 times higher in patients with de novo malignancy (48.8% versus 24.3%). The SIR for all de novo solid organ malignancies was 2.20 (95% confidence interval [CI], 2.08-2.33). The risk was higher in men (SIR = 2.23; 95% CI, 2.09-2.38) and in patients transplanted for alcoholic liver disease (ALD; SIR = 2.89; 95% CI, 2.68-3.11). The cancers with the highest excess risk were laryngeal (SIR = 7.57; 95% CI, 5.97-9.48), esophageal (SIR = 4.76; 95% CI, 3.56-6.24), lung (SIR = 2.56; 95% CI, 2.21-2.95), and lip-mouth-pharynx (SIR = 2.20; 95% CI, 1.72-2.77). In conclusion, LT recipients have an increased risk of de novo solid organ malignancies, and this is strongly related to ALD as a primary indication for LT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lt.25310DOI Listing
October 2018

Authors' Reply: Postoperative Bleeding After Laparoscopic Pancreaticoduodenectomy: The Achilles' Heel?

World J Surg 2018 09;42(9):3060-3061

Department of Digestive Disease, Institut Mutualiste Montsouris, Université Paris-Descartes, 42 Boulevard Jourdan, 75014, Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00268-018-4583-0DOI Listing
September 2018

Portal vein stenosis preconditioning of living donor liver in swine: early mechanisms of liver regeneration and gain of hepatic functional mass.

Am J Physiol Gastrointest Liver Physiol 2018 07 22;315(1):G117-G125. Epub 2018 Feb 22.

Experimental Interventional Imaging Laboratory EA-4264, European Centre for Medical Imaging Research, Aix-Marseille University , Marseille , France.

To reduce the morbidity and mortality risk for the donor in living donor liver transplantation (LDLT), we previously identified 20% left portal vein (LPV) stenosis as an effective preconditioning method to induce cell proliferation in the contralateral lobe without downstream ipsilateral atrophy. In this study, we report the pathways involved in the first hours after preconditioning and investigate the changes in liver volume and function. Fourteen pigs were used this study. Five pigs were used to study the genetic, cellular and molecular mechanisms set up in the early hours following the establishment of our preconditioning. The remaining nine pigs were equally divided into three groups: sham-operated animals, 20% LPV stenosis, and 100% LPV stenosis. Volumetric scanning and 99 mTc-Mebrofenin hepatobiliary scintigraphy were performed before preconditioning and 14 days after to study morphological and functional changes in the liver. We demonstrated that liver regeneration triggered by 20% LPV stenosis in the contralateral lobe involves TNF-α, IL-6, and inducible nitric oxide synthase 2 by means of STAT3 and hepatocyte growth factor. We confirmed that our preconditioning was responsible for an increase in the total liver volume. Finally, we demonstrated that this volumetric gain was associated with an increase in hepatic functional capacity. NEW & NOTEWORTHY We describe a new preconditioning method for major hepatectomy that is applicable to hepatectomy for donation. We identified 20% left portal vein stenosis as effective preconditioning that is capable of inducing cell proliferation in the contralateral lobe without the downstream ipsilateral atrophy. In this study, we report the pathways involved in the first hours following preconditioning, and we confirm that 20% left portal vein stenosis is responsible for an increase in the functional capacity and total liver volume in a porcine model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpgi.00390.2017DOI Listing
July 2018

Postoperative Bleeding After Laparoscopic Pancreaticoduodenectomy: the Achilles' Heel?

World J Surg 2018 04;42(4):1138-1146

Department of Digestive Disease, Institut Mutualiste Montsouris, Université Paris-Descartes, 42 Boulevard Jourdan, 75014, Paris, France.

Background: Laparoscopic pancreaticoduodenectomy (LPD) is technically demanding, and its impact on postoperative outcomes remains controversial.

Objective: To compare short-term outcomes between laparoscopic versus open pancreaticoduodenectomy (OPD) in order to assess the safety of LPD.

Methods: From 2002 to 2014, all consecutive patients undergoing LPD or OPD at two tertiary centers were retrospectively analyzed. Patients were matched for demographics, comorbidities, pathological diagnosis, and pancreatic texture. Results for the two groups were compared for postoperative outcomes.

Results: Sixty-five LPD were performed and compared to 290 OPD. In the whole population, postoperative pancreatic fistula (PF) was higher in the LPD group, but the proportion of ampullary adénocarcinoma (25 vs. 10%, p = 0.004) and soft pancreatic parenchyma (52 vs. 38%, p = 0.001) were higher in the LDP group. After matching (n = 65), LPD was associated with longer operative time (429 vs. 328 min, p < 0.001) and lower blood loss (370 vs. 515 mL, p = 0.047). The PF rate and its severity were similar (33 vs. 27%, p = 0.439, p = 0.083) in the two groups. However, both complications (78 vs. 71%, p = 0.030) and major complications (40 vs. 23%, p = 0.033) were more frequent in the LPD group. LPD patients experience more postoperative bleeding (21 vs. 14%, p = 0.025) compared to their open counterparts. In multivariate analysis, perioperative transfusion (OR = 5 IC 95% (1.5-16), p = 0.008), soft pancreas (OR = 2.5 IC 95% (1.4-4.6), p = 0.001), and ampullary adenocarcinoma (OR = 2.6 IC 95% (1.2-5.6), p = 0.015) were independent risks factors of major complications.

Conclusion: Despite lower blood loss and lower intraoperative transfusion, LPD leads to higher rate of postoperative complications with postoperative bleeding in particular.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00268-017-4269-zDOI Listing
April 2018

Comparison of different feeding regimes after pancreatoduodenectomy - a retrospective cohort analysis.

Nutr J 2017 Jul 4;16(1):42. Epub 2017 Jul 4.

Department of Digestive Surgery, Hôpital Nord, Aix-Marseille University, Chemin des Bourrely 13915, cedex 20, Marseille, France.

Background: Delayed gastric emptying (DGE) is the most frequent pancreatic specific complication (PSC) after pancreaticoduodenectomy (PD). Several gastric decompression systems exist to manage DGE. Patients with a pancreatic tumor require prolonged nutrition; however, controversies exist concerning nutrition protocol after PD. The aim of the study was to assess the safety and efficacy of nasogastric (NG), gastrostomy (GT), and gastrojejunostomy (GJ) tubes with different feeding systems on postoperative courses.

Methods: Between January 2013 and March 2016, 86 patients underwent PD with pancreaticogastrostomy. Patients were divided into three groups: GJ group with enteral nutrition (EN, n = 12, 14%), NG (n = 31, 36%) and GT groups (n = 43, 50%), both with total parenteral nutrition (TPN).

Results: Patients in the GJ (n = 9, 75%) and GT (n = 18, 42%) groups had an American Society of Anesthesiologists (ASA) score of 3 more often than those in the NG group (n = 5, 16%, p ≤ 0.01). Multivariate analysis identified the GT tube with TPN as an independent risk factor of severe morbidity (p = 0.02) and DGE (p < 0.01). An ASA score of 3, jaundice, common pancreatic duct size ≤3 mm and soft pancreatic gland texture (p < 0.05) were found as independent risk factors of PSCs. Use of a GJ tube with EN, GT tube with TPN, jaundice, and PSCs were identified as independent risk factors for greater postoperative length of hospital stay (p < 0.01). Mean global hospitalization cost did not differ between groups.

Conclusion: GT tube insertion with TPN was associated with increased severe postoperative morbidity and DGE and should not be recommended. EN through a GJ tube after PD is feasible but does not have clear advantages on postoperative courses compared to an NG tube.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12937-017-0265-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496601PMC
July 2017

Short-term outcomes of laparoscopic vs. open liver resection for hepatocellular adenoma: a multicenter propensity score adjustment analysis by the AFC-HCA-2013 study group.

Surg Endosc 2017 10 9;31(10):4136-4144. Epub 2017 Mar 9.

Department of Digestive, Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Henri Mondor University Hospital, Paris Est University, APHP, 51 Avenue du Maréchal de Lattre de Tassigny, 94010, Creteil, France.

Background: Patients with hepatocellular adenomas are, in selected cases, candidates for liver resection, which can be approached via laparoscopy or laparotomy. The present study aimed to investigate the effects of the surgical approach on the postoperative morbidities of both minor and major liver resections.

Methods: In this multi-institutional study, all patients who underwent open or laparoscopic hepatectomies for hepatocellular adenomas between 1989 and 2013 in 27 European centers were retrospectively reviewed. A multiple imputation model was constructed to manage missing variables. Comparisons of both the overall rate and the types of complications between open and laparoscopic hepatectomy were performed after propensity score adjustment (via the standardized mortality ratio weighting method) on the factors that influenced the choice of the surgical approach.

Results: The laparoscopic approach was selected in 208 (38%) of the 533 included patients. There were 194 (93%) women. The median age was 38.9 years. After the application of multiple imputation, 208 patients who underwent laparoscopic operations were compared with 216 patients who underwent laparotomic operations. After adjustment, there were 20 (9.6%) major liver resections in the laparoscopy group and 17 (7.9%) in the open group. The conversion rate was 6.3%. The two surgical approaches exhibited similar postoperative morbidity rates and severities. Laparoscopic resection was associated with significantly less blood loss (93 vs. 196 ml, p < 0.001), a less frequent need for pedicle clamping (21 vs. 40%, p = 0.002), a reduced need for transfusion (8 vs. 24 red blood cells units, p < 0.001), and a shorter hospital stay (5 vs. 7 days, p < 0.001). The mortality was nil.

Conclusions: Laparoscopy can achieve short-term outcomes similar to those of open surgery for hepatocellular adenomas and has the additional benefits of a reduced blood loss, need for transfusion, and a shorter hospital stay.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00464-017-5466-4DOI Listing
October 2017

Intensive Early Rehabilitation in the Intensive Care Unit for Liver Transplant Recipients: A Randomized Controlled Trial.

Arch Phys Med Rehabil 2017 08 6;98(8):1518-1525. Epub 2017 Mar 6.

Aix-Marseille University, Assistance Publique des Hôpitaux de Marseille, Department of General Surgery and Liver Transplantation, Hôpital de la Conception, Marseille, France. Electronic address:

Objective: To validate the feasibility and tolerance of an intensive rehabilitation protocol initiated during the postoperative period in an intensive care unit (ICU) in liver transplant recipients.

Design: Prospective randomized study.

Setting: ICU.

Participants: Liver transplant recipients over a period of 1 year (N=40).

Interventions: The "usual treatment group" (n=20), which benefited from the usual treatment applied in the ICU (based on physician prescription for the physiotherapist, with one session a day), and the experimental group (n=20), which followed a protocol of early and intensive rehabilitation (based on a written protocol validated by physicians and an evaluation by physiotherapist, with 2 sessions a day), were compared.

Main Outcome Measures: Our primary aims were tolerance, assessed from the number of adverse events during rehabilitation sessions, and feasibility, assessed from the number of sessions discontinued.

Results: The results revealed a small percentage of adverse events (1.5% in the usual treatment group vs 1.06% in the experimental group) that were considered to be of low intensity. Patients in the experimental group sat on the edge of their beds sooner (2.6 vs 9.7d; P=.048) and their intestinal transit resumed earlier (5.6 vs 3.7d; P=.015) than patients in the usual treatment group. There was no significant difference between the 2 arms regarding length of stay (LOS), despite a decrease in duration in the experimental group.

Conclusions: The introduction of an intensive early rehabilitation program for liver transplant recipients was well tolerated and feasible in the ICU. We noted that the different activities proposed were introduced sooner in the experimental group. Moreover, there is a tendency to decreased LOS in the ICU for the experimental group. These results now need to be confirmed by studies on a larger scale.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.apmr.2017.01.028DOI Listing
August 2017

NIACE score for hepatocellular carcinoma patients treated by surgery or transarterial chemoembolization.

Eur J Gastroenterol Hepatol 2017 Jun;29(6):706-715

aDepartment of Hepato-Gastroenterology bDepartment of Hepatobiliary Surgery cDepartment of Radiology, Hôpital Saint-Joseph dAlphaBio Laboratory eDepartment of Hepato-Gastroenterology and Digestive Oncology, Institut Paoli-Calmette fDepartment of Hepatobiliary Surgery, Centre Hospitalo-Universitaire Timone, Marseille gDepartment of Hepato-Gastroenterology, Centre Hospitalo-Universitaire de Nancy hINSERM U954, Université de Lorraine, CHU de Nancy, Vandoeuvre les Nancy, France.

Background And Aims: Hepatocellular carcinoma (HCC) prognostic scores could be useful in addition to the Barcelona Clinic Liver Cancer (BCLC) system to clarify patient prognosis and guide treatment decision. The NIACE (tumor Nodularity, Infiltrative nature of the tumor, serum Alpha-fetoprotein level, Child-Pugh stage, ECOG performance status) score distinguishes different prognosis groups among BCLC A, B, and C HCC patients. Our aims are to evaluate the NIACE score and its additive value in two HCC cohorts treated either by surgery or by chemoembolization, and then according to the BCLC recommendations.

Patients And Methods: This was a retrospective multicenter study with two BCLC A, B, and C HCC cohorts treated either by surgery (n=207) or by chemoembolization (n=168) carried out between 2008 and 2013. We studied survival time according to the baseline NIACE score and compared it with the Cancer of the Liver Italian Program score and the BCLC system.

Results: The NIACE score differentiates between subgroups of patients with different prognosis within each BCLC class. Among BCLC A patients treated by surgery and BCLC B patients treated by chemoembolization, the NIACE score differentiates between two subgroups with a significant difference in survival time: 68 (55-81) months versus 35 (21-56) months (P=0.0004) and 20 (17-24) months versus 13 (7-17) months (P=0.0008), respectively. Among those subgroups, the NIACE score has a significantly better prognostic value than the BCLC system or the Cancer of the Liver Italian Program score.

Conclusion: In this study, among HCC patients treated according to the BCLC recommendations, the NIACE score predicts more accurately than any other system the survival time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MEG.0000000000000852DOI Listing
June 2017

European experience of 573 liver resections for hepatocellular adenoma: a cross-sectional study by the AFC-HCA-2013 study group.

HPB (Oxford) 2016 09 22;18(9):748-55. Epub 2016 Jul 22.

Department of Surgery, Hôpital de la Timone, Marseille, France.

Background: Hepatocellular adenoma (HCA) is a benign hepatic lesion that may be complicated by bleeding and malignant transformation. The aim of the present study is to report on large series of liver resections for HCA and assess the incidence of hemorrhage and malignant transformation.

Methods: A retrospective cross-sectional study, from 27 European high-volume HPB units.

Results: 573 patients were analyzed. The female: male gender ratio was 8:2, mean age: 37 ± 10 years. Of the 84 (14%) patients whose initial presentation was hemorrhagic shock (Hemorrhagic HCAs), hemostatic intervention was urgently required in 25 (30%) patients. No patients died after intervention. Tumor size was >5 cm in 74% in hemorrhagic HCAs and 64% in non-hemorrhagic HCAs (p < 0.001). In non-hemorrhagic HCAs (n = 489), 5% presented with malignant transformation. Male status and tumor size >10 cm were the two predictive factors. Liver resections included major hepatectomy in 25% and a laparoscopic approach in 37% of the patients. In non-hemorrhagic HCAs, there was no mortality and major complications occurred in 9% of patients.

Discussion: Liver resection for HCA is safe. Presentation with hemorrhage was associated with larger tumor size. In males with a HCA >10 cm, a HCC should be suspected. In such situation, a preoperative biopsy is preferable and an oncological liver resection should be considered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hpb.2016.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011084PMC
September 2016

Usefulness of staging systems and prognostic scores for hepatocellular carcinoma treatments.

World J Hepatol 2016 Jun;8(17):703-15

Xavier Adhoute, Paul Castellani, Hervé Perrier, Marc Bourlière, Department of Hepato-Gastroenterology, Hôpital Saint-Joseph, 13008 Marseille, France.

Therapeutic management of hepatocellular carcinoma (HCC) is quite complex owing to the underlying cirrhosis and portal vein hypertension. Different scores or classification systems based on liver function and tumoral stages have been published in the recent years. If none of them is currently "universally" recognized, the Barcelona Clinic Liver Cancer (BCLC) staging system has become the reference classification system in Western countries. Based on a robust treatment algorithm associated with stage stratification, it relies on a high level of evidence. However, BCLC stage B and C HCC include a broad spectrum of tumors but are only matched with a single therapeutic option. Some experts have thus suggested to extend the indications for surgery or for transarterial chemoembolization. In clinical practice, many patients are already treated beyond the scope of recommendations. Additional alternative prognostic scores that could be applied to any therapeutic modality have been recently proposed. They could represent complementary tools to the BCLC staging system and improve the stratification of HCC patients enrolled in clinical trials, as illustrated by the NIACE score. Prospective studies are needed to compare these scores and refine their role in the decision making process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4254/wjh.v8.i17.703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911504PMC
June 2016

Cold Preservation of Human Adult Hepatocytes for Liver Cell Therapy.

Cell Transplant 2015 23;24(12):2541-55. Epub 2015 Jan 23.

INSERM, U1040, Institut de Recherche en Biothérapie, F-34295 Montpellier, France.

Hepatocyte transplantation is a promising alternative therapy for the treatment of hepatic failure, hepatocellular deficiency, and genetic metabolic disorders. Hypothermic preservation of isolated human hepatocytes is potentially a simple and convenient strategy to provide on-demand hepatocytes in sufficient quantity and of the quality required for biotherapy. In this study, first we assessed how cold storage in three clinically safe preservative solutions (UW, HTS-FRS, and IGL-1) affects the viability and in vitro functionality of human hepatocytes. Then we evaluated whether such cold-preserved human hepatocytes could engraft and repopulate damaged livers in a mouse model of liver failure. Human hepatocytes showed comparable viabilities after cold preservation in the three solutions. The ability of fresh and cold-stored hepatocytes to attach to a collagen substratum and to synthesize and secrete albumin, coagulation factor VII, and urea in the medium after 3 days in culture was also equally preserved. Cold-stored hepatocytes were then transplanted in the spleen of immunodeficient mice previously infected with adenoviruses containing a thymidine kinase construct and treated with a single dose of ganciclovir to induce liver injury. Engraftment and liver repopulation were monitored over time by measuring the blood level of human albumin and by assessing the expression of specific human hepatic mRNAs and proteins in the recipient livers by RT-PCR and immunohistochemistry, respectively. Our findings show that cold-stored human hepatocytes in IGL-1 and HTS-FRS preservative solutions can survive, engraft, and proliferate in a damaged mouse liver. These results demonstrate the usefulness of human hepatocyte hypothermic preservation for cell transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3727/096368915X687020DOI Listing
October 2016

Germinal center reentries of BCL2-overexpressing B cells drive follicular lymphoma progression.

J Clin Invest 2014 Dec 10;124(12):5337-51. Epub 2014 Nov 10.

It has recently been demonstrated that memory B cells can reenter and reengage germinal center (GC) reactions, opening the possibility that multi-hit lymphomagenesis gradually occurs throughout life during successive immunological challenges. Here, we investigated this scenario in follicular lymphoma (FL), an indolent GC-derived malignancy. We developed a mouse model that recapitulates the FL hallmark t(14;18) translocation, which results in constitutive activation of antiapoptotic protein B cell lymphoma 2 (BCL2) in a subset of B cells, and applied a combination of molecular and immunofluorescence approaches to track normal and t(14;18)(+) memory B cells in human and BCL2-overexpressing B cells in murine lymphoid tissues. BCL2-overexpressing B cells required multiple GC transits before acquiring FL-associated developmental arrest and presenting as GC B cells with constitutive activation-induced cytidine deaminase (AID) mutator activity. Moreover, multiple reentries into the GC were necessary for the progression to advanced precursor stages of FL. Together, our results demonstrate that protracted subversion of immune dynamics contributes to early dissemination and progression of t(14;18)(+) precursors and shapes the systemic presentation of FL patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI72415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348942PMC
December 2014

Transjugular intrahepatic porto-systemic shunt is a risk factor for liver dysplasia but not hepatocellular carcinoma: a retrospective study of explanted livers.

Dig Liver Dis 2015 Jan 11;47(1):57-61. Epub 2014 Oct 11.

Department of Hepato-Gastroenterology, Hôpital de la Conception, Marseille, France; UMR 911, Université de la Méditerranée, Marseille, France.

Background: Conflicting data exist regarding the risk for hepatocellular carcinoma after transjugular intrahepatic porto-systemic shunt (TIPS) insertion in cirrhotic patients.

Methods: We retrospectively analysed histopathological data from 214 patients who were transplanted in our Institution including 68 patients who underwent TIPS placement before transplantation. Pathological lesions from explanted livers, including incidental hepatocellular carcinoma, small cell dysplasia and large cell dysplasia were recorded.

Results: Pathological lesions were found in 36.4% of explanted livers. TIPS insertion was an independent risk factor for pathological lesion (HR = 2.11, p < 0.05), concurrently with age (HR = 1.10 per year, p < 0.001) and viral aetiology of cirrhosis (HR = 3.05, p < 0.001). When considering the different type of lesions, TIPS insertion was not associated with an increased risk for hepatocellular carcinoma but was an independent risk factor for liver dysplasia (HR = 2.15, p = 0.042).

Conclusion: Although a direct relationship between TIPS insertion and hepatocellular carcinoma risk was not demonstrated in this study, the increased frequency of liver dysplasia observed in TIPS-bearing explanted livers deserves further prospective investigations with adequate follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dld.2014.09.009DOI Listing
January 2015

Further characterization of HDAC and SIRT gene expression patterns in pancreatic cancer and their relation to disease outcome.

PLoS One 2014 2;9(9):e108520. Epub 2014 Oct 2.

Aix-Marseille University, CRO2, UMR_S 911, Marseille, France; INSERM UMR 911, Marseille, France.

Ductal adenocarcinoma of the pancreas is ranking 4 for patient' death from malignant disease in Western countries, with no satisfactory treatment. We re-examined more precisely the histone deacetylases (HDAC) and Sirtuin (SIRT) gene expression patterns in pancreatic cancer with more pancreatic tumors and normal tissues. We also examined the possible relationship between HDAC gene expression levels and long term disease outcome. Moreover, we have evaluated by using an in vitro model system of human pancreatic tumor cell line whether HDAC7 knockdown may affect the cell behavior. We analyzed 29 pancreatic adenocarcinoma (PA), 9 chronic pancreatitis (CP), 8 benign pancreatic (BP) and 11 normal pancreatic tissues. Concerning pancreatic adenocarcinoma, we were able to collect biopsies at the tumor periphery. To assess the possible involvement of HDAC7 in cell proliferation capacity, we have generated recombinant human Panc-1 tumor which underexpressed or overexpressed HDAC7. The expression of HDAC1,2,3,4,7 and Nur77 increased in PA samples at levels significantly higher than those observed in the CP group (p = 0.0160; 0.0114; 0.0227; 0.0440; 0.0136; 0.0004, respectively). The expression of HDAC7, was significantly greater in the PA compared with BP tissue samples (p = 0.05). Mean mRNA transcription levels of PA for HDAC7 and HDAC2 were higher when compared to their counterpart biopsies taken at the tumor periphery (p = 0.0346, 0.0053, respectively). Moreover, the data obtained using confocal microscopy and a quantitative method of immunofluorescence staining strongly support the HDAC7 overexpression in PA surgical specimens. The number of deaths and recurrences at the end of follow up were significantly greater in patients with overexpression of HDAC7. Interestingly, the rate of growth was significantly reduced in the case of cell carrying shRNA construct targeting HDAC7 encoding gene when compared to the parental Panc-1 tumor cells (p = 0.0015) at 48 h and 96 h (p = 0.0021). This study strongly support the notion that HDAC7play a role in pancreatic adenocarcinoma progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0108520PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183483PMC
June 2015

Surgical management of advanced pancreatic neuroendocrine tumors: short-term and long-term results from an international multi-institutional study.

Ann Surg Oncol 2015 Mar 5;22(3):1000-7. Epub 2014 Sep 5.

Department of Visceral Surgery, Hôpital Nord, Marseille, France,

Background: The role of extended resections in the management of advanced pancreatic neuroendocrine tumors (PNETs) is not well defined.

Methods: Between 1995 and 2012, 134 patients with PNET underwent isolated (isoPNET group: 91 patients) or extended pancreatic resection (synchronous liver metastases and/or adjacent organs) (advPNET group: 43 patients).

Results: The associated resections included 27 hepatectomies, 9 vascular resections, 12 colectomies, 10 gastrectomies, 4 nephrectomies, 4 adrenalectomies, and 3 duodenojejunal resections. R0 was achieved in 41 patients (95%) in the advPNET. The rates of T3-T4 (73 vs 16%; p < .0001) and N+ (35 vs 13%; p = .007) were higher in the advPNET group. Mortality (5 vs 2%) and major morbidity (21 vs 19%) rates were similar between the 2 groups. The 5-year overall survival (OS) of the series was 87% in the isoPNET group and 66% in the advPNET group (p = .006). Only patients with both locally advanced disease and liver metastases showed worse survival (p = .0003). The advPNET group developed recurrence earlier [disease-free survival (DFS) at 5 years: 26 vs 81%; p < .001]. In univariate analysis, negative prognostic factors of survival were: poor degree of differentiation (p < .001), liver metastasis (p = .011), NE carcinoma (p < .001), and resection of adjacent organs (p = .013). The multivariate analysis did not highlight any factor that influenced OS. In multivariate analysis independent DFS factors were a poor degree of differentiation (p = .03) and the European Neuroendocrine Tumor Society stage (p = .01).

Conclusions: An aggressive surgical approach for locally advanced or metastatic tumors is safe and offers long-term survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-014-4016-8DOI Listing
March 2015

Successful treatment with sofosbuvir of fibrosing cholestatic hepatitis C after liver transplantation in an HIV-HCV-coinfected patient.

Antivir Ther 2015 8;20(3):353-6. Epub 2014 Aug 8.

Service d'Hépato-Gastroentérologie, Centre Hospitalo-Universitaire Conception, Assistance Publique-Hôpitaux de Marseille, Marseille, France.

Fibrosing cholestatic hepatitis is a severe form of post-liver transplantation HCV recurrence. Fibrosing cholestatic hepatitis is characterized by its early onset and severe prognosis in HIV-infected patients. We report the case of an HIV-HCV genotype-4 coinfected patient successfully treated with a combination of sofosbuvir and ribavirin. After 4 weeks of treatment we observed a resolution of HCV recurrence related symptoms associated with a normalization of liver biochemistry and dramatic decrease of HCV viral load. This case illustrates the efficiency and tolerance of a sofosbuvir-based anti-HCV interferon-free regimen in post-liver HCV recurrence. Because of the absence of drug interactions between sofosbuvir and antiretroviral treatment or calcineurin inhibitors, its administration in HIV-HCV-coinfected liver transplanted patients is very promising.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3851/IMP2841DOI Listing
February 2016

Severe fibrosis in patients with recurrent hepatitis C after liver transplantation: a French experience on 250 patients over 15 years (the Orfèvre study).

Clin Res Hepatol Gastroenterol 2014 Jun 29;38(3):292-9. Epub 2014 Mar 29.

Service d'hépatologie, hôpital Henri-Mondor, AP-HP, 94000 Créteil, France.

Background And Aims: Recurrent hepatitis C after liver transplantation (LT) is associated with rapid fibrosis progression. The aim of this study was to evaluate the cumulative risk for severe fibrosis and the factors influencing it.

Patients And Methods: Two hundred and fifty LT patients were included 1 to 15years after LT. Recurrence of chronic hepatitis C on liver graft was classified according to Metavir score.

Results: Kaplan-Meyer estimates for actuarial progression to severe fibrosis (Metavir>F3) showed a probability of 15.2% and 44.5% at 5 and 10years, respectively. Predictive factors for progression to severe fibrosis were: use of tacrolimus as main CNI, recipient age at time of biopsy<55, donor age ≥45, graft HCV re-infection<3months, biologically suspected graft re-infection and lack of response to antiviral treatment after LT. Multivariate analysis disclosed that only donor age ≥45 (hazard ratio 2.243, 95%CI 1.264-3.983, P=0.0058) and lack of response to antiviral treatment (hazard ratio 2.816, 95%CI 1.227-6.464, P=0.0146) were associated to severe fibrosis.

Conclusions: Our study confirms that donor age ≥45 and lack of response to antiviral treatment after LT are major predictive factors of progression of HCV recurrence on liver graft.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinre.2014.02.007DOI Listing
June 2014

Liver transplantation for acute liver failure related to autochthonous genotype 3 hepatitis E virus infection.

Clin Res Hepatol Gastroenterol 2014 Feb 23;38(1):24-31. Epub 2014 Jan 23.

Service d'hépatogastroentérologie, centre hospitalo-universitaire Conception, 147, boulevard Baille, 13385 Marseille cedex 05, France. Electronic address:

Hepatitis E virus of genotype 3 (HEV-3) is an emerging cause of sporadic autochthonous acute hepatitis in Europe. Although spontaneous outcome of hepatitis E is usually favorable, fulminant liver failure has been described worldwide. In Europe, autochthonous hepatitis E associated with fulminant hepatic failure and leading to liver transplantation has been exceptionally reported. We report here four cases of fulminant and sub-fulminant hepatitis E proposed for liver transplantation in Marseille University hospitals between July 2006 and March 2010. HEV diagnosis relied on detection of anti-HEV IgM antibodies and HEV RNA in serum samples. All cases were men, with no travel history in hyperendemic areas. HEV sequence analyses revealed genotype 3 HEV in the four patients. Liver histology indicated severe acute hepatitis in all of them, pre-existing fibrosis being found in two cases. Two patients underwent liver transplantation, and the two other patients could not be transplanted due to septic complications and died. HEV testing should be performed for the initial evaluation of every acute liver failure regardless of the epidemiological and clinical context. With respect to the potentially fulminant evolution of HEV genotype 3 infections, treatment with ribavirin of severe acute hepatitis E should be considered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinre.2013.05.013DOI Listing
February 2014
-->