Philippe Compagnon

Pretreatment with Mangafodipir Improves Liver Graft Tolerance to Ischemia/Reperfusion Injury in Rat

Ischemia/reperfusion injury occurring during liver transplantation is mainly due to the generation of reactive oxygen species (ROS) upon revascularization. Thus, delivery of antioxidant enzymes might reduce the deleterious effects of ROS and improve liver graft initial function. Mangafodipir trisodium (MnDPDP), a contrast agent currently used in magnetic resonance imaging of the liver, has been shown to be endowed with powerful antioxidant properties. We hypothesized that MnDPDP could have a protective effect against liver ischemia reperfusion injury when administrated to the donor prior to harvesting. Livers from Sprague Dawley rats pretreated or not with MnDPDP were harvested and subsequently preserved for 24 h in Celsior® solution at 4°C. Organs were then perfused ex vivo for 120 min at 37°C with Krebs Henseleit solution. In MnDPDP (5 µmol/kg) group, we observed that ATP content was significantly higher at the end of the cold preservation period relative to untreated group. After reperfusion, livers from MnDPDP-treated rats showed better tissue integrity, less hepatocellular and endothelial cell injury. This was accompanied by larger amounts of bile production and higher ATP recovery as compared to untreated livers. The protective effect of MnDPDP was associated with a significant decrease of lipid peroxidation, mitochondrial damage, and apoptosis. Interestingly, MnDPDP-pretreated livers exhibited activation of Nfr2 and HIF-1α pathways resulting in a higher catalase and HO-1 activities. MnDPDP also increased total nitric oxide (NO) production which derived from higher expression of constitutive NO synthase and lower expression of inducible NO synthase. In conclusion, our results show that donor pretreatment with MnDPDP protects the rat liver graft from cold ischemia/reperfusion injury and demonstrate for the first time the potential interest of this molecule in the field of organ preservation. Since MnDPDP is safely used in liver imaging, this preservation strategy holds great promise for translation to clinical liver transplantation.

Parenchymal-sparing hepatectomies (PSH) for bilobar colorectal liver metastases are associated with a lower morbidity and similar oncological results: a propensity score matching analysis.

OBJECTIVEnThe aim of this study is to evaluate whether a parenchymal-sparing strategy provides similar results in terms of morbidity, mortality, and oncological outcome of non-PSH hepatectomies in a propensity score matched population (PSMP) in case of multiple (>3) bilobar colorectal liver metastases (CLM).nnnBACKGROUNDnThe surgical treatment of bilobar liver metastasis is challenging due to the necessity to achieve complete resection margins and a sufficient future remnant liver. Two approaches are adaptable as follows: parenchymal-sparing hepatectomies (PSH) and extended hepatectomies (NON-PSH).nnnMETHODSnA total of 3036 hepatectomies were analyzed from a multicentric retrospective cohort of hepatectomies. Patients were matched in a 1:1 propensity score analysis in order to compare PSH versus NON-PSH resections.nnnRESULTSnPSH was associated with a lower number of complications (≥1) (25% vs. 34%, pxa0=xa00.04) and a lower grade of Dindo-Clavien III and IV (10 vs. 16%, pxa0=xa00.03). Liver failure was less present in PSH (2 vs. 7%, pxa0=xa00.006), with a shorter ICU stay (0 day vs. 1 day, pxa0=xa00.004). No differences were demonstrated in overall and disease-free survival.nnnCONCLUSIONnIn conclusion, PSH resection for bilobar multiple CLMs represents a valid alternative to NON-PSH resection in selected patients with a reduced morbidity and comparable oncological results.

Robotic-Assisted Versus Laparoscopic Left Lateral Sectionectomy: Analysis of Surgical Outcomes and Costs by a Propensity Score Matched Cohort Study

BackgroundAfter comparing with open approach, left lateral sectionectomy (LLS) has become standard in terms of short-term outcomes without jeopardizing long-term survival when performed for malignancy. The aim of this study was to compare the short-term and economic outcomes of laparoscopic (L-LLS) and robotic (R-LLS) LLS.MethodsAll consecutive patients who underwent L-LLS or R-LLS from 1997 to 2014 were analyzed. Short-term and economic outcomes were compared between the two groups using a propensity score matching (PSM).ResultsNinety-six consecutive cases of LLS were performed using the laparoscopic (80 cases; 83xa0%) or robotic (16 cases; 17xa0%) approach. The two groups were similar for operative and surgical outcomes. Operation time was similar in the R-LLS compared to the L-LLS group (190 vs. 162xa0min; pxa0=xa00.10). Perioperative costs were higher (1457 € vs. 576 €; pxa0<xa00.0001) in the R-LLS group than in the L-LLS group; however, postoperative costs were similar between the two groups (4065 € in the R-LLS group vs. 5459 € in the L-LLS group; pxa0=xa00.30). Total costs were similar between the two groups (5522 € in the R-LLS group vs. 6035€ in the L-LLS group; pxa0=xa00.70). The PSM included 14 patients for each group. Surgical and economic outcomes remained similar after PSM, except for total operating time which was significantly longer in the R-LLS group than in the L-LLS group.ConclusionsEven if feasible and safe, the robotic approach does not seem so far to offer additional benefit in terms of intra- and postoperative outcomes over the laparoscopic approach in patients requiring LLS. Total costs associated with the R-LLS group are not greater than that associated with the L-LLS group, which is the standard of care so far.

Hepatectomy for hepatocellular carcinoma larger than 10 cm: preoperative risk stratification to prevent futile surgery

OBJECTIVESnAppropriate patient selection is important to achieving good outcomes and obviating futile surgery in patients with huge (≥10 cm) hepatocellular carcinoma (HCC). The aim of this study was to identify independent predictors of futile outcomes, defined as death within 3 months of surgery or within 1 year from early recurrence following hepatectomy for huge HCC.nnnMETHODSnThe outcomes of 149 patients with huge HCCs who underwent resection during 1995-2012 were analysed. Multivariate logistic regression analysis was performed to identify preoperative independent predictors of futility.nnnRESULTSnIndependent predictors of 3-month mortality (18.1%) were: total bilirubin level >34 μmol/l [P = 0.0443; odds ratio (OR) 16.470]; platelet count of <150 000 cells/ml (P = 0.0098; OR 5.039), and the presence of portal vein tumour thrombosis (P = 0.0041; OR 5.138). The last of these was the sole independent predictor of 1-year recurrence-related mortality (17.2%). Rates of recurrence-related mortality at 3 months and 1 year were, respectively, 6.3% and 7.1% in patients with Barcelona Clinic Liver Cancer (BCLC) stage A disease, 12.5% and 14% in patients with BCLC stage B disease, and 37.8% (P = 0.0002) and 75% (P = 0.0002) in patients with BCLC stage C disease.nnnCONCLUSIONSnAccording to the present data, among patients submitted to hepatectomy for huge HCC, those with a high bilirubin level, low platelet count and portal vein thrombosis are at higher risk for futile surgery. The presence of portal vein tumour thrombosis should be regarded as a relative contraindication to surgery.

Acute kidney injury following hepatectomy for hepatocellular carcinoma: incidence, risk factors and prognostic value

BACKGROUNDnAcute kidney injury (AKI) following hepatectomy remains understudied in terms of diagnosis, severity, recovery and prognostic value. The aim of this study was to assess the risk factors and prognostic value of AKI on short- and long-term outcomes following hepatectomy for hepatocellular carcinoma (HCC).nnnMETHODnThis is a retrospective analysis of a single-center cohort of 457 consecutive patients who underwent hepatectomy for HCC. The KDIGO criteria were used for AKI diagnosis. The incidence, risk factors, and prognostic value of AKI were investigated.nnnRESULTSnAKI occurred in 67 patients (15%). The mortality and major morbidity rates were significantly higher in patients with AKI (37% and 69%) than in those without (6% and 22%; pxa0<xa00.001). Renal recovery was complete in 35 (52%), partial in 25 (37%), and absent in 7 (11%) patients. Advanced age, an increased MELD score, major hepatectomy and prolonged duration of operation were identified as independent predictors of AKI. AKI was identified as the strongest independent predictor of postoperative mortality but did not impact survival.nnnCONCLUSIONnAKI is a common complication after hepatectomy for HCC. Although its development is associated with poor short-term outcomes, it does not appear to be predictive of impaired long-term survival.

Laparoscopic Isolated Resection of Caudate Lobe (Segment 1): A Safe and Versatile Technique

Surgical resection for liver tumors of the caudate lobe is challenging owing to its location between the inferior vena cava and the portal bifurcation and its relationship to the hepatic veins. Some case reports of isolated laparoscopic caudate lobe resection have been reported in the literature with various techniques. The aim of this study was to propose a standardized technique of laparoscopic isolated caudate lobe resection.

Sleeve Gastrectomy After Liver Transplantation: Feasibility and Outcomes

BackgroundKnowledge regarding the feasibility and safety of sleeve gastrectomy (SG) in obese liver transplant recipients is scarce. We report our experience of sleeve gastrectomy following liver transplantation (LT).MethodsAll patients who had undergone LT and subsequently underwent SG at our institution were retrospectively reviewed. Surgical outcomes, liver and kidney function tests, outcomes of obesity-related comorbidities, and excess weight loss were analyzed.ResultsBetween May 2008 and February 2015, six consecutive patients underwent SG after LT. Three procedures (50%) were performed totally by laparoscopy, and three by upfront laparotomy for concomitant incisional hernia complex repair. Within the first 30xa0days, one complication occurred: early gastric fistula that required multiple endoscopic procedures and re-intervention, followed by death 19xa0months after SG due to multi-organ failure. Another patient had one late complication: chronic infection on a parietal mesh successfully controlled by mesh removal. Excess weight loss averaged 76% at 2xa0years with a median BMI of 28 (21–39) kg/m2. Median follow-up was 37.2xa0months (range 13–101xa0months). Median length of stay was 9xa0days (range: 6–81xa0days).ConclusionsSG is technically feasible after LT and resulted in weight loss without adversely affecting graft function and immunosuppression. However, morbidity and mortality are high.

Complications after Hepatectomy for Hepatocellular Carcinoma Independently Shorten Survival: A Western, Single-Center Audit

AbstractBackgroundnThe impact of postoperative complications (POCs) on long-term outcomes following hepatocellular carcinoma (HCC) resection remains to be ascertained.MethodsAll consecutive HCC resected at a single center were analyzed. Patients with POCs, classified according to Clavien classification, were compared to those without in terms of demographics, pathology, management, overall survival (OS), and disease-free survival (DFS). Independent prognostic factors of POCs were identified using multivariable regression models.ResultsAmong 341 patients, overall POCs rate was 34% (nxa0=xa0116) and grade III–IV POCs rate was 14.4% (nxa0=xa049). POCs were an independent negative factor for OS [hazard ratio (HR) 1.40, 95% confidence interval (CI) 1.12–2.26, pxa0=xa00.009] with BCLC stage, the need for combined procedure, intraoperative transfusion, and the METAVIR score of the underlying parenchyma. Similarly, occurrence of POCs was associated independently with DFS (HR 1.59, 95% CI 1.18–2.15, pxa0=xa00.002), together with the presence of portal hypertension, BCLC stage, the need for combined procedure, intraoperative transfusion, and the presence of satellite nodules. After stratification, the negative impact of morbidity on OS and DFS reached statistical significance in the BCLC stage A subset only (pxa0=xa00.026, and pxa0<xa00.001, respectively). Open resection, intraoperative transfusion, and the existence of underlying liver injury were independent predictors of POCs.ConclusionsPOCs should be considered as a long-term prognostic factor. Careful patient selection requiring underlying liver assessment and appropriate strategy, such as mini-invasive surgery and restricted transfusion policy, might be promoted to prevent POCs.

Evaluation of the current guidelines for resection of hepatocellular carcinoma using the Appraisal of Guidelines for Research and Evaluation II instrument

BACKGROUND & AIMSnNumerous guidelines for the management of hepatocellular carcinoma (HCC) have been developed. The Appraisal of Guidelines for Research & Evaluation (AGREE II) is the only validated instrument to assess the methodological quality of guidelines. We aim to appraise the methodological quality of existing guidelines for the resection of HCC using the AGREE II instrument.nnnMETHODSnCochrane, Medline, Google Scholar and Embase were searched using both PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria and free text. The assessment of the included clinical practice guidelines and consensuses were performed using the AGREE II instrument, version 2013. Guidelines with a score ⩾80% for the overall appraisal item were considered as applicable without modifications.nnnRESULTSnLiterature searches identified 22 clinical practice guidelines. Five out of 22 guidelines passed the 70% mark on overall assessment, 11 out of 22 had shortcomings on indications, contraindications, side effects, key recommendations, technical aspects, transparency and health economics. Ten of 22 scored below the 50% mark showing that the guideline had low methodological and overall quality. Only 3/22 clinical practice guidelines were considered applicable without modifications.nnnCONCLUSIONSnThe methodological quality of guidelines for the surgical management of HCC is generally poor. Future guideline development should be informed by the use of the AGREE II instrument. Guidelines based upon high quality evidence could improve stratification of patients and individualized treatment strategies. Lay summary: The methodology of clinical practice guidelines for resection for hepatocellular carcinoma (HCC) evaluated with the Appraisal of Guidelines for Research & Evaluation (AGREE II) instrument is generally poor. However, there are some clinical practice guidelines that are based upon higher quality evidence and can form the framework within which patients with HCC can be selected for surgical resection. Future guideline development should be informed by the use of the AGREE II instrument.

Congenital bile duct cyst (BDC) is a more indolent disease in children compared to adults, except for Todani type IV-A BDC: results of the European multicenter study of the French Surgical Association

AIMnTo compare clinical presentation, operative management and short- and long-term outcomes of congenital bile duct cysts (BDC) in adults with children.nnnMETHODSnRetrospective multi-institutional Association Francaise de Chirurgie study of Todani types I+IVB and IVA BDC.nnnRESULTSnDuring the 37-year period to 2011, 33 centers included 314 patients (98 children; 216 adults). The adult population included more high-risk patients, with more active, more frequent prior treatment (47.7% vs 11.2%; pxa0<xa00.0001), more complicated presentation (50.5% vs 35.7%; pxa0=xa00.015), more synchronous biliary cancer (11.6% vs 0%; pxa0=xa00.0118) and more major surgery (23.6% vs 2%; pxa0<xa00.0001), but this latter feature was only true for type I+IVB BDC. Compared to children, the postoperative morbidity (48.1% vs 20.4%; pxa0<xa00.0001), the need for repeat procedures and the status at follow-up were worse in adults (27% vs 8.8%; pxa0=xa00.0009). However, severe postoperative morbidity and fair or poor status at follow-up were not statistically different for type IVA BDC, irrespective of patients age. Synchronous cancer, prior HBP surgery and Todani type IVA BDC were independent predictive factors of poor or fair long-term outcome.nnnCONCLUSIONnBDC is a more indolent disease in children compared to adults, except for Todani type IV-A BDC.