European validation of the classification for the anticipated difficulty of liver transplantation.

BACKGROUND: Appropriate risk stratification for the difficulty of liver transplantation (LT) is essential to guide the selection and acceptance of grafts and avoid morbidity and mortality. METHODS: Based on 987 LTs collected from 5 centers, perioperative outcomes were analyzed across the 3 difficulty levels. Each LT was retrospectively scored from 0 to 10. Scores of 0-2, 3-5 and 6-10 were then translated into respective difficulty levels: low, moderate and high. Complications were reported according to the comprehensive complication index (CCI). RESULTS: The difficulty level of LT in 524 (53%), 323 (32%), and 140 (14%) patients was classified as low, moderate and high, respectively. The values of major intraoperative outcomes, such as cold ischemia time (p = 0.04) and operative time (p < 0.0001) increased gradually with statistically significant values among difficulty levels. There was a corresponding increase in CCI (p = 0.04), severe complication rates (p = 0.05) and length of ICU (p = 0.01) and hospital (p = 0.004) stays across the different difficulty levels. CONCLUSION: The LT difficulty classification has been validated.

Comparing indications, complexity and outcomes of laparoscopic liver resection between centers with and without a liver transplant program: a French nationwide study.

BACKGROUND: There are no data to evaluate the difference in populations and impact of centers with liver transplant programs in performing laparoscopic liver resection (LLR). METHODS: This was a multicenter study including patients undergoing LLR for benign and malignant tumors at 27 French centers from 1996 to 2018. The main outcomes were postoperative severe morbidity and mortality. RESULTS: A total of 3154 patients were included, and 14 centers were classified as transplant centers (N = 2167 patients, 68.7 %). The transplant centers performed more difficult LLRs and more resections for hepatocellular carcinoma (HCC) in patients who more frequently had cirrhosis. A higher rate of performing the Pringle maneuver, a lower rate of blood loss and a higher rate of open conversion (all p < 0.05) were observed in the transplant centers. There was no association between the presence of a liver transplant program and either postoperative severe morbidity (<10 % in each group; p = 0.228) or mortality (1 % in each group; p = 0.915). CONCLUSIONS: Most HCCs, difficult LLRs, and cirrhotic patients are treated in transplant centers. We show that all centers can achieve comparable safety and quality of care in LLR independent of the presence of a liver transplant program.

Nestin as a diagnostic and prognostic marker for combined hepatocellular-cholangiocarcinoma.

BACKGROUND & AIMS: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer (PLC) associated with a poor prognosis. Given the challenges in its identification and its clinical implications, biomarkers are critically needed. We aimed to investigate the diagnostic and prognostic value of the immunohistochemical expression of Nestin, a progenitor cell marker, in a large multicentric series of PLCs. METHODS: We collected 461 cHCC-CCA samples from 32 different clinical centers. Control cases included 368 hepatocellular carcinomas (HCCs) and 221 intrahepatic cholangiocarcinomas (iCCAs). Nestin immunohistochemistry was performed on whole tumor sections. Diagnostic and prognostic performances of Nestin expression were determined using receiver-operating characteristic curves and Cox regression modeling. RESULTS: Nestin was able to distinguish cHCC-CCA from HCC with AUCs of 0.85 and 0.86 on surgical and biopsy samples, respectively. Performance was lower for the distinction of cHCC-CCA from iCCA (AUCs of 0.59 and 0.60). Nestin, however, showed a high prognostic value, allowing identification of the subset of cHCC-CCA ("Nestin High", >30% neoplastic cells with positive staining) associated with the worst clinical outcome (shorter disease-free and overall survival) after surgical resection and liver transplantation, as well as when assessment was performed on biopsies. CONCLUSION: We show in different clinical settings that Nestin has diagnostic value and that it is a useful biomarker to identify the subset of cHCC-CCA associated with the worst clinical outcome. Nestin immunohistochemistry may be used to refine risk stratification and improve treatment allocation for patients with this highly aggressive malignancy. LAY SUMMARY: There are different types of primary liver cancers (i.e. cancers that originate in the liver). Accurately identifying a specific subtype of primary liver cancer (and determining its associated prognosis) is important as it can have a major impact on treatment allocation. Herein, we show that a protein called Nestin could be used to refine risk stratification and improve treatment allocation for patients with combined hepatocellular carcinoma, a rare but highly aggressive subtype of primary liver cancer.

Risk of diverticulitis and gastrointestinal perforation in rheumatoid arthritis treated with tocilizumab compared to rituximab or abatacept.

OBJECTIVE: To compare the risk of diverticulitis and gastrointestinal perforation (GIP) in RA treated with tocilizumab (TCZ) compared with rituximab (RTX) and abatacept (ABA). METHODS: We conducted a population-based study using three observational French registries on TCZ, RTX and ABA in RA. Using a propensity score approach, we compared the risk of diverticulitis or GIP in these patients. RESULTS: With inverse probability weighting, there was an increased risk of diverticulitis in TCZ-treated patients compared with RTX- or ABA-treated patients [hazard ratio (HR)=3.1 (95% CI: 1.5, 6.3), P =0.002]. Moreover, patients treated with TCZ had also an increased risk of GIP due to diverticulitis compared with those treated with RTX or ABA [HR=3.8 (1.1-13.6), P =0.04], resulting in an overall increased risk of GIP [HR=2.9 (1.1-7.8), P =0.03], while no significant increased risk of GIP due to any other aetiology was found in TCZ treated patients. Diverticulitis and GIP occurred earlier with TCZ than other drugs after the last perfusion (P =0.01), with atypical clinical presentation (slow transit in 30%, P =0.04) and lower acute-phase reactants at the time of the event (P =0.005). CONCLUSION: TCZ for RA was associated with increased odds of diverticulitis as well as GIP due to diverticulitis as compared with RTX and ABA. Our study confirms the increased odds of GIP in patients receiving TCZ, which might be explained by an increased risk of diverticulitis with misleading clinical presentation.

Benefit of a flash dose of corticosteroids in digestive surgical oncology: a multicenter, randomized, double blind, placebo-controlled trial (CORTIFRENCH).

BACKGROUND: The modulation of perioperative inflammation seems crucial to improve postoperative morbidity and cancer-related outcomes in patients undergoing oncological surgery. Data from the literature suggest that perioperative corticosteroids decrease inflammatory markers and might be associated with fewer complications in esophageal, liver, pancreatic and colorectal surgery. Their benefit on cancer-related outcomes has not been assessed. METHODS: The CORTIFRENCH trial is a phase III multicenter randomized double-blind placebo-controlled trial to assess the impact of a flash dose of preoperative corticosteroids versus placebo on postoperative morbidity and cancer-related outcomes after elective curative-intent surgery for digestive cancer. The primary endpoint is the frequency of patients with postoperative major complications occurring within 30 days after surgery (defined as all complications with Clavien-Dindo grade > 2). The secondary endpoints are the overall survival at 3 years, the disease-free survival at 3 years, the frequency of patients with intraabdominal infections and postoperative infections within 30 days after surgery and the hospital length of stay. We hypothesize a reduced risk of major complications and a better disease-survival at 3 years in the experimental group. Allowing for 5% of drop-out, 1 200 patients (600 per arm) should be included. DISCUSSION: This will be the first trial focusing on the impact of perioperative corticosteroids on cancer related outcomes. If significant, it might be a strong improvement on oncological outcomes for patients undergoing surgery for digestive cancers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03875690, Registered on March 15, 2019, URL: https://clinicaltrials.gov/ct2/show/NCT03875690 .

Progression of AFP SCORE is a Preoperative Predictive Factor of Microvascular Invasion in Selected Patients Meeting Liver Transplantation Criteria for Hepatocellular Carcinoma.

Microvascular invasion (MVI) is one of the main prognostic factors of hepatocellular carcinoma (HCC) after liver transplantation (LT), but its occurrence is unpredictable before surgery. The alpha fetoprotein (AFP) model (composite score including size, number, AFP), currently used in France, defines the selection criteria for LT. This study's aim was to evaluate the preoperative predictive value of AFP SCORE progression on MVI and overall survival during the waiting period for LT. Data regarding LT recipients for HCC from 2007 to 2015 were retrospectively collected from a single institutional database. Among 159 collected cases, 34 patients progressed according to AFP SCORE from diagnosis until LT. MVI was shown to be an independent histopathological prognostic factor according to Cox regression and competing risk analysis in our cohort. AFP SCORE progression was the only preoperative predictive factor of MVI (OR = 10.79 [2.35-49.4]; p 0.002). The 5-year overall survival in the progression and no progression groups was 63.9% vs. 86.3%, respectively (p = 0.001). Cumulative incidence of HCC recurrence was significantly different between the progression and no progression groups (Sub-HR = 4.89 [CI 2-11.98]). In selected patients, the progression of AFP SCORE during the waiting period can be a useful preoperative tool to predict MVI.

Alcohol Consumption the Day of Liver Transplantation for Alcohol-Associated Liver Disease Does Not Affect Long-Term Survival: A Case-Control Study.

Alcohol abstinence before liver transplantation (LT) for alcohol-associated liver disease (ALD) is required for every candidate. Some listed patients might relapse, resulting in LT for patients nonabstinent during the pretransplant period. Long-term survival outcomes of these patients have never been studied. We sought to determine whether alcohol consumption on the day of the LT influenced long-term survival after LT. We conducted a retrospective case-control study among French LT centers. Cases were defined as recipients between January 1995 and December 2007 having positive blood and/or urine alcohol levels the day of LT. Each case was paired with 2 controls corresponding to patients transplanted for ALD during the same trimester. Patients were classified into 3 categories per alcohol consumption: abstainers, occasional or transitory excessive consumers, or patients with a sustained excessive consumption (daily consumption >20-30 g/day). During the study period, 3052 LTs for ALD were conducted in France. We identified 42 cases paired with 84 controls. Median blood alcohol level was 0.4 g/L (range 0.1-4.1 g/L) and median urine alcohol level was 0.2 g/L (range 0.1-2.0 g/L). Median follow-up period until death or censoring was 12.9 years (CI95% = [12.3; 13.6]). Long-term survival was not different between the groups. Relapse to any alcohol consumption rate was higher in the case group (59.5%) than in the control group (38.1%, odds ratio 2.44; CI95% = [1.13; 5.27]), but sustained excessive consumption was not significantly different between the groups (33.3% versus 29.8% in case and control groups respectively, χ2  = 0.68). Rates of recurrent cirrhosis and cirrhosis-related deaths were more frequent in the case group. Liver transplantation for nonabstinent patients during the immediate pretransplant period does not result in impaired long-term survival despite higher relapse and recurrent cirrhosis rates.

Peritoneal Carcinomatosis Risk and Long-Term Survival Following Hepatectomy for Spontaneous Hepatocellular Carcinoma Rupture: Results of a Multicenter French Study (FRENCH-AFC).

BACKGROUND: Spontaneous rupture of hepatocellular carcinoma (HCC) remains a life-threatening complication, with a reported mortality rate of between 16 and 30% and an incidence rate of approximately 3% in Europe. Survival data and risk factors after ruptured HCC are lacking, especially for peritoneal metastasis (PM). OBJECTIVES: The aims of this study were to evaluate the pattern of recurrence and mortality after hepatectomy for ruptured HCC, and to focus on PM. METHODS: We retrospectively reviewed the files of patients admitted to 14 French surgical centers for spontaneous rupture of HCC between May 2000 and May 2012. RESULTS: Overall, 135 patients were included in this study. The median disease-free survival and overall survival (OS) rates were 16.1 (11.0-21.1) and 28.7 (26.0-31.5) months, respectively, and the median follow-up period was 29 months. At last follow-up, recurrences were observed in 65.1% of patients (n = 88). The overall rate of PM following ruptured HCC was 12% (n = 16). Surgical management of PM was performed for six patients, with a median OS of 36.6 months. An α-fetoprotein level > 30 ng/mL (p = 0.0009), tumor size at rupture > 70 mm (p = 0.0009), and vascular involvement (p < 0.0001) were found to be independently associated with an increased likelihood of recurrence. No risk factor for PM was observed. CONCLUSION: This large-cohort French study confirmed that 12% of patients had PM after ruptured HCC. A curative approach may be an option for highly selected patients with exclusive PD because of the survival benefit it could provide.

Endovascular balloon occlusion during reconstruction of portal vein injury.

PURPOSE: Repair of portal vein injury in a hostile abdomen can be very challenging, complicated by massive hemorrhage or stenosis. It can seldom be successfully carried out, even by experienced hepatobiliary surgeons. The ideal venous clamping technique is often not feasible and increases the risk of lethal portal vein laceration. The common mistake being the forceful use of clamps around the vein in the attempt to obtain vascular control, resulting in additional injuries. METHODS: We provide a descriptive report of two cases detailing a careful step-by-step technique for the management of portal vein injury by inserting an endovascular balloon inflated with serum to control bleeding and repair the vein. RESULTS: In patients who required this technique, no bleeding recurrence, nor portal vein thrombosis or stenosis was detected by CT-scan during follow-up. CONCLUSION: The endovascular balloon occlusion technique for the reconstruction of portal vein injuries in hostile abdomen is a safe and life-saving procedure that should be part of the armamentarium of visceral surgeons.

Integration of an Addiction Team in a Liver Transplantation Center.

Up to 50% of liver transplantation (LT) recipients with known or clandestine alcohol-use disorder (AUD) before surgery return to alcohol use after LT. However, only severe alcohol relapse, which varies in frequency from 11% to 26% of patients, has an impact on longterm survival and significantly decreases survival rates after 10 years. Therefore, it is crucial to identify patients with the highest risk of severe relapse in order to arrange specific, standardized monitoring by an addiction team before and after LT. The aims of this study were to describe the effects of combined management of AUD on the rate of severe alcohol relapse and to determine the risk factors before LT that predict severe relapse. Patients transplanted between January 2008 and December 2014 who had met with the LT team's addiction specialist were included in the study. Patients who exhibited alcohol-related relapse risk factors received specific addiction follow-up. A total of 235 patients were enrolled in the study. Most of them were men (79%), and the mean age at the time of the LT was 55.7 years. Severe relapse occurred in only 9% of the transplant recipients. Alcohol-related factors of severe relapse were a pretransplant abstinence of 6 months and family, legal, or professional consequences of alcohol consumption, whereas the nonalcohol-related factors were being single and being eligible for a disability pension. In conclusion, the integration of an addiction team in a LT center may be beneficial. The addiction specialist can identify patients at risk of severe relapse in the pretransplantation period and hence arrange for specific follow-up.

Epidermal Growth Factor Represses Constitutive Androstane Receptor Expression in Primary Human Hepatocytes and Favors Regulation by Pregnane X Receptor.

Growth factors have key roles in liver physiology and pathology, particularly by promoting cell proliferation and growth. Recently, it has been shown that in mouse hepatocytes, epidermal growth factor receptor (EGFR) plays a crucial role in the activation of the xenosensor constitutive androstane receptor (CAR) by the antiepileptic drug phenobarbital. Due to the species selectivity of CAR signaling, here we investigated epidermal growth factor (EGF) role in CAR signaling in primary human hepatocytes. Primary human hepatocytes were incubated with CITCO, a human CAR agonist, or with phenobarbital, an indirect CAR activator, in the presence or absence of EGF. CAR-dependent gene expression modulation and PXR involvement in these responses were assessed upon siRNA-based silencing of the genes that encode CAR and PXR. EGF significantly reduced CAR expression and prevented gene induction by CITCO and, to a lower extent, by phenobarbital. In the absence of EGF, phenobarbital and CITCO modulated the expression of 144 and 111 genes, respectively, in primary human hepatocytes. Among these genes, only 15 were regulated by CITCO and one by phenobarbital in a CAR-dependent manner. Conversely, in the presence of EGF, CITCO and phenobarbital modulated gene expression only in a CAR-independent and PXR-dependent manner. Overall, our findings suggest that in primary human hepatocytes, EGF suppresses specifically CAR signaling mainly through transcriptional regulation and drives the xenobiotic response toward a pregnane X receptor (PXR)-mediated mechanism.

Robotic versus laparoscopic distal pancreatectomy: a French prospective single-center experience and cost-effectiveness analysis.

BACKGROUND: Benefits and cost-effectiveness of robotic approach for distal pancreatectomy (DP) remain debated. In this prospective study, we aim to compare the short-term results and real costs of robotic (RDP) and laparoscopic distal pancreatectomy (LDP). METHODS: From 2011 until 2016, all consecutive patients underwent minimally invasive DP were included and data were prospectively collected. Patients were assigned in two groups, RDP and LDP, according to the availability of the Da Vinci® Surgical System for our Surgical Unit. RESULTS: A minimally invasive DP was performed in 38 patients with a median age of 61 years old (44-83 years old) and a BMI of 26 kg/m2 (20-31 kg/m2). RDP group (n = 15) and LDP group (n = 23) were comparable concerning demographic data, BMI, ASA score, comorbidities, malignant lesions, lesion size, and indication of spleen preservation. Median operative time was longer in RDP (207 min) compared to LDP (187 min) (p = 0.047). Conversion rate, spleen preservation failure, and perioperative transfusion rates were nil in both groups. Pancreatic fistula was diagnosed in 40 and 43% (p = 0.832) of patients and was grade A in 83 and 80% (p = 1.000) in RDP and LDP groups, respectively. Median postoperative hospital stay was similar in both groups (RDP: 8 days vs. LDP: 9 days, p = 0.310). Major complication occurred in 7% in RDP group and 13% in LDP group (p = 1.000). Ninety-days mortality was nil in both groups. No difference was found concerning R0 resection rate and median number of retrieved lymph nodes. Total cost of RDP was higher than LDP (13611 vs. 12509 €, p < 0.001). The difference between mean hospital incomes and costs was negative in RDP group contrary to LDP group (- 1269 vs. 1395 €, p = 0.040). CONCLUSION: Short-term results of RDP seem to be similar to LDP but the high cost of RDP makes this approach not cost-effective actually.

Impact of laparoscopy in patients aged over 70 years requiring distal pancreatectomy: a French multicentric comparative study.

BACKGROUND: Few data are available concerning short-term results of minimally invasive surgery in patients > 70 years old requiring distal pancreatectomy. The aim of this study was to compare short-term results after laparoscopic (LDP) versus open distal pancreatectomy (ODP) in this subgroup of patients. METHODS: All patients > 70 years who underwent distal pancreatectomy in 3 expert centers between 1995 and 2017 were included and data were retrospectively analyzed. Demographic, intraoperative data and postoperative outcomes in LDP and ODP groups were compared. RESULTS: A distal pancreatectomy was performed in 109 elderly patients; LDP group included 53 patients while ODP group included 56. There were 55 (50.5%) males and 54 (49.5%) women with a median age of 75 years (range 70-87). Fifty (45.9%) patients were 70-74, 40 (36.7%) patients were 75-79, and 19 (17.4%) patients were over 80 years. Nine (8.2%) patients required conversion to open surgery. The median operative time was not different between LDP and ODP (204 vs. 220 min, p = 0.62). The intraoperative blood loss was significantly lower in the LDP group (238 ± 312 vs. 425 ± 582 ml, p = 0.009) with no difference regarding the intraoperative transfusion rate. 90-day mortality (0 vs. 5%, p = 0.42), overall complication (45.4 vs. 51.8%, p = 0.53), major complication (18.2 vs. 12.5%, p = 0.43), grade B/C pancreatic fistula (6.8 vs. 7.1%, p = 0.71), were comparable in the 2 groups. Only postoperative confusion rate was significantly lower in the LDP group (4.5 vs. 25%, p = 0.01). Median length of stay was significantly lower in the LDP group (14 ± 10 vs. 16 ± 11 days, p = 0.04). R0 resection was performed in 94% of LDP patients and 89% in ODP patients without significant difference (p = 0.73). CONCLUSIONS: The laparoscopic approach seems to reduce blood loss, postoperative confusion, and length of stay in elderly patients requiring distal pancreatectomy.

Bleeding Recurrence and Mortality Following Interventional Management of Spontaneous HCC Rupture: Results of a Multicenter European Study.

BACKGROUND: The incidence of spontaneous rupture of hepatocellular carcinoma (HCC) is low in Europe, at less than 3%. HCC rupture remains a life-threatening complication, with mortality reported between 16 and 30%. The risk of bleeding recurrence has never been clearly evaluated in such clinical situation. The objectives of this study were to evaluate the current risk of mortality related to HCC rupture and to focus on the risk of bleeding recurrence following interventional management. METHODS: All patients admitted to 14 French-Italian surgical centers for spontaneous rupture of HCC between May 2000 and May 2012 were retrospectively included. Clinical data, imaging features, relevant laboratory data, treatment strategies, and prognoses were analyzed. RESULTS: Overall, 58 of the 138 included patients (42%) had cirrhosis. Thirty-five patients (25%) presented with hemorrhagic shock, and 19% with organ(s) dysfunction. Bleeding control was obtained by interventional hemostasis, emergency liver resection, and conservative medical management in 86 (62%), 24 (18%), and 21 (15%) patients, respectively. Best supportive care was chosen for 7 (5%) patients. The mortality rate following rupture was 24%. The bleeding recurrence rate was 22% with related mortality of 52%. In multivariate analysis, a bilirubin level >17 micromol/L (HR 3.768; p = 0.006), bleeding recurrence (HR 5.400; p < 0.0001), and ICU admission after initial management (HR 8.199; p < 0.0001) were associated with in-hospital mortality. CONCLUSION: This European, multicenter, large-cohort study confirmed that the prognosis of ruptured HCC is poor with an overall mortality rate of 24%, despite important advances in endovascular techniques. Overall, the rate of bleeding recurrence was more than 20%, with a related high risk of mortality.

Early Hepatic Artery Thrombosis After Liver Transplantation: What is the Impact of the Arterial Reconstruction Type?

OBJECTIVE: Hepatic artery thrombosis (HAT) is the most severe vascular complication occurring after liver transplantation, with an incidence ranging from 2 to 9% in adults. Although the ideal arterial reconstruction is often described as a short and non-redundant anastomosis fashioned between the recipient and donor hepatic arteries, there is no strong evidence about this ideal reconstruction in the literature. The aim of this study was to assess the impact of the type of arterial reconstruction on early HAT after primary liver transplantation. METHODS: We retrospectively reviewed a contemporary MELD era cohort of 282 patients who underwent deceased donor primary liver transplantation from 2007 to 2012. Graft artery was classified as "short" when the section was located at the proper/common hepatic artery or "long" when the celiac trunk was used for anastomosis. Recipient arterial sites for arterial anastomosis were classified in three sites: (1) "distal" (proper hepatic artery or common hepatic artery/gastro-duodenal bifurcation), (2) "intermediate" (common hepatic artery) and (3) "proximal" (celiac trunk-splenic artery-aorta). We used univariate and multivariate analyses to assess the impact of different types of arterial reconstruction on early HAT. RESULTS: Of 282 primary liver transplantations, 17 patients (6%) developed early HAT. Patients with and without early HAT had comparable demographic and operative data. The main anastomotic combination was short graft artery on the recipient-common hepatic artery (n = 111, 39%). A long graft artery was used in 91 patients (32%) and was associated with hepatic artery variations (56%; n = 51; p = 0.001). Arterial reconstructions using a long graft artery (p = 0.003), a recipient proximal site as celiac trunk-splenic artery-aorta (p = 0.02) and the combination of a long graft artery on the recipient distal hepatic artery (p = 0.02) were significantly associated with early HAT. The early HAT rate in patients with a long graft artery was not significantly different between patients with or without donor arterial variation (respectively, 12% (n = 6/51) vs. 12% (n = 5/40); p = 1). In multivariate analysis, the use of a long graft artery, whatever the recipient anastomosis site, was an independent risk factor of early HAT (OR 3.2; 95% CI 1.2-9; p = 0.02). CONCLUSION: The type of arterial reconstruction used for arterial anastomosis during primary liver transplantation has an impact on the occurrence of early HAT. The use of a long graft artery is an independent risk factor of early HAT. Thereby, we recommend the use of a short graft artery with a direct path when feasible to reduce the occurrence of early HAT after primary liver transplantation.

Vena cava encirclement predicts difficult native hepatectomy.

Recipient hepatectomy is a challenging liver transplantation (LT) procedure that has life-threatening complications. The current predictive mortality clinic-biological scores (Child/Model for End-Stage Liver Disease [MELD]) do not take into consideration the recipient's liver anatomy. The aim of this study was to evaluate the impact of the dorsal sector anatomy of a cirrhotic liver on the morbidity/mortality rates of hepatectomy. A multicenter retrospective study (clinic-biological and morphologic) was performed from 2013 to 2014. The degree of encirclement of the inferior vena cava (IVC) by the dorsal sector of the liver was measured. The study population included 320 patients. Seventy-four (23%) patients had complete IVC encirclement. A correlation (P = 0.01) has been reported between the existence of a circular dorsal sector and the number of transfusions during LT (4 packed red blood cell [PRBC] transfusions in the group without IVC versus 7 PRBC transfusions in the other group). The existence of such anatomy increases the relative risk of early reoperation for IVC bleeding by 31% (P = 0.05). There is a correlation between alcoholic cirrhosis and dorsal-sector hypertrophy (126 cc versus 147.5 cc; P = 0.05). Concerning surgical time, we found no significant between-group differences. Compared to the severity of cirrhosis, an inverse correlation was observed between the MELD and Child scores and the dorsal sector hypertrophy (P < 0.001). No significant difference in terms of transfusion was found between the temporary portocaval shunt group (n = 168) and the other group (n = 152). The presence of a circular sector is associated with an increased risk of hemorrhage during hepatectomy, as well as an immediate postoperative risk of reoperation. Liver Transplantation 22 906-913 2016 AASLD.

Simultaneous trans-hepatic portal and hepatic vein embolization before major hepatectomy: the liver venous deprivation technique.

PURPOSE: To assess technical feasibility, safety, and efficacy of the liver venous deprivation (LVD) technique that combines both portal and hepatic vein embolization during the same procedure for liver preparation before major hepatectomy. MATERIALS AND METHODS: Seven patients (mean age:63.6y[42-77y]) underwent trans-hepatic LVD for liver metastases (n = 2), hepatocellular carcinoma (n = 1), intrahepatic cholangiocarcinoma (n = 3) and Klatskin tumour (n = 1). Assessment of future remnant liver (FRL) volume, liver enzymes and histology was performed. RESULTS: Technical success was 100 %. No complication occurred before surgery. Resection was performed in 6/7 patients. CT-scan revealed hepatic congestion in the venous-deprived area (6/7 patients). A mean of 3 days (range: 1-8 days) after LVD, transaminases increased (AST: from 42 ± 24U/L to 103 ± 118U/L, ALT: from 45 ± 25U/L to 163 ± 205U/L). Twenty-three days (range: 13-30 days) after LVD, FRL increased from 28.2 % (range: 22.4-33.3 %) to 40.9 % (range: 33.6-59.3 %). During the first 7 days, venous-deprived liver volume increased (+13.4 %) probably reflecting vascular congestion, whereas it strongly decreased (-21.3 %) at 3-4 weeks. Histology (embolized lobe) revealed sinusoidal dilatation, hepatocyte necrosis and important atrophy in all patients. CONCLUSION: Trans-hepatic LVD technique is feasible, well tolerated and provides fast and important hypertrophy of the FRL. This new technique needs to be further evaluated and compared to portal vein embolization. KEY POINTS: • Twenty-three days after LVD, FRL increased from 28.2 % (range:22.4-33.3 %) to 40.9 % (range:33.6-59.3 %) • During the first 7 days, venous-deprived liver volume increased (+13.4 %) • Venous-deprived liver volume strongly decreased (mean atrophy:229 cc; -21.3 %) at 3-4 weeks • Histology of venous-deprived liver revealed sinusoidal dilatation, hepatocyte necrosis and important atrophy.

Improved stability of lipiodol-drug emulsion for transarterial chemoembolisation of hepatocellular carcinoma results in improved pharmacokinetic profile: Proof of concept using idarubicin.

OBJECTIVES: To investigate the relationship between the improved stability of an anticancer drug-lipiodol emulsion and pharmacokinetic (PK) profile for transarterial chemoembolisation (TACE) of hepatocellular carcinoma (HCC). METHODS: The stability of four doxorubicin- or idarubicin-lipiodol emulsions was evaluated over 7 days. PK and clinical data were recorded after TACE with the most stable emulsion in eight unresectable HCC patients, after institutional review board approval. RESULTS: The most stable emulsion was the one that combined idarubicin and lipiodol (1:2 v:v). At 7 days, the percentages of aqueous, persisting emulsion and oily phases were 50-0-50, 33-0-67, 31-39-30, and 10-90-0 for the doxorubicin-lipiodol (1:1 v:v), doxorubicin-lipiodol (1:2 v:v), idarubicin-lipiodol (1:1 v:v), and the idarubicin-lipiodol (1:2 v:v) emulsion, respectively. After TACE, mean idarubicin Cmax and AUC0-24h were 12.5 ± 9.4 ng/mL and 52 ± 16 ng/mL*h. Within 24 h after injection, 40% of the idarubicin was in the liver, either in vessels, tumours, or hepatocytes. During the 2 months after TACE, no clinical grade >3 adverse events occurred. One complete response, five partial responses, one stabilisation, and one progression were observed at 2 months. CONCLUSION: This study showed a promising and favourable PK and safety profile for the idarubicin-lipiodol (1:2 v:v) emulsion for TACE. KEY POINTS: • Transarterial chemoembolisation (TACE) regimens that improve survival in hepatocellular carcinoma are needed. • Improved emulsion stability for TACE resulted in a favourable pharmacokinetic profile. • Preliminary safety and efficacy data for the idarubicin-lipiodol emulsion for TACE were encouraging.

Risk factors for postoperative bile leakage: a retrospective single-center analysis of 411 hepatectomies.

BACKGROUND: The primary focus of the study was to analyze the risk factors for bile leakage after hepatectomy for benign or malignant tumors. METHODS: A total of 411 patients who had undergone hepatectomy between December 2006 and December 2011 were retrospectively analyzed. The severity of bile leakage was graded according to the ISGLS classification. Twenty-eight pre- and postoperative parameters were analyzed. RESULTS: The overall bile leakage incidence was 10.2% (42/411). The severity of the leakage was classified according to the ISGLS classification. Bile leakage was detected early in case of abdominal drainage (11.4% vs 1.9%, P=0.034). It prolonged the time of hospitalization (16 vs 9 days, P=0.001). In all patients, wedge resection was associated with a higher incidence of bile leakage in contrast to anatomical resections (25.6% vs 4.1%, P<0.0001) regardless of the underlying liver disease. Furthermore, total vascular exclusion increased risk of bile leakage (P=0.008). CONCLUSIONS: Bile leakage as a major issue after hepatic resection is related to the postoperative morbidity and the hospitalization time. It is associated with non-anatomical resection and a total vascular exclusion.

Recurrent alcoholic cirrhosis in severe alcoholic relapse after liver transplantation: a frequent and serious complication.

OBJECTIVES: Alcoholic liver disease (ALD) is a major indication for liver transplantation (LT). Recurrent alcoholic cirrhosis (RAC) after LT can occur but has not been studied. The aims of this study were to estimate the prevalence, predictive factors, and natural history of RAC after LT. METHODS: All patients transplanted for ALD between 1990 and 2007 in three French centers were included. The diagnosis of RAC was based on histological evidence or a series of features combined with severe alcoholic relapse. RESULTS: Among 1,894 adult LT patients, 712 were transplanted for alcoholic cirrhosis and survived >6 months. After a mean follow-up of 9 years, 128 patients (mean age at LT 47.2±7.1 years old, 78.9% men) experienced severe alcoholic relapse (18.0% of cases). Severe alcoholic relapse occurred after a median delay of 25 months (range 4-157) after LT. RAC was diagnosed in 41 patients with severe relapse (32%). The diagnosis of RAC was made after a median delay of 5.1 years (range 1.8-13.9) after LT and of 4.0 years (range 1.2-11.5) after relapse. RAC was significantly associated with younger age and a shorter period of pre-LT abstinence. One-, 5-, 10-, and 15-year survival was 100, 87.6, 49.7, and 21.0%, respectively, for RAC patients vs. 100, 89.4, 69.9, and 41.1%, respectively, for the patients without RAC (P<0.001). CONCLUSIONS: RAC occurs in <6% of ALD transplant patients. One-third of severe alcoholic relapse patients develop RAC <5 years after transplantation with a very poor prognosis.