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Split liver transplantation (SLT) using extended right grafts is associated with complications related to ischemia of hepatic segment 4 (S4), and these complications are associated with poor outcomes. We retrospectively analyzed 36 SLT recipients so that we could assess the association of radiological, biological, and clinical features with S4 ischemia. The overall survival rates were 84.2%, 84.2%, and 77.7% at 1, 3, and 5 years, respectively. The recipients were mostly male (24/36 or 67%) and had a median age of 52 years (range = 13-63 years), a median body mass index of 22.9 kg/m2 (range = 17.3-29.8 kg/m2), and a median graft-to-recipient weight ratio of 1.3% (range = 0.9%-1.9%). S4-related complications were diagnosed in 22% of the patients (8/36) with a median delay of 22 days (range = 10-30 days). Secondary arterial complications were seen in 3 of these patients and led to significantly decreased graft survival in comparison with the graft survival of patients without complications (50.0% versus 85.6%, P = 0.017). Patients developing S4-related complications had significantly elevated aspartate aminotransferase (AST) levels (>1000 IU/L) on postoperative day (POD) 1 and elevated gamma-glutamyl transpeptidase (GGT) levels (>300 IU/L) on PODs 7 and 10 (P < 0.05). These AST and GGT elevations conferred a significantly high risk of developing these complications (odds ratio = 42, 95% confidence interval = 4-475, P < 0.05). The ischemic volume of S4 was extremely variable (0%-95%) and did not correlate with S4-related complications. In conclusion, our results suggest that S4-related complications are risk factors for worse graft survival, and the development of these complications can be anticipated by the early identification of a specific biological profile and a routine radiological examination. Liver Transpl 18:413–422, 2012. © 2011 AASLD.

Two stage hepatectomy is currently a method of choice for the treatment of multifocal bilobar hepatic lesions, especially in the setting of hepatic metastases of colorectal malignancies. We describe a technique that facilitates second-stage hepatectomy by taping the major vascular structures of the right liver and performing a hanging maneuver during the first stage.At the first-stage hepatectomy, the right hepatic artery and the right portal branch are dissected free and taped with color-coded silicone tapes. A classic hanging maneuver is performed using a silicone loop. These three loops are left in situ until the second-stage hepatectomy.During the second-stage hepatectomy, the presence of the vascular tapes appears a major aid in the subsequent dissection and control of the major vascular structures, and the hanging loop helps parenchymal section and surgeon orientation, without liver mobilization. Six patients underwent this procedure. In one patient a biliary leak developed after the first-stage procedure, and this required reoperation for drainage. Although there is a risk of thrombosis in this setting, there were no vascular complications related to the tape positioning, nor was there any incidence of infection related to the use of the silicone tape.The technique described here has been in regular use in our department since 2009, and in our experience, it may facilitate second-stage hepatectomy.

Biliary reconstruction during liver transplantation (LT) is most oftenly performed by duct-to-duct biliary anastomosis. We hypothesized that the internal stenting might diminish the incidence and severity of biliary complications in patients receiving small duct size donor grafts. The purpose of this study was to report a technique of biliary reconstruction, including intraductal stent tube (IST) placement followed by postoperative endoscopic removal. A custom-made segment of a T-tube was placed into the bile in 20 patients in whom the diameter of the graft bile duct was smaller than 5 mm. The tube was removed endoscopically 4-8 months after LT, or in case of IST-related adverse events. After a median follow-up of 15.2 (range 2.5-27.5) months, endoscopic removal of the IST was performed in 17 patients. No technical failure and no procedure-related complications were recorded during drain removal. Biliary complications occurred in four patients, including one cholangitis, one hemobilia, one asymptomatic biliary leakage, and one anastomotic stricture. No biliary complication occurred in the group of patients who underwent deceased donor whole graft LT. IST is technically feasible and safe, and may help to prevent severe biliary complication when duct-to-duct biliary anastomosis is performed on small size bile ducts.

Background Vascular inflow occlusion is effective in avoiding excessive blood loss during hepatic parenchymal transection but may cause ischaemic damage to the remnant liver. Intermittent portal triad clamping (IPTC) is superior to continuous hepatic pedicle clamping as it avoids severe ischaemia–reperfusion (IR) injury in the liver remnant. Ischaemic preconditioning (IPC) before continuous Pringle manoeuvre may protect against IR during major liver resection. Methods This RCT assessed the impact of IPC in major liver resection with intermittent vascular inflow occlusion. Patients undergoing major liver resection with intermittent vascular inflow occlusion were randomized, during surgery, to receive IPC (10 min inflow occlusion followed by 10 min reperfusion) or no IPC (control group). Data analysis was on an intention-to-treat basis. The primary endpoint was serum alanine aminotransferase (ALT) level on the day after surgery. Results Eighty four patients were enrolled and randomized to IPC (n = 41) and no IPC (n = 43). The groups were comparable in terms of demographic data, preoperative American Society of Anesthesiologists grade and extent of liver resection. Intraoperative morbidity and postoperative outcomes were also similar. ALT levels on the day after operation were not decreased by IPC (mean(s.d.) 537·6(358·5) versus 525·0(400·6) units/ml in IPC and control group respectively; P = 0·881). Liver biochemistry tests in the week after operation showed the same pattern in both groups. Conclusion IPC did not reduce liver damage in patients undergoing major liver resection with IPTC. Registration number: NCT00908245 (http://www.clinicaltrials.gov).

At present, no method is available for accurately monitoring the degree of immunosuppression induced by antirejection therapies. The aim of this study was to determine whether CD28 and CD38 expression by peripheral blood mononuclear cells could be useful in predicting the development of de novo malignancies after liver transplantation. Flow cytometry analysis was used to measure the expression of CD28 and CD38 by peripheral blood lymphocytes in 134 stable, long-term survivors of liver transplantation. Patients who developed a de novo malignancy after undergoing a medical checkup were entered into a cancer group. Twenty-two patients (16.4%) developed at least 1 de novo malignancy over a mean interval of 22 ± 14 months (1.2-49.4 months) after the checkup. The mean frequency of CD28+CD8+ cells was significantly lower in the cancer group versus the noncancer group (39% ± 22 versus 51% ± 21, P = 0.008), but CD38 expression was similar in the 2 groups. Multivariate analysis indicated that an age greater than 50 years (odds ratio = 5.81) and a low frequency of CD28+CD8+ cells at the time of the checkup (odds ratio =3.16) were the only significant predictors of the development of de novo malignancies (P = 0.027). The actuarial proportion of patients with de novo malignancies was significantly lower when the frequency of CD28+CD8+ cells was greater than or equal to 40% instead of less than 40% (P = 0.01). Flow cytometry measurements of CD28 expression by peripheral blood lymphocytes may facilitate the identification of patients at a high risk of developing de novo malignancies. Further prospective studies are necessary to determine whether such measurements could have a place in routine clinical practice to enable the intensity of immunosuppression to be minimized in patients who have an increased risk of developing cancer. Liver Transpl, 2011. © 2011 AASLD.

Background Management of anastomotic biliary strictures after liver transplantation deserves optimization. Objective To evaluate placement and removal of partially covered self-expandable metal stents (PCSEMSs) in this setting. Design Prospective, multicenter, uncontrolled study. Setting Three French academic hospitals with liver transplantation units and tertiary referral endoscopy centers. Patients Twenty-two patients (18 men, 4 women, aged 49.7 ± 12 years) with anastomotic biliary stricture. Seventeen (77.3%) presented stricture recurrence after plastic stenting. Interventions PCSEMSs were placed across the stricture for 2 months and then removed. Patients were followed by clinical examination and liver function tests 1, 3, 6, 9, and 12 months after PCSEMS removal. Main Outcome Measurement The ability to remove PCSEMS. Results PCSEMS placement was successful in all patients, after sphincterotomy in 21 patients. Stent-related complications included minor pancreatitis (3 patients), transient pain (1 patient), and cholangitis (1 patient). Stent removal was achieved in all patients but 2 whose stents had migrated distally. Partial stent dislocation was noted in 5 patients (upward in 4, downward in 1). Complications associated with stent removal were minor, including self-contained hemorrhage (1 patient) and fever (1 patient). The stricture persisted at the end of treatment in 3 patients (13.6%), all of whom had stent migration or dislocation. Recurrence of anastomotic stricture after initial success occurred in 9 of 19 patients (47.4%) within 3.5 ± 2.1 months. Sustained stricture resolution was observed in 10 of 19 patients (52.6%), 45.6% from an intent-to-treat perspective. Limitations Uncontrolled study with limited follow-up. Conclusions Temporary placement and removal of PCSEMSs in anastomotic biliary strictures after liver transplantation is feasible, although sometimes demanding. Stent migration may impair final outcome.

Although laparoscopic liver resection is widely performed, many technical difficulties remain, such as accurate isolation/division of hepatic vessels in laparoscopic right hepatectomy (LRH). Innovative surgical devices, such as three-dimensional (3D) laparoscopy and optimized carbon dioxide (CO2) insufflation system, may help to overcome technical difficulties in LRH. The purpose of this study was to analyze the efficacy of 3D vision associated with active pneumoperitoneum maintenance in LRH. In our prospectively maintained database from 2006, 75 consecutive LRH from May 2011 to June 2017 were included in this study. All LRH were performed with 2D vision and standard CO2 insufflator (2D-LRH group, 45 cases) or 3D vision with optimized CO2 insufflator (3D-LRH group, 30 cases). Preoperative clinical characteristics, surgical data including operation time of separate steps within the procedure, and postoperative complications were compared between the two groups. Clinical and pathological factors were comparable between two groups. Total operative time was significantly shorter in 3D-LRH group than in 2D-LRH (360 vs 390 min, P = 0.029). Right hepatic pedicle dissection time was significantly shorter in 3D-LRH group (101 vs 123 min, P = 0.003). Liver parenchyma transection time was also shorter in 3D-LRH group (138 vs 151 min, P = 0.089), although not significant. There was no significant difference in liver mobilization time, intraoperative bleeding/transfusion, and postoperative complications. 3D vision with maintenance of pneumoperitoneum facilitates hepatic vascular isolation/division, and may contribute to the development of LRH.

Objective: To retrospectively evaluate the feasibility of thoracoscopic removal of mediastinal parathyroids. Summary Background Data: Mediastinal exploration to resect ectopic parathyroid(s) is needed in approximately 2% of cases in hyperparathyroidism. Recent advances in thoracoscopic surgery allow for a minimally invasive treatment. Methods: From 1999 through 2007, 13 patients affected by primary hyperparathyroidism (11 females, mean age 60 years, range: 22–88) underwent thoracoscopic removal of mediastinal parathyroids. Scintigraphy produced positive results in 11 of 13 cases, computed tomography scan in 9 of 10, parathyroid hormone venous sampling in 10 of 10 patients, and magnetic resonance imaging in 5 of 7. Right thoracoscopic access was used in 9 patients, left in 4. Postoperative outcome was analyzed. Results: Thoracoscopy enabled retrieval of mediastinal parathyroids in 10 of 13 (78%) cases. Mean operating time was 92 minutes (range: 50–240). One procedure (8%) was converted. No perioperative deaths/major complications occurred. Mild complications occurred in 2 of 13 (15%) patients (pneumothorax/pneumonia, transient recurrent nerve palsy). Mean hospital stay was 4.7 days (range: 2–15). At a mean follow-up of 73 months (range: 16–105), parathyroid hormone and calcium venous concentrations were high in 3 patients. Unsuccessful procedures were related to doubtful or non–concordant preoperative localization. Conclusions: The thoracoscopic approach for mediastinal parathyroidectomy is feasible and safe. An accurate preoperative work-up should be standardized to avoid useless procedures. In case of negative preoperative localization of the abnormal gland, thoracoscopy should not be adopted as a diagnostic tool.

Background/Objective: Oxaliplatin-based chemotherapy induces sinusoidal obstruction syndrome (SOS) lesions in the nontumorous liver parenchyma, which may increase the risk of liver resection for colorectal liver metastases. The objective of this study was to evaluate the accuracy of aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 scoring systems to predict chemotherapy-associated liver injury and to correlate the severity of sinusoidal injury with postoperative outcome. Methods: Between 1998 and 2007, 78 patients were operated for colorectal liver metastases after preoperative oxaliplatin-based chemotherapy. Grading of steatosis and SOS in the nontumorous liver parenchyma was obtained in these patients. Univariate analysis of 18 preoperative factors to predict SOS occurrence was performed as well as multivariate analysis. Relevance of preoperative platelet count level, transaminase levels, and fibrosis scoring systems were evaluated to predict high grade lesions of SOS using a receiving operative curve analysis. Ninety-day mortality and morbidity were studied according to SOS severity in 51 patients who underwent major liver resection. Results: Overall, pathologic examination showed high-grade lesions of SOS (SOS 2/3) in 46 (59%) patients. Univariate analysis showed that a low preoperative platelet count, elevated preoperative aspartate aminotransferase, short interval between chemotherapy and surgery were significant factors associated with high-grade lesions of SOS. Multivariate analysis showed that only the APRI score was an independent predictive factor for severe SOS. Receiving operative curve analysis revealed that the cut-off value predicting high-grade lesions of SOS with the best accuracy was an APRI score of 0.36 (area under the curve, 0.85; sensitivity, 87%; specificity, 69%). After major liver resection (n = 51), SOS 2/3 (n = 38) was associated with postoperative hepatic dysfunction (26/38 in SOS 2/3 vs. 3/13 in SOS 0/1; P = 0.004) and ascites (P = 0.03). Conclusion: A low preoperative platelet count and high APRI score seem to be the most reliable indicators to predict SOS severity.

Background/Aims In France, the most common cause of cirrhosis is excessive alcohol consumption. Post-transplant survival rates in patients with alcoholic liver disease (ALD) are at least as good as those seen with other indications. However, fewer of these patients are found on the waiting list. To understand the reasons for this discrepancy, it was decided to examine physicians' attitudes concerning the allocation of deceased donor liver allografts. Methods Using a standardized postal questionnaire, 1739 physicians were asked to allocate 100 liver transplants to two competing groups of patients who were equivalent except for the cause of their cirrhosis (i.e. alcohol-related or primary biliary cirrhosis). A composite score was then used to assess their attitude regarding the behavior of alcoholics and their responsibility for their illness. Results Among the 475 respondents (response rate: 27.3%), 55.2% allocated fewer than 50 transplants to ALD patients. This lower rate was independently associated with factors such as being a general practitioner (odds ratio [OR]=3.2, 95% confidence interval [95%CI]=1.8–5.9), a misinterpretation of ALD patients being equivalent to others (OR=1.8, 95%CI=1.1–3.0) or unfavorable attitudes regarding alcoholics (OR=4.0, 95%CI=1.7–9.5, to OR=126.8, 95%CI=34.0–472.1). Conclusions Greater information and education of physicians may improve access to liver transplantation for ALD patients.

Points essentiels Pour des raisons de volume, une greffe « donneur vivant » chez l’adulte necessite de prelever dans la grande majorite des cas un foie droit chez le donneur . Une greffe pediatrique necessite le prelevement du lobe gauche chez le donneur. La mortalite et la morbidite postoperatoires de la lobectomie gauche sont significativement inferieures a celles d’une hepatectomie droite pour le donneur. Malgre des contraintes techniques plus importantes, les resultats de la « transplantation hepatique a donneur vivant » (THDV) sont comparables a ceux de la TH cadaverique a la condition qu’elle soit realisee dans un centre expert. L’indice de masse corporelle eleve, des troubles de l’hemostase et des anomalies du bilan de thrombose representent les premieres contre-indications au don .

Cholecystocolonic fistula (CCF) is the second most common cholecystoenteric fistula and is often discovered intraoperatively, resulting in a challenging situation for the surgeon, who is forced to switch to a complex procedure, often in old, unfit patients. Management of this uncommon but possible finding is still ill defined. An extensive review of 160 articles published from 1950 to 2006 concerning 231 cases of CCF was performed. CCF is mostly an affliction of women in their sixth to seventh decades and is rarely diagnosed preoperatively. Chronic diarrhea is the key symptom in nonemergency patients, but, in one-fourth of cases, CCF presents with an acute onset, mostly biliary ileus. In one-fourth of patients, a second hepatobiliary abnormality is present, including gallbladder cancer in 2% of cases. In uncomplicated cases, diverting colostomy is not performed anymore, and laparoscopy treatment has been described in specialized centers. Symptomatic treatment of concomitant biliary ileus (without treating CCF) is a feasible option. Resolution of colonic biliary ileus by interventional endoscopy is reported. CCF should be considered in differential diagnosis of diarrhea, especially in old, female patients. A possible second hepatobiliary abnormality should be always investigated. Extemporaneous frozen section should be performed if gallbladder cancer is suspected. Depending on clinical presentation, different treatments for CCF are indicated, ranging from minimally invasive procedures to extensive resection.

IL-4 is overexpressed in liver grafts during severe recurrent hepatitis C and rejection. Hepatocyte apoptosis is involved in both these phenomena. We therefore examined the proapoptotic effect of IL-4 on HepG2 cells and human hepatocytes in vitro, together with the underlying mechanisms. We first measured IL-4 receptor expression, STAT6 activation by IL-4, and STAT6 inhibition by an anti-IL-4 antibody or by STAT6 siRNA transfection. We then focused on the pathways involved in IL-4-mediated apoptosis and the role of STAT6 activation in apoptosis initiation. The IL-4 receptor was expressed on both cell types, and STAT6 was activated by IL-4. Both anti-IL-4 and STAT-6 siRNA inhibited this activation. IL-4 induced apoptosis of both HepG2 cells (P=0.008 vs. untreated control) and human hepatocytes (P

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) got wide success among hepatic surgeons as an efficient way to shorten to 7 days from the 4 weeks interval of classic 2-staged hepatectomy. The main disadvantage of ALPPS is the onset of inflammatory adhesions, particularly on the hepatic pedicle region, previously dissected. The aim of the study is the evaluation of a resorbable collagen membrane (CM) indicated in the prevention of postoperative adhesions as an alternative to the use of a plastic bag (PB) during ALPPS procedure. All patients undergoing ALPPS procedure in our department were prospectively included in a database. At the end of the first surgery, at least one resorbable CM (COVA+™, Biom’Up, France) was placed instead of a PB. Intraoperative adhesions during the second step and clinical short-term safety were assessed. Ten patients with a mean age of 57.5 years underwent a 2-staged hepatectomy through ALPPS approach. At the second stage, 90 % of the patients experienced either grade-0 (no adhesion) or grade-I adhesions (mild adhesions easily divided). None of the reported complications were related to the use of the CM. To our knowledge, this is the first clinical study evaluating the use of an anti-adhesion resorbable CM as a safe and efficient alternative to PB in ALPPS procedures.

Background The incidence of biliary complications following liver transplantation (LT) remains high, ranging from 10 to 50 % of patients, especially when the diameter of the bile duct is smaller than 7 mm. Biliary reconstruction is most often performed by duct-to-duct anastomosis. In a preliminary study (n = 20), we previously reported a technique of biliary reconstruction using an intraductal stent tube followed by its endoscopic removal and showed both the feasibility and safety of this innovative procedure. The next step is to validate the potential benefit of this procedure in a randomized controlled trial. Design This is a multicenter randomized controlled trial in France comparing the efficacy of biliary reconstruction with or without a removable intraductal stent on reducing biliary complications. Inclusion and randomization are performed during LT when a duct-to-duct biliary anastomosis smaller than 7 mm in diameter is envisioned. In the intraductal stent group, a custom-made segment of a T-tube is placed into the bile duct and removed endoscopically 4 to 6 months later. The surgical technique is described in a video during randomization and is available on the secure website used for inclusion and randomization. The primary endpoint is the occurrence of biliary complications, including biliary fistulae and strictures, during the 6 months of follow-up. Secondary evaluation criteria are the incidence of complications related to the stent placement and its extraction by endoscopy. The inclusion of 248 patients in total has been determined based on an expected incidence of biliary complications of 25 % in the non-IST group and a 60 % reduction of biliary complications (10 %) in the IST group. Discussion Biliary complications following LT are significant causes of morbidity, retransplantation, and mortality. Although controversial, the use of a T-tube has been proven to be useless and even responsible for specific complications related to the external part of the tube in many studies, including several randomized trials. However, several studies have identified a small bile duct diameter as a risk factor for biliary stenosis. A threshold of 7 mm was found to be significantly associated with biliary stenosis. Our team published a preliminary study that included 20 patients using a new technique of intraductal stenting. Only four complications were reported in the overall study population, whereas no biliary complication occurred in the subgroup of patients who received a whole graft LT. Moreover, no technical failures and no procedure-related complications were noted before and during the drain removal. Although an intraductal stent tube in duct-to duct biliary anastomosis seems feasible and safe, a multicenter randomized controlled trial is needed to validate its benefit as a protective tool against the occurrence of biliary complications. One original aspect of this protocol is the video demonstration of the surgical procedure, which is available on the web to standardize and homogenize the technique. The surgical community may be inspired by this type of tool in the future to minimize technical bias related to technical issues. Trial registration NCT02356939, date of registration 2 February 2015.

International audience; The nodular lymphoid lesion of the liver known as reactive lymphoid hyperplasia or pseudolymphoma is rare and its pathogenesis is unknown. We report two cases of nodular lymphoid lesions of the liver with numerous IgG4-positive plasma cells in patients with primary biliary cirrhosis. Histologically, in both cases, the lesion showed a dense lymphoplasmacytic infiltrate with lymphoid follicles and granulomas. Fibrous tissue was scarce and without a storiform pattern. Obliterative phlebitis was not identified. The IgG4+ plasma cell counts were 82 and 76 per high power field, with an IgG4/IgG ratio of 75 and 64 %, respectively, which qualifies the lesions according to the diagnostic criteria for IgG4-related disease as « probable histological feature of IgG4-related disease ». There were no rearrangements of immunoglobulin heavy-chain genes and plasma cells had a polytypic pattern of kappa and lambda light-chain expression. The non-tumor liver showed primary biliary cirrhosis with destructive cholangitis without IgG4 plasma cells. In both cases, IgG4-related disease was not found in other organs neither at the time of diagnosis nor 3 years later. Serum IgG4 levels normalized after local ablation of the lesions. It seems unlikely that these lesions are a manifestation of IgG4-related disease. However, because the pathogenesis of both nodular lymphoid lesions and IgG4-related disease remains unclear, further studies are needed to elucidate a potential link between nodular lymphoid lesions of the liver and an increased number of IgG4 plasma cells. More definite conclusions will be possible when the pathogenesis of IgG4-related disease has been clarified.

Background Although recent reports have suggested the potential advantages of laparoscopy in patients undergoing major hepatectomy, the benefits of this approach in elderly patients remain unclear. This study aimed to compare the short-term outcomes of laparoscopic major hepatectomy (LMH) and open major hepatectomy (OMH) in elderly patients. Study Design All patients aged 55 years and older undergoing laparoscopic LMH between 2000 and 2013 at 2 centers were retrospectively analyzed and divided into 3 groups (group 1: 55 to 64 years old; group 2: 65 to 74 years old; and group 3: 75 years and older). Risk factors for postoperative complications were determined on multivariable analysis in the overall LMH population and in each LMH group. Outcomes of LMH patients were compared with those of patients of similar age undergoing OMH at another center after propensity score matching. Results Laparoscopic major hepatectomy was performed in 174 patients, including 72 (41.4%) in group 1, 67 (38.5%) in group 2, and 35 (20.1%) in group 3. On multivariable analysis, diabetes (odds ratio [OR] = 2.349; 95% CI, 1.251–2.674; p = 0.047), American Society of Anesthesiologists status (OR = 2.881; 95% CI, 2.193–3.71; p = 0.017), cirrhosis (OR = 1.426; 95% CI, 1.092–2.025; p = 0.043), right-sided resection (OR = 2.001; 95% CI, 1.492–2.563; p = 0.037), conversion (OR = 1.950; 95% CI, 1.331–2.545; p = 0.024), and intraoperative transfusion (OR = 2.338, 95% CI, 1.738–2.701, p = 0.032) were associated with increased risk of postoperative complications in the whole LMH population. After propensity score matching, laparoscopy was associated with significantly decreased rates of pulmonary complications and shorter hospital stays in all groups, decreased rates of overall complications in group 2 and group 3, and decreased rates of postoperative confusion in group 3. Conclusions The current study supports the benefits of laparoscopy in decreasing postoperative complications in elderly patients requiring major hepatectomy.

Liver injuries most often (>90% of all cases) are associated with other injuries such as ipsilateral rib fractures, lung contusions, other intra-abdominal lesions, or injuries of the extremities, the pelvis and the head. Hepatic injuries are graded according to the Organ Injury Scale of the American Association for the Surgery of Trauma (AAST-OIS) (Table1).

We have developed a culture model to assess antifibrotic drugs using normal human liver myofibroblasts (HLMFs) obtained from 31 subjects. Activation was evaluated in terms of α-smooth muscle actin (α-SMA) and collagen 1 (Coll1) expression using RT-PCR, and proliferation as the uptake of 5-ethynil-2'-deoxyuridine. Under analysis of variance, between-subject differences accounted for 70% of all variability and inter-experiment differences for 30%. The sensitivity of the model was determined by quantifying the effects in terms of relative expression, which were 0.74±0.03 for cyclosporine A (CsA) and 2.4±0.10 for transforming growth factor-beta (TGF-β) (P

Bile leakage (BL) remains a common cause of major morbidity after open major liver resection but has only been poorly described in patients undergoing laparoscopic major hepatectomy (LMH). The present study aimed to determine the incidence, risk factors and consequences of BL following LMH.All 223 patients undergoing LMH between 2000 and 2013 at two tertiary referral centres were retrospectively analysed. BL was defined according to the International Study Group of Liver Surgery, and its incidence and consequences were assessed. Risk factors for BL were determined on multivariate analysis.BL occurred in 30 (13.5 %) patients, and its incidence remained stable over time (p = 0.200). BL was diagnosed following the presence of bile into the abdominal drain in 14 (46.7 %) patients and after drainage of symptomatic abdominal collections in 16 (53.3 %) patients without intra-operative drain placement. Grade A, B and C BL occurred in 3 (10.0 %), 23 (76.6 %) and 4 (13.4 %) cases, respectively. Interventional procedures for BL included endoscopic retrograde cholangiography, percutaneous and surgical drainage in 10 (33.3 %), 23 (76.7 %) and 4 (13.3 %) patients, respectively. BL was associated with significantly increased rates of symptomatic pleural effusion (30.0 vs. 11.4 %, p = 0.006), multiorgan failure (13.3 vs. 3.6 %, p = 0.022), postoperative death (10.0 vs. 1.6 %, p = 0.008) and prolonged hospital stay (18 vs. 8 days, p 0.001). On multivariable analysis, BMI 28 kg/m(2) (OR 2.439, 95 % CI 1.878-2.771, p = 0.036), history of hepatectomy (OR 1.675, 95 % CI 1.256-2.035, p = 0.044) and biliary reconstruction (OR 1.975, 95 % CI 1.452-2.371, p = 0.039) were significantly associated with increased risk of BL.After LMH, BL occurred in 13.5 % of the patients and was associated with significant morbidity. Patients with one or several risk factors for BL should benefit intra-operative drain placement.

Background & aims The contribution of liver biopsy for the diagnosis of presumed benign hepatocellular lesions lacking the diagnostic features of focal nodular hyperplasia (FNH) on magnetic resonance imaging (MRI) is unknown. We evaluated liver biopsy and MRI performances in this setting. Methods Magnetic resonance imaging and slides of liver biopsies performed for a presumed benign hepatocellular lesion (2006-2013) without the typical features of FNH on MRI were blindly reviewed (n = 45). Eighteen lesions were surgically removed and also analyzed. The final diagnosis was the diagnosis established after surgery or on the biopsy in the absence of surgery. Results The final diagnosis was FNH (n = 19), hepatocellular adenoma (HCA, n = 15), hepatocellular carcinoma (n = 3) and indefinite (n = 4). Four lesions corresponded to non hepatocellular lesions. FNH, HNF1A mutated and inflammatory HCA were diagnosed accurately on the biopsy in 95%, 67% and 100% of the cases respectively. Diagnostic performance of liver biopsy for HNF1A mutated HCA was lower because of the lack of non-tumoral tissue. Diagnosis based on morphological analysis was certain and correct in 27 cases. Immunostaining allowed a definite diagnosis in 12 additionnal cases. Radiological diagnosis was in agreement with the histological diagnosis in 75.6% of the cases, with a very high sensitivity (97%) and specificity (100%) for the diagnosis of HNF1A mutated HCA. Conclusions Liver biopsy has a good diagnostic performance particularly for FNH and inflammatory HCA, and sampling of non-lesional tissue is highly recommended. A biopsy does not seem necessary if H-HCA is diagnosed on MRI.

The aim of this study was to compare survival outcomes in patients enlisted for liver transplantation following liver resection for hepatocellular carcinoma before or at recurrence. All patients enlisted for liver transplantation following liver resection for hepatocellular carcinoma from 1996 to 2013 were included and compared according to their status at the time of enlistment: before (de principe) or at (salvage) recurrence. Primary end-point was survival since resection. One hundred and twenty-one patients were enlisted for liver transplantation following liver resection for hepatocellular carcinoma. Ten patients enlisted for cirrhosis decompensation were excluded from the analysis. Sixty-three patients were enlisted de principe, and 48 for a salvage transplantation. Eleven patients dropped-out. According to per-protocol analysis, the mean diameter of the largest tumor was the only different pathological characteristic of initial resection between groups (31.6 mm in the de principe group versus 48.3 in the salvage, p = 0.017). The 5-year overall survival rate was significantly increased in the de principe group compared to salvage (84.6 versus 74.8 %, p = 0.017). In a multivariate analysis, the salvage strategy was the only independent prognostic factor for death (p = 0.040; OR = 2.5 [1.1–5.8]). De principe enlistment for liver transplantation following liver resection for hepatocellular carcinoma is associated with greater survival.

International audience; The development and progression of liver cancer are characterized by increased levels of reactive oxygen species (ROS). ROS-induced oxidative stress impairs cell proliferation and ultimately leads to cell death. Although liver cancer cells are especially resistant to oxidative stress, mechanisms of such resistance remain understudied. We identified the MAPK-activated protein kinase 2 (MK2)/Heat shock protein 27 (Hsp27) signaling pathway mediating defenses against oxidative stress. Besides to MK2 and Hsp27 overexpression in primary liver tumors compared to adjacent non-tumorous tissues, MK2/Hsp27 pathway is activated by hydrogen peroxide-induced oxidative stress in hepatobiliary cancer cells. MK2 inactivation or inhibition of MK2 or Hsp27 expression increases Caspase-3 and PARP cleavage and DNA breaks, and therefore cell death. Interestingly, MK2/Hsp27 inhibition decreases antioxidant defenses such as heme-oxygenase 1 (HO-1) through down-regulation of the transcription factor nuclear factor-erythroid-derived 2-like 2 (Nrf2). Moreover, MK2/Hsp27 inhibition decreases both phosphorylation of epidermal growth factor receptor (EGFR) and expression of its ligand, heparin-binding EGF-like growth factor (HB-EGF). A new identified partner of MK2, the scaffold PDZ-protein EBP50, could facilitate these effects through MK2/Hsp27 pathway regulation. These findings demonstrate that MK2/Hsp27 pathway actively participates in resistance to oxidative stress and may contribute to liver cancer progression.

Transection methods and hemostasis achievement have an impact on blood loss, and consequently on outcome and survival. However, no consensus exists on parenchymal transection or hemostasis techniques in laparoscopic liver resection (LLR). The aim of this review is to clarify the role of energy devices (ED) in LLR. ED is a generator of mechanic or electric energy transfer to an operating tool, used for transection, sealing or both. Searches were performed in PubMed, PubMed Central, Cochrane, Embase, Google Scholar in human or animal experimental models. Each study quality was graded following the GRADE system. From 1996 to 2014, 30 studies were found: five comparative, one prospective, two case-control, and 16 case series and some case reports, with level of evidence ranging from Moderate to Very Low. Since 2012, the Research and Development of new tools raised quicker than clinical studies could follow. The two main techniques emerged are blind transection versus sharp dissection: due to the low quality and heterogeneity of the studies, no firm conclusion can be drawn, but meticulous dissection of vessels usually never leads to vascular damage. As a matter of fact, ED, though efficient and reliable, cannot replace the basic skills of hepatic surgery: sharp dissection, vascular control and elective sealing.

Living Donors are the best theoretical candidates to benefit from the advantages of laparoscopy, but development was slow because of concerns about graft integrity and donor safety. Herein our 13-year experience in laparoscopic Living Donor Liver Transplantation (LDLT) is presented. Laparoscopic Left Lateral Section (LLLS) was performed in children receiver, while Laparoscopic Left Hepatectomy (LLH)—including or not the middle hepatic vein—and Laparoscopic Right Hepatectomy (LRH) in adults. Two senior surgeons were always involved for each procedure. All donors were first-degree relatives. From 2001 to 2014, 71 procedures were performed: 63 LLLS (88.7 %, 6 LLH (8.4 %), and 2 LRH (2.8 %). Surgical procedures required a mean of 271.1 ± 65.9, 318 ± 40.2, and 480 ± 0 min for LLLS, LLH, and LRH, respectively with a learning curve toward LLLH over the years (r = 0.09). Seven procedures (9.8 %) required conversion. The mean hospital stay was 5.5 ± 3.4, 5.3 ± 0.6, and 8 ± 0 days for LLLS, LLH, and LRH, respectively. Complications occurred in 11 patients (17.3 %) undergoing LLLS: 8 (12.7 %) grade I and 3 (4.7 %) grade II, according to the Modified Clavien–Dindo classification. Laparoscopic liver resection for LDLT requires an equivalent and parallel expertise in open LDLT and LLR. If LLLS for LDLT is now in an exploration phase in highly specialized centers, LLH and LRH for LDLT in adults lack evidence and cannot be recommended for wide introduction. For laparoscopic LDLT beginners, LLLS offers optimal conditions.

SummaryLaparoscopic liver resection has been recognized as a safe and efficient approach since the Louisville Conference in 2008, but its use still remains confined to experienced teams in specialized centers, and may lack some standardization. The 2013 Session of French Association for Hepatobiliary and Pancreatic Surgery (ACHBT) specifically focused on laparoscopic liver surgery and the particular aspects and issues arising since the 2008 conference. Our objective is to provide an update and summarize the current French position on laparoscopic liver surgery. An overview of the current practice of laparoscopic liver resections in France since 2008 is presented. The issues surrounding standardization for left lateral sectionectomy and right hepatectomy, hybrid and hand-assisted techniques are raised and discussed. Finally, future technologies and technical perspectives are outlined.

To compare both incidence and types of postoperative pulmonary complications (PPCs) between laparoscopic major hepatectomy (LMH) and open major hepatectomy (OMH).LMHs are increasingly performed. Yet, the benefits of laparoscopy over laparotomy regarding PPCs remain unknown.In this multi-institutional study, all patients undergoing OMH or LMH between 1998 and 2013 were retrospectively reviewed. Risk factors for PPCs were analyzed on multivariate analysis. Comparison of both overall rate and types of PPCs between OMH and LMH patients was performed after propensity score adjustment on factors influencing the choice of the approach.LMH was performed in 226 (18.6%) of the 1214 included patients. PPCs occurred in 480 (39.5%) patients including symptomatic pleural effusion in 366 (30.1%) patients, respiratory insufficiency in 141 (11.6%), acute respiratory distress syndrome in 84 (6.9%), pulmonary infection in 80 (6.5%), and pulmonary embolism in 47 (3.8%) patients. On multivariate analysis, preoperative hypoprotidemia [hazard ratio (HR): 1.341, 95% confidence interval (CI): 1.001-1.795; P = 0.049], open approach (HR: 2.481, 95% CI: 1.141-6.024; P = 0.024), right-sided hepatectomy (HR: 2.143, 95% CI: 1.544-2.975; P0.001), concomitant extrahepatic procedures (HR: 1.742, 95% CI: 1.103-2.750; P = 0.017), transfusion (HR: 2.851, 95% CI: 2.067-3.935; P0.001), and operative time more than 6 hours (HR: 1.510, 95% CI: 1.127-2.022; P = 0.006) were independently associated with PPCs. After propensity score matching, the overall incidence of PPCs (13.2% vs 40.5%, P0.001), symptomatic pleural effusion (11.6% vs 26.4%, P = 0.003), pleural effusion requiring drainage (1.7% vs 9.9%, P = 0.006), and acute respiratory distress syndrome (1.7% vs 9.9%, P = 0.006) were significantly lower in the laparoscopy group than in the open group.Pure laparoscopy allows reducing PPCs in patients requiring major liver resection.

If advances on radiotherapy allowed closing the page on poor Hodgkin Lymphoma prognosis, a new one opens dramatically on the long term effects, as second malignancies radiotherapy-related. Clinician and surgeons are faced to a new dilemma towards these patients, when surgical incision and intervention has to be performed in the radiation field, known to be fraught with serious consequences from delayed cicatrisation to death.

Hepatocellular carcinoma (HCC) often recurs after curative resection, and thus the optimal treatment strategy to treat recurrences remains uncertain. We analyzed the results of different options to treat recurrent HCC and emphasized the impact of pathologic patterns of the tumor at initial resection.Between 2000 and 2014, 293 patients underwent potentially curative hepatic resection for HCC. Among them, 150 experienced a recurrence and have been treated by repeat resection (RR), radiofrequency ablation (RFA), salvage liver transplantation (SLT), transarterial chemoembolization (TACE), or conservative treatment, including systemic or targeted chemotherapy. Clinical outcomes were analyzed and compared between the treatment groups, focusing on clinical and pathologic characteristics of the tumor at initial resection.After a median follow-up of 26 months, the overall survival (OS) at 1, 3, and 5 years after recurrence was 62%, 48%, and 40%, respectively. Survival rates were greater in patients treated by a curative approach (RR, RFA, SLT) than those treated by TACE, with 5-year OS of70% and 37%, respectively. Univariate analysis showed satellitosis and microvascular invasion (MVI) at initial resection as negative prognostic factors of survival after recurrence (P.05). On multivariate analysis, type of treatment was the only independent factor associated with survival. A subgroup analysis showed that RR/RFA led to better survival outcomes than TACE for early stage intrahepatic recurrences in the absence of satellitosis or MVI on the primary resected tumor.Curative treatments of recurrent HCC improve patient survival. Satellitosis and MVI on the primary resected specimen may be used as selection criteria for the best treatment strategy for intrahepatic recurrences.

Living donor liver transplantation has become a widely accepted alternative to cadaveric transplantation in children. The use of liver grafts from living donors provides similar or even better short-term graft function and long-term survival rates, especially in children, as compared with whole and split cadaver liver grafts.1,2 The number of children receiving liver grafts from living donors is increasing annually in our institution. This procedure is, however, limited by surgical risks brought upon donors. Left lateral sectionectomy performed through open approach is a well-standardized procedure, associated with a lower rate of complications and mortality than right hepatectomy in living donors for adult transplantation. In living donations for liver transplantation in children, optimizing the postoperative course and limiting abdominal wall injury, especially in those young donors, remain of special concern. Minimally invasive donor nephrectomy using laparoscopic techniques has been widely reported and appeared beneficial for the donor as compared with standard open surgery, decreasing the overall morbidity, and improving donors' quality of life at low cost3–5 without deleterious effects on recipient's long-term kidney function.6 Considering our acquired expertise in laparoscopic liver resection7,8 and our training of standard open surgery as well as liver graft harvesting in living donors, we decided to propose laparoscopic left lateral sectionectomy in donors for liver transplantation in children. Since describing its technical feasibility with the first 2 cases,9 we have developed this procedure and we are now able to assess its safety and reproducibility in our center. Furthermore, during the first period of our experience in graft harvesting for children, a standard open surgical approach was used. This initial experience allowed us to compare both techniques of left lateral section harvesting. The primary goals of the present study were to validate the safety and reproducibility of the laparoscopic technique within our department of surgery.

Resume Lorsque le rapport poids d’un greffon hepatique/poids corporel du receveur est inferieur a 0,8 %, le risque de non fonction primaire du greffon est proche de 50 %. Nous rapportons la premiere experience mondiale d’une transplantation auxiliaire orthotopique pour cirrhose utilisant un greffon gauche issu d’une bipartition de foie cadaverique et dont le rapport poids du greffon/poids corporel du receveur etait de 0,6 %. Le foie droit natif restant a ete reseque deux mois apres la transplantation. A cinq ans, le malade va bien et son bilan hepatique est normal. Les indications de l’utilisation de petits greffons gauches issus de la bipartition de foie cadaverique ou de donneur vivant sont discutees.

Cystic fibrosis (CF) is the most frequent genetic disease in the Caucasian population. It seems to be associated with an increased risk of digestive cancer but only few cases of pancreatic tumors have been reported. As pancreatic lesions of the pancreas in CF patients are not rare, their etiological diagnosis is substantial. We report herein a case of a mucinous cystadenoma in a patient with CF. Diagnosis and management of pancreatic cystic tumors in patients at high risk of operative morbidity are challenging. When the potential malignancy of a pancreatic cystic mass cannot be well established in a CF patient, partly because of frequent chronic pancreatitis lesions, we suggest that surgical management should be undertaken instead of radiological surveillance.

Background Although recent reports have suggested potential benefits of the laparoscopic approach in patients requiring major hepatectomy, it remains unclear whether conversion to open surgery could offset these advantages. This study aimed to determine the risk factors for and postoperative consequences of conversion in patients undergoing laparoscopic major hepatectomy (LMH). Methods Data for all patients undergoing LMH between 2000 and 2013 at two tertiary referral centres were reviewed retrospectively. Risk factors for conversion were determined using multivariable analysis. After propensity score matching, the outcomes of patients who underwent conversion were compared with those of matched patients undergoing laparoscopic hepatectomy who did not have conversion, operated on at the same centres, and also with matched patients operated on at another tertiary centre during the same period by an open laparotomy approach. Results Conversion was needed in 30 (13·5 per cent) of the 223 patients undergoing LMH. The most frequent reasons for conversion were bleeding and failure to progress, in 14 (47 per cent) and nine (30 per cent) patients respectively. On multivariable analysis, risk factors for conversion were patient age above 75 years (hazard ratio (HR) 7·72, 95 per cent c.i. 1·67 to 35·70; P = 0·009), diabetes (HR 4·51, 1·16 to 17·57; P = 0·030), body mass index (BMI) above 28 kg/m2 (HR 6·41, 1·56 to 26·37; P = 0·010), tumour diameter greater than 10 cm (HR 8·91, 1·57 to 50·79; P = 0·014) and biliary reconstruction (HR 13·99, 1·82 to 238·13; P = 0·048). After propensity score matching, the complication rate in patients who had conversion was higher than in patients who did not (75 versus 47·3 per cent respectively; P = 0·038), but was not significantly different from the rate in patients treated by planned laparotomy (79 versus 67·9 per cent respectively; P = 0·438). Conclusion Conversion during LMH should be anticipated in patients with raised BMI, large lesions and biliary reconstruction. Conversion does not lead to increased morbidity compared with planned laparotomy.

Mammalian target rapamycin inhibitors (m-TORi) are increasingly used in patients undergoing liver transplantation (LT). Yet, there is rising concern that they also could impair wound healing and favor the development of several surgical complications. This report was designed to evaluate both feasibility and safety of major surgery in liver transplant recipients receiving m-TORi–based immunosuppression without therapeutic discontinuation. From 2007 to 2012, six liver transplant recipients underwent nine major abdominal or thoracic surgical procedures without m-TORi discontinuation or specific dosage adjustment. Their characteristics and postoperative outcomes were retrospectively analyzed. Indications for m-TORi were de novo or recurrent malignant disease in five patients and calcineurin inhibitors related neurologic toxicity in one patient. Abdominal procedures, thoracic procedures, and combined thoracic and abdominal procedures were performed in six, two, and one cases respectively. Emergency surgery was performed in one case and elective procedures were performed in eight cases, including five for malignant disease and three for late surgical complications following LT. No patient died postoperatively. One major complication was observed, but no patient required reoperation. No evisceration, incisional surgical site infection, or lymphocele occurred. Major surgery in liver transplant recipients receiving m-TOR inhibitors appears both feasible and safe without therapeutic discontinuation or specific dosage adjustment.

In Western countries, living donor liver transplantation (LDLT) may represent a valuable alternative to deceased donor liver transplantation. Yet, after an initial peak of enthusiasm, reports of high rates of complications and of fatalities have led to a certain degree of reluctance towards this procedure especially in Western countries. As for living donor kidney transplantation, the laparoscopic approach could improve patient's tolerance in order to rehabilitate this strategy and reverse the current trend. In this setting however, initial concerns regarding patient's safety and graft integrity, need for acquiring surgical expertise in both laparoscopic liver surgery and living donor transplantation and lack of evidence supporting the benefits of laparoscopy have delayed the development of this approach. Similarly to what is performed in classical resectional liver surgery, initial experiences of laparoscopy have therefore begun with left lateral sectionectomy, which is performed for adult to child living donation. In this setting, the laparoscopic technique is now well standardized, is associated with decreased donor blood loss and hospital stays and provides graft of similar quality compared to the open approach. On the other hand laparoscopic major right or left hepatectomies for adult-adult LDLT currently lack standardization and various techniques such as the full laparoscopic approach, the hand assisted approach and the hybrid approach have been reported. Hence, even-though several reports highlight the feasibility of these procedures, the true benefits of laparoscopy over laparotomy remain to be fully assessed. This could be achieved through standardization of the procedures and creation of international registries especially in Eastern countries where LDLT keeps on flourishing.

Objective To evaluate a new conceptual technique of laparoscopic right hepatectomy. Background Despite significant improvements in surgical care in the last decades, morbidity is still high after major hepatectomy. Blood loss and transfusions are known to significantly increase the risk of postoperative complications and cancer recurrence after liver resection. A laparoscopic approach may improve perioperative outcomes in these cases, but data in literature are limited and the surgical technique is not yet standardized. Methods A new conceptual technique of right hepatectomy was designed using evidence-based facts and oncologic rules: laparoscopy with pneumoperitoneum, low central venous pressure, intermittent pedicle clamping, anterior approach without mobilization, and parenchymal section with ultrasonic dissector. Thirty patients were prospectively enrolled between October 2011 and September 2013. Primary endpoint was intraoperative blood loss. Results Eighty percent of patients underwent surgery for malignant disease and cirrhosis was present in 11 patients. Benign lesions accounted for 13% of indications, whereas living liver donation was performed in 2 cases. Median blood loss was 100 mL (50-700) and transfusion rate was 7%. Five patients (16.6%) required conversion to laparotomy, including 2 using hybrid technique. The median operative time was 360 minutes (210-510). R0 resection rate was 87% (21/24). Postoperative morbidity rate was 23% (7/30) with 8 complications including 6 Clavien III-IV. No respiratory complication occurred. The median hospital stay was 8 days. No patient died. Conclusions This study showed that several evidence-based facts could be combined to define a new conceptual technique of laparoscopic right hepatectomy allowing for low blood loss and morbidity.

International audience

Objective: In this study, we report the results obtained from 70 living donors in France. Background: Left lateral sectionectomy for pediatric live donor liver transplantation is a well-standardized surgical procedure. Our team introduced the laparoscopic approach to live donation in 2002, and the reproducibility and safety of this method was discussed in 2006. Methods: Between March 2001 and October 2012, a total of 70 donors underwent a liver procurement. Sixty-seven donors (95.7%) underwent a left lateral sectionectomy, and 3 underwent a left hepatectomy without middle hepatic vein procurement. All data were prospectively recorded in a database. Results: Of the 70 donors, 66 (94%) liver grafts were procured by laparoscopy, whereas 4 (6%) patients required conversion into an open technique. Seventeen donors experienced complications, leading to an overall complication rate of 24.2%. Eleven donors (16%) had grade 1 complications, according to the Clavien system. Five donors (7.1%) presented grade 2 complications, and 1 donor (1.4%) had a grade 3 complication. No death occurred. Overall, patient and graft survival rates for pediatric recipients were 95% and 92% at 1 year, 95% and 88% at 3 years, and 95% and 84% at 5 years, respectively. Conclusions: The laparoscopic retrieval of the left lateral section for live donor liver transplantation is safe and reproducible and has transitioned from an innovative surgery to a development phase in France.