Search

Postoperative early recurrence after hepatic resection for hepatocellular carcinoma (HCC) poses a challenge to surgeons, and the effect of a surgical margin is still controversial. This study aimed to identify an ideal margin to prevent early recurrence. A total of 226 consecutive patients who underwent primary curative hepatic resection for solitary and primary HCC were enrolled. The definition of early recurrence was determined using the minimum P value approach. Logistic regression analysis was used to identify the risk factors of early recurrence. The receiver-operating characteristic (ROC) curve was used to identify the optimal cut-off of the surgical margin and early recurrence. Recurrence within 8 months induced the poorest overall survival (P = 2×10−15). ROC analysis showed that the optimal cut-off value of the surgical margin was 7 mm. The risk factors of early recurrence (≤ 8-month recurrence) were preoperative alpha-fetoprotein levels ≥ 100 ng/ml (Odds ratio [OR] 4.92 [2.28–10.77], P 7-mm margin is important to prevent early recurrence. Patients with HCC and alpha-fetoprotein levels > 100 ng/ml, non-capsule formation, or microvascular invasion may have a survival benefit from a ≥ 7-mm margin.

Assessing the risk of significant macrosteatosis in donors is crucial before considering hepatic graft procurement. We aimed to build a model to predict significant macrosteatosis based on noninvasive methods. From January 2012 to December 2018, liver attenuation indices and liver-to-spleen (L/S) ratio were measured in 639 brain-dead donors by local radiologists. Quantity and quality of steatosis were evaluated by an expert pathologist, blinded for attenuation indices measurement. Macrosteatosis ≥ 30% was found in 33 donors (5.2%). Body weight, body mass index (BMI), abdominal perimeters, history of alcohol abuse, L/S ratio, and liver parenchyma attenuation were associated with macrosteatosis ≥ 30%. The L/S ratio, BMI, and a history of alcohol abuse remained independent predictors in multivariate analysis and were used to build a predictive model (C-index: 0.77). The optimal cutoff to predict macrosteatosis ≥ 60% was 0.85. Our model, including L/S ratio, BMI, and history of alcohol, might be helpful to refine indication for liver biopsy before donation after brain death. External validation is required.

Background The aim was to develop a model to predict clinically significant portal hypertension, hepatic venous pressure gradient (HVPG) ≥10mmHg using pre-operative noninvasive makers. Methods Patients who have been programmed for liver resection/transplantation were enrolled prospectively. Preoperative liver stiffness measurement (LSM), liver function test (LFT), and intraoperative HVPG were assessed. A probability score model to predict HVPG≥10mmHg called HVPG10 score was developed and validated. Results A total of 161 patients [66% men, median age of 63 years] were recruited for the study. Median LSM, and HVPG were 9.5kPa, and 5mmHg respectively. HVPG10 score was developed using independent predictors of HVPG≥10mmHg in the training set were LSM, total bilirubin, alkaline phosphatase, and international normalized ratio. Area under receiver operating curve of HVPG10 score in the training and validation sets were 0.91 and 0.93 respectively with a cutoff of 15. In the overall cohort, HVPG10 score≥15 had 83% accuracy, 90% sensitivity, 81% specificity and 96% negative predictive value in predicting HVPG≥10mmHg. Conclusion HVPG10 score is an easy-to-use noninvasive continuous scale tool to rule out clinically significant portal hypertension in >95% patients with chronic liver disease.

Ischemic cholangiopathy (IC) has a known poor prognosis. However, the risks and outcomes of this complication after transcatheter arterial chemoembolization (TACE) in hepatectomized patients are poorly documented. This study aimed to evaluate the incidence of and to identify the predictive factors for IC following TACE for recurrent hepatocellular carcinoma (HCC) after hepatectomy. From a cohort with a total of 486 patients who underwent resection for HCC, we included all consecutive patients who were treated with TACE for recurrent HCC after hepatectomy between 2000 and 2017. IC was defined by the coexistence of biological cholestasis and morphological lesions. A total of 156 patients underwent TACE for the treatment of HCC recurrence after hepatectomy. Of them, eight (5.1%) developed IC. Their prognosis was poor compared with patients without IC (3-year survival 23.4% vs 76.2%; P = 0.008). Two factors, namely, time between hepatectomy and TACE (4.8 months vs. 16.0 months, P = 0.001) and TACE for a remnant liver mobilized during hepatectomy (P = 0.001), were associated with IC. Receiver operating characteristic (ROC) curve analysis showed that 7 months was the more discriminant cutoff for the time period. IC occurred in 33.3% of the patients with the two factors, in 5.0% of those with one factor, and 0% in the absence of any factors. TACE for treating HCC recurrence carries a high risk of IC when performed early after hepatectomy in a previously mobilized liver. Our results might aid in identifying candidates for TACE for recurrent HCC, considering the major effect on patient outcomes.

Although many prognostic factors of primary graft dysfunction after liver transplantation (LT) are available, it remains difficult to predict failure in a given recipient.We aimed to determine whether the intraoperative assay of arterial lactate concentration at the end of LT (LCEOT) might constitute a reliable biological test to predict early outcomes [primary nonfunction (PNF), early graft dysfunction (EAD)].We reviewed data from a prospective database in a single center concerning patients transplanted between January 2015 and December 2016 (n = 296).There was no statistical imbalance between the training (year 2015) and validation groups (year 2016) for epidemiological and perioperative feature. Ten patients (3.4%) presented with PNF, and EAD occurred in 62 patients (20.9%); 9 patients died before postoperative day (POD) 90. LCEOT ≥5 mmol/L was the best cut-off point to predict PNF (Se=83.3%, SP=74.3%, positive likelihood ratio (LR+)=3.65, negative likelihood ratio (LR-)=0.25, diagnostic odds ratio (DOR)=14.44) and was predictive of PNF (P = 0.02), EAD (P = 0.05), and death ≤ POD90 (P = 0.06). Added to the validated BAR-score, LCEOT improved its predictive value regarding POD 90 survival with a better AUC (0.87) than BAR score (0.74). The predictive value of LCEOT was confirmed in the validation cohort.As a reflection of both hypoperfusion and tissue damage, the assay of arterial LCEOT ≥5 mmol/L appears to be a strong predictor of early graft outcomes and may be used as an endpoint in studies assessing the impact of perioperative management. Its accessibility and low cost could impose it as a reliable parameter to anticipate postoperative management and help clinicians for decision-making in the first PODs.

There are few reports on microvascular invasion (MVI) located intra- or extratumorally and prognosis of hepatocellular carcinoma (HCC). The aim of this study was to evaluate patient outcome according to the location of MVI, and to build a nomogram predicting extratumoral MVI. We included 681 consecutive patients who underwent hepatic resection (HR) or liver transplantation (LT) for HCC from January 1994 to June 2012, and evaluated patient outcome according to the degree of vascular invasion (VI). A nomogram for predicting extratumoral MVI was created using 637 patients, excluding 44 patients with macrovascular invasion, and was validated using an internal (n = 273) and external patient cohort (n = 256). The 681 patients were classified into four groups based on pathological examination (148 no VI, 33 intratumoral MVI, 84 extratumoral MVI, and 29 macrovascular invasion in patients who underwent HR; 238 no VI, 50 intratumoral MVI, 84 extratumoral MVI, and 15 macrovascular invasion in patients who underwent LT). Multivariate analysis revealed that extratumoral MVI was an independent risk factor for overall survival in patients who underwent HR (hazard ratio 2.62, p

Objective: To evaluate the impact of repeat surgery for recurrence on the long-term survival after 2-stage hepatectomy (TSH) for extensive colorectal liver metastases (CRLM). Background: Although TSH is now deemed effective for selected patients with extensive bilobar CRLM, disease recurrence after TSH is very frequent because of the extensive tumor load. Methods: Among a total cohort of 1235 patients who underwent hepatectomy for CRLM between 1992 and 2012, 139 with extensive bilobar CRLM were scheduled for TSH. Of these, 93 patients had completion of TSH and were enrolled in this study. Results: The 5-year overall survival (OS) rate after TSH was 41.3%. Twenty-two patients (23.7%) had a concomitant extrahepatic disease (EHD), and curative resection of concomitant EHD was achieved in 13 patients. Among the 81 patients who achieved complete tumor removal for primary, CRLM, and concomitant EHD, 62 (76.5%) had recurrence. Repeat surgery was performed in 38 patients; 35 for recurrence after curative surgery and 3 for liver recurrence with unresected concomitant EHD or primary tumor. Of these 38 patients, 31 were salvaged. The patients who underwent repeat surgery had a significantly longer OS than those who did not (45.8% vs 26.3%; P = 0.0041). A multivariate analysis revealed that repeat surgery was an independent prognostic factor of the OS after TSH (hazard ratio 0.31, P = 0.0012). Conclusions: Repeat surgery for recurrence after TSH may be crucial for the long-term survival in patients with extensive bilobar CRLM. Intensive oncosurgical surveillance is essential to avoid missing the chance for repeat surgery after TSH.

Postoperative early recurrence after hepatic resection for hepatocellular carcinoma (HCC) poses a challenge to surgeons, and the effect of a surgical margin is still controversial. This study aimed to identify an ideal margin to prevent early recurrence.A total of 226 consecutive patients who underwent primary curative hepatic resection for solitary and primary HCC were enrolled. The definition of early recurrence was determined using the minimum P value approach. Logistic regression analysis was used to identify the risk factors of early recurrence. The receiver-operating characteristic (ROC) curve was used to identify the optimal cut-off of the surgical margin and early recurrence.Recurrence within 8 months induced the poorest overall survival (P = 2×10A7-mm margin is important to prevent early recurrence. Patients with HCC and alpha-fetoprotein levels100 ng/ml, non-capsule formation, or microvascular invasion may have a survival benefit from a ≥ 7-mm margin.

International audience; Background: The curative treatment of perihilar cholangiocarcinomas and centrally located intrahepatic cholangiocarcinomas often requires major hepatectomy preceded by portal vein embolization. This strategy, however, is associated with a high rate of dropouts before operation or failure of resection at the time of operative exploration. We aimed to identify predictors of unresectability (dropout or failure of resection) after portal vein embolization for centrally located cholangiocarcinoma, including perihilar cholangiocarcinomas and intrahepatic cholangiocarcinomas.Method: All patients undergoing portal vein embolization for a planned resection of a centrally located cholangiocarcinoma between 2000 and 2018 in our center were evaluated retrospectively. Predictors of unresectability were determined under intention-to-treat conditions, based on clinical, biologic, and radiologic data collected before portal vein embolization.Results: Eighty-eight consecutive patients scheduled for portal vein embolization before operative exploration were included, 56 of whom (64%) underwent curative resection and 32 (36%) of whom were not resected, including those who did not undergo exploration (n = 11) and those operated on but not resected (n = 21). The most common cause of unresectability was tumor progression (62%). A psoas muscle index

Background Resection is rarely indicated in giant hepatic hemangiomas (HHs) that are symptomatic. Enucleation (EN), compared with anatomical resection (AR), is considered the better technique to resect them as EN has been reported to have lower morbidity while conserving the normal liver tissue. But no study has yet clearly established the superiority of EN over AR. In addition, the independent predictors of postoperative morbidity have not been established. Methods All consecutive patients operated for HH at two specialized hepatobiliary centers were reviewed. Patient demographics, operative variables, and postoperative outcomes were analyzed and compared between two techniques. Postoperative complications were graded as per Clavien-Dindo classification of surgical complications. The aims of this study were to compare two techniques of HH resection with respect to postoperative outcomes and to identify the risk factors for 90-day major postoperative morbidity and mortality. Results A total of 64 patients, including 41 who underwent AR, 22 who underwent EN, and 1 who underwent liver transplantation, were operated for hemangiomas during the study period. Ten patients (9 who were operated for hemangiomas of size ≤4 cm and 1 who underwent transplantation) were excluded. Fifty-four patients, the majority being women (85%), with a median age of 48 years, were operated for giant HH. These patients were classified into two groups based on the technique of resection, namely, EN (22 patients) and AR (32 patients). Both groups were comparable in all aspects except that the number of liver segments resected was significantly more with AR. Postoperative outcomes were similar in both groups. Independent predictors of 90-day major complications including mortality were the use of total vascular exclusion (relative risk [RR]: 2.3, p = 0.028) and duration of surgery >4.5 h (RR: 2.3, p = 0.025). Conclusion Both techniques yield similar results with respect to 90-day postoperative morbidity and mortality. The choice of technique should be based on the location of tumor and simplicity of liver resection.

International audience; Background: To address the results of resection for hepatocellular carcinoma (HCC) in human immunodeficiency virus (HIV)-carriers, and to compare them against survival after liver transplantation (LT).Methods: All patients with HIV and HCC listed for LT (candidates = LTc+) or resection (LR+) between 2000 and 2017 in our centre were analysed and compared for overall survival (OS) and disease-free survival (DFS).Results: The LTc + group (n = 43) presented with higher MELD scores and more advanced portal hypertension and HCC stages than LR + group (n = 15). One-, 3- and 5-year intention-to-treat survival rates were: 81%, 60% and 44%, versus 86%, 58% and 58% in the LTc+ and LR + groups, respectively (p = 0.746). Eleven LTc + patients dropped out. After LT, OS was 81%, 68% and 59% (no difference with LR + group; p = 0.844). There tended to be better DFS after LT, reaching 78%, 68% and 56% versus 53%, 33% and 33% in the LR + group (p = 0.062).Conclusion: This was the largest series of resections for HCC in HIV + patients and the first intention-to-treat analysis. Although LT and resection do not always concern the same population, they enable equivalent survival. At the price of higher recurrence rate, resection could be integrated in the global armoury of liver surgeons.

In France, liver grafts which have been refused by at least five centers are proposed as rescue allocation (RA). The aim of this study is to clarify the feasibility and safety of RA grafts in liver transplantation (LT). Short- and long-term outcomes of patients who received RA grafts (RA group) were compared with those of patients who received standard allocation (SA) grafts (SA group). From a total of 1635 patients, 102 patients received RA grafts. Before matching, the RA group was characterized primarily by less severe liver disease, but the quality of graft was worse. After matching recipients' characteristics of 102 patients who used RA grafts with 306 patients who used SA grafts, recipients' characteristics were well balanced (1:3 matching). Although the rate of primary dysfunction was significantly higher in the RA group, there is no significant difference in the occurrence of major complications, length of hospitalization, and mortality between two groups. Graft survival (GS) and overall survival (OS) in the RA group were not significantly different from the SA group (GS; HR = 1.03 P = .89, OS; HR = 1.03 P = .90). In the French allocation system, the feasibility and safety of RA grafts might be comparable to SA grafts for carefully selected patients.

Background: Hereditary transthyretin amyloidosis (ATTR) is a multisystemic disease involving mainly the peripheral nervous system and the heart. Liver transplantation (LT) is the reference treatment for ATTR neuropathy and preoperative detection of high risk patients is crucial. We aimed to document the causes of death of ATTR patients after LT, their temporal trends, and to evaluate whether the available preoperative tools that predict the risk of death after LT for hereditary ATTR amyloidosis matched with these trends. Methods: A retrospective longitudinal cohort study was performed on 215 consecutive ATTR patients who underwent LT between January 1993 and January 2011. Each patient’s death cause and timing were classified. Results: Over a median follow up of 5.9 years, 84 patients died. The rate of death was higher in the first year following LT than thereafter (13.0 vs. 4.3 ± 1.8%/year; p = .004). Cardiac events ranked as the leading cause of death (C: 38%), followed by infections (I: 24%), graft complications (G: 17%), end stage amyloidosis, stroke and others (ASO: 7% each). Deaths due to graft complications and infections (GI) occurred earlier than those due to end stage amyloidosis and stroke. Death prediction was less accurate for GI-related mortality than for other causes, which blunted the accuracy of the early-term risk prediction scores. Conclusions In ATTR amyloidosis, cardiac events were the leading cause of death after liver transplantation. Close preoperative evaluation allowed for accurate mid-term prediction of mortality, but the high rate of graft complications and infections blunted the early-term risk prediction.

Resume Introduction Le traitement chirurgical est le traitement de reference des volumineux carcinomes hepatocellulaires (VCHC) ≥ 5 cm. La fibrose peut constituer une contre-indication a la resection en raison du surrisque d’insuffisance hepatique postoperatoire mais son impact sur les suites postoperatoires et la recidive demeure mal defini. Notre objectif etait donc de comparer les facteurs pronostiques de survie chez les patients cirrhotiques ou non, apres hepatectomie pour VCHC. Methodes Les donnees des patients reseques pour VCHC entre 2012 et 2016 dans deux centres de reference ont ete analysees. Les resultats obtenus chez les patients cirrhotiques (fibrose F4) et non cirrhotiques (F0–F3) ont ete compares. Les patients ayant recu un traitement medical (sorafenib) ou radiologique (chimioembolisation intra-arterielle, radiofrequence) ont ete exclus. Resultats Soixante patients ont ete inclus. Les donnees preoperatoires et peroperatoires etaient identiques entre les deux groupes. Les patients cirrhotiques (n = 15) etaient plus souvent porteurs de nodules satellites a l’anatomopathologie definitive (73 % vs 44 % ; p = 0,073) mais leurs tumeurs etaient mieux differenciees que celles des patients non-cirrhotiques (p = 0,041). La survie mediane des patients cirrhotiques etait de 34 mois vs 29 mois chez les non-cirrhotiques (p = 0,8) et la survie sans recidive etait respectivement de 14 mois vs 18 mois (p = 0,9). Le degre de fibrose n’avait pas d’impact sur la survie globale (p = 0,2) ou la survie sans recidive (p = 0,6). Conclusion Le traitement chirurgical des VCHC chez les patients cirrhotiques permet d’obtenir des resultats oncologiques satisfaisants et comparables a ceux obtenus chez les patients non-cirrhotiques. Le traitement curatif des VCHC doit donc etre envisage, sous reserve d’une fonction hepatique conservee, quel que soit le degre de fibrose.

Background and Aims Intrahepatic cholangiocarcinoma (ICC) is a severe malignant tumor in which the standard therapies are mostly ineffective. The biological significance of the desmoplastic tumor microenvironment (TME) of ICC has been stressed but was insufficiently taken into account in the search for classifications of ICC adapted to clinical trial design. We investigated the heterogeneous tumor stroma composition and built a TME‐based classification of ICC tumors that detects potentially targetable ICC subtypes. Approach and Results We established the bulk gene expression profiles of 78 ICCs. Epithelial and stromal compartments of 23 ICCs were laser microdissected. We quantified 14 gene expression signatures of the TME and those of 3 functional indicators (liver activity, inflammation, immune resistance). The cell population abundances were quantified using the microenvironment cell population‐counter package and compared with immunohistochemistry. We performed an unsupervised TME‐based classification of 198 ICCs (training set) and 368 ICCs (validation set). We determined immune response and signaling features of the different immune subtypes by functional annotations. We showed that a set of 198 ICCs could be classified into 4 TME‐based subtypes related to distinct immune escape mechanisms and patient outcomes. The validity of these immune subtypes was confirmed over an independent set of 368 ICCs and by immunohistochemical analysis of 64 ICC tissue samples. About 45% of ICCs displayed an immune desert phenotype. The other subtypes differed in nature (lymphoid, myeloid, mesenchymal) and abundance of tumor‐infiltrating cells. The inflamed subtype (11%) presented a massive T lymphocyte infiltration, an activation of inflammatory and immune checkpoint pathways, and was associated with the longest patient survival. Conclusion We showed the existence of an inflamed ICC subtype, which is potentially treatable with checkpoint blockade immunotherapy.

Background Portal vein embolization (PVE) use is nowadays debated due to the risk of technical or biological unresectability after the period of time needed to achieve future liver remnant (FLR) hypertrophy. We evaluated the safety and efficacy of PVE in a single high-volume hepatobiliary center, with emphasis in the feasibility to achieve tumor resection. Methods Patients undergoing PVE before major hepatectomy at our institution between 1993 and 2015 were retrospectively analyzed. Results A total of 431 patients formed the study population. Morbidity and mortality rates of PVE were 16.7% and 0.2% respectively. Morbidity was similar between percutaneous and ileocolic approaches or between histoacryl and ethanol as embolization materials (P > 0.05). On the contrary, the percutaneous ipsilateral approach was associated with significantly less complications than the contralateral approach (10.3% vs 19.4%; P = 0.024). Almost all patients (96%) achieved sufficient FLR volume after embolization, but only 66% finally underwent planned liver resection. Disease progression was the most common cause of unresectability (67%). Patients with extrahepatic biliary tumors experienced significantly higher unresectability rates compared to other entities (45.1% vs 31.4%; P = 0.019). Conclusion PVE was not followed by hepatectomy in 34% of our patients. Biliary tumors displayed the higher dropout rates after PVE and the higher chances of tumor progression preventing curative resection. Although PVE may be performed with acceptable morbidity, PVE-related complications prevented curative resection in 5% of patients. Careful multidisciplinary selection is crucial to avoid PVE overuse in technically resectable patients who will experience a not negligible risk of futile use and non-therapeutic laparotomy.

Effective individualized treatment of patients with colorectal liver metastases (CLM) requires tumor genotyping, usually based on the analysis of one single sample per patient. Therapy failure may partially be explained by sampling errors and/or intratumoral genetic heterogeneity. We aimed to demonstrate intratumoral genetic heterogeneity in CLM and enable pathologists to select tumor tissue for genotyping. All the tumors of 86 patients who underwent liver resection for a single CLM were reviewed. Of the 86 patients, 66 patients received chemotherapy and 20 patients did not receive chemotherapy before liver resection. All the tumor areas sampled were analyzed for KRAS, BRAF, PIK3CA, and NRAS mutations. The mutational status was tested in 74 cases, 7 cases had no tumoral cells due to complete responses and 5 blocks were unavailable. Of the 59/74 CLM with > 1 sample, 56 showed the same mutational status between the samples. The remaining 3 cases (5% of all cases) showed genetic heterogeneity for KRAS in 2 and BRAF in 1 patient. Genetic heterogeneity correlated with lower rate of viable tumor cells (p=0.009) and higher rate of mucin pools (p=0.013). We demonstrate for the first time the existence of genetic intratumoral heterogeneity in 5% of CLM. In routine practice, this low incidence does not require the genotyping of additional tumor samples. The correlation between the genetic heterogeneity and some histological components of the CLM should be verified by further in situ mutation assay.

Surgical resection is an established therapeutic strategy for colorectal cancer (CRC) metastasis. However, controversies exist when CRC liver and lung metastases (CLLMs) are found concomitantly or when recurrence develops after either liver or lung resection. No predictive score model is available to risk stratify these patients in preparation for surgery, and cure has not yet been reported.All consecutive patients who had undergone surgery for CLLMs at our institution during a 20-year period were reviewed. Our policy was to propose sequential surgery of both sites with perioperative chemotherapy, if the strategy was potentially curative. Overall survival, disease-free survival, and cure were evaluated.Sequential resection was performed in 150 patients with CLLMs. The median number of liver and lung metastases resected was 3 and 1, respectively. The median follow-up period was 59 months (range, 7-274 months). The median, 5-year, and 10-year overall survival was 76 months, 60%, and 35% respectively. CRC that was metastatic at the initial diagnosis (P = .012), a prelung resection carcinoembryonic antigen level100 ng/mL (P = .014), a prelung resection cancer antigen 19-9 level37 U/mL (P = .034), and an interval between liver and lung resection of 24 months (P = .024) were independent poor prognostic factors for survival. The 5-year survival was significantly different for patients with ≤ 2 and ≥ 3 risk factors (77.3% vs. 26.5%). Of 75 patients with ≥ 5 years of follow-up data available from the first metastasis resection, 15 (20%) with disease-free survival ≥ 5 years were considered cured. The use of targeted therapy was the only independent predictor of cure.Curative-intent surgery provides good long-term survival and offers a chance of cure in select patients. Patients with ≤ 2 risk factors are good candidates for sequential resection.

Vascular complications following liver transplantation (LT) may result from technical deficiencies. Intraoperative diagnosis remains challenging but can prevent serious delayed complications. Intraoperative Doppler ultrasonography (IOUS) represents the gold standard for imaging, although it requires radiological skills. Contrast-enhanced ultrasonography has been reported during postoperative assessments, but never intraoperatively (CE-IOUS). The aim of this study was to assess the feasibility of routine CE-IOUS, to evaluate its impact on surgical strategy and its usefulness. All 553 whole LTs performed in our tertiary centre between 01/2010 and 12/2014 were reviewed. We compared perioperative outcomes and long-term survival in IOUS (n = 370) versus CE-IOUS (n = 103) groups. Secondarily, the seven cases where the two imaging findings conflicted (CE+ Group) were matched 1:2 and compared with an exclusively IOUS procedure (CE− Group, n = 14) to assess the consequences of a specific CE-guided strategy. CE-IOUS assessments were successful in 100% of cases, without any adverse effects. Vascular complications and patient/graft survival rates were identical in the IOUS and CE-IOUS groups (p = 0.65, 0.95 and 0.86, respectively). CE-IOUS confirmed IOUS findings in 93% of cases (n = 96) and led to the realization of an additional procedure (median arcuate ligament lysis) and six conservative strategies despite poor arterial (n = 5) or venous flow (n = 1) under Doppler analysis. The CE+ and CE− groups presented statistically identical perioperative and long-term outcomes. This study demonstrated the feasibility of CE-IOUS during whole LT. However, we failed to demonstrate any advantages of CE-IOUS over IOUS. Therefore, IOUS currently remains the gold-standard imaging technique for the intraoperative assessment of vascular patency.

There is currently no tool available to predict extreme large-for-size (LFS) syndrome, a potentially disastrous complication after adult liver transplantation (LT). We aimed to identify the risk factors for extreme LFS and to build a simple predictive model. A cohort of consecutive patients who underwent LT with full grafts in a single institution was studied. The extreme LFS was defined by the impossibility to achieve direct fascial closure, even after delayed management, associated with early allograft dysfunction or nonfunction. Computed tomography scan-based measurements of the recipient were done at the lower extremity of the xiphoid. After 424 LTs for 394 patients, extreme LFS occurred in 10 (2.4%) cases. The 90-day mortality after extreme LFS was 40.0% versus 6.5% in other patients (P = 0.003). In the extreme LFS group, the male donor-female recipient combination was more often observed (80.0% versus 17.4%; P < 0.001). The graft weight (GW)/right anteroposterior (RAP) distance ratio was predictive of extreme LFS with the highest area under the curve (area under the curve, 0.95). The optimal cutoff was 100 (sensitivity, 100%; specificity, 88%). The other ratios based on height, weight, body mass index, body surface area, and standard liver volume exhibited lower predictive performance. The final multivariate model included the male donor-female recipient combination and the GW/RAP. When the GW to RAP ratio increases from 80, 100, to 120, the probability of extreme LFS was 2.6%, 9.6%, and 29.1% in the male donor-female recipient combination, and

The optimal management of the open abdomen (OA) after liver transplantation (LT) is unclear. The negative pressure wound therapy (NPWT) has been shown to be safe and can increase the chance for early fascial closure in trauma or septic patients. However, little data are available on the specific setting of LT. We aimed to report our experience of OA after LT, marked by the recent use of NPWT. All patients with postponed wall closure after LT, from 2002 to 2014, in a single institution were included and retrospectively analyzed. Our management of OA after LT has shifted from skin-only closure (SOC) followed by abdominal wall reconstruction at a distance to the use of NPWT with early fascial closure. Of the 1559 LTs performed during the study period, immediate abdominal wall closure at the end of transplantation could not be achieved in 46 (2.9%) patients. Of them, SOC was performed in 22 (47.8%) patients, whereas vacuum-assisted closure (VAC) therapy was used in 24 (52.1%) patients. The comprehensive complication indexes (CCI) were similar [CCI: 66 (0–100) in the SOC group vs. 56 (0–100) in the VAC group; p = 0.55]. No evisceration or fistula occurred in both groups. One (4.2%) postoperative bleeding case was reported in the VAC group. Early fascial closure was achieved within a median of 5.5 days (1–12) for the 24 patients (100%) of the VAC group. In four of them, a biological mesh was necessary. Only nine patients (52.9%) of the survivors in the SOC group underwent abdominal reconstruction. The NPWT in patients with OA after LT enables early fascial closure with limited morbidity provided a specific attention is given to the risk of bleeding. These results support the use of NPWT as the first option in OA patients after LT.

Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is widely considered as a terminal condition. Therefore, the role of surgery is uncertain in this case. The purpose of this study was to identify the prognostic factors of survival after post-LT HCC recurrence and to evaluate the impact of surgery in this setting. All patients transplanted for HCC between 1991 and 2013 in a single institution and who further developed a post-LT recurrence were included in this study. Univariate and multivariate analyses were performed to identify factors affecting postrecurrence survival. Of the 493 patients transplanted for HCC, a total of 70 (14.2%) consecutive patients developed a recurrence after a median disease-free interval of 17 months. Median survival (MS) from the time of recurrence was 19 months, with a 3-year postrecurrence survival of 26%. Most recurrences were extrahepatic (lung, lymph node, and bone; n = 51; 72.9%), whereas only intrahepatic recurrences were observed in 2 (2.8%) patients. Both intrahepatic and extrahepatic locations were found in 17 (24.3%) patients. A total of 22 (31.4%) patients underwent macroscopically complete resection of the recurrence (intrahepatic [n = 2] and extrahepatic [n = 20]). The MS for resected patients after transplantation was 35 months compared with 15 months for nonresected patients (P 0.001). In multivariate analysis, the independent unfavorable factors of postrecurrence survival were alpha-fetoprotein level 100 ng/mL at relapse (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.1-4.1; P = 0.03), intrahepatic location (HR, 1.8; 95% CI, 1.0-3.2; P = 0.05), and multifocal recurrence (HR, 1.8; 95% CI, 1.1-3.1; P = 0.04). The management including surgery (HR, 0.4; 95% CI, 0.2-0.7; P = 0.004) was identified as an independent favorable factor. In conclusion, recurrence of HCC after LT is associated with a poor prognosis. However, resection is associated with improved survival and should therefore be considered when feasible. Liver Transplantation 23 440-447 2017 AASLD.

Although sarcopenia is a common complication of cirrhosis, its diagnosis remains nonconsensual: computed tomography (CT) scan determinations vary and no cutoff values have been established in cirrhotic populations undergoing liver transplantation (LT). Our aim was to compare the accuracy of the most widely used measurement techniques and to establish useful cutoffs in the setting of LT. From the 440 patients transplanted between January 2008 and May 2011 in our tertiary center, we selected 256 patients with cirrhosis for whom a recent CT scan was available during the 4 months prior to LT. We measured different muscle indexes: psoas muscle area (PMA), PMA normalized by height or body surface area (BSA), and the third lumbar vertebra skeletal muscle index (L3SMI). Receiver operating characteristic curves were evaluated and prognostic factors for post-LT 1-year survival were then analyzed. PMA offered better accuracy (area under the curve [AUC] = 0.753) than L3SMI (AUC = 0.707) and PMA/BSA (AUC = 0.732), and the same accuracy as PMA/squared height. So, for its accuracy and simplicity of use, the PMA index was used for the remainder of the analysis and to define sarcopenia. In men, the better cutoff value for PMA was 1561 mm2 (Se = 94%, Sp = 57%), whereas in women, it was 1464 mm2 (Se = 52%, Sp = 91%). A PMA lower than these values defined sarcopenia in patients with cirrhosis awaiting LT. One- and 5-year overall survival rates were significantly poorer in the sarcopenic group (n = 57) than in the nonsarcopenic group (n = 199), at 59% versus 94% and 54% versus 80%, respectively (P

The management of late hepatic artery thrombosis (LHAT) after liver transplantation (LT) is not codified. The objective of this study was to retrospectively evaluate outcomes after LHAT. All patients with HAT diagnosed 3 months or later after LT on computed tomography between 1993 and 2017 were included. Our policy was to apply a conservative management for asymptomatic or mild symptomatic patients and reserve retransplantation to symptomatic patients with diffuse cholangitis or liver abscess. A total of 56 patients were analyzed. LHAT diagnosis was made after a median interval of 48 months from LT (ranging from 3 to 368.3). At diagnosis, 28 (50%) patients were asymptomatic, 10 (17.8%) had mild symptoms (transient acute cholangitis), and 18 (32.1%) had severe complications. Asymptomatic patients experienced a 5-year graft survival of 57% vs. 40% in those with mild symptoms and 11% in those with severe complications (P < 0.001). However, there was no difference in overall patient survival between groups. Our results suggest that conservative management of LHAT for asymptomatic patients or patients with mild complications is safe. Retransplantation should be reserved to patients with severe biliary complications.

International audience; BACKGROUND & AIMS: Liver macrosteatosis (MS) is a major predictor of graft dysfunction after transplantation. However, frozen section techniques to quantify steatosis are often unavailable in the context of procurements, and the findings of preoperative imaging techniques correlate poorly with those of permanent sections, so that the surgeon is ultimately responsible for the decision. Our aim was to assess the accuracy of a non-invasive pocket-sized micro-spectrometer (PSM) for the real-time estimation of MS. METHODS: We prospectively evaluated a commercial PSM by scanning the liver capsule. A double pathological quantification of MS was performed on permanent sections. Initial calibration (training cohort) was performed on 35 livers (MS\textless/=60%) and an algorithm was created to correlate the estimated (PSM) and known (pathological) MS values. A second assessment (validation cohort) was then performed on 154 grafts. RESULTS: Our algorithm achieved a coefficient of determination R2=0.81. Its validation on the second cohort demonstrated a Lin's concordance coefficient of 0.78. Accuracy reached 0.91%, with reproducibility of 86.3%. The sensitivity, specificity, positive and negative predictive values for MS \textgreater/=30% were 66.7%, 100%, 100% and 98%, respectively. The PSM could predict the absence (\textless30%)/presence (\textgreater/=30%) of MS with a kappa coefficient of 0.79. Neither graft weight nor height, donor body mass index nor the CT-scan liver-to-spleen attenuation ratio could accurately predict MS. CONCLUSION: We demonstrated that a PSM can reliably and reproducibly assess mild-to-moderate MS. Its low cost and the immediacy of results may offer considerable added-value decision support for surgeons. This tool could avoid the detrimental and prolonged ischaemia caused by the pathological examination of (potentially) marginal grafts. This device now needs to be assessed in the context of a large-scale multicentre study. LAY SUMMARY: Macro-vacuolar liver steatosis is a major prognostic factor for outcomes after liver transplantation. However, it is often difficult for logistical reasons to get this estimation during procurement. Therefore, we developed an algorithm for a commercial, portable and affordable spectrometer to accurately estimate this content in a real-time fashion. This device could be of great interest for clinical decision-making to accept or discard a potential human liver graft.

BACKGROUND DATA In compensated cirrhotics with early hepatocellular carcinoma (HCC-cirr), upfront liver resection (LR) and salvage liver transplantation (SLT) in case of recurrence may have outcomes comparable to primary LT (PLT). OBJECTIVE An intention-to-treat (ITT) analysis comparing PLT and SLT strategies. METHODS Of 130 HCC-cirr patients who underwent upfront LR (group LR), 90 (69%) recurred, 31 could undergo SLT (group SLT). During the same period, 366 patients were listed for LT (group LLT); 26 dropped-out (7.1%), 340 finally underwent PLT (group PLT). We compared survival between groups LR and LLT, LR and PLT, and PLT and SLT. RESULTS Feasibility of SLT strategy was 34% (31/90). In an ITT analysis, group LLT had better 5-yr/10-yr overall survival (OS) compared with group LR (68%/58% vs. 58%/35%; P = 0.008). Similarly, 5-yr/10-yr OS and disease-free survival (DFS) were better in group PLT versus group LR (OS 73%/63% vs. 58%/35%, P = 0.0007; DFS 69%/61% vs. 27%/21%, P

The specific definition of central hepatectomy (CH) (i.e., resection of segments 4-5-8 ± 1) is not uniformly used, resulting in conflicting comparisons with the more commonly performed extended hepatectomy (EH). The study aimed to compare, using propensity score matching (PSM) analysis, the incidence of postoperative complications between CH and EH for centrally located liver tumors (CLLT). All consecutive CH and EH procedures for CLLT performed from 1980 to 2011 were retrospectively reviewed. Independent predictors of postoperative complications were identified. CH was compared to EH after PSM. The study population consisted of 373 patients, 44 (11.8 %) of whom underwent CH and 329 (88.2 %) of whom underwent EH. Before PSM, the overall 90-day mortality was 7.2 % (27 patients) without a group difference (2 (4.5 %) for CH vs. 25 (7.6 %) for EH, p = 0.756). The CH and EH groups had similar postoperative morbidity rates (43.2 vs. 55.3 %; p = 0.108). Blood transfusion was the only independent predictor of postoperative complications (Hazard Ratio: 1.73; 95 % confidence interval: 1.11–2.68; p = 0.014). After PSM, 43 CH patients were matched with 43 EH patients. No group difference was observed for the postoperative mortality, morbidity, or duration of hospital stay. A higher number of EH patients (30.2 vs. 9.3 %, p = 0.028) presented with more than one postoperative complication. CH and EH yield similar mortality and morbidity. For CLLT, CH may be an attractive procedure with the advantage of sparing the liver parenchyma compared with EH.

Although efficient chemotherapy regimens have improved outcomes after R1 resection (positive margins) for colorectal liver metastases (CLMs), the long-term survival benefit and potential for cure after R1 resection have not been clearly demonstrated. The aim of this study was to evaluate the long-term outcome after R1 resection for CLM, and to identify factors predictive of cure. All resected CLM patients at our institution from 2000 to 2009 were prospectively evaluated. Cure was defined as a disease-free interval ≥5 years from the last hepatic or extrahepatic resection to last follow-up. Of 628 patients consecutively resected for CLM, 428 were eligible for the study, of whom 219 (51 %) underwent R0 resection (negative margins) and 209 (49 %) underwent R1 resection. Overall, 130 patients with R0 resection and 141 patients with R1 resection had more than 5 years of follow-up. Five- and 10-year overall survival rates were 56 and 34 % for R0 patients, and 48 and 36 % for R1 patients, respectively (p = 0.37). Of the 141 patients who underwent R1 resection, 26 patients (18 %) were considered ‘cured’, and 106 patients (75 %) were considered ‘noncured’. Independent predictive factors of cure after R1 resection included ≤10 total cycles of preoperative chemotherapy and objective response to preoperative chemotherapy. Overall, potential cure can be achieved in 18 % of patients after R1 resection for CLM. The best conditions to achieve long-term survival after R1 resection rely on a good response to efficient and short first-line chemotherapy.

Background Management of portal inflow to the graft in patients with spontaneous splenorenal shunts (SRS) is a matter of concern especially in case of large varices (more than 1 cm). In case of portal vein (PV) thrombosis (PVT), renoportal anastomosis (RPA) directly diverts the splanchnic and renal venous blood assuring a good portal inflow to the graft. Disconnection of the portacaval shunt by left renal vein ligation (LRVL) is another option but requires a patent PV. The indication of primary RPA rather than LRVL in patients with small native PV, especially in case of large graft, should be questioned in these complex cases of liver transplantation. Methods From 1998 to 2012, 17 patients with RPA and 15 patients with LRVL were transplanted in our center. We compared these 2 techniques for short- and long-term results. Results The rate of preliver transplantation PVT (76% vs 27%) and graft weight (1538 ± 383 g vs 1293 ± 216 g) was significantly higher in the RPA group. Renoportal anastomosis was performed in 4 cases of small but patent PV. Three-month mortality, morbidity, and massive ascitis were similar. No patient was retransplanted. One year after transplantation, PV diameter was still larger in RPA group. Three-year survival was similar (RPA: 79% vs LRVL: 53%, P = 0.1). Conclusions In cirrhotic patients transplanted with large splenorenal shunts, RPA and LRVL reach similar survivals. In case of complete PVT and failure of thrombectomy, the RPA offers satisfactory long-term results.

Microvascular invasion is the strongest prognostic factor of survival in patients with hepatocellular carcinoma. We therefore developed a predictive model for microvascular invasion of hepatocellular carcinoma to help guide treatment strategies in patients scheduled for either hepatic resection or liver transplantation.Patients with hepatocellular carcinoma who underwent hepatic resection or liver transplantation from 1994 to 2016 were divided into training and validation cohorts. A predictive model for microvascular invasion was developed based on microvascular invasion risk factors in the training cohort and validated in the validation cohort.A total of 910 patients (425 having received hepatic resection, 485 having received liver transplantation) were included in the training (n = 637) and validation (n = 273) cohorts. Multivariate analysis identified α-fetoprotein ≥100 ng/mL (relative risk 3.05, P.0001), tumor size ≥40 mm (relative risk 1.98, P = .0002), nonboundary hepatocellular carcinoma type (relative risk 1.91, P = .001), neutrophil-to-lymphocyte ratio (relative risk 1.86, P = .002), and aspartate aminotransferase (relative risk 1.53, P = .02) as associated with microvascular invasion. The estimated probability of microvascular invasion ranged from 17.0% in patients with none of these factors to 86.9% in the presence of all factors. This model achieved a C-index of 0.732 in the validation cohort. The 5-year overall survival of patients with ≥50% probability of microvascular invasion was poorer than that of patients with50% probability (hepatic resection; 39.1% vs 61.2%, P.0001, liver transplantation; 5-year overall survival, 54.8% vs 79.0%, P = .05).This model developed from preoperative data allows reliable prediction of microvascular invasion in candidates for either hepatic resection or liver transplantation.

Summary Background Hepatectomy remains the standard treatment for large hepatocellular carcinoma (LHCC) ≥ 5 cm. Fibrosis may constitute a contraindication for resection because of high risk of post-hepatectomy liver failure, but its impact on patient outcome and cancer recurrence remains ill defined. Our aim was to compare predictors of survival in patients with and without cirrhosis following hepatectomy for LHCC. Methods The data on consecutive patients undergoing hepatectomy for LHCC in two tertiary centres between 2012 and 2016 were reviewed. The outcomes of cirrhotic (F4) and non-cirrhotic (F0–F3) patients were compared. Patients with perioperative medical (sorafenib) or radiological (transarterial chemoembolization, radiofrequency) treatments were excluded. Results Sixty patients were included. Preoperative and intraoperative features were identical between both groups. Cirrhotics (n = 15) presented more satellite nodules on specimens (73% vs. 44%; P = 0.073) but better differentiated lesions than non-cirrhotics (P = 0.041). The median overall survival of cirrhotics was 34 vs. 29 months for non-cirrhotics (P = 0.8), and their disease-free survival was 14 versus 18 months (P = 0.9). Fibrosis stage did not impact overall (P = 0.2) nor disease-free survivals (P = 0.6). Conclusion Hepatectomy for LHCC in cirrhotics can achieve acceptable oncological results when compared to non-cirrhotic patients. Curative resection of LHCC should be attempted if liver function is acceptable, whatever the fibrosis stage.

Introduction: Long-term survival is still rarely achieved with current systemic treatment in patients with breast cancer liver metastases (BCLM). Extended survival after hepatectomy was examined in a select group of BCLM patients. Patients and methods: Hepatectomy for BCLM was performed in 139 consecutive patients between 1985 and 2012. Patients who survived

Resection of breast cancer liver metastases (BCLM) combined with systemic treatment is increasingly accepted but not offered as therapeutic option. New evidence of the additional value of surgery in these patients is scarce while prognoses without surgery remains poor.For this case matched analysis, all nationally registered patients with BCLM confined to the liver in the Netherlands (systemic group; N = 523) were selected and compared with patients who received systemic treatment and underwent hepatectomy (resection group; N = 139) at a hepatobiliary centre in France. Matching was based on age, decade when diagnosed, interval to metastases, maximum metastases size, single or multiple tumours, chemotherapy, hormonal or targeted therapy after diagnosis. Based on published guidelines, palliative systemic treatment strategies are similar in both European countries.Between 1983 and 2013, 3894 patients were screened for inclusion. Overall median follow-up was 80 months (95% CI 70-90 months). The median, 3- and 5-year overall survival of the whole population was 19 months, 29% and 19%, respectively. The resection and systemic group had median survival of 73 vs. 13 months (P 0.001), respectively. Three and 5-year survival was 18% and 10% for the systemic group and 75% and 54% for the resection group, respectively. After matching, the resection group had a median overall survival of 82 months with a 3- and 5-year overall survival of 81% and 69%, respectively, compared with a median overall survival of 31 months in the systemic group with a 3- and 5-year overall survival of 32% and 24%, respectively (HR 0.28, 95% CI 0.15-0.52; P 0.001).For patients with BCLM, liver resection combined with systemic treatment results in improved overall survival compared to systemic treatment alone. Liver resection should be considered in selected cases.

OBJECTIVE: To evaluate the European experience after Adult-to-adult living donor liver transplantation using the left liver (LL-aLDLT). SUMMARY BACKGROUND DATA: LL-aLDLT decreases donor risk but provides a smaller graft that increases recipient risk as compared with right liver (RL-aLDLT). However, there is little knowledge of results obtained after LL-aLDLT in Europe. METHODS: This is a European multicenter retrospective study which aims to analyze donor and recipient outcomes after 46 LL-aLDLT. RESULTS: Seventy-six percent of the grafts were harvested by minimally invasive approach. Mean donor hospital stay was 7.5 ± 3.5 days. Donor liver function was minimally impaired, with 36 donors (78.3%) without any 90-day complication, and 4 (8.7%) presenting major complications. One, 3, and 5-year recipient survival was 90.9%, 82.7%, and 82.7%, respectively. However, graft survival was of 59.4%, 56.9%, and 56.9% at 1, 3, and 5 years respectively, due to a 26.1% urgent liver retransplantation (ReLT) rate, mainly due to SFSS (n = 5) and hepatic artery thrombosis (HAT, n = 5). Risk factor analysis for ReLT and HAT showed an association with a graft to body weight ratio (GBWR) 0.6% was associated with a lower ReLT rate (0% vs. 33%, P = 0.044). CONCLUSIONS: Our analysis showed low donor morbidity and preserved liver function. Recipient outcomes, however, were hampered by a high ReLT rate. A strict selection of both donor and recipients is the key to minimize graft loss.

To test the prognostic impact of arterial lactate concentration at the end-of-surgery (LCT-EOS) on postoperative outcome after elective liver-resections and to identify the predictors of an increase in LCT-EOS.A recent systematic-review of risk-prediction-models for liver resections has evidenced their poor accuracy and a deficit in the evaluation of intraoperative events. LCT-EOS is a marker of impaired tissue oxygenation.This prospectively-designed study was based on a training-cohort of 519 patients and a validation-cohort of 466 patients. For each of the endpoints (high comprehensive complication index (CCI) scores, 90-day-mortality and severe-morbidity), prognostic-models were built by logistic-regression using the training-cohort. These models were thereafter tested in the validation-cohort and their performance (discrimination, accuracy, calibration) assessed. Independent predictors of LCT-EOS were also identified.In the training-cohort, LCT-EOS cutoff best discriminating high-CCI, 90-day-mortality and severe-morbidity were 3, 3 and 2.8 mmol/L (and the corresponding AUROC 0.86, 0.87 and 0.76). LCT-EOS was an independent predictor of endpoints and adding LCT-EOS to the other predictors increased by 16.4%, 34.5% and 17.7% the accuracy of the models for high-CCI, 90-day-mortality and severe-morbidity, respectively. The models had high calibration and accuracy. Diabetes, repeat-hepatectomy, major-hepatectomy, synchronous-major-procedure, inflow-occlusion and blood-transfusion were independent predictors of LCT-EOS3 mmol/L.LCT-EOS3 mmol/L is an early predictor of postoperative-outcome and should be used as a tool to determine patients requiring critical-care and as an endpoint in studies measuring the impact of perioperative interventions.

The aim of the study was to identify predictive factors of failure of 2-stage hepatectomy (TSH) for the selection of patients with extensive bilobar colorectal liver metastases (CRLM), who are candidates for TSH.The main weakness of TSH is the risk of failure to complete both the sequential procedures.Between 2000 and 2012, from a total cohort of 845 patients resected for CRLM, 125 patients (14.8%) with extensive CRLM were planned for TSH. All factors related to the failure of TSH were analyzed, and a predictive model was built utilizing the independent predictive factors of failure.Forty-four patients (35.2%) could not proceed to the second stage, and their overall survival (OS) was significantly worse than that of those who completed the TSH (5-year OS: 0% vs 44.2%; P 0.0001). Multivariate analysis revealed that carcinoembryonic antigen30 ng/mL [relative risk (RR) 2.73, P = 0.03], tumor size40 mm (RR 2.89, P = 0.04), chemotherapy cycles12 (RR 3.46, P = 0.01), and tumor progression during first-line chemotherapy (RR 6.56, P = 0.01) were independent predictive factors of failure. For patients not presenting any factors, the probability of failure was 10.5%, with a 5-year OS rate of 41.9%. The addition of each subsequent factor increased the risk to 43.5%, 72.7%, 88.5%, and 95.5%, and decreased the 5-year OS to 38.8%, 29.2%, 0%, and 0%, respectively, for 1, 2, 3, and 4 factors.TSH should not be recommended in patients with more than 2 risk factors. Avoidance of these factors significantly reduces the risk of failure and is crucial for long-term survival.

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

Arterial complications are a major cause of graft lost after liver transplantation (LT). The aim of our study was to assess the clinical impact of systematic early postoperative injected computed tomographic (CT) scans after LT rather than its performance on demand in the event of abnormalities. Two series of consecutive transplantation patients in different periods (1997-1999, 231 patients versus 2008-2010, 250 patients) were analyzed. During the first period, an injected CT scan was only performed in the event of clinical, biological, or ultrasound abnormalities revealed by tests performed daily during the first week after surgery. During the second period, in addition to standard follow-up examination, an injected CT scan was performed systematically at approximately postoperative day 7. During the first (versus the more recent) period, both recipients (whose ages were 46 ± 13 years versus 50 ± 12 years; P = .004) and donors (whose ages were 42 ± 17 versus 52 ± 17 years; P = .0001) were younger and end-stage liver disease was more common (34% versus 12%; P = .0001), but hepatocellular carcinoma (7% vs 26%; P = .0001) and retransplantation (2% versus 7%; P = .01) were less frequent. Postoperative mortality was higher during the first period (14% versus 4%; P = .0003). The incidence of early arterial thrombosis (

Background Indications for surgical resection of non-colorectal, non-neuroendocrine (NCNNE) liver metastases are unclear. This study analysed the influence of response to neoadjuvant chemotherapy and the presence of extrahepatic disease (EHD) on outcomes. Methods Patients who underwent hepatic resection for NCNNE liver metastases and who received neoadjuvant chemotherapy at a single centre between 1982 and 2016 were analysed retrospectively. Patients were classified as having no EHD, controlled EHD or non-controlled EHD. Results Hepatic resection was performed in 199 patients (81·2 per cent) after partial or complete response to chemotherapy or disease stabilization, and 46 patients (18·8 per cent) after tumour progression. Patients with progressive disease after chemotherapy had worse overall survival than those without (23 versus 50·4 per cent at 5 years; P = 0·004). Median survival was 63·6 (range 31·1–94·8) months for patients without EHD, 34·8 (19·2–49·2) months for those with controlled EHD and 7·2 (1·2–13·2) months for patients with non-controlled EHD (P = 0·004). In multivariable analysis, EHD (P = 0·004), response to chemotherapy (P = 0·004) and resection margins (P = 0·002) were all independent predictors of overall survival, regardless of primary tumour site. Conclusion The prognosis of patients with NCNNE liver metastases is influenced by preoperative chemotherapy and resectability.

Background Postoperative hepatic decompensation is a serious complication of liver resection in patients undergoing hepatectomy for hepatocellular carcinoma. Liver fibrosis and clinical significant portal hypertension are well-known risk factors for hepatic decompensation. Liver stiffness measurement is a noninvasive method of evaluating hepatic venous pressure gradient and functional hepatic reserve by estimating hepatic fibrosis. Effectiveness of liver stiffness measurement in predicting persistent postoperative hepatic decompensation has not been investigated. Methods Consecutive patients with resectable hepatocellular carcinoma were recruited prospectively and liver stiffness measurement of nontumoral liver was measured using FibroScan. Hepatic venous pressure gradient was measured intraoperatively by direct puncture of portal vein and inferior vena cava. Hepatic venous pressure gradient ≥10 mm Hg was defined as clinically significant portal hypertension. Primary outcome was persistent hepatic decompensation defined as the presence of at least one of the following: unresolved ascites, jaundice, and/or encephalopathy >3 months after hepatectomy. Results One hundred and six hepatectomies, including 22 right hepatectomy (20.8%), 3 central hepatectomy (2.8%), 12 left hepatectomy (11.3%), 11 bisegmentectomy (10.4%), 30 unisegmentectomy (28.3%), and 28 partial hepatectomy (26.4%) were performed in patients for hepatocellular carcinoma (84 men and 22 women with median age of 67.5 years; median model for end-stage liver disease score of 8). Ninety-day mortality was 4.7%. Nine patients (8.5%) developed postoperative hepatic decompensation. Multivariate logistic regression bootstrapped at 1,000 identified liver stiffness measurement (P = .001) as the only preoperative predictor of postoperative hepatic decompensation. Area under receiver operating characteristic curve for liver stiffness measurement and hepatic venous pressure gradient was 0.81 (95% confidence interval, 0.506–0.907) and 0.71 (95% confidence interval, 0.646–0.917), respectively. Liver stiffness measurement ≥22 kPa had 42.9% sensitivity and 92.6% specificity and hepatic venous pressure gradient ≥10 mm Hg had 28.6% sensitivity and 96.3% specificity. Conclusion In selected patients undergoing liver resection for hepatocellular carcinoma, transient elastography is an easy and effective test to predict persistent hepatic decompensation preoperatively.

International audience; BACKGROUND & AIMS: Hepatocellular adenomas (HCAs) are benign liver tumors that can be assigned to molecular subtypes based on inactivating mutations in hepatocyte nuclear factor 1A, activating mutations in β-catenin, or activation of inflammatory signaling pathways. We aimed to update the classification system for HCA and associate the subtypes with disease risk factors and complications.METHODS: We analyzed expression levels of 20 genes and sequenced exon regions of 8 genes (HNF1A, IL6ST, CTNNB1, FRK, STAT3, GNAS, JAK1, and TERT) in 607 samples of 533 HCAs from 411 patients, collected from 28 centers mainly in France from 2000 and 2014. We performed gene expression profile, RNA sequence, whole-exome and genome sequence, and immunohistochemical analyses of select samples. Molecular data were associated with risk factors, histopathology, bleeding, and malignant transformation.RESULTS: Symptomatic bleeding occurred in 14% of the patients (85% of cases were female, median age, 38 years); 7% of the nodules were borderline between HCA and hepatocellular carcinoma, and 3% of patients developed hepatocellular carcinoma from HCA. Based on molecular features, we classified HCA into 8 subgroups. One new subgroup, composed of previously unclassified HCA, represented 4% of HCAs overall and was associated with obesity and bleeding. These tumors were characterized by activation of sonic hedgehog signaling, due to focal deletions that fuse the promoter of INHBE with GLI1. Analysis of genetic heterogeneity among multiple HCAs, from different patients, revealed a molecular subtype field effect; multiple tumors had different mutations that deregulated similar pathways. Specific molecular subtypes of HCA associated with various HCA risk factors, including imbalances in estrogen or androgen hormones. Specific molecular subgroup of HCA with β-catenin and sonic hedgehog activation associated with malignant transformation and bleeding, respectively.CONCLUSIONS: Using sequencing and gene expression analyses, we identified a subgroup of HCA characterized by fusion of the INHBE and GLI1 genes and activation of sonic hedgehog pathway. Molecular subtypes of HCAs associated with different patients' risk factors for HCA, disease progression, and pathology features of tumors. This classification system might be used to select treatment strategies for patients with HCA.

International audience; BACKGROUND & AIMS: Liver transplantation (LT) is the therapeutic option for severe complications of Wilson's disease (WD). We aimed to report on the long-term outcome of WD patients following LT. METHODS: The medical records of 121 French patients transplanted for WD between 1985 and 2009 were reviewed retrospectively. Seventy-five patients were adults (median age: 29 years, (18-66)) and 46 were children (median age: 14 years, (7-17)). The indication for LT was (1) fulminant/subfulminant hepatitis (n = 64, 53%), median age = 16 years (7-53), (2) decompensated cirrhosis (n = 50, 41%), median age = 31.5 years (12-66) or (3) severe neurological disease (n = 7, 6%), median age = 21.5 years (14.5-42). Median post-transplant follow-up was 72 months (0-23.5). RESULTS: Actuarial patient survival rates were 87% at 5, 10, and 15 years. Male gender, pre-transplant renal insufficiency, non elective procedure, and neurological indication were significantly associated with poorer survival rate. None of these factors remained statistically significant under multivariate analysis. In patients transplanted for hepatic indications, the prognosis was poorer in case of fulminant or subfulminant course, non elective procedure, pretransplant renal insufficiency and in patients transplanted before 2000. Multivariate analysis disclosed that only recent period of LT was associated with better prognosis. At last visit, the median calculated glomerular filtration rate was 93 ml/min (33-180); 11/93 patients (12%) had stage II renal insufficiency and none had stage III. CONCLUSIONS: Liver failure associated with WD is a rare indication for LT (\textless1%), which achieves an excellent long-term outcome, including renal function.

The postresection alpha-fetoprotein (AFP) in cirrhotic patients with hepatocellular carcinoma (HCC) may predict overall survival (OS) and recurrence beyond Milan criteria (MC) among the subgroup of initially transplantable patients.All patients with cirrhosis resected for HCC between January 1990 and December 2010 in a single institution and presenting a serum AFP value 15 ng/ml at diagnosis were included. The postresection AFP was analyzed as a dichotomized variable: normalization (norm + group) or not (norm - group) within the 90-day postresection period.Among 271 resected patients, 141 patients (52%) had a level of serum AFP ≥ 15 ng/ml at diagnosis. Five-year OS and median survival were 42% and 52 months in group norm + versus 20% and 23 months in the group norm - (P = 0.009). On multivariate analysis, the absence of AFP normalization was an independent factor of poor OS as well as microvascular invasion, and satellites nodules. Among theoretically transplantable patients, independent predictors of recurrence beyond MC were the absence of AFP normalization (risk ratio (RR) 5.02 [1.53-16.34]) and microvascular invasion (RR 4.76 [1.42-15.34]).The postresection AFP has an independent prognostic value. Transplantable patients resected for HCC without 90-day AFP normalization should be discussed for early liver transplantation.

Familial transthyretin amyloidosis (ATTR) is a rare, life-threatening, autosomal dominant disease involving mainly the heart and the peripheral nervous system due to a point mutation of the transthyretin ( TTR ) gene. By removing the main source of the mutated TTR , liver transplantation (LT) has