Predictive nomograms for postoperative 90-day morbidity and mortality in patients undergoing liver resection for various hepatobiliary diseases.

BACKGROUND: Postoperative complications affect the long-term survival and quality of life in patients undergoing liver resection. No model has yet been validated to predict 90-day severe morbidity and mortality. METHODS: The prospective recruitment of patients undergoing liver resection for various indications was performed. Preoperative clinical and laboratory data, including liver stiffness, indocyanine green retention, and intraoperative parameters, were analyzed to develop predictive nomograms for postoperative severe morbidity and mortality. Calibration plots were used to perform external validation. RESULTS: The most common indications in 418 liver resections performed were colorectal metastases (N = 149 [35.6%]), hepatocellular carcinoma (N = 106 [25.4%]), and benign liver tumors (N = 60 [14.3%]). Major liver resections were performed in 164 (39.2%) patients. Severe morbidity and mortality were observed in 87 (20.8%) and 9 (2.2%) of patients, respectively, during the 90-day postoperative period. Post-hepatectomy liver failure was observed in 19 (4.5%) patients, resulting in the death of 4. The independent predictors of 90-day severe morbidity were age (odds ratio:1.02, P = .06), liver stiffness (odds ratio: 1.23, P = .04], number of resected segments (odds ratio: 1.28, P = .004), and operative time (odds ratio: 1.01, P = .01). Independent predictors of 90-day mortality were diabetes mellitus (odds ratio: 6.6, P = .04), tumor size >50 mm (odds ratio:4.8, P = .08), liver stiffness ≥22 kPa (odds ratio:7.0, P = .04), and operative time ≥6 hours (odds ratio: 6.1, P = .05). Nomograms were developed using these independent predictors and validated by testing the Goodness of fit in calibration plots (P = .64 for severe morbidity; P = .8 for mortality). CONCLUSION: Proposed nomograms would enable a personalized approach to identifying patients at risk of complications and adapting surgical treatment according to their clinical profile and the center's expertise.

Revisiting the Surgical Management of Giant Hepatic Hemangiomas: Enucleation Versus Anatomical Resection?

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.

Ideal Surgical Margin to Prevent Early Recurrence After Hepatic Resection for Hepatocellular Carcinoma.

BACKGROUNDS AND AIMS: 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. METHODS: 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. RESULTS: 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 < 0.0001) and a surgical margin < 7 mm (OR 3.09 [1.26-8.85], P = 0.01) by multivariable analysis. The probability of early recurrence ranged from 5.0% in the absence of any factors to 43.5% in the presence of both factors. Among patients with alpha-fetoprotein levels ≥ 100 ng/ml, non-capsule formation, or microvascular invasion, there was a significant difference in 5-year overall survival between surgical margins of < 7 mm and ≥ 7 mm. CONCLUSIONS: A > 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.

Liver Resection for Early Hepatocellular Carcinoma: Preoperative Predictors of Non Transplantable Recurrence and Implications for Treatment Allocation.

BACKGROUND AND AIMS: LR and LT are the standard curative options for early HCC. LT provides best long-term survival but is limited by organ shortage. LR, readily available, is hampered by high recurrence rates. Salvage liver transplantation is an efficient treatment of recurrences within criteria. The aim of the study was to identify preoperative predictors of non transplantable recurrence (NTR) to improve patient selection for upfront LR or LT at initial diagnosis. STUDY DESIGN: Consecutive LR for transplantable HCC between 2000 and 2015 were studied. A prediction model for NTR based on preoperative variables was developed using sub-distribution hazard ratio after multiple imputation and internal validation by bootstrapping. Model performance was evaluated by the concordance index after correction for optimism. RESULTS: A total of 148 patients were included. Five-year overall survival and recurrence free survival were 73.6% and 29.3%, respectively (median follow-up 45.8 months). Recurrence rate was 54.8%. NTR rate was 38.2%. Preoperative model for NTR identified >1 nodule [sub-distribution hazard ratio 2.35 95% confidence interval (CI) 1.35-4.09], AFP >100 ng/mL (2.14 95% CI 1.17-3.93), and F4 fibrosis (1.93 95% CI 1.03-3.62). The apparent concordance index of the model was 0.664 after correction for optimism. In the presence of 0, 1, and ≥2 factors, NTR rates were 2.6%, 22.7%, and 40.9%, respectively. The number of prognostic factors was significantly associated with the pattern of recurrence (P = 0.001) and 5-year recurrence free survival (P < 0.001). CONCLUSIONS: Cirrhosis, >1 nodule, and AFP >100 ng/mL were identified as preoperative predictors of NTR. In the presence of 2 factors or more upfront transplantation should be probably preferred to resection in regard of organ availability. Other patients are good candidates for LR and salvage liver transplantation should be encouraged in eligible patients with recurrence.

Predictors of unresectability after portal vein embolization for centrally located cholangiocarcinoma.

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 <500 mm2/m2 (P = .04), high body mass index (P = .023), and low serum albumin level (P = .007) were associated with unresectabilty on multivariate analysis. A composite score including these variables (cutoffs determined after receiver operating characteristic curve analysis) was proposed and achieved accurate discrimination regarding unresectability (area under the curve = 0.82, P < .001). CONCLUSION: Predictors of unresectability after portal vein embolization for centrally located cholangiocarcinoma were identified, with sarcopenic overweight patients having a greater risk of unresectability. This preoperative score enables a fairly accurate prediction of unresectability in a given patient. These simple, objective, and inexpensive parameters should be considered in all patients with centrally located cholangiocarcinoma scheduled to undergo portal vein embolization.

Spleen volumetry and liver transient elastography: Predictors of persistent posthepatectomy decompensation in patients with hepatocellular carcinoma.

BACKGROUND: Posthepatectomy decompensation remains a frequent and poor outcome after hepatectomy, but its prediction is still inaccurate. Liver stiffness measurement can predict posthepatectomy decompensation, but there is a so-called "gray zone" that requires another predictor. Because splenomegaly is an objective sign of portal hypertension, we hypothesized that spleen volumetry could improve the identification of patients at risk. METHODS: Patients with hepatocellular carcinoma who underwent hepatectomy in our tertiary center between August 2014 and December 2017 were reviewed. The primary endpoint was to determine if the spleen volumetry and liver stiffness measurement were independent predictors of posthepatectomy decompensation, and secondarily, to determine if they were synergistic through a theoretic predictive model. RESULTS: One hundred and seven patients were included. The median follow-up time was 3 months (3-5). Postoperative 90-day mortality was 4.7%. By multivariate analysis, liver stiffness measurement and spleen volumetry predicted posthepatectomy decompensation. The liver stiffness measurement had a cutoff point of 11.6 kPa (area under receiver operating curve = 0.71 confidence interval 95% 0.71-0.88, sensitivity: 89%, specificity: 47%). The spleen volumetry cutoff point was 381.1 cm3 (area under receiver operating curve = 0.78, 95% confidence interval 0.77-0.93, sensitivity: 55%, specificity: 91%). The spleen volumetry improved prediction of posthepatectomy decompensation, because use of the spleen volumetry increased sensitivity (from 62% to 97%) and the negative predictive value (from 96% to 100%) along with a negligible decrease in specificity (from 96.7 to 93.4) and positive predictive value (from 64% to 59%) (P = .003). CONCLUSION: Spleen volumetry (>380 cm3) and liver stiffness measurement (>12 kPa) are non-invasive, independent, and synergistic tools that appear to be able to predict posthepatectomy decompensation. The importance of this finding is that these measurements may help to anticipate posthepatectomy decompensation and may possibly be used to direct alternative treatments to resection.

A Model to Predict Significant Macrosteatosis in Hepatic Grafts.

BACKGROUND AND AIMS: 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. 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. RESULTS: 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. CONCLUSION: 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.

Identification of Four Immune Subtypes Characterized by Distinct Composition and Functions of Tumor Microenvironment in Intrahepatic Cholangiocarcinoma.

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.

Ischemic Cholangiopathy Following Transcatheter Arterial Chemoembolization for Recurrent Hepatocellular Carcinoma After Hepatectomy: an Underestimated and Devastating Complication.

BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Comparative analysis of outcomes after liver resection and liver transplantation for early stages hepatocellular carcinoma in HIV-infected patients. An intention-to-treat analysis.

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.

Prognostic Value and Prediction of Extratumoral Microvascular Invasion for Hepatocellular Carcinoma.

BACKGROUND: There are few reports on microvascular invasion (MVI) located intra- or extratumorally and prognosis of hepatocellular carcinoma (HCC). OBJECTIVE: The aim of this study was to evaluate patient outcome according to the location of MVI, and to build a nomogram predicting extratumoral MVI. METHODS: 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). RESULTS: 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 < 0.0001) or LT (hazard ratio 1.99, p = 0.0005). Multivariate logistic regression analysis identified six independent risk factors for extratumoral MVI: α-fetoprotein, tumor size, non-boundary type, alkaline phosphatase, neutrophil-to-lymphocyte ratio, and aspartate aminotransferase. The nomogram for predicting extratumoral MVI using these factors showed good concordance indices of 0.774 and 0.744 in the internal and external validation cohorts, respectively. CONCLUSIONS: The prognostic value of MVI differs according to its invasiveness. The nomogram allows reliable prediction of extratumoral MVI in patients undergoing HR or LT.

Predictive model for microvascular invasion of hepatocellular carcinoma among candidates for either hepatic resection or liver transplantation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 with <50% probability (hepatic resection; 39.1% vs 61.2%, P < .0001, liver transplantation; 5-year overall survival, 54.8% vs 79.0%, P = .05). CONCLUSION: This model developed from preoperative data allows reliable prediction of microvascular invasion in candidates for either hepatic resection or liver transplantation.

Impact of Surgical Treatment for Recurrence After 2-Stage Hepatectomy for Colorectal Liver Metastases, on Patient Outcome.

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.

Arterial Lactate Concentration at the End of Liver Transplantation Is an Early Predictor of Primary Graft Dysfunction.

BACKGROUND: Although many prognostic factors of primary graft dysfunction after liver transplantation (LT) are available, it remains difficult to predict failure in a given recipient. OBJECTIVE: 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)]. METHODS: We reviewed data from a prospective database in a single center concerning patients transplanted between January 2015 and December 2016 (n = 296). RESULTS: 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. CONCLUSION: 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.

Evaluation of a micro-spectrometer for the real-time assessment of liver graft with mild-to-moderate macrosteatosis: A proof of concept study.

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 ≤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 ≥30% were 66.7%, 100%, 100% and 98%, respectively. The PSM could predict the absence (<30%)/presence (≥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.

Late hepaticartery thrombosis after liver transplantation: which strategy? A single-center retrospective study.

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.

Left-liver Adult-to-Adult Living Donor Liver Transplantation: Can It Be Improved? A Retrospective Multicenter European Study.

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 ±â€Š3.5 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% (P = 0.01 and P = 0.024, respectively) while SFSS was associated with a recipient MELD ≥14 (P = 0.019). A combination of donor age <45 years, MELD <14 and actual 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.

Rare genetic heterogeneity within single tumor discovered for the first time in colorectal liver metastases after liver resection.

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.

Natural history of portal vein embolization before liver resection: a 23-year analysis of intention-to-treat results.

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.

Long-term survival and cure model following liver resection for breast cancer metastases.

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 < 5 years were compared to those who survived ≥ 5 years from first diagnosis of hepatic metastases. Predictive factors for survival were analyzed. Statistically cured, defined as those patients who their hazard rate returned to that of the general population, was analyzed. RESULTS: Of the 139, 43 patients survived ≥ 5 years. Significant differences between patient groups (< 5 vs. ≥ 5 years) were mean time interval between primary tumor and hepatic metastases diagnosis (50 vs. 43 months), mean number of resected tumors (3 vs. 2), positive estrogen receptors (54% vs. 79%), microscopic lymphatic invasion (65% vs. 34%), vascular invasion (63% vs. 37%), hormonal therapy after resection (34% vs. 74%), number of recurrence (40% vs. 65%) and repeat hepatectomy (1% vs. 42%), respectively. The probability of statistical cure was 14% (95% CI 1.4-26.7%) in these patients. CONCLUSIONS: Hepatectomy combined with systemic treatment can provide a chance of long-term survival and even cure in selected patients with BCLM. Microscopic vascular/lymphatic invasion appears to be a novel predictor for long-term survival after hepatectomy for BCLM and should be part of the review when discussing multidisciplinary treatment strategies.