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Objectives: To analyze long-term oncological outcome along with prognostic risk factors in a large cohort of patients with colorectal liver metastases (CRLM) undergoing ALPPS., Background: ALPPS is a two-stage hepatectomy variant that increases resection rates and R0 resection rates in patients with primarily unresectable CRLM as evidenced in a recent randomized controlled trial. Long-term oncologic results, however, are lacking., Methods: Cases in- and outside the International ALPPS Registry were collected and completed by direct contacts to ALPPS centers to secure a comprehensive cohort. Overall, cancer-specific (CSS), and recurrence-free (RFS) survivals were analyzed along with independent risk factors using Cox-regression analysis., Results: The cohort included 510 patients from 22 ALPPS centers over a 10-year period. Ninety-day mortality was 4.9% and median overall survival, CSS, and RFS were 39, 42, and 15 months, respectively. The median follow-up time was 38 months (95% confidence interval 32-43 months). Multivariate analysis identified tumor-characteristics (primary T4, right colon), biological features (K/N-RAS status), and response to chemotherapy (Response Evaluation Criteria in Solid Tumors) as independent predictors of CSS. Traditional factors such as size of metastases, uni versus bilobar involvement, and liver-first approach were not predictive. When hepatic recurrences after ALPPS was amenable to surgical/ablative treatment, median CSS was significantly superior compared to chemotherapy alone (56 vs 30 months, P < 0.001)., Conclusions: This large cohort provides the first evidence that patients with primarily unresectable CRLM treated by ALPPS have not only low perioperative mortality, but achieve appealing long-term oncologic outcome especially those with favorable tumor biology and good response to chemotherapy.

Background: Post hepatectomy liver failure (PHLF) after ALPPS has been related to the discrepancy between liver volume and function. Pre-operative hepatobiliary scintigraphy (HBS) can predict post-operative liver function and guide when it is safe to proceed with major hepatectomy. Aim of this study was to evaluate the role of HBS in predicting PHLF after ALPPS, defining a safe cut-off., Methods: A multicenter retrospective study was approved by the ALPPS Registry. All patients selected for ALPPS between 2012 and 2018, were evaluated. Every patient underwent HBS during ALPPS evaluation. PHLF was reported according to ISGLS definition, considering grade B or C as clinically significant., Results: 98 patients were included. Thirteen patients experienced PHLF grade B or C (14%) following ALPPS-2. The HBS and the daily gain in volume (KGR FLR ) of the future liver remnant (FLR) were significantly lower in PHLF B and C (p = .004 and .041 respectively). ROC curves indicated safe cut-offs of 4.1%/day (AUC = 0.68) for KGR FLR , and of 2.7 %/min/m 2 (AUC = 0.75) for HBS FLR . Multivariate analysis confirmed these cut-offs as variables predicting PHLF after ALPPS-2., Conclusion: Patients presenting a KGR FLR ≤4.1%/day and a HBS FLR ≤2.7%/min/m 2 are at high risk of PHLF and their second stage should be re-discussed., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: ALPPS is found to increase the resectability of primary and secondary liver malignancy at the advanced stage. The aim of the study was to verify the surgical and oncological outcome of ALPPS for intrahepatic cholangiocarcinoma (ICC)., Methods: The study cohort was based on the ALPPS registry with patients from 31 international centers between August 2009 and January 2018. Propensity score matched patients receiving chemotherapy only were selected from the SEER database as controls for the survival analysis., Results: One hundred and two patients undergoing ALPPS were recruited, 99 completed the second stage with median inter-stage duration of 11 days. The median kinetic growth rate was 23 ml/day. R0 resection was achieved in 87 (85%). Initially high rates of morbidity and mortality decreased steadily to a 29% severe complication rate and 7% 90-day morbidity in the last 2 years. Post-hepatectomy liver failure remained the main cause of 90-day mortality. Multivariate analysis revealed insufficient future liver remnant at the stage-2 operation (FLR2) to be the only risk factor for severe complications (OR 2.91, p = 0.02). The propensity score matching analysis showed a superior overall survival in the ALPPS group compared to palliative chemotherapy (median overall survival: 26.4 months vs 14 months; 1-, 2-, and 3-year survival rates: 82.4%, 70.5% and 39.6% vs 51.2%, 21.4% and 11.3%, respectively, p < 0.01). The survival benefit, however, was not confirmed in the subgroup analysis for patients with insufficient FLR2 or multifocal ICC., Conclusion: ALPPS showed high efficacy in achieving R0 resections in locally advanced ICC. To get the most oncological benefit from this aggressive surgery, ALPPS would be restricted to patients with single lesions and sufficient FLR2.

Improving the protection of marginal liver grafts during static cold storage is a major hurdle to increase the donor pool of organs. The endothelium glycocalyx quality of preservation influences future inflammatory and oxidative responses. One cellular pathway responsible for the formation of nitric oxide by endothelial cells is dependent on the stimulation of proteoglycans present in the glycocalyx. We investigated the impact of the glycocalyx preservation in static cold storage of fatty liver preserved in different preservation solutions on the endothelium-mediated production of NO. Zucker fatty rat livers were preserved 24 h in static cold storage in either Institut Georges Lopez-1 (IGL-1) ( n = 10), IGL-0 (i.e., without PEG35) ( n = 5) or Histidine-Tryptophan-Ketoglutarate (HTK) ( n = 10) preservation solutions before being processed for analysis. For Sham group ( n = 5), the fatty livers were immediately analyzed after procurement. The level of transaminases and nitrites/nitrates were measured in the washing perfusate. Glycocalyx proteins expressions, Syndecan-1, glypican-1 and heparan sulfate (HS), were determined in the tissue (ELISA). Steatotic livers preserved 24 h in IGL-1 preservation solution have a significant lower level of transaminases (aspartate aminotransferase (AST), alanine aminotransferase (ALT)) and less histological damages than steatotic livers preserved 24 h with HTK ( p = 0.0152). The syndecan-1 is significantly better preserved in IGL-1 group compared to HTK ( p < 0.0001) and we observed the same tendency compared to IGL-0. No significant differences were observed with glypican-1. HS expression in HTK group was significantly higher compared to the three other groups. HS level in IGL-1 was even lower than IGL-0 ( p = 0.0005) which was similar to Sham group. The better protection of the glycocalyx proteins in IGL-1 group was correlated with a higher production of NO than HTK ( p = 0.0055) or IGL-0 ( p = 0.0433). IGL-1 protective mechanisms through the formation of NO could be due to its better protective effects on the glycocalyx during SCS compared to other preservation solutions. This beneficial effect could involve the preservation state of syndecan-1 and the internalization of HS.

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.

Background: Many factors may compromise the functional recovery of a harvested potential liver for engraftment. Normothermic machine perfusion (NMP) can revive hepatic metabolism ex vivo enabling subsequent transplantation. In this study, we evaluated the recovery of 11 discarded livers' function utilizing NMP., Materials and Methods: Eleven consecutive discarded livers underwent NMP for 6 hours. Liver function recovery was defined by lactate levels of ≤3 mmol/L and continuous bile production., Results: Ten of 11 livers perfused were fatty. The median percentage of macrosteatosis (MaS) and microsteatosis (MiS) was 40% (10%-90%) and 40% (20%-50%), respectively, based on a review of paraffin-embedded sections of preperfusion biopsies. A discarded "amyloid" liver from an HIV-positive donor was also studied. Recovery of liver function was observed in 4 livers, including that with the amyloid deposition. These livers sustained shorter cold ischemia times and seemed to have increased portal and arterial blood flow. No significant change in MiS or MaS was observed before and after perfusion., Conclusion: Our results suggest that some discarded grafts might have been salvaged for transplantation. Further studies utilizing NMP with subsequent transplantation would validate this strategy., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: 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., Patients and Methods: 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., Results: 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)., Conclusions: 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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The performance of linear models predicting Total Liver Weight (TLW) remains moderate. The use of more complex models such as Artificial Neural Network (ANN) and Generalized Additive Model (GAM) or including the variable "steatosis" may improve TLW prediction. This study aimed to assess the value of ANN and GAM and the influence of steatosis for predicting TLW., Methods: Basic clinical and morphological variables of 1560 cadaveric donors for liver transplantation were randomly split into a training (2/3) and validation set (1/3). Linear models, ANN and GAM were built by using the training cohort and evaluated with the validation cohort., Results: The TLW is subject to major variations among donors with similar morphological parameters. The performance of ANN and GAM were moderate and similar to that of linear models (concordance coefficient from 0.36 to 0.44). In 28-30% of cases, TLW cannot be predicted with a margin of error ≤20%. The addition of the variable "steatosis" to each model did not improve their performance., Conclusion: TLW prediction based on anthropological parameters carry a significant risk of error despite the use of more complex models. Others determinants of TLW need to be identified and imaging-based volumetric measurements should be preferred when feasible., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Combining radiofrequency ablation (RFA) with hepatectomy may enable treatment with curative intent for patients with colorectal liver metastasis (CRLM). However, the oncological outcomes in comparison with resection alone remain to be clarified., Methods: Patients who underwent a first hepatectomy between 2001 and 2012 for CRLM were enrolled. Short- and long-term outcomes of patients who underwent hepatectomy plus RFA were compared with those of patients who had hepatectomy alone using propensity score matching., Results: Of a total of 553 patients, hepatectomy + RFA and hepatectomy alone were performed in 37 and 516 respectively. Before matching, patients in the hepatectomy + RFA group were characterized primarily by a larger tumour burden. After matching of 31 patients who underwent hepatectomy + RFA with 93 who had hepatectomy alone, background characteristics were well balanced. In the matched cohort, overall and disease-free survival in the hepatectomy + RFA group were no different from those among patients who had hepatectomy alone (5-year overall survival rate 57 versus 61 per cent, P = 0·649; 5-year disease-free survival rate 19 versus 17 per cent, P = 0·865). Local recurrence at the ablated site was observed in four of 31 patients (13 per cent). Although overall local recurrence (ablated site and/or cut surface) was more frequent in the hepatectomy + RFA group (9 of 31 (29 per cent) versus 11 of 93 (12 per cent); P = 0·032), there was no difference in intrahepatic disease-free survival between the two groups (P = 0·705)., Conclusion: Hepatectomy + RFA achieved outcomes comparable to hepatectomy alone. Combining RFA with hepatectomy should be considered as an option to achieve cure., (© 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background and Objectives: We aimed to define the cure rate in patients with colorectal liver metastases (CRLM) and concomitant extrahepatic disease (EHD) on the 5-year disease-free survival (DFS) after surgery, and identify the factors for predicting a cure., Methods: Patients who underwent hepatectomy for CRLM with concomitant EHD were identified. Those followed for >5 years after surgery were enrolled. A cure was defined as DFS of >5 years after the last curative surgery., Results: A cure was achieved in 24/175 (13%) patients (intention-to-treat [ITT] cohort), and 22/109 (19%) patients who underwent complete resection for both hepatic and extrahepatic metastases (EHD resection cohort). A multivariate analysis identified primary T1-2 (relative risk [RR] 47.4, P = 0.0001), metachronous metastasis (RR 4.9, P = 0.026), carbohydrate antigen 19-9 (CA19-9) ≤37 U/mL (RR 8.37, P = 0.015), number of liver and EHD tumors (RR 11.2, P = 0.0058), and non-incidental EHD diagnosis (RR 8.41, P = 0.018) as independent factors that predicted a cure in the ITT cohort; and primary T1-2 (RR 22.2, P = 0.013), primary N0 (RR 4.42, P = 0.031), metachronous metastasis (RR 6.48, P = 0.013), and CA19-9 ≤37 U/mL (RR 27.4, P = 0.012) in the EHD resection cohort., Conclusions: Even when concomitant EHD is present, a potential of cure could be achieved with aggressive oncosurgical approach., (© 2017 Wiley Periodicals, Inc.)

Background: Breast cancer liver metastases (BCLM) are considered the most lethal compared with other sites of metastases in patients with breast cancer. This study aimed to evaluate the outcome after hepatectomy for BCLM within current multidisciplinary treatment and to develop a clinically useful nomogram to predict survival., Methods: Between January 1985 and December 2012, 139 consecutive female patients underwent liver resection for BCLM at the authors' institution. Clinicopathologic data were collected and analyzed for survival outcome with determination of prognostic factors. A nomogram to predict survival was developed based on a multivariate Cox model. The predictive performance of the model was assessed according to the C-statistic and calibration plots., Results: After a median follow-up period of 55 months, the overall 3- and 5-year survival rates after hepatectomy were respectively 58 and 47 %. The median overall survival period was 56 months, and the median disease-free survival period after surgical resection was 33 months. A single hepatic metastasis, no triple negative tumors, no microscopic vascular invasion, and perioperative hormonal or targeted therapy were related to improved overall survival. The model achieved good discrimination and calibration, with a C-statistic of 0.80., Conclusions: Liver resection for selected patients with breast cancer metastases can provide significant survival benefit. It should be part of a multidisciplinary treatment program in experienced liver surgery centers. The authors' nomogram facilitates personalized assessment of prognosis for these patients.

Background: Although associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been increasingly adopted by many centres, the oncological outcome for colorectal liver metastases compared with that after two-stage hepatectomy is still unknown., Methods: Between January 2010 and June 2014, all consecutive patients who underwent either ALPPS or two-stage hepatectomy for colorectal liver metastases in a single institution were included in the study. Morbidity, mortality, disease recurrence and survival were compared., Results: The two groups were comparable in terms of clinicopathological characteristics. ALPPS was completed in all 17 patients, whereas the second-stage hepatectomy could not be completed in 15 of 41 patients. Ninety-day mortality rates for ALPPS and two-stage resection were 0 per cent (0 of 17) versus 5 per cent (2 of 41) (P = 0·891). Major complication rates (Clavien grade at least III) were 41 per cent (7 of 17) and 39 per cent (16 of 41) respectively (P = 0·999). Overall survival was significantly lower after ALPPS than after two-stage hepatectomy: 2-year survival 42 versus 77 per cent respectively (P = 0·006). Recurrent disease was more often seen in the liver in the ALPPS group. Salvage surgery was less often performed after ALPPS (2 of 8 patients) than after two-stage hepatectomy (10 of 17)., Conclusion: Although major complication and 90-day mortality rates of ALPPS were similar to those of two-stage hepatectomy, overall survival was significantly lower following ALPPS., (© 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: Although recent advances in surgery and chemotherapy have increasingly enabled hepatectomy in patients with initially unresectable colorectal liver metastases (CRLM), not all such patients benefit from surgery. The aim of this study was to develop a nomogram to predict survival after hepatectomy for initially unresectable CRLM., Methods: Patients with initially unresectable CRLM treated with chemotherapy followed by hepatectomy between 1990 and 2012 were included in the study. A nomogram to predict survival was developed based on a multivariable Cox model. The predictive performance of the model was assessed according to the C-statistic, Kaplan-Meier curve and calibration plots., Results: Of a total of 439 patients, liver and globally completed surgery was achieved in 380 (86·6 per cent) and 335 (76·3 per cent) patients respectively. The 5-year overall and disease-free survival rates were 39·9 and 10·0 per cent respectively. Based on the Cox model, the following five factors were selected for the nomogram and assigned specific scores: node-positive primary, 5; more than six metastases at hepatectomy, 7; carbohydrate antigen 19-9 level at hepatectomy above 37 units/ml, 10; disease progression during first-line chemotherapy, 9; and presence of extrahepatic disease, 4. The model achieved relatively good discrimination and calibration, with a C-statistic of 0·66. The overall survival rate for patients with a score greater than 16 was significantly worse than that for patients with a score of 16 or less (5-year survival rate 4 versus 46·3 per cent respectively; P < 0·001)., Conclusion: The nomogram facilitates personalized assessment of prognosis for patients with initially unresectable CRLM treated with chemotherapy and with planned resection., (© 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: Resection of breast cancer liver metastases (BCLM) combined with systemic treatment is increasingly accepted as a therapeutic option; however, the potential benefit of repeat hepatectomy for recurrent BCLM is unknown., Methods: All consecutive female patients who underwent liver resection for BCLM at our center between January 1985 and December 2012 were included. Patients who had a single hepatectomy (N = 120) were compared with those who also underwent repeat hepatectomy (N = 19). Patients were selected for repeat hepatectomy based on operability and disease control. Prognostic factors of survival after repeat hepatectomy were determined., Results: Median overall survival since first hepatectomy was 35 months, with a 3- and 5-year survival rate of 50 and 38 %, respectively. Overall survival following repeat hepatectomy was 64 and 46 % at 3 and 5 years, respectively. From the time of first hepatectomy, patients who underwent repeat hepatectomy had a better survival than those who had only one hepatectomy (95 and 84 vs. 50 and 38 % at 3 and 5 years, respectively) (p = 0.002). Median survival was 35 and 100 months, respectively, and median survival since the diagnosis of BCLM was 51 and 112 months in the single and repeat hepatectomy groups, respectively. Since the time of diagnosis, overall 3-, 5-, and 7-year survival rates were 75, 57, and 44 %, respectively, for all 139 patients. Improved overall survival after repeat hepatectomy was related to a time interval between breast cancer diagnosis and first hepatectomy of >2 years, a limited hepatectomy, solitary liver metastasis, positive progesterone receptor status, and chemotherapy following repeat hepatectomy. Patients with single BCLM at first hepatectomy had a 3- and 5-year overall survival rate of 76 and 76 % compared with 51 and 17 % in patients with multiple metastases (p = 0.023)., Conclusion: In selected patients with BCLM, repeat hepatectomy for liver recurrence combined with systemic treatment provided survival rates comparable to those after first hepatectomy.

Background: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was recently developed to induce rapid hypertrophy and reduce post-hepatectomy liver failure in patients with insufficient remnant liver volume (RLV). However, mortality rates >12% have been reported. This study aimed to analyze the perioperative course of ALPPS and to identify factors associated with morbi-mortality., Methods: Between April 2011 and September 2013, 62 patients operated in 9 Franco-Belgian hepatobiliary centres underwent ALPPS for colorectal metastases (N = 50) or primary tumors, following chemotherapy (N = 50) and/or portal vein embolization (PVE; N = 9)., Results: Most patients had right (N = 31) or right extended hepatectomy (N = 25) (median RLV/body weight ratio of 0.54% [0.21-0.77%]). RLV increased by 48.6% [-15.3 to 192%] 7.8 ± 4.5 days after stage1, but the hypertrophy decelerated beyond 7 days. Stage2 was cancelled in 3 patients (4.8%) for insufficient hypertrophy, portal vein thrombosis or death and delayed to ≥9 days in 32 (54.2%). Overall, 25 patients (40.3%) had major complication(s) and 8 (12.9%) died. Fourteen patients (22.6%) had post-stage1 complication of whom 5 (35.7%) died after stage2. Factors associated with major morbi-mortality were obesity, post-stage1 biliary fistula or ascites, and infected and/or bilious peritoneal fluid at stage2. The latter was the only predictor of Clavien ≥3 by multivariate analysis (OR: 4.9; 95% CI: 1.227-19.97; p = 0.025). PVE did not impact the morbi-mortality rates but prevented major cytolysis that was associated with poor outcome., Conclusions: The inter-stages course was crucial in determining ALPPS outcome. The factors of high morbi-mortality rates associated with ALPPS are linked to the technique complexity., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Posthepatectomy liver failure (PHLF) is a severe complication after hepatectomy for colorectal liver metastases. This study evaluated its actual incidence and its effects on short- and long-term overall survival (OS) in a specialized center., Materials and Methods: Between 2006 and 2008, 193 patients who underwent 232 hepatectomies (147 minor and 85 major) for colorectal liver metastasis were studied prospectively. Hepatectomy was performed if the remnant liver volume was >0.5% of body weight. Uni- and multivariate analyses on OS after all hepatectomies (n = 232) or major resection only (n = 85) were then performed on pre-, intra-, and postoperative (including pathological) data to determine the consequences of PHLF by comparison with those of other intra- and postoperative events., Results: The 3-month postoperative mortality rate was 0.8%. PHLF was observed in six patients (7%) after major hepatectomy and in one (0.6%) after minor hepatectomy. With a 25-month follow-up, the 2-year OS rate was 84%. Preoperatively, pulmonary metastasis was the only determinant of OS. Intra- and postoperatively, four factors were determinant of OS: PHLF (risk ratio [RR] = 3.84, P = .04), mental confusion (RR = 3.11, P = .006), fluid collection (RR = 2.9, P = .01) and transfusion (RR = 2.27, P = .009). After major hepatectomy, only PHLF (RR = 4.14, P = .01) and confusion (RR = 3.6, P = .02) were identified., Conclusion: With improvements in postoperative management, PHLF was found to be less responsible for 3-month mortality but remains an event that exerts a major impact on 2-year survival., (Copyright © 2014 Mosby, Inc. All rights reserved.)