Showing papers by "René Adam published in 2015"

Liver Transplantation for Hereditary Transthyretin Amyloidosis: After 20 Years Still the Best Therapeutic Alternative?

Abstract: BACKGROUND: Until recently, liver transplantation (Ltx) was the only available treatment for hereditary transthyretin (TTR) amyloidosis; today, however, several pharmacotherapies are tested. Herein ...

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS): Impact of the inter-stages course on morbi-mortality and implications for management

Abstract: 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.

Surgical management of patients with colorectal cancer and simultaneous liver and lung metastases

Abstract: The management of patients with colorectal cancer and simultaneously diagnosed liver and lung metastases (SLLM) remains controversial.

Early and Long-term Oncological Outcomes After Laparoscopic Resection for Colorectal Liver Metastases: A Propensity Score-based Analysis.

Abstract: Objective:To compare early and long-term outcomes in patients undergoing resection for colorectal liver metastases (CLM) by either a laparoscopic (LA) or an open (OA) approach.Background:The LA is still a matter of debate regarding the surgical management of CLM.Methods:Data of all patients from 32

Emerging concepts in liver graft preservation.

Abstract: The urgent need to expand the donor pool in order to attend to the growing demand for liver transplantation has obliged physicians to consider the use of suboptimal liver grafts and also to redefine the preservation strategies. This review examines the different methods of liver graft preservation, focusing on the latest advances in both static cold storage and machine perfusion (MP). The new strategies for static cold storage are mainly designed to increase the fatty liver graft preservation via the supplementation of commercial organ preservation solutions with additives. In this paper we stress the importance of carrying out effective graft washout after static cold preservation, and present a detailed discussion of the future perspectives for dynamic graft preservation using MP at different temperatures (hypothermia at 4 ℃, normothermia at 37 ℃ and subnormothermia at 20 ℃-25 ℃). Finally, we highlight some emerging applications of regenerative medicine in liver graft preservation. In conclusion, this review discusses the “state of the art” and future perspectives in static and dynamic liver graft preservation in order to improve graft viability.

Failure to Achieve a 2-Stage Hepatectomy for Colorectal Liver Metastases: How to Prevent It?

Abstract: Objectives:The aim of the study was to identify predictive factors of failure of 2-stage hepatectomy (TSH) forthe selection of patients with extensive bilobar colorectal liver metastases (CRLM), who are candidates for TSH.Background:The main weakness of TSH is the risk of failure to complete both th

Arterial Lactate Concentration at the End of an Elective Hepatectomy Is an Early Predictor of the Postoperative Course and a Potential Surrogate of Intraoperative Events

Abstract: Objectives: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.Background Data:A recent systematic-review of risk-prediction-models for liver

Role of neoadjuvant chemotherapy in resectable synchronous colorectal liver metastasis; An international multi-center data analysis using LiverMetSurvey.

Abstract: The use of neo-adjuvant chemotherapy in resectable synchronous liver metastasis is ill defined. The aim of this study was to evaluate neo-adjuvant chemotherapy on outcomes following liver resection for synchronous CLM.

Spontaneous splenorenal shunt in liver transplantation: Results of left renal vein ligation versus renoportal anastomosis

Abstract: 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.

Comparison of Complete Pathologic Response and Hepatic Injuries Between Hepatic Arterial Infusion and Systemic Administration of Oxaliplatin in Patients with Colorectal Liver Metastases

Abstract: Whether hepatic arterial infusion (HAI) of oxaliplatin influences the rates of complete pathologic response (CPR) and severe oxaliplatin-related lesions (SOxL) in patients with colorectal liver metastases (CRLM) is unknown. This study aimed to compare the incidence of CPR and SOxL between systemic (intravenous, IV) and HAI administration. All patients with initially unresectable CRLM who had undergone hepatic resection in two expert centers between 2004 and 2010 after at least 6 cycles of oxaliplatin-based chemotherapy administered either via HAI (n = 18) or IV (n = 50) were included. The presence of CPR and SOxL were evaluated by two pathologists. A 1:2 case match using a propensity score was used. A CPR was observed significantly more often after HAI (33 vs. 10 %, P = 0.03). However, SOxL had occurred more frequently in patients in the HAI group versus the IV group, 66 and 20 %, respectively (P < 0.001). On a well-balanced cohort, HAI was associated with higher chance of CPR (odds ratio 9.33, 95 % confidence interval 1.59–54.7) but also higher risk of SOxL (odds ratio 13.7, 95 % confidence interval 3.08–61.3). A CPR markedly enhanced overall survival (OS) and disease-free survival (median OS of 114 vs. 42 months, P = 0.02; median disease-free survival of 51 vs. 12 months, P = 0.002). Patients with SOxL did not experience different outcome (median OS of 42 vs. 50 months, respectively; P = 0.92) HAI of oxaliplatin increases the likelihood of a CPR at the cost of a higher incidence of SOxL in patients with initially unresectable CRLM.

Repeat Hepatectomy for Breast Cancer Liver Metastases

Abstract: 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. 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. 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). In selected patients with BCLM, repeat hepatectomy for liver recurrence combined with systemic treatment provided survival rates comparable to those after first hepatectomy.

Protective Effect of Intravenous High Molecular Weight Polyethylene Glycol on Fatty Liver Preservation

Abstract: Ischemia reperfusion injury (IRI) leads to significant tissue damage in liver surgery. Polyethylene glycols (PEGs) are water soluble nontoxic polymers that have proved their effectiveness against IRI. The objective of our study was to investigate the potential protective effects of intravenous administration of a high molecular weight PEG of 35 kDa (PEG 35) in steatotic livers subjected to cold ischemia reperfusion. In this study, we used isolated perfused rat liver model to assess the effects of PEG 35 intravenous administration after prolonged cold ischemia (24 h, 4°C) and after reperfusion (2 h, 37°C). Liver injury was measured by transaminases levels and mitochondrial damage was determined by confocal microscopy assessing mitochondrial polarization (after cold storage) and by measuring glutamate dehydrogenase activity (after reperfusion). Also, cell signaling pathways involved in the physiopathology of IRI were assessed by western blot technique. Our results show that intravenous administration of PEG 35 at 10 mg/kg ameliorated liver injury and protected the mitochondria. Moreover, PEG 35 administration induced a significant phosphorylation of prosurvival protein kinase B (Akt) and activation of cytoprotective factors e-NOS and AMPK. In conclusion, intravenous PEG 35 efficiently protects steatotic livers exposed to cold IRI.

Colorectal liver metastases are more often super wild type. Toward treatment based on metastatic site genotyping

Abstract: Recent data showed that metastatic colorectal (mCRC) tumors exhibiting extended RAS-BRAF mutations were resistant to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, making these drugs suitable for the so-called “super” wild-type (WT) patients only. This study aimed to compare the extended RAS-BRAF mutation frequency and characteristics according to location of tumor sampling. All consecutive mCRC specimens (N = 1659) referred to our institution from January 2008 till June 2014 were included in the analysis. Tumor genotyping (first for KRAS exon 2, then for BRAF exon 15, and later for KRAS exons 2, 3, and 4 and NRAS exons 2, 3, and 4) was performed with high-resolution melting analysis or allelic discrimination. The factors predicting for the presence of mutation were explored using multivariate binary logistic regression. Overall, the prevalence of KRAS exon 2 was 36.8 %, and it was lower in liver metastases (N = 138/490; 28.2 %) in comparison with primary tumors (N = 442/1086; 40.7 %), lung metastases (16/32; 50 %), or other metastatic sites (15/51; 29.4 %; P < 0.0001). Similarly, in the 1428 samples analyzed, BRAF mutations were less often found in liver metastases (N = 9/396; 2.3 %) as compared to primary tumors (N = 79/959; 8.2 %), lung metastases (N = 2/29; 6.9 %), or other metastatic locations (N = 2/44; 4.5 %; P < 0.0002). Overall occurrence of extended RAS mutation was 51.7 %. Of the 503 samples tested, the prevalence of extended RAS-BRAF mutations was twice as low in liver metastases (N = 53/151; 34.2 %) as compared to primary tumors (N = 191/322; 59.3 %, P < 0.0001). Univariate analysis identified age ≤65 years, male gender, and liver localization as predictors of super WT status. At multivariate analysis, only liver metastases were retained (RR 2.85 [95 % CI 1.91–4.30]). Colorectal liver metastases are twice as likely to exhibit a super WT genotype as compared to other tumor locations independently from other factors. This molecular feature has the potential to influence therapeutic strategy in mCRC patients.

Resection of liver metastases in breast cancer

Abstract: Liver metastases have the poorest prognosis of all types of breast cancer metastases, with a 5-year survival rate of 0 to 12%. In comparison, the 5-year overall survival rate of patients with colorectal liver metastases undergoing curative liver resection is approximately 30 to 40% and even 50% in selected patients. Partial liver resection in combination with systemic treatment for patients with hepatogenic metastases from breast cancer may lead to improved survival rates for selected patients.

Is R2 resection a valuable salvage treatment for colorectal liver metastases

Abstract: e14602 Background: Patients with multiple colorectal liver metastases (CRLM) are always considered in an intention to resect all metastases (R0/R1resection). However technical constraints make that...