New Biomarkers to Define a Biological Borderline Situation for Pancreatic Adenocarcinoma: Results of an Ancillary Study of the PANACHE01-PRODIGE48 Trial.

OBJECTIVE: To investigate in patients treated for a resectable pancreatic ductal adenocarcinoma [pancreatic adenocarcinoma (PA)], the prognostic value of baseline carbohydrate antigen 19.9 (CA19-9) and circulating tumor DNA (ctDNA) for overall survival (OS), to improve death risk stratification, based on a planned ancillary study from PANACHE01-PRODIGE 48 trial. BACKGROUND: Biological borderline situation that was first used by the MD Anderson, became a standard practice following the international consensus conference in 2016 to manage PA. Regarding the risk of systemic disease, especially in the setting of "markedly elevated" CA19-9, neoadjuvant therapy is advised to avoid unnecessary surgery, with a risk of early recurrence. To best define biological borderline situations, new biomarkers are needed. METHODS: Characteristics at diagnosis and OS were compared between patients with or without ctDNA status available. OS was estimated with the Kaplan-Meier method and compared with a log-rank test. The restricted cubic spline approach was used to identify the optimal threshold for biological parameters for death risk stratification. Univariate and multivariate Cox proportional hazard models were estimated to assess the association of ctDNA status and other parameters with OS. RESULTS: Among the 132 patients from the primary population for analysis in the PANACHE01 -PRODIGE 48 trial, 92(71%) were available for ctDNA status at diagnosis. No selection bias was identified between patients with or without ctDNA status. Fourteen patients (15%) were ctDNA+ and exhibited a higher risk for death [ P = 0.0188; hazard ratio (95% CI): 2.28 (1.12-4.63)]. In the 92 patients with ctDNA status available among the other parameters analyzed, only CA19-9 was statically associated with OS in univariate analysis. Patients with a log of CA19-9 equal or superior to 4.4 that corresponds to a CA19-9 of 80 UI/mL were identified at higher risk for death [ P = 0.0143; hazard ratio (95% CI): 2.2 (1.15-4.19)]. In multivariate analysis, CA19-19 remained independently associated with OS ( P = 0.0323). When combining the 2 biomarkers, the median OS was 19.4 [IC 95%: 3.8-not reached (NR)] months, 30.2 (IC 95%: 17.1-NR) months and NR (IC 95%: 39.3-NR) for "CA19-9 high and ctDNA+ group," "CA19-9 high or ctDNA+ group," and "CA19-9 low and ctDNA- group," respectively (log-rank P = 0.0069). CONCLUSIONS: Progress in the management of potentially operable PA remains limited, relying solely on strategies to optimize the sequence of complete treatment, based on modern multidrug chemotherapy (FOLFIRINOX, GemNabPaclitaxel) and surgical resection. The identification of risk criteria, such as the existence of systemic disease, is an important issue, currently referred to as "biological borderline disease." Few data, particularly from prospective studies, allow us to identify biomarkers other than CA19-9. Combining ctDNA with CA19-9 could be of interest to best define biological borderline situations in PA.

Somatostatin Versus Octreotide for Prevention of Postoperative Pancreatic Fistula: The PREFIPS Randomized Clinical Trial: A FRENCH 007-ACHBT Study.

OBJECTIVE: Pharmacological prevention of postoperative pancreatic fistula (POPF) after pancreatectomy is open to debate. The present study compares clinically significant POPF rates in patients randomized between somatostatin versus octreotide as prophylactic treatment. METHODS: Multicentric randomized controlled open study in patient's candidate for pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) comparing somatostatin continuous intravenous infusion for 7 days versus octreotid 100 µg, every 8 hours subcutaneous injection for 7 days, stratified by procedure (PD vs DP) and size of the main pancreatic duct (>4 mm) on grade B/C POPF rates at 90 days based on an intention-to-treat analysis. RESULTS: Of 763 eligible patients, 651 were randomized: 327 in the octreotide arm and 324 in the somatostatin arm, with comparable the stratification criteria - type of surgery and main pancreatic duct dilatation. Most patients had PD (n=480; 73.8%), on soft/normal pancreas (n=367; 63.2%) with a nondilated main pancreatic duct (n=472; 72.5%), most often for pancreatic adenocarcinoma (n=311; 47.8%). Almost all patients had abdominal drainage (n=621; 96.1%) and 121 (19.5%) left the hospital with the drain in place (median length of stay=16 days). A total of 153 patients (23.5%) developed a grade B/C POPF with no difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (χ 2 test, P =0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis. CONCLUSION: Continuous intravenous somatostatin is not statistically different from subcutaneous octreotide in the prevention of grade B/C POPF after pancreatectomy. FINDINGS: In the PREFIPS Randomized Clinical Trial including 651 patients, a total of 153 patients (23.5%) developed a grade B/C POPF with no significant difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (χ 2 test, P =0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis.

Right Ex-situ split grafts for adult liver transplantation - A Multicenter Benchmarking Analysis.

OBJECTIVE: To analyse outcomes after adult right ex-situ split graft liver transplantations (RSLT) and compare with available outcome benchmarks from whole liver transplantation (WLT). SUMMARY BACKGROUND DATA: Ex-situ SLT may be a valuable strategy to tackle the increasing graft shortage. Recently established outcome benchmarks in WLT offer a novel reference to perform a comprehensive analysis of results after ex-situ RSLT. METHODS: This retrospective multicenter cohort study analyzes all consecutive adult SLT performed using right ex-situ split grafts from 01.01.2014 to 01.06.2022. Study endpoints included 1 year graft and recipient survival, overall morbidity expressed by the comprehensive complication index (CCI©) and specific post-LT complications. Results were compared to the published benchmark outcomes in low-risk adult WLT scenarii. RESULTS: In 224 adult right ex-situ SLT, 1y recipient and graft survival rates were 96% and 91.5%, within the WLT benchmarks. The 1y overall morbidity was also within the WLT benchmark (41.8 CCI points vs. <42.1). Detailed analysis, revealed cut surface bile leaks (17%, 65.8% Grade IIIa) as a specific complication without a negative impact on graft survival. There was a higher rate of early hepatic artery thrombosis (HAT) after SLT, above the WLT benchmark (4.9% vs. ≤4.1%), with a significant impact on early graft but not patient survival. CONCLUSION: In this multicentric study of right ex-situ split graft LT, we report 1-year overall morbidity and mortality rates within the published benchmarks for low-risk WLT. Cut surface bile leaks and early HAT are specific complications of SLT and should be acknowledged when expanding the use of ex-situ SLT.

Intraoperative indocyanine green fluorescence imaging to predict early hepatic arterial complications after liver transplantation.

The purpose of this study was to propose an innovative intraoperative criterion in a liver transplantation setting that would judge arterial flow abnormality that may lead to early hepatic arterial occlusion, that is, thrombosis or stenosis, when left untreated and to carry out reanastomosis. After liver graft implantation, and after ensuring that there is no abnormality on the Doppler ultrasound (qualitative and quantitative assessment), we intraoperatively injected indocyanine green dye (0.01 mg/Kg), and we quantified the fluorescence signal at the graft pedicle using ImageJ software. From the obtained images of 89 adult patients transplanted in our center between September 2017 and April 2019, we constructed fluorescence intensity curves of the hepatic arterial signal and examined their relationship with the occurrence of early hepatic arterial occlusion (thrombosis or stenosis). Early hepatic arterial occlusion occurred in 7 patients (7.8%), including 3 thrombosis and 4 stenosis. Among various parameters of the flow intensity curve analyzed, the ratio of peak to plateau fluorescence intensity and the jagged wave pattern at the plateau phase were closely associated with this dreaded event. By combining the ratio of peak to plateau at 0.275 and a jagged wave, we best predicted the occurrence of early hepatic arterial occlusion and thrombosis, with sensitivity/specificity of 0.86/0.98 and 1.00/0.94, respectively. Through a simple composite parameter, the indocyanine green fluorescence imaging system is an additional and promising intraoperative modality for identifying recipients of transplant at high risk of developing early hepatic arterial occlusion. This tool could assist the surgeon in the decision to redo the anastomosis despite normal Doppler ultrasonography.

Association Between Liver Graft to Recipient Weight Ratio and Acute Kidney Injury Following Liver Transplantation: A Historical Cohort Study.

INTRODUCTION: Acute kidney injury (AKI) is a frequent complication following liver transplantation (LT) that has a multifactorial etiology. While some perioperative risk factors have been associated with postoperative AKI, the impact of liver graft weight to recipient body weight ratio (GW/RBW) has been poorly explored. We hypothesized that a high GW/RBW ratio would be associated with AKI after LT. METHODS: This single-center historical cohort study included all consecutive adults who had LT at Paul Brousse Hospital between 2018 and 2022. Patients requiring preoperative renal replacement therapy, combined solid organ transplantation, retransplantation, split or domino graft were excluded, as well as those with missing graft weight and creatinine values during the first postoperative week. The primary exposure was GW/RBW ratio expressed as a proportion. The primary outcome was the incidence of postoperative AKI within 7 days after surgery, defined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The secondary outcome was the AKI severity (KDIGO grades). We estimated logistic and ordinal regression models adjusted for potential confounding factors and explored nonlinear associations. RESULTS: Of 467 patients analyzed, 211 (45%) developed AKI. A high GW/RBW ratio was associated with both the risk of postoperative AKI and the severity of AKI (KDIGO grades), especially above a threshold of 2.5% (non-linear effect). CONCLUSION: A high GW/RBW ratio was associated with an exponential increase in the risk of AKI after LT. A high GW/RBW ratio was also associated with an increased AKI severity. Our findings may help improve graft allocation in patients undergoing LT.

Study protocol of the FRENCH24-ANIS study: postoperative anti-infective strategy following pancreaticoduodenectomy in patients with preoperative biliary stents-an intergroup FRENCH-ACHBT-SFAR prospective randomized controlled trial.

BACKGROUND: Despite advances in surgical techniques and care, pancreatoduodenectomy (PD) continues to have high morbidity and mortality rates. Complications such as sepsis, hemorrhage, pulmonary issues, shock, and pancreatic fistula are common postoperative challenges. A key concern in PD outcomes is the high incidence of infectious complications, especially surgical site infections (SSI) and postoperative pancreatic fistula (POPF). Bacteriobilia, or bile contamination with microorganisms, significantly contributes to these infections, increasing the risk of early postoperative complications. The occurrence of SSI in patients who undergo hepatobiliary and pancreatic (HPB) surgeries such as PD is notably higher than that in patients who undergo other surgeries, with rates ranging from 20 to 55%. Recent research by D'Angelica et al. revealed that, compared to cefoxitin, piperacillin/tazobactam considerably lowers the rate of postoperative SSI. However, these findings do not indicate whether extending the duration of antibiotic treatment is beneficial for patients at high risk of bacterial biliary contamination. In scenarios with a high risk of SSI, the specific agents, doses and length of antibiotic therapy remain unexplored. The advantage of prolonged antibiotic prophylaxis following PD has not been established through prospective studies in PD patients following biliary drainage. METHODS: This is an intergroup FRENCH-ACHBT-SFAR multicenter, open-labelled randomized, controlled, superiority trial comparing 2 broad-spectrum antibiotic (piperacillin/tazobactam) treatment modalities to demonstrate the superiority of 5-day postoperative antibiotic therapy to antibiotic prophylaxis against the occurrence of surgical site infections (SSI) following pancreaticoduodenectomy in patients with preoperative biliary stents. The primary endpoint of this study is the overall SSI rate, defined according to the ACS NSQIP, as a composite of superficial SSI, deep incisional SSI, and organ/space SSI. In addition, we will analyze overall morbidity, antibiotic resistance profiles, the pathogenicity of bacteriological and fungal cocontamination, the impact of complications after bile drainage and neoadjuvant treatment on the bacteriological and fungal profile of biliculture and cost-effectiveness. CONCLUSION: This FRENCH24-ANIS study aims to evaluate 5-day post-operative antibiotic therapy combined with antibiotic prophylaxis on the occurrence of surgical site infections (SSI) following pancreaticoduodenectomy in patients with preoperative biliary stents. TRIAL REGISTRATION: ClinicaTrials.gov number, NCT06123169 (Registration Date 08-11-2023); EudraCT number 2021-006991-18; EUCT Number: 2024-515181-14-00.

Repeat laparoscopic liver resection after an initial open hepatectomy.

BACKGROUND: Repeat open hepatectomy (ROH) for recurrent liver tumors is the preferred approach especially after initial open hepatectomy (OH). The aim of this study is to assess feasibility and safety of repeat laparoscopic hepatectomy (RLH) after initial OH in 2 high volume hepato-biliary hospitals. METHODS: Patients were retrieved from prospective data bases from 2012 to 2020. The patients were divided into two groups according to the approach used for repeat hepatectomy, ROH and RLH groups. RESULTS: Sixty-seven patients matched the criteria, 20 in RLH and 47 in ROH. Diagnoses were hepatocellular carcinoma in 52.3%, intrahepatic cholangiocarcinoma in 7.7% and colorectal liver metastases in 40%. Median operative time and blood loss were lower in RLH (199 vs 260 min, and 100 vs 400 ml respectively), as well as overall postoperative complications (20% vs 49%). There were 2 conversions (10%) due to adhesions and one died of postoperative pancreatitis in RLH. Median hospital stay was lower in RLH (5 vs 9 days). CONCLUSION: RLH is a feasible, safe technique and a realistic option to be considered in selected patients after previous OH. Early conversion should be considered when adhesions are more severe than expected.

Towards refining the utility of dual (18F-FDG / 18F-Choline) PET/CT for the management of hepatocellular carcinoma: a tertiary center study.

BACKGROUND: The role of positron emission tomography/computed tomography (PET/CT) in hepatocellular carcinoma (HCC) management is not clearly defined. Our objective was to analyze the utility of dual-PET/CT (18F-FDG + 18F-Choline) imaging findings on the BCLC staging and treatment decision for HCC patients. METHODS: Between January 2011 and April 2019, 168 consecutive HCC patients with available baseline dual-PET/CT imaging data were retrospectively analyzed. To identify potential refinement criteria for surgically-treated patients, survival Kaplan-Meier curves of various standard-of-care and dual-PET/CT baseline parameters were estimated. Finally, multivariate cox proportional hazard ratios of the most relevant clinico-biological and/or PET parameters were estimated. RESULTS: Dual-PET/CT findings increased the score of BCLC staging in 21 (12.5%) cases. In 24.4% (N.=41) of patients, the treatment strategy was modified by the PET findings. Combining AFP levels at a threshold of 10 ng/mL with 18F-FDG or 18F-Choline N status significantly impacted DFS (P<0.05). In particular, the combined criteria of the N+ status assessed by 18F-Choline with AFP threshold of 10 ng/mL provided a highly predictive composite parameter for estimation of DFS according to multivariate analysis (HR=10.6, P<0.05). CONCLUSIONS: The 18F-Choline / AFP composite parameter appears promising, and further prospective studies are mandatory to validate its oncological impact.

Effect of the Use of Reinforced Stapling on the Occurrence of Pancreatic Fistula After Distal Pancreatectomy: Results of the REPLAY (REinforcement of the Pancreas in distaL pAncreatectomY) Multicenter Randomized Clinical Trial.

OBJECTIVE: The aim of the study was to evaluate the impact of the use of a reinforced stapler (RS) during distal pancreatectomy (DP) on postoperative outcomes. BACKGROUND: DP remains associated with significant postoperative morbidity owing to pancreatic fistula (PF). To date, there is no consensus on the management of the pancreatic stump. The use of an RS potentially represents a simple way to decrease the rate of PF. METHODS: The REPLAY study (NCT03030170) is a prospective, multicenter, randomized study. Patients who underwent DP were randomized (1:1 ratio) in 2 groups for the use of a standard stapler (SS) or an RS to close remnant pancreatic parenchyma. The primary endpoint was the rate of overall PF. Secondary endpoints included severity of PF, length of hospital stay, overall morbidity, and rate of readmission for a PF within 90 days. Participants were blinded to the procedure actually carried out. RESULTS: A total of 199 were analyzed (SS, n=99; RS, n=100). One patient who did not undergo surgery was excluded. Baseline characteristics were comparable in both groups. The rate of overall PF was higher in RS group (SS: 67.7%, RS: 83%, P =0.0121), but the rate of clinically relevant PF was similar (SS: 11.1%, RS: 14%, P =0.5387). Mean length of total hospital stay, readmission for PF, postoperative morbidity, and mortality at 90 days were similar. CONCLUSION: The results of this randomized clinical trial did not favor the use of RS during DP to reduce the rate of PF.

Treatment strategies to resectable metachronous colorectal liver metastases after adjuvant oxaliplatin-based chemotherapy for primary colorectal cancer.

BACKGROUND: outcome of patients who develop resectable metachronous colorectal liver metastases (CLM) after adjuvant oxaliplatin-based chemotherapy for Stage III colorectal cancer (CRC) is not well defined and the value of preoperative chemotherapy is controversial. METHODS: From 2006 to 2013, all patients undergoing liver resection for Class I metachronous CLM after adjuvant oxaliplatin-based chemotherapy for CRC, across 32 French academic centers, were included. RESULTS: Sixty-two patients with an average of 2 ± 1 CLM were included. Thirty-two (52%) patients received preoperative chemotherapy. There was no significant difference in the characteristics of CLM between patients with or without preoperative chemotherapy. After a median follow-up of 29 months, 3-year overall and disease-free survival rates were 79.8% and 34.6%, respectively. The median disease-free survival was not different in patients with or without preoperative chemotherapy (17 vs. 35 months respectively, p = 0.112). In multivariate analysis, only CEA level > 200 ng/ml was associated with the risk of recurrence (p = 0.027; OR = 4.7, 95% CI = 1.2-18.7). CONCLUSION: Liver resection provides a good outcome in patients with limited metachronous CLM after adjuvant oxaliplatin-based chemotherapy for CRC. The interest of preoperative chemotherapy is not obvious and should be tested in a prospective controlled study.

Subjective Difficulty Scale in Liver Transplantation: A Prospective Observational Study.

The predictive value of a subjective difficulty scale (DS) after surgical procedures is unknown. The objective of this study was to evaluate the prognostic value of a DS after liver transplantation (LT) and to identify predictors of difficulty. Surgeons prospectively evaluated the difficulty of 441 consecutive liver transplantations from donation after brain death at the end of the surgery by using a DS from 0 to 10 ("the easiest to the hardest you can imagine"). DS was associated with severe morbidity. The risk of graft loss at 1 year remained unchanged from 0 to 6 but increased beyond 6. Graft survival and patient survival of group with DS 7-10 was significantly impaired compared to groups with DS: 0-3 or DS: 4-6 but were significantly impaired for the group with DS: 7-10. Independent predictors of difficult LT (DS ≥ 7) were annular segment 1, transjugular intrahepatic portosystemic shunt, retransplantation beyond 30 days, portal vein thrombosis, and ascites. Of them, ascites was a borderline non-significant covariate (p = .04). Vascular complications occurred more often after difficult LT (20.5% vs. 5.9%), whereas there was no difference in the other types of complications. DS can be used to tailor monitoring and anticipate early complications. External validation is needed.

The rex shunt for left portal vein reconstruction during hepatectomy for malignancy using of rex-shunt in adults for oncoliver surgery.

BACKGROUND: Immediate portal reperfusion is mandatory following hepatectomy combined with portal vein (PV) resection. This retrospective study analyzes the feasibility and the outcomes of the Rex shunt (RS) for reconstruction of the left portal vein (LPV) and reperfusion of the remnant left liver or lobe following hepatectomy for cancer combined with resection of the PV in adult patients. METHODS: From 2018 to 2021, an RS was used in the above setting to achieve R0 resection or when the standard LPV reconstruction failed or was deemed technically impossible. RESULTS: There were 6 male and 5 female patients (median age, 58 years) with perihilar cancer (5 cases) or miscellaneous cancers invading the PV (6 cases). A major hepatectomy was performed in 10/11 patients. The RS was indicated to achieve R0 resection or for technical reasons in 8 and 3 cases, respectively, and was feasible in all consecutive attempts with (10 cases) or without an interposed synthetic graft (1 case). Two fatal complications (PV thrombosis and pulmonary embolism) and three non-severe complications occurred in four patients within 90 days of surgery. Two patients died of tumor recurrence with a patent RS at 13 and 29 months, and 7 were recurrence free with a patent shunt with a follow-up of 1 to 37 months (median, 15 months). CONCLUSION: In case of remnant left liver or lobe following hepatectomy combined with resection of the PV, the RS may help to achieve R0 resection and is a valuable option to perform technically satisfying portal reperfusion of the remnant left liver or lobe.

Prognostic impact of surgical margins for hepatocellular carcinoma according to preoperative alpha-fetoprotein level.

BACKGROUND: HCC are known to have satellite nodules and microvascular invasions requiring sufficient margins. An alpha-fetoprotein (AFP) level >100 ng/mL is associated with worse pathological features in HCC. In practice, large resection margins, particularly >1 cm, are infrequently retrieved on the specimens. METHODS: 397 patients from 5 centres were included from 2012 to 2017. The primary endpoint was time-to-recurrence in relation to AFP level (> or <100 ng/ml) as well as surgical margins (> or <1 cm). The secondary endpoint was overall survival (OS). RESULTS: The median follow-up was 25 months. In Low AFP group, median time to recurrence (TTR) for patients with margins <1 cm was 36 months and for patients with margins ≥1 cm was 34 months (p = 0.756), and overall survival (OS) was not significantly different according to margins (p = 0.079). In High-AFP group, patients with margins <1 cm had a higher recurrence rate than patients with margins ≥1 cm (p = 0.016): median TTR for patients with margins <1 cm was 8 months whereas it was not reached for patients with margins ≥1 cm. Patients with margins <1 cm had a significantly worse OS compared to the patients with margins ≥1 cm (p = 0.043). CONCLUSION: Preoperative AFP level may help determine margins to effectively treat high AFP tumours. For low-AFP tumours, margins didn't have an impact on TTR or OS.

Predicting the risk of post-hepatectomy portal hypertension using a digital twin: A clinical proof of concept.

BACKGROUND & AIMS: Despite improvements in medical and surgical techniques, post-hepatectomy liver failure (PHLF) remains the leading cause of postoperative death. High postoperative portal vein pressure (PPV) and portocaval gradient (PCG), which cannot be predicted by current tools, are the most important determinants of PHLF. Therefore, we aimed to evaluate a digital twin to predict the risk of postoperative portal hypertension (PHT). METHODS: We prospectively included 47 patients undergoing major hepatectomy. A mathematical (0D) model of the entire blood circulation was assessed and automatically calibrated from patient characteristics. Hepatic flows were obtained from preoperative flow MRI (n = 9), intraoperative flowmetry (n = 16), or estimated from cardiac output (n = 47). Resection was then simulated in these 3 groups and the computed PPV and PCG were compared to intraoperative data. RESULTS: Simulated post-hepatectomy pressures did not differ between the 3 groups, comparing well with collected data (no significant differences). In the entire cohort, the correlation between measured and simulated PPV values was good (r = 0.66, no adjustment to intraoperative events) or excellent (r = 0.75) after adjustment, as well as for PCG (respectively r = 0.59 and r = 0.80). The difference between simulated and measured post-hepatectomy PCG was ≤3 mmHg in 96% of cases. Four patients suffered from lethal PHLF for whom the model satisfactorily predicted their postoperative pressures. CONCLUSIONS: We demonstrated that a 0D model could correctly anticipate postoperative PHT, even using estimated hepatic flow rates as input data. If this major conceptual step is confirmed, this algorithm could change our practice toward more tailor-made procedures, while ensuring satisfactory outcomes. LAY SUMMARY: Post-hepatectomy portal hypertension is a major cause of liver failure and death, but no tool is available to accurately anticipate this potentially lethal complication for a given patient. Herein, we propose using a mathematical model to predict the portocaval gradient at the end of liver resection. We tested this model on a cohort of 47 patients undergoing major hepatectomy and demonstrated that it could modify current surgical decision-making algorithms.

Effectiveness of first-line cetuximab in wild-type RAS metastatic colorectal cancer according to tumour BRAF mutation status from the EREBUS cohort.

AIMS: Poor efficacy has been reported for patients with BRAF mutations for metastatic colorectal cancer (mCRC). METHODS: EREBUS is a French cohort study of wild-type (wt) KRAS unresectable mCRC patients initiating a first-line treatment with cetuximab from 2009 to 2010, followed for two years (five years for vital status). Molecular genetics platforms have provided additional RAS and BRAF mutation testing results. Progression-free survival (PFS) and overall survival (OS) were assessed according to tumour mutation (mt) status: RASmt/BRAFany, RASwt/BRAFmt and RASwt/BRAFwt. Multivariate Cox analyses were used to evaluate association between mutation status and death or progression. RESULTS: A total of 389 patients were included in 65 centres and with a known tumour mutation status: 64 RASmt/BRAFany (21%), 33 RASwt/BRAFmt (13%) and 213 RASwt/BRAFwt (87%). Respective baseline characteristics were: median age 65, 64 and 63 years, male gender 63%, 64% and 69%, Eastern Cooperative Oncology Group performance status ≤ 1 75%, 76% and 79%, and liver-only metastases 39%, 33% and 40%. Median progression-free survival was 8.0 months [5.9-9.3] for patients with RASmt/BRAFany, 6.0 months [2.3-7.2] for patients with RASwt/BRAFmt, and 10.4 months [9.5-11.0] for patients with RASwt/BRAFwt. Respectively, median overall survival was 18.4 months [10.9-23.3], 9.7 months [6.9-16.6] and 29.3 months [26.3-36.1]. In multivariate analyses, progression (HR = 2.71 [1.79-4.10]) and death (HR = 2.79 [1.81-4.30]) were more likely for RASwt/BRAFmt vs RASwt/BRAFwt patients. CONCLUSIONS: BRAF mutations were associated with markedly poorer outcomes in initially unresectable RASwt mCRC patients treated by cetuximab in first-line treatment.

Early- and long-term outcomes of liver transplantation with rescue allocation grafts.

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.

Initial piggyback technique facilitates late liver retransplantation - a retrospective monocentric study.

Optimal management of inferior vena cava (IVC) is crucial to ensure safety in late liver retransplantation (ReLT). The aim of this study was to evaluate different surgical strategies with regard to IVC in late ReLT. All consecutive late ReLT (≥90 days from the previous transplant) from 2013 to 2018 in a single center was reviewed (n = 66). Of them, 46 (69.7%) were performed without venovenous bypass (VVB) including 29 with caval preservation (CP) and 17 with caval replacement (CR). The remaining 20 cases (30.3%) required the use of VVB. Among ReLT without VVB, CP was associated with a lower number of packed red blood cells (median 4 vs. 7; P = 0.016) and a lower incidence of post-transplant acute kidney injury (6.9% vs. 47.1%; P = 0.003). The feasibility of CP was 95% (14/15) in patients with previous 3-vein piggyback caval anastomosis versus 48.3% (15/31) after other techniques (P = 0.003). Indirect signs of portal hypertension (PHT) before retransplantation were predictive of VVB requirement. Early and long-term outcomes were similar across the three groups (CP without VVB, CR without VVB, and VVB). Preserving the IVC in late ReLT is associated with better postoperative renal function and is facilitated by a previous 3-vein piggyback. Routine CR is not justified in late ReLT.

Number of hepatocellular carcinoma nodules in patients listed for liver transplantation within alpha-fetoprotein score: a new prognostic risk factor.

In France, the listing for liver transplantation (LT) for hepatocellular carcinoma (HCC) requires an AFP score ≤2. This study evaluates whether the number of nodules assessed immediately before LT has a prognostic value among patients already listed within AFP score. Among 143 recipients transplanted with an AFP score ≤2 between 2013 and 2017 in our center, the number of nodules was considered at listing on the waiting list and at last imaging before LT. We compared the overall survival (OS) and disease-free survival (DFS) post-LT of patients with ≤3 and >3 nodules (current classification), and aimed to propose a new criteria to exclude patients on list at high risk of recurrence. The 3-year OS of patients with ≤3 HCC vs. >3 HCC at listing was of 90.3% vs. 67.3%, respectively (P = 0.04). At last imaging, eight listed patients presented ≥5 HCC nodules and had a significantly lower OS than <5 nodules patients (5-year OS: 24.4% vs. 78.1%; P = 0.01). Although the current AFP score offers satisfactory outcomes, we highlight the poorer outcomes when ≥5 nodules persist or appear after listing. A modification of the AFP score is mandatory to consider exclusion of high-risk patients already listed for LT program.

The prognostic significance of serum aspartate transaminase and gamma-glutamyl transferase in liver deceased donors.

The impact of aspartate transaminases (AST) and gamma-glutamyl transferase (GGT) in serum of deceased donors on outcomes after liver transplantation (LT) is unclear. This study aimed to explore the relationship between donor highest AST value or first donor GGT value and graft survival. All consecutive patients who underwent a primary LT in a single center with available donor AST (N = 1253) and GGT value (N = 1152) were included. There was no significant association between donor AST and 90-day graft survival. We found a moderate association between GGT and 90-day graft survival. We found a significant interaction with a donor history of alcohol abuse (HAA). The risk of graft loss was associated with AST and GGT in donors with an HAA but remains unchanged in donors without HAA. There was no difference in graft survival according to donor AST or GGT with a cutoff ≥95th percentile (475 UI/l for AST and 170 UI/l for GGT). However, graft survival was significantly decreased when donors combined GGT ≥ 170 UI/l and HAA (61% at one year). Hepatic grafts from donors with high AST or high GGT but without alcohol history and no additional risk factors can be transplanted in low-risk recipient.

Middle and left hepatic vein trunk control during laparoscopic liver resection (with video).

BACKGROUND: While inflow control can be easily applied by Pringle maneuver, outflow control of the left liver has not been formally described. We report here a safe and reproductible technique of middle and left hepatic veinous trunk control (MLHVC) before parenchymal transection during laparoscopic left hepatectomy. METHODS: A retrospective review of laparoscopic liver resection was conducted from January 2013 to March 2018 from our prospective database. All cases of laparoscopic left hepatectomy (LLH) were included, and intra- and postoperative outcomes data collected. We collected cases where the middle and left hepatic vein trunk control has been attempted and clamping used, and we analyzed outcomes associated with this maneuver. RESULTS: MLHVC was attempted in 28 cases (77.8) of the 36 LLH identify in a monocentric study. It was technically not feasible only in 3 cases (8.3%) and clamping applied in 15 cases (41.7%). No significant intraoperative unexpected event occurred. CONCLUSION: We present here a technique for left liver outflow control that can be safely added to the armamentarium of laparoscopic liver surgery.