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.

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 (PA), the prognostic value of baseline CA19-9 and circulating tumour DNA (ctDNA) for overall survival (OS), to improve death risk stratification, based on a planned ancillary study from PANACHE01-PRODIGE 48 trial. SUMMARY BACKGROUND DATA: 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 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 Kaplan Meier method and compared with log-rank test. Restricted cubic spline approach was used to identify 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. 14 patients (15%) were ctDNA+ and exhibited a higher risk for death (P=0,0188; HR95% CI: 2.28 (1.12-4.63). In the 92 patients with ctDNA status available among the others parameter analysed only CA19-9 was statically associated with OS in univariate analysis. Patients with 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; HR95% CI: 2.2 (1.15-4.19). In multivariate analysis CA19-19 remained independently associated with OS (p-value=0.0323). When combining the two biomarkers, median OS was of 19.4 (IC 95% 3.8-Not reached) months, 30.2 (IC 95% 17.1-NR) months and not reached (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 (logrank P=0,0069). DISCUSSION: 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 "biologic borderline disease". Few data, particularly from prospective studies, allow us to identify biomarkers other than CA19-9. CONCLUSION: Combining ctDNA to CA19-9 could be of interest to best define biological borderline situations in PA.

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.

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.

Closed-loop insulin delivery systems in patients with pancreatitis or pancreatectomy-induced diabetes: A case series.

Pancreatic diabetes is associated with glycemic variability, poor metabolic control, and reduced quality of life. Though hybrid closed-loop (HCL) insulin delivery systems were not originally developed for these types of diabetes, they could address the therapeutic challenge. We aimed to evaluate long-term metabolic control in ten adult patients (mean ± SD age: 59 ± 12) treated with HCL insulin delivery systems for pancreatitis or pancreatectomy-induced diabetes. After a median of 346 days (range 64 - 631) with HCL insulin delivery, continuous glucose monitoring showed 59±19 % time-in-range [70-180 mg/dl] (versus 49±24 % before HCL insulin delivery, P = 0. 049) and 0.8 ± 1.0 % time-below-range [< 70 mg/dl] (versus 2.2 ± 2.6 %, P = 0.142), with the coefficient of glucose variability at 35.4 ± 7.6 (versus 37.8 ± 7.1, P = 0.047). HbA1c decreased from 8.5 ± 1.7 % to 7.7 ± 1.3 % [69±18 to 60±14 mmol/mol] (P = 0.076). No patient experienced an acute adverse metabolic event.

Liver Transplantation from Elderly Donors (≥85 Years Old).

BACKGROUND: Despite the ongoing trend of increasing donor ages in liver transplantation (LT) setting, a notable gap persists in the availability of comprehensive guidelines for the utilization of organs from elderly donors. This study aimed to evaluate the viability of livers grafts from donors aged ≥85 years and report the post-LT outcomes compared with those from "ideal" donors under 40 years old. METHODS: Conducted retrospectively at a single center from 2005 to 2023, this study compared outcomes of LTs from donors aged ≥85 y/o and ≤40 y/o, with the propensity score matching to the recipient's gender, age, BMI, MELD score, redo-LT, LT indication, and cause of donor death. RESULTS: A total of 76 patients received grafts from donors ≥85 y/o and were compared to 349 liver grafts from donors ≤40 y/o. Prior to PSM, the 5-year overall survival was 63% for the elderly group and 77% for the young group (p = 0.002). After PSM, the 5-year overall survival was 63% and 73% (p = 0.1). A nomogram, developed at the time of graft acceptance and including HCC features, predicted 10-year survival after LT using a graft from a donor aged ≥85. CONCLUSIONS: In the context of organ scarcity, elderly donors emerge as a partial solution. Nonetheless, without proper selection, LT using very elderly donors yields inferior long-term outcomes compared to transplantation from very young donors ≤40 y/o. The resulting nomogram based on pre-transplant criteria allows for the optimization of elderly donor/recipient matching to achieve satisfactory long-term results, in addition to traditional matching methods.

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.

Activation of lysosomal iron triggers ferroptosis in cancer.

Iron catalyses the oxidation of lipids in biological membranes and promotes a form of cell death referred to as ferroptosis1-3. Identifying where this chemistry takes place in the cell can inform the design of drugs capable of inducing or inhibiting ferroptosis in various disease-relevant settings. Whereas genetic approaches have revealed underlying mechanisms of lipid peroxide detoxification1,4,5, small molecules can provide unparalleled spatiotemporal control of the chemistry at work6. Here, we show that the ferroptosis inhibitor liproxstatin-1 (Lip-1) exerts a protective activity by inactivating iron in lysosomes. Based on this, we designed the bifunctional compound fentomycin that targets phospholipids at the plasma membrane and activates iron in lysosomes upon endocytosis, promoting oxidative degradation of phospholipids and ferroptosis. Fentomycin effectively kills primary sarcoma and pancreatic ductal adenocarcinoma cells. It acts as a lipolysis-targeting chimera (LIPTAC), preferentially targeting iron-rich CD44high cell-subpopulations7,8 associated with the metastatic disease and drug resistance9,10. Furthermore, we demonstrate that fentomycin also depletes CD44high cells in vivo and reduces intranodal tumour growth in an immunocompetent murine model of breast cancer metastasis. These data demonstrate that lysosomal iron triggers ferroptosis and that lysosomal iron redox chemistry can be exploited for therapeutic benefits.

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.

Rescue Liver Transplantation for Posthepatectomy Liver Failure: A Systematic Review and Survey of an International Experience.

BACKGROUND: Rescue liver transplantation (LT) is the only life-saving option for posthepatectomy liver failure (PHLF) whenever it is deemed as irreversible and likely to be fatal. The goals were to perform a qualitative systematic review of rescue LT for PHLF and a survey among various international LT experts. METHODS: A literature search was performed from 2000 to 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Population, Intervention, Comparison, Outcome framework, and to this, the authors' experience was added. The international online open survey included 6 cases of PHLF extracted from the literature and submitted to 976 LT experts. The primary outcome was whether experts would consider rescue LT for each case. Interrater agreement among experts was calculated using the free-marginal multirater kappa methodology. RESULTS: The review included 40 patients. Post-LT mortality occurred in 8 (20%) cases (7/28 with proven cancer and 1/12 with benign disease). In the long term, 6 of 21 (28.6%) survivors with cancer died of recurrence (median = 38 mo) and 15 (71.4%) were alive with no recurrence (median = 111 mo). All 11 survivors with benign disease were alive and well (median = 39 mo). In the international survey among experts in LT, the percentage agreement to consider rescue LT was 28%-98%, higher for benign than for malignant disease ( P = 0.011). Interrater agreement for the primary endpoint was low, expected 5-y survival >50% being the strongest independent predictor to consider LT. CONCLUSIONS: Rescue LT for PHLF may achieve good results in selected patients. Considerable inconsistencies of decision-making exist among LT experts when considering LT for PHLF.

Early portal vein thrombosis after hepatectomy for perihilar cholangiocarcinoma: Incidence, risk factors, and management.

AIM: To study the incidence, risk factors and management of portal vein thrombosis (PVT) after hepatectomy for perihilar cholangiocarcinoma (PHCC). PATIENTS AND METHOD: Single-center retrospective analysis of 86 consecutive patients who underwent major hepatectomy for PHCC, between 2012 and 2019, with comparison of the characteristics of the groups with (PVT+) and without (PVT-) postoperative portal vein thrombosis. RESULTS: Seven patients (8%) presented with PVT diagnosed during the first postoperative week. Preoperative portal embolization had been performed in 71% of patients in the PVT+ group versus 34% in the PVT- group (P=0.1). Portal reconstruction was performed in 100% and 38% of PVT+ and PVT- patients, respectively (P=0.002). In view of the gravity of the clinical and/or biochemical picture, five (71%) patients underwent urgent re-operation with portal thrombectomy, one of whom died early (hemorrhagic shock after surgical treatment of PVT). Two patients had exclusively medical treatment. Complete recanalization of the portal vein was achieved in the short and medium term in the six survivors. After a mean follow-up of 21 months, there was no statistically significant difference in overall survival between the two groups. FINDINGS: Post-hepatectomy PVT for PHCC is a not-infrequent and potentially lethal event. Rapid management, adapted to the extension of the thrombus and the severity of the thrombosis (hepatic function, signs of portal hypertension) makes it possible to limit the impact on postoperative mortality. We did not identify any modifiable risk factor. However, when it is oncologically and anatomically feasible, left±extended hepatectomy (without portal embolization) may be less risky than extended right hepatectomy, and portal vein resection should only be performed if there is strong suspicion of tumor invasion.

Features Importance in Acute Kidney Injury After Liver Transplant: Which Predictors Are Relevant?

OBJECTIVES: Acute kidney injury after liver transplant results from several interconnected factors related to graft, recipient, intraoperative, and postoperative events. The random decision forest model enables an appreciation of each factor's contribution, which may be helpful in setting up a preventive strategy. This study aimed to evaluate the importance of covariates at different times (pretransplant, end of surgery, postoperative day 7) with a random forest permutation algorithm. MATERIALS AND METHODS: We used a retrospective singlecenter cohort of patients, without preoperative renal failure, who underwent primary liver transplants from deceased donors (N =1104). Significant covariates for stage 2-3 acute kidney injurywere included in a random forest model, and features importance was evaluated with mean decrease accuracy and Gini index. RESULTS: Stage 2-3 acute kidney injury occurred in 200 patients (18.1%) and was associated with lower patient survival, even after exclusion of early graftloss. At univariate analysis, recipient factors (serum creatinine level, Model for End-Stage Liver Disease score, body weight, body mass index), graft variables (weight, macrosteatosis), intraoperative factors (number of red blood cells, duration of surgery, cold ischemia time), and postoperative event (graft dysfunction) were associated with kidney failure. The pretransplant model found that macrosteatosis and graft weight contributed to acute kidney injury. The postoperative model indicated that graft dysfunction and the number of intraoperative packed red blood cells were ranked as the 2 most essential factors in posttransplant renal failure. CONCLUSIONS: The application of a random forestfeature identified graft dysfunction, even transient and reversible, and the number of intraoperative packed red blood cells as the 2 most crucial contributors to acute kidney injury,thus indicating that prevention of graft dysfunction and bleeding are key points to limit the risk of renal failure after liver transplant.

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.

Resectable and transplantable hepatocellular carcinoma: Integration of liver stiffness assessment in the decision-making algorithm.

BACKGROUND: Liver resection is a curative treatment for hepatocellular carcinoma (HCC) and an alternative to liver transplantation (LT). However, post-liver resection recurrence rates remain high. This study aimed to determine whether liver stiffness measurement (LSM) correlated with recurrence and to propose a method for predicting HCC recurrence exclusively using pre-liver resection criteria. METHODS: This retrospective monocentric study included patients who had undergone LR liver resection for HCC between 2015 and 2018 and who had (1) preoperative alpha-fetoprotein scores indicating initial transplant viability and (2) available preoperative LSM data. We developed a predictive score for recurrence over time using Cox univariate regression and multivariate analysis with a combination plot before selecting the optimal thresholds (receiver operating characteristic curves + Youden test). RESULTS: Sixty-six patients were included. After an average follow-up of 40 months, the recurrence rate was 45% (n = 30). Three-year overall survival was 88%. Four preoperative variables significantly impacted the time to recurrence: age ≥70 years, LSM ≥11 kPa, international normalized ratio (INR) ≥1.2, and maximum HCC diameter ≥3 cm. By assigning 1 point per positive item, patients with a score <2 (n = 22) demonstrated greater mean overall survival (69.7 vs 54.8 months, P = .02) and disease-free survival (52.2 vs 34.7 months, P = .02) than those with a score ≥2. Patients experiencing early recurrence (<1 year) presented a significantly higher preoperative LSM (P = .06). CONCLUSION: We identified a simple preoperative score predictive of early hepatocellular carcinoma recurrence after liver resection, highlighting the role of liver stiffness. This score could help physicians select patients and make decisions concerning perioperative medical treatment.

Impact of DSA and immunosuppression minimization on rejection, graft, and patient survival after simultaneous liver-kidney transplantation.

Background: Acute rejection rate is low after simultaneous liver-kidney transplantation (SLKT), leading some groups to minimize immunosuppressive (IS) regimens. However, the impact of preformed (pDSA) or de novo donor-specific antibodies (dnDSA) on the graft remains unclear. Methods: We performed a retrospective analysis of 102 consecutive SLKT patients to study the impact of anti-HLA antibodies. Results: Anti-HLA antibodies were detected in 75 recipients (class I 23.8%, both classes I and II 23.8%, and class II 14.3%). In total, 42.8% of the patients had pDSA and 21.7% developed dnDSA. Overall patient survival at 1-3 and 5 years, was respectively 88, 84, and 80%. Acute rejection occurred respectively in 3 (2.9%) liver and 6 kidney (5.9%) recipients. pDSA with titers over 10,000 mean fluorescence intensity (14.3%) was associated with lower patient survival (40 vs. 82%) but not with acute rejection. In a multivariable Cox regression analysis, the risk of death was associated with maleness, the highest titer of pDSA (p < 0.0007) or the sum of pDSA >10,000. Renal function did not differ between patients with class I pDSA (p = 0.631) and those with class II pDSA (p = 0.112) or between patients with and without a positive cross-match (p = 0.842). dnDSA were not associated with acute rejection, graft dysfunction or patient survival. IS minimization was not associated with rejection, graft dysfunction or death. Conclusion: In SLKT, high levels of pDSA >10,000 were associated with lower patient survival, but not rejection or graft survival. Minimization of maintenance immunosuppression regimen was not associated with a poorer outcome.

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.