The impact of cirrhosis on short and long postoperative outcomes after distal pancreatectomy.

BACKGROUND: The impact of cirrhosis on the postoperative outcomes of distal pancreatectomy is yet to be reported. We aimed to evaluate the outcomes of distal pancreatectomy in patients with cirrhosis. METHODS: We conducted a retrospective, multicentric study patients with cirrhosis who underwent planned distal pancreatectomy between 2008 and 2020 in French high volume centers. Patients with cirrhosis were matched 1:4 for demographic, surgical, and histologic criteria with patients without cirrhosis. The primary endpoint was severe morbidity (Clavien-Dindo grade ≥III). The secondary endpoints were postoperative complications, specifically related to cirrhosis and pancreatic surgery, and survival for patients with pancreatic adenocarcinoma. RESULTS: Overall, 32 patients with cirrhosis were matched with 128 patients without cirrhosis. Most patients (93.5%) had Child-Pugh A cirrhosis. The severe morbidity rate after distal pancreatectomy was higher in patients with cirrhosis than in those without cirrhosis (28.13% vs 25.75%, P = .11. The operative time was significantly longer in the cirrhotic group compared with controls (P = .01). However, patients with and without cirrhosis had comparable blood loss and conversion rates. Postoperatively, the two groups had similar rates of pancreatic fistula, hemorrhage, reoperation, postoperative mortality, and survival rates at 1, 3, and 5 years. CONCLUSION: The current study suggests that distal pancreatectomy in high-volume centers is feasible for patients with compensated cirrhosis.

Graft reduction in adult liver transplantation: indications, techniques, and outcomes.

PURPOSE: Graft reduction can be a patient's graft-saving option to avoid large-for-size (LFS) syndrome. This study aimed to summarize the literature on graft reduction in adult liver transplantation and to demonstrate the technique of H67 graft hepatectomy. METHODS: The technique, shown in a didactical video, entails an ex situ posterior sectionectomy under hypothermic perfusion. The right hepatic vein is identified, and the transection line follows the right hepatic fissure. The Glissonean pedicles are ligated during parenchymal transection. RESULTS: A narrative review of the literature yielded 7 studies. A total of 15 liver grafts were reduced in adult liver transplantations. Most of the reductions were ex situ (11/15 [73.3%]). Graft reduction entailed an H67 sectionectomy in 10 cases and an H23 sectionectomy in 1 case. In situ reduction included 1 right hepatectomy (H5678), 2 H67 sectionectomies, and 1 H23 left lateral sectionectomy. The duration of the ex situ reduction averaged 56 minutes (median: 40.5 minutes; IQR, 33.0-130.0), and the graft weight-to-recipient weight ratio decreased from 3.57% ± 0.40% to 2.70% ± 0.50% after graft reduction. The average cold ischemia time was 390 minutes (IQR, 230-570). There was no liver retransplantation. CONCLUSION: Graft reduction in adult liver transplantation may be necessary to avoid LFS syndrome. Ex-situ H67 posterior sectionectomy represents the easiest graft reduction hepatectomy and is able to minimize the occurrence of graft compression while leaving enough functional liver parenchyma.

Minimally invasive versus open distal pancreatectomy for resectable pancreatic neuroendocrine tumors: A propensity score matched multicentric comparative French study.

BACKGROUND: Minimally invasive surgery has gained momentum for left pancreatic resections. However, debate remains about whether it has any advantage over open surgery for distal pancreatectomy for pancreatic neuroendocrine tumors. METHODS: This retrospective review examined pancreatectomies performed for resectable pancreatic neuroendocrine tumors at 21 centers in France between January 2014 and December 2018. Short and long-term outcomes were compared before and after propensity score matching based on tumor size, sex, age, body mass index, center, and method of pancreatic transection. RESULTS: During the period study, 274 patients underwent left pancreatic resection for pancreatic neuroendocrine tumors [109 underwent distal splenopancreatectomy, and 165 underwent spleen-preserving distal pancreatectomy [(splenic vessel preservation (n = 97; 58.7%)/splenic vessel resection (n = 68; 41.3%)]. Before propensity score matching, minimally invasive surgery was associated with a lower rate of major morbidity (P = .004), lower rate of postoperative delayed gastric emptying (P = .04), and higher rate of "textbook" outcomes (P = .04). After propensity score matching, there were 2 groups of 54 patients (n = 30 distal splenopancreatectomy; n = 78 spleen-preserving distal pancreatectomy). Minimally invasive surgery was associated with less blood loss (P = .05), decreased rate of major morbidity (6% vs. 24%; P = .02), less delayed gastric emptying (P = .05) despite similar rates of postoperative fistula, hemorrhage, and reoperation (P > .05). The 5-year overall survival (79% vs. 75%; P = .74) and recurrence-free survival (10% vs 17%; P = .39) were similar. CONCLUSION: Minimally invasive surgery for left pancreatic resection can be safely proposed for patients with resectable left pancreatic neuroendocrine tumors. Minimally invasive surgery decreases the rate of major complications while providing comparable long-term oncologic outcomes.

Evaluation of a delayed liver transplantation strategy for patients with HCC receiving bridging therapy: the DELTA-HCC study.

BACKGROUND & AIMS: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy (DS) was adopted in France in 2015 in patients listed for any single HCC treated with resection or thermal ablation during the waiting phase. The DS involves postponing LT until recurrence. The purpose of this study was to evaluate the DS to make sure that it did not hamper pre- and post-LT outcomes. METHODS: Patients listed for HCC in France between 2015 and 2018 were studied. After data extraction from the national LT database, 2,025 patients were identified and classified according to six groups: single tumor entering DS, single tumor not entering DS, multiple tumors, no curative treatment, untreatable HCC or T1 tumors. Kaplan-Meier estimates of the 18-month risk of dropout for death, too sick to be transplanted or tumor progression before LT, 5-year post-LT HCC recurrence and post-LT survival rates were compared. RESULTS: Median waiting-time in the DS group was 910 days. Pre-LT dropout probability was significantly lower in the DS group compared to other groups (13% vs. 19%, p = 0.0043) and significantly higher in the T1 group (25.4%, p = 0.05). Post-LT HCC recurrence rate in the multiple nodules group was significantly higher (19.6%, p = 0.019), while 5-year post-LT survival did not differ among groups and was 74% in the DS group (p = 0.22). CONCLUSION: The DELTA-HCC study shows that DS does not negatively impact either pre- nor post-LT patient outcomes, and has the potential to allow for redistribution of organs to patients in more urgent need of LT. It can reasonably be proposed and pursued. The unexpectedly high risk of dropout in T1 patients seems related to the MELD-based offering rules underserving this subgroup. IMPACTS AND IMPLICATIONS: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy was adopted in France in 2015. It involves postponing LT until recurrence in patients listed for any single HCC curatively treated by surgical resection or thermal ablation. The DELTA-HCC study was conducted to evaluate this nationwide strategy. It shows in a European LT program that delayed strategy does not negatively impact pre- nor post-LT patient outcomes and is relevant to up to 20% of LT candidates; thus, it could potentially enable the redistribution of organs to patients in more urgent need of LT. Such a delayed strategy can reasonably be pursued and extended to other LT programs. Of note, an unexpectedly high risk of dropout in T1 patients, seemingly related to MELD-based offering rules which underserve these patients, calls for further scrutinization and revision of allocation rules in this subgroup.

Comparing indications, complexity and outcomes of laparoscopic liver resection between centers with and without a liver transplant program: a French nationwide study.

BACKGROUND: There are no data to evaluate the difference in populations and impact of centers with liver transplant programs in performing laparoscopic liver resection (LLR). METHODS: This was a multicenter study including patients undergoing LLR for benign and malignant tumors at 27 French centers from 1996 to 2018. The main outcomes were postoperative severe morbidity and mortality. RESULTS: A total of 3154 patients were included, and 14 centers were classified as transplant centers (N = 2167 patients, 68.7 %). The transplant centers performed more difficult LLRs and more resections for hepatocellular carcinoma (HCC) in patients who more frequently had cirrhosis. A higher rate of performing the Pringle maneuver, a lower rate of blood loss and a higher rate of open conversion (all p < 0.05) were observed in the transplant centers. There was no association between the presence of a liver transplant program and either postoperative severe morbidity (<10 % in each group; p = 0.228) or mortality (1 % in each group; p = 0.915). CONCLUSIONS: Most HCCs, difficult LLRs, and cirrhotic patients are treated in transplant centers. We show that all centers can achieve comparable safety and quality of care in LLR independent of the presence of a liver transplant program.

Preoperative pancreatic radiologic characteristics predict pancreatic-specific complications before pancreaticoduodenectomy: the pancreatic acinar radiologic score.

BACKGROUND: High acinar pancreatic contents are associated with a higher rate of postpancreatectomy acute pancreatitis and pancreatic fistula formation (POPF). Predicting acinar contents preoperatively might identify those at high risk of developing postoperative complications. METHODS: A multivariable analysis was performed to identify radiological factors associated with high pancreatic acinar content at histology in patients undergoing pancreaticoduodenectomy. Clinical and radiological variables identified were used to build a composite score predicting low, moderate, and high acinar pancreatic contents. RESULTS: Pancreatic density, wirsung caliber, and pancreatic thickness on preoperative CT-scan predicted acinar contents. These three variables predicted low, moderate, and high acinar content in 94 (26%), 122 (33.6%), and 147 (40.5%) patients, respectively. Patients with high radiological acinar scores compared with patients with intermediate-low risk scores were more frequently male (73.4% vs. 54.1%; p = 0.0003), obese (14% vs. 6%; p = 0.01), and had a statistically significant higher rate of pancreatic-specific complications (23.8% vs. 8.33%; p = 0.01), POPF (12.9% vs. 4.63%; p = 0.005) and pancreaticogastrostomy bleeding (10.8% vs. 4.17%; p = 0.01). CONCLUSION: A simple radiological score combining pancreatic thickness, density, and wirsung caliber at CT scan preoperatively predicts patients with pancreatic parenchyma that are at higher risk of postoperative pancreatic-specific complications.

REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer.

OBJECTIVE: The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking. METHODS: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines. RESULTS: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ). CONCLUSIONS: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population.

Volumetric Remodeling of the Left Liver After Right Hepatectomy: Analysis of Factors Predicting Degree of Hypertrophy and Post-hepatectomy Liver Failure.

BACKGROUND: This study investigated the volumetric remodeling of the left liver after right hepatectomy looking for factors predicting the degree of hypertrophy and severe post-hepatectomy liver failure (PHLF). METHODS: In a cohort of 121 right hepatectomies, we performed CT volumetrics study of the future left liver remnant (FLR) preoperatively and postoperatively. Factors influencing FLR degree of hypertrophy and severe PHLF were identified by multivariate analysis. RESULTS: After right hepatectomy, the mean degree of hypertrophy and kinetic growth rate of the left liver remnant were 25% and 3%/day respectively. The mean liver volume recovery rate was 77%. Liver remodeling volume was distributed for 79% on segments 2 and 3 and 21% on the segment 4 (p<0.001). Women showed a greater hypertrophy of segments 2 and 3 compared with men (p=0.002). The degree of hypertrophy of segment 4 was lower in case of middle hepatic vein resection (p=0.004). Left liver remnant kinetic growth rate was associated with the standardized future liver remnant (sFLR) (p<0.001) and a two-stage hepatectomy (p=0.023). Severe PHLF were predicted by intraoperative transfusion (p=0.009), biliary tumors (p=0.013), and male gender (p=0.022). CONCLUSIONS: Volumetric remodeling of the left liver after right hepatectomy is not uniform and is mainly influenced by gender and sacrifice of middle hepatic vein. Male gender, intraoperative transfusion, and biliary tumors increase the risk of postoperative liver failure after right hepatectomy.

Sequential Y90 liver radioembolization and portal vein embolization: an additional strategy to downstage liver tumors and to enhance liver hypertrophy before major hepatectomies.

BACKGROUND: Yttrium (Y)90 liver radioembolization (TARE) induces both tumor downsizing and contralateral liver hypertrophy. In this study, we report the preliminary results of a sequential strategy combining Y90 radioembolization and portal vein embolization (PVE) before major right liver resections. METHODS: We retrospectively reviewed clinical, radiological, and biological data of 5 consecutive patients undergoing Y90 TARE-PVE before major right liver resections. Comparison was made with patients undergoing PVE alone or liver venous deprivation (LVD) during the same period. RESULTS: Between January 2019 and September 2022, five patients underwent sequential TARE-PVE. Type of resection included the following: right hepatectomy (n = 1), right hepatectomy + 1 (n = 2), and right hepatectomy + 1 + 4 (n = 2) with no postoperative mortality. Volumetric data showed a mean hypertrophy ratio of 30.4% after TARE and an additional 37.4% after sequential PVE. Patients undergoing sequential TARE-PVE had higher hypertrophy ratio (p = 0.02; p = 0.004), hypertrophy degree (p = 0.02; p < 0.0001), shorter time to normalize bilirubin (p = 0.04), and prothrombin time (p = 0.003; p < 0.0001) compared with patients receiving LVD or PVE. Time from diagnosis to surgery was statistically significant longer in patients undergoing sequential TARE-PVE compared with LVD or PVE (293.4 ± 169.1 vs 54.18 ±18.26 vs 58.62±13.15; p = 0.0008; p = <0.0001). CONCLUSIONS: This preliminary report suggests that sequential PVE and TARE can represent a safe and an alternative strategy to downstage liver tumors and to enhance liver hypertrophy before major hepatectomies. When compared with PVE and LVD, sequential TARE/PVE takes longer times but achieves some advantages which warrant further evaluation in a larger setting.

Incidence and outcomes of post-hepatectomy diaphragmatic hernia: a systematic review.

BACKGROUND: Post-hepatectomy diaphragmatic hernia is the second most common cause of acquired diaphragmatic hernia. This study aims to review the literature on this complication's incidence, treatment and prognosis. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched PubMed for all studies related to acquired diaphragmatic hernias after hepatectomy. RESULTS: We included 28 studies in our final analysis, comprising 11,368 hepatectomies. The incidence of post-hepatectomy diaphragmatic hernia was 0.75% (n = 86). The most frequent type of hepatectomy performed was right hepatectomy (79%, n = 68), and the indications for liver resection were a liver donation for living donor transplantation (n = 40), malignant liver tumors (n = 13), and benign tumors (n = 11). The mean onset between liver resection and the diagnosis of diaphragmatic hernia was 25.7 months (range, 1-72 months), and the hernia was located on the right diaphragm in 77 patients (89.5%). Pain was the most common presenting symptom (n = 52, 60.4%), while six patients were asymptomatic (6.9%). Primary repair by direct suture was the most frequently performed technique (88.3%, n = 76). Six patients experienced recurrence (6.9%), and three died before diaphragmatic hernia repair (3.5%). CONCLUSION: Diaphragmatic hernia is a rare complication occurring mainly after right liver resection. Repair should be performed once detected, given the not-negligible associated mortality in the emergency setting.

Extended Right Hepatectomy to Inferior Vena Cava Under Total Vascular Exclusion, Veno-Venous Bypass and In Situ Hypothermic Perfusion of the Future Liver Remnant.

BACKGROUND: Venous obstruction at the hepatic veins-inferior vena cava confluence can be particularly challenging to manage if an associated liver resection is needed. Total vascular exclusion (TVE) with veno-venous bypass (VVB) and hypothermic in situ perfusion (HP) of the future liver remnant can be used in these conditions.1,2 METHODS: The patient was a 58-year-old with a voluminous adrenal cancer invading the kidney, the right liver and the retrohepatic inferior vena cava with intraluminal thrombus extending up to the hepatic veins confluence. A right hepatectomy, extended to segment 1, the right kidney, and the retrohepatic inferior vena cava was planned. RESULTS: The parenchymal liver transection was performed under a TVE, VVB, and HP of the left liver to decrease blood losses and risk of postoperative liver failure. Vena cava reconstruction was achieved by a ringed Gore-Tex prosthesis with reimplantation of the left renal vein. Total duration of veno-venous bypass and liver vascular exclusion were 2 h 40 min and 2 h 10 min, respectively. The patient was discharged on postoperative day 17. CONCLUSIONS: Total vascular exclusion with veno-venous bypass and in-situ liver hypothermic perfusion increases the safety of major liver resection requiring complex vascular reconstruction.1,2 TVE under VVB and HP of the future liver remnant is used at our institution when: (1) TVE will last more than 30 min; (2) vascular reconstruction is needed; (3) in the presence of venous obstruction; (4) in the presence of injured liver parenchyma; and (5) in the presence of cardiovascular comorbidities.

End-ischemic hypothermic oxygenated perfusion for extended criteria donors in liver transplantation: a multicenter, randomized controlled trial-HOPExt.

BACKGROUND: Given the scarce donor supply, an increasing number of so-called marginal or extended criteria donor (ECD) organs are used for liver transplantation. These ECD liver grafts are however known to be associated with a higher rate of early allograft dysfunction and primary non-function because of a greater vulnerability to ischemia-reperfusion injury. The end-ischemic hypothermic oxygenated machine perfusion (HOPE) technique may improve outcomes of liver transplantation with ECD grafts by decreasing reperfusion injury. METHODS: HOPExt trial is a comparative open-label, multicenter, national, prospective, randomized, controlled study, in two parallel groups, using static cold storage, the gold standard procedure, as control. The trial will enroll adult patients on the transplant waiting list for liver failure or liver cirrhosis and/or liver malignancy requiring liver transplantation and receiving an ECD liver graft from a brain-dead donor. In the experimental group, ECD liver grafts will first undergo a classical static cold (4 °C) storage followed by a hypothermic oxygenated perfusion (HOPE) for a period of 1 to 4 h. The control group will consist of the classic static cold storage which is the gold standard procedure in liver transplantation. The primary objective of this trial is to study the efficacy of HOPE used before transplantation of ECD liver grafts from brain-dead donors in reducing postoperative early allograft dysfunction within the first 7 postoperative days compared to simple cold static storage. DISCUSSION: We present in this protocol all study procedures in regard to the achievement of the HOPExt trial, to prevent biased analysis of trial outcomes and improve the transparency of the trial results. Enrollment of patients in the HOPExt trial has started on September 10, 2019, and is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov NCT03929523. Registered on April 29, 2019, before the start of inclusion.

Additional value of interleukin-6 level to predict histopathological features of hepatocellular carcinoma before liver transplantation.

BACKGROUND & AIMS: Inflammatory biomarkers are increasingly used as outcome predictors in the field of oncology and liver transplantation for HCC, but no study has shown the prognostic value of IL6 after LT. The goal of this study was to evaluate the predictive value of IL-6 on histopathological features of HCC on explant, its predictive value on recurrence risk and its additional value to other scores and inflammatory markers at the time of transplantation. METHODS: From 2009 to 2019, all adults transplanted with a first liver graft and diagnosed with HCC on the explant analysis were retrospectively included (n = 229). Only patients who had a pre-LT IL6 level determination were analysed in this study (n = 204). RESULTS: High IL-6 level at transplantation was associated with a significantly higher risk of vascular invasion (15% vs 6%; p = 0.023), microsatellitosis (11% vs 3%; p = 0.013), lower rate of histological response both in terms of complete response (2% vs 14%, p = 0.004) and of necrosis (p = 0.010). Patients with pre-LT IL-6 level > 15 ng/ml had a lower overall and cancer-specific survival (p = 0.013). Recurrence-free survival was lower in patients with IL-6 > 15 ng/ml with a 3-year recurrence-free survival of 88% versus 78% (p = 0.034). IL6 levels were significantly higher in patients with early recurrence compared to patients without (p = 0.002) or with late recurrence (p = 0.044). CONCLUSIONS: IL6 level at transplantation is an independent predictor of pejorative histological features of HCC and is associated to the risk of recurrence.