Safety and performance of a synthetic sealant patch aimed to prevent postoperative pancreatic fistula after distal pancreatectomy (SHIELDS) - Prospective international multicenter phase II study.

OBJECTIVE: The incidence for clinically relevant postoperative pancreatic fistulas (CR-POPF) in distal pancreatectomy (DP) ranges up to 25%. None of the available sealants significantly reduce CR-POPF. A new biodegradable sealant patch was able to reduce POPF and to achieve bleeding control in a preclinical porcine DP model. The aim of this first-in-human study was to assess the safety and performance of the sealant patch. METHODS: In this multicenter, single-arm study, 40 patients undergoing distal pancreatectomy were prospectively enrolled from 8 centers. Following surgical resection, the transection plane was closed according to the standard of care and manually covered with the sealant patch. As primary endpoint the incidence of CR-POPF up to 30-days postoperatively was evaluated. The secondary endpoints included the assessment of complications and device usability. RESULTS: Among 40 patients after distal pancreatectomy, CR-POPF occurred in 7 (17.5%) up to postoperative day 30. No type C POPF was observed. There was no intraoperative bleeding observed after patch application. CONCLUSION: The results of this international phase II study demonstrate promising results of a new sealant patch regarding the rate of CR-POPF. Randomized studies are now needed to confirm the superiority of the current patch as compared to the best current practice.

Protocol for an independent patient data meta-analysis of prophylactic mesh placement for incisional hernia prevention after abdominal aortic aneurysm surgery: a collaborative European Hernia Society project (I-PREVENT-AAA).

INTRODUCTION: Incisional hernia (IH) is a prevalent and potentially dangerous complication of abdominal surgery, especially in high-risk groups. Mesh reinforcement of the abdominal wall has been studied as a potential intervention to prevent IHs. Randomised controlled trials (RCTs) have demonstrated that prophylactic mesh reinforcement after abdominal surgery, in general, is effective and safe. In patients with abdominal aortic aneurysm (AAA), prophylactic mesh reinforcement after open repair has not yet been recommended in official guidelines, because of relatively small sample sizes in individual trials. Furthermore, the identification of subgroups that benefit most from prophylactic mesh placement requires larger patient numbers. Our primary aim is to evaluate the efficacy and effectiveness of the use of a prophylactic mesh after open AAA surgery to prevent IH by performing an individual patient data meta-analysis (IPDMA). Secondary aims include the evaluation of postoperative complications, pain and quality of life, and the identification of potential subgroups that benefit most from prophylactic mesh reinforcement. METHODS AND ANALYSIS: We will conduct a systematic review to identify RCTs that study prophylactic mesh placement after open AAA surgery. Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase, Web of Science Core Collection and Google Scholar will be searched from the date of inception onwards. RCTs must directly compare primary sutured closure with mesh closure in adult patients who undergo open AAA surgery. Lead authors of eligible studies will be asked to share individual participant data (IPD). The risk of bias (ROB) for each included study will be assessed using the Cochrane ROB tool. An IPDMA will be performed to evaluate the efficacy, with the IH rate as the primary outcome. Any signs of heterogeneity will be evaluated by Forest plots. Time-to-event analyses are performed using Cox regression analysis to evaluate risk factors. ETHICS AND DISSEMINATION: No new data will be collected in this study. We will adhere to institutional, national and international regulations regarding the secure and confidential sharing of IPD, addressing ethics as indicated. We will disseminate findings via international conferences, open-source publications in peer-reviewed journals and summaries posted online. PROSPERO REGISTRATION NUMBER: CRD42022347881.

Evolution in liver trauma management: a single centre experience.

OBJECTIVES: Liver trauma is common and can be treated non-operatively, through radiological embolisation, or surgically. Non-operative management (NOM) is preferred when possible, but specific criteria remain unclear. This retrospective study at a level I trauma centre assessed the evolution and outcomes of liver injury management over more than 20 years. METHODS: Data from January 1996 to June 2020 were analysed for liver trauma cases. Variables were evaluated, including the type of injury, diagnostic modalities, liver injury grade, transfer from other hospitals, treatment type, and length of hospital stay. Outcomes were assessed using soft (hospitalisation time and intensive care unit stay) and hard (mortality) endpoints. RESULTS: In total 406 patients were analysed, of which 375 (92.4%) had a blunt and 31 (7.6%) a penetrating liver trauma. Approximately one-third (31.2%) were hemodynamically unstable, although 78.8% had low-grade liver lesions. The initial treatment was non-operative in 72.9% of the patients (68.5% conservative, 4.4% interventional radiology). Blunt trauma was treated by surgery in 23.2% of the patients, while 74.2% in case of penetrating trauma. Overall mortality was 11.1% including death caused by associated lesions. The 24-h mortality was 5.7%. Indication for surgical treatment was determined by hemodynamic instability, high grade liver lesion, penetrating trauma, and associated lesions. CONCLUSIONS: Although the role of surgery in liver trauma management has strongly diminished over recent decades, hemodynamically unstable patients, high-grade lesions, penetrating trauma, and severe associated lesions are the main indications for surgery. In other situations, NOM by full conservative therapy or radiological embolisation seems effective.

Laparoscopic Versus Open Hemihepatectomy: The ORANGE II PLUS Multicenter Randomized Controlled Trial.

PURPOSE: To compare outcomes after laparoscopic versus open major liver resection (hemihepatectomy) mainly for primary or metastatic cancer. The primary outcome measure was time to functional recovery. Secondary outcomes included morbidity, quality of life (QoL), and for those with cancer, resection margin status and time to adjuvant systemic therapy. PATIENTS AND METHODS: This was a multicenter, randomized controlled, patient-blinded, superiority trial on adult patients undergoing hemihepatectomy. Patients were recruited from 16 hospitals in Europe between November 2013 and December 2018. RESULTS: Of the 352 randomly assigned patients, 332 patients (94.3%) underwent surgery (laparoscopic, n = 166 and open, n = 166) and comprised the analysis population. The median time to functional recovery was 4 days (IQR, 3-5; range, 1-30) for laparoscopic hemihepatectomy versus 5 days (IQR, 4-6; range, 1-33) for open hemihepatectomy (difference, -17.5% [96% CI, -25.6 to -8.4]; P < .001). There was no difference in major complications (laparoscopic 24/166 [14.5%] v open 28/166 [16.9%]; odds ratio [OR], 0.84; P = .58). Regarding QoL, both global health status (difference, 3.2 points; P < .001) and body image (difference, 0.9 points; P < .001) scored significantly higher in the laparoscopic group. For the 281 (84.6%) patients with cancer, R0 resection margin status was similar (laparoscopic 106 [77.9%] v open 122 patients [84.1%], OR, 0.60; P = .14) with a shorter time to adjuvant systemic therapy in the laparoscopic group (46.5 days v 62.8 days, hazard ratio, 2.20; P = .009). CONCLUSION: Among patients undergoing hemihepatectomy, the laparoscopic approach resulted in a shorter time to functional recovery compared with open surgery. In addition, it was associated with a better QoL, and in patients with cancer, a shorter time to adjuvant systemic therapy with no adverse impact on cancer outcomes observed.

Minimally invasive robot-assisted and laparoscopic distal pancreatectomy in a pan-European registry a retrospective cohort study.

BACKGROUND: International guidelines recommend monitoring of the use and outcome of minimally invasive pancreatic surgery (MIPS). However, data from prospective international audits on minimally invasive distal pancreatectomy (MIDP) are lacking. This study examined the use and outcome of robot-assisted (RDP) and laparoscopic (LDP) distal pancreatectomy in the E-MIPS registry. MATERIALS AND METHODS: Post-hoc analysis in a prospective audit on MIPS, including consecutive patients undergoing MIDP in 83 centers from 19 European countries (01-01-2019/31-12-2021). Primary outcomes included intraoperative events (grade 1: excessive blood loss, grade 2: conversion/change in operation, grade 3: intraoperative death), major morbidity, and in-hospital/30-day mortality. Multivariable logistic regression analyses identified high-risk groups for intraoperative events. RDP and LDP were compared in the total cohort and in high-risk groups. RESULTS: Overall, 1672 patients undergoing MIDP were included; 606 (36.2%) RDP and 1066 (63.8%) LDP. The annual use of RDP increased from 30.5% to 42.6% (P<0.001). RDP was associated with fewer grade 2 intraoperative events compared to LDP (9.6% vs. 16.8%, P<0.001), with longer operating time (238 vs. 201 minutes,P<0.001). No significant differences were observed between RDP and LDP regarding major morbidity (23.4% vs. 25.9%, P=0.264) and in-hospital/30-day mortality (0.3% vs. 0.8%, P=0.344). Three high-risk groups were identified; BMI>25 kg/m2, previous abdominal surgery, and vascular involvement. In each group, RDP was associated with fewer conversions and longer operative times. CONCLUSION: This European registry-based study demonstrated favorable outcomes for MIDP, with mortality rates below 1%. LDP remains the predominant approach, whereas the use of RDP is increasing. RDP was associated with less conversions and longer operative time, including in high-risk subgroups. Future randomized trials should confirm these findings and assess cost differences.

Bariatric surgery post-Liver Transplantation: A Belgian nationwide study.

BACKGROUND: Weight gain poses a rising concern post-liver transplantation (LT), and metabolic dysfunction-associated steatotic liver disease (MASLD) might impair graft health. The timing is crucial when considering bariatric surgery (BS) in a population with liver disease or transplantation. BS can be considered for post-LT weight gain, although the evidence is limited and the long-term outcome still uncertain. METHODS: We conducted a national retrospective analysis in 5 Belgian transplant centres and included 25 patients with a liver transplantation followed by a bariatric procedure. 187 LT patients without BS were included for comparison. Clinical, biochemical and outcome data were retrospectively retrieved. RESULTS: In our nationwide cohort, 25 patients had undergone BS post-LT, at a median 3.5 years after LT. Twenty-one (84.0%) patients received a sleeve gastrectomy (SG). Patients were predominantly male (72.0%), with a lower age at time of transplantation compared to non-BS population (54.5 vs. 60.6, p<0.001). Weight loss was significant and sustained, with a decrease in BMI from 41.0±4.5 pre-BS to 32.6±5.8 1-3 years post-BS (p<0.001) and 31.1±5.8 3-5 years post-BS (p<0.001). Post-LT pre-BS three (12.0%) patients presented with recurrent and one (4.0%) de novo MASLD, with 100% resolution post-BS (p=0.016). Notable reductions were observed in ALT levels (40.5±28.5 U/L to 27.1±25.1 U/L post-BS, p=0.05) and HbA1c levels (6.9±1.6 to 6.0±1.4 post-BS, p<0.001). Three patients were re-transplanted, and eight patients died, of which five (20.0%) due to a non-hepatic malignancy and one (4.0%) due to liver failure. CONCLUSIONS: SG is the favored BS post-LT and has proven to be safe and feasible in a post-LT setting with favorable metabolic consequences. SG post-LT is a valid treatment for de novo and recurrent MASLD post-LT. Although we report on the largest cohort to date, there is still a need for larger cohorts to examine the effect of BS on patient and graft survival.

Machine learning improves prediction of postoperative outcomes after gastrointestinal surgery: a systematic review and meta-analysis.

BACKGROUND: Machine learning (ML) approaches have become increasingly popular in predicting surgical outcomes. However, it is unknown whether they are superior to traditional statistical methods such as logistic regression (LR). This study aimed to perform a systematic review and meta-analysis to compare the performance of ML vs LR models in predicting postoperative outcomes for patients undergoing gastrointestinal (GI) surgery. METHODS: A systematic search of Embase, MEDLINE, Cochrane, Web of Science, and Google Scholar was performed through December 2022. The primary outcome was the discriminatory performance of ML vs LR models as measured by the area under the receiver operating characteristic curve (AUC). A meta-analysis was then performed using a random effects model. RESULTS: A total of 62 LR models and 143 ML models were included across 38 studies. On average, the best-performing ML models had a significantly higher AUC than the LR models (ΔAUC, 0.07; 95% CI, 0.04-0.09; P < .001). Similarly, on average, the best-performing ML models had a significantly higher logit (AUC) than the LR models (Δlogit [AUC], 0.41; 95% CI, 0.23-0.58; P < .001). Approximately half of studies (44%) were found to have a low risk of bias. Upon a subset analysis of only low-risk studies, the difference in logit (AUC) remained significant (ML vs LR, Δlogit [AUC], 0.40; 95% CI, 0.14-0.66; P = .009). CONCLUSION: We found a significant improvement in discriminatory ability when using ML over LR algorithms in predicting postoperative outcomes for patients undergoing GI surgery. Subsequent efforts should establish standardized protocols for both developing and reporting studies using ML models and explore the practical implementation of these models.

Intraductal papillary neoplasms of the bile ducts: a comparative study of a rare disease in Europe and Nagoya, Japan.

BACKGROUND: Intraductal papillary neoplasm of the bile ducts (IPNB) is a rare disease in Western countries. The aim of this study was to compare tumor characteristics, management strategies, and outcomes between Western and Eastern patients who underwent surgical resection for IPNB. METHODS: A multi-institutional retrospective series of patients with IPNB undergoing surgery between January 2010 and December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA), and at Nagoya University Hospital, Japan. RESULTS: A total of 85 patients (51% male; median age 66 years) from 28 E-AHPBA centers were compared to 91 patients (64% male; median age 71 years) from Nagoya. Patients in Europe had more multiple lesions (23% vs 2%, P < .001), less invasive carcinoma (42% vs 85%, P < .001), and more intrahepatic tumors (52% vs 24%, P < .001) than in Nagoya. Patients in Europe experienced less 90-day grade >3 Clavien-Dindo complications (33% vs 68%, P < .001), but higher 90-day mortality rate (7.0% vs 0%, P = .03). R0 resections (81% vs 82%) were similar. Overall survival, excluding 90-day postoperative deaths, was similar in both regions. DISCUSSION: Despite performing more extensive resections, the low perioperative mortality rate observed in Nagoya was probably influenced by a combination of patient-, tumor-, and surgery-related factors.

Recent outcomes of liver transplantation for Budd-Chiari syndrome: A study of the European Liver Transplant Registry (ELTR) and affiliated centers.

BACKGROUND AND AIMS: Management of Budd-Chiari syndrome (BCS) has improved over the last decades. The main aim was to evaluate the contemporary post-liver transplantant (post-LT) outcomes in Europe. APPROACH AND RESULTS: Data from all patients who underwent transplantation from 1976 to 2020 was obtained from the European Liver Transplant Registry (ELTR). Patients < 16 years with secondary BCS or HCC were excluded. Patient survival (PS) and graft survival (GS) before and after 2000 were compared. Multivariate Cox regression analysis identified predictors of PS and GS after 2000. Supplemental data was requested from all ELTR-affiliated centers and received from 44. In all, 808 patients underwent transplantation between 2000 and 2020. One-, 5- and 10-year PS was 84%, 77%, and 68%, and GS was 79%, 70%, and 62%, respectively. Both significantly improved compared to outcomes before 2000 ( p < 0.001). Median follow-up was 50 months and retransplantation rate was 12%. Recipient age (aHR:1.04,95%CI:1.02-1.06) and MELD score (aHR:1.04,95%CI:1.01-1.06), especially above 30, were associated with worse PS, while male sex had better outcomes (aHR:0.63,95%CI:0.41-0.96). Donor age was associated with worse PS (aHR:1.01,95%CI:1.00-1.03) and GS (aHR:1.02,95%CI:1.01-1.03). In 353 patients (44%) with supplemental data, 33% had myeloproliferative neoplasm, 20% underwent TIPS pre-LT, and 85% used anticoagulation post-LT. Post-LT anticoagulation was associated with improved PS (aHR:0.29,95%CI:0.16-0.54) and GS (aHR:0.48,95%CI:0.29-0.81). Hepatic artery thrombosis and portal vein thrombosis (PVT) occurred in 9% and 7%, while recurrent BCS was rare (3%). CONCLUSIONS: LT for BCS results in excellent patient- and graft-survival. Older recipient or donor age and higher MELD are associated with poorer outcomes, while long-term anticoagulation improves both patient and graft outcomes.

The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS).

OBJECTIVE: To develop and update evidence-based and consensus-based guidelines on laparoscopic and robotic pancreatic surgery. SUMMARY BACKGROUND DATA: Minimally invasive pancreatic surgery (MIPS), including laparoscopic and robotic surgery, is complex and technically demanding. Minimizing the risk for patients requires stringent, evidence-based guidelines. Since the International Miami Guidelines on MIPS in 2019, new developments and key publications have been reported, necessitating an update. METHODS: Evidence-based guidelines on 22 topics in 8 domains were proposed: terminology, indications, patients, procedures, surgical techniques and instrumentation, assessment tools, implementation and training, and artificial intelligence. The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS, September 2022) used the Scottish Intercollegiate Guidelines Network (SIGN) methodology to assess the evidence and develop guideline recommendations, the Delphi method to establish consensus on the recommendations among the Expert Committee, and the AGREE II-GRS tool for guideline quality assessment and external validation by a Validation Committee. RESULTS: Overall, 27 European experts, 6 international experts, 22 international Validation Committee members, 11 Jury Committee members, 18 Research Committee members, and 121 registered attendees of the 2-day meeting were involved in the development and validation of the guidelines. In total, 98 recommendations were developed, including 33 on laparoscopic, 34 on robotic, and 31 on general MIPS, covering 22 topics in 8 domains. Out of 98 recommendations, 97 reached at least 80% consensus among the experts and congress attendees, and all recommendations were externally validated by the Validation Committee. CONCLUSIONS: The EGUMIPS evidence-based guidelines on laparoscopic and robotic MIPS can be applied in current clinical practice to provide guidance to patients, surgeons, policy-makers, and medical societies.

Global surgery education in Belgium: Student's knowledge, attitudes and exposure.

PURPOSE: Understanding how medical students perceive global surgery will be essential in strengthening the global surgery workforce by 2030. This study investigated the knowledge, attitudes and exposure of Belgian medical students towards global surgery and identified avenues for medical institutions to include meaningful educational opportunities. METHODS: An online survey was distributed to first to final year medical students across Belgian universities using social media. Data were collected on demographics, exposure, knowledge and attitudes towards global surgery. Odds ratios with 95% confidence intervals were calculated. RESULTS: A total of 304 medical students participated from four Belgian universities. A minority reported having exposure to global surgery (24.7%), and most wanted more exposure (75.3%). Almost all respondents agreed (94.4%) that it is a relevant topic for medical students, and most agreed (71%) more compulsory education on the topic is needed. Only 13 to 44% of students could correctly answer questions testing global surgery knowledge. Personal/family responsibilities were the most important barrier to pursuing global surgery careers. CONCLUSIONS: Global surgery knowledge and exposure is limited among Belgian medical students despite interest in the field. These results advocate for the inclusion of decolonised global surgery education alongside equitable international clinical internships in medical education worldwide.

Update of the international HerniaSurge guidelines for groin hernia management.

BACKGROUND: Groin hernia repair is one of the most common operations performed globally, with more than 20 million procedures per year. The last guidelines on groin hernia management were published in 2018 by the HerniaSurge Group. The aim of this project was to assess new evidence and update the guidelines. The guideline is intended for general and abdominal wall surgeons treating adult patients with groin hernias. METHOD: A working group of 30 international groin hernia experts and all involved stakeholders was formed and examined all new literature on groin hernia management, available until April 2022. Articles were screened for eligibility and assessed according to GRADE methodologies. New evidence was included, and chapters were rewritten. Statements and recommendations were updated or newly formulated as necessary. RESULTS: Ten chapters of the original HerniaSurge inguinal hernia guidelines were updated. In total, 39 new statements and 32 recommendations were formulated (16 strong recommendations). A modified Delphi method was used to reach consensus on all statements and recommendations among the groin hernia experts and at the European Hernia Society meeting in Manchester on October 21, 2022. CONCLUSION: The HerniaSurge Collaboration has updated the international guidelines for groin hernia management. The updated guidelines provide an overview of the best available evidence on groin hernia management and include evidence-based statements and recommendations for daily practice. Future guideline development will change according to emerging guideline methodology.

Predictive factors for survival in borderline resectable and locally advanced pancreatic cancer: are these really two different entities?

BACKGROUND: The treatment of borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) has evolved with a wider application of neoadjuvant chemotherapy (NACHT). The aim of this study was to identify predictive factors for survival in BR and LA PDAC. METHODS: Clinicopathologic data of patients with BR and LA PDAC who underwent surgical exploration between January 2011 and June 2021 were retrospectively collected. Survival from the date of surgery was estimated using the Kaplan-Meier method. Simple and multiple Cox proportional hazards models were fitted to identify factors associated with survival. Surgical resection was analyzed in combination with the involvement of lymph nodes as this last was only known after a formal resection. RESULTS: Ninety patients were surgically explored (BR: 45, LA: 45), of which 51 (57%) were resected (BR: 31, LA: 20). NACHT was administered to 43 patients with FOLFIRINOX being the most frequent regimen applied (33/43, 77%). Major complications (Clavien-Dindo grade III and IV) occurred in 7.8% of patients and 90-day mortality rate was 3.3%. The median overall survival since surgery was 16 months (95% CI 12-20) in the group which underwent surgical resection and 10 months (95% CI 7-13) in the group with an unresectable tumor (p=0.001). Cox proportional hazards models showed significantly lower mortality hazard for surgical resection compared to no surgical resection, even after adjusting for National Comprehensive Cancer Network  (NCCN) classification and administration of NACHT [surgical resection with involved lymph nodes vs no surgical resection (cHR 0.49; 95% CI 0.29-0.82; p=0.007)]. There was no significant difference in survival between patients with BR and LA disease (cHR= 1.01; 95% CI 0.63-1.62; p=0.98). CONCLUSIONS: Surgical resection is the only predictor of survival in patients with BR and LA PDAC, regardless of their initial classification as BR or LA. Our results suggest that surgery should not be denied to patients with LA PDAC a priori. Prospective studies including patients from the moment of diagnosis are required to identify biologic and molecular markers which may allow a better selection of patients who will benefit from surgery.

Concurrent Ocular and Cerebral Toxoplasmosis in a Liver Transplant Patient Treated with Anti-CD40 Monoclonal Antibody.

Toxoplasma gondii, an obligate intracellular parasitic protozoon, usually causes a mild, acute infection followed by a latent asymptomatic phase with tissue cysts or a chronic form with recurrent retinochoroiditis. However, immunocompromised patients can cause disseminated disease due to the reactivation of the latent tissue cysts or due to a primary infection. Here, we present a rare case of bilateral ocular toxoplasmosis and concurrent subacute toxoplasma encephalitis in a 70-year-old patient on anti-CD40 treatment following his liver transplant. The diagnosis was confirmed by PCR of anterior chamber fluid and brain biopsy, and no other sites of disseminated disease were detected on PET-CT. The patient has been treated with sulfamethoxazole-trimethoprim 800/160 mg with virtually complete resolution of the neurological and ocular symptoms. Iatrogenic blockade of the CD40 pathway may elicit a particular susceptibility for CNS reactivation of T. gondii.

Safety and Hemostatic Effectiveness of SURGICEL® Powder in Mild and Moderate Intraoperative Bleeding.

This postmarket clinical study evaluated the safety and effectiveness of the novel adjunctive topical hemostat SURGICEL® Powder (SURGICEL®-P), a powdered form of oxidized regenerated cellulose. In a prospective, open-label, single-arm multicenter trial, adult surgical subjects with mild-to-moderate bleeding for which conventional hemostatic methods were impractical/ineffective were treated with SURGICEL®-P. Descriptive analyses included hemostatic success rate at 3, 5, and 10 min, rebleeding and thromboembolic events, SURGICEL®-P-related serious adverse events requiring surgical intervention, and SURGICEL®-P ease of use (questionnaire). In 8 centers, 103 subjects were enrolled with a median (range) age of 64.0 (33.0-88.0) years. Surgeries were open (53.4%) or laparoscopic/thoracoscopic (46.6%) and mostly urological (37.9%) and abdominal (32.0%) procedures. Bleeding sites included various tissue types, with a median (range) surface area of 4 (0.02-72.0) cm2. Hemostatic success rates were 77.7%, 87.4%, and 92.2% at 3, 5, and 10 min, respectively. In 7 subjects (6.8%), investigators reverted to standard of care. No safety signals were identified. Two deaths occurred with causes unrelated to SURGICEL®-P. Investigators favorably evaluated the ease of use of the SURGICEL®-P device. SURGICEL®-P is safe and effective in controlling mild-to-moderate bleeding in a broad range of surgical procedures. The trial was registered at https://clinicaltrials.gov as NCT03762200.

Study protocol for a multicenter randomized controlled trial to compare radiofrequency ablation with surgical resection for treatment of pancreatic insulinoma.

BACKGROUND: Insulinoma is the most common functional pancreatic neuroendocrine tumor and treatment is required to address symptoms associated with insulin hypersecretion. Surgical resection is effective but burdened by high rate of adverse events (AEs). Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) demonstrated encouraging results in terms of safety and efficacy for the management of these tumors. However, studies comparing surgery and EUS-RFA are lacking. AIMS: The primary aim is to compare EUS-RFA with surgery in term of safety (overall rate of AEs). Secondary endpoints include: (a) severe AEs rate; (b) clinical effectiveness; (c) patient's quality of life; (d) length of hospital stay; (e) rate of local/distance recurrence; (f) need of reintervention; (g) rate of endocrine and exocrine pancreatic insufficiency; (h) factors associated with EUS-RFA related AEs and clinical effectiveness. METHODS: ERASIN-RCT is an international randomized superiority ongoing trial in four countries. Sixty patients will be randomized in two arms (EUS-RFA vs surgery) and outcomes compared. Two EUS-RFA sessions will be allowed to achieve symptoms resolution. Randomization and data collection will be performed online. DISCUSSION: This study will ascertain if EUS-RFA can become the first-line therapy for management of small, sporadic, pancreatic insulinoma and be included in a step-up approach in case of clinical failure.

The Role of Donor Gamma-Glutamyl Transferase as a Risk Factor for Early Graft Function after Liver Transplantation.

BACKGROUND: Growing interest has been recently reported in the potential detrimental role of donor gamma-glutamyl transferase (GGT) peak at the time of organ procurement regarding the risk of poor outcomes after liver transplantation (LT). However, the literature on this topic is scarce and controversial data exist on the mechanisms justifying such a correlation. This study aims to demonstrate the adverse effect of donor GGT in a large European LT cohort regarding 90-day post-transplant graft loss. METHODS: This is a retrospective international study investigating 1335 adult patients receiving a first LT from January 2004 to September 2018 in four collaborative European centers. RESULTS: Two different multivariable logistic regression models were constructed to evaluate the risk factors for 90-day post-transplant graft loss, introducing donor GGT as a continuous or dichotomous variable. In both models, donor GGT showed an independent role as a predictor of graft loss. In detail, the log-transformed continuous donor GGT value showed an odds ratio of 1.46 (95% CI = 1.03-2.07; p = 0.03). When the donor GGT peak value was dichotomized using a cut-off of 160 IU/L, the odds ratio was 1.90 (95% CI = 1.20-3.02; p = 0.006). When the graft-loss rates were investigated, significantly higher rates were reported in LT cases with donor GGT ≥160 IU/L. In detail, 90-day graft-loss rates were 23.2% vs. 13.9% in patients with high vs. low donor GGT, respectively (log-rank p = 0.004). Donor GGT was also added to scores conventionally used to predict outcomes (i.e., MELD, D-MELD, DRI, and BAR scores). In all cases, when the score was combined with the donor GGT, an improvement in the model accuracy was observed. CONCLUSIONS: Donor GGT could represent a valuable marker for evaluating graft quality at transplantation. Donor GGT should be implemented in scores aimed at predicting post-transplant clinical outcomes. The exact mechanisms correlating GGT and poor LT outcomes should be better clarified and need prospective studies focused on this topic.