Sealive: the use of technical vessel-sealing devices for recipient hepatectomy in liver transplantation: study protocol for a randomized controlled trial

Background: The surgical technique used in liver transplantation has undergone constant evolution in an effort to develop a safe, highly standardized procedure. Despite this, the initial step of recipient hepatectomy has not been the focus of clinical research thus far. Due to advanced coagulopathy in liver transplant recipients, this part of the operation still carries the risk of severe hemorrhage. This trial is designed to compare an electrothermal bipolar vessel sealing device (LigaSure™) and an ultrasound dissector (HARMONIC ACE®+7) with standard surgical techniques during the recipients’ hepatectomy in liver transplantation. Methods/design: In a single-center, prospective, randomized, controlled, parallel, three-armed, confirmatory, open trial, LigaSure™ and HARMONIC ACE®+7 will be compared with standard surgical techniques that use titanium clips and conventional knot-tying ligations during recipient hepatectomy in liver transplantation. Intraoperative total blood loss is the primary endpoint of the trial. Secondary endpoints include blood loss during hepatectomy, the duration of both the hepatectomy and the entire surgical procedure, and blood transfusion requirements of the procedure. To generate reliable data, intraoperative blood loss will be recorded with respect to all rinse fluids during surgery, ascites, and by weighing used swabs. At 80% power and an alpha of 0.025 for both of the experimental groups, 23 subjects will be analyzed per protocol in each study arm in order to detect clinically relevant reduction of intraoperative blood loss. The intention-to-treat analysis will include 69 patients. The follow-up period for each patient will be 90 days for safety reasons, whereas all clinical outcomes will be measured within the first 10 postoperative days. Discussion: To our knowledge, this is the first prospective, randomized trial comparing two innovative technical methods of vessel sealing and dissection with standard techniques for recipient hepatectomy. This will be done to detect relevant reduction of intraoperative blood loss during liver transplant. The results of the trial are expected to improve patient outcome and safety after liver transplant and to increase the general safety of this procedure. Trial registration: ClinicalTrials.gov, NCT 03323242 . Registered on October 26, 2017

Hand-Assisted laparoscopic donor nephrectomy PERiumbilical versus Pfannenstiel incision and return to normal physical ACTivity (HAPERPACT): study protocol for a randomized controlled trial

Background: Hand-assisted laparoscopic living donor nephrectomy (HALDN) using a periumbilical or Pfannenstiel incision was developed to improve donor outcome after a kidney transplant. The aim of this study was to investigate two methods of hand assistance and kidney removal during HALDN and their effect on the time it takes for the donor to return to normal physical activity. Methods/design: This study was initiated in November 2017 and is expected to last for 2 years. To be eligible for the study, donors must be more than 20 years of age and must not be receiving permanent pain therapy. Only donors with a single artery and vein in the graft are being enrolled in this trial. Donors with infections or scars in the periumbilical or hypogastric area, bleeding disorders, chronic use of immunosuppressive agents, or active infection will be excluded. Donors will be randomly allocated to either a control arm (periumbilical incision) or an intervention arm (Pfannenstiel incision). The sample size was calculated as 26 organ donors in each group. The primary endpoint is the number of days it takes the donor to return to normal physical activity (up to 4 weeks after the operation). Secondary endpoints are intraoperative outcomes, including estimated blood loss, warm ischemia time, and duration of the operation. Postoperative pain will be assessed using the visual analog scale, rescue analgesic use, and peak expiratory flow rate. Length of hospital stay, physical activity score, time to return to work, donor satisfaction, cosmetic score, postoperative complications, and all-cause mortality in living donors will also be reported. Delayed graft function, primary non-function, serum creatinine levels, and glomerular filtration rate will also be assessed in the recipients after transplantation. Discussion: This is the first randomized controlled trial to compare the time it takes the living donor to return to normal physical activity after HALDN using two different types of incision. The comprehensive findings of this study will help decide which nephrectomy procedure is best for living donors with regard to patient comfort and satisfaction as well as graft function in the recipient after transplantation. Trial registration: ClinicalTrials.gov, NCT03317184 . Registered on 23 October 2017

Outcomes of Robot-Assisted Surgery in Rectal Cancer Compared with Open and Laparoscopic Surgery

With increasing trends for the adoption of robotic surgery, many centers are considering changing their practices from open or laparoscopic to robot-assisted surgery for rectal cancer. We compared the outcomes of robot-assisted rectal resection with those of open and laparoscopic surgery. We searched Medline, Web of Science, and CENTRAL databases until October 2022. All randomized controlled trials (RCTs) and prospective studies comparing robotic surgery with open or laparoscopic rectal resection were included. Fifteen RCTs and 11 prospective studies involving 6922 patients were included. The meta-analysis revealed that robotic surgery has lower blood loss, less surgical site infection, shorter hospital stays, and higher negative resection margins than open resection. Robotic surgery also has lower conversion rates, lower blood loss, lower rates of reoperation, and higher negative circumferential margins than laparoscopic surgery. Robotic surgery had longer operation times and higher costs than open and laparoscopic surgery. There were no differences in other complications, mortality, and survival between robotic surgery and the open or laparoscopic approach. However, heterogeneity between studies was moderate to high in some analyses. The robotic approach can be the method of choice for centers planning to change from open to minimally invasive rectal surgery. The higher costs of robotic surgery should be considered as a substitute for laparoscopic surgery (PROSPERO: CRD42022381468)

Outcomes of Robot-Assisted Surgery in Rectal Cancer Compared with Open and Laparoscopic Surgery

With increasing trends for the adoption of robotic surgery, many centers are considering changing their practices from open or laparoscopic to robot-assisted surgery for rectal cancer. We compared the outcomes of robot-assisted rectal resection with those of open and laparoscopic surgery. We searched Medline, Web of Science, and CENTRAL databases until October 2022. All randomized controlled trials (RCTs) and prospective studies comparing robotic surgery with open or laparoscopic rectal resection were included. Fifteen RCTs and 11 prospective studies involving 6922 patients were included. The meta-analysis revealed that robotic surgery has lower blood loss, less surgical site infection, shorter hospital stays, and higher negative resection margins than open resection. Robotic surgery also has lower conversion rates, lower blood loss, lower rates of reoperation, and higher negative circumferential margins than laparoscopic surgery. Robotic surgery had longer operation times and higher costs than open and laparoscopic surgery. There were no differences in other complications, mortality, and survival between robotic surgery and the open or laparoscopic approach. However, heterogeneity between studies was moderate to high in some analyses. The robotic approach can be the method of choice for centers planning to change from open to minimally invasive rectal surgery. The higher costs of robotic surgery should be considered as a substitute for laparoscopic surgery (PROSPERO: CRD42022381468)

Plasma Apelin and Asymmetric Dimethylarginine (ADMA) Levels Shortly After Laparoscopic Greater Curvature Plication

We sought to investigate the short-term effect of weight loss following restrictive bariatric surgery on plasma concentrations of apelin and asymmetric dimethylarginine (ADMA) in individuals with morbid obesity

Interdisciplinary approach allows minimally invasive, nerve-sparing removal of retroperitoneal peripheral nerve sheath tumors

Purpose!#!En bloc resection of retroperitoneal peripheral nerve sheath tumors (PNST) is advocated by a variety of surgical disciplines. Yet, microsurgical, nerve-sparing tumor resection might be better suited to improve symptoms and maintain neurological function, especially in cases where patients present with preoperative neurological deficits. However, neurosurgeons, versed in nerve-sparing techniques to remove PNST, are generally unfamiliar with the visceral approaches to retroperitoneal PNST.!##!Methods!#!We retrospectively evaluate a series of 16 patients suffering from retroperitoneal PNST. Patients were treated by a unique interdisciplinary approach, combining the visceral surgeon's skills to navigate the complex anatomy of the retroperitoneal space and the neurosurgeon's familiarity with microsurgical, nerve-sparing tumor removal. Specifically, we assess whether our interdisciplinary approach is suited to improve preoperative symptoms and maintain neurological function and study whether oncological outcome, surgical morbidity, and operative times are comparable to those reported for 'classical' retroperitoneal PNST resection. In addition, we study two cases of suspected PNST that were diagnosed as malignant peripheral nerve sheath tumors (MPNST) after surgery.!##!Results!#!Total macroscopic tumor resection was achieved in 14/16 PNST patients. Mean intraoperative blood loss was 680.6 ml (95% CI, 194.3-1167.0 ml) and mean operative time was 162.5 min (95% CI, 121.6-203.4 min). We did not record any major postoperative surgical or neurological complications. A total of 8/11 patients with preoperative pain symptoms reported long-lasting improvement of their symptoms. In terms of oncological outcome, all patients that had been subjected to total tumor removal and for whom follow-up was available, were tumor-free after a mean follow-up of 761.9 days (95% CI, 97.6-1426.0 days). One of the two MPNST patients, who presented with tumor progress 15 months after initial surgery, was subjected to radical re-resection.!##!Conclusions!#!Interdisciplinary, nerve-sparing removal of retroperitoneal PNST is well suited to improve preoperative symptoms and maintain neurological function, while achieving an oncological outcome and a surgical morbidity similar to previously reported results for radical retroperitoneal PNST resection. Radical re-resection was feasible in a patient with post hoc MPNST diagnosis

Kynurenine Is the Main Metabolite of Tryptophan Degradation by Tryptophan 2,3-Dioxygenase in HepaRG Tumor Cells

There are two main enzymes that convert tryptophan (Trp) to kynurenine (Kyn): tryptophan-2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO). Kyn accumulation can promote immunosuppression in certain cancers. In this study, we investigated Trp degradation to Kyn by IDO and TDO in primary human hepatocytes (PHH) and tumoral HepaRG cells. To quantify Trp-degradation and Kyn-accumulation, using reversed-phase high-pressure liquid chromatography, the levels of Trp and Kyn were determined in the culture media of PHH and HepaRG cells. The role of IDO in Trp metabolism was investigated by activating IDO with IFN-γ and inhibiting IDO with 1-methyl-tryptophan (1-DL-MT). The role of TDO was investigated using one of two TDO inhibitors: 680C91 or LM10. Real-time PCR was used to measure TDO and IDO expression. Trp was degraded in both PHH and HepaRG cells, but degradation was higher in PHH cells. However, Kyn accumulation was higher in the supernatants of HepaRG cells. Stimulating IDO with IFN-γ did not significantly affect Trp degradation and Kyn accumulation, even though it strongly upregulated IDO expression. Inhibiting IDO with 1-DL-MT also had no effect on Trp degradation. In contrast, inhibiting TDO with 680C91 or LM10 significantly reduced Trp degradation. The expression of TDO but not of IDO correlated positively with Kyn accumulation in the HepaRG cell culture media. Furthermore, TDO degraded L-Trp but not D-Trp in HepaRG cells. Kyn is the main metabolite of Trp degradation by TDO in HepaRG cells. The accumulation of Kyn in HepaRG cells could be a key mechanism for tumor immune resistance. Two TDO inhibitors, 680C91 and LM10, could be useful in immunotherapy for liver cancers

Systematic reviews in surgery—recommendations from the Study Center of the German Society of Surgery

Background!#!Systematic reviews are an important tool of evidence-based surgery. Surgical systematic reviews and trials, however, require a special methodological approach.!##!Purpose!#!This article provides recommendations for conducting state-of-the-art systematic reviews in surgery with or without meta-analysis.!##!Conclusions!#!For systematic reviews in surgery, MEDLINE (via PubMed), Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) should be searched. Critical appraisal is at the core of every surgical systematic review, with information on blinding, industry involvement, surgical experience, and standardisation of surgical technique holding special importance. Due to clinical heterogeneity among surgical trials, the random-effects model should be used as a default. In the experience of the Study Center of the German Society of Surgery, adherence to these recommendations yields high-quality surgical systematic reviews