Alexander F. M. Schaapherder

Laparoscopic donor nephrectomy (LDN) is the current gold standard in kidney donation. Mini-incision open donor nephrectomy (MINI) techniques have been used extensively but have become less popular. The aim of the present study was to compare the results and safety of a non-muscle-splitting MINI technique with the current gold standard of LDN. A single center retrospective cohort study of all living donor nephrectomies between 2011 and 2019 was used for the study. The primary outcome of this study was short term (<30 days) with Clavien–Dindo grade complications. Secondary outcomes included multivariable regression analysis of perioperative data. No differences in complication rates were observed between MINI and LDN and also after correction for known confounders. As expected, the operative time and first warm ischemia were significantly shorter in the MINI group and less blood loss was observed in the LDN group. Complications and conversion rate (LDN to open) among the LDN patients were in line with recent published meta-analyses. This study confirms the perioperative safety of living kidney donation in modern practice. Complication rates of both MINI and LDN procedures are limited and not different between procedures. In specific circumstances, the MINI procedure can still be considered a safe and feasible alternative for living kidney donation.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary disorders. Once progressed to end-stage renal disease, kidney transplantation may be needed. Whether and when to perform a (bilateral) native nephrectomy in case of end-stage renal failure are issues under debate. At our institution, with a growing number of living kidney donations, the general trend is to perform a native nephrectomy prior to transplantation. Our aim was to compare the outcomes of this approach to a nephrectomy during or after transplantation and to compare our findings to results reported in the literature. Data were prospectively collected from all ADPKD patients undergoing native nephrectomy and kidney transplantation at the Leiden University Medical Center between 2000–2017. A literature search was performed in the PubMed and Scopus databases. The clinical results were retrospectively reviewed and were stratified according to the timing of the nephrectomy. From the literature review, the most practiced approach was a combined unilateral nephrectomy and kidney transplantation. However, in our series, the favored approach was to perform a scheduled bilateral nephrectomy prior to kidney transplantation. A total of 114 patients underwent a native nephrectomy prior to (group 1, n = 85), during (group 2, n = 5), or after (group 3, n = 24) kidney transplantation. There were no statistically significant differences in postoperative morbidity after nephrectomy nor differences in kidney transplant outcome. Bilateral nephrectomy prior to kidney transplantation is a safe, controlled approach carrying minimal complication and mortality rates and facilitating a subsequent transplant procedure without mechanical or hemodynamic limitations for the graft.

Infected necrosis complicates 10% of all acute pancreatitis episodes and is associated with 15–20% mortality. The current standard treatment for infected necrotizing pancreatitis is the step-up approach (catheter drainage, followed, if necessary, by minimally invasive necrosectomy). Catheter drainage is preferably postponed until the stage of walled-off necrosis, which usually takes 4 weeks. This delay stems from the time when open necrosectomy was the standard. It is unclear whether such delay is needed for catheter drainage or whether earlier intervention could actually be beneficial in the current step-up approach. The POINTER trial investigates if immediate catheter drainage in patients with infected necrotizing pancreatitis is superior to the current practice of postponed intervention. POINTER is a randomized controlled multicenter superiority trial. All patients with necrotizing pancreatitis are screened for eligibility. In total, 104 adult patients with (suspected) infected necrotizing pancreatitis will be randomized to immediate (within 24 h) catheter drainage or current standard care involving postponed catheter drainage. Necrosectomy, if necessary, is preferably postponed until the stage of walled-off necrosis, in both treatment arms. The primary outcome is the Comprehensive Complication Index (CCI), which covers all complications between randomization and 6-month follow up. Secondary outcomes include mortality, complications, number of (repeat) interventions, hospital and intensive care unit (ICU) lengths of stay, quality-adjusted life years (QALYs) and direct and indirect costs. Standard follow-up is at 3 and 6 months after randomization. The POINTER trial investigates if immediate catheter drainage in infected necrotizing pancreatitis reduces the composite endpoint of complications, as compared with the current standard treatment strategy involving delay of intervention until the stage of walled-off necrosis. ISRCTN, 33682933 . Registered on 6 August 2015. Retrospectively registered.

Infected necrotising pancreatitis is a potentially lethal disease that nearly always requires intervention. Traditionally, primary open necrosectomy has been the treatment of choice. In recent years, the surgical step-up approach, consisting of percutaneous catheter drainage followed, if necessary, by (minimally invasive) surgical necrosectomy has become the standard of care. A promising minimally invasive alternative is the endoscopic transluminal step-up approach. This approach consists of endoscopic transluminal drainage followed, if necessary, by endoscopic transluminal necrosectomy. We hypothesise that the less invasive endoscopic step-up approach is superior to the surgical step-up approach in terms of clinical and economic outcomes. The TENSION trial is a randomised controlled, parallel-group superiority multicenter trial. Patients with (suspected) infected necrotising pancreatitis with an indication for intervention and in whom both treatment modalities are deemed possible, will be randomised to either an endoscopic transluminal or a surgical step-up approach. During a 4 year study period, 98 patients will be enrolled from 24 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite of death and major complications within 6 months following randomisation. Secondary endpoints include complications such as pancreaticocutaneous fistula, exocrine or endocrine pancreatic insufficiency, need for additional radiological, endoscopic or surgical intervention, the need for necrosectomy after drainage, the number of (re-)interventions, quality of life, and total direct and indirect costs. The TENSION trial will answer the question whether an endoscopic step-up approach reduces the combined primary endpoint of death and major complications, as well as hospital stay and related costs compared with a surgical step-up approach in patients with infected necrotising pancreatitis.

Kidney transplantation represents one of the medical achievements of the 20th century. However, its continued success is limited by the increasing shortage of donor grafts. As a result, more kidney grafts from marginal donors are being considered for transplantation, with concomitantly more initial graft injury and limited organ and patient survival. This has led to an increased need for interventions aiming to optimize and preserve graft quality. Interventions within the donor may protect against ischemia/reperfusion injury, and therefore, donor pre-treatment is a promising strategy to increase graft function and survival. During the last decade, diverse donor pre-treatment interventions have been explored in animal studies. Moreover, the first human trials concerning donor pre-treatment in kidney transplantation have provided encouraging results. Unfortunately, it remains difficult to determine how and where to intervene in the multifactorial and complex processes that affect the donor kidney. Moreover, ethical matters play a critical role in donor interventions, and pre-treatment should principally not have any potentially unfavorable effects on other organs to be transplanted or on the living donor. This review provides an overview of promising therapeutical strategies for donor pre-treatment in kidney transplantation and discusses the clinical trials that have been conducted thus far.

Background: After an initial attack of biliary pancreatitis, cholecystectomy minimizes the risk of recurrent biliary pancreatitis and other gallstone-related complications. Guidelines advocate performing cholecystectomy within 2 to 4 weeks after discharge for mild biliary pancreatitis. During this waiting period, the patient is at risk of recurrent biliary events. In current clinical practice, surgeons usually postpone cholecystectomy for 6 weeks due to a perceived risk of a more difficult dissection in the early days following pancreatitis and for logistical reasons. We hypothesize that early laparoscopic cholecystectomy minimizes the risk of recurrent biliary pancreatitis or other complications of gallstone disease in patients with mild biliary pancreatitis without increasing the difficulty of dissection and the surgical complication rate compared with interval laparoscopic cholecystectomy. Methods/Design: PONCHO is a randomized controlled, parallel-group, assessor-blinded, superiority multicenter trial. Patients are randomly allocated to undergo early laparoscopic cholecystectomy, within 72 hours after randomization, or interval laparoscopic cholecystectomy, 25 to 30 days after randomization. During a 30-month period, 266 patients will be enrolled from 18 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite endpoint of mortality and acute re-admissions for biliary events (that is, recurrent biliary pancreatitis, acute cholecystitis, symptomatic/obstructive choledocholithiasis requiring endoscopic retrograde cholangiopancreaticography including cholangitis (with/without endoscopic sphincterotomy), and uncomplicated biliary colics) occurring within 6 months following randomization. Secondary endpoints include the individual endpoints of the composite endpoint, surgical and other complications, technical difficulty of cholecystectomy and costs. Discussion: The PONCHO trial is designed to show that early laparoscopic cholecystectomy (within 72 hours) reduces the combined endpoint of mortality and re-admissions for biliary events as compared with interval laparoscopic cholecystectomy (between 25 and 30 days) after recovery of a first episode of mild biliary pancreatitis. Trial registration: Current Controlled Trials: ISRCTN72764151

Background: In predicted severe acute pancreatitis, infections have a negative effect on clinical outcome. A start of enteral nutrition (EN) within 24 hours of onset may reduce the number of infections as compared to the current practice of starting an oral diet and EN if necessary at 3-4 days after admission. Methods/Design: The PYTHON trial is a randomised controlled, parallel-group, superiority multicenter trial. Patients with predicted severe acute pancreatitis (Imrie-score ≥ 3 or APACHE-II score ≥ 8 or CRP > 150 mg/L) will be randomised to EN within 24 hours or an oral diet and EN if necessary, after 72 hours after hospital admission. During a 3-year period, 208 patients will be enrolled from 20 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite of mortality or infections (bacteraemia, infected pancreatic or peripancreatic necrosis, pneumonia) during hospital stay or within 6 months following randomisation. Secondary endpoints include other major morbidity (e.g. new onset organ failure, need for intervention), intolerance of enteral feeding and total costs from a societal perspective. Discussion: The PYTHON trial is designed to show that a very early (< 24 h) start of EN reduces the combined endpoint of mortality or infections as compared to the current practice of an oral diet and EN if necessary at around 72 hours after admission for predicted severe acute pancreatitis. Trial Registration: ISRCTN: ISRCTN18170985

Background: Emergency treatment for patients with a ruptured hepatocellular adenoma is controversial. The aim of this study was to evaluate management with selective arterial embolization. Methods: The study included 11 consecutive patients treated for ruptured hepatocellular adenomas between 2001 and 2006. After initial haemodynamic support, all patients received selective embolization of branches of the hepatic artery. The primary outcome was effectiveness in stopping the bleeding. Secondary outcomes were complications and changes in tumour size after embolization. Results: A single embolization brought haemorrhaging under control in ten patients; one patient needed three embolizations. None of the patients required emergency surgery. In the follow-up of 19 (range 7–49) months, no general or hepatobiliary complications were observed. All 25 adenomas, including those without signs of haemorrhaging in the same liver lobe, were either smaller or not detectable on computed tomography or magnetic resonance imaging after embolization, with the median diameter decreasing from 7·0 to 2·5 cm (P < 0·001). Conclusion: Selective embolization of the hepatic artery is a safe and adequate first approach in the management of patients with haemorrhaging hepatocellular adenomas. Furthermore, arterial embolization reduces the size of adenomas in the liver.

Background: The initial treatment of acute necrotizing pancreatitis is conservative. Intervention is indicated in patients with (suspected) infected necrotizing pancreatitis. In the Netherlands, the standard intervention is necrosectomy by laparotomy followed by continuous postoperative lavage (CPL). In recent years several minimally invasive strategies have been introduced. So far, these strategies have never been compared in a randomised controlled trial. The PANTER study (PAncreatitis, Necrosectomy versus sTEp up appRoach) was conceived to yield the evidence needed for a considered policy decision. Methods/design: 88 patients with (suspected) infected necrotizing pancreatitis will be randomly allocated to either group A) minimally invasive 'step-up approach' starting with drainage followed, if necessary, by videoscopic assisted retroperitoneal debridement (VARD) or group B) maximal necrosectomy by laparotomy. Both procedures are followed by CPL. Patients will be recruited from 20 hospitals, including all Dutch university medical centres, over a 3-year period. The primary endpoint is the proportion of patients suffering from postoperative major morbidity and mortality. Secondary endpoints are complications, new onset sepsis, length of hospital and intensive care stay, quality of life and total (direct and indirect) costs. To demonstrate that the 'step-up approach' can reduce the major morbidity and mortality rate from 45 to 16%, with 80% power at 5% alpha, a total sample size of 88 patients was calculated. Discussion: The PANTER-study is a randomised controlled trial that will provide evidence on the merits of a minimally invasive 'step-up approach' in patients with (suspected) infected necrotizing pancreatitis.