Nationwide Outcome of Tailored Surgery for Symptomatic Chronic Pancreatitis based on Pancreatic Morphology: Validation of the International guidelines.

OBJECTIVE: To determine the nationwide use and outcome of tailored surgical treatment for symptomatic chronic pancreatitis (CP) as advised by recent guidelines. SUMMARY BACKGROUND DATA: Randomized trials have shown that surgery is superior to endoscopy in patients with symptomatic CP, although endoscopy remains popular Recent guidelines advice to "tailor surgery" based on pancreatic morphology meaning that the least extensive procedure should be selected based on pancreatic morphology. However, nationwide, and multicenter studies On tailored surgery for symptomatic CP are lacking. METHODS: Nationwide multicenter retrospective analysis of consecutive patients undergoing surgical treatment for symptomatic CP in all seven Dutch university medical centers (2010-2020). Outcomes included volume trend, major complications, 90-day mortality, postoperative opioid use and clinically relevant pain relief. Surgical treatment was tailored based on the size of the main pancreatic duct and pancreatic head (e.g. surgical drainage for a dilated pancreatic duct, and normal size pancreatic head). RESULTS: Overall, 381 patients underwent surgery for CP: 127 surgical drainage procedures ( 33%; mostly extended lateral pancreaticojejunostomy), 129 duodenum-preserving pancreatic head resections (DPPHR, 34%, mostly Frey), and 125 formal pancreatic resections (33%, mostly distal pancreatectomy). The annual surgical volume increased slightly (Pearson r=0.744). Mortality (90-day) occurred in 6 patients (2%), and was non-significantly lower after surgical drainage (0%, 3%, 2%; P =0.139). Major complications (12%, 24%, 26%; P =0.012), postoperative pancreatic fistula grade B/C (0%, 3%, 22%; P =0.038), surgical reintervention (4%, 16%, 12%; P =0.006), and endocrine insufficiency ( 14%, 21%, 43%; P <0.001) occurred less often after surgical drainage. After a median follow-up of 11 months [IQR 3-23] good rates of clinically relevant pain relief ( 83%, 69%, 80%; P =0.082) were observed and 81% of opioid users had stopped using (83%, 78%, 84%, P =0.496). CONCLUSION: The use of surgery for symptomatic CP increased over the study period. Drainage procedures were associated with the best safety profile and excellent functional outcome, highlighting the importance of tailoring surgery based on pancreatic morphology.

Surgical techniques for mesenteric lengthening in ileoanal pouch surgery: a systematic review.

AIM: The key to successful construction of an ileal pouch-anal anastomosis (IPAA) following proctocolectomy in patients with ulcerative colitis or familial adenomatous polyposis is the ability of the pouch reservoir to reach the anus well vascularized and without tension. The aim of this systematic review was to provide an overview of previously described different surgical lengthening techniques to achieve adequate length for a tension-free IPAA. METHOD: Pubmed, Embase and Cochrane Library databases were systematically searched. Two reviewers conducted a systematic search with combinations of keywords for the surgical procedure and surgical lengthening techniques. All publications that reported one or more surgical lengthening techniques during IPAA surgery in adult patients were selected, consisting of reviews, cohort studies, case reports, human cadaver studies and expert opinions. The primary outcomes measured were the different surgical lengthening techniques and the step-by-step approach they involve that can be used during surgery to achieve adequate length for an IPAA. RESULTS: Of 1577 records reviewed, 19 articles were included in this systematic review describing at least 1181 patients (i.e. one review, four retrospective studies, five human cadaver studies, two case reports and seven expert opinions). A total of six different surgical lengthening techniques with various subtechniques were found and described, consisting of pouch folding, construction of different types of pouches, stepladder incisions, skeletonization of vessels, division and ligation of mesenteric vessels and using an interposition vein graft. No prospective or randomized controlled trials were performed regarding this topic. Quality assessment showed a medium quality of the included studies. CONCLUSION: Different surgical lengthening techniques are described in a step-by-step approach to create adequate mesenteric length during IPAA surgery, in patients in whom the ileal pouch cannot reach the dentate line.

Hypothermic oxygenated machine perfusion of the human pancreas for clinical islet isolation: a prospective feasibility study.

Due to an increasing scarcity of pancreases with optimal donor characteristics, islet isolation centers utilize pancreases from extended criteria donors, such as from donation after circulatory death (DCD) donors, which are particularly susceptible to prolonged cold ischemia time (CIT). We hypothesized that hypothermic machine perfusion (HMP) can safely increase CIT. Five human DCD pancreases were subjected to 6 h of oxygenated HMP. Perfusion parameters, apoptosis, and edema were measured prior to islet isolation. Five human DBD pancreases were evaluated after static cold storage (SCS). Islet viability, and in vitro and in vivo functionality in diabetic mice were analyzed. Islets were isolated from HMP pancreases after 13.4 h [12.9-14.5] CIT and after 9.2 h [6.5-12.5] CIT from SCS pancreases. Histological analysis of the pancreatic tissue showed that HMP did not induce edema nor apoptosis. Islets maintained >90% viable during culture, and an appropriate in vitro and in vivo function in mice was demonstrated after HMP. The current study design does not permit to demonstrate that oxygenated HMP allows for cold ischemia extension; however, the successful isolation of functional islets from discarded human DCD pancreases after performing 6 h of oxygenated HMP indicates that oxygenated HMP may be a useful technology for better preservation of pancreases.

Oxygenated End-Hypothermic Machine Perfusion in Expanded Criteria Donor Kidney Transplant: A Randomized Clinical Trial.

Importance: Continuous hypothermic machine perfusion during organ preservation has a beneficial effect on graft function and survival in kidney transplant when compared with static cold storage (SCS). Objective: To compare the effect of short-term oxygenated hypothermic machine perfusion preservation (end-HMPo2) after SCS vs SCS alone on 1-year graft survival in expanded criteria donor kidneys from donors who are brain dead. Design, Setting, and Participants: In a prospective, randomized, multicenter trial, kidneys from expanded criteria donors were randomized to either SCS alone or SCS followed by end-HMPo2 prior to implantation with a minimum machine perfusion time of 120 minutes. Kidneys were randomized between January 2015 and May 2018, and analysis began May 2019. Analysis was intention to treat. Interventions: On randomization and before implantation, deceased donor kidneys were either kept on SCS or placed on HMPo2. Main Outcome and Measures: Primary end point was 1-year graft survival, with delayed graft function, primary nonfunction, acute rejection, estimated glomerular filtration rate, and patient survival as secondary end points. Results: Centers in 5 European countries randomized 305 kidneys (median [range] donor age, 64 [50-84] years), of which 262 kidneys (127 [48.5%] in the end-HMPo2 group vs 135 [51.5%] in the SCS group) were successfully transplanted. Median (range) cold ischemia time was 13.2 (5.1-28.7) hours in the end-HMPo2 group and 12.9 (4-29.2) hours in the SCS group; median (range) duration in the end-HMPo2 group was 4.7 (0.8-17.1) hours. One-year graft survival was 92.1% (n = 117) in the end-HMPo2 group vs 93.3% (n = 126) in the SCS group (95% CI, -7.5 to 5.1; P = .71). The secondary end point analysis showed no significant between-group differences for delayed graft function, primary nonfunction, estimated glomerular filtration rate, and acute rejection. Conclusions and Relevance: Reconditioning of expanded criteria donor kidneys from donors who are brain dead using end-HMPo2 after SCS does not improve graft survival or function compared with SCS alone. This study is underpowered owing to the high overall graft survival rate, limiting interpretation. Trial Registration: isrctn.org Identifier: ISRCTN63852508.

Factors That Complicated the Implementation of a Program of Donation After Unexpected Circulatory Death of Lungs and Kidneys. Lessons Learned From a Regional Trial in the Netherlands.

BACKGROUND: Organ shortage remains a problem in transplantation. An expansion of the donor pool could be the introduction of unexpected donation after circulatory death (uDCD) donors. The goal of this study was to increase the number of transplantable kidneys and lungs by implementing a uDCD protocol. METHODS: A comprehensive protocol for uDCD donation was developed and implemented in the emergency departments (EDs) of 3 transplant centers. All out-of-hospital cardiac arrest (OHCA) patients were screened for uDCD donation. Inclusion criteria were declaration of death in the ED, age (<50 y for kidneys, <65 y for lungs), witnessed arrest, and basic and advanced life support started within 10 and 20 min, respectively. RESULTS: A total of 553 OHCA patients were reported during the project, of which 248 patients survived (44.8%). A total of 87 potential lung and 42 potential kidneys donors were identified. A broad spectrum of reasons resulted in termination of all uDCD procedures. Inclusion and organ-specific exclusion criteria were the most common reason for not proceeding followed by consent. None of the potential donors could be converted into an actual donor. CONCLUSION: Although uDCD potential was shown by successful recognition of potential donors in the ED, we were not able to transplant any organs during the study period. The Dutch Emergency medical service guidelines to stop futile OHCA in the prehospital setting and the strict use of inclusion and exclusion criteria like age and witnessed arrest hampered the utilization. A prehospital uDCD protocol to bring all OHCA patients who are potential uDCD candidates to an ED would be helpful in creating a successful uDCD program.

Hypothermic Oxygenated Machine Perfusion of the Human Donor Pancreas.

BACKGROUND: Transplantation of beta cells by pancreas or islet transplantation is the treatment of choice for a selected group of patients suffering from type 1 diabetes mellitus. Pancreata are frequently not accepted for transplantation, because of the relatively high vulnerability of these organs to ischemic injury. In this study, we evaluated the effects of hypothermic machine perfusion (HMP) on the quality of human pancreas grafts. METHODS: Five pancreata derived from donation after circulatory death (DCD) and 5 from donation after brain death (DBD) donors were preserved by oxygenated HMP. Hypothermic machine perfusion was performed for 6 hours at 25 mm Hg by separate perfusion of the mesenteric superior artery and the splenic artery. Results were compared with those of 10 pancreata preserved by static cold storage. RESULTS: During HMP, homogeneous perfusion of the pancreas could be achieved. Adenosine 5'-triphosphate concentration increased 6,8-fold in DCD and 2,6-fold in DBD pancreata. No signs of cellular injury, edema or formation of reactive oxygen species were observed. Islets of Langerhans with good viability and in vitro function could be isolated after HMP. CONCLUSIONS: Oxygenated HMP is a feasible and safe preservation method for the human pancreas that increases tissue viability.

Early Steroid Withdrawal Compared With Standard Immunosuppression in Kidney Transplantation - Interim Analysis of the Amsterdam-Leiden-Groningen Randomized Controlled Trial.

BACKGROUND: The optimal immunosuppressive regimen in kidney transplant recipients, delivering maximum efficacy with minimal toxicity, is unknown. METHODS: The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open-label trial in 305 kidney transplant recipients, in which 2 immunosuppression minimization strategies-one consisting of early steroid withdrawal, the other of tacrolimus minimization 6 months after transplantation-were compared with standard immunosuppression with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid. The primary endpoint was kidney function. Secondary endpoints included death, primary nonfunction, graft failure, rejection, discontinuation of study medication, and a combined endpoint of treatment failure. An interim analysis was scheduled at 6 months, that is, just before tacrolimus minimization. RESULTS: This interim analysis revealed no significant differences in Modification of Diet in Renal Disease between the early steroid withdrawal group and the standard immunosuppression groups (43.2 mL/min per 1.73 m2 vs 45.0 mL/min per 1.73 m2, P = 0.408). There were also no significant differences in the secondary endpoints of death (1.0% vs 1.5%; P = 0.737), primary nonfunction (4.1% vs 1.5%, P = 0.159), graft failure (3.1% vs 1.5%, P = 0.370), rejection (18.6% vs 13.6%, P = 0.289), and discontinuation of study medication (19.6% vs 12.6%, P = 0.348). Treatment failure, defined as a composite endpoint of these individual secondary endpoints, was more common in the early steroid withdrawal group (P = 0.027), but this group had fewer serious adverse events and a more favorable cardiovascular risk profile. CONCLUSIONS: Based on these interim results, early steroid withdrawal is a safe short-term immunosuppressive strategy. Long-term outcomes, including a comparison with tacrolimus minimization after 6 months, will be reported in the final 2-year analysis.

Abdominal organ procurement in the Netherlands - an analysis of quality and clinical impact.

Between March 2012 and August 2013, 591 quality forms were filled out for abdominal organs in the Netherlands. In 133 cases (23%), there was a discrepancy between the evaluation from the procuring and transplanting surgeons. Injuries were seen in 148 (25%) organs of which 12 (2%) led to discarding of the organ: one of 133 (0.8%) livers, five of 38 (13%) pancreata and six of 420 (1.4%) kidneys (P < 0.001). Higher donor BMI was a risk factor for procurement-related injury in all organs (OR: 1.06, P = 0.011) and donor after cardiac death (DCD) donation in liver procurement (OR: 2.31, P = 0.034). DCD donation is also associated with more pancreata being discarded due to injury (OR: 10.333, P = 0.046). A higher procurement volume in a centre was associated with less injury in pancreata (OR = -0.95, P = 0.013) and kidneys (OR = -0.91, P = 0.012). The quality form system efficiently monitors the quality of organ procurement. Although there is a relatively high rate of organ injury, the discard rate is low and it does not significantly affect 1-year graft survival for any organ. We identified higher BMI as a risk factor for injury in abdominal organs and DCD as a risk factor in livers. A higher procurement volume is associated with fewer injuries.

Outcome of pancreas transplantation from donation after circulatory death compared to donation after brain death.

INTRODUCTION: To overcome the gap of organ shortage grafts from donation after circulatory death (DCD) can be used. This review evaluates the outcomes after DCD pancreas donation compared to donation after brain death (DBD). MATERIALS AND METHODS: A literature search was performed using Medline, Embase, and PubMed databases. All comparative cohort studies reporting the outcome after DCD and DBD pancreas transplantation were included. All data were assessed according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. To evaluate the event rates, pooled odds ratios (ORs) as well as the 95% confidence intervals (CI) were calculated. Since the number of studies is small we used the random-effects model only to overcome heterogeneity. RESULTS: There is no difference in 1-year pancreas graft survival (OR 1.092, CI 95% 0.649-1.837, P = 0.741) or patient survival (OR 0.699, CI 95% 0.246-1.985, P = 0.502). Simultaneous pancreas-kidney (SPK) transplantation showed significantly higher graft survival rates compared to pancreas transplantation alone (87.2% vs. 76.6%, P < 0.001 in DBD and 86.5% vs. 74.9%, P < 0.001 in DCD). DCD SPK grafts show a higher delayed kidney graft function rate compared to DBD SPK-grafts (OR 0.209, CI 95% 0.104-0.421, P < 0.001). There is significantly less pancreas graft thrombosis after DBD-donation (OR 0.567, CI 95% 0.340-0.946, P = 0.030). We found no difference in the HbA1c level at 1-year follow-up with a median of 5.4% in both groups and a mean of 5.63% (DCD) vs 5.43% (DBD). DISCUSSION: DCD pancreas transplantation has comparable patient and 1-year graft survival rates and should be considered a safe alternative for DBD pancreas transplantation.

Kidney temperature course during living organ procurement and transplantation.

Little is known about the actual kidney graft temperature during the 2nd warm ischemia time (WIT2). We aimed to determine the actual temperature course of the WIT2, with emphasis on the 15 °C metabolic threshold. Data of 152 consecutive adult living donor kidney transplantations were collected. The mean WIT2 was 41.3 ± 10.1 (SD) minutes with a temperature of 5.4 °C at baseline which gradually increased to 13.7, 17.4, and 20.2 °C after 10, 20, and 30 min, respectively. The percentage of kidneys with a temperature of 15 °C or higher was 81.2% after 20 min and 97.5% after 30 min. Duration of surgery (95% CI: -0.017 to -0.002, P = 0.02), multiple veins (95% CI: 0.0003-2.720, P = 0.05) and WIT2 (95% CI: 0.016-0.099, P = 0.006) were associated with a rapid temperature increase. No correlation could be determined between a rapid temperature rise and diminished graft function. This study showed a rapid increase in kidney temperature during WIT2, wherein the 15 °C threshold was reached within 20 min in more than 80% of the patients.

Chronic Inguinal Pain After Kidney Transplantation, a Common and Underexposed Problem.

BACKGROUND: The incidence and impact of chronic inguinal pain after kidney transplantation is not clearly established. A high incidence of pain after inguinal hernia repair, a comparable surgical procedure, suggests an underexposed problem. METHODS: Between 2011 and 2013, 403 consecutive patients who underwent kidney transplantation were invited to complete the Caroline Comfort Scale (CCS) and Visual Analog Scale (VAS) in order to assess the incidence of chronic inguinal pain and movement disabilities, complemented by questions regarding comorbidity during follow-up. RESULTS: The response rate was 58 % (n = 199) with a median follow-up of 22 months (IQR 12-30). In total, 90 patients (45 %) reported a CCS > 0 and 64 patients (32 %) experienced at least mild but bothersome complaints. Most inguinal complaints were reported during bending over and walking with a mean CCS score of 1.1 (SD ± 2.2) and 1.2 (SD ± 2.4), respectively. A high body mass index (BMI), delayed graft function, and the need for a second operation were associated with a higher CCS score on univariate analysis. Using multivariate analysis, only BMI (p = 0.02) was considered an independent risk factor for chronic inguinal pain. CONCLUSIONS: The incidence of chronic inguinal pain is a common though underexposed complication after kidney transplantation. More awareness to prevent neuropathic pain seems indicated.

Successful Kidney and Lung Transplantation From a Deceased Donor With Blunt Abdominal Trauma and Intestinal Perforation.

The number of organ donors is limited by many contraindications for donation and poor quality of potential organ donors. Abdominal infection is a generally accepted contraindication for donation of abdominal organs. We present a 43-year-old man with lethal brain injury, blunt abdominal trauma, and intestinal perforation. After withdrawal of life-sustaining treatment and circulatory arrest, a minilaparotomy confirmed abdominal contamination with intestinal content. After closure of the abdomen, organs were preserved with in situ preservation with an aortic cannula inserted via the femoral artery. Thereafter, the kidneys were procured via bilateral lumbotomy to reduce the risk of direct bacterial contamination; lungs were retrieved following a standard practice. There was no bacterial or fungal growth in the machine preservation fluid of both kidneys. All organs were successfully transplanted, without postoperative infection, and functioned well after 6 months. We hereby show that direct contamination of organs can be avoided with the use of in situ preservation and retroperitoneal procurement. Intestinal perforation is not an absolute contraindication for donation, although the risk of bacterial or fungal transmission has to be evaluated per case.

Multiple Renal Arteries in Kidney Transplantation: A Systematic Review and Meta-Analysis.

BACKGROUND: The use of grafts with multiple renal arteries (MRA) in renal transplantation has not been clearly established. MATERIAL/METHODS: A systematic literature review used predefined terms to search PubMed, EMBASE, and the Cochrane Library for all studies since 1985 that included more than 50 MRA grafts. A total of 23 studies, comprising a total of 18,289 patients, were eligible to be included in the meta-analysis. RESULTS: Patients who received an MRA graft compared to single renal artery (SRA) grafts showed significantly higher complication rates (13.8% vs. 11.0%, OR 1.393, p<0.0001), more delayed graft function (10.3% vs. 8.2%, OR 1.333, p=0.022), and had an associated significantly lower 1-year graft survival (93.2% vs. 94.5%, OR 0.819, p=0.034). Both the creatinine level and the warm ischemia time (WIT) were significantly higher in patients with MRA grafts but showed high heterogeneity (I² 98% for WIT and I² 70% for creatinine level). Although MRA grafts were associated with more complications compared to SRA grafts, long-term outcomes were similar for 5-year graft survival (81.4% vs. 81.6%) and 1- and 5-year patient survival (95.4% and 89.6% in MRA group vs. 95.4% and 87.0% in SRA group, respectively). CONCLUSIONS: MRA grafts were associated with a higher risk of complication and delayed graft function but had comparable long-term outcomes for graft and patient survival.

Hypoxia and Complement-and-Coagulation Pathways in the Deceased Organ Donor as the Major Target for Intervention to Improve Renal Allograft Outcome.

BACKGROUND: In the last few decades, strategies to improve allograft survival after kidney transplantation have been directed to recipient-dependent mechanisms of renal injury. In contrast, no such efforts have been made to optimize organ quality in the donor. Optimizing deceased donor kidney quality opens new possibilities to improve renal allograft outcome. METHODS: A total of 554 kidney biopsies were taken from donation after brain death (DBD) and donation after cardiac death (DCD) kidneys before donation, after cold ischemia and after reperfusion. Healthy living donor kidney biopsies served as controls. Transcriptomics was performed by whole genome microarray analyses followed by functional pathway analyses. RESULTS: Before organ retrieval and before cessation of blood circulation, metabolic pathways related to hypoxia and complement-and-coagulation cascades were the major pathways enhanced in DBD donors. Similar pathways were also enriched in DCD donors after the first warm ischemia time. Shortly after reperfusion of DCD grafts, pathways related to prolonged and worsening deprivation of oxygen were associated with delayed graft function in the recipient. CONCLUSION: In conclusion, this large deceased donor study shows enrichment of hypoxia and complement-and-coagulation pathways already in DBD donors before cessation of blood flow, before organ retrieval. Therefore, future intervention therapies should target hypoxia and complement-and-coagulation cascades in the donor to improve renal allograft outcome in the recipient.

Novel insights in localization and expression levels of C5aR and C5L2 under native and post-transplant conditions in the kidney.

AIMS: The complement system, and especially C5a, plays an important role in the pathophysiology of renal diseases and post-transplant renal injury. The two receptors for C5a are C5a receptor (C5aR) and C5a-like-receptor-2 (C5L2). Only renal C5aR expression has been reported, although exact localization and alterations in expression after transplantation are unknown. MATERIALS AND RESULTS: Renal C5aR and C5L2 expression and localization were analyzed immunohistochemically. C5aR and C5L2 expression was analyzed in human kidney biopsies obtained from living donors and patients suffering from acute tubular necrosis, acute cellular and vascular rejection or IF/TA. C5aR was expressed in the thick ascending limb of Henle's loop and first part of the distal convoluted tubule (DCT). Under inflammatory conditions, C5aR was de novo expressed in proximal tubuli. C5L2 was expressed in the kidney and localized to DCT1, DCT2 and connecting tubule. Persistent distal tubular expression of both receptors was demonstrated after renal transplantation. CONCLUSIONS: This study shows distinct renal expression patterns for C5aR and C5L2. Our findings suggest a functional role for renal C5L2 rather than being a C5a decoy receptor. Future studies focusing on renal C5a-C5aR interaction should take differential C5aR and C5L2 expression into account, alongside abundant C5aR expression on infiltrating cells.

A randomized clinical trial of living donor nephrectomy: a plea for a differentiated appraisal of mini-open muscle splitting incision and hand-assisted laparoscopic donor nephrectomy.

A randomized controlled trial was designed to compare various outcome variables of the retroperitoneal mini-open muscle splitting incision (MSI) technique and the transperitoneal hand-assisted laparoscopic technique (HAL) in performing living donor nephrectomies. Fifty living kidney donors were randomized to MSI or HAL. Primary endpoint was pain experience scored on a visual analogue scale (VAS). After MSI living donors indicated lower median (range) VAS scores at rest than HAL living donors on postoperative day 2.5 [10 (0-44) vs. 15 (0-70), P = 0.043] and day 3 [7 (0-28) vs. 10 (0-91), P = 0.023] and lower VAS scores while coughing on postoperative day 3 [20 (0-73) vs. 42 (6-86), P = 0.001], day 7 [8 (0-66) vs. 33 (3-76), P < 0.001] and day 14 [2 (0-17) vs. 12 (0-51), P = 0.009]. The MSI technique also resulted in reduced morphine requirement, better scores on three domains of the RAND-36, reduced costs and reduced CRP and IL-6 levels. The HAL technique was superior in operating time and postoperative decrease of hemoglobin level. The MSI technique is superior to the HAL technique in performing living donor nephrectomies with regard to postoperative pain experience. This study reopens the discussion of the way to go in performing the living donor nephrectomy.