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.

Diaphragm Pacing in Patients with Spinal Cord Injury: A European Experience.

BACKGROUND: Patients with high spinal cord injury (SCI) are unable to breathe on their own and require mechanical ventilation (MV). The long-term use of MV is associated with increased morbidity and mortality. In patients with intact phrenic nerve function, patients can be partially or completely removed from MV by directly stimulating the diaphragm motor points with a diaphragm pacing system (DPS). OBJECTIVES: We describe our multicenter European experience using DPS in SCI patients who required MV. METHODS: We conducted a retrospective study of patients who were evaluated for the implantation of DPS. Patients evaluated for DPS who met the prospectively defined criteria of being at least 1 year of age, and having cervical injury resulting in a complete or partial dependency on MV were included. Patients who received DPS implants were followed for up to 1 year for device usage and safety. RESULTS: Across 3 centers, 47 patients with high SCI were evaluated for DPS, and 34 were implanted. Twenty-one patients had 12 months of follow-up data with a median DPS use of 15 h/day (interquartile range 4, 24). Eight patients (38.1%) achieved complete MV weaning using DPS 24 h/day. Two DPS-related complications were surgical device revision and a wire eruption. No other major complications were associated with DPS use. CONCLUSIONS: Diaphragm pacing represents an attractive alternative stand-alone treatment or adjunctive therapy compared to MV in patients with high SCI. After a period of acclimation, the patients were able to reduce the daily use of MV, and many could be completely removed from MV.

Comparing bowel lengthening procedures: which, when, and why?

PURPOSE OF REVIEW: Intestinal failure secondary to short bowel syndrome is still a very serious condition. Treatment consists of parenteral nutrition to provide nutrients and maintain body weight. During the last decades, intestinal lengthening procedures have become more available. The goal of this review is to discuss the results of the literature on the most commonly performed intestinal lengthening procedures. RECENT FINDINGS: Longitudinal Intestinal Lengthening, Serial Transverse Enteroplasty (STEP), and Spiral Intestinal Lengthening and Tailoring (SILT) are currently the most frequently reported intestinal lengthening procedures. The most recent literature of these procedures is described with respect to indication, technical details, complications, short and long-term outcome, and PN independence. SUMMARY: On the basis of indication, surgical complexity, complications, and clinical success, we conclude that the STEP procedure is probably the best choice for most centers.

Oxygenated versus standard cold perfusion preservation in kidney transplantation (COMPARE): a randomised, double-blind, paired, phase 3 trial.

BACKGROUND: Deceased donor kidneys are preserved in cold hypoxic conditions. Providing oxygen during preservation might improve post-transplant outcomes, particularly for kidneys subjected to greater degrees of preservation injury. This study aimed to investigate whether supplemental oxygen during hypothermic machine perfusion (HMP) could improve the outcome of kidneys donated after circulatory death. METHODS: This randomised, double-blind, paired, phase 3 trial was done in 19 European transplant centres. Kidney pairs from donors aged 50 years or older, donated after circulatory death, were eligible if both kidneys were transplanted into two different recipients. One kidney from each donor was randomly assigned using permuted blocks to oxygenated hypothermic machine perfusion (HMPO2), the other to HMP without oxygenation. Perfusion was maintained from organ retrieval to implantation. The primary outcome was 12-month estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation in pairs of donated kidneys in which both transplanted kidneys were functioning at the end of follow-up. Safety outcomes were reported for all transplanted kidneys. Intention-to-treat analyses were done. This trial is registered with the ISRCTN Registry, ISRCTN32967929, and is now closed. FINDINGS: Between March 15, 2015, and April 11, 2017, 197 kidney pairs were randomised with 106 pairs transplanted into eligible recipients. 23 kidney pairs were excluded from the primary analysis because of kidney failure or patient death. Mean eGFR at 12 months was 50·5 mL/min per 1·73 m2 (SD 19·3) in the HMPO2 group versus 46·7 mL/min per 1·73m2 (17·1) in HMP (mean difference 3·7 mL/min per 1·73m2, 95% CI -1·0 to 8·4; p=0·12). Fewer severe complications (Clavien-Dindo grade IIIb or more) were reported in the HMPO2 group (46 of 417, 11%, 95% CI 8% to 14%) than in the HMP group (76 of 474, 16%, 13% to 20%; p=0·032). Graft failure was lower with HMPO2 (three [3%] of 106) compared with HMP (11 [10%] of 106; hazard ratio 0·27, 95% CI 0·07 to 0·95; p=0·028). INTERPRETATION: HMPO2 of kidneys donated after circulatory death is safe and reduces post-transplant complications (grade IIIb or more). The 12-month difference in eGFR between the HMPO2 and HMP groups was not significant when both kidneys from the same donor were still functioning 1-year post-transplant, but potential beneficial effects of HMPO2 were suggested by analysis of secondary outcomes. FUNDING: European Commission 7th Framework Programme.

Prolonged Organ Extraction Time Negatively Impacts Kidney Transplantation Outcome.

Main Problem: Following cold aortic flush in a deceased organ donation procedure, kidneys never reach the intended 0-4°C and stay ischemic at around 20°C in the donor's body until actual surgical retrieval. Therefore, organ extraction time could have a detrimental influence on kidney transplant outcome. Materials and Methods: We analyzed the association between extraction time and kidney transplant outcome in multicenter data of 5,426 transplant procedures from the Dutch Organ Transplantation Registry (NOTR) and 15,849 transplant procedures from the United Network for Organ Sharing (UNOS). Results: Extraction time was grouped per 10-min increment. In the NOTR database, extraction time was independently associated with graft loss [HR 1.027 (1.004-1.050); p = 0.022] and with DGF [OR 1.043 (1.021-1.066); p < 0.005]. An extraction time >80 min was associated with a 27.4% higher hazard rate of graft failure [HR 1.274 (1.080-1.502); p = 0.004] and such kidneys had 43.8% higher odds of developing DGF [OR 1.438, (1.236-1.673); p < 0.005]. In the UNOS database, increasing extraction times in DCD donors were associated with DGF [OR 1.036 (1.016-1.055); p < 0.005]. An extraction time >30 min was associated with 14.5% higher odds of developing DGF [OR 1.145 (1.063-1.233); p < 0.005]. Discussion: Prolonged kidney extraction time negatively influenced graft survival in Dutch donors and increased DGF risk in all deceased donor recipients.

Same-admission versus interval cholecystectomy for mild gallstone pancreatitis (PONCHO): a multicentre randomised controlled trial.

BACKGROUND: In patients with mild gallstone pancreatitis, cholecystectomy during the same hospital admission might reduce the risk of recurrent gallstone-related complications, compared with the more commonly used strategy of interval cholecystectomy. However, evidence to support same-admission cholecystectomy is poor, and concerns exist about an increased risk of cholecystectomy-related complications with this approach. In this study, we aimed to compare same-admission and interval cholecystectomy, with the hypothesis that same-admission cholecystectomy would reduce the risk of recurrent gallstone-related complications without increasing the difficulty of surgery. METHODS: For this multicentre, parallel-group, assessor-masked, randomised controlled superiority trial, inpatients recovering from mild gallstone pancreatitis at 23 hospitals in the Netherlands (with hospital discharge foreseen within 48 h) were assessed for eligibility. Adult patients (aged ≥18 years) were eligible for randomisation if they had a serum C-reactive protein concentration less than 100 mg/L, no need for opioid analgesics, and could tolerate a normal oral diet. Patients with American Society of Anesthesiologists (ASA) class III physical status who were older than 75 years of age, all ASA class IV patients, those with chronic pancreatitis, and those with ongoing alcohol misuse were excluded. A central study coordinator randomly assigned eligible patients (1:1) by computer-based randomisation, with varying block sizes of two and four patients, to cholecystectomy within 3 days of randomisation (same-admission cholecystectomy) or to discharge and cholecystectomy 25-30 days after randomisation (interval cholecystectomy). Randomisation was stratified by centre and by whether or not endoscopic sphincterotomy had been done. Neither investigators nor participants were masked to group assignment. The primary endpoint was a composite of readmission for recurrent gallstone-related complications (pancreatitis, cholangitis, cholecystitis, choledocholithiasis needing endoscopic intervention, or gallstone colic) or mortality within 6 months after randomisation, analysed by intention to treat. The trial was designed to reduce the incidence of the primary endpoint from 8% in the interval group to 1% in the same-admission group. Safety endpoints included bile duct leakage and other complications necessitating re-intervention. This trial is registered with Current Controlled Trials, number ISRCTN72764151, and is complete. FINDINGS: Between Dec 22, 2010, and Aug 19, 2013, 266 inpatients from 23 hospitals in the Netherlands were randomly assigned to interval cholecystectomy (n=137) or same-admission cholecystectomy (n=129). One patient from each group was excluded from the final analyses, because of an incorrect diagnosis of pancreatitis in one patient (in the interval group) and discontinued follow-up in the other (in the same-admission group). The primary endpoint occurred in 23 (17%) of 136 patients in the interval group and in six (5%) of 128 patients in the same-admission group (risk ratio 0·28, 95% CI 0·12-0·66; p=0·002). Safety endpoints occurred in four patients: one case of bile duct leakage and one case of postoperative bleeding in each group. All of these were serious adverse events and were judged to be treatment related, but none led to death. INTERPRETATION: Compared with interval cholecystectomy, same-admission cholecystectomy reduced the rate of recurrent gallstone-related complications in patients with mild gallstone pancreatitis, with a very low risk of cholecystectomy-related complications. FUNDING: Dutch Digestive Disease Foundation.

A step-up approach or open necrosectomy for necrotizing pancreatitis.

BACKGROUND: Necrotizing pancreatitis with infected necrotic tissue is associated with a high rate of complications and death. Standard treatment is open necrosectomy. The outcome may be improved by a minimally invasive step-up approach. METHODS: In this multicenter study, we randomly assigned 88 patients with necrotizing pancreatitis and suspected or confirmed infected necrotic tissue to undergo primary open necrosectomy or a step-up approach to treatment. The step-up approach consisted of percutaneous drainage followed, if necessary, by minimally invasive retroperitoneal necrosectomy. The primary end point was a composite of major complications (new-onset multiple-organ failure or multiple systemic complications, perforation of a visceral organ or enterocutaneous fistula, or bleeding) or death. RESULTS: The primary end point occurred in 31 of 45 patients (69%) assigned to open necrosectomy and in 17 of 43 patients (40%) assigned to the step-up approach (risk ratio with the step-up approach, 0.57; 95% confidence interval, 0.38 to 0.87; P=0.006). Of the patients assigned to the step-up approach, 35% were treated with percutaneous drainage only. New-onset multiple-organ failure occurred less often in patients assigned to the step-up approach than in those assigned to open necrosectomy (12% vs. 40%, P=0.002). The rate of death did not differ significantly between groups (19% vs. 16%, P=0.70). Patients assigned to the step-up approach had a lower rate of incisional hernias (7% vs. 24%, P=0.03) and new-onset diabetes (16% vs. 38%, P=0.02). CONCLUSIONS: A minimally invasive step-up approach, as compared with open necrosectomy, reduced the rate of the composite end point of major complications or death among patients with necrotizing pancreatitis and infected necrotic tissue. (Current Controlled Trials number, ISRCTN13975868.)

Evaluation of the appendix during diagnostic laparoscopy, the laparoscopic appendicitis score: a pilot study.

BACKGROUND: Diagnostic laparoscopy is the ultimate diagnostic tool to evaluate the appendix. Still, according to the literature, this strategy results in a negative appendectomy rate of approximately 12-18 % and associated morbidity. Laparoscopic criteria for determining appendicitis are lacking. The goal of this study is to define clear and reliable criteria for appendicitis during diagnostic laparoscopy that eventually may safely reduce the negative appendectomy rate. METHODS: From December 2009 through April 2011, 134 patients were included and analysed in a single-centre prospective pilot study. Intraoperatively, the appendix was evaluated by the surgeon according to nine criteria for appendicitis. The operating surgeon decided whether it should be removed or not. Immediately after the operation the surgeon had to complete a questionnaire on nine criteria for appendicitis. All removed appendices were examined by a pathologist. In case the appendix was not removed, the clinical postoperative course was decisive for the (missed) presence of appendicitis. RESULTS: In 109 cases an inflamed appendix was removed; in 25 patients the appendix was normal, 3 of which had been removed. After univariate analysis and clinical judgement six variables were included in the Laparoscopic APPendicitis score (LAPP score). In this study, use of the LAPP score would have led to a positive predictive value of 99 % and a negative predictive value of 100 %. CONCLUSIONS: This study presents the LAPP score. The LAPP score is an easily applicable score that can be used by surgeons to evaluate the appendix during diagnostic laparoscopy. The score has high positive and negative predictive value. The LAPP score needs to be validated in a multicentre validation study.

Kumar versus Olsen cannulation technique for intraoperative cholangiography: a randomized trial.

BACKGROUND: There is resistance to routine intraoperative cholangiography (IOC) during cholecystectomy because it prolongs surgery and may be experienced as cumbersome. An alternative instrument may help to reduce these drawbacks and lower the threshold for IOC. This trial compared the Kumar cannulation technique to the more commonly used Olsen clamp for IOC (KOALA trial; Dutch Trial Register NTR2582). METHODS: Patients undergoing elective laparoscopic cholecystectomy were randomized between IOC using the Kumar clamp and the Olsen clamp. Primary end points were the time that the IOC procedure took and its perceived ease as measured on a visual analog scale from 0 (impossible) to 10 (effortless). To detect a difference of 33 % in IOC time, a total sample size of 40 patients was required. RESULTS: Fifty-nine patients were randomized. Nine were excluded because of conversion to open cholecystectomy before the IOC procedure. Twenty-eight patients underwent IOC with the Kumar clamp and 22 with the Olsen clamp. The success rate was 23 (82.1 %) of 28 for the Kumar clamp and 19 (86.4 %) of 22 for the Olsen clamp (p > 0.999). The mean IOC time was 10 min 27 s ± 6 min 17 s using the Kumar clamp and 11 min 34 s ± 7 min 27 s using the Olsen clamp (p = 0.537). Surgeons graded the ease of the Kumar clamp as 6.8 ± 2.7 and the Olsen clamp as 6.8 ± 2.1 (p = 0.977). CONCLUSIONS: IOC using the Kumar clamp was neither faster nor easier than using the Olsen clamp. Both clamps facilitated IOC in just over 10 min. Individual surgeon preference should dictate which clamp is used.

H2S-Enriched Flush out Does Not Increase Donor Organ Quality in a Porcine Kidney Perfusion Model.

Kidney extraction time has a detrimental effect on post-transplantation outcome. This study aims to improve the flush-out and potentially decrease ischemic injury by the addition of hydrogen sulphide (H2S) to the flush medium. Porcine kidneys (n = 22) were extracted during organ recovery surgery. Pigs underwent brain death induction or a Sham operation, resulting in four groups: donation after brain death (DBD) control, DBD H2S, non-DBD control, and non-DBD H2S. Directly after the abdominal flush, kidneys were extracted and flushed with or without H2S and stored for 13 h via static cold storage (SCS) +/- H2S before reperfusion on normothermic machine perfusion. Pro-inflammatory cytokines IL-1b and IL-8 were significantly lower in H2S treated DBD kidneys during NMP (p = 0.03). The non-DBD kidneys show superiority in renal function (creatinine clearance and FENa) compared to the DBD control group (p = 0.03 and p = 0.004). No differences were seen in perfusion parameters, injury markers and histological appearance. We found an overall trend of better renal function in the non-DBD kidneys compared to the DBD kidneys. The addition of H2S during the flush out and SCS resulted in a reduction in pro-inflammatory cytokines without affecting renal function or injury markers.

Adequate debridement and drainage of the mediastinum using open thoracotomy or video-assisted thoracoscopic surgery for Boerhaave's syndrome.

BACKGROUND: Boerhaave's syndrome has a high mortality rate (14-40%). Surgical treatment varies from a minimal approach consisting of adequate debridement with drainage of the mediastinum and pleural cavity to esophageal resection. This study compared the results between a previously preferred open minimal approach and a video-assisted thoracoscopic surgery (VATS) procedure currently considered the method of choice. METHODS: In this study, 12 consecutive patients treated with a historical nonresectional drainage approach (1985-2001) were compared with 12 consecutive patients treated prospectively after the introduction of VATS during the period 2002-2009. Baseline characteristics were equally distributed between the two groups. RESULTS: In the prospective group, 2 of the 12 patients had the VATS procedure converted to an open thoracotomy, and 2 additional patients were treated by open surgery. In the prospective group, 8 patients experienced postoperative complications compared with all 12 patients in the historical control group. Four patients (17%), two in each group, underwent reoperation. Six patients, three in each group, were readmitted to the hospital. The overall in-hospital mortality was 8% (1 patient in each group), which compares favorably with other reports (7-27%) based on drainage alone. CONCLUSIONS: Adequate surgical debridement with drainage of the mediastinum and pleural cavity resulted in a low mortality rate. The results for VATS in this relatively small series were comparable with those for an open thoracotomy.

Intra-abdominal hypertension and abdominal compartment syndrome in patients admitted to the ICU.

BACKGROUND: Intra-abdominal hypertension is frequently present in critically ill patients and is an independent predictor for mortality. Risk factors for intra-abdominal hypertension and abdominal compartment syndrome have been widely investigated. However, data are lacking on prevalence and outcome in high-risk patients. Our objectives in this study were to investigate prevalence and outcome of intra-abdominal hypertension and abdominal compartment syndrome in high-risk patients in a prospective, observational, single-center cohort study. RESULTS: Between March 2014 and March 2016, we included 503 patients, 307 males (61%) and 196 females (39%). Patients admitted to the intensive care unit with a diagnosis of pancreatitis, elective or emergency open abdominal aorta surgery, orthotopic liver transplantation, other elective or emergency major abdominal surgery and trauma were enrolled. One hundred and sixty four (33%) patients developed intra-abdominal hypertension and 18 (3.6%) patients developed abdominal compartment syndrome. Highest prevalence of abdominal compartment syndrome occurred in pancreatitis (57%) followed by orthotopic liver transplantation (7%) and abdominal aorta surgery (5%). Length of intensive care stay increased by a factor 4 in patients with intra-abdominal hypertension and a factor 9 in abdominal compartment syndrome, compared to patients with normal intra-abdominal pressure. Rate of renal replacement therapy was higher in abdominal compartment syndrome (38.9%) and intra-abdominal hypertension (8.2%) compared to patients with normal intra-abdominal pressure (1.2%). Both intensive care mortality and 90-day mortality were significantly higher in intra-abdominal hypertension (4.8% and 15.2%) and abdominal compartment syndrome (16.7% and 38.9%) compared to normal intra-abdominal pressure (1.2% and 7.1%). Body mass index (odds ratio 1.08, 95% confidence interval 1.03-1.13), mechanical ventilation at admission (OR 3.52, 95% CI 2.08-5.96) and Apache IV score (OR 1.03, 95% CI 1.02-1.04) were independent risk factors for the development of intra-abdominal hypertension or abdominal compartment syndrome. CONCLUSIONS: The prevalence of abdominal compartment syndrome was 3.6% and the prevalence of intra-abdominal hypertension was 33% in this cohort of high-risk patients. Morbidity and mortality increased when intra-abdominal hypertension or abdominal compartment syndrome was present. The patient most at risk of IAH or ACS in this high-risk cohort has a BMI > 30 kg/m2 and was admitted to the ICU after emergency abdominal surgery or with a diagnosis of pancreatitis.

Reducing the negative appendectomy rate with the laparoscopic appendicitis score; a multicenter prospective cohort and validation study.

BACKGROUND: Approximately nine percent of all acute appendectomies are unintentionally performed on a normal appendix. Failure of treatment (negative appendectomy or missed appendicitis) is associated with higher morbidity and mortality when compared to appendectomy for uncomplicated appendicitis. The Laparoscopic APPendicitis (LAPP) score was developed in order to systematically evaluate the appendix for the presence of inflammation. This study aims to determine whether the LAPP score reduces the negative appendectomy rate without missing appendicitis. METHODS: From September 2013 through May 2016, 322 adult patients presenting with a clinical suspicion of acute appendicitis and an indication for diagnostic laparoscopy were included and analyzed in this multicenter prospective validation study. Depending on the LAPP score, the appendix was either removed (n = 300) or left in situ (n = 22). These patients were compared to a historical control group of 584 patients treated at the same hospitals. The appendix was examined by a pathologist and the negative appendectomy rate was calculated. RESULTS: The negative appendectomy rate was significantly lower when the LAPP score was used (4,7% vs. 8,4%; P = 0,034). None of the patients with a negative LAPP score, in which the appendix remained in situ, developed acute appendicitis within three months. There were no significant differences in operation time, complications, or readmissions. Using the LAPP score was associated with significantly higher rates of preoperative radiological imaging (98% vs. 70%; P < 0,001). After adjusting for covariables, including radiological imaging, use of the LAPP score led to fewer treatment failures when compared to not using the LAPP score (OR: 0,48, 95% C.I. 0,251 to 0,914; P = 0,025). CONCLUSION: The LAPP score is a safe and simple tool to reduce the negative appendectomy rate during laparoscopic surgery without missing cases of acute appendicitis.

Prevention, detection, and management of infected necrosis in severe acute pancreatitis.

The management of infected peripancreatic or pancreatic necrosis in patients with severe pancreatitis has changed considerably in recent years. This review discusses the recent literature on prevention, detection, and management of infected necrosis. Though antibiotics, probiotics, and enteral nutrition have been tried to prevent infected necrosis, only enteral nutrition has consistently proven to be effective. Antibiotics and probiotics have not shown a consistent beneficial effect on outcome. Enteral nutrition reduced infectious complications and mortality in severe pancreatitis, compared with parenteral nutrition. The detection of infection of pancreatic necrosis is important for clinical decision making. Fine-needle aspiration may be used to confirm suspected infection, but if its results will not change clinical decisions, it should be omitted, as it may even introduce infection. Minimally invasive surgical, radiologic, or endoscopic intervention is increasingly being applied. In the absence of level 1 evidence, local expertise dictates which type of intervention is applied.

Matrix metalloproteinases as profibrotic factors in terminal ileum in Crohn's disease.

BACKGROUND: Returning stenosis in Crohn's disease (CD) patients is poorly understood. After resection, newly developed strictures are seen within 10 years in 50% to 70%. Matrix metalloproteinases (MMPs) are involved in matrix-turnover processes. This study analyzes spatial expression of MMP-1, MMP-3, MMP-9, tissue inhibitor of MMP-1, and collagen III to get better insight in tissue remodeling of terminal ileum of CD patients. METHODS: Expressions were analyzed on mRNA and the protein level (MMP-1, MMP-3) in segments from resected terminal ileum from CD and control patients. In CD, macroscopic distinction was made between proximal resection margin, prestenotic, and stenotic tissue. Immunohistochemistry allowed for expression analyses transmurally. RESULTS: MMP-1 and MMP-3 gene expression was up-regulated (P < 0.05) in both prestenotic and stenotic tissue. MMP-1 protein was significantly up-regulated in submucosal and muscular tissue of prestenotic parts and in muscular tissue of stenotic Crohn samples. MMP-3 protein was significantly up-regulated in all layers of prestenotic and stenotic Crohn samples. Even in submucosa of proximal resection margin tissue, MMP-3 expression was significantly higher than in controls. CONCLUSION: Surprisingly, in proximal resection margin tissue up-regulated MMP-3 was seen. This suggests that in nonresected terminal ileum, in which anastomosis is made, tissue turnover is present, which may account for the high recurrence of intestinal strictures.

Towards a standardised informed consent procedure for live donor nephrectomy: the PRINCE (Process of Informed Consent Evaluation) project-study protocol for a nationwide prospective cohort study.

INTRODUCTION: Informed consent is mandatory for all (surgical) procedures, but it is even more important when it comes to living kidney donors undergoing surgery for the benefit of others. Donor education, leading to informed consent, needs to be carried out according to certain standards. Informed consent procedures for live donor nephrectomy vary per centre, and even per individual healthcare professional. The basis for a standardised, uniform surgical informed consent procedure for live donor nephrectomy can be created by assessing what information donors need to hear to prepare them for the operation and convalescence. METHODS AND ANALYSIS: The PRINCE (Process of Informed Consent Evaluation) project is a prospective, multicentre cohort study, to be carried out in all eight Dutch kidney transplant centres. Donor knowledge of the procedure and postoperative course will be evaluated by means of pop quizzes. A baseline cohort (prior to receiving any information from a member of the transplant team in one of the transplant centres) will be compared with a control group, the members of which receive the pop quiz on the day of admission for donor nephrectomy. Donor satisfaction will be evaluated for all donors who completed the admission pop-quiz. The primary end point is donor knowledge. In addition, those elements that have to be included in the standardised format informed consent procedure will be identified. Secondary end points are donor satisfaction, current informed consent practices in the different centres (eg, how many visits, which personnel, what kind of information is disclosed, in which format, etc) and correlation of donor knowledge with surgeons' estimation thereof. ETHICS AND DISSEMINATION: Approval for this study was obtained from the medical ethical committee of the Erasmus MC, University Medical Center, Rotterdam, on 18 February 2015. Secondary approval has been obtained from the local ethics committees in six participating centres. Approval in the last centre has been sought. RESULTS: Outcome will be published in a scientific journal. TRIAL REGISTRATION NUMBER: NTR5374; Pre-results.

[Laparoscopic evaluation of the appendix]. / Laparoscopische beoordeling van de appendix.

In the Netherlands every year about 16,000 appendectomies are carried out. Despite the increase in preoperative radiological evaluation of the appendix, the negative appendectomy rate is still around 16%, with a morbidity of approximately 5%. The Dutch practice guideline on appendicitis states that a normal appendix should not be removed, although laparoscopic criteria to establish appendicitis are lacking. Retrospective analysis of negative appendectomies shows that in 51% of cases the surgeon was convinced the appendix was inflamed. Furthermore, in an online survey, 78% of responding Dutch surgeons stated that if good and reproducible criteria for identifying appendicitis during laparoscopy were available they would use them. In conclusion, laparoscopic evaluation of the appendix is not always easy and use of the laparoscopic appendicitis score (LAPP) might lead to fewer negative appendectomies with their associated morbidity. Surgeons should be more aware of the morbidity associated with a negative appendectomy.

Nonesterified fatty acids and development of graft failure in renal transplant recipients.

BACKGROUND: Chronic transplant dysfunction is the most common cause of graft failure on the long term. Proteinuria is one of the cardinal clinical signs of chronic transplant dysfunction. Albumin-bound fatty acids (FA) have been hypothesized to be instrumental in the etiology of renal damage induced by proteinuria. We therefore questioned whether high circulating FA could be associated with an increased risk for future development of graft failure in renal transplant recipients (RTR). To this end, we prospectively investigated the association of fasting concentrations of circulating nonesterified FA (NEFA) with the development of graft failure in RTR. METHODS: Baseline measurements were performed between 2001 and 2003 in outpatient RTR with a functioning graft of more than 1 year. Follow-up was recorded until May 19, 2009. Graft failure was defined as return to dialysis or retransplantation. RESULTS: We included 461 RTR at a median (interquartile range [IQR]) of 6.1 (3.3-11.3) years after transplantation. Median (IQR) fasting concentrations of NEFA were 373 (270-521) µM/L. Median (IQR) follow-up for graft failure beyond baseline was 7.1 (6.1-7.5) years. Graft failure occurred in 23 (15%), 14 (9%), and 9 (6%) of RTR across increasing gender-specific tertiles of NEFA (P=0.04). In a gender-adjusted Cox-regression analysis, log-transformed NEFA level was inversely associated with the development of graft failure (hazard ratio, 0.61; 95% confidence interval, 0.47-0.81; P<0.001). CONCLUSIONS: In this prospective cohort study in RTR, we found an inverse association between fasting NEFA concentrations and risk for development of graft failure. This association suggests a renoprotective rather than a tubulotoxic effect of NEFA. Further studies on the role of different types of NEFA in the progression of renal disease are warranted.