H. Sijbrand Hofker

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.)

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.

Renal Function Equations before and after Living Kidney Donation: A Within-Individual Comparison of Performance at Different Levels of Renal Function

BACKGROUND AND OBJECTIVES The Modification of Diet in Renal Disease (MDRD) study equation and the Cockcroft-Gault (CG) equation perform poorly in the (near-) normal range of GFR. Whether this is due to the level of GFR as such or to differences in individual characteristics between healthy individuals and patient with chronic kidney disease (CKD) is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We evaluated the performance of MDRD, CG per BSA (CG/(BSA)) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations compared with measured GFR (mGFR; I-iothalamate) at 4 months before and 2 months after donation in 253 consecutive living kidney donors. RESULTS mGFR declined from 103 ± 15 to 66 ± 11 ml/min per 1.73 m(2) after donation. All equations underestimated mGFR at both time points. Arithmetic performance analysis showed improved performance after donation of all equations, with significant reduction of bias after donation. Expressed as percentage difference, mGFR-estimated GFR (eGFR) bias was reduced after donation only for CG/(BSA). Finally, in 295 unselected individuals who were screened for donation, mGFR was below the cutoff for donation of 80 ml/min per 1.73 m(2) in 19 individual but in 166, 98, and 74 for MDRD, CDK-EPI, and CG/(BSA), respectively. CONCLUSIONS A higher level of GFR as such is associated with larger absolute underestimation of true GFR by eGFR. For donor screening purposes, eGFR should be interpreted with great caution; when in doubt, true GFR should be performed to prevent unjustified decline of prospective kidney donors.

Effects of preexistent hypertension on blood pressure and residual renal function after donor nephrectomy.

Background. Living kidney donor selection has become more liberal with acceptation of hypertensive donors. Here, we evaluate short-term and 1- and 5-year renal outcome of living kidney donors with preexistent hypertension. Methods. We compared outcome of hypertensive donors by gender, age, and body mass index with matched control donors. Hypertension was defined as predonation antihypertensive drug use. All donors had glomerular filtration rate (125I-iothalamate) and effective renal plasma flow (131I-hippuran) measured 4 months before and 2 months after donation. A subset of donors had serum creatinine measured 1 year after donation or a renal function measurement 5 years after donation. Results. Included were 47 hypertensive donors and 94 control donors (both 53% male; mean age, 57±7 years; and body mass index, 28±4 kg/m2). Pre- and early postdonation, systolic blood pressure, and mean arterial pressure were significantly higher in hypertensive donors. Control donors showed a rise in diastolic blood pressure after donation, and thus the predonation difference was lost postdonation. Both at 1 year (29 hypertensive donors, 58 controls) and 5 years after donation (13 hypertensive donors and 26 controls) blood pressure was similar. Renal function was similar at all time points. Discussion. In summary, hypertensive living kidney donors have similar outcome in terms of blood pressure and renal function as control donors, early and 1 and 5 years after donation.

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

Background: Returning stenosis in Crohns 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.

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

BackgroundBoerhaave’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.MethodsIn 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.ResultsIn 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.ConclusionsAdequate 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.

Late anastomotic leakage in colorectal surgery: a significant problem.

Reported incidence rates of colorectal anastomotic leakage (AL) vary between 2.5 and 20%. There is little information on late anastomotic leakage (LAL). The aim of this study was to determine the incidence of LAL after colorectal resection.

A human model of intra-abdominal hypertension: even slightly elevated pressures lead to increased acute systemic inflammation and signs of acute kidney injury

Intra-abdominal hypertension may have catastrophic effects in the critically ill, but its pathophysiology is only partially understood. In a human model of intra-abdominal hypertension of 12 mmHg, 50 living kidney donors were randomized between hand-assisted laparoscopic nephrectomy and open nephrectomy. In the laparoscopic group intra-abdominal hypertension of 12 mmHg was induced. Markers of inflammation and renal function were obtained in both groups peri-operatively. Slightly elevated intra-abdominal pressure leads to increased acute CRP, IL-6 and plasma NGAL.

Analysis of biomarker expression in severe endometriosis and determination of possibilities for targeted intraoperative imaging

To evaluate the expression of biomarkers in endometriotic tissue in order to determine the most promising molecules for targeted intraoperative imaging.

The Value of a 24/7 Online Nationwide Multidisciplinary Expert Panel for Acute Necrotizing Pancreatitis

Figure 1.Work flow expert panel consultation. 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 Acommon gastrointestinal reason for acute hospitalization. Approximately 20% of patients with acute pancreatitis develop necrotizing pancreatitis. In approximately 30% of these patients, secondary infection of the necrosis occurs, which almost always requires an invasive intervention. Diagnosing infected necrosis on clinical grounds can be difficult. Furthermore, even if infected necrosis is proven, international guidelines advise to postpone invasive intervention to around 4 weeks after disease onset. This allows for necrotic collections to encapsulate (ie, walled-off necrosis), thereby technically facilitating intervention and reducing the risk of complications such as perforation and bleeding. However, the clinical condition of some patients does not permit a delay in intervention. Clinical decision making regarding the indications for and timing of invasive intervention and preferred approach (percutaneous, surgical, or endoscopic) can, therefore, be challenging. Moreover, the incidence of infected necrotizing pancreatitis is low and even tertiary referral centers may only treat 10–15 patients per year. Several international, multidisciplinary, and multicenter approaches have been initiated to improve the care for patients with pancreatitis and facilitate clinical research. In recent years, multiple national study groups have been formed worldwide, for example, in the Netherlands, the United States, Germany, Switzerland, and Hungary. Also evidenceand consensus-based guidelines were composed by international experts in the field. International scientific collaborations were initiated, for example, Pancreas2000