Erik Buskens

Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial.

BACKGROUNDnInfectious complications and associated mortality are a major concern in acute pancreatitis. Enteral administration of probiotics could prevent infectious complications, but convincing evidence is scarce. Our aim was to assess the effects of probiotic prophylaxis in patients with predicted severe acute pancreatitis.nnnMETHODSnIn this multicentre randomised, double-blind, placebo-controlled trial, 298 patients with predicted severe acute pancreatitis (Acute Physiology and Chronic Health Evaluation [APACHE II] score > or =8, Imrie score > or =3, or C-reactive protein >150 mg/L) were randomly assigned within 72 h of onset of symptoms to receive a multispecies probiotic preparation (n=153) or placebo (n=145), administered enterally twice daily for 28 days. The primary endpoint was the composite of infectious complications--ie, infected pancreatic necrosis, bacteraemia, pneumonia, urosepsis, or infected ascites--during admission and 90-day follow-up. Analyses were by intention to treat. This study is registered, number ISRCTN38327949.nnnFINDINGSnOne person in each group was excluded from analyses because of incorrect diagnoses of pancreatitis; thus, 152 individuals in the probiotics group and 144 in the placebo group were analysed. Groups were much the same at baseline in terms of patients characteristics and disease severity. Infectious complications occurred in 46 (30%) patients in the probiotics group and 41 (28%) of those in the placebo group (relative risk 1.06, 95% CI 0.75-1.51). 24 (16%) patients in the probiotics group died, compared with nine (6%) in the placebo group (relative risk 2.53, 95% CI 1.22-5.25). Nine patients in the probiotics group developed bowel ischaemia (eight with fatal outcome), compared with none in the placebo group (p=0.004).nnnINTERPRETATIONnIn patients with predicted severe acute pancreatitis, probiotic prophylaxis with this combination of probiotic strains did not reduce the risk of infectious complications and was associated with an increased risk of mortality. Probiotic prophylaxis should therefore not be administered in this category of patients.

A Step-up Approach or Open Necrosectomy for Necrotizing Pancreatitis

BACKGROUNDnNecrotizing 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.nnnMETHODSnIn 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.nnnRESULTSnThe 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).nnnCONCLUSIONSnA 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.)

Patient-reported outcome in total hip replacement: A COMPARISON OF FIVE INSTRUMENTS OF HEALTH STATUS

Our aim was to define the minimum set of patient-reported outcome measures which are required to assess health status after total hip replacement (THR). In 114 patients, we compared the pre-operative characteristics and sensitivity to change of the Oxford hip score (OHS), the Western Ontario and McMaster Universities osteoarthritis index (WOMAC), the SF-36, the SF-12 (derived from the SF-36), and the Euroqol questionnaire (EQ-5D). At one year after operation, very large effect sizes were found for the disease-specific measures, the physical domains of the SF-12, SF-36 and the EQ-5Dindex (1.3 to 3.0). Patients in Charnley class A showed more change in the OHS, WOMAC pain and function, the physical domains of the SF-36 and the EQ-5Dvas (p < 0.05) compared with those in the Charnley B and C group. In this group, the effect size for the OHS more than doubled the effect sizes of WOMAC pain and physical function. We found high correlations and correlations of change between the OHS, the WOMAC, the physical domains of the SF-12 and the SF-36 and EQ-5Dindex. The SF-36 and EQ-5D scores at one year after operation approached those of the general population. Furthermore, we found a binomial distribution of the pre-operative EQ-5Dindex score and a pre-operative discrepancy and post-operative agreement between the EQ-5Dvas and EQ-5Dindex. We recommend the use of the OHS and SF-12 in the assessment of THR. The SF-36 may be used in circumstances when smaller changes in health status are investigated, for example in the follow-up of THR. The EQ-5D is useful in situations in which utility values are needed in order to calculate cost-effectiveness or quality-adjusted life years (QALYs), such as in the assessment of new techniques in THR.

Results and Complications after Ileal Pouch Anal Anastomosis: A Meta-Analysis of 43 Observational Studies Comprising 9,317 Patients

Objective: To analyze the literature of ileal pouch anal anastomosis (IPAA) regarding complications and functional outcome, to provide audit data for individual surgeons and units to assess their own performance against and also to serve as reference standard for the assessment of novel alternatives. Background: IPAA is the standard restorative procedure for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). This operation is, however, associated with distinct rates of failure, complications and fecal incontinence. Methods: A meta-analysis on pooled incidences of complications of IPAA was conducted. Medline search and cross-reference search identified studies on IPAA (n ≧ 50). Two authors independently performed the data extraction on study characteristics, diagnosis, type of operation, pouch-related complications, pouch failure and functional results. In case of disagreement consensus was reached by joint review of the study. Estimates of pouch-related complications, pouch failure and functional results are described as pooled percentages with 95% confidence interval. Results: The initial search based on 1,206 abstracts yielded 43 studies eligible for further analysis. Indications for IPAA were UC in 87.5%, FAP in 8.9% and other diagnoses in 3.6%. The median follow-up was 36.7 months. Pouch failure was 6.8%, increasing to 8.5% in case of follow-up of more than 60 months. Pelvic sepsis occurred in 9.5%. Severe, mild and urge fecal incontinence were reported in 3.7, 17, and 7.3%, respectively.No effect of experience, duration of follow-up and type of surgical technique on the incidence of pouch failure and pelvic sepsis was demonstrable. Conclusions: Current techniques for restorative surgery after proctocolectomy are associated with non-negligible complication rates and leave room for improvement and continuation of development of alternative procedures.

Molecular genetic tests as a guide to surgical management of familial adenomatous polyposis

BACKGROUNDnIn familial adenomatous polyposis the only curative treatment is colectomy, and the choice of operation lies between restorative proctocolectomy (RPC) and colectomy with ileorectal anastomosis (IRA). The RPC procedure carries a higher morbidity but, unlike IRA, removes the risk of subsequent rectal cancer. Since the course of familial adenomatous polyposis is influenced by the site of mutation in the polyposis gene, DNA analysis might be helpful in treatment decisions.nnnMETHODSnWe evaluated the incidence of rectal cancer in polyposis patients who had undergone IRA, and examined whether the requirement for subsequent rectal excision because of cancer or uncontrollable polyps was related to the site of mutation.nnnFINDINGSnBetween 1956 and mid-1995, 225 patients registered at the Netherlands Polyposis Registry had undergone IRA. In 87 of them, a pathogenetic mutation was detected. 72 patients had a mutation located before codon 1250 and 15 patients after this codon. The cumulative risk of rectal cancer 20 years after surgery was 12%, and at that time 42% had undergone rectal excision. The risk of secondary surgery was higher in patients with mutations in the region after codon 1250 than in patients with mutations before this codon (relative risk 2.7, p < 0.05).nnnINTERPRETATIONnOn this evidence, IRA should be the primary treatment for polyposis in patients with mutations before codon 1250, and RPC in those with mutations after this codon.

Decision analysis in the management of duodenal adenomatosis in familial adenomatous polyposis.

BACKGROUND: Patients with familial adenomatous polyposis are not only at high risk of developing adenomas in the colorectum but a substantial number of patients also develop polyps in the duodenum. Because treatment of duodenal polyps is extremely difficult and it is unknown how many patients ultimately develop duodenal cancer, the value of surveillance of the upper digestive tract is uncertain. AIMS: (1) To assess the cumulative risk of duodenal cancer in a large series of polyposis patients. (2) To develop a decision model to establish whether surveillance would lead to increased life expectancy. METHODS: Risk analysis was performed in 155 Dutch polyposis families including 601 polyposis patients, and 142 Danish families including 376 patients. Observation time was from birth until date of last contact, death, diagnosis of duodenal cancer, or closing date of the study. RESULTS: Seven Dutch and five Danish patients developed duodenal cancer. The lifetime risk of developing this cancer by the age of 70 was 4% (95% confidence interval 1-7%) in the Dutch series and 3% (95% confidence interval 0-6%) in the Danish series. Decision analysis showed that surveillance led to an increase in life expectancy by seven months. CONCLUSIONS: Surveillance of the upper digestive tract led to a moderate gain in life expectancy. Future studies should evaluate whether this increase in life expectancy outweighs the morbidity of endoscopic examination and proximal pancreaticoduodenectomy.

Minimally invasive 'step-up approach' versus maximal necrosectomy in patients with acute necrotising pancreatitis (PANTER trial): design and rationale of a randomised controlled multicenter trial [ISRCTN13975868]

BackgroundThe 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/design88 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.DiscussionThe 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.

Decision analysis in the surgical treatment of colorectal cancer due to a mismatch repair gene defect

Background: In view of the high risk of developing a new primary colorectal carcinoma (CRC), subtotal colectomy rather than segmental resection or hemicolectomy is the preferred treatment in hereditary non-polyposis colorectal cancer (HNPCC) patients. Subtotal colectomy however implies a substantial decrease in quality of life. To date, colonoscopic surveillance has been shown to reduce CRC occurrence. Aims: To compare the potential health effects in terms of life expectancy (LE) for patients undergoing subtotal colectomy or hemicolectomy for CRC. Methods: A decision analysis (Markov) model was created. Information on the 10 year risk of CRC after subtotal colectomy (4%) and hemicolectomy (16%) and stages of CRCs detected within a two year surveillance interval (32% Dukes’ A, 54% Dukes’ B, and 14% Dukes’ C) were derived from two cohort studies. Five year survival rates used for the different Dukes stages (A, B, and C) were 98%, 80%, and 60%, respectively. Remaining LE values were calculated for hypothetical cohorts with an age at CRC diagnosis of 27, 47, and 67 years, respectively. Remaining LE values were also calculated for patients with CRC of Dukes’ stage A. Results: The overall LE gain of subtotal colectomy compared with hemicolectomy at ages 27, 47, and 67 was 2.3, 1, and 0.3 years, respectively. Specifically for Dukes’ stage A, this would be 3.4, 1.5, and 0.4 years. Conclusions: Unless surveillance results improve, subtotal colectomy still seems the preferred treatment for CRC in HNPCC in view of the difference in LE. For older patients, hemicolectomy may be an option as there is no appreciable difference in LE.

Attributable Risk of Common and Rare Determinants of Subarachnoid Hemorrhage

Background and Purpose— Smoking, hypertension, alcohol consumption, autosomal dominant polycystic kidney disease (ADPKD), and positive family history for subarachnoid hemorrhage (SAH) are well-known risk factors for SAH. For effective prevention, knowledge about the contribution of these risk factors to the overall occurrence of SAH in the general population is pivotal. We therefore investigated the population attributable risks of the risk factors for SAH. Methods— We retrieved the relative risk and prevalence of established risk factors for SAH from the literature and calculated the population attributable risks of these risk factors. Results— Drinking alcohol 100 to 299 g/wk accounted for 11% of the cases of SAH, drinking alcohol ≥300 g/wk accounted for 21%, and smoking accounted for 20%. An additional 17% of the cases could be attributed to hypertension, 11% to a positive family history for SAH, and 0.3% to ADPKD. Conclusions— Screening and preventive treatment of patients with familial preponderance of SAH alone will cause a modest reduction of the incidence of SAH in the general population. Further reduction can be achieved by reducing the prevalence of the modifiable risk factors alcohol consumption, smoking, and hypertension.

Comparison of the SF-6D and the EQ-5D in patients with coronary heart disease

BackgroundThe SF-6D was derived from the SF-36. A single summary score is obtained allegedly preserving the descriptive richness and sensitivity to change of the SF-36 into utility measurement. We compared the SF-6D and EQ-5D on domain content, scoring distribution, pre-treatment and change scores.MethodsThe SF-6D and the EQ-5D were completed prior to intervention and 1, 3, 6 and 12 months post-intervention in a study enrolling 561 patients with symptomatic coronary stenosis. Patients were randomized to off-pump coronary artery bypass surgery (CABG), standard on-pump CABG, or percutaneous transluminal coronary angioplasty (PTCA). Baseline and change over time scores were compared using parametric and non-parametric tests.ResultsThe relative contribution of similar domains measuring daily functioning to the utility scores differed substantially. SF-6D focused more on social functioning, while EQ-5D gave more weight to physical functioning. Pain and mental health had similar contributions. The scoring range of the EQ-5D was twice the range of the SF-6D. Before treatment, EQ-5D and SF-6D mean scores appeared similar (0.64 versus 0.63, p = 0.09). Median scores, however, differed substantially (0.69 versus 0.60), a difference exceeding the minimal important difference of both instruments. Agreement was low, with an intra-class correlation of 0.45.Finally, we found large differences in measuring change over time. The SF-6D recorded greater intra-subject change in the PTCA-group. Only the EQ-5D recorded significant change in the CABG-groups. In the latter groups changes in SF-6D domains cancelled each other out.ConclusionAlthough both instruments appear to measure similar constructs, the EQ-5D and SF-6D are quite different. The low agreement and the differences in median values, scoring range and sensitivity to change after intervention show that the EQ-5D and SF-6D yield incomparable scores in patients with coronary heart disease.