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Background Immunomodulators and biologicals are essential in current IBD management, but are associated with increased risk of infections. Considering the growing number of treatment options, the benefit-risk balance of drugs is becoming increasingly important in clinical decision making. To date, post-marketing surveillance studies mainly focus on severe infections. As a result, data on mild and moderate infections are scarce. These infections take longer to clear in immunosuppressed patients and can substantially impact quality of life. We aimed to assess the incidence of all infections and identify risk factors for the development of infections in IBD patients. Methods We previously developed and validated a Patient-Reported Infections Questionnaire (PRIQ), with excellent diagnostic accuracy, covering 15 infection categories with a 3-month recall period. The current prospective, multicentre, observational cohort study was performed between Jun, 1 2020 and Jul, 1 2021, enrolling consecutive IBD patients using the PRIQ implemented in myIBDcoach, an established telemedicine platform. Infection severity was defined as mild (self-limiting or topical treatment), moderate (oral antibiotics, antivirals or antifungals) or severe (hospitalization or IV treatment). Incidence rates (IR) were calculated for all infections, stratified for severity and subtype. Risk factors for infections were identified using multivariable logistic regression. Results In total, 629 IBD patients were included which completed 2391 PRIQs during 572 person-years (PY) of follow-up, resulting in 990 reported infections, corresponding to IRs of 17.3, 11.8, 5.1, and 0.4 per 10PY for all, mild, moderate, and severe infections, respectively (Tables 1-2). Upper respiratory tract (IR 26.9/100PY) and urinary tract infections (IR 14.8/100PY) were the most commonly reported mild and moderate infections (Table 3). Compared to patients without treatment, patients on immunosuppressives more frequently experienced infections of any severity (mild: IR ratio (IRR) 1.57 [95%CI 1.21-2.06] p Conclusion In this real-world prospective study, immune suppressive therapy was associated with mild and moderate infections of any kind in IBD patients. These infections particularly occur in females, smokers, patients with higher BMI and more comorbidities. This information should be considered in personalised treatment selection.

Background Clinicians face difficulty in positioning biologics and JAK inhibitors in anti-TNF refractory ulcerative colitis (UC) patients. Head-to-head trials comparing the efficacy of vedolizumab and tofacitinib in UC patients are lacking. We aimed to compare the effectiveness and safety of vedolizumab and tofacitinib in anti-TNF experienced UC patients in our prospective, nationwide registry using a propensity score weighted cohort. Methods UC patients who failed anti-TNF treatment (with or without thiopurine) and initiated vedolizumab or tofacitinib treatment subsequently, were identified in the observational prospective Initiative on Crohn and Colitis (ICC) Registry. We selected patients with both clinical (Simple Clinical Colitis Activity Index (SCCAI) >2) and biochemical (C-reactive protein (CRP) >5mg/L or faecal calprotectin (FC) >250 µg/g) or endoscopic disease activity (endoscopic MAYO score ≥ 1) at initiation of therapy. Patients previously treated with vedolizumab or tofacitinib were excluded. Corticosteroid-free clinical remission (SCCAI Results Overall, 83 vedolizumab and 65 tofacitinib treated patients were included (table 1). Propensity score weighted analysis showed that tofacitinib treated patients were more likely to achieve corticosteroid-free clinical remission at week 12, 24 and 52 compared to vedolizumab treated patients (OR: 5.87, 95%CI:3.55–9.70, P Conclusion In tofacitinib treated, anti-TNF experienced, UC patients, we observed that a higher proportion of patients achieved corticosteroid-free remission after 12, 24 and 52 weeks compared to vedolizumab treated patients. In addition, more tofacitinib treated patients achieved biochemical remission at week 12 and 24. There was no statistically significant difference in severe adverse events.

Background Therapeutic drug monitoring (TDM) is an approach to improve treatment effectiveness of anti-TNF therapy in Inflammatory Bowel Disease (IBD), but timing and threshold trough levels (TL) are still subject of investigation, especially in paediatric populations. The aims of our study were (1) to analyse induction – and post-induction infliximab TLs (respectively after 6 and 14 weeks) to predict sustained biochemical and clinical remission between 6 and 12 months in paediatric patients with IBD, and (2) to define paediatric threshold TLs at these timepoints. Methods We performed a retrospective study in 70 anti-TNF naïve paediatric IBD patients from two centres who were treated with an induction scheme of 5 mg/kg on 0, 2 and 6 weeks, and subsequently every approximately 8 weeks. We measured infliximab TLs at week 6 and 14 combined with (non)-invasive markers for disease activity. Patients were in sustained biochemical and clinical remission when they were asymptomatic and had normalised CRP and faecal calprotectin between 6 and 12 months after initiating therapy. Receiver operating characteristic (ROC) analysis was used to determine infliximab TL thresholds that best predicted sustained biochemical remission. Results Median infliximab TL at 6 and 14 weeks were higher for children in sustained remission versus children who were not (TL6 p=0.028 and TL14 p=0.028). Area under the ROC curve (AUROC) for infliximab TL6 and TL14 to predict sustained biochemical remission was 0.68 (95% Confidence Interval [CI] 0.53-0.83) and 0.67 (95%CI 0.53-0.82), respectively (Figure 1 and 2). The optimal infliximab thresholds were 13.2 mg/L and 6.9 mg/L for TL6 and TL14, respectively, yielding a sensitivity and specificity of 70% and 68% for TL6 and 57% and 76% for TL14. Figure 1 ROC curve of infliximab trough level at 6 weeks for predicting sustained remission between 6 months to 12 months. Figure 2 ROC curve of infliximab trough level at 14 weeks for predicting sustained remission between 6 months to 12 months. Conclusion In children with IBD treated with a regular infliximab induction scheme, infliximab TLs at week 6 and 14 both predicted sustained clinical and biochemical remission between 6 and 12 months after initiating therapy. TDM and early dose optimization may improve infliximab effectiveness and drug survival.

Background Real-world treatment of ulcerative colitis (UC) requires a patient-centric, holistic definition of ‘comprehensive remission' that goes beyond standard regulatory definitions. In an international initiative, we reviewed aspects of UC that affect patients and attempted to achieve consensus on which aspects should be considered in a definition of ‘comprehensive remission’, using a modified Delphi process. This initiative summarized expert consensus recommendations on aspects of UC that are important to patients and that affect their lives, how to measure and score these aspects, and objective markers of mucosal inflammation that are relevant to evaluate in remission, such as endoscopic and histological activity and inflammatory biomarkers. Methods The Delphi consensus panel comprised 10 physicians with expertise in UC and one patient advocate, and two additional physicians chaired the process. To inform the Delphi statements, we asked 18 patients about their experiences of living with UC in remission, asked panel members about their experience of treating patients and systematically reviewed associations between outcome measures in UC. Panel members voted on a 6-point Likert scale in three rounds of anonymous voting, the final round of which was preceded by a live discussion. Consensus was met if ≥ 67% of the panel agreed with the statement (4–6 on the 6-point Likert scale). Statements not meeting consensus in voting rounds 1 and 2 were revised and any not meeting consensus by the end of voting round 3 were discarded (Figure 1). Results The panel agreed that a definition of comprehensive remission should include aspects of UC that are currently measured in clinical trials (blood in stools, stool frequency, disease-related quality of life [QoL], endoscopic remission, histological inflammatory activity, inflammatory biomarkers and discontinuation of corticosteroids), but also additional patient-reported symptoms should be added. These were bowel urgency, abdominal pain, extra-intestinal manifestations, fatigue and sleep disturbance (Table 1). Suggestions for how the severity could be measured and thresholds for remission were agreed for each aspect, with the exception of extra-intestinal manifestations. Disease activity evaluated using ultrasound was voted as important to consider but was not recommended to be included in a measure of comprehensive remission at this stage. Conclusion We used a robust methodology to reach agreement and provide recommendations on the aspects of UC that can be used to define comprehensive remission and assessed in clinical practice. We plan to develop this as a combined measure which may also have applicability in clinical trials.

BACKGROUND: The LIR!C trial showed that laparoscopic ileocaecal resection is a cost-effective treatment that has similar quality-of-life outcomes to treatment with infliximab, an anti-tumour necrosis factor (TNF) drug. We aimed to compare long-term outcomes of both interventions and identify baseline factors associated with the duration of treatment effect in each group.METHODS: In this retrospective follow-up study, we collected data from patients who participated in the LIR!C trial, a multicentre randomised controlled trial that compared quality of life after surgical resection versus infliximab in adult patients with non-stricturing and immunomodulator-refractory ileocaecal Crohn's disease. From Jan 1 to May 1, 2018, we collected follow-up data from the time from enrolment in the LIR!C trial until the last visit at either the gastrointestinal surgeon or gastroenterologist. In this study, outcomes of interest were need for surgery or repeat surgery or anti-TNF therapy, duration of treatment effect, and identification of factors associated with the duration of treatment effect. Duration of treatment effect was defined as the time without need for additional Crohn's disease-related treatment (corticosteroids, immunomodulators, biologics, or surgery).FINDINGS: We collected long-term follow-up data for 134 (94%) of 143 patients included in the LIR!C trial, of whom 69 were in the resection group and 65 were in the infliximab group. Median follow-up was 63·5 months (IQR 39·0-94·5). In the resection group, 18 (26%) of 69 patients started anti-TNF therapy and none required a second resection. 29 (42%) patients in the resection group did not require additional Crohn's disease-related medication, although 14 (48%) of these patients were given prophylactic immunomodulator therapy. In the infliximab group, 31 (48%) of 65 patients had a Crohn's disease-related resection, and the remaining 34 patients maintained, switched, or escalated their anti-TNF therapy. Duration of treatment effect was similar in both groups, with a median time without additional Crohn's disease-related treatment of 33·0 months (95% CI 15·1-50·9) in the resection group and 34·0 months (0·0-69·3) in the infliximab group (log-rank p=0·52). In both groups, therapy with an immunomodulator, in addition to the allocated treatment, was associated with duration of treatment effect (hazard ratio for resection group 0·34 [95% CI 0·16-0·69] and for infliximab group 0·49 [0·26-0·93]).INTERPRETATION: These findings further support laparoscopic ileocaecal resection as a treatment option in patients with Crohn's disease with limited (affected segment ≤40 cm) and predominantly inflammatory terminal ileitis for whom conventional treatment is not successful.FUNDING: None.

OBJECTIVE: To describe the pooled learning curves of Ivor Lewis totally minimally invasive esophagectomy (TMIE) in hospitals stratified by predefined hospital- and surgeon-related factors.BACKGROUND: Ivor Lewis (TMIE is known to have a long learning curve which is associated with considerable learning associated morbidity. It is unknown whether hospital and surgeon characteristics are associated with more efficient learning.METHODS: A retrospective analysis of prospectively collected data of consecutive Ivor Lewis TMIE patients in 14 European hospitals was performed. Outcome parameters used as proxy for efficient learning were learning curve length, learning associated morbidity, and the plateau level regarding anastomotic leakage and textbook outcome. Pooled incidences were plotted for the factor-based subgroups using generalized additive models and 2-phase models. Casemix predicted outcomes were plotted and compared with observed outcomes. The investigated factors included annual volume, TMIE experience, clinic visits, courses and fellowships followed, and proctor supervision.RESULTS: This study included 2121 patients. The length of the learning curve was shorter for centers with an annual volume >50 compared to centers with an annual volume CONCLUSIONS: More efficient learning was observed in centers with higher annual volume. Visiting an expert clinic, completing a fellowship, or implementation under a proctor's supervision were not associated with more efficient learning.

Background Crohn’s disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel diseases (IBD), affect approximately seven million people globally. The continuous rise in IBD prevalence and the aging of populations will inevitably lead to an increasing use of health care resources. In parallel with these trends, continuing innovations in IBD therapeutics, diagnostics, and preventatives are creating more options for IBD patients seeking to reduce their disease burden. These trends pose an imminent burden on health care systems and require that we identify modifiable cost drivers in IBD care and develop strategies for delivering equitable and affordable care for all patients. Methods This Lancet Gastroenterology & Hepatology Commission, consisting of a diverse faculty of health care professionals with expertise in the field of IBD and health economists, was formed to deliver an extensive summary of the literature and discuss key topics on the costs and cost-effectiveness of treating IBD in the present, and how this is likely to look in the future. Furthermore, it offers suggestions for how to deliver affordable IBD care in the coming years. The report’s focus was on high-income countries in Europe, North America, Australia and New Zealand, and Asia. Results The Commission drew together a wide range of expertise to discuss the current costs of IBD care, the drivers of increasing costs, as well as how to deliver affordable care for IBD in the future. The key conclusions are that (i) increases in health care costs must be evaluated against improved disease control and reductions in indirect costs, and (ii) that overarching systems for data interoperability, registries, and big data approaches must be established for continuous assessment of effectiveness, costs, and cost-effectiveness of care. International collaborations should be sought in order to evaluate novel models of care (such as value-based health care, including integrated health care and participatory health care models), as well as to improve the education and training of clinicians, patients, and policymakers. Measures to reduce the costs of IBD care are summarised in Table 1. Conclusion Increases in health care costs must be evaluated against improved disease control and reductions in indirect costs. Evaluations should be systematically aligned between countries and regions. Detailed analysis of the current epidemiology and the likely effects of changing IBD management on disease course and socioeconomic outcomes is essential; and will become even more imperative in the era of precision medicine, where complex biotechnologies will require expensive analyses, highly skilled personnel, and drug development for what may sometimes be relatively small patient groups.

Background Crohn’s disease (CD) patients often require surgical interventions and post operative recurrence is common. Data regarding risk factors for recurrence in representative cohorts are scarce. We assessed the risk-factors of recurrence of CD after ileocolic resection (ICR) in a population based cohort. Methods Patients who underwent a primary or re-resection for ileocolic CD between 2003 and 2017 were included. The primary endpoint was clinical recurrence. The secondary outcome was surgical recurrence. A Cox regression model was used to assess recurrence free survival. Results 289 patients were included of which 120 male (41.5%). Most common indication for ICR was stricturing (B2) disease in 146 (50.5)%), followed by penetrating (B3) disease in 101 (34.9%). Recurrence occurred in 189/289 patients (65.4%) after a median follow up of 2.3 years and surgical recurrence in 22 (7.6%) after median follow up of 4.8 years. Multivariate analysis showed a significant higher chance of clinical recurrence in smokers (HR: 1.659 (95% CI: 1.230; 2.238)) (p Conclusion Our study in a population based cohort confirmed risk factors for recurrence consistent with current evidence, but also identifies novel and less frequently found risk factors. Medical therapy reduces the risk for recurrence on a population level. We found an association between involved resection margin and recurrence. Differences between studies may be caused by differences in patient selection or definition of recurrence. Confirmation of this finding in independent representative cohort is necessary. This indicates a need for a standardised scientific database for future prospective research.

Background Treatment goals for Crohn’s disease (CD) tend to shift from clinical towards endoscopic remission as a potential means to reduce intestinal damage. Additionally, sustained corticosteroid (CS) free remission is warranted to prevent drug related side effects. In clinical trials, long-term efficacy of treatment is assessed by a range of outcome measures at variable time points. Besides clinical activity, it is recommended by the EMA to measure biochemical and endoscopic activity, given the poor correlation between commonly applied clinical activity indices and mucosal inflammation. Finally, STRIDE advices to add a PROM given the frequent perception gap in disease control between patient and health care professionals. Moreover, the relapsing-remitting nature of CD challenges timing of efficacy evaluations. Use of cross-sectional outcomes only on predetermined moments disregards the health status in between these measurements. In this systematic review, we provide an overview of the outcomes employed to assess long-term efficacy of maintenance (drug) therapy or treatment strategies in randomized controlled trials and their open label extensions in CD patients. Methods A systematic search of Pubmed and Embase databases was performed. Giving the emerging treatment goals, the search was restricted to trials published since 2007. Two independent reviewers screened titles and abstracts and selected eligible trials. We assessed whether and when long-term (i.e. >48 weeks) clinical, biochemical and/or endoscopic efficacy outcomes were used. In addition, data on patient perspective and CS use were collected. Results Sixty-seven out of 1947 articles were included (figure 1). Clinical activity indices were used in 66 studies (99%) as long-term efficacy outcome, with 20 studies (30%) taking into account concomitant CS use. C-reactive protein concentration was (part of) an outcome in 29 studies (43%), and faecal calprotectin in 15 studies (22%). Endoscopic activity was evaluated in 30 studies (45%). PROMs were used in 29 studies (43%), with IBDQ being the most frequently used. Seven studies measure long-term clinical, biochemical, endoscopic activity and patient perspective, in three studies a sustained CS free status as part of the outcome was required (table 1). In most studies cross-sectional measures or multiple measurements over time, so-called panel data, were used. Conclusion We established a lack of objective outcome measures of inflammation and patient perspective in clinical trials in CD, consequently missing pivotal data to evaluate current treatment goals. Additionally, cross-sectional outcomes on fixed time points were mostly applied, resulting in loss of efficacy information in chronic relapsing-remitting diseases.

Background The thiopurines, azathioprine (AZA) and mercaptopurine (MP), are effective and remain standard treatment options in steroid sparing and maintaining remission in patients with inflammatory bowel disease (IBD). Approximately 25% of patients discontinue within three months after treatment initiation due to adverse events, of which about half due to hepatotoxicity. We hypothesise that identification of patients with an increased risk of adverse events and timely treatment optimisation (e.g. dose adjustment, adjuvant allopurinol) can prevent treatment failure due to adverse events. The primary objective of this prospective observational multicentre study was to optimise and validate a proposed hepatotoxicity predictive algorithm in IBD patients starting AZA or MP therapy. Methods We adapted an algorithm from a previous study to predict the risk of developing hepatotoxicity in thiopurine drug treatment using multivariable logistic regression and a receiver operating characteristic curve. The determinants age, BMI and 6-MMPR-concentration one week after start of treatment (T=1) were inserted as continuous variables in this algorithm. Sex was inserted as a dichotomous variable. Inclusion criteria were adult thiopurine-naive IBD patients initiating AZA or MP treatment. Subjects were treated according to guidelines and followed for 12 weeks. The primary study outcome was hepatotoxicity within 12 weeks, defined as ALAT > 2x ULN or an R value ((ALAT / ULN ALAT)/(AP / ULN ALP)) ≥ 5. The hepatotoxicity- and no-hepatotoxicity groups were compared using the Mann-Whitney U-test. Results In total, 255 patients were included from Dec 2015 to June 2019, of whom 26 were excluded because of no actual start with AZA or MP (n=18), loss to follow up (n=7) or no IBD diagnosis (n=1). Out of 229 patients 21 (9%) developed hepatotoxicity. Five out of 21 patients (24%) in the hepatotoxicity-group and 123 out of 208 patients (59%) in the no-hepatotoxicity-group had to be excluded for analysis (see Figure 1). Ninety-three % of patients received MP with a median dose of 0.7 mg/kg (95%CI 0.3–1.4 mg/kg). Median dose of AZA (7%) was 2.0 mg/kg (95%CI 1.1 - 2.6 mg/kg). There was a difference between the hepatotoxicity and no-hepatotoxicity group in BMI (28 versus 24, p=0.022) and 6-MMPR/6-TGN ratio at T=1 (16 versus 9, p=0.027). In Table 1, the number of true positives, true negatives, false positives and false negatives are presented. The diagnostic values are shown in Table 2. A specificity of 77% (95%CI 66–85%) and a sensitivity of 50% (95%CI 26–75%) was obtained. Conclusion In conclusion, the adapted algorithm does not accurately predict hepatotoxicity in this cohort of patients on relatively low-dose thiopurine treatment.

Background Conventional thiopurines such as azathioprine (AZA) and mercaptopurine (MP) remain drugs of choice in maintaining remission and corticosteroid sparing in inflammatory bowel disease (IBD). Early discontinuation of thiopurine therapy occurs frequently, due to slow onset of effect and a relatively high frequency of early adverse drug reactions (ADR). Some ADR such as hepatotoxicity and gastro-intestinal complaints are associated with the thiopurine metabolite concentrations 6-thioguanine nucleotides (6-TGN) or 6-methylmercaptopurine ribonucleotides (6-MMPR), in particular elevated 6-MMPR concentrations or unfavorable 6-MMPR/6-TGN ratios. Early measurement of thiopurine metabolites may help to optimize thiopurine therapy in IBD. The aim of this study was to assess the predictive value of thiopurine metabolite measurement one week after thiopurine therapy initiation on discontinuation during the first three months of therapy. Methods This was a multicenter prospective observational study in the Netherlands. Consecutive IBD patients who initiated thiopurine therapy were included and measurement of thiopurine metabolites was performed after 7 days (6 – 8) of treatment (T1). Patients were monitored for 12 weeks to document occurrence of ADR and early treatment discontinuation. Switching to an alternative thiopurine or adding allopurinol (as co-medication) was also considered as treatment discontinuation (to prevent ADR). 6-MMPR concentrations and 6-MMPR/6-TGN ratios were separately analyzed (Mann-Whitney U-tests) regarding therapy discontinuation within 12 weeks. P-values of ≤0.05 were considered statistically significant. Results In total, 255 patients were included, of which 83 were excluded due to either missing blood samples on T1 (n=54), dose adjustments within 12 weeks (n=25) or a delayed T1 measurement (n=4). Of the remaining 172 patients, 79 patients were male (46%), 102 patients had Crohn’s disease (59%) and 157 patients were treated with MP (91%). In total, 88 (51%) patients continued thiopurine therapy and 84 patients (49%) discontinued therapy within 12 weeks. Median 6-MMPR concentrations (1,295 versus 1,589 pmol x 108 red blood cells) and 6-TGN/6-MMPR ratios (8.8 versus 11.4) did not differ significantly between patients who continued versus discontinued therapy within 12 weeks (Figures 1 and 2). Conclusion In this study thiopurine metabolites at T1 did not relate to discontinuation of thiopurine therapy within 12 weeks. We will conduct additional pharmacodynamic studies to corroborate our hypothesis that early metabolite measurements may be of individual patients’ benefit.

Background Ustekinumab (UST) is a monoclonal antibody which binds to the p40 subunit of interleukins-12/23 and is an effective and safe treatment for patients with Crohn’s disease (CD). An association between serum drug concentrations and therapeutic outcomes is required to justify Therapeutic Drug Monitoring (TDM). However, it is currently unknown if TDM is of additional value in UST treatment. We assessed the exposure-biochemical response relationship of UST trough concentrations at week, 8 in a prospective, real-world setting. Methods We performed a prospective study in CD patients with biochemical, radiologic or endoscopic disease activity in four academic centers in the Netherlands. All patients (n=90) received weight adjusted intravenously (IV) UST induction. First subcutaneous (SC), 90 mg induction dose was administered at week, 8 followed by a maintenance dose of, 90 mg SC every, 8 or, 12 weeks, at the discretion of the physician. Blood for drug levels were drawn at different time points during follow up (median follow up was, 52 weeks (IQR, 50–52)) with a median amount of, 2 measurements (IQR, 1–4) per patient. Plasma concentrations of UST were determined by means of a validated enzyme-linked immune assay. A population pharmacokinetic (PK) model was developed based on these measurements and the UST FDA review documents. Subsequently, the individual UST concentration time course during treatment were predicted using the developed model. Corticosteroid-free clinical remission (HBI ≤, 4) and biochemical remission (C-reactive protein (CRP) ≤5 mg/L or faecal calprotectin (FC) ≤, 250) were assessed at week, 12 and, 24. Quartile analysis and logistic regression was performed to analyse if UST concentration at week, 8 was associated with biochemical remission rates at week, 24. An independent cohort of, 34 patients was used to validate the primary outcomes. Results Basis characteristics of all patients are shown in table 1. Median estimated trough concentrations of UST were, 4.23 µg/mL (IQR, 2.79–5.83) and, 7.19 µg/mL (IQR, 3.30–10.67) at week, 8 in the primary and validation cohort respectively. Patients achieving biochemical remission at week, 12 and, 24 had statistically significantly higher UST levels at week, 8 (P Conclusion In this real-world cohort of CD patients, ustekinumab levels of ≥5.9 µg/mL at week, 8 were associated with higher biochemical remission rates at week, 12 and, 24.

The well-being of residents, our future medical specialists, is not only beneficial to the individual physician but also conditional for delivering high-quality patient care. Therefore, the authors further explored how residents experience their own well-being in relation to their professional and personal life. The authors conducted a qualitative study based on a phenomenological approach. From June to October 2013, 13 in-depth interviews were conducted with residents in various training programs using a semi-structured interview guide to explore participants’ experience of their well-being in relation to their professional life. The data were collected and analyzed through an iterative process using the thematic network approach. Effort–reward balance and perceived autonomy were dominant overarching experiences in influencing residents’ well-being. Experiencing sufficient autonomy was important in residents’ roles as caregivers, as learners and in their personal lives. The experienced effort–reward balance could both positively and negatively influence well-being. We found two categories of ways that influence residents’ experience of well-being; (1) professional lives: delivering patient care, participating in teamwork, learning at the workplace and dealing with the organization and (2) personal lives: dealing with personal characteristics and balancing work–life. In residents’ well-being experiences, the effort–reward balance and perceived autonomy are crucial. Additionally, ways that influence residents’ well-being are identified in both their professional and personal lives. These dominant experiences and ways that influence well-being could be key factors for interventions and residency training adaptations for enhancing residents’ well-being.

Neoadjuvant treatment consisting of five cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.4 Gy), followed by esophagectomy, is the standard treatment for resectable esophageal cancer in The Netherlands. It remains unclear whether intensification of neoadjuvant therapy leads to better outcomes. This study analyzed the outcomes of intensified chemoradiotherapy. We included patients who were deemed eligible for esophagectomy between January 2008 and December 2014. Neoadjuvant therapy consisted of six cycles of carboplatin (area under the curve = 2 mg/mL/min) and paclitaxel (50 mg/m2 of body surface area) and concurrent radiotherapy (50.4 Gy administered in 28 fractions of 1.8 Gy each, 5 days per week), followed by esophagectomy. Of the 176 patients included in this study, 73% underwent a resection. At a median follow-up of 29.3 months for the total cohort, median disease-free survival (DFS) was 22.5 months. DFS at 3 and 5 years was 42% and 36%, respectively, while the overall survival (OS) rates were 47% and 38%, respectively. In addition, the 5-year DFS and OS rates of our resection group were 44% and 48%, respectively. In 102 patients (58%), grade 3 or higher adverse events were observed, mainly hematological. The postoperative mortality rate within 30 days was 4%, and pathological complete response was achieved in 35% of patients. Intensification of neoadjuvant chemoradiotherapy for patients with potentially resectable esophageal cancer is well tolerated, yielding high pathological complete response rates, but adverse events occurred frequently, and survival compared with conventional neoadjuvant chemoradiotherapy seems similar. Therefore, intensification of neoadjuvant chemoradiotherapy should not be routinely used.

Background Treatment of patients with ileocaecal Crohn's disease who have not responded to conventional therapy is commonly scaled up to biological agents, but surgery can also offer excellent short-term and long-term results. We compared laparoscopic ileocaecal resection with infliximab to assess how they affect health-related quality of life. Methods In this randomised controlled, open-label trial, in 29 teaching hospitals and tertiary care centres in the Netherlands and the UK, adults with non-stricturing, ileocaecal Crohn's disease, in whom conventional therapy has failed were randomly allocated (1:1) by an internet randomisation module with biased-coin minimisation for participating centres and perianal fistula to receive laparoscopic ileocaecal resection or infliximab. Eligible patients were aged 18–80 years, had active Crohn's disease of the terminal ileum, and had not responded to at least 3 months of conventional therapy with glucocorticosteroids, thiopurines, or methotrexate. Patients with diseased terminal ileum longer than 40 cm or abdominal abscesses were excluded. The primary outcome was quality of life on the Inflammatory Bowel Disease Questionnaire (IBDQ) at 12 months. Secondary outcomes were general quality of life, measured by the Short Form-36 (SF-36) health survey and its physical and mental component subscales, days unable to participate in social life, days on sick leave, morbidity (additional procedures and hospital admissions), and body image and cosmesis. Analyses of the primary outcome were done in the intention-to-treat population, and safety analyses were done in the per-protocol population. This trial is registered at the Dutch Trial Registry (NTR1150). Findings Between May 2, 2008, and October 14, 2015, 73 patients were allocated to have resection and 70 to receive infliximab. Corrected for baseline differences, the mean IBDQ score at 12 months was 178·1 (95% CI 171·1–185·0) in the resection group versus 172·0 (164·3–179·6) in the infliximab group (mean difference 6·1 points, 95% CI −4·2 to 16·4; p=0·25). At 12 months, the mean SF-36 total score was 112·1 (95% CI 108·0–116·2) in the resection group versus 106·5 (102·1–110·9) in the infliximab group (mean difference 5·6, 95% CI −0·4 to 11·6), the mean physical component score was 47·7 (45·7–49·7) versus 44·6 (42·5–46·8; mean difference 3·1, 4·2 to 6·0), and the mean mental component score was 49·5 (47·0–52·1) versus 46·1 (43·3–48·9; mean difference 3·5, −0·3 to 7·3). Mean numbers of days of sick leave were 3·4 days (SD 7·1) in the resection group versus 1·4 days (4·7) in the infliximab group (p

BACKGROUND: Previous studies have suggested that sigmoidectomy with primary anastomosis is superior to Hartmann's procedure. The likelihood of stoma reversal after primary anastomosis has been reported to be higher and reversal seems to be associated with lower morbidity and mortality. Although promising, results from these previous studies remain uncertain because of potential selection bias. Therefore, this study aimed to assess outcomes after Hartmann's procedure versus sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy, for perforated diverticulitis with purulent or faecal peritonitis (Hinchey III or IV disease) in a randomised trial. METHODS: A multicentre, randomised, open-label, superiority trial was done in eight academic hospitals and 34 teaching hospitals in Belgium, Italy, and the Netherlands. Patients aged between 18 and 85 years who presented with clinical signs of general peritonitis and suspected perforated diverticulitis were eligible for inclusion if plain abdominal radiography or CT scan showed diffuse free air or fluid. Patients with Hinchey I or II diverticulitis were not eligible for inclusion. Patients were allocated (1:1) to Hartmann's procedure or sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy. Patients were enrolled by the surgeon or surgical resident involved, and secure online randomisation software was used in the operating room or by the trial coordinator on the phone. Random and concealed block sizes of two, four, or six were used, and randomisation was stratified by age (

Background Residents' well-being is essential for both the individual physician and the quality of patient care they deliver. Therefore, it is important to maintain or possibly enhance residents' well-being. We investigated (i) the influence of mind fitness training (MFT) on quality of care-related well-being characteristics: work engagement, empathy, work satisfaction and stress perception and explored (ii) residents' perceptions of MFT.Methods A multicenter study was conducted in eight Dutch teaching hospitals, from September 2012 to February 2014, using mixed methods-that is, quantitative and qualitative approaches to data collection and analysis. Eighty-nine surgical residents were invited to participate in pre- and post-intervention questionnaire surveys. Twenty-two residents participated in MFT and were additionally invited to evaluate the training by post-intervention interviews including open questions.Results At baseline 22 (100 %) residents in intervention group and 47 (70.2 %) residents in control group, and post-intervention 20 (90.9 %) residents in intervention group and 41 (66.1 %) residents in control group completed the questionnaires. In intervention-group, residents' specialty satisfaction increased by 0.23 point on 5-point Likert scale (95 % CI 0.23-0.24, P Conclusion Mind fitness training could improve residents' empathy, specialty satisfaction, stress perception, and focusing skills, and was positively received by surgical residents.

Summary Background Incisional hernia is a frequent long-term complication after abdominal surgery, with a prevalence greater than 30% in high-risk groups. The aim of the PRIMA trial was to evaluate the effectiveness of mesh reinforcement in high-risk patients, to prevent incisional hernia. Methods We did a multicentre, double-blind, randomised controlled trial at 11 hospitals in Austria, Germany, and the Netherlands. We included patients aged 18 years or older who were undergoing elective midline laparotomy and had either an abdominal aortic aneurysm or a body-mass index (BMI) of 27 kg/m 2 or higher. We randomly assigned participants using a computer-generated randomisation sequence to one of three treatment groups: primary suture; onlay mesh reinforcement; or sublay mesh reinforcement. The primary endpoint was incidence of incisional hernia during 2 years of follow-up, analysed by intention to treat. Adjusted odds ratios (ORs) were estimated by logistic regression. This trial is registered at ClinicalTrials.gov, number NCT00761475. Findings Between March, 2009, and December, 2012, 498 patients were enrolled to the study, of whom 18 were excluded before randomisation. Therefore, we included 480 patients in the primary analysis: 107 were assigned primary suture only, 188 were allocated onlay mesh reinforcement, and 185 were assigned sublay mesh reinforcement. 92 patients were identified with an incisional hernia, 33 (30%) who were allocated primary suture only, 25 (13%) who were assigned onlay mesh reinforcement, and 34 (18%) who were assigned sublay mesh reinforcement (onlay mesh reinforcement vs primary suture, OR 0·37, 95% CI 0·20–0·69; p=0·0016; sublay mesh reinforcement vs primary suture, 0·55, 0·30–1·00; p=0·05). Seromas were more frequent in patients allocated onlay mesh reinforcement (34 of 188) than in those assigned primary suture (five of 107; p=0·002) or sublay mesh reinforcement (13 of 185; p=0·002). The incidence of wound infection did not differ between treatment groups (14 of 107 primary suture; 25 of 188 onlay mesh reinforcement; and 19 of 185 sublay mesh reinforcement). Interpretation A significant reduction in incidence of incisional hernia was achieved with onlay mesh reinforcement compared with sublay mesh reinforcement and primary suture only. Onlay mesh reinforcement has the potential to become the standard treatment for high-risk patients undergoing midline laparotomy. Funding Baxter; B Braun Surgical SA.

Questions: What are important forest characteristics determining colonization of forest patches by forest understorey species? Location: Planted forests on land recently reclaimed from the sea, the Netherlands. Methods: We related the distribution of forest specialist species in the understorey of 55 forests in Dutch IJsselmeer polders to the following forest characteristics: age, area, connectivity, distance to mainland (as a proxy for distance to seed source) and path density. We used species of the Fraxino-Ulmetum association for the Netherlands as reference for species that could potentially occur in the study area. Results: Area and age of the surveyed forests explained a large part of the variation in overall species composition and species number of forest plant species. The importance of connectivity and distance to the mainland of forest habitats became apparent only at a more detailed level of dispersal groups and individual species. The importance of forest parameters differed between dispersal groups and also between individual species. After 60 years, 75% of the potential pool of wind-dispersed species has reached the polders, whereas this was only 50% for species lacking specific adaptations to long-distance dispersal. However, the average percentage of successful colonizing species present per forest was substantially lower, ranging from 15 to 37%. Conclusions: The data strongly suggest that the colonization process in polder forests is still in its initial phase, during which easily dispersed species dominate the vegetation. Colonization success of common species that lack adaptations to long-distance dispersal is affected by spatial configuration of the forests, and most rare species that could potentially occur in these forests are still absent. Implications for conservation of rare species in fragmented landscapes are discussed

Background Long-term results of laparoscopically assisted versus open ileocolic resection for Crohn's disease were evaluated in a randomized trial. Methods Sixty patients who underwent ileocolic resection between 1999 and 2003 were followed prospectively. Primary outcomes were reoperation, readmission and repeat resection rates for recurrent Crohn's disease. Secondary outcomes were quality of life (QOL), body image and cosmesis. Results Five patients were lost to follow-up. Median follow-up was 6·7 (interquartile range 5·7–7·9) years. Sixteen of 29 and 16 of 26 patients remained relapse free after ileocolic resection in the laparoscopic and open groups respectively (risk difference 6 (95 per cent confidence interval − 20 to 32) per cent). Resection of recurrent Crohn's disease was necessary in two of 29 versus three of 26 patients (risk difference 5 (−11 to 20) per cent). Overall reoperation rates for recurrent Crohn's disease, incisional hernia and adhesion-related problems were two of 29 versus six of 26 (risk difference 16 (−3 to 35) per cent). QOL was similar, whereas body image and cosmesis scores were significantly higher after laparoscopy (P = 0·029 and P < 0·001 respectively). Conclusion Laparoscopically assisted ileocolic resection results in better body image and cosmesis, whereas open surgery is more likely to produce incisional hernia and obstruction.

Over the past 20 years evidence has accumulated confirming the immunomodulatory role of the appendix in ulcerative colitis (UC). This led to the idea that appendectomy might alter the clinical course of established UC. The objective of this body of research is to evaluate the short-term and medium-term efficacy of appendectomy to maintain remission in patients with UC, and to establish the acceptability and cost-effectiveness of the intervention compared to standard treatment.These paired phase III multicenter prospective randomised studies will include patients over 18 years of age with an established diagnosis of ulcerative colitis and a disease relapse within 12 months prior to randomisation. Patients need to have been medically treated until complete clinical (Mayo score3) and endoscopic (Mayo score 0 or 1) remission. Patients will then be randomised 1:1 to a control group (maintenance 5-ASA treatment, no appendectomy) or elective laparoscopic appendectomy plus maintenance treatment. The primary outcome measure is the one year cumulative UC relapse rate - defined both clinically and endoscopically as a total Mayo-score ≥5 with endoscopic subscore of 2 or 3. Secondary outcomes that will be assessed include the number of relapses per patient at 12 months, the time to first relapse, health related quality of life and treatment costs, and number of colectomies in each arm.The ACCURE and ACCURE-UK trials will provide evidence on the role and acceptability of appendectomy in the treatment of ulcerative colitis and the effects of appendectomy on the disease course.NTR2883 ; ISRCTN56523019.

Background Publications in peer-reviewed journals are the main determinants of research rating and funding. The present study assesses worldwide scientific contributions in the field of surgical research. Methods Fifteen major surgical journals were selected for a bibliometric search in Medline/PubMed over a 6-year period (2000–2005). All articles with abstracts were totalled according to country of corresponding author. Publications (total and corrected for population size) and journal impact factor were assessed according to country. Results A total of 18 717 articles were identified. Fifteen countries generated 88·8 per cent of these: the USA produced 42·1 per cent, Japan 9·1 per cent and the UK 7·6 per cent. When corrected for population size, the Netherlands, Sweden and Switzerland topped the ranking; the USA was sixth. Ireland and Switzerland scored the highest mean impact factor. Conclusion The USA is the most productive country in terms of absolute number of surgical publications in the selected journals. However, when population size is taken into consideration, certain smaller European countries were more prolific.

OBJECTIVE: The aim of the study was to compare laparoscopic-assisted and open ileocolic resection for primary Crohn's disease in a randomized controlled trial. METHODS: Sixty patients were randomized for laparoscopic-assisted or open surgery. Primary outcome parameter was postoperative quality of life (QoL) during 3 months of follow-up, measured by SF-36 and GIQLI questionnaire. Secondary parameters were operating time, morbidity, hospital stay, postoperative morphine requirement, pain, and costs. RESULTS: Patient characteristics were not different. Conversion rate was 10% (n=3). Median operating time was longer in laparoscopic compared with open surgery (115 versus 90 minutes; P

Since an active isoform of plasma hemopexin (Hx) has been proposed to be a potential effector molecule in minimal change disease (MCD), we tested plasma and urine samples from subjects with MCD in relapse (n =18) or in remission (n =23) (after treatment with prednisolone) for presence or activity of Hx. For comparison, plasma or urine from proteinuric subjects with focal and segmental glomerulosclerosis (FSGS, n =11), membranoproliferative glomerulonephritis (MPGN, n =9), IgA nephropathy (n =5) or healthy control donors (n =10), were incorporated into the study. Electrophoresis and Western blotting methods were used for evaluation of the Hx status, whereas protease activity of Hx was tested upon kidney tissue in vitro according to standard methods. The results show (1) a decreased mean titer of plasma Hx exclusively in MCD relapse subjects as compared with MCD in remission (0.21 +/- 0.14 mg/ml vs 0.44 +/- 0.06 mg/ml; p

Contains fulltext : 152458.pdf (Publisher’s version ) (Closed access) Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterized by the development of multiple hamartomatous polyps in the gastrointestinal tract. Polyps are most common in the colorectum (98 % of patients) and the stomach (14 %). Causative mutations for JPS have been identified in two genes to date, SMAD4 and BMPR1A. SMAD4 mutations are associated with a higher incidence of gastric polyposis. In this case report, we describe two patients with massive gastric polyposis associated with a SMAD4 mutation. Both presented with anaemia and both had colonic polyps. Initial endoscopic findings revealed giant rugal folds suggestive of Menetrier disease. However, as other possible gastropathies could not be differentiated on the basis of histology, a definitive diagnosis of JPS required additional mutation analysis. In patients with polyposis predominant in or limited to the stomach, establishing a diagnosis based solely on the pathological features of polyps can be challenging due to difficulties in differentiating JPS from other hypertrophic gastropathies. Mutation analysis should be considered early in the diagnostic process in cases of suspected juvenile polyposis, thus facilitating rapid diagnosis and adequate follow-up.

Background: Incisional hernia is one of the most frequent postoperative complications after abdominal surgery. Patients with an abdominal aortic aneurysm and patients with a body mass index of 27 or higher have an increased risk to develop incisional hernia. Primary mesh augmentation is a method in which the abdominal wall is strengthened to reduce incisional hernia incidence. This study focused on the short-term results of the PRImary Mesh Closure of Abdominal Midline Wounds trial, a multicenter double blind randomized controlled trial. Methods: Between 2009 and 2012 patients were included if they were operated via midline laparotomy, and had an abdominal aortic aneurysm or a body mass index of 27 or higher. Patients were randomly assigned to either receive primary suture, onlay mesh augmentation (OMA), or sublay mesh augmentation. Results: Outcomes represent results after 1-month follow-up. A total of 480 patients were randomized. During analysis, significantly (P = 0.002) more seromas were detected after OMA (n = 34, 18.1%) compared with primary suture (n = 5, 4.7%) and sublay mesh augmentation (n = 13, 7%). No differences were discovered in any of the other outcomes such as surgical site infection, hematoma, reintervention, or readmission. Multivariable analysis revealed an increase in seroma formation after OMA with an odds ratio of 4.3 (P = 0.004) compared with primary suture and an odds ratio of 2.9 (P = 0.003) compared with sublay mesh augmentation. Conclusions: On the basis of these short-term results, primary mesh augmentation can be considered a safe procedure with only an increase in seroma formation after OMA, but without an increased risk of surgical site infection.

Partial hypoxanthine-guanine phosphoribosyl transferase (HGPRT) deficiency, also known as the Kelley-Seegmiller syndrome, can give rise to a wide range of neurological symptoms, and renal insufficiency. Biochemically, it is characterized by high uric acid concentrations in blood, high uric acid and hypoxanthine excretion in urine, and decreased activity of hypoxanthine-guanine phosphoribosyl transferase activity (HGPRT). However, normal uric acid concentrations in blood and uric acid excretions in urine have been reported. Here, a boy is presented with normal development and suffering from recurrent attacks of acute renal failure with slightly to clearly increased urinary uric acid excretion. Between these attacks, episodes of elevated urinary excretion of uric acid were observed with normal blood concentrations of uric acid and normal urinary excretion of hypoxanthine. HGPRT activity in erythrocytes, leukocytes, and fibroblasts was found to be strongly decreased. This case shows that not only normal blood uric acid but also normal urinary hypoxanthine concentrations do not exclude the diagnosis of partial HGPRT deficiency. (c) 2006 Elsevier Inc. All rights reserved.

In recent decades, numerous prospective randomized surgical trials have been performed in the Netherlands. Due to the unexpected high mortality rate in the PROPATRIA-trial, legislation pertaining to research involving human subjects has recently been changed. The resulting considerable legal and administrative burdens and financial consequences now necessitate a different way of organising clinical research in non-academic hospitals.

Improvements in quality of life (QOL) obtained by weight loss have mainly been reported after bariatric surgery. QOL has not been investigated in surgical patients first losing weight by nonsurgical means followed by a surgical intervention and never simultaneously by two QOL-a generic and a disease-specific-questionnaires. Prospective data were obtained from 40 consecutive patients (mean age 36.6 years, body weight 142.4 kg, body mass index (BMI) 46.5 kg/m2). Two different QOL questionnaires, the generic Medical Outcomes Study Short Form-36 (SF-36) and the disease-specific Health-Related Quality of Life (HRQL) questionnaire, were evaluated at three points in time: at the start, 3 months after the placement of an intragastric balloon that remained in situ for 6 months, and 3 months after subsequent gastric banding. QOL scores revealed a significant improvement in many health domains, with an earlier improvement with the disease-specific HRQL, whereas the generic QOL questionnaire lagged behind. However, in the end, the SF-36 caught up completely to normal-weight levels, whereas some scales of the HRQL remained below these levels. Work productivity and involvement in sports improved significantly. BMI declined significantly over time, but no correlation with SF-36 and HRQL score changes was found. The QOL improved substantially independent of changes in BMI. Because of the divergent outcomes of generic and disease-specific QOL questionnaires, prospective studies should examine the sensitivity to changes of both kinds of QOL questionnaires

BACKGROUND: We studied whether weight loss by intragastric balloon would predict the outcome of subsequent gastric banding with regard to weight loss and BMI reduction. METHODS: A prospective cohort of patients with a body mass index (BMI)>40 kg/m(2) received an intragastric balloon for 6 months followed by laparoscopic adjustable gastric banding (LAGB). Successful balloon-induced weight loss was defined as > or =10% weight loss after 6 months. Successful surgical weight loss was defined as an additional 15% weight loss in the following 12 months. Patients were divided in group A, losing > or =10% of their initial weight with 6 months' balloon treatment, and group B, losing or =10% of their starting weight during 6 months balloon treatment as well as > or =15% 12 months following LAGB. 6 patients in group B lost or =15% 12 months following LAGB. CONCLUSION: Intragastric balloon did not predict the success of subsequent LAGB

Hereditary tyrosinaemia type I is an autosomal recessive inborn error of tyrosine catabolism caused by a deficiency of the enzyme fumarylacetoacetase that results in liver failure, hepatocellular carcinoma, renal tubular dysfunction and acute intermittent porphyria. When treated with liver transplantation, tyrosinaemia type I was considered to be cured. Some years after the first liver transplantations in these patients, some reports focused on the renal function after transplantation. These reports showed that urinary succinylacetone excretion remained but that tubular function normalized. In this report we discuss the long-term renal follow-up (mean follow-up time 11 years, range 7-14 years) after liver transplantation in 9 patients with tyrosinaemia type I treated by liver transplantation in our centre. An evaluation was made of renal function and succinylacetone excretion in urine. In all patients we found a persistent excretion of succinylacetone in the urine. With respect to the glomerular function, we can conclude that there is no clear change in GFR. At the same time, tubulopathy persisted in some patients. We consider that excretion of metabolites such as succinylacetone will be an important contributing factor to tubular dysfunction after liver transplantation in patients with tyrosinaemia type I. Therefore, notwithstanding the major effect of liver transplantation on tyrosine metabolism, renal tubular dysfunction remains at risk and needs careful monitoring. Progressive tubular dysfunction can cause glomerular damage. The use of low-dose NTBC might be considered after liver transplantation in case of tubulopathy to prevent progression of tubular and glomerular dysfunction.

The role of tumour necrosis factor-alpha in the pathogenesis of inflammatory bowel disorders is well-known and is underscored by the effectiveness of antitumour necrosis factor-alpha treatment. Tumour necrosis factor-alpha exerts its effect by binding TNFR1 and TNFR2, which genes map to inflammatory bowel disorders susceptibility loci.Since TNFR1 and TNFR2 are good candidate genes for inflammatory bowel disorders, we studied the functional TNFR2T587G and the TNFR1A36G mutation in 344 Crohn's disease and 152 ulcerative colitis patients and investigated the relation with disease phenotypes. An association with response to infliximab was evaluated in 166 Crohn's disease patients.The TNFR2 587G allele was more frequent in ulcerative colitis compared with controls (P = 0.03). Both single nucleotide polymorphisms were negatively associated with smoking at diagnosis in Crohn's disease (TNFR1A36G odds ratio: 0.614, 95% confidence interval: 0.452, 0.99 and TNFR2T587G odds ratio: 0.572, 95% confidence interval: 0.820, 0.875). There was a positive association between pancolitis and the TNFR1A36G polymorphism in ulcerative colitis (odds ratio: 5.341, 95% confidence interval: 1.484, 19.39). The biological response to infliximab was lower in patients carrying TNFR1 36G (odds ratio: 0.47, 95% confidence interval: 0.234, 0.946).The TNFR2 587G allele was more frequent in ulcerative colitis. Both single nucleotide polymorphisms were negatively associated with smoking in Crohn's disease. A relation between TNFR1A36G and pancolitis was found in ulcerative colitis. There was no clear effect of the polymorphisms on infliximab response although, the TNFR1 minor was associated with a lower response to infliximab.

Peritonitis is the most common complication in patients receiving chronic ambulatory peritoneal dialysis (CAPD). It is normally readily diagnosed and successfully treated conservatively without serious complications. However, when peritonitis is resistant to standard intraperitoneal antibiotic therapy, underlying intra-abdominal pathology should be suspected [1]. Of all peritonitis in CAPD patients, 6–9% is caused by (multiple) enteric micro-organisms suggestive of gastrointestinal perforation [2]. It is often necessary to perform surgical exploration to confirm such a diagnosis [2,3]. A laparoscopic approach with these patients is gaining popularity as an alternative to open surgery. Finding a bowel perforation often means conversion to laparotomy and (long-term) cessation of PD because the CAPD catheter is removed. The idea behind this strategy is that foreign bodies should always be removed from infected areas. We present a case of a perforated appendicitis in a CAPD patient, diagnosed and treated laparoscopically, without loss of the peritoneal catheter.

Background Several methods for skin closure are used, i.e. sutures, adhesive papertape and tissue adhesives. Little is known about the efficacy of these techniques in laparoscopic surgery. This study was performed to analyse the efficacy of octylcyanoacrylate, a new tissue adhesive, adhesive papertape and poliglecaprone for wound closure in laparoscopy. Methods From May 2000 to September 2001, 140 patients were included in a prospective randomized trial. Wounds were closed with octylcyanoacrylate (n = 48), adhesive papertape (n = 42) or poliglecaprone (n = 50). Closing time, wound infection, cosmetic results and costs were evaluated. A time–motion analysis was also performed. Results The patients in the three groups were well matched for age, gender and body mass index. Closing times per wound were 26, 33 and 65 s respectively for adhesive papertape, octylcyanoacrylate and poliglecaprone (P < 0·001). Cosmetic results, as scored by the patients, were no different. The number of actions required to close each wound was 5·7, 8·3 and 21·0 for octylcyanoacrylate, adhesive papertape (P = 0·05 versus octylcyanoacrylate) and poliglecaprone (P < 0·01 versus octylcyanoacrylate and adhesive papertape) respectively. Octylcyanoacrylate was significantly more expensive than poliglecaprone and adhesive papertape. Conclusion Closure with adhesive papertape was the fastest method. The smallest number of actions required to close a wound was with octylcyanoacrylate. Adhesive papertape was the most cost-effective.

The formation of adventitious roots is an essential process in propagation systems for rose. For that reason, we decided to study adventitious root formation on excised stem expiants in a well defined culture medium in vitro, under controlled physical growth conditions. This system helped us to gain a better insight into the plant, nutritional and physical factors determining the formation of adventitious roots.