Dutch University Medical Centers Research Articles

Molecular characterization of p16-immunopositive but HPV DNA-negative oropharyngeal carcinomas

Recent studies have reported that p16 protein overexpression qualifies as a surrogate marker identifying an oncogenic human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC). However, there is still a percentage of OPSCCs that are positive for p16 immunohistochemistry (p16 IHC) but lack HPV DNA. The objective of this study was to characterize this group at the molecular level by performing sensitive HPV DNA- and RNA-based PCR methods and genetic profiling. All patients diagnosed with an OPSCC in the period 2000-2006 in two Dutch university medical centers were included (n = 841). The presence of HPV in a tumor sample was tested by p16 IHC followed by an HPV DNA GP5+/6+ PCR. p16 IHC scored positive in 195 samples, of which 161 were HPV DNA-positive and 34 (17%) HPV DNA-negative. In the latter group, a SPF10-LiPA25 assay, an HPV16 type-specific E7 PCR and an E6 mRNA RT-PCR were performed. Next, ten of these cases were further analyzed for loss of heterozygosity (LOH) of 15 microsatellite markers at chromosome arms 3p, 9p and 17p. Of the 34 p16-positive but PCR-negative OPSCCs, two samples tested positive by SPF10 assay, HPV16 E7 PCR and HPV16 E6 mRNA RT-PCR. Three samples tested positive by SPF10 assay but negative by the HPV16-specific assays. Nine of ten cases that were tested for LOH showed a genetic pattern comparable to that of HPV-negative tumors. This study categorizes p16-positive but HPV DNA-negative OPSCCs as HPV-negative tumors based on genetic profiling. This study highlights the importance of performing HPV testing in addition to p16 IHC for proper identification of HPV-associated OPSCCs.

Key factors in work engagement and job motivation of teaching faculty at a university medical centre.

This study reports about teacher motivation and work engagement in a Dutch University Medical Centre (UMC). We examined factors affecting the motivation for teaching in a UMC, the engagement of UMC Utrecht teaching faculty in their work, and their engagement in teaching compared with engagement in patient care and research. Based on a pilot study within various departments at the UMCU, a survey on teaching motivation and work engagement was developed and sent to over 600 UMCU teachers. About 50 % responded. Work engagement was measured by the Utrecht Work Engagement Scale, included in this survey. From a list of 22 pre-defined items, 5 were marked as most motivating: teaching about my own speciality, noticeable appreciation for teaching by my direct superior, teaching small groups, feedback on my teaching performance, and freedom to determine what I teach. Feedback on my teaching performance showed the strongest predictive value for teaching engagement. Engagement scores were relatively favourable, but engagement with patient care was higher than with research and teaching. Task combinations appear to decrease teaching engagement. Our results match with self-determination theory and the job demands–resources model, and challenge the policy to combine teaching with research and patient care.

Low Accuracy of Tumor Markers for Diagnosing Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1 Patients

The assessment of tumor markers for diagnosing pancreatic neuroendocrine tumors (pNET) in multiple endocrine neoplasia type 1 (MEN1) patients is advised in the current guidelines but has never been validated for this purpose. The objective of the study was to assess the diagnostic accuracy of chromogranin A (CgA), pancreatic polypeptide (PP), and glucagon for pNET in MEN1. This was a diagnostic study. The study was conducted at Dutch university medical centers from 2008 to 2011, representing 90% of the total Dutch MEN1 population. Patients for whom data on tumor markers in combination with the reference standard (ie, radiological imaging) were available between 2008 and 2011 were included. The reference standard for the presence of pNET was pathology or detection on magnetic resonance imaging, computed tomography, or endoscopic ultrasound confirmed on subsequent imaging, irrespective of modality at follow-up. The area under the receiver-operating characteristic curve (AUC), positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, sensitivity, and specificity were calculated for each marker. For the analysis of PP, CgA, and glucagon, 73, 81, and 94 patients were available, respectively. The AUC for CgA was 0.48 [95% confidence interval (CI) 0.35-0.61] with a sensitivity 0.33 and a specificity 0.73; the AUC for glucagon was 0.58 (95% CI 0.46-0.70) with a sensitivity 0.43 and a specificity 0.73; and the AUC for PP was 0.64 (95% CI 0.50-0.77) with a sensitivity 0.36 and a specificity 0.74. Age, imaging modality, tumor size, and number did not influence the outcomes. The diagnostic accuracy of the tumor markers CgA, PP, and glucagon for pNET in MEN1 is low.

Planning and process evaluation of a multi-faceted influenza vaccination implementation strategy for health care workers in acute health care settings

BackgroundInfluenza transmitted by health care workers (HCWs) is a potential threat to frail patients in acute health care settings. Therefore, immunizing HCWs against influenza should receive high priority. Despite recommendations of the World Health Organization, vaccine coverage of HCWs remains low in all European countries. This study explores the use of intervention strategies and methods to improve influenza vaccination rates among HCWs in an acute care setting.MethodsThe Intervention Mapping (IM) method was used to systematically develop and implement an intervention strategy aimed at changing influenza vaccination behaviour among HCWs in Dutch University Medical Centres (UMCs). Carried out during the influenza seasons 2009/2010 and 2010/2011, the interventions were then qualitatively and quantitatively evaluated by way of feedback from participating UMCs and the completion of a web-based staff questionnaire in the following spring of each season.ResultsThe IM method resulted in the development of a transparent influenza vaccination intervention implementation strategy. The intervention strategy was offered to six Dutch UMCs in a randomized in a clustered Randomized Controlled Trial (RCT), where three UMCs were chosen for intervention, and three UMCs acted as controls. A further two UMCs elected to have the intervention. The qualitative process evaluation showed that HCWs at four of the five intervention UMCs were responsive to the majority of the 11 relevant behavioural determinants resulting from the needs assessment in their intervention strategy compared with only one of three control UMCs. The quantitative evaluation among a sample of HCWs revealed that of all the developed communication materials, HCWs reported the posters as the most noticeable.ConclusionsOur study demonstrates that it is possible to develop a structured implementation strategy for increasing the rate of influenza vaccination by HCWs in acute health care settings. The evaluation also showed that it is impossible to expose all HCWs to all intervention methods (which would have been the best case scenario). Further study is needed to (1) improve HCW exposure to intervention methods; (2) determine the effect of such interventions on vaccine uptake among HCWs; and (3) assess the impact on clinical outcomes among patients when such interventions are enacted.

Effect of Inspiratory Muscle Training Before Cardiac Surgery in Routine Care

Inspiratory muscle training (IMT) before cardiac surgery has proved to be a promising intervention to reduce postoperative pneumonia in a randomized controlled trial setting. Effects of IMT in routine care have not been reported. The purpose of this study was to investigate the effect of IMT before cardiac surgery on postoperative pneumonia in routine care at a Dutch university medical center using propensity scoring. This was an observational cohort study. All candidates for cardiac surgery were preoperatively stratified by a physical therapist for low risk or high risk for postoperative pulmonary complications. Patients at high risk either engaged in an unsupervised IMT program (20 minutes a day) at home for at least 2 weeks before surgery (group 1) or received usual care (no IMT) (group 2). Results in terms of outcome measures were adjusted with propensity scores to reduce bias caused by nonrandom treatment assignment. The results showed that of the 94 patients at high risk in group 1, 1 patient (1.1%) developed a postoperative pneumonia. In group 2, 8 out of the 252 patients at high risk (3.2%) developed this pulmonary complication (adjusted odds ratio=0.34, 95% confidence interval=0.04-3.38). No significant differences were found regarding median (25th-75th percentile) ventilation time (7 [5-9] hours versus 7 [5-10] hours), length of stay in the intensive care unit (23 [21-24] hours versus 23 [21-25] hours), or total postoperative length of stay (7 [6-11] days versus 7 [5-9] days). The most important limitations of this study were confounding, incomplete data collection, and a low incidence of the primary outcome. Propensity scoring is believed to be a valuable tool of great potential interest to researchers in the field of observational studies. Whether IMT in routine care resulted in less postoperative pneumonia cannot be concluded.

Design of the muscles in motion study: a randomized controlled trial to evaluate the efficacy and feasibility of an individually tailored home-based exercise training program for children and adolescents with juvenile dermatomyositis

BackgroundJuvenile dermatomyositis (JDM) is a rare, often chronic, systemic autoimmune disease of childhood, characterized by inflammation of the microvasculature of the skeletal muscle and skin. Prominent clinical features include significant exercise intolerance, muscle weakness, and fatigue. Despite pharmacological improvements, these clinical features continue to affect patients with JDM, even when the disease is in remission. Exercise training is increasingly utilized as a non-pharmacological intervention in the clinical management of (adult) patients with chronic inflammatory conditions; however no randomized controlled trials (RCT) have been performed in JDM. In the current study, the efficacy and feasibility of an exercise training program in patients with JDM will be examined.Methods/designSubjects (n = 30) will include 8–18 year olds diagnosed with JDM. The intervention consists of an individually tailored 12-weeks home-based exercise training program in which interval training on a treadmill is alternated with strength training during each session. The program is based on previous literature and designed with a defined frequency, intensity, time, and type of exercise (FITT principles). Primary outcome measures include aerobic exercise capacity, isometric muscle strength, and perception of fatigue. The study methodology has been conceived according to the standards of the CONSORT guidelines. The current study will be a multi-center (4 Dutch University Medical Centers) RCT, with the control group also entering the training arm directly after completion of the initial protocol. Randomization is stratified according to age and gender.DiscussionThe current study will provide evidence on the efficacy and feasibility of an individually tailored 12-week home-based exercise training program in youth with JDM.Trial registrationMedical Ethics Committee of the University Medical Center Utrecht, the Netherlands: 11–336; Netherlands Trial Register (NTR): NTR 3184.

Design of the Quality of Life in Motion (QLIM) study: a randomized controlled trial to evaluate the effectiveness and cost-effectiveness of a combined physical exercise and psychosocial training program to improve physical fitness in children with cancer

BackgroundChildhood cancer and its treatment have considerable impact on a child's physical and mental wellbeing. Especially long-term administration of chemotherapy and/or radiotherapy impairs physical fitness both during and after therapy, when children often present with muscle weakness and/or low cardiorespiratory fitness. Physical exercise can improve these two elements of physical fitness, but the positive effects of physical exercise might be further increased when a child's wellbeing is simultaneously enhanced by psychosocial training. Feeling better may increase the willingness and motivation to engage in sports activities. Therefore, this multi-centre study evaluates the short and long-term changes in physical fitness of a child with a childhood malignancy, using a combined physical exercise and psychosocial intervention program, implemented during or shortly after treatment. Also examined is whether positive effects on physical fitness reduce inactivity-related adverse health problems, improve quality of life, and are cost-effective.MethodsThis multi-centre randomized controlled trial compares a combined physical and psychosocial intervention program for children with cancer, with care as usual (controls). Children with cancer (aged 8-18 years) treated with chemotherapy and/or radiotherapy, and who are no longer than 1 year post-treatment, are eligible for participation. A total of 100 children are being recruited from the paediatric oncology/haematology departments of three Dutch university medical centres. Patients are stratified according to pubertal stage (girls: age ≤10 or >10 years; boys: ≤11 or >11 years), type of malignancy (haematological or solid tumour), and moment of inclusion into the study (during or after treatment), and are randomly assigned to the intervention or control group.DiscussionChildhood cancer patients undergoing long-term cancer therapy may benefit from a combined physical exercise and psychosocial intervention program since it may maintain or enhance their physical fitness and increase their quality of life. However, the feasibility, patient need, and effectiveness of such a program should be established before the program can be implemented as part of standard care.Trial registration numberNTR1531 (The Netherlands National Trial Register)

Societal output and use of research performed by health research groups

The last decade has seen the evaluation of health research pay more and more attention to societal use and benefits of research in addition to scientific quality, both in qualitative and quantitative ways. This paper elaborates primarily on a quantitative approach to assess societal output and use of research performed by health research groups (societal quality of research). For this reason, one of the Dutch university medical centres (i.e. the Leiden University Medical Center (LUMC)) was chosen as the subject of a pilot study, because of its mission to integrate top patient care with medical, biomedical and healthcare research and education. All research departments were used as units of evaluation within this university medical centre.The method consisted of a four-step process to reach a societal quality score per department, based on its (research) outreach to relevant societal stakeholders (the general public, healthcare professionals and the private sector). For each of these three types of stakeholders, indicators within four modes of communication were defined (knowledge production, knowledge exchange, knowledge use and earning capacity). These indicators were measured by a bottom-up approach in a qualitative way (i.e. all departments of the LUMC were asked to list all activities they would consider to be of societal relevance), after which they were converted into quantitative scores. These quantitative scores could then be compared to standardised scientific quality scores that are based on scientific publications and citations of peer-reviewed articles.Based on the LUMC pilot study, only a weak correlation was found between societal and scientific quality. This suggests that societal quality needs additional activities to be performed by health research groups and is not simply the consequence of high scientific quality. Therefore we conclude that scientific and societal evaluation should be considered to be synergistic in terms of learning for the future, accountability and advocacy.This quantitative approach to assess societal quality in a quantitative sense is based on indicators that function as proxies for society quality on different levels, based on the communication of researchers with their societal stakeholders (i.e. knowledge production, knowledge exchange and knowledge use). The methodology presented is just a first attempt to compare scientific quality scores (publication and citation scores) with societal quality scores in a quantitative way. This comparison can be used by organisations (e.g. university medical centres) in their planning and control cycle.

Calcium score: a new risk factor for colorectal anastomotic leakage

Background Anastomotic leakage (AL) is the most feared complication of colorectal surgery. Atherosclerosis is suggested to have a detrimental effect on anastomotic healing. This study aimed to analyze the calcium score, a measure for atherosclerosis, as a risk factor for AL. Study design The calcium scores of colorectal patients operated on in 2 Dutch university medical centers were determined using a computed tomography scan and calcium scoring software. The aorta, common iliac arteries, internal and external iliac arteries were studied. Additionally, patient- and operation-related factors were scored. Results A total of 122 patients were included. In patients with AL, calcium scores were significantly higher in the left common iliac artery (561.4 vs 156.0, P = .028), right common iliac artery (542.0 vs 144.4, P = .041), both common iliac arteries together (1,103.3 vs 301.9, P = .046), and the left internal iliac artery (716.3 vs 35.3, P = .044). Conclusions Patients with higher calcium scores in the iliacal arteries have an increased leakage risk.

Misclassification of dysplasia in patients with inflammatory bowel disease

The natural behavior of flat low-grade (LGD) and indefinite dysplasia (IND) in patients with inflammatory bowel disease (IBD) remains uncertain and seems to be dependent on the interpretation of the pathologist. We studied the progression rate of flat LGD and IND to advanced neoplasia (high-grade dysplasia [HGD] or colorectal cancer [CRC]) before and after histopathological review by a panel of gastrointestinal expert pathologists. A nationwide pathology database was used to identify IBD patients with dysplasia in six Dutch university medical centers between 1990 and 2006. Medical charts of patients with recorded flat LGD or IND were reviewed. Histological slides from three university medical centers were reviewed by a panel of three expert gastrointestinal pathologists. We identified 113 flat LGD patients and 26 flat IND patients. Advanced neoplasia was found in 18 flat LGD patients (16%) after a median follow-up of 48 months, resulting in a 5-year progression rate of 12%. Five IND patients (19%) developed advanced neoplasia after a median follow-up of 24 months, resulting in a 5-year progression rate of 21%. Review of 1547 histological slides from 87 patients resulted in an increase of the 5-year progression rate of flat LGD to advanced neoplasia to 37%, whereas the progression rate of IND decreased to 5%. A diagnosis of flat LGD that is confirmed by a panel of expert gastrointestinal pathologists is associated with a substantial risk of progression to advanced neoplasia, while confirmed IND is associated with a low risk of progression.

OP1-5 Application of two internally-controlled multiplex real-time PCR assays detecting Adenovirus, Astrovirus, Rotavirus group A and Norovirus genogroups I and II in a Dutch university medical center

Defective oxidative phosphorylation has a crucial role in the attenuation of mitochondrial function, which confers therapy resistance in cancer. Various factors, including endogenous heat shock proteins (HSPs) and exogenous agents such as dichloroacetate, restore respiratory and other physiological functions of mitochondria in cancer cells. Functional mitochondria might ultimately lead to the restoration of apoptosis in cancer cells that are refractory to current anticancer agents. Here, we summarize the key reasons contributing to mitochondria dysfunction in cancer cells and how restoration of mitochondrial function could be exploited for cancer therapeutics.

Drug safety alert generation and overriding in a large Dutch university medical centre

To evaluate numbers and types of drug safety alerts generated and overridden in a large Dutch university medical centre. A disguised observation study lasting 25 days on two internal medicine wards evaluating alert generation and handling of alerts. A retrospective analysis was also performed of all drug safety alerts overridden in the hospital using pharmacy log files over 24 months. In the disguised observation study 34% of the orders generated a drug safety alert of which 91% were overridden. The majority of alerts generated (56%) concerned drug-drug interactions (DDIs) and these were overridden more often (98%) than overdoses (89%) or duplicate orders (80%). All drug safety alerts concerning admission medicines were overridden.Retrospective analysis of pharmacy log files for all wards revealed one override per five prescriptions. Of all overrides, DDIs accounted for 59%, overdoses 24% and duplicate orders 17%. DDI alerts of medium-level seriousness were overridden more often (55%) than low-level (22%) or high-level DDIs (19%). In 36% of DDI overrides, it would have been possible to monitor effects by measuring serum levels. The top 20 of overridden DDIs accounted for 76% of all DDI overrides. Drug safety alerts were generated in one third of orders and were frequently overridden. Duplicate order alerts more often resulted in order cancellation (20%) than did alerts for overdose (11%) or DDIs (2%). DDIs were most frequently overridden. Only a small number of DDIs caused these overrides. Studies on improvement of alert handling should focus on these frequently-overridden DDIs.

More right-sided IBD-associated colorectal cancer in patients with primary sclerosing cholangitis

Patients with inflammatory bowel disease (IBD) and concurrent primary sclerosing cholangitis (PSC) have a higher risk of developing colorectal cancer (CRC) than IBD patients without PSC. The aim of this study was to investigate potential clinical differences between patients with CRC in IBD and those with CRC in IBD and PSC, as this may lead to improved knowledge of underlying pathophysiological mechanisms of CRC development. The retrospective study from 1980-2006 involved 7 Dutch university medical centers. Clinical data were retrieved from cases identified using the national pathology database (PALGA). In total, 27 IBD-CRC patients with PSC (70% male) and 127 IBD-CRC patients without PSC (59% male) were included. CRC-related mortality was not different between groups (30% versus 19%, P = 0.32); however, survival for cases with PSC after diagnosing CRC was lower (5-year survival: 40% versus 75% P = 0.001). Right-sided tumors were more prevalent in the PSC group (67% versus 36%, P = 0.006); adjusted for age, sex, and extent of IBD, this difference remained significant (odds ratio: 4.8, 95% confidence interval [CI] 2.0-11.8). In addition, tumors in individuals with PSC were significantly more advanced. The right colon is the predilection site for development of colonic malignancies in patients with PSC and IBD. When such patients are diagnosed with cancer they tend to have more advanced tumors than patients with IBD without concurrent PSC, and the overall prognosis is worse. Furthermore, the higher frequency of right-sided tumors in patients with PSC suggests a different pathogenesis between patients with PSC and IBD and those with IBD alone.

Peripherally Inserted Central Venous Catheters: First Results after the Introduction in a Dutch University Medical Center

PurposeTo analyze patient outcomes and processes of insertion after the introduction of the peripherally inserted central catheter (PICC) in the University Medical Center Utrecht (UMC Utrecht) in the Netherlands. Patients and methodA prospective analysis of PICC inserted in the UMC Utrecht looking at patient characteristics, dwell time and infections. ResultsA total number of 510 PICCs in 439 patients with 17655 catheter days were analyzed using ultrasound (US) and modified Seldinger technique (MST). Overall there were 2.35 catheter-related bloodstream infections (CRBSI) per 100 devices and 0.68 infections per 1000 catheter days. When used specifically for home infusion, the CRBSI rates were 1.09 per 100 devices and 0.23 per 1000 catheter days. One advanced nurse practitioner (ANP) inserted all PICCs. Although a full sterile barrier (no hat and gown) was not used during insertion, the infection rate in our study was lower compared to the 1.1 infection per 1000 catheter days reported in a meta-analyses on CRBSI (Maki, Kluger, & Crnich, 2006). ConclusionThrough the use of modern techniques like US and MST and upper arm insertion of PICCs, the complication rate is lower compared to older techniques as shown in most prospective studies. Extended dwell time, as a positive outcome of using PICCs made more doctors decide to choose a PICC. Age of the patient did not influence dwell time or complications. Further research, preferably a randomized controlled trial, is needed to compare the subclavian catheter with the PICC as well as exploration of the effects of anticipatory choice for PICCs, specifically in immune compromised patients.

Residents’ perspectives on dermatology training in Dutch university medical centres in 2006

Residents’ perspectives on dermatology training in Dutch university medical centres in 2006

Chronic Kidney Disease after Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation

Because survival of recipients of allogeneic hematopoietic stem cell transplantation (HSCT) has improved, long-term complications become more important. We studied the incidence and risk factors of chronic kidney disease in these patients and evaluated associated posttransplant complications and mortality. We performed a retrospective cohort study of 266 adults who received myeloablative allogeneic HSCT and who survived for >6 months in an 11-year period at a Dutch university medical center. Primary outcome was the incidence of chronic kidney disease defined as a glomerular filtration rate (GFR) of <60 mL/min/1.73 m 2. Chronic kidney disease developed in 61 (23%) of 266 patients, with a cumulative incidence rate of 27% at 10 years. Severe kidney disease (GFR of <30 mL/min/1.73 m 2) developed in 3% of patients. Only 6 patients developed the thrombotic microangiopathic syndrome SCT nephropathy, and 2 of them needed dialysis. Pretransplant risk factors for chronic kidney disease were lower GFR at day 0 ( P < .0001, odds ratio [OR] 0.95 95% confidence interval [CI] 0.93-0.97), female gender, and higher age ( P = .001 and P < .0001, respectively). The occurrence of hypertension after transplantation was associated with chronic kidney disease ( P < .0001, OR 0.34 95% CI 0.18-0.62). Mortality was 39% after a mean follow-up of 5.1 years. There was no significant difference in survival between patients with and without chronic kidney disease. Chronic kidney disease is a common late complication of myeloablative allogeneic HSCT. Because of the natural decline in renal function with time there is a risk of developing end-stage renal disease in the future. SCT nephropathy seems to be a specific cause of chronic kidney disease that is typically associated with severe kidney disease.

Outbreak ofSerratia marcescensColonization and Infection Traced to a Healthcare Worker With Long-Term Carriage on the Hands

To reveal the source of a nosocomial outbreak of colonization and infection with a strain of Serratia marcescens positive for Guiana extended-spectrum beta-lactamase 1 (GES-1) that occurred among patients in a neurosurgical intensive care unit (ICU) in a Dutch university medical center from May 2002 through March 2003. Samples from the environment and from the hands of healthcare workers (HCWs) were cultured. A retrospective case-control study was carried out. Fifteen neurosurgical ICU patients who had 1 or more cultures that yielded the epidemic strain of S. marcescens from May 2002 through March 2003 were defined as case patients and matched with 30 control patients. Environmental cultures did not reveal a prominent source of S. marcescens. Cultures of specimens from the hands of 100 HCWs revealed colonization of a single HCW with the epidemic strain. Although this HCW instantly went on leave, serial cultures detected prolonged carriage of the epidemic strain on the hands of the HCW for 3 months. The skin of the HCW's hands was psoriatic. The epidemic abruptly ended after the colonized HCW went on leave. Retrospective case-control analysis showed that the patients colonized or infected with S. marcescens received significantly more nursing care from the colonized HCW than did control patients (P<.05). From February 2004 through October 2004, a second cluster of 3 patients was detected with the epidemic strain of S. marcescens. In October 2004, the formerly colonized HCW appeared to have carriage of the epidemic strain on the hands again. A single HCW with the epidemic strain of S. marcescens on the hands was considered the source of this outbreak.

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.

Surgical intervention in patients with necrotizing pancreatitis

This study evaluated the various surgical strategies for treatment of (suspected) infected necrotizing pancreatitis (INP) and patient referrals for this condition in the Netherlands. This retrospective study included all 106 consecutive patients who had surgical treatment for INP in the period 2000-2003 in one of eight Dutch university medical centres including three teaching hospitals. Surgical approaches included an open abdomen strategy, laparotomy with continuous postoperative lavage, minimally invasive procedures or laparotomy with primary abdominal closure. The National Hospital Registration System was searched to identify patients with acute pancreatitis who were admitted to the 90 Dutch hospitals that did not participate in the present study. The overall mortality rate was 34.0 per cent, 70 per cent (16 of 23) for the open abdomen strategy, 25 per cent (13 of 53) for continuous peritoneal lavage, 11 per cent (two of 18) for minimally invasive procedures and 42 per cent (five of 12) for primary abdominal closure (P < 0.001). During the study interval, 44 (12.2 per cent) of 362 patients with acute pancreatitis who were likely to require surgical intervention had been referred to university medical centres. Laparotomy with continuous postoperative lavage is the surgical strategy most often used in the Netherlands. The results of the open abdomen strategy are poor whereas a minimally invasive approach seems promising.

Impact of [18F]fluorodeoxyglucose positron emission tomography on surgical management of melanoma patients

Several studies have shown adequate sensitivity and specificity of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the detection of metastases from melanoma, but few have addressed its impact on treatment. The aim of this retrospective study was to assess the impact of FDG-PET on treatment of melanoma in three Dutch university medical centres. The medical records of 257 patients were reviewed. The indications for FDG-PET and findings were recorded. Unexpected findings of suspected (pre)malignant tumours other than melanoma were assessed. Treatment plans before and after FDG-PET were recorded and analysed to evaluate changes in disease management. Most scans (71.2 per cent) were requested for staging, mainly to detect distant metastases in patients with stage III disease. Overall, 56 patients (21.8 per cent) were upstaged as a result of PET. In 44 patients (17.1 per cent) treatment was changed, usually from surgery to systemic treatment in patients with stage III disease. Unexpected tumours were detected (mainly colorectal) in 11 patients (4.3 per cent). FDG-PET is most valuable in patients with stage III melanoma for detection of distant metastases and identification of candidates for surgery and/or systemic treatment. Unexpected FDG-PET findings should not be disregarded, as (pre)malignant, clinically relevant, tumours may be identified.