Endoscopic mucosal resection of large rectal adenomas in the era of centralization: Results of a multicenter collaboration.

BACKGROUND AND OBJECTIVE: Endoscopic mucosal resection (EMR) of large rectal adenomas is largely being centralized. We assessed the safety and effectiveness of EMR in the rectum in a collaboration of 15 Dutch hospitals. METHODS: Prospective, observational study of patients with rectal adenomas >3 cm, resected by piecemeal EMR. Endoscopic treatment of adenoma remnants at 3 months was considered part of the intervention strategy. Outcomes included recurrence after 6, 12 and 24 months and morbidity. RESULTS: Sixty-four patients (50% male, age 69 ± 11, 96% ASA 1/2) presented with 65 adenomas (diameter 46 ± 17 mm, distance ab ano 4.5 cm (IQR 1-8), 6% recurrent lesion). Sixty-two procedures (97%) were technically successful. Histopathology revealed invasive carcinoma in three patients (5%), who were excluded from effectiveness analyses. At 3 months' follow-up, 10 patients showed adenoma remnants. Recurrence was diagnosed in 16 patients during follow-up (recurrence rate 25%). Fifteen of 64 patients (23%) experienced 17 postprocedural complications. CONCLUSION: In a multicenter collaboration, EMR was feasible in 97% of patients. Recurrence and postprocedural morbidity rates were 25% and 23%. Our results demonstrate the outcomes of EMR in the absence of tertiary referral centers.

[Secondary data analysis of the prevalence of alcohol dependence (F10.2) in Germany]. / Sekundärdatenanalyse der Prävalenz der Alkoholabhängigkeit (F10.2) in Deutschland.

BACKGROUND AND AIM: Compared to other European countries, alcohol consumption and abuse in Germany is on a high level. Even in smaller quantities, frequent alcohol consumption can generate organic damages and thus lead to secondary diseases that have a significant societal relevance regarding direct and indirect costs for the healthcare system. After several publications have already addressed the prevalence of acute alcohol intoxication and alcohol abuse in adolescents, the question arises how the prevalence of alcohol abuse develops on the basis of the accounting data of outpatient and inpatient care providers in the population of adults aged 18 and over and what tendency can be observed within a multi-year period. Within this study, the coding of alcohol abuse (F10.2 diagnosis) was analyzed separately for outpatient and inpatient sector in the insured population ≥ 18 years and presented over time. PATIENTS AND METHODS: The development of the prevalence of alcohol abuse was analyzed on the basis of secondary random sample data from one nation-wide working statutory health insurance with a total population of more than 3 million insurants in the 5-year period from 2006 to 2010. For the presentation of the prevalences, insurant numbers were used. For the identification of the relevant insurants, only confirmed outpatient F10.2 diagnoses or inpatient F10.2 diagnoses were used. The age and sex distributions of the dataset were adjusted to the distribution in the statutory health insurance to ensure representativeness. The analyses of each single year only allude to insured persons aged ≥ 18 years. With the help of the statistics of the insured of statutory health insurance, for each calendar year, projections of the detected prevalence rates were determined to estimate the number of cases on the statutory health insurance level and their development over time. RESULTS: The results show a tendency of slightly increasing prevalence of alcohol dependence from 2006 to 2010. For insured persons with at least one inpatient or outpatient F10.2 diagnosis, the prevalence continuously rises from 1,04% in 2006 to 1.14% in 2010; the prevalence of insured persons who received an alcohol dependence diagnosis only in the outpatient sector, increased from 0,67% to 0,79% in that time scale. In all analyzes, there was a ratio of 30% affected women to 70% affected men. From 2006 to 2010, the proportion of insured persons with hospitalization caused by alcohol dependence decreased steadily from 14,51% to 12,24%. CONCLUSION: For the analyzed group of persons aged ≥ 18 years, the present analysis results show a tendency of slightly increasing prevalences of alcohol abuse, however at the same time combined with a decreasing proportion of hospitalized patients. Similar nationwide studies from 2010 on the basis of secondary data of a health insurance company and inclusion of outpatient and inpatient diagnoses also indicate prevalences of alcohol dependence of about 1.18%, but they base on the age range of 15- to 64-year-old insurants.

Esophageal perforation due to removal of partially covered self-expanding metal stents placed for a benign perforation or leak.

Benign esophageal perforations and anastomotic leaks can be effectively managed by stent placement. However, when partially covered self-expanding metal stents (SEMS) are used, safe removal may be complicated. In this case series, we evaluated the complicated removal of SEMS placed for a benign esophageal perforation or leak in four patients. In all patients a partially covered SEMS was placed. After a median stent time of 29 days (range 21 - 30), the SEMS were found to have become embedded in the esophageal wall. Endoscopic removal resulted in perforation in all patients. All patients recovered uneventfully, although one patient underwent esophagectomy. If uncovered SEMS ends become embedded, removal of the stent may cause major damage to the esophageal wall. It is therefore recommended to remove embedded partially covered SEMS only after first placing a fully covered SEMS or self-expanding plastic stent inside this stent to necrotize the ingrown tissue at the uncovered stent ends.

Allele-sharing of cytokine genes in familial inflammatory bowel disease.

BACKGROUND/AIMS: The pathogenesis of inflammatory bowel disease is complex, multifactorial, and involves genetic predisposition. This predisposition is likely to include various chromosomal loci, but simple Mendelian inheritance cannot be excluded in a subset of families with inflammatory bowel disease. METHODOLOGY: We evaluated allele-sharing in 17 sib-pairs with inflammatory bowel disease as an approach to select candidate genes for further studies in individual families. It was determined whether each sib-pair had inherited the same alleles for interleukin-2, interleukin-2 receptor beta, interleukin-4, interleukin-4 receptor, interleukin-10, interleukin-10 receptor, tumor necrosis factor alpha, tumor necrosis factor alpha receptor 1 and 2. RESULTS: The results were very different per individual family. The estimated probability of sharing both alleles identical-by-descent at interleukin-4 receptor, interleukin-10, interleukin-10 receptor, and tumor necrosis factor alpha were 50%, 39%, 40%, and 33% respectively. The LOD score was significant for interleukin-4 receptor (p = 0.04). CONCLUSIONS: In this small group of sib-pairs with inflammatory bowel disease a modestly increased allele-sharing was found for some inflammatory related genes. Different results per family may suggest genetic heterogeneity. This method can be useful as a first step to further evaluation of specific candidate genes which may play a pathogenetic role in individual families.

The extent of variation in male song, wing and genital characters among allopatric Drosophila montana populations.

Drosophila montana, a species of the Drosophila virilis group, has distributed around the northern hemisphere. Phylogeographic analyses of two North American and one Eurasian population of this species offer a good background for the studies on the extent of variation in phenotypic traits between populations as well as for tracing the selection pressures likely to play a role in character divergence. In the present paper, we studied variation in the male courtship song, wing and genital characters among flies from Colorado (USA), Vancouver (Canada) and Oulanka (Finland) populations. The phenotypic divergence among populations did not coincide with the extent of their genetic divergence, suggesting that the characters are not evolving neutrally. Divergence in phenotypic traits was especially high between the Colorado and Vancouver populations, which are closer to each other in terms of their mtDNA genotypes than they are to the Oulanka population. The males of the Colorado population showed high divergence especially in song traits and the males of the Vancouver population in wing characters. Among the male song traits, two characters known to be under sexual selection and a trait important in species recognition differed clearly between populations, implying a history of directional and/or diversifying rather than balancing selection. The population divergence in wing characters is likely to have been enhanced by natural selection associated with environmental factors, whereas the male genitalia traits may have been influenced by sexual selection and/or sexual conflict.

CARD15 in inflammatory bowel disease and Crohn's disease phenotypes: an association study and pooled analysis.

BACKGROUND: Three major polymorphisms of the Caspase-Activation Recruitment Domain containing protein 15 gene have been described to be associated with Crohn's disease. Genotype-phenotype studies reported in literature provide conflicting data on disease localisation and behaviour. We investigated the relation of Caspase-Activation Recruitment Domain containing protein 15 with inflammatory bowel disease and Crohn's disease phenotypic characteristics in a large Dutch cohort and performed a pooled analysis on inflammatory bowel disease patients and Crohn's disease phenotypic characteristics reported in association studies. METHODS: We genotyped 781 cases and 315 controls for the R702W, G908R and 1007fsinsC variants and for six microsatellite markers in and close to Caspase-Activation Recruitment Domain containing protein 15. In the pooled analysis data of 7201 inflammatory bowel disease patients and 3720 controls from 20 studies were included. RESULTS: Association was found for Crohn's disease with R702W and 1007fsinsC, including several disease characteristics, and not for ulcerative colitis. In the pooled analysis all three common Caspase-Activation Recruitment Domain containing protein 15 variants showed strong association with Crohn's disease (p<0.00001; odds ratio varying from 3.0 for single heterozygotes to 14.7 for compound heterozygotes) and not with ulcerative colitis. Phenotype analysis showed association with small bowel involvement, stricturing and penetrating disease. CONCLUSION: Caspase-Activation Recruitment Domain containing protein 15 is associated with Crohn's disease and not with ulcerative colitis. All three common Crohn's disease-associated variants are associated with small bowel involvement, the G908R and 1007fsinsC alleles also being associated with a complicated disease course.

A functional interleukin-10 mutation in Dutch patients with Crohn's disease.

BACKGROUND AND AIMS: Interleukin-10 is an anti-inflammatory and immunomodulatory cytokine. Interleukin-10 deficient mice are prone to develop chronic colitis. Administration of recombinant human interleukin-10 has been proposed to have a beneficial effect in a subgroup of patients with Crohn's disease. Recently, we found an interleukin-10 Gly15Arg mutation in a family with Crohn's disease which is associated with reduced interleukin-10 secretion by in vitro stimulated monocytes and lymphocytes. We hypothesised that this interleukin-10 mutation plays a role in maintaining the inflammatory process in Crohn's disease in some families. PATIENTS AND METHODS: We evaluated interleukin-10 Gly15Arg in 379 patients with Crohn's disease, and 75 unrelated healthy controls. Also, first degree family members of interleukin-10 Gly15Arg carriers were evaluated. Additionally, mutation carriers and their relatives were evaluated for CARD15 R702W, G908R, and 1007fs. RESULTS: Two patients with Crohn's disease were heterozygous for the interleukin-10 Gly15Arg mutation. No homozygotes were found. The Gly15Arg mutation was not observed in the controls. In first degree family members of the Crohn's disease-affected interleukin-10 Gly15Arg carriers, the mutation was found in Crohn's disease-affected as well as in their apparently healthy individuals. All family members carried one or two CARD15 mutation(s). CONCLUSION: The interleukin-10 Gly15Arg mutation is rare in patients with Crohn's disease, and is not associated with the disease in the Netherlands.

The effects of larval density on adult life-history traits in three species of Drosophila.

There is evidence that longevity and starvation resistance are determined by a common genetic mechanism. Starvation resistance in Drosophila strongly correlates with both fat content and longevity, and is affected by density during rearing. In this study, we examine how three species, Drosophila melanogaster, Drosophila ananassae and Drosophila willistoni, respond to three larval density treatments. Starvation resistance after adult eclosion, and after 2 days of feeding, and longevity were examined in each sex. D. willistoni reacted differently to larval density than the other two species. This species showed an effect of density on longevity whilst D. ananassae and D. melanogaster showed no such effects. The results also indicate that starvation resistance is not solely determined by fat content. Resistance to starvation at two time points after eclosion differed among species. This may reflect differences in resource acquisition and allocation, and we discuss our findings in relation to how selection may operate in the different species.

A Gly15Arg mutation in the interleukin-10 gene reduces secretion of interleukin-10 in Crohn disease.

BACKGROUND: Genetic susceptibility, probably involving cytokines and their receptors, plays an important role in inflammatory bowel disease (IBD). In this study we examine the potential role of the interleukin-10 (IL-10) gene as a susceptibility gene in IBD. METHODS: We studied 17 sib-pairs with either Crohn disease (CD) or ulcerative colitis. After microsatellite analysis for allele-sharing, the IL-10 gene of sib-pairs who shared alleles was screened for nucleotide alterations in and around exons and the promoter region. The IL-10 promoter polymorphism at position -1082 was also determined. Function was evaluated by measuring IL-10 secretion by peripheral blood mononuclear cells stimulated with lipopolysaccharide or phorbol ester. The activity of recombinant immature wild-type and mutated IL-10 was tested in a proliferation assay with a human monocytic leukaemia cell line (HL60 cells). RESULTS: DNA sequencing revealed a G --> A point mutation in exon 1 at base position 43 in one sib-pair, both affected with CD. It was also found in 2 of their healthy siblings, but not in 75 unrelated healthy controls. This mutation results in a glycine to arginine substitution at amino acid position 15 of the leader sequence (Gly15Arg). The in vitro IL-10 secretion by mononuclear cells of the IL-10 Gly15Arg carriers was about 50% of healthy controls, matched for the -1082 polymorphism in the IL-10 promoter region. Incubation of HL60 cells with recombinant mutated IL-10 showed a markedly reduced cell proliferation compared to wild-type IL-10. CONCLUSION: A Gly15Arg mutation in the leader sequence of IL-10 was found in a multiple CD-affected family. This altered leader sequence decreases IL-10 secretion, thereby reducing the anti-inflammatory effect.

[From gene to disease; 'frame shift'-mutation in the CARD15-gene and Crohn's disease]. / Van gen naar ziekte; 'frame shift'-mutatie in het CARD15-gen en de ziekte van Crohn.

A pericentromeric region on chromosome 16 (IBD1 locus) has been linked with Crohn's disease (CD). Very recently, three genetic variants in the CARD15 gene within the IBD1 locus have been identified which were highly associated with CD. Carriage increases the relative risk of developing CD. One specific mutation (3020insC) leads to a stop codon and truncation of the C-terminal tandem leucine-rich repeats (LRR) of the CARD15 protein. Of all patients with Crohn's disease, 11-19% are heterozygous and 3-7% homozygous for this frameshift mutation. The CARD15 gene is expressed in monocytes. The LRR-domain is thought to be involved in the binding of bacterial lipopolysaccharide and subsequent activation of nuclear factor kappa-B (NF kappa B). NF kappa B plays a central role in the regulation of the expression of other genes involved in the inflammatory response. In vitro, embryonic kidney cells transfected with the CARD15 3020insC mutant showed a reduced activity of NF kappa B after exposure to lipopolysaccharide compared to cells transfected with the wild-type CARD15 gene. How the reduced response to lipopolysaccharide contributes to CD is not yet clear.

Improved bacteriological surveillance of haemodialysis fluids: a comparison between Tryptic soy agar and Reasoner's 2A media.

BACKGROUND: Accurate microbiological surveillance in haemodialysis centres is important as end-stage renal patients can suffer from pyrogenic reactions due to bacterial contamination of dialysis fluids. To evaluate the microbiological quality of haemodialysis fluids, special nutrient-poor culture techniques are necessary. Although the Association for the Advancement of Medical Instrumentation (AAMI) recommends Tryptic soy agar (TSA) as the standard agar, several studies have resulted in a general preference for Reasoner's 2A (R2A) agar, as it appeared to be more sensitive in demonstrating contamination of typical haemodialysis associated bacteria. In the Netherlands TSA is still used for culturing dialysate, while dialysis water is cultured on R2A. Therefore, the aims of our study were to evaluate bacterial yields of dialysis fluids on both media, and to qualify their use in routine microbiological monitoring within our haemodialysis centre. METHODS: Between April 1995 and March 1996, 229 samples of pre-treated and final purified dialysis water, and samples of dialysates were collected. The specimens were aseptically taken from the tap, various points of the reverse osmosis (RO) water-treatment system, and the effluent tubes of 32 bicarbonate haemodialysis machines. Samples of 0.1 ml were inoculated in duplicate on spread plates with TSA and R2A agars. After 10 days of incubation at 25+/-2 degrees C, the numbers of colonies were quantified. The ranges of spread were taken 0-100 and 0-200 colony-forming units per milliliter (c.f.u./ml). RESULTS: The R2A agar had significantly higher colony counts than TSA agar for both dialysis water and dialysates. Considering 100 c.f.u./ml as the upper allowable bacterial limit for all dialysis fluids, microbiological non-compliance (bacterial growth) would be missed in 16% when using only TSA media (TSA < or =100 c.f.u./ml and R2A >100 c.f.u./ml), while this was 3% when using only R2A (TSA >100 c.f.u./ml and R2A < or =100 c.f.u./ml, P<0.0001). Considering 200 c.f.u./ml as the upper limit, non-compliance would have been missed in 10% when using only TSA (TSA < or =200 c.f.u./ml and R2A >200 c.f.u./ml), and 2% when using R2A (TSA > 200 c.f.u./ml and R2A < or =200 c.f.u./ml, P = 0.0011). CONCLUSIONS: Microbiological surveillance of haemodialysis fluids, including pre-treated dialysis water samples collected from RO treatment systems, can be performed more precisely with R2A media than TSA, when incubated at 25+/-2 degrees C for 10 days.

Occurrence of thyroid carcinoma in Dutch patients with familial adenomatous polyposis. An epidemiological study and report of new cases.

OBJECTIVES: To assess the occurrence of thyroid cancer in Dutch patients with familial adenomatous polyposis (FAP) and to discuss the value of surveillance. DESIGN: Retrospective analysis of medical records. SETTING: The data were collected from the Dutch FAP registry. PARTICIPANTS: 601 patients with FAP, 339 males and 262 females. RESULTS: The registry contained four female cases with a thyroid carcinoma. The mean age at diagnosis was 30 years (range: 16-46). In two patients it was the presenting symptom of FAP. None of the women died from their thyroid carcinoma during a mean follow-up of 13 years (range: 6-31). The histology revealed one papillary carcinoma, one follicular carcinoma and two mixed papillary/follicular carcinomas. The relative risk (RR) of developing thyroid carcinoma compared with the general Dutch population was 23 (95% confidence interval: 9-61). At the age of 60 years, the cumulative risk (CR) of thyroid carcinoma for female FAP patients was 2.8%. CONCLUSIONS: Young female FAP patients have a significantly increased RR to develop a thyroid carcinoma. It may even be the presenting symptom of FAP. As the CR of thyroid carcinoma is low and the prognosis seems to be good, we recommend only periodical physical examination of the thyroid.

Food impaction in a duodenal diverticulum as an unusual cause of biliary obstruction: case reports and review of the literature.

We present two patients with upper abdominal complaints and symptoms of biliary obstruction. Endoscopic retrograde cholangiopancreatography showed that the common bile duct was obstructed by a juxtapapillary duodenal diverticulum filled with a food bezoar. There were no gallstones or other potential causes of obstruction. The bile flow was restored and symptoms disappeared after rinsing the diverticulum. Eventually, both of the patients were treated surgically because of recurrent symptoms.

Thyroid carcinoma as first manifestation of familial adenomatous polyposis.

A 22-year-old female member of a family with familial adenomatous polyposis (FAP) presented with a thyroid nodule. Histology revealed a follicular carcinoma. The patient was on regular follow-up as part of the FAP screening program; 1.5 years after the thyroidectomy she appeared to have multiple adenomatous polyps in her colon and FAP was diagnosed. Thyroid-carcinoma is one of the extraintestinal manifestations of FAP and particularly women in the age of 25-35 years are at risk according to the literature.