Mutations in RPSA and NKX2-3 link development of the spleen and intestinal vasculature.

Idiopathic intestinal varicosis is a developmental disorder defined by dilated and convoluted submucosal veins in the colon or small bowel. A limited number of families with idiopathic intestinal varices has been reported, but the genetic cause has not yet been identified. We performed whole-exome and targeted Sanger sequencing of candidate genes in five intestinal varicosis families. In four families, mutations in the RPSA gene were found, a gene previously linked to congenital asplenia. Individuals in these pedigrees had intestinal varicose veins and angiodysplasia, often in combination with asplenia. In a further four-generation pedigree that only showed intestinal varicosities, the RPSA gene was normal. Instead, a nonsense mutation in the homeobox gene NKX2-3 was detected which cosegregated with the disease in this large family with a LOD (logarithm of the odds) score of 3.3. NKX2-3 is a component of a molecular pathway underlying spleen and gut vasculature development in mice. Our results provide a molecular basis for familial idiopathic intestinal varices. We provide evidence for a relationship between the molecular pathways underlying the development of the spleen and intestinal mucosal vasculature that is conserved between humans and mice. We propose that clinical management of intestinal varices, should include assessment of a functional spleen.

Circulating plasma microRNAs as a screening method for detection of colorectal adenomas.

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNA molecules. Reduced or increased levels of specific miRNAs are observed in colon and other cancers, supporting their role in carcinogenesis. Detection of colorectal polyps is the cornerstone of the Bowel Cancer Screening Programme in the UK. However, uptake of screening nationally remains under 60%. We aimed to see whether circulating plasma miRNAs can be used to screen for patients with colorectal polyps, adenomas, or both. METHODS: Blood samples were taken from patients from the Bowel Cancer Screening Programme (asymptomatic but faecal occult blood testing [FOBt] positive). Plasma RNA was extracted, target miRNAs (19a, 98, 146b, 186, 191, 222*, 331-5p, 452, 625, 664, 1247) were identified on pooled case miRNA assay cards, and miRNA fraction was quantified by quantitative RT-PCR assay. Results were compared with endoscopy reports and with histology of any polyps identified and removed. Analysis was done with Excel (2011) and SPSS (version 20) software. FINDINGS: 210 patients were included (117 with polyps, 12 with cancer, 81 healthy controls [FOBt positive]). The miRNA panel showed significant differences in expression (on t testing) for patients compared with controls for those with polyps, cancer, or both (miR-19a, p=0·0184; miR-98, p=0·0206; miR-146b, p=0·0029; miR-186, p=0·0006; miR-62,5 p=0·0008), polyps (miR-19a, p=0·0233; miR-98, p=0·0224; miR-146b, p=0·003; miR-186, p=0·0004; miR-625, p=0·001), adenomas (miR-19a, p=0·0339; miR-98, p=0·0266; miR-146b, p=0·0045; miR-186, p=0·0008; miR-625, p=0·0049), multiple adenomas (both sides of colon; miR-146b, p=0·0194; miR-186, p=0·0226; miR-625, p=0·0013), and right-sided adenomas (miR-98, p=0·031; miR-146b, p=0·0076; miR-186, p=0·0041; miR-331-5p, p=0·0142; miR-625, p=0·0049). Receiver operating characteristic analysis showed sensitivity of 60% or more, and specificity of 86% or more for men with polyps, men with adenomas, all patients with haemorrhoids or diverticulosis and polyps, and all patients with haemorrhoids or diverticulosis and adenomas. INTERPRETATION: The target miRNAs that we identified showed significant differences in expression levels for patients with polyps and patients with adenomas from controls. Use of this panel has potential as a screening test. FUNDING: Bowel Disease Research Foundation.

Efficacy of the revised Enzian classification: a retrospective analysis. Does the revised Enzian classification solve the problem of duplicate classification in rASRM and Enzian?

PURPOSE: The most widely accepted classification for endometriosis is the Revised American Society for Reproductive Medicine (rASRM) system, but this does not take deeply infiltrating endometriosis (DIE) into account. The Enzian classification enables clinicians to classify DIE. Due to complexity and partial overlap with rASRM, it was revised for a second time in February 2011. Using both the systems to classify lesions would be inappropriate, as they refer to different locations. The aim of this study was to analyze whether the revised Enzian classification is easier to use and avoids duplicate classifications. METHODS: Retrospective study of 460 women admitted for endometriosis. RESULTS: One hundred and eighty-seven of 460 patients (41 %) had histologically confirmed DIE based on the revised Enzian classification. Further classification of these 187 patients using Enzian revealed 270 retroperitoneal lesions, as some patients had several DIE-type lesions simultaneously: 66 in compartment A (rectovaginal septum, vagina), 112 in compartment B (sacrouterine ligaments, pelvic wall), 58 in compartment C (bowel), 15 with adenomyosis uteri, 7 with bladder involvement, 8 with intrinsic involvement of the ureter, and 4 with bowel involvement. All 270 lesions were classified using Enzian alone and not with the rASRM score. There were no duplicate classifications (rASRM and Enzian). CONCLUSIONS: The revised Enzian classification is an excellent complement to the rASRM score for morphological description of DIE.

Endometriosis: a premenopausal disease? Age pattern in 42,079 patients with endometriosis.

PURPOSE: The objectives of this study were to examine the age distribution among women suffering from endometriosis and to establish that endometriosis is not a disease that occurs only in premenopausal women. The null hypothesis was that there are also postmenopausal women with endometriosis. METHODS: In a retrospective epidemiological study, a descriptive analysis of data from the Federal Statistical Office in Germany for 2005 and 2006 was carried out. A total of 42,079 women in Germany were admitted for surgical treatment due to histologically confirmed endometriosis during this period. The patients' age distribution was examined and they were assigned to 5-year age groups and then to premenopausal, perimenopausal, and postmenopausal subgroups. RESULTS: A total of 20,835 women in 2005 and 21,244 in 2006 were admitted to hospital for the treatment of endometriosis. In the premenopausal group (age 0-45 years), there were 33,814 patients (80.36 %); 23 patients (0.05 %) in this premenopausal group were younger than 15. There were 7,191 patients (17.09 %) in the perimenopausal group (45-55 years), and the postmenopausal group (55-95 years) included 1,074 patients (2.55 %). CONCLUSIONS: The assumption that endometriosis is a disease of the premenopausal period and in women of reproductive age needs to be called into question, as well as the influence of estrogen in fully developed endometriosis. Due to the relatively high prevalence of the condition in patients aged over 40, physicians should consider endometriosis in cases of unclear pelvic pain in this age group.

Emerging drugs for gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease is a common medical problem caused by the exposure of the distal oesophagus to gastric contents. Existing medical therapy is very effective, but symptomatic relief with acid suppressants is often delayed. Treatment focuses on the suppression of gastric acid rather than on the underlying pathophysiological abnormalities, such as transient non-swallow-related lower oesophageal sphincter relaxation. Current pharmacological developments concentrate on drugs with lasting acid suppression and a faster onset of action. Compounds interacting with the complex neuromuscular regulation of the gastro-oesophageal junction are also being developed and offer exciting prospects.

Ulcerative colitis, primary sclerosing cholangitis and coeliac disease: two cases and review of the literature.

The combination of ulcerative colitis, sclerosing cholangitis and coeliac disease is unusual. The two cases described here illustrate that the investigation and management of such patients can be difficult. Other diagnoses should be considered when a patient with a known pathology fails to respond to treatment. Review of the literature suggests an increased malignant potential in these patients. We conclude that patients with a combination of ulcerative colitis, sclerosing cholangitis and coeliac disease should undergo annual colonoscopic surveillance. In those with clinical deterioration and weight loss, early liver and bowel imaging should be carried out.

Pharmacotherapy for chronic gastro-oesophageal reflux disease and Barrett's oesophagus.

Over the last two decades there have been major advances in the medical treatment of gastro-oesophageal reflux disease (GORD) and Barrett's oesophagus. Motility agents, H(2)-receptor antagonists and proton-pump inhibitors (PPI) have all been evaluated in short- and long-term studies. Symptomatic response needs to be differentiated from healing of oesophagitis and maintenance of remission. Clinical trials have convincingly demonstrated the superiority of PPIs to motility agents and H(2)-receptor antagonists for all clinical aspects of GORD. Barrett's oesophagus requires lifelong acid suppression. Treatment with standard doses of PPIs is often insufficient and higher doses are frequently required. Medical treatment does not appear to result in clinically significant regression of Barrett's oesophagus.

Endometriosis patients in the postmenopausal period: pre- and postmenopausal factors influencing postmenopausal health.

OBJECTIVE: To evaluate patients' health status and the course of endometriosis from the premenopausal to the postmenopausal period and evaluate influencing factors that may be relevant. METHODS: Questionnaire completed by 35 postmenopausal women in whom endometriosis had been histologically confirmed premenopausally. Correlation and regression analyses were carried out to identify factors relevant to their postmenopausal health status. RESULTS: Overall, there was clear improvement in typical endometriosis symptoms and sexual life. Clear associations (P < 0.005) were observed between premenopausal factors like physical limitations caused by the disease, impaired social contacts and psychological problems, and postmenopausal pain and impairment of sexual life. Three statistical models for assessing pain and impairment of sexual life in the postmenopausal period were calculated on the basis of clinical symptoms in the premenopausal period, with a very high degree of accuracy (P < 0.001; R(2) = 0.833/0.857/0.931). CONCLUSIONS: The results of the survey strongly suggest that physical fitness and freedom from physical restrictions, a good social environment, and psychological care in both the premenopausal and postmenopausal periods lead to marked improvements in the postmenopausal period with regard to pain, dyspareunia, and influence on sexual life in endometriosis patients.

Provision of an out-of-hours emergency endoscopy service: the Leicester experience.

INTRODUCTION: The British Society of Gastroenterology (BSG) Strategy document 'Care of patients with Gastrointestinal (GI) disorders' recommends that all acute hospitals should have arrangements for out-of-hours (OOH) endoscopy staffed with appropriately trained endoscopists. The UK national audit published in 2010 found that only 52% of hospitals across the UK had a formal consultant-led OOH endoscopy on-call rota. The University Hospitals of Leicester (UHL) established a consultant-led rota in 2006, which now provides 24/7 endoscopy cover. To define the workload of a newly established OOH service, we examined procedures performed since the introduction of an OOH service in 2006. METHODS: The audit period covered August-January (6 months) for each of five consecutive years. Data were gathered from formal endoscopy reports on Unisoft reporting tool and OOH record books. We examined indication for endoscopy, timing of procedure, findings at index endoscopy, intervention and immediate outcome. RESULTS: Across the three UHL sites, data on 982 patients were analysed. Eighty-one percent of procedures performed were gastroscopies. 63% of the procedures were performed for GI bleed indications. Over the five years, there was an overall increase in the number of procedures performed where no pathology was found. Immediate outcomes postendoscopy were good, with over 90% being returned to their base ward. CONCLUSIONS: The experience at UHL appears to show a trend towards an increasing number of procedures performed OOH, with fewer positive findings and less need for therapy. A likely contributing factor is the ongoing shortage of medical beds, requiring more routine work to be done OOH in order to expedite discharges. However, early specialist endoscopic input is likely to improve patient management. The impact of an OOH service on other services, however, needs to be carefully considered.

Imaging findings post colorectal endoscopic mucosal resection.

Endoscopic mucosal resection is commonly the treatment regime of choice for large sessile colonic polyps. We describe the computed tomography findings of a 51 year old female who presented with transient severe abdominal pain without systemic upset post endoscopic mucosal polyp resection, which resolved with conservative management. This is the second case in the literature that demonstrates 'normal' appearances post endoscopic mucosal resection. The clinical team and radiologist need to be aware of these findings when making management decisions in patients who present with acute pain post endoscopic mucosal resection.

Crohn's disease presenting with pyogenic liver abscess: a case report.

Pyogenic liver abscess (PLA) is a rare extraintestinal complication of Crohn's disease (CD), and the clinical and laboratory findings may emulate the reactivation of CD, therefore, delaying diagnosis. In this paper the patient presented with PLA as the initial manifestation of CD and experienced severe disease. The finding of PLA was established by computed tomography and initial treatment involved percutaneous drainage and antibiotics. The diagnosis of CD was made after colonoscopy and histological investigations.

Scope to improve: a multi-centre audit of 16 064 colonoscopies looking at caecal intubation rates, over a 2-year period.

OBJECTIVE: Colonoscopy is the 'gold standard' assessment for large bowel mucosal pathology, but a complete examination is essential. The first national colonoscopy audit carried out in 1999 demonstrated caecal intubation rates (CIRs) of 56.9%. As a result, the Joint Advisory Group (JAG) on gastrointestinal endoscopy launched a programme of continuous quality improvement. JAG recommends that practitioners undertake 100+ procedures per annum with a target CIR of 90%. This current audit provides an assessment of performance against this quality standard. DESIGN: Data were collected from all procedures undertaken in 2008-2009 from six hospitals across three English regions. RESULTS: 16064 colonoscopies performed: CIR = 90.57% (95% CI 90.11% to 91.01%). Operators doing 100+ procedures per annum, CIR=91.76% (91.24% to 92.25%). Operators doing <100 procedures per annum, CIR=87.77% (86.82% to 88.67%). Gastroenterologists, CIR=91.01% (90.32% to 91.70%). Surgeons, CIR=91.03% (90.27% to 91.79%). Other practitioners, CIR=81.51% (78.79% to 84.22%). Bowel cancer screening programme (BCSP) colonoscopies, CIR=97.71% (97.07% to 98.34%). Non-screening colonoscopies, CIR=88.31% (95% CI 87.68% to 88.94%). CONCLUSION: This audit of 16064 colonoscopies across three regions demonstrates aggregated achievement of the CIR quality standard. However, there is a significant performance gap when comparing BCSP colonoscopists with non-screening colonoscopists and the overall CIR of >90% is supported by the volume of BCSP colonoscopy. Endoscopists performing low volume colonoscopy (<100 per annum), have CIR of <90%. Endoscopists with low volume practice who do not meet the quality standards should engage in skills augmentation plus further training and increase volume of colonoscopy with local mentorship, or stop performing colonoscopy.

Comparison of revised American Fertility Society and ENZIAN staging: a critical evaluation of classifications of endometriosis on the basis of our patient population.

OBJECTIVE: To develop a classification that takes deep infiltrating endometriosis into account, the ENZIAN score was introduced. The ENZIAN classification supplements the revised American Fertility Society (AFS) score with regard to the description of deep infiltrating endometriosis, retroperitoneal structures, and other organs. The null hypothesis was that classifying a lesion by the revised AFS as well as the ENZIAN system is not meaningful, because the two systems express different locations. DESIGN: Retrospective. SETTING: Hospital admissions. PATIENT(S): Two hundred nineteen women admitted for endometriosis. INTERVENTION(S): Surgical interventions. MAIN OUTCOME MEASURE(S): Classification of the severity of endometriosis according to the revised AFS and the ENZIAN classification, focusing on the distribution pattern in deep infiltrating endometriosis, and the identification of duplicate classifications of the same lesions in the revised AFS as well as the ENZIAN systems. RESULT(S): Deep infiltrating endometriosis was diagnosed in 160 of 219 patients (73%). These patients had 236 lesions of deep infiltrating endometriosis, which were classified by ENZIAN as follows: compartment a (vertical): 26%; compartment b (horizontal): 41%; compartment c (dorsal): 24%; uterine adenomyosis: 4%; bladder disease: 2%; ureter disease: 1%; and bowel disease: 2%. The severity of deep infiltrating endometriosis according to ENZIAN (grades 1 = mild to 4 = severe) was as follows: grade 1: 45%; grade 2: 26%; grade 3: 19%; grade 4: 10%. Fifty-eight patients were classified according to ENZIAN although they did not fulfill the criteria of deep infiltrating endometriosis and had previously been classified according to the revised AFS classification. Adaptation of the ENZIAN score would reduce the diagnoses of deep infiltrating endometriosis by 36% (95% confidence interval [CI] 29%-44%). CONCLUSION(S): The ENZIAN score is a helpful aid to describe deep infiltrating endometriosis, but needs to be adapted.