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The diagnosis of Crohn’s disease (CD) in the small bowel is generally performed by observing a very large number of images captured by capsule endoscopy (CE). This diagnostic technique entails a heavy workload for the specialists in terms of time spent reviewing the images. This paper presents a convolutional neural network capable of classifying the CE images to identify those ones affected by lesions indicative of the disease. The architecture of the proposed network was custom designed to solve this image classification problem. This allowed different design decisions to be made with the aim of improving its performance in terms of accuracy and processing speed compared to other state-of-the-art deep-learning-based reference architectures. The experimentation was carried out on a set of 15,972 images extracted from 31 CE videos of patients affected by CD, 7,986 of which showed lesions associated with the disease. The training, validation/selection and evaluation of the network was performed on 70%, 10% and 20% of the total images, respectively. The ROC curve obtained on the test image set has an area greater than 0.997, with points in a 95-99% sensitivity range associated with specificities of 99-96%. These figures are higher than those achieved by EfficientNet-B5, VGG-16, Xception or ResNet networks which also require an average processing time per image significantly higher than the one needed in the proposed architecture. Therefore, the network outlined in this paper is proving to be sufficiently promising to be considered for integration into tools used by specialists in their diagnosis of CD. In the sample of images analysed, the network was able to detect 99% of the images with lesions, filtering out for specialist review 96% of those with no signs of disease., Funding for open access charge: Universidad de Huelva / CBUA This work was part of a project funded under the 2014-2020 Andalusia ERDF Operational Programme (Project Reference: UHU-1257810- PO FEDER 2014-2020)

Hyperdensity within the small bowel is most commonly seen with positive oral contrast agents, intraluminal hemorrhage and less likely an abnormal fistulous connection with the colon containing rectally administered contrast. We present the case of a 57-year-old female with a complex history of breast cancer and multiple abdominal surgeries presenting with intraluminal hyperdense small bowel on computed tomography (CT) performed with rectal contrast. Postsurgical CT with rectal contrast, and no oral contrast, showed multifocal regions of intraluminal hyperdensity with the small bowel anterior to and close to the surgical anastomosis. This raised concerns for a fistula between the colon and small bowel; however, surgical exploration demonstrated an intact anastomosis without a coloenteric fistula. Additional history notes that the patient consumed an increased dose of calcium carbonate tablets for a few days prior to obtaining the scan and this intraluminal hyperdense appearance of the small bowel was then attributed to this. We conclude that ingested over the counter medications can pose an imaging dilemma for radiologists as their appearance on CT could falsely mimic pathology. It is imperative to obtain a thorough clinical history in such cases to provide accurate diagnoses and decrease unwanted imaging and clinical intervention. It is also important for radiologists to be aware of the appearances of commonly consumed over the counter medications that can mimic pathology as demonstrated by this case.

One of the major complications that patients experience during pharmacological treatment is the occurrence of adverse drug reactions (ADRs). The most affected organs are the liver, kidney, heart and the gastrointestinal-immune system. In comparison to the other organs, less progress has been made on human-relevant prediction of drug-induced intestinal toxicity, evidencing current large data gaps. The most widely used drugs that are associated with intestinal damage include chemotherapeutics, such as 5-Fluorouracil or Tyrosine Kinase Inhibitors (TKIs), as well as non-steroidal anti-inflammatory drugs (NSAIDs). Chemotherapeutics are regarded as inducers of acute intestinal toxicity whereas NSAIDs are associated with chronic inflammation of the intestine. In view of the fact that only a few studies have been dedicated to studying cellular and genomic responses in relation to drug-induced intestinal ADRs, little is known about how intestinal toxicity develops after exposure to such drugs or which molecular mechanisms are involved. Therefore, new models and experiments are required to establish transcriptomic responses and alterations of molecular markers induced by different medicines. This review summarizes the available information about transcriptomic responses and biomarkers of toxicity induced by 5-FU, NSAIDS or TKIs in different experimental models. Future investigation should address the challenges in predicting intestinal toxicity induced by drugs and unveil specific gene expression profiles that can be applied in the development of safer drugs.

Objective The utility of capsule endoscopy (CE) findings in the route selection for double balloon endoscopy (DBE) has not been adequately discussed. The PillCam Progress Indicator in the RAPID 6.5 software program graphically demonstrates the progress of the capsule endoscope through the small-bowel. This study aimed to clarify the usefulness of the PillCam Progress Indicator in choosing the initial DBE route. Methods We retrospectively examined 50 consecutive patients with 50 target lesions detected on both CE and DBE at Hiroshima University Hospital from January 2011 to February 2018. In this study, we selected antegrade DBE on the basis of % Capsule Progress

AIM: To assess the diagnostic signifi cance of magnetic resonance enterography (MRE) and conventional enteroclysis (CE) in patients with complicated and/or advanced stage of Crohn's disease. METHODS: Patients with abnormal CE fi ndings suggestive of mural and/or extramural involvement with the diagnosis or pre-diagnosis of CD are evaluated. After real-time bowel distension by enteroscopic examination, the patients with advanced or complicated stage were taken to the MRE examination in the same session. Mucosal-mural-extramural and activation fi ndings, presence of stenosis/stricture, skip lesions and the mean duration of exams were evaluated with both CE and MRE. The superiority of one method over the other relative to these fi ndings was evaluated. RESULTS: A total of 110 patients evaluated by CE had the fi ndings of CD. Of these, 24 patients with abnormal CE fi ndings suggestive of advanced mural and extramural involvements were subsequently evaluated with MRE. CE was superior to MRE in the depiction of early superfi cial mucosal changes (aphthous-linear ulcer), cobblestone pattern (p = 0.002, p < 0.01), obstruction (p = 0.004, p < 0.01), and differentiation between the string sign and stricture. MRE was superior to conventional enteroclysis in mural and perienteric fi ndings of bowel thickening, fi bro-fatty proliferation, abscess (p = 0.016, p < 0.05) and colonic skip lesions. No signifi cant difference was found between the evaluated methods in terms of fi stula detection (p = 1.000; p > 0.05). CONCLUSION: CE and MRE are mutually complementary imaging modalities in CD staging, evaluation of activation fi ndings, and detection of complications (Tab. 3, Fig. 8, Ref. 23). Text in PDF www.elis.sk

Background. Intestinal sensitivity to mechanical stimuli has been studied intensively in visceral pain studies. The ability to sense different stimuli in the gut and translate these to physiological outcomes relies on the mechanosensory and transductive capacity of intrinsic intestinal nerves. However, the nature of the mechanosensitive channels and principal mechanical stimulus for mechanosensitive receptors are unknown. To be able to characterize intestinal mechanoelectrical transduction, that is, the molecular basis of mechanosensation, comprehensive mathematical models to predict responses of the sensory neurons to controlled mechanical stimuli are needed. This study aims to develop a biophysically based mathematical model of the myenteric neuron with the parameters constrained by learning from existing experimental data. Findings. The conductance-based single-compartment model was selected. The parameters in the model were optimized by using a combination of hand tuning and automated estimation. Using the optimized parameters, the model successfully predicted the electrophysiological features of the myenteric neurons with and without mechanical stimulation. Conclusions. The model provides a method to predict features and levels of detail of the underlying physiological system in generating myenteric neuron responses. The model could be used as building blocks in future large-scale network simulations of intrinsic primary afferent neurons and their network.

Non-biopsy diagnosis of celiac disease is possible in children with anti-transglutaminase 2 antibodies (TGA) &gt, 10&times, the upper limit of normal (ULN) and positive anti-endomysial antibodies (EMA). Similar criteria have been suggested for adults, but evidence with different TGA assays is scarce. We compared the performance of four TGA tests in the diagnosis of celiac disease in cohorts with diverse pre-test probabilities. Serum samples from 836 adults with either clinical suspicion or family risk of celiac disease were tested with four commercial TGA assays, EmA and celiac disease-associated genetics. The diagnosis was set based on duodenal lesion or, in some cases, using special methods. 137 (57%) patients with clinical suspicion and 85 (14%) of those with family risk had celiac disease. Positive predictive value (PPV) for 10&times, ULN was 100% in each TGA test. The first non-diagnostic investigations were encountered with ULN 1.0&times, &ndash, 5.1&times, in the clinical cohort and 1.3&times, 4.9&times, in the family cohort, respectively. Using the assays&rsquo, own cut-offs (1&times, ULN) the PPVs ranged 84&ndash, 100%. Serology-based diagnosis of celiac disease was accurate in adults using different commercial kits and pre-test probabilities using 10&times, ULN. The results also suggest that the ULN threshold for biopsy-omitting approach could be lower.

Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are heterogeneous regarding site of origin, biological behavior, and malignant potential. There has been a rapid increase in data publication during the last 10 years, mainly driven by high-throughput studies on pancreatic and small intestinal neuroendocrine tumors (NETs). This review summarizes the present knowledge on genetic and epigenetic alterations. We integrated the available information from each compartment to give a pathway-based overview. This provided a summary of the critical alterations sustaining neoplastic cells. It also highlighted similarities and differences across anatomical locations and points that need further investigation. GEP-NENs include well-differentiated NETs and poorly differentiated neuroendocrine carcinomas (NECs). NENs are graded as G1, G2, or G3 based on mitotic count and/or Ki-67 labeling index, NECs are G3 by definition. The distinction between NETs and NECs is also linked to their genetic background, as TP53 and RB1 inactivation in NECs set them apart from NETs. A large number of genetic and epigenetic alterations have been reported. Recurrent changes have been traced back to a reduced number of core pathways, including DNA damage repair, cell cycle regulation, and phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling. In pancreatic tumors, chromatin remodeling/histone methylation and telomere alteration are also affected. However, also owing to the paucity of disease models, further research is necessary to fully integrate and functionalize data on deregulated pathways to recapitulate the large heterogeneity of behaviors displayed by these tumors. This is expected to impact diagnostics, prognostic stratification, and planning of personalized therapy.

Introduction Currently, there is no adequate prevention or treatment for both oral and gastrointestinal mucositis induced by chemotherapy and/or radiotherapy. Supportive care of symptoms plays a primary role during mucositis in the pediatric clinical setting. We aimed to get insight in the currently used feeding strategies in clinical practice in pediatric cancer patients with chemotherapy-induced mucositis. Methods A prospective observational study was performed to identify feeding strategies after chemotherapy courses causing mucositis in almost all patients at the University Medical Center Groningen (UMCG), the Academic Medical Center Amsterdam (AMC), and the Princess Maxima Center Utrecht (PMC). Consecutive patients, aged 0–18 years, either diagnosed with B cell non-Hodgkin lymphoma (B-NHL) or scheduled for autologous stem cell transplantation (SCT) between April 2015 and September 2016 were included in this study. In addition to the observational study in the Netherlands, an international online questionnaire was conducted for pediatric oncology centers. Results A total of 13 patients were included, after 21 chemotherapy courses. No nutritional support was administered after 23.8% courses, tube feeding after 19.0% of the courses, TPN in 19.0% of courses, and 38.1% received a combination of tube feeding and TPN. The international survey revealed that 63.2% of the centers administered tube feeding as first choice, 31.6% administered only TPN as first choice, and one center administered a combination as first choice. Conclusions There is a variability in feeding strategies in the clinical practice both in the Netherlands as well as worldwide. This study is a basis for future studies in this important clinical field to develop clinical trials comparing tube feeding and TPN both in adult and pediatric patients. Electronic supplementary material The online version of this article (doi:10.1007/s00520-017-3715-7) contains supplementary material, which is available to authorized users.

Gastrointestinal mucositis is a complex inflammatory reaction of the mucous membranes, a side effect of both chemotherapy and radiotherapy. Currently, assessment scales are used to diagnose mucositis. However, a biomarker which would determine whether there is mucositis and thereby establish the severity objectively would be very useful. This will give the opportunity to evaluate studies, to determine risk factors and incidence, and it will make it possible to compare studies. Moreover, this biomarker might improve clinical management for patients. In this paper, we reviewed studies concerning potential biomarkers in blood samples and fecal samples, and potential tests in breath samples and urine samples. We include biomarkers and tests studied in animal models and/or in clinical trials, and discuss the validity, diagnostic accuracy, and applicability.

Contains fulltext : 177302.pdf (Publisher’s version ) (Open Access) Gastrointestinal mucositis is a complex inflammatory reaction of the mucous membranes, a side effect of both chemotherapy and radiotherapy. Currently, assessment scales are used to diagnose mucositis. However, a biomarker which would determine whether there is mucositis and thereby establish the severity objectively would be very useful. This will give the opportunity to evaluate studies, to determine risk factors and incidence, and it will make it possible to compare studies. Moreover, this biomarker might improve clinical management for patients. In this paper, we reviewed studies concerning potential biomarkers in blood samples and fecal samples, and potential tests in breath samples and urine samples. We include biomarkers and tests studied in animal models and/or in clinical trials, and discuss the validity, diagnostic accuracy, and applicability.

Background: In the medical literature, the nomenclature and descriptions (ND) of small bowel (SB) ulcerative and inflammatory (U-I) lesions in capsule endoscopy (CE) are scarce and inconsistent. Inter-observer variability in interpreting these findings remains a major limitation in the assessment of the severity of mucosal lesions, which can impact negatively on clinical care, training and research on SB-CE. Objective: Focusing on SB-CE in Crohn’s disease (CD), our aim is to establish a consensus on the ND of U-I lesions. Methods: An international panel of experienced SB-CE readers was formed during the 2016 United European Gastroenterology Week meeting. A core group of five CE and inflammatory bowel disease (IBD) experts established an Internet-based, three-round Delphi consensus but did not participate in the voting process. The core group built illustrated questionnaires, including SB-CE still frames of U-I lesions from patients with documented CD. Twenty-seven other experts were asked to rate and comment on the different proposals for the ND of the most frequent SB U-I lesions. For each round, we used a 6-point rating scale (varying from ‘strongly disagree’ to ‘strongly agree’). The consensus was reached when at least 80 % of the voting members scored the statement within the ‘agree’ or ‘strongly agree’ categories. Results: A 100% participation rate was obtained for all the rounds. Consensual ND were reached for the following seven U-I lesions: aphthoid erosion, deep ulceration, superficial ulceration, stenosis, edema, hyperemia and denudation. Conclusion: Considering the most frequent SB U-I lesions seen in CE in CD, a consensual ND was reached by the international group of experts. These descriptions and names are useful not only for daily practice and medical education, but also for medical research.

Objective The aim of the present study is to assess the difference in the detection rates of small-bowel lesions in chronic abdominal pain (CAP) patients with irritable bowel syndrome (IBS) and non-IBS. Patients Ninety-nine CAP patients who were scheduled to undergo capsule endoscopy (CE) to investigate their abdominal symptoms were included in this study. Among the subjects, 34 patients fulfilled the Rome III criteria for IBS (IBS group); the remaining 65 patients were categorized as the non-IBS group. CE was performed in both groups and the total enteroscopy achievement rate, small-bowel lesion detection rate, and the presence of small-bowel lesions were evaluated. We also evaluated the patients' blood test results and the rate at which abdominal symptoms improved following internal medication. Results Total enteroscopy was achieved in 62% (21/34) and 86% (56/65) of the IBS and non-IBS patients, respectively. The total enteroscopy achievement rate was significantly higher in non-IBS patients. The small-bowel lesion detection rates were 3% (1/34) and 19% (12/65), respectively, and the detection rate was significantly higher in the non-IBS patients. In the non-IBS patients, mean C-reactive protein (CRP) was significantly higher in the patients with small-bowel lesions. The abdominal symptoms of 12 (92%) of the CAP patients with small-bowel lesions were improved by internal medication. Conclusion CE may be considered for non-IBS CAP patients with high levels of CRP.

Highlights • Pre-operative diagnosis of fish bone perforation of the bowel is difficult. • It usually mimics common abdominal pathology. • A low threshold must be maintained to perform a diagnostic laparoscopy., Introduction The diagnosis of abdominal complications due to fish bone ingestion is particularly difficult as the presentation may mimic common abdominal pathologies. Presentation of case 65 year-old male presented with a two day history of right iliac fossa pain. He denied any nausea and vomiting. He had no systemic systems including fever, change in bowel habit. He had tenderness and guarding localized to the right iliac fossa. He had raised inflammatory markers. A CT scan of the abdomen was performed which showed fat standing in proximity to the terminal ileum, with the appearance of Crohn’s disease. The clinical picture did not match the imaging and so the patient underwent a diagnostic laparoscopy. Findings included an acutely inflamed terminal ileum. A foreign body was identified piercing through at the small bowel wall at the terminal ileum. The foreign body was removed and revealed a fish bone. Intracorporeal sutures were inserted at the site of the microperforation. The patient was discharged well two days post operatively. Discussion Fish bone perforation is not a common cause of gastrointestinal perforation. Unfortunately the history is often non-specific and these people can be misdiagnosed with acute appendicitis & other pathologies. CT scans can be useful to aid diagnostics. It is not however fully sensitive in detecting complications arising from fishbone ingestion. Conclusion Management therefore, should be based taking into account primarily the clinical picture & may necessitate diagnostic laparoscopy.

Purpose: to compare diagnostic performance of CT-arterial vs. CT-venous phase, to assess decreased small bowell-wall enhancement (DBE) as a sign of ischemia in adhesive small bowell obstruction (ASBO). Material and methods: a total of 59 consecutives patients (mean age, 73.3 years) explored by a triphasic CT (unenhanced, arterial and venous phases) with a final diagnosis of ASBO were included. Two gastrointestinal radiologists performed two blinded, independent, and retrospective reviews of CT studies, for evaluating DBE and reporting their confidence level. Read 1 included an unenhanced CT and CT-arterial phase images, and read 2, one month later: an unenhanced CT and CT-venous phase images. Reference standard for ischemia was proved by surgery. Diagnostic performances of DBE for ischemia were calculated for each reader and for consensual reading and compared between the two readings by using McNemar rank tests. Kappa statistics were used to analyze interobserver agreement. Results: ischemia was confirmed in 21 of 59 (35.6%) cases. There was no significant difference in interobserver agreement (kappa=0.62 and 0.61) for assessing DBE between the 2 readings. Global diagnostic performance using ROC curves for each reader was not significantly different between the 2 readings (p=0.11 and 0.86). After consensus, sensitivity, specificity, positive and negative predictive values were 81%, 74%, 63% and 87%; and 81%, 79%, 68% and 88%, without significant differences for read 1 and 2 respectively. Conclusion: CT-arterial phase does not improve interobserver agreement, nor the diagnostic performance for assessment of DBE as a sign of ischemia in ASBO.; Objectifs : comparer la performance diagnostique du temps artériel versus portal pour l’évaluation en scanner de l’asymétrie ou du défaut de rehaussement pariétal (ADRP), comme signe d’ischémie, dans les occlusions mécaniques du grêle (OMG). Méthodes : 59 patients explorés par scanner triphasique, avec diagnostic final d’OMG étaient inclus. 2 radiologues digestifs ont analysé, en aveugle, de manière indépendante et rétrospective les scanners. La lecture 1 incluait une phase sans contraste et une phase artérielle, et la lecture 2 incluait une phase sans contraste et une phase portale. Le standard de référence pour l’ischémie était la chirurgie. La performance diagnostique de l’ADRP pour le diagnostic d’ischémie était calculée pour chaque lecteur et pour la lecture consensuelle et comparée entre les 2 lectures en utilisant le test de McNemar. La reproductibilité inter-observateur était analysée par le test statistique du Kappa. Résultats : une ischémie était présente dans 21 cas sur 59 (35,6%). Il n’y avait pas de différence significative pour la reproductibilité inter-observateur (kappa = 0,62 et 0,61, p=0.56) entre les phases artérielle et portale. Les performances diagnostiques globales pour chaque lecteur n’étaient pas différentes entre les 2 lectures (p=0.11 and 0.86). Après consensus, la sensibilité, la spécificité, la VPP et la VPN n’étaient pas statistiquement différentes entre les 2 lectures (81%, 74%, 63% et 87 % ; et 81%, 79%, 68% et 88% pour la lecture1 et 2 respectivement. Conclusion : la phase artérielle en scanner n’augmente pas la reproductibilité interobservateur, ni la performance diagnostique de l’ADRP pour le diagnostic d’ischémie dans les OMG.

Fijlstra M, Rings EH, Verkade HJ, van Dijk TH, Kamps WA, Tissing WJ. Lactose maldigestion during methotrexate-induced gastrointestinal mucositis in a rat model. Am J Physiol Gastrointest Liver Physiol 300: G283-G291, 2011. First published November 18, 2010; doi:10.1152/ajpgi.00462.2010.-Patients with chemotherapy-induced gastrointestinal mucositis suffer from anorexia, diarrhea, and stomach pain, often causing weight loss and malnutrition. When the intestinal function during mucositis would be known, a rational feeding strategy might improve the nutritional state, accelerate recuperation, and increase survival of mucositis patients. We developed a methotrexate (MTX)-induced mucositis rat model to study nutrient digestion and absorption. To determine lactose digestion and absorption of its derivative glucose during mucositis, we injected Wistar rats intravenously with MTX (60 mg/kg) or 0.9% NaCl (controls). Four days later, we orally administered trace amounts of [1-C-13] lactose and [U-C-13] glucose and quantified the appearance of labeled glucose in the blood for 3 h. Finally, we determined plasma citrulline level and harvested the small intestine to assess histology, myeloperoxidase level, glycohydrolase activity, immunohistochemical protein, and mRNA expression. MTX-treated rats showed profound villus atrophy and epithelial damage. During the experimental period, the absorption of lactose-derived [1-C-13] glucose was 4.2-fold decreased in MTX-treated rats compared with controls (P

Bayramoglu Z, Yilmaz R, Demir AA, Ataizi-Celikel C, Kombak FE, Ikinci A, Yekeler E. Multimodality imaging findings of visceral myopathy in a child presenting with palpable abdominal mass. Turk J Pediatr 2019; 61: 120-125. Visceral myopathy is a rare cause of intestinal obstruction characterized by intestinal dysmotility and constipation. Patients often present with recurrent abdominal pain, vomiting and abdominal distension. We report a rare case of visceral myopathy in a child presenting with intraabdominal mass. We aimed to describe ultrasound, computed tomography and magnetic resonance enterography findings of this rare disease that has not been demonstrated before. Differential diagnosis of mural thickening with distinguishable layers in addition to intestinal dilatation in the absence of mesenteric inflammation includes visceral myopathy.

Background Information about the extent of carbohydrate digestion and fermentation is critical to our ability to explore the metabolic effects of carbohydrate fermentation in vivo. We used cooked (13)C-labelled barley kernels, which are rich in indigestible carbohydrates, to develop a method which makes it possible to distinguish between and to assess carbohydrate digestion and fermentation. Materials and methods Seventeen volunteers ingested 86 g (dry weight) of cooked naturally (13)C enriched barley kernels after an overnight fast. (13)CO(2) and H(2) in breath samples were measured every half hour for 12 h. The data of (13)CO(2) in breath before the start of the fermentation were used to fit the curve representing the digestion phase. The difference between the area under curve (AUC) of the fitted digestion curve and the AUC of the observed curve was regarded to represent the fermentation part. Different approaches were applied to determine the proportion of the (13)C-dose available for digestion and fermentation. Results Four hours after intake of barley, H(2)-excretion in breath started to rise. Within 12 h, 24-48% of the (13)C-dose was recovered as (13)CO(2), of which 18-19% was derived from colonic fermentation and the rest from digestion. By extrapolating the curve to baseline, it was estimated that eventually 24-25% of the total available (13)C in barley would be derived from colon fermentation. Conclusion Curve fitting, using (13)CO(2)- and H(2)-breath data, is a feasible and non-invasive method to assess carbohydrate digestion and fermentation after consumption of (13)C enriched starchy food.

Contains fulltext : 69805.pdf (Publisher’s version ) (Closed access) Most Gram-positive bacteria inhabiting the gastrointestinal tract are capable of hydrolysing bile salts. Bile salt hydrolysis is thought to play an important role in various biological processes in the host. Therefore, correct annotation of bacterial bile salt hydrolases (Bsh) in public databases (EC 3.5.1.24) is of importance, especially for lactobacilli, which are considered to play a major role in bile salt hydrolysis in vivo. In the present study, all enzymes listed in public databases that belong to the Bsh family and the closely related penicillin V acylase (Pva; EC 3.5.1.11) family were compared with the sequences annotated as Bsh in Lactobacillus plantarum WCFS1, as an example. In Gram-positive bacteria, a clear distinction was made between the two families using sequence alignment, phylogenetic clustering, and protein homology modelling. Biochemical and structural data on experimentally verified Bsh and Pva enzymes were used for validation of function prediction. Hidden Markov models were constructed from the sequence alignments to enable a more accurate prediction of Bsh-encoding genes, and their distinction from those encoding members of the Pva family. Many Pva-related sequences appeared to be annotated incorrectly as Bsh in public databases. This refinement in the annotation of Bsh family members influences the prediction of the function of bsh-like genes in species of the genus Lactobacillus, and it is discussed in detail.

Keliakia on ravinnon gluteenin laukaisema krooninen suolistosairaus, jota sairastaa jopa 2-3% suomalaisista. Sairauden ilmiasu voi vaihdella suolisto-oireista suoliston ulkopuolisiin oireisiin, pelkkiin verenkuvamuutoksiin ja jopa oireettomiin potilaisiin, jotka löytyvät vain seulomalla riskiryhmiä. Taudin seulonnassa käytetään veren vasta-ainetutkimuksia, mutta diagnoosi tehdään ohutsuolen koepalassa todetun tyypillisen limakalvovaurion perusteella. Limakalvovaurion arvioinnissa on kuitenkin mahdollisia virhelähteitä, jotka pitää ottaa huomioon oikean diagnoosin varmistamiseksi. Tavallisesti koepaloista tehdyt leikkeet luokitellaan kategorisesti numeroarvolla tai sanallisesti, mutta valitettavasti tämä tapa on osoittautunut epätarkaksi ja arviot koepaloista vaihtelevat usein riippuen arvioitsijasta. Koepaloista tehdyistä leikkeistä voidaan myös suoraan mitata suolinukan pituuden ja suolikuopakkeiden syvyyden suhde ja limakalvotulehduksen aste, jotka kuvaisivat suolen tilaa tarkemmin ja olisivat sopivampia erityisesti tutkimuskäyttöön. Tämän tutkimuksen tarkoituksena oli tutkia näiden suorien mittareiden luotettavuutta keliakian diagnostiikassa ja tutkimuskäytössä. Lisäksi tutkittiin pohjukaissuolen alkuosan eli bulbuksen näytteiden merkitystä keliakian diagnosoinnissa sekä arvioitiin suolivaurion verrannollisuutta keliakian kliiniseen taudinkuvaan. Väitöskirjatutkimuksen tulokset osoittivat toimintatapamme ja suorat limakalvomittarit luotettavaksi arvioitaessa limakalvovauriota. Lisäksi tulokset osoittivat ohutsuolen suolivaurion asteen olevan verrannollinen potilaiden kokemiin suolisto-oireisiin ja elämänlaatuun, laboratorioarvoihin, limakalvotulehduksen voimakkuuteen sekä keliakiavasta-ainetasoihin. Myös seerumin vasta-ainetasot olivat verrannolliset lähes samoihin muuttujiin kuin suolivaurio. Pohjukaissuolen alkuosan näytteet osoittautuivat olevan huonolaatuisia ja siellä esiintyy hämäävästi limakalvovauriota monien muidenkin tautitilojen yhteydessä. Suolen vasta-ainekertymiä löydettiin kaikilta keliakia-potilailta ja nämä voisivatkin olla keino epävarmoissa tapauksissa todeta keliakia. Suolen suorat limakalvomittarit todettiin luotettaviksi diagnostiikassa ja tutkimuskäytössä. Näytteiden pitää kuitenkin olla hyvänlaatuisia tai jopa väärä diagnoosi on mahdollinen. Erityisesti pohjukaissuolen alkuosan limakalvovauriota pitää tulkita varoen. Oireiden ja suolivaurion verrannollisuus luo uusia työkaluja keliaakikkojen seurantaan. Coeliac disease is an autoimmune reaction triggered by dietary gluten in the small-bowel mucosa of genetically susceptible patients. The clinical presentation is diverse, ranging from classical gastrointestinal symptoms to extraintestinal manifestations, mild laboratory abnormalities or seemingly asymptomatic patients who are found by screening in at-risk groups. Antibody assays from serum are nowadays widely used in screening patients, but the final diagnosis requires villous atrophy and crypt hyperplasia in small-bowel biopsy. It has however recently been recommended in the new European guidelines that children with very high antibody titres could be diagnosed without biopsy. The biopsies are taken via oesophagogastroduodenoscopy from the second part of the duodenum, but according to recent guidelines also from the proximal duodenal bulb. The specimens are usually graded with a categorical variable such as the Marsh classification as this suits for quick visual estimates. However, the reliability and reproducibility of such classifications has been found to be poor in many studies and they are thus too rough and inaccurate for academic, clinical and pharmacological studies. Quantitative histological measurements such as the villous height crypt depth ratio (VH: CrD) and intraepithelial lymphocyte (IEL) density would more accurately represent the spectrum of mucosal damage as a continuum. The aim of this study was to assess the reliability and reproducibility of the reading of biopsy specimens with specific emphasis on the use of these quantitative methods in coeliac disease. Additionally, the link between the degree of mucosal damage and symptoms and signs of coeliac disease and the reliability of bulb biopsies in coeliac disease was further evaluated. The dissertation comprises three separate studies. Study I investigated the reliability and reproducibility of quantitative histological measurements and possible pitfalls due to specimen sectioning in coeliac disease diagnostics. Altogether 93 samples with different grades of mucosal injury were evaluated in blinded fashion. In study II symptoms and signs of coeliac disease were assessed against the degree of mucosal damage and serum antibody titres. Duodenal samples were collected from 638 consecutive oesophagogastroduodenoscopies and the results were compared to patient reported symptoms, quality of life, laboratory parameters and bone mineral density. Finally, study III was a prospective multicentre study assessing the reliability of duodenal bulb specimens in coeliac disease diagnostics in children. Sera and biopsy samples were collected from 22 coeliac disease patients and 22 non-coeliac disease controls. Study I showed that the VH:CrD is a reliable and reproducible method in measuring small-bowel mucosal damage. A new cut-off for clinically significant change was set at 0.4, which may be used in future clinical trials. The reason for faulty diagnoses from tangential cuttings was apparent in the 3D models of mucosal damage presented. The results from study II showed significant correlations between VH:CrD and gastrointestinal symptoms, quality of life, laboratory parameters, mucosal inflammation and serum antibody titres. Also, serum antibody titres correlated with almost all the same parameters as the VH:CrD. In study III, the anatomical duodenal bulb samples were of inadequate quality and mucosal damage was also present in bulb specimens from disease control patients. Bulb mucosal transglutaminase 2 targeted intestinal IgA deposits found coeliac disease patients in all. The results of this investigation proved that quantitative small-bowel morphometric measurements are a reliable method in evaluating mucosal injury in coeliac disease. The samples must be well oriented and of good quality to ensure reliable results. The degree of small-bowel mucosal damage correlated with most of the patient-reported symptoms and signs, thus adding informational value to the pathological diagnostics, while on the other hand the symptoms may be used as an indicator of mucosal status in large population studies. Damage in anatomical bulb specimens must be interpreted with caution and in uncertain cases analysis of IgA deposits is an effective tool in finding celiac disease patients. More studies are needed to assess the diagnostic yield acquired with the addition of bulb biopsies.

Background: Apple peel atresia is the rarest type of small bowel atresia. Because of its rare occurrence and high mortality rate, little is known about the long-term outcome of these children.Methods: The patient charts, operative reports, and office notes of 15 children with apple peel atresia from 6 pediatric surgical centers in the Netherlands were reviewed. Longterm follow-up was assessed through review of office notes and through questionnaires.Results: The median age at the time of operation was 1.5 days. Postoperatively, 53% suffered from cholestasis, and 40% were septic. Three patients died (20%). At follow-up at a median age of 24 months, 1 child showed growth retardation and 2 children suffered from short bowel syndrome. At the time of the questionnaire, all children showed normal growth and development.Conclusions: Even though children with apple peel atresia often suffer serious morbidity like short bowel syndrome and sepsis during the postoperative course, late morbidity turned out to be low. If the patients survive the operative and direct postoperative period, and survive the morbidity associated with malnutrition and the long-term use of total parenteral nutrition, they have a good chance of having normal bowel function with normal growth and development. J Pediatr Surg 37:61-65. Copyright (C) 2002 by W.B. Saunders Company.

AIM: To highlight magnetic resonance enterography (MRE) for diagnosis of patients with refractory iron deficiency anemia and normal endoscopy results. METHODS: Fifty-three patients diagnosed with iron deficiency anemia refractory to treatment and normal gastroscopy and colonoscopy results were admitted to this prospective study between June 2013 and December 2013. All patients underwent a standardized MRE examination with a 1.5 Tesla magnetic resonance imaging system using two six-channel phased-array abdominal coils. Adequate bowel distention and fast imaging sequences were utilized to achieve diagnostic accuracy. All segments of the small bowel, duodenum, jejunum, and ileum were examined in detail. All cases were examined independently by two radiologists with > 5 years of experience in abdominal magnetic resonance imaging. A consensus reading was performed for each patient following image examination. Both radiologists were blinded to patient history, laboratory findings, and endoscopy results. RESULTS: Twenty (37.7%) male and 33 (62.3%) female patients were included in the study. The mean age of the patients was 52.2 +/- 13.6 years (range: 19-81 years, median 51.0). The age difference between the male and female patient groups was not statistically significant (54.8 +/- 16.3 years vs 50.7 +/- 11.7 years). MRE results were normal for 49 patients (92.5%). Four patients had abnormal MRE results. One patient with antral thickening was diagnosed with antral gastritis in the second-look gastroscopy. One patient had focal wall thickening in the 3rd and 4th portions of the duodenum. The affected areas were biopsied in a subsequent duodenoscopy, and adenocarcinoma was diagnosed. One patient had a fistula and focal contrast enhancement in the distal ileal segments, consistent with Crohn's disease. One patient had focal wall thickening with luminal narrowing in the mid-jejunum that was later biopsied during a double-balloon enteroscopy, and lymphoma was diagnosed. CONCLUSION: MRE is a non-invasive and effective alternative for evaluating possible malignancies of the small intestines and can serve as a guide for a second-look endoscopy. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Background Lewis Score (LS) is an inflammatory score in small-bowel capsule endoscopy (SBCE). Fecal calprotectin (FC) is considered the non-invasive, ‘gold standard’ marker of gastrointestinal (GI) inflammation. Recently, we reported that LS shows only a moderate correlation with FC. In this study, we aim to evaluate which LS parameters have greater correlation with FC. Methods A retrospective, two-center study; 74 patients who underwent SBCE within 7 (median 1.5) days from a FC measurement. LS was calculated; univariate and multivariate analyses were performed, investigating LS correlation with FC, and which LS parameters had stronger correlation coefficient (rs) with FC. Results 74 patients had an FC measurement within 7 days of their SBCE examination (median 22 time-interval: 1.5 days; IQR: 5). Coefficient rs between LS and FC was moderate (0.454). In univariate analysis, the variables that gave the strongest association with FC were: the higher tertile subscore for ulcer, the summative ulcer subscore, the higher tertile ulcer score (only with descriptors of ulcer size and number), the summative ulcer score (only with descriptors of ulcer size and number), and subscores including various combinations of the stenosis descriptors. In multivariate analysis, the only positive predictor for FC was the higher tertile ulcer subscore (only with descriptors of ulcer size and number). Conclusion LS shows only moderate correlation to FC. This is due to a) an inherent limitation of LS, and b) the notion of correlating the 2 parameters, and consideration should be given to development of a new, simplified (or composite) inflammation score/index for SBCE.

INTRODUCTIONSmall-bowel myeloid sarcoma is rare. Acute bowel obstruction is its usual clinical presentation.PRESENTATION OF CASEWe report a case of small-bowel myeloid sarcoma that occurred in a 64-year-old woman who presented chronic secretory diarrhoea, hypokalaemia, and weight loss. Immature white blood cells in a peripheral smear and small-bowel capsule endoscopic features were the main diagnostic clues. The patient experienced capsule retention and developed acute bowel obstruction. Urgent laparotomy showed a stricturing ileal mass and pathology of the resected bowel specimen unveiled a CD34+, CD117+, and myeloperoxidase-positive myeloid sarcoma. The diarrhoea promptly resolved after surgery, and the patient is now undergoing chemotherapy.DISCUSSIONSecretory diarrhoea can be the first manifestation of small-bowel myeloid sarcoma. Capsule endoscopy may provide a diagnostic clue, but it can trigger an acute bowel obstruction. Differential diagnosis of the pathologic specimen may be difficult and a high suspicion index of is mandatory to perform immunophenotyping to determine the correct management.CONCLUSIONChronic diarrhoea with alarm features can be the first manifestation of small-bowel myeloid sarcoma.

Heat-induced tissue fusion via radio-frequency (RF) energy has gained wide acceptance clinically and here we present the first optical-Raman-spectroscopy study on tissue fusion samples in vitro. This study provides direct insights into tissue constituent and structural changes on the molecular level, exposing spectroscopic evidence for the loss of distinct collagen fibre rich tissue layers as well as the denaturing and restructuring of collagen crosslinks post RF fusion. These findings open the door for more advanced optical feedback-control methods and characterization during heat-induced tissue fusion, which will lead to new clinical applications of this promising technology. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Many celiac disease patients tolerate oats, but limited data are available on its long-term consumption. This was evaluated in the present study, focusing on small-bowel mucosal histology and gastrointestinal symptoms in celiac adults maintaining a strict gluten-free diet with or without oats. Altogether 106 long-term treated celiac adults were enrolled for this cross-sectional follow-up study. Daily consumption of oats and fiber was assessed, and small-bowel mucosal morphology and densities of CD3+, αβ+ and γσ+ intraepithelial lymphocytes determined. Gastrointestinal symptoms were assessed by a validated Gastrointestinal Symptom Rating Scale questionnaire. Seventy (66%) out of the 106 treated celiac disease patients had consumed a median of 20 g of oats (range 1–100 g) per day for up to eight years; all consumed oat products bought from general stores. Daily intake and long-term consumption of oats did not result in small-bowel mucosal villous damage, inflammation, or gastrointestinal symptoms. Oat-consumers had a significantly higher daily intake of fiber than those who did not use oats. Two thirds of celiac disease patients preferred to use oats in their daily diet. Even long-term ingestion of oats had no harmful effects.

textabstractBackground Two strategies for prevention of upper gastrointestinal (UGI) events for nonselective nonsteroidal anti-inflammatory drug (nsNSAID) users are replacement of the nsNSAID by a cyclo-oxygenase-2-selective inhibitor (coxib) or co-prescription of a gastroprotective agent (GPA). Aim To identify whether and in whom either of these strategies should be preferred in daily practice. Methods A nested case-control study was conducted using three European primary care databases. We selected a cohort including all naive nsNSAID+GPA (≥80% GPA adherence) and coxib users (without GPA use) aged ≥50 years. Cases with an UGI event (i.e. symptomatic UGI ulcer or bleeding) were matched to cohort members without an UGI event on age, sex and number of individual UGI risk factors (i.e. UGI event history, age ≥65 years, concomitant use of anticoagulants, antiplatelets, or glucocorticoids) and calendar time. Conditional logistic regression analysis was used to calculate odds ratios (ORs) with 95% CI, while adjusting for potential confounders. Results Within the NSAID cohort (n = 617 220), 398 UGI cases were identified. The risk of UGI events was equivalent for coxib and nsNSAID+GPA (≥80% adherence) users (OR: 1.02; 95%CI: 0.77-1.37). In concurrent glucocorticoid users, the risk of UGI events was significantly elevated for nsNSAID+GPA (≥80% adherence) compared with coxib users (OR: 9.01; 95%CI: 1.61-50.50). Conclusions The risk of UGI events was similar in nsNSAID+GPA (≥80% adherence) and coxibs users. In patients concurrently using glucocorticoids, a significant increase in the risk of UGI events for nsNSAID+GPA users was observed and coxibs should be preferred.

Purpose: The aim of this study was to measure and improve the quality of target volume delineation by means of national consensus on target volume definition in early-stage rectal cancer.Methods and materials: The CTV's for eight patients were delineated by 11 radiation oncologists in 10 institutes according to local guidelines (phase 1). After observer variation analysis a workshop was organized to establish delineation guidelines and a digital atlas, with which the same observers re-delineated the dataset (phase 2). Variation in volume, most caudal and cranial slice and local surface distance variation were analyzed.Results: The average delineated CTV volume decreased from 620 to 460 cc (p Conclusions: The large variation in target volume delineation could significantly be reduced by use of consensus guidelines and a digital delineation atlas. Despite the significant reduction there is still a need for further improvement. (C) 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 102 (2012) 14-21