Severe Mucosal Atrophy Research Articles

A Proton Pump Inhibitor Independently Elevates Gastrin Levels as a Marker for Metachronous Gastric Cancer After Endoscopic Submucosal Dissection.

Background and Objective: Serum markers such as gastrin and pepsinogen are useful for stratifying gastric cancer risk. However, their utility in predicting metachronous gastric cancer after endoscopic submucosal dissection (ESD) in patients with gastric cancer after Helicobacter pylori eradication (GCAE) is unclear. This study aimed to clarify predictive factors for metachronous gastric cancer after ESD with a focus on serum markers. Methods: A retrospective analysis was conducted on 197 patients with 224 GCAE lesions who underwent ESD at Hiroshima University Hospital between April 2010 and December 2019. In total, 63 patients with 74 differentiated-type lesions were classified into metachronous gastric cancer (MG) and non-metachronous gastric cancer (NMG) groups, excluding proton pump inhibitor (PPI) users, female patients, and undifferentiated-type cases. The predictive value of serum markers was assessed using ROC curve analysis, and their association with carcinogenesis was evaluated using multiple logistic regression. Furthermore, the incidence of MG was compared between long-term PPI users and non-users. Results: ROC analysis revealed that serum gastrin had the highest discriminative ability for MG (AUC 0.77, cut-off 99 pg/mL, sensitivity 61.6%, and specificity 80.0%). Severe mucosal atrophy and high gastrin levels were significantly more common in the MG group and were independent predictors (p < 0.01). Although serum gastrin levels were significantly elevated in PPI users, no increased risk of MG was observed. Conclusions: In addition to severe mucosal atrophy, PPI-independent elevated serum gastrin levels may be associated with an increased risk of MG after ESD. Serum gastrin may serve as a valuable marker for post-ESD cancer surveillance in GCAE patients.

Endoscopic Features of Synchronous Multiple Early Gastric Cancers: Findings from a Nationwide Cohort

Introduction: We investigated the factors associated with synchronous multiple early gastric cancers and determined their localization. Methods: We analyzed 8,191 patients who underwent endoscopic submucosal dissection for early gastric cancers at 33 hospitals in Japan from November 2013 to October 2016. Background factors were compared between single-lesion (n = 7,221) and synchronous multi-lesion cases (n = 970) using univariate and multivariate analyses. We extracted cases with two synchronous lesions (n = 832) and evaluated their localization. Results: Significant independent risk factors for synchronous multiple early gastric cancer were older age (≥75 years old) (odds ratio [OR] = 1.257), male sex (OR = 1.385), severe mucosal atrophy (OR = 1.400), tumor localization in the middle (OR = 1.362) or lower region (OR = 1.404), and submucosal invasion (OR = 1.528 [SM1], 1.488 [SM2]). Depressed macroscopic type (OR = 0.679) and pure undifferentiated histology OR = 0.334) were more common in single early gastric cancers. When one lesion was in the upper region, the other was more frequently located in the lesser curvature of the middle region. When one lesion was in the middle region, the other was more frequently located in the middle region or the lesser curvature of the lower region. When one lesion was in the lower region, the other was more frequently located in the lesser curvature of the middle region or the lower region. Conclusion: Factors associated with synchronous multiple early gastric cancer included older age, male sex, severe mucosal atrophy, tumor localization in the middle or lower region, and tumor submucosal invasion. Our findings provide useful information regarding specific areas that should be examined carefully when one lesion is detected.

Multicenter study of invasive gastric cancer detected after 10 years of Helicobacter pylori eradication in Japan: Clinical, endoscopic, and histopathologic characteristics.

Gastric cancer can be diagnosed even in patients long after Helicobacter pylori eradication. Most cases involve intramucosal lesions; however, some are invasive and require surgery. To clarify appropriate long-term surveillance methods, this study compared invasive gastric cancer diagnosed ≥10 and <10 years after eradication. This retrospective multicenter study included 14 institutions. We included 377 patients with gastric cancer with submucosal or deep invasion after surgical or endoscopic resection. Ordered logistic regression analysis was used to explore the factors contributing to the pathological stage and histological type. Invasive gastric cancer was detected in 84 patients (Group L) and 293 patients (Group S) ≥10 and <10 years after H. pylori eradication, respectively. Endoscopic mucosal atrophy at the time of cancer detection was similar in both groups; 50% of the patients had severe atrophy. Annual endoscopy correlated with early pathological stage (odds ratio [OR] 0.28, 95% confidence interval [CI] 0.14-0.54, p < 0.001). Group L exhibited an independent correlation with the advanced pathological stage (OR 2.27, 95% CI 1.06-4.88, p = 0.035) and the undifferentiated type (OR 2.12, 95% CI 1.16-3.90, p = 0.015). The pure differentiated type and early pathological stage significantly (p = 0.001) correlated with severe mucosal atrophy in Group S but not in Group L. Invasive cancers diagnosed ≥10 years after H. pylori eradication were likely to be more malignant in histological type and pathological stage. Gastric cancer surveillance should continue regardless of endoscopic atrophy, particularly ≥10 years after eradication.

Marked intestinal trans-differentiation by autoimmune gastritis along with ectopic pancreatic and pulmonary trans-differentiation

BackgroundAutoimmune gastritis (AIG) is a prevalent chronic inflammatory disease with oncogenic potential that causes destruction of parietal cells and severe mucosal atrophy. We aimed to explore the distinctive gene expression profiles, activated signaling pathways, and their underlying mechanisms.MethodsA comprehensive gene expression analysis was conducted using biopsy specimens from AIG, Helicobacter pylori-associated gastritis (HPG), and non-inflammatory normal stomachs. Gastric cancer cell lines were cultured under acidic (pH 6.5) conditions to evaluate changes in gene expression.ResultsGastric mucosa with AIG had a unique gene expression profile compared with that with HPG and normal mucosa, such as extensively low expression of ATP4A and high expression of GAST and PAPPA2, which are involved in neuroendocrine tumorigenesis. Additionally, the mucosa with AIG and HPG showed the downregulation of stomach-specific genes and upregulation of small intestine-specific genes; however, intestinal trans-differentiation was much more prominent in AIG samples, likely in a CDX-dependent manner. Furthermore, AIG induced ectopic expression of pancreatic digestion-related genes, PNLIP, CEL, CTRB1, and CTRC; and a master regulator gene of the lung, NKX2-1/TTF1 with alveolar fluid secretion-related genes, SFTPB and SFTPC. Mechanistically, acidic conditions led to the downregulation of master regulator and stemness control genes of small intestine, suggesting that increased environmental pH may cause abnormal intestinal differentiation in the stomach.ConclusionsAIG induces diverse trans-differentiation in the gastric mucosa, characterized by the transactivation of genes specific to the small intestine, pancreas, and lung. Increased environmental pH owing to AIG may cause abnormal differentiation of the gastric mucosa.

Iron Deficiency Anaemia and Anaemia of Inflammation in Enteropathies Caused by Commonest Small Intestine Disorders: Current Evidence

Abstract It is no mystery that iron deficiency is the most common anaemia and multiple studies have shown that anaemia is a main factor for decreased quality of life. The focus of our article is an up-to-date review of different enteropathies caused by specific disorders and the prevalence of iron deficiency anaemia (IDA), starting with the understanding of physiology of iron absorption and regulation in the intestine. The pathologies that we tried to cover were celiac disease, Crohn’s disease, nonsteroidal anti-inflammatory drugs (NSAID)-induced enteropathy and protein losing enteropathy. Unfortunately, not everything still understood and questions still remain. The main questions are associated with our understanding of iron regulation beyond the ferroportin-hepcidin axis and what mechanism is behind changes of epithelium in different conditions. Depending on the study and pathology of enteropathy, almost half of the studied patients had iron deficiency anaemia. However, in all enteropathies, IDA is more an additional finding or an additional symptom that needs further investigations. That is why many authors consider that IDA is caused by secondary mechanisms and not enteropathy per se and should be correlating with undernourishment, severe mucosal atrophy, malabsorption, and bleeding.

Endoscopic severe mucosal atrophy indicates the presence of gastric cancer after Helicobacter pylori eradication -analysis based on the Kyoto classification

BackgroundGastric cancer after Helicobacter pylori (HP) eradication is a crucial clinical challenge today as HP eradication therapy is widely performed. Detecting gastric cancer after HP eradication tends to be difficult with normal white-light endoscopy. In the present study, we aimed to identify easily-evaluated endoscopic findings that indicate the presence of gastric cancer after HP eradication so that endoscopists can consider additional detailed examinations at the site.MethodsWe analyzed the endoscopic images of 43 patients who underwent endoscopic submucosal dissection for early gastric cancer after HP eradication and 119 patients with an HP eradication history who underwent esophagogastroduodenoscopy for a medical checkup. Endoscopic findings were evaluated according to the Kyoto classification of gastritis (atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness) and map-like redness.ResultsPatients with gastric cancer had significantly higher total Kyoto risk scores; more atrophy, intestinal metaplasia, and diffuse redness; and a significantly higher prevalence of map-like redness compared with those without gastric cancer, in the univariate analyses. We used logistic regression analysis with forward selection based on the likelihood ratio to develop a model using atrophy and diffuse redness. Receiver operating characteristic analysis showed that a score of A2 in the Kyoto classification of gastritis (open-type atrophic pattern in the Kimura–Takemoto classification) was an endoscopic marker for the presence of post-HP-eradication gastric cancer.ConclusionsEndoscopic severe gastric mucosal atrophy is useful to screen patients for gastric cancer after HP eradication.

Modern Possibilities of the Use of Non-Invasive Serological Biomarkers Severe in Population Studies

The ethnic and the gender factors materially affect the prevalence of gastric atrophy.? All the patients were divided into five ethnic groups: Russians, Karachays, Abazins, Circassians, Nogais. The decrease in serum gastrin-17 less than 10 pmol/l is a sensitive and specific biomarker for antral mucosal atrophy, pepsinogen-I less than 25 µg/l is a corpus mucosal atrophy biomarker (Se - 89% and 92%, Sp - 97% and 96%). Gastrin-17 and pepsinogen-I are also sensitive and specific biomarkers for mild, moderate, severe atrophy of the antrum and corpus (for severe antral mucosal atrophy Se - 96%, Sp - 92%, for severe corpus mucosal atrophy Se - 88%, Sp - 97%). A total of 75 patients with multifocal atrophic gastritis were examined histologically. 67 patients had gastrin-17 <10 pmol/l and pepsinogen-I <25 µg/l at the same time. 7 patients had gastrin-17 from 10 to 11.5 pmol/l, 1 patient had gastrin-17 = 19 pmol/l (Se - 89%). Therefore, the level of gastrin-17 and pepsinogen-I simultaneously decreases among patients with multifocal atrophic gastritis. The prevalence of atrophic gastritis is significantly different among some ethnic populations living in the same territory under the same environmental and living conditions. These differences prove the presence of genetic polymorphism in different ethnic groups of the population.

Screening for coeliac disease in type 1 diabetes

In this issue of Acta Paediatrica, Laitinen et al. 1 explore symptoms and mucosal damage in 22 patients with type 1 diabetes who were screened for coeliac disease and compared them to 498 individuals diagnosed with coeliac disease on a clinical basis. The authors concluded that screening for coeliac disease should be considered among children with type 1 diabetes, which is in line with current recommendations 2-4. A meta-analysis found that coeliac disease occurred in more than one in 20 patients with type 1 diabetes 5, and long-term coeliac disease may influence the risk of both retinopathy and chronic renal disease in type 1 diabetes 6, 7, potentially due to an increased prevalence of microvascular complications in patients with both type 1 diabetes and coeliac disease 8. The paper by Laitinen et al. 1 is interesting for several reasons. First of all, the authors found that patients with type 1 diabetes and coeliac disease did differ from patients diagnosed with coeliac disease due to clinical symptoms. For instance, patients with type 1 diabetes and coeliac disease did not experience such poor growth as those with clinically diagnosed coeliac disease. That is reassuring, as poor growth in childhood can have long-term consequences. Although catch-up growth is commonly seen in children with coeliac disease just after diagnosis, restricting food intake to make a diet suitable for both type 1 diabetes and coeliac disease could theoretically make catch-up growth more difficult to achieve. The authors also found that while children with type 1 diabetes and coeliac disease often had unrecognised gluten-dependent symptoms, these were less severe than in children who were clinically diagnosed with coeliac disease. That was to be expected, because otherwise the children with type 1 diabetes and coeliac disease should have been diagnosed before, due to gastrointestinal symptoms, rather than just after their diagnosis of type 1 diabetes. We believe that the lower prevalence of symptoms reflects the fact that patients with type 1 diabetes and coeliac disease may have less severe small-bowel mucosal atrophy than patients who just have coeliac disease. We disagree with Laitinen et al. on their interpretation in this regard, as we believe that the lack of difference with regard to mucosal atrophy in their study was due to lack of power. Laitinen et al. based their findings on only 22 patients with type 1 diabetes and coeliac disease and the statistical lack of difference was probably due to the equal proportions of patients with subtotal villous atrophy. Estimating total villous atrophy from their Figure 1B seems to indicate that it was more common in patients with clinical suspicion of coeliac disease (roughly 23% versus 9%), while partial villous atrophy was more common in patients with type 1 diabetes (52% versus roughly 32%). The same objection could be raised about the conclusion that dietary adherence was similar in patients with both type 1 diabetes and coeliac disease and those with just coeliac disease. The power for dietary adherence was limited in type 1 diabetes and coeliac disease patients as there was only dietary data for 16 of the 22 patients, and the p value of 0.086 may have reached statistical significance if the type 1 diabetes and coeliac disease group had been larger. This said, it should be emphasised that a very high proportion of patients with type 1 diabetes and coeliac disease did comply with the diet. Nevertheless, the long-term implications of prescribing a life-long diet for a child based on screening are unknown, as adherence to a gluten-free diet may decline in adolescence among children with screen-detected coeliac disease. While the strongest evidence for the value of screening for coeliac disease would be derived from a randomised trial, in which a nonscreened group would be compared to a screened group with regard to morbidity, the length and expense of such a trial would probably be prohibitive. As such, we rely on observational studies, such as those by Laitinen et al., to inform us of the potential outcomes of screening. In conclusion, this article makes a valuable contribution to the literature and once again underlines the potential value of examining children with type 1 diabetes for other autoimmunity problems, including coeliac disease. None. None.

PO5 GIARDIASIS IN SUSPECTED CELIAC DISEASE

Background and Objectives: Celiac disease (CD) is an immunemediated enteropathy induced by gluten ingestion in a genetically susceptible patient. Giardia lamblia is the most common human parasite with a worldwide distribution and fecal-oral way of transmission. Giardia lamblia has a cosmopolitan distribution. Infected children may have acute or chronic diarrhea, crampy abdominal pain, anorexia, malasorption and poor weight gain and may be misdiagnosed as celiac disease. Diagnosis is usually made by finding the characteristic cysts in stool specimens or by duodenal aspiration. In most cases histology reveals a dense accumulation of the parasites on the surface of the duodenal mucosa with no or only slight inflammation. In rare cases, a dense inflammatory infiltrate with severe mucosal atrophy and increased count of intraepithelial lymphocytes may be seen. If in such cases the amount of parasites is low, the histological picture may mimic celiac disease. We report the case of a child 2 years old who presented poor growth, recurrent aphtous stomatitis, abdominal pain and recurrent diarrhea. No family history of CD. Material and Methods: In suspected CD, were assayed the IgA anti-endomysium antibodies (EmA-IgA) that resulted doubt and the IgA anti-tissue transglutaminase antibodies (TgA-IgA) that were found weakly positive (17.50UA; normal value 16UA). He was referred to our hospital for further diagnostic. We performed the search for genetic susceptibility of CD; the antibodies assay was repeated after 3 months. These investigations documented the presence of HLADQ2, positivity of EmA-IgA and an increase value of TgA-IgA (20.70UA). In the meantime symptoms worsened, so we proceeded performing the esophagogastroduodenoscopy and duodenal biopsies. The macroscopic appearance of duodenal mucosa was of villous atrophy, but microscopic examination showed a parasitic duodenitis, with the presence of microorganisms like Giardia lamblia. Then was started medical therapy with metronidazole per os for 10 days, and the child continued to eat gluten. Results: Abdominal pain and diarrhea disappeared gradually but rapidly; the parasitological examination was negative on 3 consecutive samples (at 3 weeks after eradication therapy); EmA-IgA and TgAIgA were negative at 1 month after eradication. The follow up to 1 year had confirmed that the increase in IgA was secondary to giardiasis, and that the symptoms were due to the histological damage of the parasite. Conclusions: When investigating a patient with suspected celiac disease (CD), several other conditions must be considered, including potential infection with Giardia lamblia. In doubtful cases like our patient, are of fundamental support an accurate assessment and appropriate follow up.

Outbreak of Porcine Epidemic Diarrhea in Suckling Piglets, China

Outbreak of Porcine Epidemic Diarrhea in Suckling Piglets, China

Long-term effect of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic resection of early gastric cancer

A prospective, randomized trial proved that Helicobacter pylori eradication significantly reduces the incidence of metachronous gastric cancer during a 3-year follow-up. To investigate the long-term effect of H pylori eradication on the incidence of metachronous gastric cancer after endoscopic resection of early gastric cancer. Retrospective, multicenter study. Kyushu University Hospital and 6 other hospitals in Fukuoka Prefecture, Japan. Follow-up data for 268 H pylori-positive patients who had undergone endoscopic resection of early gastric cancer were retrospectively investigated. A total of 177 patients underwent successful H pylori eradication (eradicated group), whereas 91 had persistent H pylori infection (persistent group). The incidence of metachronous gastric cancer was compared in these 2 groups. When the follow-up period was censored at 5 years, the incidence rate in the eradicated group was lower than that observed in the persistent group (P = .007). During the overall follow-up period ranging from 1.1 to 11.1 years (median 3.0 years), metachronous gastric cancer developed in 13 patients (14.3%) in the persistent group and in 15 patients (8.5%) in the eradicated group (P = .262, log-rank test). Based on a multivariate logistic regression analysis, baseline severe mucosal atrophy and a follow-up of more than 5 years were found to be independent risk factors for the development of metachronous gastric cancer. Retrospective study. H pylori eradication does not reduce the incidence of metachronous gastric cancer. H pylori eradication should be performed before the progression of gastric mucosal atrophy.

Lamblieninfektion als Differenzialdiagnose der Zöliakie in der Duodenalbiopsie

Giardia lamblia is the most common human parasite with a worldwide distribution and fecal-oral way of transmission. Diagnostic procedures include stool examination and gastroduodenoscopy with biopsy or secret aspiration. In most cases histology reveals a dense accumulation of the parasites on the surface of the duodenal mucosa with no or only slight inflammation. In rare cases, a dense inflammatory infiltrate with severe mucosal atrophy and increased count of intraepithelial lymphocytes may be seen. If in such cases the amount of parasites is low, the histological picture may mimic celiac disease. The two presented cases demonstrate the close morphological relationship and show the importance of considering giardiasis in the differential diagnosis in patients with suspected celiac disease.

The Interleukin-8–251 A Allele is Associated With Increased Risk of Noncardia Gastric Adenocarcinoma in Helicobacter pylori-infected Koreans

Chronic inflammation associated with Helicobacter pylori infection is a risk factor of gastric adenocarcinoma. Interleukin-8 (IL-8) plays an important role in gastric mucosal inflammation induced by H. pylori infection. Recently, studies on the association of genetic polymorphisms of various proinflammatory cytokines with gastric carcinogenesis showed varying results on the basis of the ethnicity. We conducted this study to investigate the association of IL-8-251 A/T polymorphism with gastric carcinogenesis in H. pylori-infected Koreans. The IL-8-251 A/T polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism using DNA from a total of 605 H. pylori-infected subjects; 206 controls, 149 chronic atrophic gastritis and/or intestinal metaplasia, 97 gastric dysplasia, and 153 gastric adenocarcinoma. Degrees of gastric mucosal inflammation and mucosal IL-8 level were also assessed. The IL-8-251 A carriers showed a higher risk of gastric adenocarcinoma (adjusted odds ratio 2.06, 95% confidence interval 1.16-3.68) than IL-8-251 T/T genotypes. The IL-8-251 A allele was also significantly associated with the degree of neutrophil infiltration, atrophy, and intestinal metaplasia in a younger age group. Among the chronic atrophic gastritis and/or intestinal metaplasia group, mucosal IL-8 level was significantly higher in subjects with IL-8-251 A allele than those with IL-8-251 T/T genotypes (P=0.011). The IL-8-251 A allele is associated with higher IL-8 production, more severe inflammation, mucosal atrophy, and intestinal metaplasia than IL-8-251 T/T genotype in H. pylori-infected hosts. The IL-8-251 A allele may also increase the risk of gastric adenocarcinoma through an enhanced inflammatory process in H. pylori-infected Koreans.

A Polymorphism of microRNA 27a Genome Region Is Associated With the Development of Gastric Mucosal Atrophy in Japanese Male Subjects

Noncoding microRNAs regulate the expression of various mRNAs. We attempted to clarify the relationship between miR-27a genome polymorphism and chronic gastritis. The study was performed in 179 patients with no evidence of gastric malignancy. The severity of histologic chronic gastritis was classified according to the updated Sydney system. The frequency of miR-27a G allele was 34.6%. Although the frequencies of miR-27a G allele were increased in subjects with peptic ulcer or severe mucosal atrophy, no significant differences were seen. The miR-27a polymorphism showed an interaction with gender in relation to gastric mucosal atrophy (P=.090). In only male subjects, the miR-27a polymorphism was associated with the gastric mucosal atrophy (P=.039) and both atrophy and metaplasia scores in G/G group were significantly higher than those in the other groups. The miR-27a genome region polymorphism may be an important definitive factor to develop the gastric mucosal atrophy in Japanese male subjects.

The relationship between Helicobacter pylori infection and promoter polymorphism of the Nrf2 gene in chronic gastritis

The transcription factor Nrf2 regulates the expression of detoxifying and antioxidant genes. Three polymorphisms of the Nrf2 gene have been reported. We attempted to clarify the relationship between Nrf2 gene polymorphism and chronic gastritis in a Japanese population. The study was performed in 159 patients with no evidence of gastric malignancy on upper gastrointestinal endoscopy (mean age, 62.03 years; male:female ratio, 102:57; peptic ulcer diseases in 69 patients, and Helicobacter pylori (H. pylori) positivity in 73.0%). We employed the PCR-SSCP method to detect gene polymorphisms using DNA extracted from peripheral blood cells or from antral biopsy specimens obtained by endoscopy. The severity of the histological chronic gastritis in antral biopsy specimens was classified according to the updated Sydney system. Although the frequencies of the SNP(-686) and SNP(-650) A alleles were decreased in subjects with peptic ulcers or severe mucosal atrophy, no significant differences were seen. However, the number of -686 G alleles was correlated with both neutrophil activity and mononuclear cell infiltration (p=0.036 and p=0.010, respectively), while the -650 C/C genotype was an independent risk factor for mononuclear cell infiltration (p=0.021 by ANOVA). In addition, both the number of -686 G alleles and the -650 C/C genotype showed an interaction with H. pylori infection to promote the infiltration of mononuclear cells (p=0.037 by ANCOVA and p=0.041 by ANOVA, respectively). Nrf2 promoter polymorphisms are significantly associated with the development of gastric mucosal inflammation, either independently or by interacting with H. pylori infection.

Radiological investigation of the mucosae around early gastric cancers

To clarify the corresponding histological structures, double-contrast images of mucosae around early gastric cancers were examined. A total of 332 areas of double-contrast images of the gastric mucosae around early gastric cancers and corresponding specimens resected in operations were selected. The size, shape, and regularity of the granules in the images were inspected. Bull's-eye shadows and dot shadows in the images were also investigated. These findings were compared with the severity of mucosal atrophy, hyperplasia of lymph follicles, and intestinal metaplasia in the corresponding specimens. In fundic gland mucosae, granules which were small, oval, irregular, or unaccompanied by bull's-eye shadows indicated severe atrophy. Granules which were irregular or accompanied by dot shadows indicated severe intestinal metaplasia. Granules which were small, oval, or irregular indicated severe hyperplasia of lymph follicles. In pyloric gland mucosae, oval or irregular granules accompanied by dot shadows indicated severe mucosal atrophy and severe intestinal metaplasia. Diamond-shaped granules indicated severe hyperplasia of lymph follicles. The histological structure of normal gastric mucosae around gastric cancers can be inferred from the size, shape, and regularity of granules, and the presence of bull's-eye or dot shadows in double-contrast images.

Gluten-Free Diet Impact on Leptin Levels in Asymptomatic Coeliac Adolescents: One Year of Follow-Up

Coeliac disease, daily more frequently diagnosed in our population, involves many organs also in oligosymptomatic patients and with an adequate nutritional regime. Possible endocrine implications include failure to thrive, pubertal delay and reproduction diseases due to deregulation of GH, FSH and LH secretion. Leptin, an adipose tissue hormone, can be decreased as well and its deficiency could be related to growth and puberty anomalies. We studied 14 asymptomatic coeliac patients in peripubertal age (7.5–13.8 years) and tested their leptin levels in order to correlate them with endocrine and anthropometric data. Before the diet was started leptinaemia (M±DS) was: 4.94 ± 5.53 ng/ml. In 10/14 patients (71%) leptinaemia was ≤2 DS for gender and age. In all the patients, after a period of 6–12 months of gluten-free diet, Leptin levels appreciably raised to 10.8 ± 7.9 ng/ml, with a significant correlation to the time of the diet. Leptinaemia was actually lower in patients with a severe mucosal atrophy, and in these patients it increased more significantly after the diet was started. The removal of gluten itself may reduce immunological hit to adipose tissue and the ‘malnutrition’ of adipocytes: leptin can hence increase despite no significant increase of body mass index occurs. This study could partially explain the correlation between body mass index, Coeliac disease and the deregulation of puberty and fertility, mainly in patients who started the diet late. It could also explain the reversibility of this alteration if the cause is removed.

Clinical features of gastric cancer discovered after successful eradication of Helicobacter pylori: results from a 9‐year prospective follow‐up study in Japan

Eradication of Helicobacter pylori is expected to prevent the development of gastric cancer. However, gastric cancer is sometimes discovered after successful eradication of H. pylori. To conduct a prospective study to determine the clinical features of patients who underwent successful eradication and were later diagnosed with gastric cancer. A total of 1787 patients (1299 males and 488 females; mean age, 58.2 years; range: 15-84) who underwent successful eradication therapy between April 1994 and March 2001 were our study subjects. Gastric cancer occurred at a rate of 1.1% (20 of 1787) during the follow-up period. Gastric cancer comprises six of 105 (5.7%) with early gastric cancer after endoscopic resection, 12 of 575 (2.1%) with gastric ulcer and two of 453 (0.4%) with atrophic gastritis. Gastric cancer did not develop in any patient with duodenal ulcer. All patients with gastric cancer had baseline severe atrophic gastritis in the corpus. Careful endoscopic examination is necessary even after successful eradication of H. pylori in patients with early gastric cancer or gastric ulcer with severe mucosal atrophy in the corpus.

Necrotizing enterotyphlocolitis in dogs treated with a potent antimuscarinic.

To assess the safety of a potent muscarinic receptor antagonist (antimuscarinic) for human clinical testing, repeat-dose oral toxicity studies were conducted in the Beagle dog. Treatment resulted in unexpected gastrointestinal system effects that were likely mediated by the exaggerated pharmacologic effects of the antimuscarinic on intestinal motility. Dogs developed profound anorexia followed by severe bloody diarrhea, and at necropsy, the intestinal tract was distended, filled with red-tinged fluid, and the mucosa was reddened. Histologically, intestinal lesions consisted of severe epithelial necrosis and mucosal atrophy localized predominantly to the ileum and large intestine. Feces from dogs with diarrhea were culture-positive for Clostridium perfringens (CP), suggesting that CP might be the etiologic agent; however, the intestinal lesions were not consistent with histologic findings reported in dogs with hemorrhagic canine enteritis.

Atrophy and neoplastic transformation of the ileal pouch mucosa in patients with ulcerative colitis and primary sclerosing cholangitis: a case control study.

Patients with ulcerative colitis and primary sclerosing cholangitis have an increased risk of developing carcinoma both in the bile ducts and in the colon. To investigate whether this patient group also has an increased risk of developing atrophy and neoplasia in the ileal pouch mucosa after construction of a pelvic pouch with an ileoanal anastomosis or a continent Kock ileostomy. Flexible video endoscopic examinations of the ileal pouch were performed in 16 patients with ulcerative colitis and primary sclerosing cholangitis and in 16 matched patients with ulcerative colitis without sclerosing cholangitis. Biopsies were sampled from different locations in the pouch for histologic assessment of mucosal atrophy and dysplasia and for flow cytometric DNA analysis assessing chromosomal aberrations. The patients with sclerosing cholangitis developed moderate or severe atrophy in the pouch significantly more often (P < 0.01). Persistent severe mucosal atrophy was revealed in eight patients with sclerosing cholangitis and only in two controls. One patient with sclerosing cholangitis had high-grade dysplasia in multiple locations. Low-grade dysplasia was assessed in three patients with sclerosing cholangitis and in two of the controls. DNA aneuploidy was displayed in three patients, all with sclerosing cholangitis and dysplasia. All patients with neoplastic transformation had a pouch with ileoanal anastomosis and a long pouch duration (> 8 years). Patients with ulcerative colitis and primary sclerosing cholangitis with an ileal reservoir are more prone to developing mucosal atrophy in the pouch and seem to have a higher risk of neoplastic transformation in the pouch mucosa than patients with ulcerative colitis without sclerosing cholangitis.