Claudin-2: A marker for a better evaluation of histological mucosal healing in inflammatory bowel diseases.

BACKGROUND: Histological mucosal healing has become a paramount target goal to achieve in the treatment of inflammatory bowel diseases. However, there is still a lack of agreement on the best way to reach this goal, since numerous histological scores are available worldwide. AIMS: We investigated whether claudin-2, a member of claudin family involved in the regulation of intestinal tight junctions, might be useful to assess the presence of active disease in patients with inflammatory bowel diseases. METHODS: Biopsies from 123 patients with ulcerative colitis, Crohn's disease, infectious colitides and irritable bowel syndrome patients where tested with immunohistochemistry for claudin-2. RESULTS: Claudin-2 appeared to be a very sensitive marker of disease activity in inflammatory bowel diseases, but was negative in the other kinds of patients. In addition, immunohistochemistry for claudin-2 showed good reproducibility by different pathologists. CONCLUSIONS: Should these findings be confirmed in more numerous cohorts of patients, and especially in those with minimal or focal residual disease activity, this simple assessment could be useful in the routine daily practice to facilitate the task of pathologists and clinicians in the diagnosis and management of patients with inflammatory bowel diseases.

The development of artificial intelligence in the histological diagnosis of Inflammatory Bowel Disease (IBD-AI).

BACKGROUND: Inflammatory bowel disease (IBD) includes Crohn's Disease (CD) and Ulcerative Colitis (UC). Correct diagnosis requires the identification of precise morphological features such basal plasmacytosis. However, histopathological interpretation can be challenging, and it is subject to high variability. AIM: The IBD-Artificial Intelligence (AI) project aims at the development of an AI-based evaluation system to support the diagnosis of IBD, semi-automatically quantifying basal plasmacytosis. METHODS: A deep learning model was trained to detect and quantify plasma cells on a public dataset of 4981 annotated images. The model was then tested on an external validation cohort of 356 intestinal biopsies of CD, UC and healthy controls. AI diagnostic performance was calculated compared to human gold standard. RESULTS: The system correctly found that CD and UC samples had a greater prevalence of basal plasma cells with mean number of PCs within ROIs of 38.22 (95 % CI: 31.73, 49.04) for CD, 55.16 (46.57, 65.93) for UC, and 17.25 (CI: 12.17, 27.05) for controls. Overall, OR=4.968 (CI: 1.835, 14.638) was found for IBD compared to normal mucosa (CD: +59 %; UC: +129 %). Additionally, as expected, UC samples were found to have more plasma cells in colon than CD cases. CONCLUSION: Our model accurately replicated human assessment of basal plasmacytosis, underscoring the value of AI models as a potential aid IBD diagnosis.

Mucin Expression Profiles in Ulcerative Colitis: New Insights on the Histological Mucosal Healing.

A structural weakness of the mucus barrier (MB) is thought to be a cause of ulcerative colitis (UC). This study aims to investigate the mucin (MUC) composition of MB in normal mucosa and UC. Ileocolonic biopsies were taken at disease onset and after treatment in 40 patients, including 20 with relapsing and 20 with remitting UC. Ileocolonic biopsies from 10 non-IBD patients were included as controls. Gut-specific MUC1, MUC2, MUC4, MUC5B, MUC12, MUC13, MUC15, and MUC17 were evaluated immunohistochemically. The promoters of mucin genes were also examined. Normal mucosa showed MUC2, MUC5B, and MUC13 in terminal ileum and colon, MUC17 in ileum, and MUC1, MUC4, MUC12, and MUC15 in colon. Membranous, cytoplasmic and vacuolar expressions were highlighted. Overall, the mucin expression was abnormal in UC. Derangements in MUC1, MUC4, and MUC5B were detected both at onset and after treatment. MUC2 and MUC13 were unaffected. Sequence analysis revealed glucocorticoid-responsive elements in the MUC1 promoter, retinoic-acid-responsive elements in the MUC4 promoter, and butyrate-responsive elements in the MUC5B promoter. In conclusion, MUCs exhibited distinct expression patterns in the gut. Their expression was disrupted in UC, regardless of the treatment protocols. Abnormal MUC1, MUC4, and MUC5B expression marked the barrier dysfunction in UC.

Amoebic colitis and liver abscess: A rare case of autochthonous invasive infection due to Entamoeba histolytica.

We report an unusual and confirmed case of invasive amebiasis in a non-endemic area where the source of infection remains unknown. During her admission, the patient developed amebic colitis and extraintestinal liver abscess with a favorable outcome following the antiparasitic therapy.

Mastocytic enterocolitis: Increase of mast cells in the gastrointestinal tract of patients with chronic diarrhea / Enterocolitis mastocítica: aumento de los mastocitos en el tracto gastrointestinal de pacientes con diarrea crónica

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The importance of a second opinion in the diagnosis of Barrett’s esophagus: a 'real life' study

Background: Barrett's esophagus is a precancerous lesion, and its identification with the early detection of dysplasia is of paramount importance to prevent adenocarcinoma onset. However, there is still debate on the correct pathological identification of Barrett’s esophagus (and of associated dysplasia), and most studies have been conducted in an experimental setting. Aims: To assess previous uncertain diagnoses of Barrett’s (with and without dysplasia) via a second opinion of an expert pathologist in a real life setting. Patients and methods: Histological sections of 32 suspected Barrett’s patients from ten general Pathology units were centralized into one single unit in which an expert pathologist reviewed the slides blindly. Results: Overall, in 78% of cases there was diagnostic discordance; in particular, in 64% of cases the presence of low grade dysplasia was not confirmed. Of interest, 28% of cases with the original diagnosis were reclassified as non-Barrett’s. Conclusions: The pathological diagnosis of Barrett’s esophagus, especially with regard to the presence of dysplasia, is still misinterpreted, particularly in the setting of general pathology units. Thus, a second opinion from an experienced pathologist may help in the interpretation of the results and in starting appropriate followup programs (AU)

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Histopathological findings in the oral mucosa of celiac patients / Hallazgos histopatológicos en la mucosa oral de los pacientes con enfermedad celiaca

Background: Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible subjects. Although the small intestinal mucosa is the main site of the gut’s involvement in CD, other mucosal surfaces belonging to the gastrointestinal tract and the gut-associated lymphoid tissue are known to be affected. Aim: Assuming that the oral mucosa could reflect the histopathological inflammatory alterations of the intestine in CD patients, this study wishes to assess the pattern of T-cell subsets inthe oral mucosa of young adults with CD. Methods: A group of 37 patients (age range 20-38 years; female: male ratio 28:9) with CD were enrolled. Out of 37 patients, 19 patients (group A) followed a gluten free diet (GFD) -2 patients from less than one year; 6 patients between 1 and 5 years; 11 patients more than 5 years- while 18 patients (group B) were still untreated. Fifteen healthy volunteers (age range 18-35 years, female: Male ratio 11:4) served as controls for the CD patients. Ethical approval for the research was granted by the Ethics Committee. Biopsy specimens were taken from normal looking oral mucosa. The immunohistochemical investigation was performed with monoclonal antibodies to CD3, CD4, CD8, and γδ-chains T cell receptor (TCR). Results: The T-lymphocytic inflammatory infiltrate was significantly (p < 0.0001) increased in group B (both compared with group A and with the control group). Conclusion: This study confirms the oral cavity to be a site of involvement of CD and its possible diagnostic potentiality in this disease (AU)

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Severe spruelike enteropathy due to olmesartan / Enteropatía grave similar a la enfermedad celiaca debido al olmesartán

Villous atrophy and negative serologic testing is a diagnostic challenge, and the rarer possibility of drug-induced enteritis should be considered. We report a rare case of severe spruelike enteritis due to olmesartan that completely resolved after withdrawal of the drug. The possibility that patient labeled as "refractory" celiac disease may actually be due to drug treatment should always be taken into consideration, to avoid unnecessary investigations (AU)

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Perihepatic splenosis simulating a focal liver lesion in a patient with chronic hepatitis C / Esplenosis perihepática simulando una lesión focal hepática en un paciente con hepatitis crónica C

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Influence of genetics on tumoral pathologies: The example of the adenocarcinoma arising in Barrett’s esophagus / Influencia de la genética en la patología tumoral. El ejemplo del adenocarcinoma desarrollado sobre el esófago de Barrett

Barrett's esophagus (BE) refers to an abnormal change (metaplasia) in the cells of the inferior portion of the esophagus. About 10% of patients with symptomatic gastroesophageal reflux disease (GERD) have BE. In some cases, BE develops as an advanced stage of erosive esophagitis. The risk of esophageal cancer appears to be increased in patients with BE. The only way to diagnose BE is by endoscopy and histology. Some studies suggest that intensive treatment of Barrett’s esophagus with effective acid suppression can reduce the amount of abnormal lining in the esophagus. It is not clear whether such treatment also prevents esophageal cancer. Generally, the cancer starts out as carcinoma of the esophagus on the surface, and then invades the surrounding tissue. Surgery offers the best chance of long-term survival. There are many events that occur in Barrett’s esophagus that lead to the development of cancer and most of them appear to occur early, before high-grade dysplasia or cancer develops. No one knows what the late events are and how cells acquire the ability to leave their normal growth boundaries. It is now widely accepted that the development of most cancers is due to something called genomic or genetic instability. The aim of this review is to show BE pathology in its progression to cancer looking for new biomarkers to distinguish between BE -dysplasia (low grade and high grade)- adenocarcinoma (ADC) and to characterize the ADC, giving more hope for its treatment(AU)

HLA-DQ typing in the diagnostic algorithm of celiac disease

Objective: celiac disease (CD) is an immune-mediated chronic inflammatory disease associated with HLA-DQ2 and DQ8 molecules. We evaluated the role of HLA in the CD diagnostic algorithm in order to contribute to the development of practical indications for the use of HLA typing. Material and methods: we selected 317 subjects typed for DR-DQ genes. CD was present in 123 patients, and 89 were included in the study; a control sample of 70 healthy individuals was recruited. Results: 64% of patients with CD carried DQ2 heterodimer (a5b2), 13.5% carried DQ8 heterodimer without DQ2, 21.4% only showed b2 chain and 1.1% were positive for DQ2 a5 chain. The only presence of a5 chain did not predispose to CD, while DQB1*02 allele resulted more frequent than in other reports, pointing out the intrinsic correlation between b2 chain and CD. In the case-control study we observed a progression of increased risk, ranging from 1:7 for HLA-DQ2 homozygous to 1:85 for DQ8 heterozygous subjects. Overall, 8,6% of first degree family members were affected, exclusively in presence of HLA-DQ2, -DQ8 or DQB1*02, and CD was significantly more frequent among siblings than parents. Finally, considering the different patterns of clinical presentation among the HLA-DQ risk classes identified we found no relationship between CD clinical presentation and HLA-DQ risk categories. Conclusions: our results strengthen the evidence that HLA-DQ status strongly influences the development of CD and demonstrate that knowledge of a patient’s HLA-DQ genotype allows to establish clinically relevant genetic risk profiles(AU)

Chronic hepatitis in man and in dog: a comparative update / Hepatitis crónica en el hombre y en el perro: una actualización comparativa

Chronic hepatitis is a frequent pathologic condition encountered in both dogs and humans; however, in the latter etiologic factors are usually searched and found that allow targeted therapeutic approaches, whereas in dogs this is less frequent. This review will take into consideration chronic hepatitis in dogs, and discuss differences and similarities between the two species with respect to this disease(AU)

Epidermal growth factor receptor overexpression/amplification in adenocarcinomas arising in the gastrointestinal tract

Introduction: it has been suggested that EGFR might be valuable to select patients for immunotherapy for various types of cancers. Aims: we investigated: a) the gene/proteins alterations in gastrointestinal cancers using immunohistochemistry (IHC) (gene overexpression) and fluorescence in situ hybridisation (FISH) (gene amplification); and b) the associations between EGFR overexpression and amplification and chromosome 7 aneusomy (CEP7) in these cancers. Methods: 64 tumor specimens were evaluated by IHC and FISH: 17 adenocarcinoma arising in Barrett’s esophagus, 21 stomach cancers, 17 colon cancers, and 9 liver metastasis of colon carcinoma. IHC for EGFR was scored at 4 levels of intensity of membrane staining. EGFR gene in FISH was considered as amplified or not and chromosome 7 (where EGFR is located) as polisomic or disomic. The ratio between EGFR gene and chromosome 7 was performed by FISH and classified the case as gene amplification when the ratio was > 2. Polisomy was identified when the copies of chromosome 7 were > 2 in more than 8% malignant cells. Results: no difference was found between EGFR gene amplification/ protein overexpression according to cancer site. Concerning IHC, most cases were positive for EGFR intensity (84.4%), while only 50% of cases were positive considering a cut-off of 10%. EGFR FISH amplification was found in 4 cases only (6.2%) and FISH CEP7 aneusomy in 40.6%. A statistically significant association was found between EGFR protein positivity (IHC) in term of intensity and EGFR gene amplification by FISH (p = 0.003), and between the EGFR protein positivity (IHC) and chromosome 7 aneusomy (FISH) (p = 0.004). Conclusions: EGFR amplification assessed by FISH was found in only 4 cases (6.2%) while chromosome 7 aneusomy was identified in 26 (40.6%) cases. IHC proved that EGFR protein overexpression in gastrointestinal cancers is common but FISH assessment showed that EGFR gene amplification is rare. An association was observed between EGFR gene amplification and EGFR protein overexpression in a low number of cases (p = 0.003). A statistically significant association was found between EGFR protein overexpression and chromosome7 polisomy (p = 0.004)(AU)

Non-IBD colitides: clinically useful histopathological clues / Colitis no relacionadas con la enfermedad inflamatoria intestinal: claves histopatológicas de utilidad clínica

Apart from inflammatory bowel diseases (IBD), there are several other form of colitis that may resemble macroscopically IBD, entering the differential diagnosis. These forms are represented by infectious colitis, ischemic colitis, pseudomembranous colitis, colitis related to diverticular disease, colitis related to mucosal prolapse, drug colitis, allergic colitis, and microscopic colitis. However, to distinguish be - tween these forms is not always easy, and it frequently requires a strict interrelationship between the pathologist and the gastroenterologist. Here we discuss the more frequent forms of non- inflammatory bowel diseases colitides, trying to give useful hints for helping the clinician to better understand the extent to which the pathologist is called to give a definitive response in the differential diagnosis of these entities(AU)