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Clostridioides difficile (C. difficile) is responsible for a spectrum of nosocomial/antibiotic-associated gastrointestinal diseases that are increasing in global incidence and mortality rates. The C. difficile pathogenesis is due to toxin A and B (TcdA/TcdB), both causing cytopathic and cytotoxic effects and inflammation. Recently, we demonstrated that TcdB induces cytopathic and cytotoxic (apoptosis and necrosis) effects in enteric glial cells (EGCs) in a dose/time-dependent manner and described the underlying signaling. Despite the role played by lipids in host processes activated by pathogens, to counter infection and/or induce cell death, to date no studies have investigated lipid changes induced by TcdB/TcdA. Here, we evaluated the modification of lipid composition in our in vitro model of TcdB infection. Apoptosis, cell cycle, cell viability, and lipidomic profiles were evaluated in EGCs treated for 24 h with two concentrations of TcdB (0.1 ng/mL; 10 ng/mL). In EGCs treated with the highest concentration of TcdB, not only an increased content of total lipids was observed, but also lipidome changes, allowing the separation of TcdB-treated cells and controls into different clusters. The statistical analyses also allowed us to ascertain which lipid classes and lipid molecular species determine the clusterization. Changes in lipid species containing inositol as polar head and plasmalogen phosphatidylethanolamine emerged as key indicators of altered lipid metabolism in TcdB-treated EGCs. These results not only provide a picture of the phospholipid profile changes but also give information regarding the lipid metabolism pathways altered by TcdB, and this might represent an important step for developing strategies against C. difficile infection.

Percutaneous endoscopic gastrostomy is the method of choice to allow enteral access in patients requiring long-term enteral nutrition. However, although generally safe, percutaneous tube positioning may be plagued by several complications. Among these, the deterioration and/or deflation of balloons serving as internal bolster is particularly worrisome in that it may lead to gastrostomy cannulas dislocation. Of interest, such balloon deflation may occur in up to 30% of cases for apparently unexplained causes. Here, we provide a hypothesis that could explain some of these causes.

Bacterial infections are characterized by an inflammatory response, which is essential for infection containment but is also responsible for negative effects on the host. The pathogen itself may have evolved molecular mechanisms to antagonize the antimicrobial effects of an inflammatory response and to enhance its pathogenicity using inflammatory response mediators, such as cytokines. Clostridioides difficile (C. difficile) infection (CDI) causes gastrointestinal diseases with markedly increasing global incidence and mortality rates. The main C. difficile virulence factors, toxin A and B (TcdA/TcdB), cause cytopathic/cytotoxic effects and inflammation. We previously demonstrated that TcdB induces enteric glial cell (EGC) apoptosis, which is enhanced by the pro-inflammatory cytokine tumor necrosis factor alpha plus interferon gamma (CKs). However, it is unknown whether CKs-enhanced TcdB cytotoxicity (apoptosis/necrosis) is affected by the timing of the appearance of the CKs. Thus, we simulated in vitro, in our experimental model with TcdB and EGCs, three main situations of possible interactions between TcdB and the timing of CK stimulation: before TcdB infection, concomitantly with infection, or at different times after infection and persisting over time. In these experimental conditions, which all represent situations of possible interactions between C. difficile and the timing of CK stimulation, we evaluated apoptosis, necrosis, and cell cycle phases. The CKs, in all of these conditions, enhanced TcdB cytotoxicity, which from apoptosis became necrosis when CK stimulation persisted over time, and was most relevant after 48 h of TcdB:EGCs interaction. Particularly, the enhancement of apoptosis by CKs was dependent on the TcdB dose and in a less relevant manner on the CK stimulation time, while the enhancement of necrosis occurred always independently of the TcdB dose and CK stimulation time. However, since in all conditions stimulation with CKs strongly enhanced the TcdB cytotoxicity, it always had a negative impact on C. difficile pathogenicity. This study might have important implications for the treatment of CDI.

Clostridioides difficile (C. difficile), responsible for 15–25% of gastrointestinal infections, causes health problems mainly due to the toxic activity of toxins A and B (Tcds). These are responsible for its clinical manifestations, including diarrhea, pseudomembranous colitis, toxic megacolon and death, with a mortality of 5–30% in primary infection, that increase following relapses. Studies on Tcd-induced cell death have highlighted a key role of caspases, calpains, and cathepsins, with involvement of mitochondria and reactive oxygen species (ROS) in a complex signaling pathway network. The complex response in the execution of various types of cell death (apoptosis, necrosis, pyroptosis and pyknosis) depends on the amount of Tcd, cell types, and Tcd receptors involved, and could have as initial/precocious event the alterations in calcium homeostasis. The entities, peculiarities and cell types involved in these alterations will decide the signaling pathways activated and cell death type. Calcium homeostasis alterations can be caused by calcium influx through calcium channel activation, transient intracellular calcium oscillations, and leakage of calcium from intracellular stores. These increases in cytoplasmic calcium have important effects on all calcium-regulated molecules, which may play a direct role in several cell death types and/or activate other cell death effectors, such as caspases, calpains, ROS and proapoptotic Bcl-2 family members. Furthermore, some support for the possible role of the calcium homeostasis alteration in Tcd-induced cell death originates from the similarity with cytotoxic effects that cause pore-forming toxins, based mainly on calcium influx through plasma membrane pores.

Mucosal healing (MH) is the main treatment target in ulcerative colitis (UC) and Crohn’s disease, and it is defined by the combination of complete endoscopic and histologic remission. The complete resolution of mucosal inflammation should be confirmed by histology but its assessment is not always univocal. Neutrophil infiltration represents the unique histological marker in discriminating the active vs. quiescent phases of the disease, together with crypt injuries (cryptitis and crypt abscesses), erosions, and ulcerations. On the contrary, basal plasmacytosis is not indicative of activity or the remission of inflammatory bowel diseases (IBDs) but instead represents a diagnostic clue, mostly at the onset. Several histological scoring systems have been developed to assess grade severity, particularly for UC. However, most are complex and/or subjective. The aim of this review was to summarize available scores, their characteristics and limitations, and to present the advantages of a simplified mucosa healing scheme (SHMHS) based on neutrophils and their distribution in the gut mucosa. Finally, we overview future developments including artificial intelligence models for standardization of disease assessments and novel molecular markers of inflammation with potential application in diagnostic practice.

Clostridioides difficile (C. difficile) is responsible for a high percentage of gastrointestinal infections and its pathological activity is due to toxins A and B. C. difficile infection (CDI) is increasing worldwide due to the unstoppable spread of C. difficile in the anthropized environment and the progressive human colonization. The ability of C. difficile toxin B to induce senescent cells and the direct correlation between CDI, irritable bowel syndrome (IBS), and inflammatory bowel diseases (IBD) could cause an accumulation of senescent cells with important functional consequences. Furthermore, these senescent cells characterized by long survival could push pre-neoplastic cells originating in the colon towards the complete neoplastic transformation in colorectal cancer (CRC) by the senescence-associated secretory phenotype (SASP). Pre-neoplastic cells could appear as a result of various pro-carcinogenic events, among which, are infections with bacteria that produce genotoxins that generate cells with high genetic instability. Therefore, subjects who develop IBS and/or IBD after CDI should be monitored, especially if they then have further CDI relapses, waiting for the availability of senolytic and anti-SASP therapies to resolve the pro-carcinogenic risk due to accumulation of senescent cells after CDI followed by IBS and/or IBD.

Background: There are no evidence-based recommendations for performing upper gastrointestinal endoscopy (UGIE) in patients with extra-oesophageal symptoms of gastro-oesophageal reflux disease (GORD). However, UGIEs are often performed in clinical practice in these patients. We aimed to assess the prevalence of gastro-oesophageal lesions in patients with atypical GORD symptoms. Methods: Patients complaining of at least one extra-oesophageal GORD symptom and undergoing UGIE in seven centres were prospectively enrolled. Clinically relevant lesions (Barrett’s oesophagus, erosive oesophagitis, gastric precancerous conditions, peptic ulcer, cancer, and H. pylori infection) were statistically compared between groups regarding GORD symptoms (atypical vs. both typical and atypical), type of atypical symptoms, age, and presence of hiatal hernia. Results: Two hundred eleven patients were enrolled (male/female: 74/137; mean age: 55.5 ± 14.7 years). Barrett’s oesophagus was detected in 4 (1.9%), erosive oesophagitis in 12 (5.7%), gastric precancerous conditions in 22 (10.4%), and H. pylori infection in 38 (18%) patients. Prevalence of clinically relevant lesions was lower in patients with only atypical GORD symptoms (28.6 vs. 42.5%; p = 0.046; χ2 test), in patients ≤50 years (20 vs. 44.8%; p = 0.004; χ2 test), and in those in ongoing proton pump inhibitor (PPI) therapy (21.1 vs. 40.2%; p = 0.01; χ2 test). No clinically relevant lesions were detected in patients ≤50 years, without alarm symptoms, and receiving PPI therapy. Hiatal hernia was diagnosed in only 6 patients with cardiologic and in 41 patients with ear-nose-throat symptoms (11.3 vs. 35.1%; p = 0.03; χ2 test). Conclusions: Clinically relevant lesions are uncommon among young (≤50 years) patients with extra-oesophageal GORD symptoms. Hiatal hernia is not more prevalent in patients with cardiologic symptoms and suspicion of GORD. The usefulness of UGIE in these patients is questionable.

Clostridioides difficile infection (CDI) is on the rise worldwide and is associated with an increase in deaths and socio-health burden. C. difficile has become ubiquitous in anthropized environments because of the extreme resistance of its spores. Based on the epidemiological data and knowledge of molecular pathogenesis of C. difficile , it is possible to predict its progressive colonization of the human population for the following reasons: first, its global spread is unstoppable; second, the toxins (Tcds) produced by C. difficile , TcdA and TcdB, mainly cause cell death by apoptosis, but the surviving cells acquire a senescence state that favours persistence of C. difficile in the intestine; third, proinflammatory cytokines, tumour necrosis factor-α and interferon-γ, induced during CDI, enhance the cytotoxicity of Tcds and can increase the survival of senescent cells; fourth, Tcds block mobility and induce apoptosis in immune cells recruited at the infection site; and finally, after remission from primary infection or relapse, C. difficile causes functional abnormalities in the enteric glial cell (EGC) network that can result in irritable bowel syndrome, characterized by a latent inflammatory response that contributes to C. difficile survival and enhances the cytotoxic activity of low doses of TcdB, thus favouring further relapses. Since a ‘global endemy’ of C. difficile seems inevitable, it is necessary to develop an effective vaccine against Tcds for at-risk individuals, and to perform a prophylaxis/selective therapy with bacteriophages highly specific for C. difficile. We must be aware that CDI will become a global health problem in the forthcoming years, and we must be prepared to face this menace.

Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in μm), crypt depth (CrD, in μm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400–705) than controls (900, IQR: 667–1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390–620) vs. 427 µm (IQR: 348–569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.

Abstract Clostridioides difficile infection (CDI) represents an important health problem worldwide, with significant morbidity and mortality. This infection has also high recurrence rates, whose pathophysiological grounds are still poorly understood. Based on our experiments in vitro with Clostridioides difficile toxin B and existing experimental and clinical evidence, we propose that primary CDI and relapses might be favored by a mechanism that involves the enhancement of the toxicity of toxin B by proinflammatory cytokines, tumor necrosis factor alpha, and interferon gamma on the enteric glial cells and their network in an environment characterized by a strong dysmicrobism.

Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1), and its ligand PDL-1, are finding increasing application in the treatment of malignant neoplasms. The widespread clinical use of these drugs, however, resulted in the discovery of side effects. The occurrence of celiac disease (CD) after ICIs therapy has been reported in the literature, but its incidence remains unknown and the role of ICIs in its onset is not yet clear. In this review, we examine the published data on this topic in order to better understand and define this entity from a histological point of view. We performed an electronic literature search to identify original reports in which CD or pathological CD-like conditions were documented histologically in patients treated with ICIs. We identified ten papers. A total of twenty-five patients were included in these publications, eleven of them receiving a serologic and histological diagnosis of CD, and four a histological diagnosis of CD-like conditions, in which pathogenesis appears to be multifactorial. ICIs can cause a CD-like enteropathy and biopsies with clinical integration are crucial to diagnose this condition. CD rarely has been observed during treatment with ICIs and its morphological aspects are similar to ICIs-CD enteropathy. Moreover, the onset of ICIs-CD may have a distinct immune mechanism compared to classical CD. Thus, the pathologists must make a histological diagnosis of CD with caution and only in adequate clinical and serological context.

Background and Objective: During the COVID-19 pandemic, health systems worldwide made major changes to their organization, delaying diagnosis and treatment across a broad spectrum of pathologies. Concerning surgery, there was an evident reduction in all elective and emergency activities, particularly for benign pathologies such as acute diverticulitis, for which we have identified a reduction in emergency room presentation with mild forms and an increase with more severe forms. The aim of our review was to discover new data on emergency presentation for patients with acute diverticulitis during the Covid-19 pandemic and their current management, and to define a better methodology for surgical decision-making. Method: We conducted a scoping review on 25 trials, analyzing five points: reduced hospital access for patients with diverticulitis, the preferred treatment for non-complicated diverticulitis, the role of CT scanning in primary evaluation and percutaneous drainage as a treatment, and changes in surgical decision-making and preferred treatment strategies for complicated diverticulitis. Results: We found a decrease in emergency access for patients with diverticular disease, with an increased incidence of complicated diverticulitis. The preferred treatment was conservative for non-complicated forms and in patients with COVID-related pneumonia, percutaneous drainage for abscess, or with surgery delayed or reserved for diffuse peritonitis or sepsis. Conclusion: During the COVID-19 pandemic we observed an increased number of complicated forms of diverticulitis, while the total number decreased, possibly due to delay in hospital or ambulatory presentation because of the fear of contracting COVID-19. We observed a greater tendency to treat these more severe forms by conservative means or drainage. When surgery was necessary, there was a preference for an open approach or a delayed operation.

Abstract The concept of remission for patients with inflammatory bowel diseases has recently evolved, and should also include histological healing of the mucosa, difficult to evaluate since there is no agreement on pathological scores and those available are quite complex to use in the daily routine. We evaluated the possible usefulness of a simplified pathological score to assess histological healing of the mucosa in inflammatory bowel diseases patients compared with four commonly proposed pathological scores. Slides from 24 patients (12 Crohn’s disease, 12 ulcerative colitis, age range 24–62 years), pre- and post-treatment with biological agents and displaying endoscopic remission were assessed by two pathologists. Pre- and post-treatment results and the time employed to calculate the various scores were obtained. All scores were useful to document highly significant post-treatment decreases of histological activity. However, the simplified score needed significant less time to be calculated for each slide, had high inter-rater agreement, and avoided subjectivity from the pathologists. The simplified score is easy to calculate and seems apt to document histological healing of the mucosa, in a manner similar to the more complex scores. It remains to be established whether this score could simplify the daily routinary practice in this context.

Guanylate cyclase-C (GC-C) is a multifunctional receptor encoded by the GUCY2C gene, representing an attractive target for therapy in several gastrointestinal diseases in humans. Little is known about this system in horses. We investigated for the first time the gene expression of guanylin, uroguanylin and GC-C receptors in different horse’s gastrointestinal tracts. Tissue samples from stomach, duodenum, jejunum, ileum, head and body of cecum, left and right dorsal colon, left and right ventral colon, pelvic flexure, transverse colon, descending colon and rectum were collected from adult horses within 1 h post mortem. For each sample, total RNA was extracted from 100 mg of ground tissue, and qRT-PCR performed on GUCA2a, GUCA2b and GUCY2 transcripts on a CFX96 Touch instrument. Data analysis was carried out with Bio-Rad CFX Manager software, and genes of interest normalized relative to the abundance of the two reference genes (SDHA, HPRT). Additionally, the protein expression levels of GC-C receptor were analyzed through western blotting. A common pattern of expression throughout the gastrointestinal lumen for all three investigated transcripts was found. The expression of GUCA2a, GUCA2b and GUCY2 genes was higher in jejunum, ileum, descending colon and rectum. The levels of expression of GC-C protein confirmed these data. The findings of this study might open new scenarios for the therapeutic approach to enteric diseases of horse using selective agonists of GC-C.

A limited number of sclerosing Angiomatoid Nodular Transformation (SANT) have been reported in pediatric age. We describe the first case of SANT occurring in a nine-week-old female infant that was admitted to our unit for severe abdominal distension and rectal bleeding. Enlarged spleen was detected on physical examination. Laboratory investigations revealed severe anemia and coagulation abnormalities. Abdominal ultrasound and computed tomography revealed ascites and splenomegaly with a large mass at the lower medial splenic pole. A diagnosis of intraabdominal hemorrhage was presumed and an exploratory laparotomy was performed. A complete transformation of the giant splenomegaly to bossellated masses and multiple bleeding capsular ruptures without subcapsular hematoma were found and an urgent splenectomy was performed. At histology, a SANT was diagnosed (CD34, CD31, CD8 positivity). The postoperative follow up was uneventful. SANT may also occur in infancy with a potentially lifethreatening presentation. Splenectomy may represent the only treatment in severe cases.

Background: Irritable bowel syndrome (IBS) is frequently associated with celiac disease (CD) and nonceliac gluten/wheat sensitivity (NCGS/NCWS), but epidemiological and pathophysiological aspects are still unclear. Furthermore, a gluten-free diet (GFD) can positively influence IBS symptoms. Methods: A comprehensive online search for IBS related to CD, NCGS and GFD was made using the Pubmed, Medline and Cochrane databases. Results: Although a systematic screening for CD in IBS is not recommended, CD prevalence can be increased in diarrhea-predominant IBS patients. On the other hand, IBS symptoms can be persistent in treated CD patients, and their prevalence tends to decrease on a GFD. IBS symptoms may overlap and be similar to those associated to nonceliac gluten and/or wheat sensitivity. Increased gut permeability could explain the gluten/wheat effects in IBS patients. Finally, a GFD could improve symptoms in a subgroup of IBS patients. Conclusions: The possible interplay between IBS and gluten-related disorders represents a scientifically and clinically challenging issue. Further studies are needed to confirm these data and better clarify the involved pathophysiological mechanisms.

Background and study aims Endoscopic treatment is the mainstay approach for gastrointestinal bleeding, in either upper (UGIB) or lower (LGIB) tract. The over-the-scope clip (OTSC) may overcome limitations of standard clips or thermocoagulation in high-risk bleeding lesions. We evaluate the main clinically relevant outcomes following endoscopic hemostasis with OTSC in high-risk lesions and/or patients. Patients and methods This was a retrospective analysis of prospectively collected databases including all patients with UGIB and LGIB who underwent OTCS placement as first-line treatment in eleven tertiary endoscopic referral centers. Technical success, primary hemostasis, rebleeding, blood transfusion, hospital stay, and hemorrhage-related mortality rates were evaluated. Results Data from 286 patients, with either UGIB (N = 214) or LGIB (N = 72) were available. Overall, 112 patients (39.2 %) were receiving antithrombotic therapy. Technical success and primary hemostasis rates were 97.9 % and 96.4 %, respectively. Early rebleeding occurred in 4.4 %, more frequently in those on antithrombotic therapy, and no late rebleeding was observed. Following a successful primary haemostasis, only 5.2 % patients needed blood transfusions, and the median hospital stay was 4 days (range: 3 – 11). Eighteen patients with either technical failure (N = 6) or rebleeding (N = 12) underwent radiological or surgical approaches. Overall, bleeding-related deaths occurred in 5 (1.7 %) patients, including 3 patients with technical procedural failure, and 2 in the rebleeding group. Conclusions Data from our large, multicenter study show that OTSC placement is an effective first-line treatment for hemostasis in high-risk patients and/or lesions both in upper and lower gastrointestinal tract.

BACKGROUND:We determined the range of normal spleen dimensions evaluated by ultrasonography (US) in children according to sex and age and the relationship between splenic measurements, auxological data and body proportions, in order to define splenomegaly parameters in support of the surgical mini-invasive approaches in pediatrics. METHODS:We prospectively examined 317 caucasian children of both sexes. The patients were divided into three groups: 0-3 years; 4-10 years; 11-18 years. Sex, weight, height/length, body mass index (BMI), waist circumference and xipho-pubic distance were determined for each child. US spleen evaluation included longitudinal/antero-posterior/transverse diameters, transverse area and volume. Spleen volume/abdominal volume, longitudinal spleen diameter/longitudinal left kidney diameter and longitudinal spleen diameter/xipho-pubic distance ratios were also calculated. RESULTS:For caucasian subjects, in different age groups spleen volume, transverse area and diameter increased while the spleen/abdominal volume ratio decreased significantly (p

Background and aims: the diagnosis of celiac disease requires small bowel biopsies to identify the characteristic mucosal changes. The current biopsy practice among endoscopists for celiac disease is in most part unknown. The aim of this study was to compare the different diagnostic policies in various centers in their current practice. Method: information from a total of 931 confirmed celiac disease patients was retrospectively obtained retrospectively from nine centers in European and Middle Eastern countries. The number of small-bowel biopsies obtained from the duodenal bulb and the second part of the duodenum was compared among different centers. Results: the most frequent stage of mucosal changes amongst Iranian subjects was Marsh IIIa whereas in the rest of the study population was Marsh IIIc. Marsh I and Marsh II were more prevalent in adults (P < 0.05) and Marsh IIIc was significantly higher in pediatric ages between 1 and 15 (P < 0.05). The most common number of biopsy specimens obtained from Romanian subjects was 1 (52% of cases), followed by 2 for Iranian (56%), 3 for Lithuanian (66.7%) and British patients (65%) and 4 for Italian patients (48.3%). For majority of cases, anemia was the most prevalent symptom (18.7%) followed by malabsorption (10.5%), diarrhea (9.3%) and dyspepsia (8.2%), respectively. Conclusions: despite the evidence-based recommendations, this study revealed a poor compliance with major guidelines on diagnosis of celiac disease. We emphasize that taking adequate number of duodenal biopsies should be implemented for an accurate diagnosis and also for the exclusion of celiac disease.

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.

Dyspepsia is defined as symptoms related to the upper gastrointestinal tract. Approximately 25% of western populations complain of dyspeptic symptoms each year. 70% of them do not have an organic cause and symptoms are related to the so-called functional dyspepsia, characterized by epigastric pain, early satiety, and/or fullness during or after a meal occurring at least weekly and for at least 6 months according to ROME III criteria. In order to avoid invasive procedures and adverse effects, to minimize costs, to speed up diagnosis, and to provide the most appropriate treatments, primary care physicians need to recognize functional dyspepsia. Because symptoms do not reliably discriminate between organic and functional forms of the disease, anamnesis, family history of peptic ulcer and/or of gastric cancer, medication history, especially for nonsteroidal anti-inflammatory drugs, age, and physical examination could help the physician in discerning between functional dyspepsia and organic causes. For patients without alarm symptoms, noninvasive testing for H. pylori, with either carbon-13-labeled urea breath testing or stool antigen testing, is recommended as a first-line strategy. In this review, we provide recommendations to guide primary care physicians for appropriate use of diagnostic tests and for H. pylori management in dyspeptic patients.

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 (α5β2), 13.5% carried DQ8 heterodimer without DQ2, 21.4% only showed β2 chain and 1.1% were positive for DQ2 α5 chain. The only presence of α5 chain did not predispose to CD, while DQB1*02 allele resulted more frequent than in other reports, pointing out the intrinsic correlation between β2 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.

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.

Recurrent episodes of self-limiting diarrhea in the dog, due to sudden dietary changes and to stressful or exciting situations, are conditions sometimes difficult to treat. Colifagina®, a commercially available bacterial enterovaccine, showed, in previous studies performed on experimentally induced colitis in mice, to be able to improve both disease activity index and histological appearance, increase colonic secretion of IgA, and reduce inflammatory chemokine secretion. In the present study Colifagina® was administered to five dogs presenting recurrent episodes of self-limiting diarrhea and to one dog presenting chronic diarrhea. During the follow-up period, almost all patients decreased the number of episodes of abnormal defecation and the fecal score of such episodes improved in five out of six dogs. Even if further studies are needed to understand the exact potential of the compound, in dogs presenting recurrent episodes of self-limiting diarrhea due to sudden dietary changes and/or stressing or exciting situations, Colifagina® seems to be helpful in managing most of these patients.

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).

An increasing number of children, usually with gastrointestinal symptoms, is diagnosed with eosinophilic esophagitis (EE), and a particular subset of these patients complains of airway manifestations. We present the case of a 2-year-old child with chronic dry cough in whom EE was found after a first diagnosis of gastroesophageal reflux disease (GERD) due to pathological 24-hour esophageal pH monitoring. Traditional allergologic tests were negative, while patch tests were diagnostic for cow’s milk allergy. We discuss the intriguing relationship between GERD and EE and the use of patch test for the allergologic screening of patients.

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 between 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.

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.

The pathogenesis of diverticular disease (DD) is thought to result from complex interactions among dietary habits, genetic factors and coexistence of other bowel abnormalities. These conditions lead to alterations in colonic pressure and motility, facilitating the formation of diverticula. Although electrophysiological studies on smooth muscle cells (SMCs) have investigated colonic motor dysfunctions, scarce attention has been paid to their molecular abnormalities, and data on SMCs in DD are lacking. Accordingly, the main purpose of this study was to evaluate the expression patterns of molecular factors involved in the contractile functions of SMCs in the tunica muscularis of colonic specimens from patients with DD.By means of immunohistochemistry and image analysis, we examined the expression of Cx26 and Cx43, which are prominent components of gap junctions in human colonic SMCs, as well as pS368-Cx43, PKCps, RhoA and αSMA, all known to regulate the functions of gap junctions and the contractile activity of SMCs. The immunohistochemical analysis revealed significant abnormalities in DD samples, concerning both the expression and distribution patterns of most of the investigated molecular factors.This study demonstrates, for the first time, that an altered pattern of factors involved in SMC contractility is present at level of the tunica muscularis of DD patients. Moreover, considering that our analysis was conducted on colonic tissues not directly affected by diverticular lesions or inflammatory reactions, it is conceivable that these molecular alterations may precede and predispose to the formation of diverticula, rather than being mere consequences of the disease.

Caustic strictures of the gastrointestinal tract are often difficult to treat, since relapses are frequent after medical or endoscopic treatment. Thus, novel approaches are needed. We report here our experience with self-expandable metallic stents (SEMS) as a new endoscopic approach in three patients with corrosive strictures of the upper gastrointestinal tract.

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 follow-up programs.