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In vertebrate species, the MDM2 and MDM4 gene paralogs negatively regulate the activity of p53 family members and are involved in the development of a number of tumor types. Comparative genomic analyses have shown the presence of a single mdm homolog gene in invertebrates; its interaction with p53 and its involvement in tumor pathogenesis was demonstrated only in the mussel Mytilus trossulus . In addition to p53-related activity, a pro-inflammatory role for MDM2 in mammals has recently been described. In the present paper, we report the Real-time RT-PCR expression analysis of the mdm homolog gene in digestive gland tissue of Mytilus galloprovincialis collected from four different sites in the Campania region (Italy) during a single year. Our results revealed a positive correlation between the expression level of the mdm homolog and the percentage of chronic inflammatory lesions, both of which are increased during the summer period, suggesting a previously unidentified involvement of mdm in inflammatory processes in invertebrate species. Results obtained pointed out the potential interest of the use of mdm gene expression in marine food and seawater quality evaluation monitoring programs.

Archaeological research documents major technological shifts among people who have lived in the southern tip of South America (South Patagonia) during the last thirteen millennia, including the development of marine-based economies and changes in tools and raw materials. It has been proposed that movements of people spreading culture and technology propelled some of these shifts, but these hypotheses have not been tested with ancient DNA. Here we report genome-wide data from 20 ancient individuals, and co-analyze it with previously reported data. We reveal that immigration does not explain the appearance of marine adaptations in South Patagonia. We describe partial genetic continuity since ~6600 BP and two later gene flows correlated with technological changes: one between 4700-2000 BP that affected primarily marine-based groups, and a later one impacting all <2000 BP groups. From ~2200-1200 BP, mixture among neighbors resulted in a cline correlated to geographic ordering along the coast.

Fish skeletal remains recovered from two archaeological sites dated in the Middle Holocene of Tierra del Fuego (Argentina) were analysed to describe habitat use patterns by hake in the past and predict changes in a warmer world. Mitochondrial DNA was successfully extracted and amplified from 42 out of 45 first vertebra from ancient hake and phylogenetic analysis assigned all haplotypes to Argentine hake (Merluccius hubbsi). According to osteometry, the Argentine hake recovered from the archaeological site were likely adults ranging 37.2-58.1 cm in standard length. C and N stable isotope analysis showed that currently Argentine hake use foraging grounds deeper than those of Patagonian blenny and pink cusk-eel. Argentine hake, however, had a much broader isotopic niche during the Middle Holocene, when a large part of the population foraged much shallower than contemporary pink cusk-eel. The overall evidence suggests the presence of large numbers of Argentine hake onshore Tierra del Fuego during the Middle Holocene, which allowed exploitation by hunter-gatherer-fisher groups devoid of fishing technology. Interestingly, average SST off Tierra del Fuego during the Middle Holocene was higher than currently (11 °C vs 7 °C) and matched SST in the current southernmost onshore spawning aggregations, at latitude 47 °S. This indicates that increasing SST resulting from global warming will likely result into an increased abundance of adult Argentine hake onshore Tierra del Fuego, as during the Middle Holocene. Furthermore, stable isotope ratios from mollusc shells confirmed a much higher marine primary productivity during the Middle Holocene off Tierra del Fuego.

Autoimmune enteropathy (AIE) is a rare condition that may affect pediatric and adult patients, frequently associated with primary immunodeficiencies. We performed a retrospective study on clinical and histological findings from 40 AIE patients. Histological presentation showed a prevalent celiac disease pattern (50%), followed by the mixed pattern (35%), independently of age, chronic active duodenitis (10%), and GVHD-like pattern (5%). Patients with primary immunodeficiencies (24/40) presented mainly with the celiac disease pattern (72.2% versus 22.2%; p < .0001), while patients without primary immunodeficiencies presented with a mixed histological pattern (61.1% versus 13.6%; p < .0001). Our study shows that the prevalent histological presentation is the celiac disease-like pattern, independently of age, and, for the first time, that the histological presentation of AIE differs significantly between patients with and without primary immunodeficiencies. These findings may be helpful for more precise and timely diagnosis and management of this rare disorder., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Goals: The aim of this study was to analyze the performance of Fuji Intelligent Color Enhancement (FICE) using the classification of Kudo in the differentiation of neoplastic and non-neoplastic raised lesions in ulcerative colitis (UC)., Background: The Kudo classification of mucosal pit patterns is an aid for the differential diagnosis of colorectal polyps in the general population, but no systematic studies are available for all forms of raised lesions in UC., Study: All raised, polypoid and nonpolypoid, lesions found during consecutive surveillance colonoscopies with FICE for long-standing UC were included. In the primary prospective analysis, the Kudo classification was used to predict the histology by FICE. In a post hoc analysis, further endoscopic markers were also explored., Results: Two hundred and five lesions (mean size, 8 mm; range, 2 to 30 mm) from 59 patients (mean age, 56 y; range, 21 to 79 y) were analyzed. Twenty-three neoplastic (11%), 18 hyperplastic (9%), and 164 inflammatory (80%) lesions were found. Thirty-one lesions (15%), none of which were neoplastic, were unclassifiable according to Kudo. After logistic regression, a strong negative association resulted between endoscopic activity and neoplasia, whereas the presence of a fibrin cap was significantly associated with endoscopic activity. Using FICE, the sensitivity, specificity, and positive and negative likelihood ratios of the Kudo classification were 91%, 76%, 3.8, and 0.12, respectively. The corresponding values by adding the fibrin cap as a marker of inflammation were 91%, 93%, 13, and 0.10, respectively., Conclusions: FICE can help to predict the histology of raised lesions in UC. A new classification of pit patterns, based on inflammatory markers, should be developed in the setting of UC to improve the diagnostic performance.

Background & Aims: The guidelines of the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition allow for diagnosis of celiac disease without biopsies in children with symptoms and levels of immunoglobulin A against tissue-transglutaminase (TGA-IgA) 10-fold or more the upper limit of normal (ULN), confirmed by detection of endomysium antibodies (EMA) and positivity for HLA-DQ2/DQ8. We performed a large, international prospective study to validate this approach., Methods: We collected data from consecutive pediatric patients (18 years or younger) on a gluten-containing diet who tested positive for TGA-IgA from November 2011 through May 2014, seen at 33 pediatric gastroenterology units in 21 countries. Local centers recorded symptoms; measurements of total IgA, TGA, and EMA; and histopathology findings from duodenal biopsies. Children were considered to have malabsorption if they had chronic diarrhea, weight loss (or insufficient gain), growth failure, or anemia. We directly compared central findings from 16 antibody tests (8 for TGA-IgA, 1 for TGA-IgG, 6 for IgG against deamidated gliadin peptides, and 1 for EMA, from 5 different manufacturers), 2 HLA-DQ2/DQ8 tests from 2 manufacturers, and histopathology findings from the reference pathologist. Final diagnoses were based on local and central results. If all local and central results were concordant for celiac disease, cases were classified as proven celiac disease. Patients with only a low level of TGA-IgA (threefold or less the ULN) but no other results indicating celiac disease were classified as no celiac disease. Central histo-morphometry analyses were performed on all other biopsies and cases were carefully reviewed in a blinded manner. Inconclusive cases were regarded as not having celiac disease for calculation of diagnostic accuracy. The primary aim was to determine whether the nonbiopsy approach identifies children with celiac disease with a positive predictive value (PPV) above 99% in clinical practice. Secondary aims included comparing performance of different serological tests and to determine whether the suggested criteria can be simplified., Results: Of 803 children recruited for the study, 96 were excluded due to incomplete data, low level of IgA, or poor-quality biopsies. In the remaining 707 children (65.1% girls; median age, 6.2 years), 645 were diagnosed with celiac disease, 46 were found not to have celiac disease, and 16 had inconclusive results. Findings from local laboratories of TGA-IgA 10-fold or more the ULN, a positive result from the test for EMA, and any symptom identified children with celiac disease (n = 399) with a PPV of 99.75 (95% confidence interval [CI], 98.61-99.99); the PPV was 100.00 (95% CI, 98.68-100.00) when only malabsorption symptoms were used instead of any symptom (n = 278). Inclusion of HLA analyses did not increase accuracy. Findings from central laboratories differed greatly for patients with lower levels of antibodies, but when levels of TGA-IgA were 10-fold or more the ULN, PPVs ranged from 99.63 (95% CI, 98.67-99.96) to 100.00 (95% CI, 99.23-100.00)., Conclusions: Children can be accurately diagnosed with celiac disease without biopsy analysis. Diagnosis based on level of TGA-IgA 10-fold or more the ULN, a positive result from the EMA tests in a second blood sample, and the presence of at least 1 symptom could avoid risks and costs of endoscopy for more than half the children with celiac disease worldwide. HLA analysis is not required for accurate diagnosis. Clinical Trial Registration no: DRKS00003555., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Mucosal healing, determined by endoscopic evaluation, is one of the most important prognostic markers for patients with inflammatory bowel diseases. Findings from histologic evaluation, however, could complement findings from endoscopy in assessing mucosal responses to treatment. We analyzed long-term results of children treated with thalidomide to determine the association between clinical response and histology and endoscopy findings., Methods: We collected data from 2 multicenter trials of 70 children with refractory Crohn's disease (CD) or ulcerative colitis (UC) (2-18 years old; ileocolonic or colonic disease) given thalidomide or placebo (NCT00720538). Clinical remission and clinical response at 8 weeks were defined as a pediatric CD activity index scores 10 points or lower and a decrease of at least 50% from baseline, respectively, for patients with CD; and as a pediatric UC activity index score below 10 and a decrease of at least 20 points from baseline, respectively, for patients with UC. Patients with a clinical response to 8 weeks' treatment with thalidomide underwent endoscopic examination with biopsy collection at study weeks 12 and 52. Severity of inflammation in patients with UC was assessed by Mayo score and in patients with CD by 4-grade system. Biopsies were assessed for signs of active inflammation, erosion or ulceration, and crypt abscesses and assigned a histologic score., Results: Clinical remission was observed in 42 patients (60.0%) and clinical response in 45 patients (64.2%) at Week 8. At Week 52, a total of 38 patients (54.3%) were still in clinical remission or still had a clinical response; 29 patients (41.4%) had mucosal healing, defined as complete healing of erosions or ulcerations, and 20 patients (27.7%) had histologic healing, defined as complete absence of markers of inflammation. Of patients with clinical remission or clinical response, 75.3% also had mucosal healing and 52.6% also had histologic healing. The probability of achieving mucosal healing decreased significantly with increasing values of erythrocyte sedimentation rate (adjusted odds ratio, 0.96; 95% CI, 0.93-0.98; P = .006)., Conclusions: In a long-term analysis of data from 2 clinical trials of pediatric patients with CD or UC, 52 weeks' treatment with thalidomide led to clinical remission in 54.3% of patients with ileocolonic or colonic disease; of these patients, 75.3% had mucosal healing and 52.6% also had histologic healing. Further studies are needed to determine how thalidomide therapy affects long-term progression of inflammatory bowel diseases. (ClinicalTrials.gov number NCT00720538)., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aims: An increased risk of small bowel carcinoma [SBC] has been reported in coeliac disease [CD] and Crohn's disease [CrD]. We explored clinico-pathological, molecular, and prognostic features of CD-associated SBC [CD-SBC] and CrD-associated SBC [CrD-SBC] in comparison with sporadic SBC [spo-SBC]., Methods: A total of 76 patients undergoing surgical resection for non-familial SBC [26 CD-SBC, 25 CrD-SBC, 25 spo-SBC] were retrospectively enrolled to investigate patients' survival and histological and molecular features including microsatellite instability [MSI] and KRAS/NRAS, BRAF, PIK3CA, TP53, HER2 gene alterations., Results: CD-SBC showed a significantly better sex-, age-, and stage-adjusted overall and cancer-specific survival than CrD-SBC, whereas no significant difference was found between spo-SBC and either CD-SBC or CrD-SBC. CD-SBC exhibited a significantly higher rate of MSI and median tumour-infiltrating lymphocytes [TIL] than CrD-SBC and spo-SBC. Among the whole SBC series, both MSI─which was the result of MLH1 promoter methylation in all but one cases─and high TIL density were associated with improved survival at univariable and stage-inclusive multivariable analysis. However, only TILs retained prognostic power when clinical subgroups were added to the multivariable model. KRAS mutation and HER2 amplification were detected in 30% and 7% of cases, respectively, without prognostic implications., Conclusions: In comparison with CrD-SBC, CD-SBC patients harbour MSI and high TILs more frequently and show better outcome. This seems mainly due to their higher TIL density, which at multivariable analysis showed an independent prognostic value. MSI/TIL status, KRAS mutations and HER2 amplification might help in stratifying patients for targeted anti-cancer therapy., (Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

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.

Since 2014 several direct-acting antivirals (DAAs) have been made available, allowing interferon-free antiviral treatments with high sustained virological response rates. Side effects are, however, a real challenge during treatment. Sarkar et al. recently published a case of colitis following initiation of sofosbuvir and simeprevir for genotype 1 hepatitis C. We report the case of a patient with no prior history of inflammatory bowel disease, who developed significant bloody diarrhea within 3 weeks of sofosbuvir/simeprevir/ribavirin initiation. Colonoscopy and biopsy suggested a drug-induced colitis.

Background: Nonceliac gluten sensitivity (NCGS) is an emergent condition, the framework of which is yet unclear, whereas the diagnosis is suggested only by gluten-dependent symptoms after excluding wheat allergy and celiac disease (CD). Our goal was to highlight intestinal, systemic, and oral alterations to clarify the NCGS pathogenesis and identify new diagnostic tools., Study: A total of 60 NCGS patients, 20 untreated CD, 20 treated CD, and 20 healthy volunteers were recruited. The differential diagnosis among gluten-related disorders was performed by serological, allergy, and histologic tools. NCGS patients were also subjected to antigliadin antibody (AGA) detection and HLA typing. All participants underwent an oral mucosa patch test for gluten (GOMPT), whereas an oral provocation test (OPT) for gluten was performed in 26 NCGS patients., Results: About 6/60 (10%) NCGS patients showed IgG AGA-positive results, whereas 45/60 (75%) patients carried HLA-DQ2 and/or HLA-DQ8 genes. GOMPT showed positive results in 45/60 (75%) NCGS patients, 3/20 (15%) untreated CD patients, 5/20 (25%) treated CD patients, and in no healthy volunteers. No significant difference was found between the severity of symptoms reported by NCGS patients subjected to OPT with gluten-containing croissants and those who underwent OPT with gluten-free croissants., Conclusions: GOMPT seems to be a specific tool for NCGS diagnosis, although further investigations are needed to overcome limits due to the small population studied and to contextualize GOMPT false-positive results.

Barrett's esophagus (BE) is the only well-known precursor lesion of esophageal adenocarcinoma (EA). The exact estimates of the annual progression rate from BE to EA vary from 0.07% to 3.6%. The identification of BE patients at higher risk to progress to EA is hence mandatory, although difficult to accomplish. In search of novel BE biomarkers we analyzed the efficacy of hERG1 potassium channels in predicting BE progression to EA. Once tested by immunohistochemistry (IHC) on bioptic samples, hERG1 was expressed in BE, and its expression levels increased during progression from BE to esophageal dysplasia (ED) and EA. hERG1 was also over-expressed in the metaplastic cells arising in BE lesions obtained in different BE mouse models, induced either surgically or chemically. Furthermore, transgenic mice which over express hERG1 in the whole gastrointestinal tract, developed BE lesions after an esophago-jejunal anastomosis more frequently, compared to controls. A case-control study was performed on 104 bioptic samples from newly diagnosed BE patients further followed up for at least 10 years. It emerged a statistically significant association between hERG1 expression status and risk of progression to EA. Finally, a novel fluorophore- conjugated recombinant single chain variable fragment antibody (scFv-hERG1-Alexa488) was tested on freshly collected live BE biopsies: it could recognize hERG1 positive samples, perfectly matching IHC data.Overall, hERG1 can be considered a novel BE biomarker to be exploited for a novel endoscopic surveillance protocol, either in biopsies or through endoscopy, to identify those BE patients with higher risk to progress to EA.

The gluten-free diet (GFD) is the only validated treatment for celiac disease (CD), but despite strict adherence, complete mucosal recovery is rarely obtained. The aim of our study was to assess whether complete restitutio ad integrum could be achieved by adopting a restrictive diet (Gluten Contamination Elimination Diet, GCED) or may depend on time of exposure to GFD. Two cohorts of CD patients, with persisting Marsh II/Grade A lesion at duodenal biopsy after 12-18 months of GFD (early control) were identified. Patients in Cohort A were re-biopsied after a three-month GCED (GCED control) and patients in Cohort B were re-biopsied after a minimum of two years on a standard GFD subsequent to early control (late control). Ten patients in Cohort A and 19 in Cohort B completed the study protocol. There was no change in the classification of duodenal biopsies in both cohorts. The number of intraepithelial lymphocytes, TCRγδ+ (T-Cell Receptor gamma delta) T cell and eosinophils significantly decreased at GCED control (Cohort A) and at late control (Cohort B), compared to early control. Duodenal intraepithelial lymphocytosis persisting in CD patients during GFD is not eliminated by a GCED and is independent of the length of GFD. [NCT 02711696]., Competing Interests: The authors declare no conflict of interest.

Background: It is generally thought that gallbladder motility plays a more or less important role in the pathogenesis of gallstones. Some studies have shown that some abnormalities of its intrinsic innervations, but these studies were usually limited to one cell component., Aims: We investigated the main cell components of gallbladder intrinsic innervation in patients with and without gallstones., Methods: Archival gallbladder specimens from 39 patients, 27 with gallstones (age range 45-69 yrs) and 12 patients without gallstones (age range 39-71 yrs) were obtained. Full thickness sections were obtained from the gallbladder neck and immunohistochemistry was carried out for enteric neurons (neuron-specific enolase and calretinin), enteric glia (S100) and interstitial cells of Cajal (CD117 and CD34); tryptase staining was also done to distinguish the latter from mast cells., Results: Apart from calretinin-positive neurons, patients with gallstones featured a significant decrease of neurons, enteric glial cells (EGC) and mast cells compared to those without gallstones; interstitial cells of Cajal were extremely few and only found in two patients, one for each group., Conclusions: The intrinsic innervations of the gallbladder is abnormal in gallstone patients, and this may contribute to gallstone formation in these subjects., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Primary cardiac tumors are uncommon and primary liposarcoma of the pericardium is extremely rare. We describe the case of a 55-year-old Caucasian woman without significant medical history, who presented with 3weeks complain of dyspnea, peripheral edema, and gain weight. Echocardiography revealed a huge pericardial mass confirmed by computed tomography and by magnetic resonance. The lesion was primitive of the pericardium but the surgery was not able to cut it off because of the absence of cleavage planes. Histopathologic analysis detected a dedifferentiated liposarcoma. Mediastinum compression syndrome brought the patient to the exitus in a few days., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Celiac disease (CD) determines neurologic manifestations in 10% of all CD patients. We describe the most common clinical manifestations as cerebellar ataxia, gluten encephalopathy, multiple sclerosis, peripheral neuropathies, sensorineural hearing loss, epilepsy, headache, depression, cognitive deficiencies and other less described clinical conditions. Our aim is to perform, as more as possible, a review about the most recent update on the topics in international literature. It is important to consider clinical neurological manifestations in celiac patients and to research these conditions also in the follow-up because they may start also one year after the start of gluten free diet (GFD) as peripheral neuropathy. The association with autism is analysed and possible new association with non-celiac gluten sensitivity (NCGS) are considered.

Aim: To investigate the diagnostic and therapeutic assessment in children with adenomyomatosis of the gallbladder (AMG)., Methods: AMG is a degenerative disease characterized by a proliferation of the mucosal epithelium which deeply invaginates and extends into the thickened muscular layer of the gallbladder, causing intramural diverticula. Although AMG is found in up to 5% of cholecystectomy specimens in adult populations, this condition in childhood is extremely uncommon. Authors provide a detailed systematic review of the pediatric literature according to PRISMA guidelines, focusing on diagnostic and therapeutic assessment. An additional case of AMG is also presented., Results: Five studies were finally enclosed, encompassing 5 children with AMG. Analysis was extended to our additional 11-year-old patient, who presented diffuse AMG and pancreatic acinar metaplasia of the gallbladder mucosa and was successfully managed with laparoscopic cholecystectomy. Mean age at presentation was 7.2 years. Unspecific abdominal pain was the commonest symptom. Abdominal ultrasound was performed on all patients, with a diagnostic accuracy of 100%. Five patients underwent cholecystectomy, and at follow-up were asymptomatic. In the remaining patient, completely asymptomatic at diagnosis, a conservative approach with monthly monitoring via ultrasonography was undertaken., Conclusion: Considering the remote but possible degeneration leading to cancer and the feasibility of laparoscopic cholecystectomy even in small children, evidence suggests that elective laparoscopic cholecystectomy represent the treatment of choice. Pre-operative evaluation of the extrahepatic biliary tree anatomy with cholangio-MRI is strongly recommended.

Background: To date, there is still uncertainty on the role of specialized intestinal metaplasia in the carcinogenic process of Barrett's oesophagus (BE); this fact seems of importance for planning adequate surveillance programs., Aims: To predict the risk of progression towards dysplasia/cancer based on typical morphological features by evaluating the importance of intestinal metaplasia in BE patients., Methods: 647 cases with a histological diagnosis of BE, referred to the Endoscopy Unit of a tertiary centre between 2000 and 2012 were retrospectively identified, and divided into two groups according to the presence/absence of intestinal metaplasia. For each patient, all histological reports performed during a follow-up of 4-8 years were analyzed., Results: Overall, 537 cases (83%) with intestinal metaplasia and 110 cases (17%) without intestinal metaplasia were included. During the follow-up period, none of the patients without intestinal metaplasia developed dysplasia/cancer nor progressed to metaplasia, whereas 72 patients with intestinal metaplasia (13.4%) showed histological progression of the disease., Conclusion: The histological identification of intestinal metaplasia seems to be an essential factor for the progression towards dysplasia and cancer in BE patients., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Celiac disease (CD) and inflammatory bowel disease (IBD), such as Crohn's disease (CrD) and ulcerative colitis (UC), are chronic inflammatory condition of the gastro-intestinal tract. The prevalence of IBD in celiac patients has been reported as 5-10 times higher than in the general population. The possibility of the presence of CD in IBD should be considered in IBD patients with long-term iron deficiency anemia (IDA) not responsive to iron supplementation. Non-celiac gluten sensitivity (NCGS) is characterized by intestinal and extra intestinal symptoms due to the ingestion of gluten-containing food in subject without CD and/or wheat allergy. Patients with Crohn's disease and SR-NCGS were more significantly affected by joint pains compared to UC patients (50% versus 11.1%). In Crohn's patients, a higher percentage of fatigue (50% versus 38.9%) and headache (27.3% versus 22.2%) was evident. For the association between NCGS and IBD new studies are warranted and, at this moment, a gluten free diet (GFD) may be useful more in CrD than in UC.

Background: Diverticular disease of the colon is frequent in clinical practice, and a large number of patients each year undergo surgical procedures worldwide for their symptoms. Thus, there is a need for better knowledge of the basic pathophysiologic mechanisms of this disease entity., Objectives: Because patients with colonic diverticular disease have been shown to display abnormalities of the enteric nervous system, we assessed the frequency of myenteric plexitis (i.e. the infiltration of myenteric ganglions by inflammatory cells) in patients undergoing surgery for this condition., Methods: We analyzed archival resection samples from the proximal resection margins of 165 patients undergoing left hemicolectomy (60 emergency and 105 elective surgeries) for colonic diverticulitis, by histology and immunochemistry., Results: Overall, plexitis was present in almost 40% of patients. It was subdivided into an eosinophilic (48%) and a lymphocytic (52%) subtype. Plexitis was more frequent in younger patients; and it was more frequent in those undergoing emergency surgery (50%), compared to elective (28%) surgery (p = 0.007). All the severe cases of plexitis displayed the lymphocytic subtype., Conclusions: In conclusion, myenteric plexitis is frequent in patients with colonic diverticular disease needing surgery, and it might be implicated in the pathogenesis of the disease.

Background: Sensorineural hearing loss has been reported as an extraintestinal manifestation of inflammatory bowel disease, especially in adult patients with ulcerative colitis. However, to date only a few series have been reported in the literature, and none from Italy. The aim of the present investigation was to assess the prevalence of symptomatic sensorineural hearing loss in Italian patients with ulcerative colitis., Methods: We retrospectively assessed the charts of all patients with ulcerative colitis who underwent otolaryngologic investigation in a 10-year period., Results: Complete charts of 57 patients were available for the observation period. Reasons for head and neck investigation were transient, mild hearing loss and sporadic vertigo. Clinical and instrumental head and neck examination was unremarkable in all but one woman who complained of mild hearing loss without vertigo or tinnitus, in whom sensorineural hearing loss was diagnosed., Conclusions: In our series, sensorineural hearing loss was found in less than 2 % of adult patients with ulcerative colitis evaluated in a department of otolaryngology. Systematic evaluation for this extraintestinal manifestation should not be carried out unless hearing loss is present.

Background: Common variable immunodeficiency is the most common form of primary symptomatic immunodeficiency. Gastrointestinal manifestations, such as gastritis, diarrhea, gastrointestinal infections, and malabsorption, may complicate the clinical history in almost 50 % of patients., Aim: To evaluate gastrointestinal histopathological findings in pediatric- and in adult-onset common variable immunodeficiency patients., Methods: Twenty-two patients with common variable immunodeficiency (13 children, nine adults) were retrospectively studied from a clinical and histopathological point of view., Results: Increased T lymphocyte infiltrate and the absence of plasma cells in duodenal lamina propria and submucosa were the most frequent findings, independently from onset age, whereas follicular lymphoid hyperplasia and polymorphonuclear infiltrate, as well as parasitic and viral infections, were only present in the adult group. Common variable immunodeficiency patients with minor gastrointestinal symptoms also presented pathological findings, mainly the absence of plasma cells, T cell infiltrate, and infections, independently of age., Conclusions: Gastrointestinal pathological abnormalities are common in both pediatric- and adult-onset common variable immunodeficiency patients. Histological alterations may vary depending upon the age of onset, possibly due to duration of disease. Minor gastrointestinal symptoms are also associated with pathological findings; therefore, these should be searched in all symptomatic patients.

This case report concerns a 25-year-old patient with 6-7 bloody stools/d, abdominal pain, tachycardia, and weight loss occurring during the third trimester of pregnancy. Severe ulcerative colitis complicated by toxic megacolon and gravidic sepsis was diagnosed by clinical evaluation, colonoscopy, and rectal biopsy that were performed safely without risk for the mother or baby. The patient underwent a cesarean section at 28+6 wk gestation. The baby was transferred to the neonatal intensive care unit of our hospital and survived without complications. Fulminant colitis was managed conservatively by combined colonoscopic decompression and medical treatment. Although current European guidelines describe toxic megacolon as an indication for emergency surgery for both pregnant and non-pregnant women, thanks to careful monitoring, endoscopic decompression, and intensive medical therapy with nutritional support, we prevented the woman from having to undergo emergency pancolectomy. Our report seems to suggest that conservative management may be a helpful tool in preventing pancolectomy if the patient's condition improves quickly. Otherwise, surgery is mandatory.

Objectives: Dilated intercellular spaces (DIS) in the esophageal epithelium can be induced by acid and reduced by proton pump inhibitors (PPI), and are thus considered a marker of gastroesophageal reflux disease (GERD). Over the years, however, DIS have also been reported in esophagitis unrelated to GERD. Because DIS have never been formally measured in eosinophilic esophagitis (EoE), we aimed at detecting and measuring DIS in EoE before and after nutritional or pharmacological therapy., Methods: In 22 children with EoE, DIS were measured by morphometry and transmission electron microscopy (TEM), before and after treatment with topical steroids (n = 16) and/or exclusion diet (n = 13). A total of 30 children undergoing upper gastrointestinal endoscopy with biopsy for nonesophageal disorders acted as controls., Results: In controls, the mean (± standard deviation [SD]) number of esophageal eosinophils was 0.91 (± 0.47) and the mean DIS values were 0.62 (± 0.08) μm at morphometry and 0.33 (± 0.24) μm at TEM. In patients with EoE, the mean (± SD) number of esophageal eosinophils decreased from 31.8 (± 6.96) to 6.64 (± 5.01) (P < 0.0001), and the mean DIS values decreased from 2.26 (± 0.21) to 1.23 (± 0.20) μm at morphometry (P < 0.0001), and from 2.24 (± 0.28) to 0.98 (± 0.19) μm at TEM (P < 0.0001), respectively, before and after treatment., Conclusions: DIS are a prominent morphological feature of EoE, in which they can be significantly reduced by an appropriate non-PPI therapy.

Endoscopic submucosal dissection (ESD) is gaining popularity worldwide in the treatment of neoplastic lesions of the gastrointestinal tract. However, the experience in Western countries is quite limited and restricted to large or academic centers. Besides, this approach requires an optimal pathological assessment. The aim of this study was to report our experience with colonic ESD using a new device that allows complete handling of the resected specimens and especially of lateral margins, for pathological analysis. In a 1-year period, 14 patients (6 men, 8 women, age range 50-82 years) underwent colonic ESD in a non-academic hospital. The endoscopic procedure was carried out successfully en bloc in more than 90 % of cases. Perforation requiring surgery occurred in one patient (7 %). Pathological assessment with the new device allowed entire and complete examination of both the deep and lateral margins of the excised specimens. Colonic ESD is a viable option for non-surgical treatment of large bowel lesions even in relatively small centers and in non-academic settings. The new device allows good handling of the specimens, and it seems to be useful for the entire examination of the resection margins.

Background: Although it is usually not difficult to diagnose inflammatory bowel disease (IBD) on surgical resection specimens, difficulties sometimes arise in differentiating these entities from other forms of colitis on endoscopic biopsy specimens. Basal plasmacytosis is considered as an early feature of IBD colitis, but it is rare in non-IBD colitides., Aims: We assessed the value of basal plasmacytosis as an individual variable in untreated patients with colitis., Patients and Methods: Archival slides of patients with untreated colitis (66 IBD and 49 non-IBD) and 20 controls with complete (from the terminal ileum to the rectum) endoscopic biopsy sampling were evaluated blindly for the presence of basal plasmacytosis and a possible association with the presence of eosinophils in the same anatomical location., Results: Overall, basal plasmacytosis was present in at least one anatomical segment in 58% of cases, and it was always present in patients with IBD, whereas it was sparsely found (9%) in patients with other colitides and in controls. Basal plasmacytosis in three or more segments had more than 80% probability for a patient to be classified as IBD, with the segmental distribution being different between ulcerative colitis and Crohn's disease. Additionally, basal plasmacytosis was always accompanied by eosinophils intermingled with plasma cells in the same anatomical position., Conclusion: As an individual feature, basal plasmacytosis (accompanied by eosinophils) is a strong feature suggesting IBD, particularly when present in three or more colonic segments. This fact may be useful in the evaluation of endoscopic biopsies from patients with "colitis"., (Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Whipple's disease is a rare systemic condition resulting from a chronic infection by Tropheryma whipplei. Clinical presentation can be widely heterogeneous, often leading to delayed diagnosis and treatment. Furthermore, little is known about the underlying pathogenic mechanisms, although several abnormalities in immune cell function have been observed. We describe the case of a 51-year-old woman presenting with dysphagia, odynophagia, long-lasting low-grade fever, and malabsorption syndrome who underwent an upper gastrointestinal endoscopy showing esophageal candidiasis. On the same occasion, duodenal biopsies were also performed, with evidence of mucosal infiltration of periodic acid-Schiff-positive and CD68+ foamy macrophages at microscopic examination. Such findings were suggestive of Whipple's disease, as also confirmed by molecular analysis by PCR for T. whipplei. No specific risk factors were identified in our patient that could explain the occurrence of an opportunistic infection such as candida esophagitis, thus leading to the hypothesis of a direct correlation with Whipple's disease. Interestingly, a Giardia lamblia coinfection was subsequently identified, which is consistent with an underlying immune deficit although still undefined.

A 75-years-old patient with a history of prostate cancer, previously treated with radical prostatectomy, underwent C-choline PET/CT for restaging due to a rise in the prostate-specific antigen level. The study revealed a focal uptake of C-choline in the esophagus. A subsequent endoscopic examination showed the presence of an esophageal lesion, and after surgery, the histologic diagnosis was mildly differentiated squamous cell carcinoma. In our case, the incidental esophageal uptake revealed by C-choline PET/CT allowed the early diagnosis of an unsuspected esophageal carcinoma.

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 in the 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 gamma/delta-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.

The relationship between motility and inflammatory gastrointestinal disorders is at the same time complex and intriguing since these conditions might share some genetic, environmental, immunological and microbial predisposing factors. In addition, significant symptom overlapping may occur, muddling the waters within the clinical context. Although on one hand this represents a challenge for the clinician for a potential under- or over-treatment and diagnostic delay, on the other hand it possibly represents an opportunity for the researcher to better disclose the intimate relationship between chronic (often low-grade) inflammation, motor disorders and deranged sensory function. The best example is probably represented by Crohn's disease and ulcerative colitis. In fact, a number of gastrointestinal motor disorders have been described in association with these diseases, disorders which span from the esophagus to the anorectum, and which will be extensively covered in this review. It is conceivable that at least part of this derangement is strictly related to inflammatory cytokine trafficking and neuromuscular changes; however, given the high prevalence of functional gastrointestinal disorders in the general population, this overlap might also be serendipitous. However, it is worth noting that literature data on this topic are relatively scarce, sometimes quite outdated, and mostly focused on the interplay between irritable bowel syndrome and inflammatory bowel disease. Nevertheless, both researchers and clinicians must be aware that symptoms related to gastrointestinal motility disorders may be highly prevalent in both active and inactive inflammatory bowel disease, correlate with greater psychological comorbidity and poorer quality of life, and may negatively influence the therapeutic approaches.

The willingness of the cephalopod mollusc Octopus vulgaris to attack a live crab is traditionally used as a method to assess the overall health and welfare of octopuses in the laboratory. This method requires placing a crab in the home tank of an animal, measuring the time (latency) taken for the octopus to initiate an attack and withdrawing the crab immediately prior to capture. The same crab is commonly used to assess multiple octopuses as part of daily welfare assessment. Growing concern for the welfare of crustaceans and a review of all laboratory practices for the care and welfare of cephalopods following the inclusion of this taxon in 2010/63/EU prompted a study of the utility of an artificial crab to replace a live crab in the assessment of octopus health. On consecutive days O. vulgaris (N=21) were presented with a live, a dead or an artificial crab, and the latency to attack measured. Despite differences in the predatory performance towards the three different crab alternatives, octopuses readily attacked the artificial (and the dead) crab, showing that they can generalize and respond appropriately towards artificial prey. Researchers should consider using an artificial crab to replace the use of a live crab as part of the routine health assessment of O. vulgaris.