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Although a clear association has been established between IL-33 and inflammatory bowel disease, mechanistic studies to date, primarily using acute murine models of colitis, have yielded contradicting results, demonstrating both pathogenic and protective roles. We used a well-characterized, spontaneous model of inflammatory bowel disease [ie, SAMP1/YitFc (SAMP) mice] to investigate the role of IL-33 during chronic intestinal inflammation. Our results showed marked eosinophil infiltration into the gut mucosa with increased levels of eotaxins and type 2 helper T-cell (Th2) cytokines as disease progressed and became more severe, which could be reversed upon either eosinophil depletion or blockade of IL-33 signaling. Exogenous IL-33 administration recapitulated these effects in ilea of uninflamed (parental) control AKR/J mice. Human data supported these findings, showing colocalization and up-regulation of IL-33 and eosinophils in the colonic mucosa of inflammatory bowel disease patients versus noninflamed controls. Finally, colonization of commensal flora by fecal material transplantation into germ-free SAMP and the presence of the gut microbiome induced IL-33, subsequent eosinophil infiltration, and mounting of Th2 immune responses, leading to exacerbation of chronic intestinal inflammation characteristic of SAMP mice. These data demonstrate a pathogenic role for IL-33-mediated eosinophilia and activation of Th2 immunity in chronic intestinal inflammation that is dependent on the gut microbiome. Targeting IL-33 may represent a novel therapeutic approach to treat patients with inflammatory bowel disease. © 2016 American Society for Investigative Pathology.

Design, construction and performance characteristics of the ZEUS barrel and rear muon detector are presented.

Abstract In this work, the production of low cost and environment friendly anodes for sodium ion batteries is investigated. Algae are selected as bio-source of non-graphitic Hard Carbon (HC) with open structure acting as intercalation active material for Na ions storage. Chlorella vulgaris algae were pyrolyzed at temperatures comprised between 800 and 1100 °C. The decomposition products have been characterized with Scanning Electrode Microscope (SEM) and X-Ray Diffraction (XRD) analyses and their structure compared to one of the synthetic commercial HC. Thermogravimetric analysis (TGA) allowed to assess the decomposition process throughout the selected temperature scan. The obtained algae-derived HC is tested as anodic material for Na-ion battery, investigating the effect of pyrolysis temperature on the electrochemical behaviour. Their performances are compared with respect to a commercial synthetic HC active material. The results allow to consider algae as an environmentally benign and sustainable high added-value material for the production of HC anodes for Na-ion batteries. Graphic abstract

Objective: To explore the true short esophagus (TSE) frequency and longterm results of patients undergoing gastro-esophageal reflux disease (GERD) or hiatus hernia (HH) surgery. Background: The existence and treatment of TSE during GERD/HH surgery is controversial. Satisfactory long-term results have been achieved with and without surgical techniques dedicated to TSE. Methods: In 311 consecutive patients undergoing minimally invasive surgery for GERD/HH, the distance between the endoscopically-localized gastroesophageal junction (GEJ) and the apex of the diaphragmatic hiatus after maximal thoracic esophagus mobilization was measured. A standard Nissen fundoplication (SN) was performed in cases with an abdominal length >1.5 cm; in cases of TSE (abdominal length

Objectives: In Siewert type I/II oesophageal adenocarcinoma, the sensitivity and specificity of computed tomography (CT), positron emission tomography (PET)-CT and endoscopic ultrasound (EUS) for assessment of the N descriptor in defined groups of lymph nodes were investigated. Methods: CT, PET/CT, EUS images and the pathological data of 101 oesophageal adenocarcinomas submitted to primary resection were compared. The lymph nodes were identified as (a) right paratracheal/subcarinal/pulmonary ligament; (b) paraoesophageal; (c) paracardial; (d) left gastric artery, lesser curvature; (e) coeliac trunk, hepatic/splenic artery. Results: Of the 2451 lymph nodes identified, 273 (11.1%) were histologically positive. Overall sensitivity, specificity and negative and positive predictive value for detection of lymph nodes metastatic were respectively: CT sensitivity 39%, specificity 86%, negative 58% and positive 74% predictive value; PET/CT sensitivity 30%, specificity 98%, negative 58% and positive 93% predictive value; EUS sensitivity 50%, specificity 81%, negative 72% and positive 62% predictive value. The sensitivity of CT, PET/CT and EUS in the thoracic nodal groups (a) and (b) was, respectively, 58.3%, 7.1% and 87.5% and 33.3%, 20% and 80%. Sensitivity was below 47% for all tests in the abdominal nodal groups. In contrast, specificity (88.6-100%) was super imposable in all nodal groups. The strength of agreement among the 3 imaging techniques was poor (kappa < 0.30) for the thoracic anatomical groups of interest: (a) lower paratracheal/subcarinal/pulmonary ligament and (b) paraoesophageal; it was moderate/good (kappa >0.30) for the abdominal N groups of interest: c, d and e. Conclusions: The diagnostic performance of CT, PET and EUS for assessing the N descriptor in the paracardial and abdominal stations close to the primary tumour is not satisfactory. EUS can efficiently assess the presence/absence of nodal metastases in the thoracic stations.

OBJECTIVES: The risk factors for oesophageal achalasia, a precancerous condition that can lead to epidermoid carcinoma, are unknown. The aim of this study was to determine these factors. METHODS: Beginning in 1973, patients presenting with achalasia from 1955 to 2016 periodically underwent clinical assessment, the barium swallow test (the oesophageal diameter and residual barium column were measured) and endoscopy according to a prospective protocol. We included patients with the minimum follow-up duration of 12 months. RESULTS: Of 681 cases, 583 patients were considered. The median follow-up time was 147.13 months (interquartile range 70.42-257.82 months), and 17 epidermoid carcinomas and 1 carcinosarcoma were diagnosed. After excluding 4 achalasia patients admitted with a cancer diagnosis, the incidence rate of epidermoid carcinomas was 1.61/1000 persons-year, and the cumulative probability of developing cancer at 56.34 years of follow-up was 13%. Risk factors for cancer were a sigmoid oesophagus [risk ratio (RR) = 17.64, 95% confidence interval (CI) 4.13-75.43], duration of achalasia symptoms >280 months (RR = 19.62, 95% CI 4.59-83.80), duration of follow-up >353 months (RR = 5.96, 95% CI 2.50-14.18), oesophageal diameter at diagnosis >71 mm (RR = 21.07, 95% CI 9.29-47.82), residual barium column at diagnosis >23 cm (RR = 24.27, 95% CI 6.93-85.01) and residual barium column at the last follow-up >10 cm (RR = 8.15, 95% CI 2.40-27.62). Conversely, the risk of epidermoid carcinoma was lower when the residual barium swallow decreased by >57% (RR = 0.10, 95% CI 0.03-0.34). CONCLUSIONS: Patients with achalasia carry a substantial risk of developing epidermoid carcinoma. Several factors, such as sigmoid achalasia and dysphagia lasting more than 23 years, are associated with an increased risk of cancer. An effective Heller myotomy may positively influence the carcinogenetic process.

Summary The aim of the present study is to describe the histological and mutational characteristics of a series of both large and small bowel adenocarcinomas in patients with Crohn’s disease from a tertiary referral centre of inflammatory bowel disease. Bowel adenocarcinoma was diagnosed in 11 (1.7%) of 660 consecutive patients submitted to surgery for histologically proven Crohn’s disease in 5 years. The following data were collected: tumour site, stage and grade, intracellular/extra-cellular mucin, lymphovascular invasion, immunohistochem-istry for keratin 7, keratin 20 and CDX-2, mutation analyses of KRAS, B-RAF, PI3K and microsatellite instability. A strong predominance of male gender was observed (10/11). Four (36.4%) adenocarcinomas arose in the small bowel, five (45.4%) in the anus/rectum, and two (18.2%) in anastomosis. Furthermore, all cases of anorectal adenocarcinoma showed >50% of extracellular mucin, with associated KRAS mutations in three of five. No influence in cancer incidence by infliximab therapy was observed. Our series, one of the largest on the topic with immunomorphological and molecular deepening, showed that bowel adenocarcinomas in Crohn’s disease have an aggressive behaviour and a strong predominance of extracellular mucin. In surgical specimens from Crohn’s disease patients, mucinous-looking anal fistulas and ileal areas of adhesion/retraction should always be extensively sampled.

The morphologic and immunohistochemical profiles of gastric mucosa and of the tumor were assessed in Siewert type I, type II, and gastric antrum adenocarcinomas. METHODS: Sixty-two patients, prospectively operated upon, were included in the study: 37 type II, 15 type I, and 10 antrum adenocarcinoma. Samples of the tumor, the surrounding area, and the gastric corpus and antrum were analyzed histologically, and immunostained for cytokeratins (CK)7/20 (staining positive for cells labeled > or = 50%). RESULTS: Among the 37 type II adenocarcinomas were the following: (1) 13 of 37 (35%) had intestinal metaplasia (IM) in the stomach; (2) 24 of 37 (65%) did not show IM at any level; (3) 34 of 37 (92%) had Helicobacter pylori (HP) infection; (4) 13 of 37(35%) had CK7/20 expression of "Barrett's type" (CK7+/20-); 24 of 37 (65%) had a "no Barrett's type" profile (10 of 37 with CK7-/CK20+ and 14 of 37 with CK7+/CK20+); (5) 100% showed the same CK immunoprofile, both in IM and adenocarcinoma (measure of agreement k = 1, p = 0.000). Type I adenocarcinomas showed the following: (1) 87.5% CK Barrett's type, both in the tumor, and in the surrounding IM; (2) 100% gastric samples devoid of both IM and HP infection. Comparison between CK immunoprofiles in type I and type II tumors showed a difference within the two groups (p = 0.002). One hundred percent of antrum adenocarcinomas showed a no Barrett's type CK profile, both in the tumor and in the IM of the entire stomach. CONCLUSIONS: Data suggest that type II adenocarcinoma cannot be always considered a gastroesophageal reflux disease-related tumor; other pathogenetic pathways should be taken into consideration.

OBJECTIVES: Controversy exists regarding surgery for true short oesophagus (TSOE). We compared the results of thoracoscopic Collis gastroplasty-laparoscopic Nissen procedure for the treatment of TSOE with the results of standard laparoscopic Nissen fundoplication. METHODS: Between 1995 and 2013, the Collis-Nissen procedure was performed in 65 patients who underwent minimally invasive surgery when the length of the abdominal oesophagus, measured intraoperatively after maximal oesophageal mediastinal mobilization, was ≤1.5 cm. The results of the Collis-Nissen procedure were frequency-matched according to age, sex and period of surgical treatment with those of 65 standard Nissen fundoplication procedures in patients with a length of the abdominal oesophagus >1.5 cm. Postoperative mortality and morbidity were evaluated according to the Accordion classification. The patients underwent a timed clinical-instrumental follow-up that included symptoms assessment, barium swallow and endoscopy. Symptoms, oesophagitis and global results were graded according to semi-quantitative scales. The results were considered to be excellent in the absence of symptoms and oesophagitis, good if symptoms occurred two to four times a month in the absence of oesophagitis, fair if symptoms occurred two to four times a week in the presence of hyperaemia, oedema and/or microscopic oesophagitis and poor if symptoms occurred on a daily basis in the presence of any grade of endoscopic oesophagitis, hiatal hernia of any size or type, or the need for antireflux medical therapy. The follow-up time was calculated from the time of surgery to the last complete follow-up. RESULTS: The postoperative mortality rate was 1.5% for the Collis-Nissen and 0 for the Nissen procedure. The postoperative complication rate was 24% for the Collis-Nissen and 7% for Nissen (P = 0.001) procedure. The complication rate for the Collis-Nissen procedure was 43% in the first 32 cases and 6% in the last 33 cases (P < 0.0001). The median follow-up period was 96 months. The results were: excellent in 27% of Collis-Nissen and 29% of Nissen; good in 64% of Collis-Nissen and 55% of Nissen; fair in 3% of Collis-Nissen and 11% of Nissen and poor in 6% of Collis-Nissen and 5% of Nissen (P = 0.87). CONCLUSIONS: In patients affected by a TSOE, the Collis-Nissen procedure may achieve equally satisfactory results as the standard Nissen procedure in uncomplicated patients. CLINICAL REGISTRATION NUMBER: NCT02288988.

OBJECTIVES: Type III-IV hiatal hernia (HH) is associated with a true short oesophagus in more than 50% of cases; dedicated treatment of this condition might be appropriate to reduce the recurrence rate after surgery. A case series of patients receiving surgery for Type III-IV hernia was examined for short oesophagus, and the results were analysed. METHODS: From 1980 to 1994, 60 patients underwent an open surgical approach, and the position of the oesophago-gastric junction was visually localized; from 1995 to 2013, 48 patients underwent a minimally invasive approach, and the oesophago-gastric junction was objectively localized using a laparoscopic-endoscopic method. The patients underwent a timed clinical-instrumental follow-up that included symptoms assessment, barium swallow and endoscopy. The results were considered to be excellent in the absence of symptoms and oesophagitis; good, if symptoms occurred two to four times a month in the absence of oesophagitis; fair, if symptoms occurred two to four times a week in the presence of hyperaemia, oedema and/or microscopic oesophagitis; and poor, if symptoms occurred on a daily basis in the presence of any grade of endoscopic oesophagitis, HH of any size or type, or the need for antireflux medical therapy. The follow-up time was calculated from the time of surgery to the last complete follow-up. RESULTS: Among the open surgery patients, 78% underwent abdominal fundoplication, 10% the Belsey Mark IV procedure, 8% laparotomic Collis-Nissen fundoplication and 3% the Pearson operation. Among the minimally invasive surgery patients, 44% underwent a laparoscopic floppy Nissen procedure and 56% a left thoracoscopic Collis-laparoscopic Nissen procedure. The postoperative mortality and complication rates were 1.6% (1/60) and 15% for open surgery and 4.1% (2/48) and 12.5% for minimally invasive surgery. A total of 105 patients were followed up for a median period of 96 months. Five relapses occurred after open surgery (5/59, 8%) and two after minimally invasive surgery (2/46, 4%). Among the 105 patients, excellent, good, fair and poor outcomes were observed in 38%, 44%, 9% and 9%, respectively. CONCLUSIONS: These data suggested that the selective treatment of short oesophagus in association with a Type III-IV hernia reduced the anatomical recurrence rate and achieved satisfactory outcomes. CLINICALTRIALSGOV ID: NCT01606449.