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Background and aim Recurrence of diverticulitis is frequent within 5 years from the uncomplicated first attack, and its prophylaxis is still unclear. We have undertaken a multicentre, randomised, double-blind, placebo-controlled pilot study in order to evaluate the role of mesalazine in preventing diverticulitis recurrence as well as its effects on symptoms associated to diverticular disease. Methods Ninety-six patients with the recent first episode of uncomplicated diverticulitis were randomised to receive mesalazine 800 mg twice daily for 10 days every month or placebo for 24 months. The primary efficacy end point was the diverticulitis recurrence at intention to treat analysis. Clinical evaluations were performed using the Therapy Impact Questionnaire (TIQ) for physical condition and quality of life at admission and at 3-month intervals. Treatment tolerability and routine biochemistry parameters as well as the use of additional drugs were also evaluated. Results Ninety-two patients (mean age, 61.5) completed the study, 45 of whom received mesalazine, and 47, placebo. Diverticulitis relapse incidence in mesalazine-treated group was 5/45 (11 %) at the 12th month and 6/45 (13 %) at the 24th month; in the placebo-treated group, the correspondent rates were 13 % (6/47) and 28 % (13/47), respectively. Mean values of TIQ at 24 months were significantly better in mesalazine-treated group than in placebo-treated group ( p  = 0.02); in addition, average additional drug consumption was significantly lower (−20.4 %, p  < 0.03) in mesalazine than in placebo. Conclusions Diverticulitis recurrence occurred in as many as 28 % of patients under placebo within 24 months from the initial episode. Intermittent prophylaxis with mesalazine did not significantly reduce the risk of relapse but induced a significant improvement of patients' physical conditions and significantly lowered the additional consumption of other gastrointestinal drugs.

BackgroundSurgery with radical intent is the only potentially curative option for entero-pancreatic neuroendocrine tumors (EP-NETs) but many patients develop recurrence even after many years. The subset of patients at high risk of disease recurrence has not been clearly defined to date.ObjectiveThe aim of this retrospective study was to define, in a series of completely resected EP-NETs, the recurrence-free survival (RFS) rate and a risk score for disease recurrence.Patients and MethodsThis was a multicenter retrospective analysis of sporadic pancreatic NETs (PanNETs) or small intestine NETs (SiNETs) [G1/G2] that underwent R0/R1 surgery (years 2000–2016) with at least a 24-month follow-up. Survival analysis was performed using the Kaplan–Meier method and risk factor analysis was performed using the Cox regression model.ResultsOverall, 441 patients (224 PanNETs and 217 SiNETs) were included, with a median Ki67 of 2% in tumor tissue and 8.2% stage IV disease. Median RFS was 101 months (5-year rate 67.9%). The derived prognostic score defined by multivariable analysis included prognostic parameters, such as TNM stage, lymph node ratio, margin status, and grading. The score distinguished three risk categories with a significantly different RFS (p < 0.01).ConclusionsApproximately 30% of patients with EP-NETs recurred within 5 years after radical surgery. Risk factors for recurrence were disease stage, lymph node ratio, margin status, and grading. The definition of risk categories may help in selecting patients who might benefit from adjuvant treatments and more intensive follow-up programs.

Background: The available classifications of gastritis are inconsistently used, possibly because none provides immediate prognostic/therapeutic information to clinicians. As histology reporting of hepatitis in terms of stage is clinically useful and widely accepted, an international group (Operative Link on Gastritis Assessment (OLGA)) proposed an equivalent staging system for reporting gastric histology. Gastritis staging integrates the atrophy score (obtained by biopsy) and the atrophy topography (achieved through directed biopsy mapping). Aim: To test in a prospective cross-sectional study whether OLGA staging consistently stratified patients according to their cancer risk and provided clear prognostic/therapeutic information. Methods: OLGA staging for gastric cancer risk (0–IV) and gastritis grading (overall score of the inflammatory infiltrate, grade 1–4) were applied in 439 prospectively enrolled, consecutive, dyspeptic outpatients who underwent endoscopy with standardised biopsy sampling. Incidental neoplastic lesions and coexisting peptic ulcers were recorded. Results were presented as stage (including antral (A) and corpus (C) atrophy scores) and H pylori status (eg, A = 3; C = 2: stage IV; Hp+ve). Results: Benign conditions (including duodenal ulcers; p<0.001) consistently clustered in stages 0–II, whereas all neoplastic (invasive and non-invasive) lesions clustered in stages III–IV (p<0.001). Conclusions: Gastritis staging, combined with H pylori status, provided clinically relevant information on the overall status of the gastric mucosa with implications for prognosis, therapy and management.

ObjectiveMiss rate of polyps has been shown to be substantially lower with full-spectrum endoscopy (FUSE) compared with standard forward-viewing (SFV) colonoscopy in a tandem study at per polyp analysis. However, there is uncertainty on whether FUSE is also associated with a higher detection rate of colorectal neoplasia, especially advanced lesions, in per patient analysis.MethodsConsecutive subjects undergoing colonoscopy following a positive faecal immunochemical test (FIT) by experienced endoscopists and performed in the context of a regional colorectal cancer population-screening programme were randomised between colonoscopy with either FUSE or SFV colonoscopy in seven Italian centres. Randomisation was stratified by gender, age group and screening history. Primary outcomes included detection rates of advanced adenomas (A-ADR), adenomas (ADR) and sessile-serrated polyps (SSPDR).ResultsOf 741 eligible subjects, 658 were randomised to either FUSE (n=328) or SFV (n=330) colonoscopy and included in the analysis. Overall, 293/658 and 143/658 subjects had at least one adenoma (ADR 44.5%) and advanced adenoma (A-ADR 21.7%), respectively, while SSP was the most advanced lesion in 18 cases (SSPDR 2.7%). ADR and A-ADR were 43.6% and 19.5% in the FUSE arm, and 45.5% and 23.9% in the SFV arm, with no difference for both ADR (OR for FUSE: 0.96, 95% CI 0.81 to 1.14) and A-ADR (OR for FUSE: 0.82, 95% CI 0.61 to 1.09). No difference in SSPDR or multiplicity was detected between the two arms. In the per polyp analysis, the mean number of adenomas and proximal adenomas per patient was 0.81±1.25 and 0.47±0.93 in the FUSE arm, and 0.85±1.33 and 0.48±0.96 in the SFV colonoscopy arm (p=NS for both comparisons).ConclusionsNo statistically significant difference in ADR and A-ADR between FUSE and SFV colonoscopy was detected in a per patient analysis in FIT-positive patients.Trial registration numberISRCTN10357435.

Self-expanding metal stents (SEMS) provide effective palliation in patients with malignant dysphagia, although severe complications and mortality may result. We performed a prospective controlled trial to compare a new self-expanding polyester mesh stent (Polyflex) with SEMS (Ultraflex). One hundred one patients with unresectable esophageal carcinoma were randomized to placement of a Polyflex (N=47) or a partially covered Ultraflex (N=54) stent. Patients with esophagogastric junction (EGJ) malignancy were excluded. Placement was successful in 46 (98%) patients with the Polyflex and 54 (100%) patients with the Ultraflex stent. In one patient, the Polyflex stent could not be placed. After 1 wk, dysphagia was improved by at least 1 grade in 100% of the Polyflex group and in 94% of the Ultraflex group. Major complications were observed in 48% of the Polyflex group and 33% of the Ultraflex group. Intraprocedural perforation occurred in 1 Polyflex and 1 Ultraflex patient. Two Polyflex patients had postprocedural hemorrhage. Twenty (44%) patients with a Polyflex stent and 18 (33%) with an Ultraflex stent had recurrent dysphagia because of tumor overgrowth, stent migration, hyperplastic granulomatous reaction, or food bolus impaction. Multivariate analysis showed a significantly higher complication rate with Polyflex than with Ultraflex stents (odds ratio 2.3, 95% CI 1.2-4.4). However, median survival was 134 days with Polyflex and 122 days with Ultraflex stents (P=NS). No difference was seen in palliation of dysphagia between the two stents. Significantly more complications, especially late stent migration, were observed in the Polyflex group.

Background and objectives: Previous epidemiological studies have identified a group of heart diseases (here called heart diseases of uncertain etiology—HDUE) whose characteristics were rather different from cases classified as coronary heart disease (CHD), but frequently confused with them. This analysis had the purpose of adding further evidence on this issue based on a large population study. Materials and Methods: Forty-five Italian population samples for a total of 25,272 men and 21,895 women, free from cardiovascular diseases, were examined with measurement of some risk factors. During follow-up, CHD deaths were those manifested as myocardial infarction, other acute ischemic attacks, and sudden death of probable coronary origin, after reasonable exclusion of other causes. Cases of HDUE were those manifested only as heart failure, chronic arrhythmia, and blocks in the absence of typical coronary syndromes. Cox proportional hazards models were computed separately for CHD and HDUE, with 11 risk factors as possible predictors. Results: During an average of 7.4 years (extremes 1–16) there were 223 CHD and 150 HDUE fatal events. Male sex, age, smoking habits, systolic blood pressure, serum cholesterol, and plasma glucose were significantly and directly related to CHD events, while high density lipoprotein (HDL) cholesterol was so in an inverse way. The same risk factors were predictive of HDUE events except serum cholesterol and HDL cholesterol. Multivariable hazards ratio of serum cholesterol (delta = 1 mmol/L) was higher in the CHD model (1.24, 95% CI 1.11–1.39) than in the HDUE model (1.03, 0.5% C.I. 0.89–1.19) and the difference between the respective coefficients was statistically significant (p = 0.0444). Age at death was not different between the two end-points. Conclusions: CHD and HDUE are probably two different morbid conditions, only the first one is likely bound to gross atherosclerotic lesions of coronary arteries and linked to blood lipid levels. We reviewed the problem in epidemiological investigations and addressed inflammation as a potential cofactor to differentiate between CHD and HDUE.

Background/Aim: There is evidence of a possible etiological role of human papillomaviruses (HPVs) in the development of esophageal tumors. Loss of function of the wild-type p53 tumor suppressor gene product by binding to E6 oncoproteins of high-risk HPVs is considered an important event in tumor development. The aim of this study was to verify the prevalence of HPV infection and p53 mutation in esophageal tumor tissue samples and in the adjacent normal mucosa in patients from a high-risk area in Italy. Methods: DNA from 33 biopsy specimens (17 tumor sample biopsies and 16 samples of adjacent normal mucosa) was screened for HPV DNA using two polymerase chain reaction based procedures. Restriction fragment length polymorphism analysis was used for typing. Screening of p53 mutations was performed with polymerase chain reaction-single strand conformation polymorphism analysis and DNA sequencing. Results: Overall, 8 of 17 patients presented HPV DNA; HPV 16 was detected in 4 of 8 samples. Samples from tumors and adjacent mucosa were positive for mucosal HPVs in 7 of 17 and 4 of 16 cases, respectively. In 1 case, HPV DNA was detected in the normal mucosa only. None of the samples contained HPVs of the epidermodysplasia verruciformis or cutaneous groups. Mutations of p53 were detected in two HPV DNA negative samples. In both cases, the mutation was present in the tumor only. Conclusions: Our results are in favor of the involvement of both aberrant p53 expression and HPV infection in the development of esophageal tumors. The high HPV infection rate in patients from a high-risk region suggests that subjects harboring HPVs (in particular HPV 16) in the esophagus should be considered at risk of esophageal malignancies.

To the Editor: Propranolol reduces portal hypertension in cirrhosis 1 and has been evaluated for the prevention of rebleeding. 2 , 3 We report here preliminary results of a multicenter randomized clinical trial in patients with cirrhosis who had never bled but were at high risk of bleeding (patients with large varices on endoscopy: \"F3,\" according to the criteria of the Japanese Research Society for Portal Hypertension 4 ). Subjects with tense ascites, a bilirubin level over 3 mg per deciliter, heart failure, obstructive lung disease, or hepatocellular carcinoma were excluded. This allowed the admission of 174 patients of 220 consecutively observed at four centers . . .

Vascular defects are common in Amyotrophic Lateral Sclerosis (ALS). The prevailing view is that breakdown of the blood–brain and blood–spinal cord barriers contributes to neurodegeneration. Here, we reveal that selective and early vulnerability of peripheral nerve endothelium —manifested as endothelial cell activation and interlinked blood–nerve barrier dysfunction— constitutes a core feature of ALS pathogenesis, arising before vascular alterations in the central nervous system (CNS) and motor neuron pathology. Vascular changes in ALS patients have been largely studied in postmortem samples, limiting insight into their onset, causes, and pathogenic role. Surveying diagnostic motor nerve samples from ALS patients across clinical stages, we observed endothelial damage that preceded axonal loss and demyelination, marking vascular dysfunction as an early disease event. Similar ultrastructural abnormalities were detected in pre-symptomatic ALS mouse models (SOD1 and TARDBP mutants). Notably, endothelial cells became dysfunctional even when not carrying mutant TDP-43, indicating they respond to non-cell autonomous disease signals. Transcriptional, histological, and functional analyses revealed that these alterations were largely confined to peripheral nerves, while spinal cord vessels exhibited delayed and more focal changes. Single-cell sequencing identified ALS-susceptible endothelial cell subsets prone to a pro-inflammatory phenotype and impaired blood–nerve barrier function, increasing permeability via the transcellular route. These changes coincided with reactivity of nerve-resident macrophages and neutrophil infiltration. Neutrophil depletion attenuated endothelial activation and barrier leakiness, mitigating axonopathy in ALS mice. Our work unmasks the greater susceptibility of the peripheral nerve vasculature in ALS relative to the CNS. The early activation of peripheral nerve endothelium, combined with its potential reversibility, identifies a therapeutic window and suggests strategies for targeting the vascular–immune axis to protect the motor system.