Effect of Tofacitinib on One-Year Colectomy Risk in Anti-TNF Refractory Ulcerative Colitis: A Prospective Multicenter Italian Study.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor recently approved to induce and maintain remission in ulcerative colitis (UC). AIMS: Considering the number of anti-TNF non-responders, this study aims to assess the effectiveness and safety of tofacitinib in a cohort of multi-failure patients with moderate-to-severe UC at 52 weeks. METHODS: From January 2021 to March 2023, we performed a prospective multicenter study observing adult patients with moderate-to-severe UC starting tofacitinib after an anti-TNF failure for a 52-week-long period. Effectiveness and safety were assessed in terms of colectomy rate, clinical remission and response, endoscopic remission, steroid-free clinical remission, and rate of adverse events. RESULTS: We included 58 patients with UC with an age of 42 ± 14.4 years, 59% males, 96.6% left-sided or pancolitis, who were failure to a single (65.5%) or more than one anti-TNF (34.5%). Only 6 (10.3%) patients underwent colectomy. Colectomy was clinically associated with the necessity and the number of extra cycles of tofacitinib 10 mg bid at W8 (p = 0.023) and W24 (p = 0.004), and with a higher partial Mayo score at W8 (p = 0.025). At W52, clinical remission, clinical response, and steroid-free clinical remission were 53.4%, 43.1%, and 48.3%, respectively. Of 22 performed colonoscopies at W52, 11 (50%) showed endoscopic remission. Adverse events occurred in 14 (24.1%) patients, but only 2 (3.4%) led to tofacitinib discontinuation. CONCLUSIONS: In a real-life setting of patients with anti-TNF refractory UC, tofacitinib has proved to be effective in preventing colectomy and inducing clinical and endoscopic remission at 52 weeks with a good safety profile.

Gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia: Long-term results of endoscopic treatment.

Background and study aims This longitudinal prospective study evaluated the long-term outcome of endoscopic treatment of gastrointestinal bleeding in hereditary hemorrhagic telangiectases (HHT), its safety and outcome predictors. Patients and methods Consecutive patients with HHT and either anemia disproportionate to epistaxis or overt gastrointestinal bleeding received endoscopic treatment of gastrointestinal telangiectases with argon plasma coagulation (APC). Hemoglobin levels and transfusion requirements were evaluated before and after treatment. Treatment effectiveness was classified as: 1) complete: hemoglobin level during the follow-up ≥9 g/dL; 2) complete with recurrence: hemoglobin ≥9 g/dL for at least 12 months with subsequent drop to <9 g/dL; or 3) absent: no improvement of hemoglobin level. Adverse events (AEs) were classified as mild, moderate, severe or fatal. Correlations were searched between treatment outcome and demographic/genetic characteristics, number, size and site of telangiectases, and hepatic arterio-venous malformations grade. Results Forty-seven patients with HHT were enrolled. At median follow-up of 134 months (range 20-243 months), 41 of 47 patients showed treatment response (complete or with recurrence) after one (14/47) or more (27/47) endoscopic treatments. Median hemoglobin levels were 7.0 g/dL and 11.9 g/dL at baseline and at the end of follow-up, respectively. Transfusion requirement decreased from 22.8 to 7.3 red cell unit/year. A higher baseline number of telangiectases was associated with a lower chance of response ( P =0.008). Only one severe AE (0.4%, jejunal perforation) was recorded. Conclusions Endoscopic treatment of gastrointestinal teleangiectases for gastrointestinal bleeding in patients with HHT is effective in the long term and safe.

Impact of improved upper endoscopy quality on detection of gastric precancerous lesions.

OBJECTIVE: Intestinal metaplasia (IM) is the point of no return in gastric carcinogenesis, and patients with extensive (antrum plus corpus) IM are at high risk of developing gastric cancer. We evaluated the impact of improved gastroscopy quality on the detection of gastric IM in an Italian area at high risk for gastric cancer. METHODS: Data of consecutive patients with gastric biopsies according to the updated Sydney System observed in 2013, 2016 and 2019 resulting in IM diagnosis were retrieved. In the first period, endoscopy was performed with standard white light instruments. In the second period, preendoscopic gastric preparation was administered, and the examinations lasting at least 7 min with standard endoscopes were performed. In the third period, the latter procedure was followed, with virtual chromoendoscopy equipped instruments. The prevalence of IM in any gastric site and that of extensive IM were compared among the three periods. RESULTS: Data of 3485 patients were available. The detection of IM in at least one gastric site increased from 29.9 to 33.6% and 34.5% (95% CI, 32.1-36.8) in the first, second and third period, respectively. The difference was statistically significant between the first and last (P = 0.02; OR, 1.24; 95% CI, 1.04-1.48) period. When considering extensive IM, the detection increased from 4.28 to 6.1% and 5.44%, although the difference failed to reach statistical significance (P = 0.076). CONCLUSION: Our data showed that implementation of a quality protocol increased the probability to detect IM in the stomach, allowing us to select patients deserving stricter follow-up.

Quality performance measures in upper gastrointestinal endoscopy for lesion detection: Italian AIGO-SIED-SIGE joint position statement.

Esophagogastroduodenoscopy (EGD) plays a crucial role in the management of gastroduodenal diseases by allowing a direct and accurate evaluation of the mucosa and the execution of several operative maneuvers. Despite a constant development of new imaging tools and operative devices, the widespread use of EGD has not resulted in a significant reduction of mortality for patients affected by esophageal/gastric cancer during the last three decades in Western countries. Evidence indicates that this disheartening scenario derives from a high variability of execution of EGD which determines its quality and diagnostic yield, delaying the diagnosis of neoplastic diseases. Based on this evidence, in recent years many scientific societies have produced different position papers aimed at defining quality performance measures in EGD. Thus, the Italian Association of Gastroenterologists and Endoscopists, the Italian Society of Digestive Endoscopy and the Italian Society of Gastroenterology have produced this joint document based on the review of ASGE, ACG, BSG, ESGE and Asian Consensus EGD position papers with the aim of indicating the quality standards of EGD (pre-, intra- and post-procedure) focused on lesion detection to be adopted in the Italian context.

Efficacy of a computer-aided detection system in a fecal immunochemical test-based organized colorectal cancer screening program: a randomized controlled trial (AIFIT study).

BACKGROUND: Computer-aided detection (CADe) increases adenoma detection in primary screening colonoscopy. The potential benefit of CADe in a fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening program is unknown. This study assessed whether use of CADe increases the adenoma detection rate (ADR) in a FIT-based CRC screening program. METHODS: In a multicenter, randomized trial, FIT-positive individuals aged 50-74 years undergoing colonoscopy, were randomized (1:1) to receive high definition white-light (HDWL) colonoscopy, with or without a real-time deep-learning CADe by endoscopists with baseline ADR > 25 %. The primary outcome was ADR. Secondary outcomes were mean number of adenomas per colonoscopy (APC) and advanced adenoma detection rate (advanced-ADR). Subgroup analysis according to baseline endoscopists' ADR (≤ 40 %, 41 %-45 %, ≥ 46 %) was also performed. RESULTS: 800 individuals (median age 61.0 years [interquartile range 55-67]; 409 men) were included: 405 underwent CADe-assisted colonoscopy and 395 underwent HDWL colonoscopy alone. ADR and APC were significantly higher in the CADe group than in the HDWL arm: ADR 53.6 % (95 %CI 48.6 %-58.5 %) vs. 45.3 % (95 %CI 40.3 %-50.45 %; RR 1.18; 95 %CI 1.03-1.36); APC 1.13 (SD 1.54) vs. 0.90 (SD 1.32; P  = 0.03). No significant difference in advanced-ADR was found (18.5 % [95 %CI 14.8 %-22.6 %] vs. 15.9 % [95 %CI 12.5 %-19.9 %], respectively). An increase in ADR was observed in all endoscopist groups regardless of baseline ADR. CONCLUSIONS: Incorporating CADe significantly increased ADR and APC in the framework of a FIT-based CRC screening program. The impact of CADe appeared to be consistent regardless of endoscopist baseline ADR.

Adenoma detection by Endocuff-assisted versus standard colonoscopy in an organized screening program: the "ItaVision" randomized controlled trial.

BACKGROUND: The Endocuff Vision device (Arc Medical Design Ltd., Leeds, UK) has been shown to increase mucosal exposure, and consequently adenoma detection rate (ADR), during colonoscopy. This nationwide multicenter study assessed possible benefits and harms of using Endocuff Vision in a fecal immunochemical test (FIT)-based screening program. METHODS: Patients undergoing colonoscopy after a FIT-positive test were randomized 1:1 to undergo Endocuff-assisted colonoscopy or standard colonoscopy, stratified by sex, age, and screening history. Primary outcome was ADR. Secondary outcomes were ADR stratified by endoscopists' ADR, advanced ADR (AADR), adenomas per colonoscopy (APC), withdrawal time, and adverse events. RESULTS: 1866 patients were enrolled across 13 centers. After exclusions, 1813 (mean age 60.1 years; male 53.8 %) were randomized (908 Endocuff Vision, 905 standard colonoscopy). ADR was significantly higher in the Endocuff Vision arm (47.8 % vs. 40.8 %; relative risk [RR] 1.17, 95 % confidence interval [CI] 1.06-1.30), with no differences between arms regarding size or morphology. When stratifying for endoscopists' ADR, only low detectors (ADR < 33.3 %) showed a statistically significant ADR increase (Endocuff Vision 41.1 % [95 %CI 35.7-46.7] vs. standard colonoscopy 26.0 % [95 %CI 21.3-31.4]). AADR (24.8 % vs. 20.5 %, RR 1.21, 95 %CI 1.02-1.43) and APC (0.94 vs. 0.77; P  = 0.001) were higher in the Endocuff Vision arm. Withdrawal time and adverse events were similar between arms. CONCLUSION: Endocuff Vision increased ADR in a FIT-based screening program by improving examination of the whole colonic mucosa. Utility was highest among endoscopists with a low ADR.

Premedication with simethicone and N-acetylcysteine for improving mucosal visibility during upper gastrointestinal endoscopy in a Western population.

Background and study aim Pre-endoscopic use of a preparation with tensioactive and mucolytic agents improved gastric mucosa visualization in Eastern studies. Data on Western population are scanty. Patients and methods This prospective, endoscopist-blinded, randomized study enrolled patients who underwent esophagogastroduodenoscopy in a single center. Before endoscopy patients, were randomized to receive or not receive an oral preparation with simethicone and N-acetylcysteine in water. A pretested score (Crema Stomach Cleaning Score [CSCS]) for gastric mucosa cleaning evaluation was used. In detail, the stomach was divided into the antrum, body, and fundus and a score of 1 to 3 was assigned to each part (the higher the score, the better the preparation), and a total value ≤ 5 was considered as insufficient. Time between endoscope insertion and clean achievement (mouth to clean time) or the end of examination (mouth to mouth time) was recorded. Results A total of 197 patients were enrolled. The mean overall CSCS value and mucosal cleaning in all parts was better in treated patients than in controls. Prevalence total score ≤ 5 was significantly lower in patients treated before endoscopy. Need for water flush occurred less frequently in treated patients ( P  < 0.0001). The mouth to clean time was lower in the treated than in the control group (2.3 ±â€Š1.6 vs 3.8 ±â€Š1.6 min; P  < 0.001), whereas no significant difference in mouth to mouth time emerged. Conclusions Data from this study show that premedication with simethicone and N-acetylcysteine results in significantly better endoscopic visualization of gastric mucosa, and the proposed CSCS could be useful for standardizing this evaluation.

Risk of COVID 19 in patients with inflammatory bowel diseases compared to a control population.

BACKGROUND: It is unclear whether patients with inflammatory bowel disease (IBD) are at increased risk of COVID-19. OBJECTIVES: This observational study compared the prevalence of COVID-19 symptoms, diagnosis and hospitalization in IBD patients with a control population with non-inflammatory bowel disorders. METHODS: This multicentre study, included 2733 outpatients (1397 IBD patients and 1336 controls), from eight major gastrointestinal centres in Lombardy, Italy. Patients were invited to complete a web-based questionnaire regarding demographic, historical and clinical features over the previous 6 weeks. The prevalence of COVID-19 symptoms, diagnosis and hospitalization for COVID-19 was assessed. RESULTS: 1810 patients (64%) responded to the questionnaire (941 IBD patients and 869 controls). IBD patients were significantly younger and of male sex than controls. NSAID use and smoking were more frequent in controls. IBD patients were more likely treated with vitamin-D and vaccinated for influenza. Highly probable COVID-19 on the basis of symptoms and signs was less frequent in the IBD group (3.8% vs 6.3%; OR:0.45, 95%CI:0.28-0.75). IBD patients had a lower rate of nasopharyngeal swab-PCR confirmed diagnosis (0.2% vs 1.2%; OR:0.14, 95%CI:0.03-0.67). There was no difference in hospitalization between the groups (0.1% vs 0.6%; OR:0.14, 95%CI:0.02-1.17). CONCLUSION: IBD patients do not have an increased risk of COVID-19 specific symptoms or more severe disease compared with a control group of gastroenterology patients.

Dietary iron intake and anemia: food frequency questionnaire in patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a multisystemic inherited vascular disease characterized by a heterogeneous clinical presentation and prognosis. Dietary evaluation is relevant in HHT patients to provide adequate iron and nutrient intake. Additionally, different dietary items have been reported to precipitate epistaxis in this setting. Our primary aim was to investigate the dietary habits of HHT patients through a food-frequency questionnaire (FFQ) to evaluate the presence of precipitants and/or protective factors for epistaxis and the occurrence of possible dietary modifications. The secondary aims were to evaluate the nutritional intake of iron in HHT patients and the self-reported effect of iron treatments on epistaxis. From April 2018 to October 2018, a 138-item FFQ was provided to HHT patients followed up at the HHT Referral Center of Crema Maggiore Hospital. The relationship between food items and epistaxis was ascertained on a separate form. Daily iron intake was calculated to establish the mean iron content of food items reported in the FFQ. RESULTS: One hundred forty-nine questionnaires were evaluated [72 females, median age 54 years (12-76). Overall, 26 (18%) patients reported dietary items that improved epistaxis (mostly blueberries and red fruits, green vegetables and legumes), while 38 (26%) reported some dietary items that exacerbated epistaxis (spices, chocolate, alcohol, strawberries and ginger). Dietary modifications were reported in up to 58% of cases. In HHT patients, the mean daily iron intake was 8.46 ± 2.78 mg, and no differences were observed in the iron intake of patients reporting a diet modification and those who did not. CONCLUSIONS: In the comprehensive management of HHT a healthy and balanced diet, with increased consumption of dietary items with a high iron content, should be encouraged.

European Reference Network for Rare Vascular Diseases (VASCERN) position statement on cerebral screening in adults and children with hereditary haemorrhagic telangiectasia (HHT).

Hereditary haemorrhagic telangiectasia (HHT) is a multisystemic vascular dysplasia inherited as an autosomal dominant trait. Approximately 10 % of patients have cerebral vascular malformations, a proportion being cerebral arteriovenous malformations (AVMs) and fistulae that may lead to potentially devastating consequences in case of rupture. On the other hand, detection and treatment related-risks are not negligible, and immediate. While successful treatment can be undertaken in individual cases, current data do not support the treatment of unruptured AVMs, which also present a low risk of bleeding in HHT patients. Screening for these AVMs is therefore controversial.Structured discussions, distinctions of different cerebrovascular abnormalities commonly grouped into an "AVM" bracket, and clear guidance by neurosurgical and neurointerventional radiology colleagues enabled the European Reference Network for Rare Vascular Disorders (VASCERN-HHT) to develop the following agreed Position Statement on cerebral screening:1) First, we emphasise that neurological symptoms suggestive of cerebral AVMs in HHT patients should be investigated as in general neurological and emergency care practice. Similarly, if an AVM is found accidentally, management approaches should rely on expert discussions on a case-by-case basis and individual risk-benefit evaluation of all therapeutic possibilities for a specific lesion.2) The current evidence base does not favour the treatment of unruptured cerebral AVMs, and therefore cannot be used to support widespread screening of asymptomatic HHT patients.3) Individual situations encompass a wide range of personal, cultural and clinical states. In order to enable informed patient choice, and avoid conflicting advice, particularly arising from non-neurovascular interpretations of the evidence base, we suggest that all HHT patients should have the opportunity to discuss knowingly brain screening issues with their healthcare provider.4) Any screening discussions in asymptomatic individuals should be preceded by informed pre-test review of the latest evidence regarding preventative and therapeutic efficacies of any interventions. The possibility of harm due to detection of, or intervention on, a vascular malformation that would not have necessarily caused any consequence in later life should be stated explicitly.We consider this nuanced Position Statement provides a helpful, evidence-based framework for informed discussions between healthcare providers and patients in an emotionally charged area.

Linked-color imaging versus white-light colonoscopy in an organized colorectal cancer screening program.

BACKGROUND AND AIMS: Linked-color imaging (LCI), a new image-enhancing technology emphasizing contrast in mucosal color, has been demonstrated to substantially reduce polyp miss rate as compared with standard white-light imaging (WLI) in tandem colonoscopy studies. Whether LCI increases adenoma detection rate (ADR) remains unclear. METHODS: Consecutive subjects undergoing screening colonoscopy after fecal immunochemical test (FIT) positivity were 1:1 randomized to undergo colonoscopy with LCI or WLI, both in high-definition systems. Insertion and withdrawal phases of each colonoscopy were carried out using the same assigned light. Experienced endoscopists from 7 Italian centers participated in the study. Randomization was stratified by gender, age, and screening round. The primary outcome measure was represented by ADR. RESULTS: Of 704 eligible subjects, 649 were included (48.9% men, mean age ± standard deviation, 60.8 ± 7.3 years) and randomized to LCI (n = 326) or WLI (n = 323) colonoscopy. The ADR was higher in the LCI group (51.8%) than in the WLI group (43.7%) (relative risk, 1.19; 95% confidence interval, 1.01-1.40). The proportions of patients with advanced adenomas and sessile serrated lesions were, respectively, 21.2% and 8.6% in the LCI arm and 18.9% and 5.9% in the WLI arm (not significant for both comparisons). At multivariate analysis, LCI was independently associated with ADR, along with male gender, increasing age, and adequate (Boston Bowel Preparation Scale score ≥6) bowel preparation. At per-polyp analysis, the mean ± standard deviation number of adenomas per colonoscopy was comparable in the LCI and WLI arms, whereas the corresponding figures for proximal adenomas was significantly higher in the LCI group (.72 ± 1.2 vs .55 ± 1.07, P = .05) CONCLUSIONS: In FIT-positive patients undergoing screening colonoscopy, the routine use of LCI significantly increased the ADR. (Clinical trial registration number: NCT03690297.).

Epidemiology, clinical features and diagnostic work-up of cystic neoplasms of the pancreas: Interim analysis of the prospective PANCY survey.

INTRODUCTION: A prospective survey to evaluate the diagnostic workup of cystic pancreatic neoplasms (CPNs) according to the Italian guidelines. METHODS: An online data sheet was built. RESULTS: Fifteen of the 1385 patients (1.1%) had non cystic neoplastic lesions. Forty percent (518/1295) had at least one 1st degree relative affected by a solid tumor of the digestive and extra-digestive organs. Symptoms/signs associated with the cystic lesion were present in 24.5% of the patients. The cysts were localized in the head of the pancreas in 38.5% of patients. Of the 2370 examinations (1.7 examinations per patient) which were carried out for the diagnosis, magnetic resonance imaging was performed as a single test in 48.4% of patients and in combination with endoscopic ultrasound in 27% of the cases. Of the 1370 patients having CPNs, 89.9% had an intraductal papillary mucinous neoplasm (IPMN) (70.1% a branch duct IPMN, 6.2% a mixed type IPMN and 4.6% a main duct IPMN), 12.7% had a serous cystadenoma, 2.8% a mucinous cystadenoma, 1.5% a non-functioning cystic neuroendocrine neoplasm, 0.7% a solid-pseudopapillary cystic neoplasm, 0.3% a cystic adenocarcinoma, and 1.2% an undetermined cystic neoplasm. Seventy-eight (5.7%) patients were operated upon after the initial work-up. CONCLUSIONS: This prospective study offers a reliable real-life picture of the diagnostic work-up CPN.

Liver involvement in hereditary hemorrhagic telangiectasia.

Liver vascular malformations (VMs) in hereditary hemorrhagic telangiectasia (HHT) are typically diffuse and can evolve from small telangiectasias to large arteriovenous malformations, with various stages of severity. Doppler US is the ideal first-line investigation for the assessment of liver VMs in HHT due to its safety, tolerability, low costs, and accuracy for the detection of liver VMs. The caliber, course, and flow characteristics in the hepatic artery, portal vein, and hepatic vein as determined by Doppler US, together with parenchymal abnormalities, support the diagnosis of liver VMs in HHT and their severity staging. When Doppler US expertise is lacking or an assessment of HHT patients with symptoms/signs suggestive of complicated liver VMs is required, particularly if OLT is considered, multiphase CT or MRI is suitable to investigate symptomatic liver VMs. Liver biopsy is neither necessary for the diagnosis of hepatic VMs related to HHT nor should be considered in HHT patients with liver mass/es suggestive of focal nodular hyperplasia.

Body mass index, cardiovascular risk factors, and carotid intima-media thickness in a pediatric population in southern Italy.

OBJECTIVES: Obesity and exposure to cardiovascular risk factors during adolescence may be associated with the development of atherosclerosis and cardiovascular diseases later in life. The objective of the study was to investigate whether any excess body weight, including moderate overweight, is associated with a more severe cardiovascular risk profile and signs of early atherosclerosis in a pediatric population. PATIENTS AND METHODS: A cross-sectional study was conducted among 646 adolescents ages 11 to 13 years from several primary schools of Reggio Calabria, Italy. Body mass index, waist circumference, blood pressure, glucose, insulin, homeostatic model assessment of insulin resistance, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and C-reactive protein (CRP) were determined. All of the subjects underwent carotid ultrasonography for the measurement of intima-media thickness. Complete clinical data were available from 575 subjects. RESULTS: Overweight was similarly frequent in boys and girls (31.2% vs 31.0%), whereas prevalence of obesity was higher in boys (18.4% vs 10.1%). Subjects with lower levels of HDL and higher levels of triglycerides, insulin, and CRP plasma were observed more frequently among overweight and obese subjects than nonoverweight. At multivariate analysis, HDL cholesterol, insulin, and CRP were associated (P < 0.05) with overweight and obesity in girls, whereas in boys, insulin and CRP were associated (P < 0.05) with overweight and obesity, and LDL cholesterol with obesity. The association between overweight or obesity and increased intima-media thickness, a sign of early atherosclerosis, was present in girls (P < 0.05) and was close to statistical significance in obese boys (P = 0.07). CONCLUSIONS: Overweight and obese adolescents have a higher prevalence of cardiovascular risk factors and show signs of early atherosclerosis. In girls, in particular, overweight is sufficient to determine a more severe cardiovascular risk profile.

Cardiovascular risk factors, nonalcoholic fatty liver disease, and carotid artery intima-media thickness in an adolescent population in southern Italy.

The objective of this study was to determine, in an adolescent population, the prevalence of nonalcoholic fatty liver disease (NAFLD) and the association of NAFLD and cardiovascular risk factors with carotid artery intima-media thickness (IMT), a marker of subclinical atherosclerosis. The authors conducted a population-based study among 642 randomly selected adolescents aged 11-13 years in Reggio Calabria, southern Italy, between November 2007 and October 2008. Prevalences of overweight and obesity were 30.5% and 13.5%, respectively. The overall prevalence of NAFLD was 12.5%, increasing to 23.0% in overweight/obese adolescents. In univariate analysis, increased IMT was positively associated with the presence of NAFLD, body mass index (BMI), waist circumference, systolic blood pressure (all P's < 0.001), diastolic blood pressure (P = 0.006), gamma-glutamyl transpeptidase (P = 0.006), alanine aminotransferase (P = 0.007), and C-reactive protein (P = 0.008) and was inversely associated with high density lipoprotein cholesterol (P < 0.001). In multivariate analysis, NAFLD (P = 0.002), BMI (P = 0.004), waist circumference (P = 0.003), and systolic blood pressure (P = 0.005) retained significant associations. The authors conclude that NAFLD, BMI, waist circumference, and systolic blood pressure are independent markers of increased IMT in a random sample of adolescents.