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Background Colorectal cancer (CRC) is a common neoplasm in Western countries. Prioritizing access to colonoscopy appears of critical relevance. Alarm features are considered to increase the likelihood of CRC. Our aim was to assess the diagnostic performance of alarm features for CRC diagnosis. Methods We performed a systematic review and meta-analysis of studies reporting the diagnostic accuracy of alarm features (rectal bleeding, anemia, change in bowel habit, and weight loss) for CRC, published up to September 2021. Colonoscopy was required as the reference diagnostic test. Diagnostic accuracy measures were pooled by a bivariate mixed-effects regression model. The number needed to scope (NNS; i. e. the number of patients who need to undergo colonoscopy to diagnose one CRC) according to each alarm feature was calculated. Results 31 studies with 45 100 patients (mean age 31–88 years; men 36 %–63 %) were included. The prevalence of CRC ranged from 0.2 % to 22 %. Sensitivity was suboptimal, ranging from 12.4 % for weight loss to 49 % for rectal bleeding, whereas specificity ranged from 69.8 % for rectal bleeding to 91.9 % for weight loss. Taken individually, rectal bleeding and anemia would be the only practical alarm features mandating colonoscopy (NNS 5.3 and 6.7, respectively). Conclusions When considered independently, alarm features have variable accuracy for CRC, given the high heterogeneity of study populations reflected by wide variability in CRC prevalence. Rectal bleeding and anemia are the most practical to select patients for colonoscopy. Integration of alarm features in a comprehensive evaluation of patients should be considered.

APC gene target sequencing and in silico analysis

Protein quantification of WNT signaling components in DLD-1, SW480 and CACO-2 cell lines upon miR-155-5p induction.

List of primary antibodies used for western blotting analysis.

Colorectal cancer (CRC) is one of the most common cancers worldwide and its global incidence is rapidly increasing among adults younger than 50 years, especially in the 20-39 age group. Once a curative resection is achieved, surveillance is mandatory. Colonoscopy has a pivotal role aimed at resecting pre-malignant neoplasms and detecting cancer at a curable stage. In the current review, an update on the role of surveillance colonoscopy after CRC is provided, taken into account the most recent international guidelines and evidence published on this issue. In particular, several questions have been answered, why, how and how often colonoscopy should be performed, whether intensive surveillance is more effective than standard surveillance, how endoscopically resected T1 cancer should be followed, the different management existing between colon and rectal cancer, and, finally, how to improve the endoscopic surveillance. In a period of resource constraints, appropriateness will be mandatory, thus understanding how to optimize the role of colonoscopy in the surveillance of patients with a history of CRC is of crucial importance. Improving the quality of colonoscopy and identifying risk factors for recurrent and new-onset CRC, will allow us to individualize the surveillance program while sparing health care cost.

Helicobacter pylori remains a major health problem worldwide, causing considerable morbidity and mortality due to peptic ulcer disease and gastric cancer. The burden of disease falls disproportionally on less well-resourced populations. As with most infectious diseases, the largest impact on reducing this burden comes from improvement in socioeconomic status, which interrupts transmission. This has been observed in many regions of the world, but the prevalence of infection remains high in many regions where improvements in living standards are slow to occur. Meanwhile, the optimal clinical management and treatment pathways remain unsettled and are evolving with changing antimicrobial resistance patterns. Despite decades of research and clinical practice, major challenges remain. The quest for the most effective, safe, and simple therapy remains the major issue for clinicians. The search for an effective vaccine appears to be elusive still. Clinical guidelines do not infrequently proffer discordant advice. A major challenge for guidelines is for relevance across a variety of populations with a varying spectrum of disease, antimicrobial resistance rates, and vastly different resources. As local factors are central to determining the impact and management strategies for H. pylori infection, it is important that pathways are based on the best available local knowledge rather than solely extrapolating from guidelines formulated in other regions, which may be less applicable. To this end, this revision of the World Gastroenterology Organisation (WGO) H. pylori guideline uses a "Cascades" approach that seeks to summarize the principles of management and offer advice for pragmatic, relevant and achievable diagnostic and treatment pathways based on established key treatment principles and using local knowledge and available resources to guide regional practice.

Background Patients with prior colon cancer have increased risk of metachronous colorectal neoplasms; therefore, endoscopic surveillance is indicated. Current recommendations are not risk-stratified. We investigated predictive factors for colorectal neoplasms to build a model to spare colonoscopies for low-risk patients. Methods This was a multicenter, retrospective study including patients who underwent surgery for colon cancer in 2001 – 2008 (derivation cohort) and 2009 – 2013 (validation cohort). A predictive model for neoplasm occurrence at second surveillance colonoscopy was developed and validated. Results 421 and 203 patients were included in derivation and validation cohort, respectively. At second surveillance colonoscopy, 112 (26.6 %) and 55 (27.1 %) patients had metachronous neoplasms in derivation and validation groups; three cancers were detected in the latter. History of left-sided colon cancer (OR 1.64, 95 %CI 1.02 – 2.64), ≥ 1 advanced adenoma at index colonoscopy (OR 1.90, 95 %CI 1.05 – 3.43), and ≥ 1 adenoma at first surveillance colonoscopy (OR 2.06, 95 %CI 1.29 – 3.27) were independently predictive of metachronous colorectal neoplasms at second surveillance colonoscopy. For patients without such risk factors, diagnostic accuracy parameters were: 89.3 % (95 %CI 82.0 %-94.3 %) and 78.2 % (95 %CI 65.0 %-88.2 %) sensitivity, and 28.5 % (95 %CI 23.5 %-33.9 %) and 33.8 % (95 %CI 26.2 %-42.0 %) specificity in derivation and validation group, respectively. No cancer would be missed. Conclusions Patients with prior left-sided colon cancer or ≥ 1 advanced adenoma at index colonoscopy or ≥ 1 adenoma at first surveillance colonoscopy had a significantly higher risk of neoplasms at second surveillance colonoscopy; patients without such factors had much lower risk and could safely skip the second surveillance colonoscopy. A prospective, multicenter validation study is needed.

(1) Background: Whether standard bismuth quadruple therapy (BQT) is superior to concomitant therapy for the first-line treatment of Helicobacter (H.) pylori infection is unclear. The aim of this systematic review and meta-analysis was to compare the efficacy of standard BQT versus concomitant therapy for H. pylori eradication in subjects naïve to treatment. (2) Methods: Online databases were searched for randomized controlled trials. We pooled risk ratio (RR) of individual studies for dichotomous outcomes using a random-effect model. (3) Results: Six studies with 1810 adults were included. Overall intention-to-treat (ITT) eradication rate was 87.4% with BQT and 85.2% with concomitant therapy (RR 1.01, 95%CI:0.94–1.07). Subgroup analysis of five Asian studies showed a small but significant superiority of BQT over concomitant therapy (87.5% vs. 84.5%; RR 1.04, 95%CI:1.01–1.08). Pooling four studies at low risk of bias yielded a similar result (88.2% vs. 84.5%; RR 1.05, 95%CI:1.01–1.09). There was no difference between the regimens in the frequency of adverse events (RR = 0.97, 95%CI:0.79–1.2). (4) Conclusions: The efficacy of BQT seems to be similar to concomitant therapy, with similar side effect profile. However, BQT showed a small but significant benefit over concomitant therapy in Asian populations and in studies at low risk of bias.

Background Inpatients are at risk for inadequate colon cleansing. Experts recommend 4L-polyethylene-glycol (PEG) solution. A higher colon cleansing adequacy rate for a hyperosmolar 1L-PEG plus ascorbate prep has been recently reported. Aims We aimed to determine whether 1L-PEG outperforms 4L-PEG among inpatients. Methods post-hoc analysis of a large Italian multicenter prospective observational study among inpatients (QIPS study). We performed a propensity score matching between 1L-PEG and 4L-PEG group. The primary outcome was the rate of adequate colon cleansing as assessed by unblinded endoscopists through Boston scale. Secondary outcome was the safety profile. Results Among 1,004 patients undergoing colonoscopy, 724 (72%) were prescribed 4L-PEG and 280 (28%) 1L-PEG. The overall adequate colon cleansing rate was 69.2% (n = 695). We matched 274 pairs of patients with similar distribution of confounders. The rate of patients with adequate colon cleansing was higher in 1L-PEG than in 4L-PEG group (84.3% vs. 77.4%, p = 0.039). No different shift in serum concentration of electrolytes (namely Na+, K+, Ca2+), creatinine and hematocrit were observed for both preparations. Conclusion We found a higher rate of adequate colon cleansing for colonoscopy with the 1L-PEG bowel prep vs. 4L-PEG, with apparent similar safety profile, among inpatients. A confirmatory randomized trial is needed. (ClinicalTrials.gov no: NCT04310332)

Gastro-esophageal reflux (GER) is the main predisposing factor for Barrett's esophagus (BE). A more precise estimate of the association of GER symptoms with the risk of BE would be important to prioritize endoscopic screening. We conducted a systematic review and meta-analysis to examine this issue.MEDLINE, EMBASE, and EMBASE Classic were searched to identify cross-sectional studies that reported the prevalence of BE based on presence of GER symptoms. The prevalence of BE was compared according to presence or absence of GER symptoms using an odds ratio (OR), with a 95% confidence interval (CI). Specificity and sensitivity of GER symptoms for predicting BE was calculated.Of 10,463 citations evaluated, 19 studies reported the prevalence of BE in 43,017 subjects. The pooled OR among individuals with weekly GER symptoms compared with those without was 1.67 (95% CI 1.30-2.15) for endoscopically suspected BE, and 2.42 (95% CI 1.59-3.68) for histologically confirmed BE. No significant association was found between weekly GER symptoms and the presence of short segment BE (OR 1.30; 95% CI 0.86-1.97), whereas a strong association was present with long segment BE, with an OR of 6.30 (95% CI 2.26-17.61).Gastro-esophageal reflux symptoms are associated with an increased odds of BE, with a further increase when weekly symptoms are present. Overall, GER symptoms showed low sensitivity and specificity for predicting BE; however, a strong association was found between weekly GER symptoms and long segment BE, but not short segment BE, suggesting that it may be worth considering screening individuals with weekly GER symptoms to rule out long segment BE.

Given the increasing prevalence and incidence of colorectal cancer, more patients will suffer from colonic obstruction and therefore need appropriate treatment. Currently, patients can undergo either emergency surgery (ES), which encompasses colostomy, or endoscopic self-expandable metal stent (SEMS) placement. However, ES carries a substantial risk of morbidity and mortality; therefore, attention has been increasingly drawn on the endoscopic placement of SEMS. SEMS can be inserted under endoscopic and/or fluoroscopic view. Main adverse events encompass stent failure, perforation, migration, and re-obstruction. As a bridge to surgery, SEMS placement is controversial due to concern on long-term oncological outcomes. However, recent studies have shown a similar survival rate as compared to surgery, when stenting is carried out in highly experienced centers. In the palliative setting, SEMS placement is contraindicated in patients treated or planned to be treated with bevacizumab or other antiangiogenic drugs. Nevertheless, we will discuss the existing evidence showing conflicting results. In summary, this review will focus on the technique of SEMS insertion, indications, outcomes, and adverse events, both as a bridge-to-surgery strategy and in the palliative setting, disserting the most recent evidence.

Objective Atrophic gastritis may affect circulating ghrelin levels and, indirectly, body mass index. The aim of this study was to investigate the relationship between atrophic gastritis, focusing on autoimmune atrophic gastritis and advanced stages of atrophic gastritis, serum ghrelin levels and BMI. Methods Sixty-three patients, of whom 18 had autoimmune atrophic gastritis, 27 non-autoimmune antrum and corpus atrophic gastritis, and 18 non-atrophic gastritis or antrum-limited atrophic gastritis (control group) were assessed. All participants underwent endoscopy with multiple gastric biopsies. Atrophic gastritis was diagnosed by histology, classified according to the Updated Sydney System and staged by the Operative Link on Gastritis Assessment (OLGA) Classification. Total serum ghrelin, body weight and height were measured. Results Compared with control patients (144.6 ± 111 pg/ml), mean serum level of total ghrelin was higher in patients with autoimmune atrophic gastritis (226.08 ± 243.03 pg/ml, P = 0.65) and lower in those with both antrum and corpus atrophic gastritis (74.51 ± 37.38 pg/ml, P = 0.12), although differences were not statistically significant. Serum ghrelin decreased in patients with advanced OLGA stages of atrophic gastritis. In non-obese patients BMI was significantly lower in those with both antrum and corpus atrophic gastritis than in control patients (23.1 ± 1.8 vs. 24.5 ± 1.6, P = 0.01), also after adjustment for age and sex (P = 0.02); BMI was positively correlated with serum total ghrelin (r = 0.51, P < 0.001). Conclusion Advanced stages of atrophic gastritis, but not autoimmune atrophic gastritis, seem to be associated with lower serum levels of ghrelin and lower BMI. In non-obese patients, BMI was positively correlated with total serum ghrelin.

Background: Endoscopic surveillance in patients with Lynch syndrome (LS) is crucial due to a genetically based high risk of colorectal cancer (CRC). We aimed to compare the adenoma detection rate (ADR) between high-resolution white light endoscopy (WLE) alone and WLE plus dye chromoendoscopy (CE) in a cohort of LS patients. Methods: In a context of real-world data, we retrospectively enrolled 50 LS patients who had non-randomly undergone WLE versus CE surveillance examinations from 2007 to 2019. The 2 groups were compared at baseline (BL) in terms of the rate of patients with lesions and the number of lesions, and at follow-up (FU), to evaluate a possible enhanced detection rate. Longitudinal analysis of the effect of the endoscopy type on the main outcomes was performed by generalized linear mixed models. Results: Forty-two patients had undergone at least one diagnostic colonoscopy. At BL and at FU analysis, we found no significant differences in detection rates and clinical-pathological features between WLE and CE groups. At the longitudinal analysis, an increase in the endoscopy rank (i.e., the position of each colonoscopy for all the colonoscopies that a patient had undergone) was associated with an increase in polyp detection rate (p = 0.006) and ADR (p = 0.005), while a trend toward significance (p = 0.069) was found for endoscopy type (CE vs. WLE) in the detection of serrated lesions. Conclusions: CE is not superior to high-resolution WLE in increasing the ADR. Even under standard WLE, an active and careful endoscopic surveillance of LS patients can prevent CRC.

Our study aimed to investigate whether radiomics on MRI sequences can differentiate responder (R) and non-responder (NR) patients based on the tumour regression grade (TRG) assigned after surgical resection in locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT). Eighty-five patients undergoing primary staging with MRI were retrospectively evaluated, and 40 patients were finally selected. The ROIs were manually outlined in the tumour site on T2w sequences in the oblique-axial plane. Based on the TRG, patients were grouped as having either a complete or a partial response (TRG = (0,1), n = 15). NR patients had a minimal or poor nCRT response (TRG = (2,3), n = 25). Eighty-four local first-order radiomic features (RFs) were extracted from tumour ROIs. Only single RFs were investigated. Each feature was selected using univariate analysis guided by a one-tailed Wilcoxon rank-sum. ROC curve analysis was performed, using AUC computation and the Youden index (YI) for sensitivity and specificity. The RF measuring the heterogeneity of local skewness of T2w values from tumour ROIs differentiated Rs and NRs with a p-value ≈ 10−5; AUC = 0.90 (95%CI, 0.73–0.96); and YI = 0.68, corresponding to 80% sensitivity and 88% specificity. In conclusion, higher heterogeneity in skewness maps of the baseline tumour correlated with a greater benefit from nCRT.

Background and Aims: Cirrhotic patients with hepatitis C virus (HCV) infection remain at risk of developing hepatocellular carcinoma (HCC) even after the sustained virologic response (SVR). We aimed to evaluate whether the IL28 (rs12979860) single nucleotide polymorphism (SNP) may constitute a predisposing genetic factor and to identify the SVR patients at risk of HCC. Methods: Two hundred patients undergoing DAAs treatment for chronic hepatitis C with advanced fibrosis (F3- F4) were consecutively enrolled. Besides normal routine laboratory testing for HCV, patients’ sera were evaluated also for retinol, retinol-binding protein 4 and the following SNPs: PNPLA3 (rs738409), TM6SF2 (rs58542926), MBOAT7 (rs641738), IL28B (rs12979860), TIMP-1 (rs4898), TIMP-2 (rs8179090), NF-kB promoter (rs28362491). Statistical analyses were conducted using Stata/SE 14.2 statistical software (Stata Corp, College Station, TX). Results: Almost all patients (197/200) obtained SVR24. Seventeen patients had a previous history of treated HCC before DAAs. Six patients developed HCC recurrence and five patients developed de novo HCC after a mean period of 18 months since EOT. All these patients had SVR. A significant association between IL28B – TT genotype and HCC development after DAAs therapy was observed (OR 4.728, CI 95% 1.222 – 18.297, p=0.024). Conclusion: IL28B rs12979860 polymorphism was significantly associated with HCC development after DAAs. Assessment of this SNP may better identify patients at risk of developing HCC after treatment. Further prospective studies are required to confirm these hypotheses.

The role of liver stiffness (LS) on ultrasound elastography in the prediction of hepatocellular carcinoma (HCC) recurrence after treatment with radiofrequency ablation (RFA) is still unclear. Our aim was to perform a systematic review and meta-analysis to assess whether LS can predict the recurrence of HCC after RFA.Medline via PubMed, Embase, Scopus, and Cochrane Library databases, and abstracts of international conference proceedings were searched up to June 30, 2020. Cohort studies were included if they assessed the association between LS values measured by ultrasound elastography before RFA and HCC recurrence.9 studies including 1373 patients with HCC treated by RFA, 643 of whom developed HCC recurrence, were identified. The mean value of LS before RFA was significantly higher in patients who developed HCC recurrence than in those who did not (weighted mean difference=11.98 kPa, 95%CI: 7.60-16.35, I2=63.8%). There was a significant positive association between LS value and HCC recurrence both at univariate (unadjusted HR=1.03, 95%CI: 1.00-1.07, I2=72.7%) and multivariate analysis (adjusted HR=1.03, 95%CI: 1.02-1.04, I2=0). Patients with LS value ≥13-14 kPa or1.5 m/s have a higher risk of both HCC recurrence (unadjusted HR=2.18, 95%CI: 1.46-3.25, I2=49.7%; adjusted HR=2.41, 95%CI: 1.53-3.79, I2=0) and overall mortality (adjusted HR=4.38; 95%CI: 2.33-8.25, I2=0) in comparison with those with LS below these cutoffs.Liver ultrasound elastography appears to be a reliable tool to predict HCC recurrence and overall survival after RFA. This technique may be useful for the management of patients with HCC treated by RFA.ZIEL: Die Rolle der Lebersteifigkeit (LS) in der Ultraschall-Elastografie bei der Vorhersage eines Rezidivs des hepatozellulären Karzinoms (HCC) nach Behandlung mit Radiofrequenzablation (RFA) ist noch unklar. Unser Ziel war es, eine systematische Übersicht und Metaanalyse durchzuführen, um zu beurteilen, ob die LS ein Rezidiv des HCC nach RFA vorhersagen kann.Durchsucht wurden Medline über die Datenbanken PubMed, Embase, Scopus und Cochrane Library sowie Abstracts internationaler Konferenzberichte bis zum 30. Juni 2020.Es wurden 9 Studien mit 1373 Patienten mit HCC, die mit RFA behandelt wurden, identifiziert, von denen 643 ein HCC-Rezidiv entwickelten. Der mittlere LS-Wert vor RFA war bei Patienten, die ein HCC-Rezidiv entwickelten, signifikant höher als bei denen, die kein Rezidiv entwickelten (gewichtete mittlere DifferenzDie Ultraschall-Elastografie der Leber scheint eine zuverlässige Methode zur Vorhersage des HCC-Rezidivs und des Gesamtüberlebens nach RFA zu sein. Dieses Verfahren kann für das Management von Patienten mit HCC, die mit RFA behandelt wurden, nützlich sein.

This cohort study compared colorectal cancer (CRC) incidence and mortality between people who participated in an Italian regional biennial fecal immunochemical test (FIT) screening program and people who did not.The program started in 2005. The target population included over 1,000,000 people aged 50 to 69 years. The FIT was a one-sample OC-Sensor (Eiken Chemical Co, Tokyo, Japan) (cutoff, ≥20 μg hemoglobin/g feces). The average annual response rate to invitation was 51.4%. The records of people invited up to June 2016 were extracted from the screening data warehouse. Attenders were subjects who responded to the first 2 invitations or to the single invitation sent them before they became ineligible. Non-attenders were subjects who did not respond to any of these invitations. The records were linked with the regional CRC registry. People registered up to December 2016 were identified. Self-selection-adjusted incidence rate ratios (IRRs) and incidence-based CRC mortality rate ratios (MRRs) for attenders to non-attenders, with 95% confidence intervals (CIs), were calculated.The cohort generated 2,622,131 man-years and 2,887,845 woman-years at risk with 4490 and 3309 CRC cases, respectively. The cohort of attenders was associated with an IRR of 0.65 (95% CI, 0.61-0.69) for men, 0.75 (95% CI, 0.70-0.80) for women and 0.69 (95% CI, 0.66-0.72) for both sexes combined. The self-selection-adjusted IRR was 0.67 (95% CI, 0.62-0.72) for men and 0.79 (95% CI, 0.72-0.88) for women. The IRR for stage I, II, III, and IV CRC was 1.35 (95% CI, 1.20-1.50), 0.61 (95% CI, 0.53-0.69), 0.60 (95% CI, 0.53-0.68) and 0.28 (95% CI, 0.24-0.32) for men and 1.64 (95% CI, 1.43-1.89), 0.60 (95% CI, 0.52-0.69), 0.73 (95% CI, 0.63-0.85) and 0.35 (95% CI, 0.30-0.42) for women. The overall incidence-based CRC MRR was 0.32 (95% CI, 0.28-0.37) for men, 0.40 (95% CI, 0.34-0.47) for women and 0.35 (95% CI, 0.31-0.39) for both sexes combined. The adjusted MRR was 0.35 (95% CI, 0.29-0.41) for men and 0.46 (95% CI, 0.37-0.58) for women.Attendance to a FIT screening program is associated with a CRC incidence reduction of 33% among men and 21% among women, and a CRC mortality reduction of 65% and 54%, respectively.

Background and Aims The SARS-CoV-2 pandemic had a sudden, dramatic impact on healthcare. In Italy, since the beginning of the pandemic, colorectal cancer (CRC) screening programs have been forcefully suspended. We aimed to evaluate whether screening procedure delays can affect the outcomes of CRC screening. Methods We built a procedural model considering delays in the time to colonoscopy and estimating the effect on mortality due to up-stage migration of patients. The number of expected CRC cases was computed by using the data of the Italian screened population. Estimates of the effects of delay to colonoscopy on CRC stage, and of stage on mortality were assessed by a meta-analytic approach. Results With a delay of 0-3 months, 74% of CRC is expected to be stage I-II, while with a delay of 4-6 months there would be a 2%-increase for stage I-II and a concomitant decrease for stage III-IV (p=0.068). Compared to baseline (0-3-months), moderate (7-12-months) and long (>12-months) delays would lead to a significant increase in advanced CRC (from 26% to 29% and 33%, respectively; p=0.008 and p12-month delay (p=0.005), and a significant change in mortality distribution by stage when comparing the baseline with the >12-months (p

Adenomatous Polyposis Coli (APC) gene mutations are responsible for the onset of familial adenomatous polyposis (FAP) and sporadic colorectal cancer and have been associated with miRNAs dysregulation. The capacity of miR-155, a cancer-related miRNA, to target components of the WNT/β-CATENIN pathway suggests that APC gene mutations, controlling miRNAs expression, may critically regulate WNT/β-CATENIN signaling. To this end, APC gene target sequencing was performed on colonic adenomatous polyps and paired normal mucosa clinical specimens from FAP patients (n = 9) to elucidate the role of miR-155-5p in APC-mutant setting. The expression of selected miRNAs and WNT/β-CATENIN signaling components was characterized in FAP patients and non-FAP control subjects (n = 5). miR-155-5p expression and functional effects on WNT cascade, cell survival, growth, and apoptosis were investigated in different colorectal cancer cell lines. A somatic second hit in the APC gene was found in adenomatous polyps from 6 of 9 FAP patients. Heterozygous APC gene mutations in FAP patients were associated with altered expression of candidate miRNAs and increased levels of AXIN1 and AXIN2 mRNAs. miR-155-5p was downregulated in FAP patients and in the APC and β-CATENIN–mutant colorectal cancer cell lines, and critically regulates WNT/β-CATENIN cascade by targeting both AXIN1 and TCF4. Importantly, miR-155-5p may sustain long-term WNT/β-CATENIN activation in colorectal cancer cells upon WNT3A stimulation. Implications: This study supports a key role of miR-155-5p in modulating WNT/β-CATENIN signaling in colorectal cancer and unravels a new mechanism for AXIN1 regulation which represents a potential therapeutic target in specific tumor subtypes.

Helicobacter pylori infection still represents a major health issue, especially in developing countries, with an estimate of 4 billion of infected subjects in 2015. The increase of antibiotic resistance has undermined the efficacy of standard triple therapy leading to more complex regimens. This review summarizes recommendations of international guide¬ lines and reports the most recent evidence from meta-analyses and clinical trials on the treatment of Helicobacter pylori infection. The choice of H. pylori eradication regimen should be based on the local prevalence of clarithromycin resistance and the previous use of macrolides. Quadruple therapies (bismuth quadruple and concomitant) are the recommended regimens for the first-line treatment; a 14-day clarithromycin-containing triple therapy is suggested in areas with low prevalence of clarithromycin resistance and in patients without previous use of macrolides. data on the efficacy of sequential therapy against clarithromycin resistant H. pylori strains are contradictory, and its use in the treatment ofH. pylori infection is generally discouraged. Second-line treatments include levofloxacin-containing triple therapy and bismuth quadruple therapy. Probiotic supplementation should be used with the aim to reduce antibiotic-related adverse events. Recent evidence would support current guideline recommendations for the treatment of Helicobacter pylori infection.

Medical faculties have the responsibility to train tomorrow's doctors and in a crisis face the challenge of delivering students into the workforce promptly and safely. Worldwide, medical faculties have faced unprecedented disruptions from viral outbreaks and pandemics including SARS, Ebola, H1N1 and COVID-19 which bring unique challenges. Currently there is worldwide disruption to medical faculties and medical education due to COVID-19. Despite close links with clinical medicine and the known risks of pandemics, many medical faculties have been caught off guard without pandemic planning in place, to deal with an exponential rise in infections and deaths, overwhelmed health services and widespread community risk of transmission. Assessing transmission risk of COVID-19 in teaching, clinical and community attachments and continuing medical education is paramount as medical faculties face subsequent pandemics waves. Consensus statements based on best available evidence and international expertise from medical faculties in Asia, Australia and Europe were developed to help guide the protection of staff and students, priorities on teaching activities and further educational development. Infection prevention, infection control, contact tracing and medical surveillance are detailed to minimise transmission and to enhance safety. Recommendations on teaching activities planning can enhance responsiveness of medical faculties to tackle subsequent waves of COVID-19 infection. A global approach and dialogue are encouraged.

Background Gastro‐oesophageal reflux is considered the main risk factor for Barrett's oesophagus. The role of other potential risk factors for the development of Barrett's oesophagus in patients with gastro‐oesophageal reflux symptoms is controversial. Aims To perform a systematic review and meta‐analysis examining risk factors in development of Barrett's oesophagus. Methods Medline, Embase and Embase Classic were searched (until December 2020) to identify cross‐sectional studies reporting prevalence of Barrett's oesophagus based on presence of one or more proposed risk factors in individuals with gastro‐oesophageal reflux symptoms. Prevalence of Barrett's oesophagus was compared according to presence or absence of each risk factor in individuals with gastro‐oesophageal reflux symptoms. Results Of 7164 citations evaluated, 13 studies reported prevalence of Barrett's oesophagus in 11 856 subjects. Pooled prevalence of histologically confirmed Barrett's oesophagus in individuals with gastro‐oesophageal reflux symptoms in all studies was 7.0% (95% CI 4.8% to 9.6%). Prevalence was higher in subjects with hiatal hernia (OR 2.74; 95% CI 1.58 to 4.75) and in those who drank alcohol (OR 1.51; 95% CI 1.17 to 1.95). Other features including non‐steroidal anti‐inflammatory drugs and/or aspirin use (OR 1.19; 95% CI 1.00 to 1.42), smoking (OR 1.14; 95% CI 0.96 to 1.35) or obesity (OR 1.10; 95% CI 0.92 to 1.33) were not significantly associated with Barrett's oesophagus. Conclusions The prevalence of Barrett's oesophagus in individuals with gastro‐oesophageal reflux symptoms was higher in those who drank alcohol, although this association was modest. The strongest association found was between hiatal hernia and Barrett's oesophagus. Other potential risk factors assessed in this study did not appear to be associated with presence of Barrett's oesophagus among individuals with gastro‐oesophageal symptoms.

Background The SARS-CoV-2 pandemic has had a huge impact on healthcare systems, resulting in many routine diagnostic procedures either being halted or postponed. Aims To evaluate whether the diagnoses of colorectal, gastric and pancreatic cancers have been impacted by the SARS-CoV-2 pandemic in Italy. Methods A survey designed to collect the number of histologically-proven diagnoses of the three cancers in gastroenterology services across Italy from January 1 to October 31 in 2017–2020. Non-parametric ANOVA for repeated measurements was applied to compare distributions by years and macro-areas. Results Compared to 2019, in 2020 gastric cancer diagnoses decreased by 15.9%, CRC by 11.9% and pancreatic by 9.9%. CRC distributions showed significant differences between all years, stomach cancer between 2018 and 2020 and 2019–2020, and pancreatic cancer only between 2017 and 2019. The 2019–2020 comparison showed fewer CRC diagnoses in the North (-13.7%), Center (-16.5%) and South (-4.1%), fewer stomach cancers in the North (-19.0%) and South (-9.4%), and fewer pancreatic cancers in the North (-14.1%) and Center (-4.7%), with an increase in the South (+12.3%). Distributions of CRC and gastric cancer were significantly different between all years in the North. Conclusions This survey highlights the concerning effects of the COVID-19 pandemic on the diagnostic yield of gastroenterology services for stomach, colorectal and pancreatic cancers in Italy.

Background: Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality among patients with cirrhosis. The risk of HCC recurrence after a complete response among patients treated with direct-acting antivirals (DAAs) has not been fully elucidated yet. Aim: To assess the risk of HCC recurrence after DAA therapy for hepatitis C virus (HCV). Methods: A systematic review across PubMed, Scopus and Scholar up to November 2020, including full-text studies that assessed the pattern of HCC recurrence after DAA therapy for HCV. Random-effect meta-analysis and univariable metaregression were applied to obtain pooled estimates for proportions and relative risk (RR) and variables influential for the outcome, respectively. Results: Thirty-one studies with 2957 patients were included. Overall, 30% (CI, 26–34%) of the patients with a history of HCC experienced HCC recurrence after DAA therapy, at mean time intervals ranging from 4 to 21 months. This result increased when going from European studies (23%, CI, 17–28%) to US studies (34%, CI, 30–38%), to Egyptian studies (37%, CI, 27–47%), and to Asian studies (33%, CI, 27–40%). Sixty-eight percent (CI, 45–91%) of recurrent HCCs developed within 6 months of follow-up since DAA treatment, among the eight studies providing stratified data. Among the studies providing head-to-head comparisons, the HCC recurrence risk was significantly lower after DAA therapy than IFN (RR, 0.64; CI, 0.51–0.81), and after DAA therapy than no intervention (RR, 0.68; CI, 0.49–0.94). Conclusions: The recurrence of HCC after DAA is not negligible, being higher soon after the end of treatment and among non-European countries. DAA therapy seems to reduce the risk of HCC recurrence compared to an IFN regimen and no intervention.

BackgroundAlthough evidence suggests frequent gastrointestinal (GI) involvement during coronavirus disease 2019 (COVID-19), endoscopic findings are scarcely reported.AimsWe aimed at registering endoscopic abnormalities and potentially associated risk factors among patients with COVID-19.MethodsAll consecutive patients with COVID-19 undergoing endoscopy in 16 institutions from high-prevalence regions were enrolled. Mann-Whitney U, χ2 or Fisher’s exact test were used to compare patients with major abnormalities to those with negative procedures, and multivariate logistic regression to identify independent predictors.ResultsBetween February and May 2020, during the first pandemic outbreak with severely restricted endoscopy activity, 114 endoscopies on 106 patients with COVID-19 were performed in 16 institutions (men=70.8%, median age=68 (58–74); 33% admitted in intensive care unit; 44.4% reporting GI symptoms). 66.7% endoscopies were urgent, mainly for overt GI bleeding. 52 (45.6%) patients had major abnormalities, whereas 13 bled from previous conditions. The most prevalent upper GI abnormalities were ulcers (25.3%), erosive/ulcerative gastro-duodenopathy (16.1%) and petechial/haemorrhagic gastropathy (9.2%). Among lower GI endoscopies, 33.3% showed an ischaemic-like colitis.Receiver operating curve analysis identified D-dimers >1850 ng/mL as predicting major abnormalities. Only D-dimers >1850 ng/mL (OR=12.12 (1.69–86.87)) and presence of GI symptoms (OR=6.17 (1.13–33.67)) were independently associated with major abnormalities at multivariate analysis.ConclusionIn this highly selected cohort of hospitalised patients with COVID-19 requiring endoscopy, almost half showed acute mucosal injuries and more than one-third of lower GI endoscopies had features of ischaemic colitis. Among the hospitalisation-related and patient-related variables evaluated in this study, D-dimers above 1850 ng/mL was the most useful at predicting major mucosal abnormalities at endoscopy.Trial registration numberClinicalTrial.gov (ID: NCT04318366).

Background: Colonoscopy is frequently performed in industrialised countries. Inappropriate colonoscopies might lead to unnecessary exams, increasing risks and costs. Aim: To estimate the impact of colonoscopy appropriateness in terms of gain in additional diagnoses and sparing of unnecessary exams. Methods: Systematic review including studies reporting the prevalence of relevant findings, colorectal cancer (CRC) and inflammatory bowel disease (IBD) according to colonoscopy appropriateness as defined by the American Society for Gastrointestinal Endoscopy and European Panel on Appropriateness of Gastrointestinal Endoscopy. Results: Twenty-one studies with 19,822 patients were included. Colonoscopy was appropriate in 15,162 (71%, CI 64%-78%). Appropriateness significantly increased the probability of relevant findings (34% vs. 18%; RR 1.81, CI 1.53-2.14), CRC (7% vs. 2%; RR 3.62, CI 2.44-5.37) and IBD (6% vs. 4%; RR 1.86, CI 1.09-3.19). Appropriateness had sensitivity 88% (CI 85%-91%), 97% (CI 93%-98%) and 89% (CI 80%-94%), and specificity 24% (CI 20%-29%), 22% (CI 18%-26%) and 24% (CI 20%-28%) for relevant findings, CRC and IBD, respectively. On average, performing colonoscopy with appropriate indication would find 15 (CI 10-21) more relevant findings, five (CI 3-9) more CRCs and three (CI 1-9) more diagnoses of IBD per 100 patients, and save 24 (CI 20-29), 22 (CI 18-26) and 24 (CI 20-28) examinations per 100 patients for relevant findings, CRC and IBD, respectively. Conclusions: Appropriateness affects the diagnostic yield of colonoscopy for CRC, IBD and relevant findings. Appropriateness criteria are useful, although integrated with clinical evaluation of the patient.

Background: Little is known on practice patterns of endoscopists for the management of Barrett’s esophagus (BE) over the last decade. Aims: Our aim was to assess practice patterns of endoscopists for the diagnosis, surveillance and treatment of BE. Methods: All members of the Italian Society of Digestive Endoscopy (SIED) were invited to participate to a questionnaire-based survey. The questionnaire included questions on demographic and professional characteristics, and on diagnosis and management strategies for BE. Results: Of the 883 SIED members, 259 (31.1%) completed the questionnaire. Of these, 73% were males, 42.9% had > 50years of age and 68.7% practiced in community hospitals. The majority (82.9%) of participants stated to use the Prague classification; however 34.5% did not use the top of gastric folds to identify the gastro-esophageal junction (GEJ); only 51.4% used advanced endoscopy imaging routinely. Almost all respondents practiced endoscopic surveillance for non-dysplastic BE, but 43.7% performed eradication in selected cases and 30% practiced surveillance every 1–2years. The majority of endoscopists managed low-grade dysplasia with surveillance (79.1%) and high-grade dysplasia with ablation (77.1%). Attending a training course on BE in the previous 5years was significantly associated with the use of the Prague classification (OR 4.8, 95%CI 1.9–12.1), the top of gastric folds as landmark for the GEJ (OR 2.45, 95%CI 1.27–4.74) and advanced imaging endoscopic techniques (OR 3.33, 95%CI 1.53–7.29). Conclusions: Practice patterns for management of BE among endoscopists are variable. Attending training courses on BE improves adherence to guidelines.

Immunosuppressed patients represent a vulnerable population, that may be at a higher risk for an atypical presentation and more severe courses of coronavirus disease (COVID-19). Here, we present the case of a 27-year old liver transplant recipient with a mild case of COVID-19, who was successfully treated with antivirals and hydroxychloroquine. However, the patient developed an important drug-drug interaction, with overexposure to tacrolimus and subsequent acute kidney injury, despite the discontinuation of the immunosuppressive therapy. This pragmatic case raises several concerns about the management of immunosuppression and the treatment of COVID-19 in solid organ transplant patients.

Background Colonoscopy demands a considerable amount of resources, and little is known about its diagnostic yield among inpatients. Aims To assess indications, diagnostic yield and findings of colonoscopy for inpatients, and to identify risk factors for relevant findings and cancer. Methods Multicentre, prospective, observational study including 12 hospitals. Consecutive adult inpatients undergoing colonoscopy were evaluated from February through November 2019. Results 1,302 inpatients underwent colonoscopy. Diagnostic yield for relevant findings and cancer was 586 (45%) and 112 (8.6%), respectively. Adequate colon cleansing was achieved in 896 (68.8%) patients. Split-dose/same-day regimen was adopted in 847 (65%) patients. Factors associated to relevant findings were age ≥70 years (RR 1.32), male gender (RR 1.11), blood loss (RR 1.22) and adequate cleansing (RR 1.63). Age ≥70 years (RR 2.08), no previous colonoscopy (RR 2.69) and split-dose/same-day regimen (RR 1.59) significantly increased cancer detection. Implementing adequate cleansing and split-dose/same-day regimen in all patients would increase the diagnostic yield for any relevant findings and cancer from 43% to 70% and from 6% to 10%, respectively. Conclusion Relevant colorectal diseases and cancer were frequent among inpatients. Factors associated with detection of relevant findings were identified. Adequate colon cleansing and split-dose/same-day regimen significantly increased colonoscopy diagnostic yield.

Introduction Epidemiological studies assessing relative risk and incidence rate of esophageal cancer in patients with achalasia are scarce. We performed a long-term prospective cohort study to evaluate the risk of both squamous cell carcinoma and adenocarcinoma of the esophagus in these patients. Methods Between 1973 and 2018, patients with primary achalasia were followed by the same protocol including upper endoscopy with esophageal biopsies. Standardized incidence ratios (SIRs) with 95% confidence interval (CI) were used to estimate the relative risk of esophageal cancer in patients with achalasia compared with the sex- and age-matched general population. Results A cohort of 566 patients with achalasia (46% men, mean age at diagnosis: 48.1 years) was followed for a mean of 15.5 years since the diagnosis of achalasia. Overall, 20 patients (15 men) developed esophageal cancer: 15 squamous cell carcinoma and 5 adenocarcinoma. The risk of esophageal cancer was significantly greater than the general population (SIR 104.2, 95% CI 63.7-161), and this for both squamous cell carcinoma (SIR 126.9, 95% CI 71.0-209.3) and adenocarcinoma (SIR 110.2, 95% CI 35.8-257.2). The excess risk was higher in men than women. Annual incidence rate of esophageal cancer was only 0.24% and was higher for squamous cell carcinoma (0.18%) than adenocarcinoma (0.06%). Discussion Patients with achalasia have an excess risk of developing both squamous cell carcinoma and adenocarcinoma of the esophagus; however, this prospective cohort study confirms that the annual incidence of esophageal cancer is rather low. These findings may have implications for endoscopic surveillance of patients with achalasia.

Background: Bismuth quadruple (BQT) and non-bismuth quadruple (N-BQT) therapies are the recommended first-line treatments for Helicobacter (H.) pylori infection. Objective: To compare the efficacy of BQT and N-BQT in clinical practice in an area with high clarithromycin resistance, choosing the regimen on the basis of previous exposure to clarithromycin. Methods: A total of 404 consecutive Hpylori-positive, naïve patients were enrolled. A total of 203 patients without previous exposure to clarithromycin received N-BQT, 100 patients for 10days and 103 for 14days, whereas 201 with previous exposure to clarithromycin received 10-day BQT. Efficacy and treatment-related adverse events were assessed. Results and Conclusions: Eradication rates by intention-to-treat analysis were 88.2% for N-BQT and 91.5% for BQT (P=.26); per-protocol analysis eradication rates were 91.2% and 95.8% for N-BQT and BQT, respectively (P=.07). Eradication rates were significantly higher with 14-day than 10-day CT (P&nbsp

Gastric cancer (GC) is the fifth most common cancer worldwide, and mortality rates are still high. Primary preventive strategies, aimed to reduce risk factors and promote protective ones, will lead to a decrease in GC incidence. Helicobacter pylori infection is a well-established carcinogen for GC, and its eradication is recommended as the best strategy for the primary prevention. However, the role of other factors such as lifestyle, diet, and drug use is still under debate in GC carcinogenesis. Unfortunately, most patients with GC are diagnosed at late stages when treatment is often ineffective. Neoplastic transformation of the gastric mucosa is a multistep process, and appropriate diagnosis and management of preneoplastic conditions can reduce GC-related mortality. Several screening strategies in relation to GC incidence have been proposed in order to detect neoplastic lesions at early stages. The efficacy of screening strategies in reducing GC mortality needs to be confirmed. This review provides an overview of current international guidelines and recent literature on primary and secondary prevention strategies for GC.

Background: Gastro-oesophageal reflux symptoms are common in the community and may lead to the development of Barrett’s oesophagus (BO). However, potential risk factors for the development of BO in patients with gastro-oesophageal reflux symptoms are controversial. We performed a systematic review and meta-analysis to examine this issue. Methods: Medline, Embase, and Embase Classic were searched (until October 2020) to identify cross-sectional studies that reported the prevalence of BO based on presence of one or more risk factors (age, non-steroidal anti-inflammatory drug (NSAID) and/or aspirin use, Helicobacter pylori status, hiatal hernia, Body mass index, and tobacco or alcohol consumption) in individuals with gastro-oesophageal reflux symptoms.The prevalence of BO was compared according to presence or absence of each these risk factors in individuals with gastro-oesophageal reflux symptoms using an odds ratio (OR), with a 95% confidence interval (CI). Findings: Of 6593 citations evaluated, 15 studies reported the prevalence of BO in 12,113 subjects. Pooled prevalence of histologically-confirmed BO in individuals with gastro-oesophageal reflux symptom sin all studies was 7.2%(95% CI: 5.1% to 9.6%).Prevalence was significantly higher in subjects with hiatal hernia (OR 2.74; 95% CI 1.58 to 4.75) and in those who drank alcohol (OR 1.51; 95% CI 1.17 to 1.95). Interpretation: The prevalence of BO in individuals with gastro-oesophageal reflux symptoms was significantly higher in those who drank alcohol, although the association was modest. The strongest association found was between hiatal hernia and BO. Most potential risk factors did not appear to be associated with presence of BO, questioning whether they are directly involved in its development. Funding: None. Declaration of Interests:The Authors declare no competing interests. Ethics approval Statement: Not required.

Background: Many countries have adopted the fecal immunochemical test (FIT) as the primary colorectal cancer (CRC) screening tool; however, its accuracy is limited. Epidemiological studies have shown that obesity and type 2 diabetes increase risk for the disease. Objective: The objective of this article is to evaluate the association of colorectal polyps and cancer with comorbidities and lifestyle factors in a population that is part of a FIT-based CRC screening program. Methods: Between 2005 and 2013, we analyzed 3894 FIT + patients who underwent total colonoscopy. The impact of lifestyle factors on polyps and cancer was assessed using individuals with a negative colonoscopy as the control group. A multivariate logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: We collected data from 3894 FIT + patients. Obesity (OR 1.29; 95% CI 1.05–1.60) and smoking (OR 1.45; 95% CI 1.24–1.71) were significantly associated with high-risk adenomas. Smoking and heavy alcohol drinking were both independently associated with high risk of CRC (OR 1.50; 95% CI 1.10–2.04 and OR 2.29; 95% CI 1.15–4.58) and colon cancer alone (OR 1.43; 95% CI 1.01–2.02 and OR 3.09; 95% CI 1.53–6.23). Positivity to first round of FIT was associated with high-risk adenomas (OR 1.47; CI 95% 1.26–1.71) and CRC (OR 1.74; 95% CI 1.29–2.36). No associations were found for diabetes. Conclusion: In our FIT + population, lifestyle factors are significantly associated with the risk of carrying high-risk adenomas and CRC. In the future, studies could be aimed at finding better screening strategies through the development of clinical algorithms based on lifestyle changes/comorbidities.

ObjectiveEndoscopic submucosal dissection (ESD) aims to achieve en bloc resection of non-pedunculated colorectal adenomas which might be indicated in cases with superficial submucosal invasive cancers (SMIC), but the procedure is time consuming and complex. The prevalence of such cancers is not known but may determine the clinical necessity for ESD as opposed to the commonly used piecemeal mucosal resection (endoscopic mucosal resection) of colorectal adenomas. The main aim was to assess the prevalence of SMIC SM1 (ie, invasion ≤1000 µm or less than one-third of the submucosa) on colorectal lesions removed by ESD.DesignA literature review was conducted using electronic databases (up to March 2017) for colorectal ESD series reporting the histology of the dissected lesions.Results51 studies with data on 11 260 colorectal dissected lesions were included. Most resected lesions (82.2%; 95% CI 78.8% to 85.3%) were adenomas (low- and high-grade dysplasia, 26.8% and 55.4%, respectively). Overall, 15.7% were submucosal cancers, but only slightly more than half (8.0%; 95% CI 6.1% to 10.3%) had an infiltration depth of ≤1000 µm, providing a number needed to treat (NNT) to avoid one surgery of 12.5. Estimating an oncologically curative (R0; G1/2; L0/V0) resection rate of 75.3% (95% CI 52.2% to 89.4%) for malignant lesions, the prevalence of curative resection lowered to 6% (95% CI 4.2% to 7.2%) with an NNT of 16.7.ConclusionThe low prevalence of SMIC SM1 in lesions selected for ESD as well as the even lower rate of curative resection limits the clinical applicability of endoscopic en bloc resection. This calls for caution over an indiscriminate use of this technique in the resection of colorectal neoplasia.

Global eradication of Hepatitis C Virus (HCV) is hindered by infection persistence among high-prevalence ethnic groups with insufficient access to care. Educational interventions to raise awareness on HCV have led to identification of submerged HCV cases. Our aim was to evaluate the effectiveness of a web-based platform to assess and raise the awareness of HCV among Pakistani people living in northern Italy. We created a website in Italian and Urdu language (https://survey-hcv6.webnode.it), and shared it to Pakistani people in Emilia-Romagna through Facebook groups. Participants had to fill a 15-item questionnaire on HCV infection, then watch a video on HCV, and respond to the questionnaire again. McNemar's chi-square and negative binomial multivariable regression analysis yielding incidence rate ratio (IRR) were applied. 339 subjects from 600 (57%) participated and filled the baseline questionnaire. The knowledge on HCV infection was scanty. For instance, 32% were not aware of HCV, 42% only knew that HCV infection may be long term, and only 14% knew the access to DAA treatment is provided by the Health Service. Independent predictors of worse knowledge on HCV were male gender (IRR 1.19), low instruction level (IRR 1.26), Urdu language preference (IRR 1.22), past use of intravenous drugs (1.2) and no previous HCV testing (IRR 1.36). The educational video significantly improved the knowledge on HCV among 67 subjects who refilled the questionnaire, as 97% were later aware of HCV, 99% of the long-term duration of HCV infection and 93% of the access to DAAs provided by Italian Health Service. We found a modest level of knowledge on HCV infection among Pakistani people in northern Italy, identifying predictors of worse awareness. We provided a multimedia platform which significantly improved the knowledge on HCV infection. Consequently, this approach might translate into an improved linkage to care.