Diana Zaffalon

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Background: Real-world data on dupilumab for eosinophilic esophagitis (EoE), particularly regarding flexible dosing and fibrostenotic phenotypes, are scarce. Objective: To evaluate the effectiveness and safety of dupilumab in clinical practice using the EoE CONNECT registry. Methods: This cross-sectional analysis included all patients prospectively recruited in the largest European multicenter EoE registry. Baseline characteristics, dosing regimens (300 mg weekly vs. semi-weekly), clinico-histological response (CHR), dose adjustments, and treatment tolerability were assessed. Results: We analyzed 161 patients (145 adults; 16 adolescents). At baseline, 69.1% of patients displayed endoscopic fibrotic features (rings/strictures). After a median of 6.5 months, peak eosinophil count decreased from 57±45 to 8±19 eos/hpf, EREFS score declined from 3.0±1.6 to 1.3±1.3, and DSS improved from 5.8±3.7 to 2.5±2.8 (all p<0.001). CHR was achieved by 86.0% of patients on 300 mg weekly and 81.2% on semi-weekly dosing (p=0.57). Multivariate analysis identified severe atopy as the reason for starting dupilumab as the strongest predictor for semi-weekly regimen choice (OR: 26.9; p<0.001), with conjunctivitis, asthma, and having two or more food allergies being significant. Both regimens were equally effective in reducing peak eos/hpf, symptomatology and EREFS. Dose tapering from weekly to semi-weekly/monthly was successful in all evaluable cases (8/8), while dose escalation from semi-weekly to weekly rescued 80% (4/5) of non-responders. Discontinuation occurred only in 8 patients (5%), primarily due to adverse events. Conclusion: Dupilumab is effective and safe in real-world EoE management, with no significant differences between weekly and semi-weekly induction. Efficacy was generally regained after escalation or maintained after dose tapering.

Introduction: The risk stratification of gastric cancer (GC) is graded by assessing well‐established precursor lesions, glandular atrophy (GA), and intestinal metaplasia (IM), resulting in both the operative link on gastritis assessment (OLGA), and intestinal metaplasia (OLGIM) systems. Although the OLGIM stage is reproducible among pathologists, the OLGA system is laborious to calculate and has poor reproducibility. In addition, it does not comprehensively address the severity of both GA and IM as recommended by the Sydney consensus. We aimed to propose the Operative Link on Gastric Intestinal Metaplasia and Glandular Atrophy Assessment (OLGIMA) system, which identifies OLGIM III–IV and upstages 0–II with advanced GA. Methods: A cross‐sectional study of consecutive diagnostic gastroscopies in adults was designed. Systematic gastric biopsies were taken. The updated Sydney guidelines were used for histological grading of GA and IM. Higher GC risk was defined as OLGIM III–IV and advanced GA. Results: The OLGIMA stage was assessed based on the most severe GA and/or IM findings in both antrum and corpus. We included 998 patients (median age 57; 64% women; 35% Helicobacter pylori infection). Thirty‐nine (3.9%) patients had higher GC risk: 17 (1.7%) with OLGIM III–IV; 12 (1.2%) with advanced GA, and 10 (1%) meeting both criteria. Among OLGIM 0‐II, 12 (1.2%) patients had advanced GA. The OLGIMA system upstaged 39 (3.9%) patients to III–IV, being more sensitive than OLGIM. Conclusions: The new OLGIMA system identifies patients at higher GC risk (OLGIMA III–IV), encompassing all OLGIM III–IV patients, and upstaging those OLGIM 0–II with advanced GA. This approach addresses the OLGA and OLGIM limitations by integrating GA and IM severity as recommended by the Updated Sydney consensus.

Early-stage colorectal carcinoma (CRC)—pT1—is a therapeutic challenge and presents some histological features related to lymph node metastasis (LNM). A significant proportion of pT1 CRCs are treated surgically, resulting in a non-negligible surgical-associated mortality rate of 1.5–2%. Among these cases, approximately 6–16% exhibit LNM, but the impact on survival is unclear. Therefore, there is an unmet need to establish an objective and reliable lymph node (LN) staging method to optimise the therapeutic management of pT1 CRC patients and to avoid overtreating or undertreating them. In this multicentre study, 89 patients with pT1 CRC were included. All histological features associated with LNM were evaluated. LNs were assessed using two methods, One-Step Nucleic Acid Amplification (OSNA) and the conventional FFPE plus haematoxylin and eosin (H&E) staining. OSNA is an RT-PCR-based method for amplifying CK19 mRNA. Our aim was to assess the performance of OSNA and H&E in evaluating LNs to identify patients at risk of recurrence and to optimise their clinical management. We observed an 80.9% concordance in LN assessment using the two methods. In 9% of cases, LNs were found to be positive using H&E, and in 24.7% of cases, LNs were found to be positive using OSNA. The OSNA results are provided as the total tumour load (TTL), defined as the total tumour burden present in all the LNs of a surgical specimen. In CRC, a TTL ≥ 6000 CK19 m-RNA copies/µL is associated with poor prognosis. Three patients had TTL > 6000 copies/μL, which was associated with higher tumour budding. The discrepancies observed between the OSNA and H&E results were mostly attributed to tumour allocation bias. We concluded that LN assessment with OSNA enables the identification of pT1 CRC patients at some risk of recurrence and helps to optimise their clinical management.

Implementation of population-based colorectal cancer screening programs has led to increases in the incidence of pT1 colorectal cancer. These incipient invasive cancers have a very good prognosis and can be treated locally, but more than half of these cases are treated with surgery due to the presence of histological high-risk criteria. These high-risk criteria are suboptimal, with no consensus among clinical guidelines, heterogeneity in definitions and assessment, and poor concordance in evaluation, and recent evidence suggests that some of these criteria considered high risk might not necessarily affect individual prognosis. Current criteria classify most patients as high risk with an indication for additional surgery, but only 2–10.5% have lymph node metastasis, and the residual tumor is present in less than 20%, leading to overtreatment. Patients with pT1 colorectal cancer have excellent disease-free survival, and recent evidence indicates that the type of treatment, whether endoscopic or surgical, does not significantly impact prognosis. As a result, the protective role of surgery is questionable. Moreover, surgery is a more aggressive treatment option, with the potential for higher morbidity and mortality rates. This article presents a comprehensive review of recent evidence on the clinical management of pT1 colorectal cancer. The review analyzes the limitations of histological evaluation, the prognostic implications of histological risk status and the treatment performed, the adverse effects associated with both endoscopic and surgical treatments, and new advances in endoscopic treatment.

Background Current guidelines recommend genetic counseling and intensive colonoscopy surveillance for patients with ≥ 10 colorectal adenomas based on scarce data. We investigated the prevalence of this condition in a fecal immunochemical test (FIT)-based colorectal (CRC) screening program, and the incidence of metachronous lesions during follow-up. Methods We retrospectively included all FIT-positive participants with ≥ 10 adenomas at index colonoscopy between 2010 and 2018. Surveillance colonoscopies were collected until 2019. Patients with inherited syndromes, serrated polyposis syndrome, total colectomy, or lacking surveillance data were excluded. The cumulative incidence of CRC and advanced neoplasia were analyzed by Kaplan–Meier analysis. Risk factors for metachronous advanced neoplasia were investigated by multivariable logistic regression analysis. Results 215 of 9582 participants (2.2 %) had ≥ 10 adenomas. Germline genetic testing was performed in 92 % of patients with ≥ 20 adenomas, identifying two inherited syndromes (3.3 %). The 3-year cumulative incidence of CRC and advanced neoplasia were 1 % and 16 %, respectively. In 39 patients (24.2 %), no polyps were found on first surveillance colonoscopy. The presence of an advanced adenoma was independently associated with a higher risk of advanced neoplasia at first surveillance colonoscopy (odds ratio 3.91, 95 %CI 1.12–13.62; P = 0.03). Beyond the first surveillance colonoscopy, the risk of metachronous advanced neoplasia was lower. Conclusions The prevalence of ≥ 10 adenomas in a FIT-based CRC screening program was 2.2 %; a small proportion of inherited syndromes were detected, even amongst those with ≥ 20 adenomas. A low rate of post-colonoscopy CRC was observed and the risk of advanced neoplasia beyond the first surveillance colonoscopy tended to progressively decrease throughout successive follow-ups. ^* Joint senior authors Received: 14 May 2021 Accepted after revision: 04 October 2021 Accepted Manuscript online: 04 October 2021 Article published online: 21 December 2021 © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

BACKGROUND: Clinical guidelines recommend either a clear-liquid diet or a low-fiber diet for colonoscopy preparation. Participants in a screening program are usually motivated healthy individuals in which a good tolerability is important to improve adherence to potential surveillance colonoscopies. OBJECTIVE: Our aim was to assess whether or not a normocaloric low-fiber diet followed the day before a screening colonoscopy compromises the efficacy of bowel cleansing and may improve the tolerability of bowel preparation. DESIGN: This is a randomized, endoscopist-blinded, noninferiority clinical trial. SETTINGS: The study was conducted at a tertiary care center. PATIENTS: A total of 276 consecutive participants of the Barcelona colorectal cancer screening program were included. INTERVENTION: Participants were randomly assigned to a clear-liquid diet or a normocaloric low-fiber diet the day before the colonoscopy. Both groups received 4 L of polyethylene glycol in a split-dose regimen. MAIN OUTCOME MEASURES: Primary outcome was the adequate bowel preparation rate measured with the Boston bowel preparation scale. Secondary outcomes included tolerability, fluid-intake perception, hunger, side effects, and acceptability. RESULTS: Participants in both groups were similar in baseline characteristics. Adequate bowel preparation was achieved in 89.1% vs 95.7% in clear-liquid diet and low-fiber diet groups, showing not only noninferiority, but also superiority (p = 0.04). Low-fiber diet participants reported less fluid-intake perception (p = 0.04) and less hunger (p = 0.006), with no differences in bloating or nausea. LIMITATIONS: The single-center design of the study could limit the external validity of the results. The present findings may not be comparable to other clinical settings. CONCLUSION: A normocaloric low-fiber diet the day before a screening colonoscopy achieved better results than a clear-liquid diet in terms of adequate colon preparation. Moreover, it also improved the perception of hunger and excessive fluid intake. Registered at clinicaltrials.gov: NCT02401802. See Video Abstract at http://links.lww.com/DCR/A829.

International guidelines recommend a routine colonoscopy to rule out advanced neoplasm after an acute diverticulitis event. However, in recent years, this recommendation has been called into question following the advent of computerized tomography (CT), particularly with regard to uncomplicated diverticulitis. Furthermore, colonoscopy is associated with a risk and additional costs. to understand the diagnostic yield, quality and safety of colonoscopy in the setting of acute diverticulitis. this was a retrospective study of all patients diagnosed with acute diverticulitis via CT between 2005 and 2013, who subsequently underwent a colonoscopy. two hundred and sixteen patients diagnosed with acute diverticulitis via CT were enrolled. These included 58 cases with complicated diverticulitis (27%) and 158 with uncomplicated diverticulitis (73%). An advanced neoplasm was found in 12 patients (5.6%); 11.7% were complicated and 3.2% were uncomplicated (p = 0.02). No major complications were identified. The quality was low but improved over time; the complete procedure rate was 88%, an effective preparation was achieved in 75% and excision of polyps < 2 cm was performed in 78% of cases. The optimum colonoscopy quality cu-off was 9.5 weeks. routine colonoscopy is advisable after a complicated diverticulitis event but its recommendation is unclear with regard to uncomplicated episodes. Colonoscopy is safe even when performed early. The overall quality is low but may be optimized via a subsequent endoscopy, two months after a diverticulitis diagnosis.