Technical failure during Colorectal Endoscopic Full Thickness Resection: The "through thick and thin" Study.

BACKGROUND: Endoscopic full-thickness resection (EFTR) is an effective and safe technique for non-lifting colorectal lesions. Technical issues or failures with full-thickness resection device (FTRD) system are reported but there are no data about their details. The aim of our study was to quantify and classify FTRD technical failures. PATIENTS AND METHODS: We performed a retrospective study involving 17 Italian centres with experience in advanced resection techniques and OVESCO devices. Each centre shared and classified all the consecutive failures prospectively collected during colorectal EFTR by using FTRD from 2018 to 2022. Primary outcome was technical failure rate and classification; secondary outcomes included management, clinical success, and complications' assessment in this population. RESULTS: Included lesions were mainly recurrent (52%), with mean dimension of 18.4 (± 7.5) mm. Among 750 EFTRs, failures occurred in 77 patients (35 F, mean age 68.9 ±8.9 years). A classification was proposed in type I snare uncutting (53.2%), type II clip misdeployment (31.2%) and type III cap misplacement (15.6%). Among endoscopic treatment completed, rescue EMR was performed in 57 patients (79%), allowing en-bloc and R0 resection in 71% and 64% cases, respectively. Overall adverse events rate was 27.3%. Pooled estimates for the rate of failure, complications and rescue endoscopic therapy were similar between low- and high-volume centres (p=0.08, p = 0.702 and p= 0.713). CONCLUSIONS: Colorectal EFTR with FTRD is a challenging technique with a not negligible rate of technical failure and complications. Experience in rescue resection techniques and multidisciplinary management are mandatory in this setting.

Endoscopic full-thickness resection vs. endoscopic submucosal dissection of residual/recurrent colonic lesions on scars: a retrospective Italian and Japanese comparative study.

BACKGROUND AND AIMS: Endoscopic treatment of recurrent/residual colonic lesions on scars is a challenging procedure. In this setting, endoscopic submucosal dissection (ESD) is considered the first choice, despite a significant rate of complications. Endoscopic full-thickness resection (eFTR) has been shown to be well-tolerated and effective for these lesions. The aim of this study is to conduct a comparison of outcomes for resection of such lesions between ESD and eFTR in an Italian and a Japanese referral center. METHODS: From January 2018 to July 2020, we retrospectively enrolled patients with residual/recurrent colonic lesions, 20 treated by eFTR in Italy and 43 treated by ESD in Japan. The primary outcome was to compare the two techniques in terms of en-bloc and R0-resection rates, whereas complications, time of procedure, and outcomes at 3-month follow-up were evaluated as secondary outcomes. RESULTS: R0 resection rate was not significantly different between the two groups [18/20 (90%) and 41/43 (95%); P= 0.66]. En-bloc resection was 100% in both groups. No significant difference was found in the procedure time (54 min vs. 61 min; P= 0.9). There was a higher perforation rate in the ESD group [11/43 (26%) vs. 0/20 (0%); P= 0.01]. At the 3-month follow-up, two lesions relapsed in the eFTR cohort and none in the ESD cohort (P= 0.1). CONCLUSION: eFTR is a safer, as effective and equally time-consuming technique compared with ESD for the treatment of residual/recurrent colonic lesions on scars and could become an alternative therapeutic option for such lesions.

Texture and color enhancement imaging versus high definition white-light endoscopy for detection of colorectal neoplasia: a randomized trial.

BACKGROUND: Texture and color enhancement imaging (TXI) was recently proposed as a substitute for standard high definition white-light imaging (WLI) to increase lesion detection during colonoscopy. This international, multicenter randomized trial assessed the efficacy of TXI in detection of colorectal neoplasia. METHODS: Consecutive patients aged ≥ 40 years undergoing screening, surveillance, or diagnostic colonoscopies at five centers (Italy, Germany, Japan) between September 2021 and May 2022 were enrolled. Patients were randomly assigned (1:1) to TXI or WLI. Primary outcome was adenoma detection rate (ADR). Secondary outcomes were adenomas per colonoscopy (APC) and withdrawal time. Relative risks (RRs) adjusted for age, sex, and colonoscopy indication were calculated. RESULTS: We enrolled 747 patients (mean age 62.3 [SD 9.5] years, 50.2 % male). ADR was significantly higher with TXI (221/375, 58.9 %) vs. WLI (159/372, 42.7 %; adjusted RR 1.38 [95 %CI 1.20-1.59]). This was significant for ≤ 5 mm (RR 1.42 [1.16-1.73]) and 6-9 mm (RR 1.36 [1.01-1.83]) adenomas. A higher proportion of polypoid (151/375 [40.3 %] vs. 104/372 [28.0 %]; RR 1.43 [1.17-1.75]) and nonpolypoid (136/375 [36.3 %] vs. 102/372 [27.4 %]; RR 1.30 [1.05-1.61]) adenomas, and proximal (143/375 [38.1 %] vs. 111/372 [29.8 %]; RR 1.28 [1.05-1.57]) and distal (144/375 [38.4 %] vs. 98/372 [26.3 %]; RR 1.46 [1.18-1.80]) lesions were found with TXI. APC was higher with TXI (1.36 [SD 1.79] vs. 0.89 [SD 1.35]; incident rate ratio 1.53 [1.25-1.88]). CONCLUSIONS: TXI increased ADR and APC among patients undergoing colonoscopy for various indications. TXI increased detection of polyps < 10 mm, both in the proximal and distal colon, and may help to improve colonoscopy quality indicators.

Clinical outcomes of endoscopic submucosal dissection for giant rectal tumors larger than 8 cm: A European referral center experience.

BACKGROUND AND AIMS: To date, western data on colorectal ESD are limited. This study aimed to assess the efficacy and safety of rectal ESD for superficial lesions ≥ 8 cm. METHODS: A total of 138 superficial rectal neoplasms treated by ESD were allocated in two groups: 25 in the "giant" ESD group and 113 in the control group. RESULTS: En bloc resection was achieved in 96% of cases in both groups. En bloc R0 resection rate was similar between the "giant" ESD group and the control group (84% vs 86%; p: 0.5) and curative resection was higher in the control group (81%) than in "giant" ESD group (68%) without reaching statistical significance (p: 0.2). Dissection time was significantly longer in the "giant" ESD group (251 vs 108 min; p <0.001), however, dissection speed was significantly higher (0.35 vs 0.17 cm2/min; p: 0.02).). Post-ESD stenosis was observed in 2 patients from the "giant" ESD group (8% vs 0% of control group, p: 0.03). No significant differences were found in delayed bleeding, perforation, local recurrences, and need for additional surgery. CONCLUSIONS: ESD for superficial rectal tumors ≥ 8 cm is a feasible, safe, and effective therapeutic option.

Increasing the accuracy of colorectal cancer screening.

INTRODUCTION: Colorectal cancer (CRC) is a major health issue, being responsible for nearly 10% of all cancer-related deaths. Since CRC is often an asymptomatic or paucisymptomatic disease until it reaches advanced stages, screening is crucial for the diagnosis of preneoplastic lesions or early CRC. AREAS COVERED: The aim of this review is to summarize the literature evidence on currently available CRC screening tools, with their pros and cons, focusing on the level of accuracy reached by each test over time. We also provide an overview of novel technologies and scientific advances that are currently being investigated and that in the future may represent real game-changers in the field of CRC screening. EXPERT OPINION: We suggest that best screening modalities are annual or biennial FIT and colonoscopy every 10 years. We believe that the introduction of artificial intelligence (AI)-tools in the CRC screening field could lead to a significant improvement of the screening efficacy in reducing CRC incidence and mortality in the future. More resources should be put into implementing CRC programs and support research project to further increase the accuracy of CRC screening tests and strategies.

Efficacy and safety of endoscopic resection techniques of large colorectal lesions: experience of a referral center in Italy.

BACKGROUND: Endoscopic mucosal resection and submucosal dissection (ESD) are treatments of choice for superficial neoplastic colorectal lesions. Only a few studies have compared these techniques. AIM: To compare the efficacy and safety of endoscopic piecemeal mucosal resection (EPMR), ESD and hybrid-endoscopic submucosal dissection (H-ESD) of large colorectal lesions in a Western endoscopic center. METHODS: This is a retrospective analysis on a prospective medical database of consecutive colorectal superficial lesions larger than 20 mm, resected by EPMR, ESD or H-ESD collected from 2015 to 2019. RESULTS: Two hundred twenty-nine colorectal lesions were included. All lesions were completely endoscopically resected, 65.9% by EPMR, 19.7% by ESD and 14.4% by H-ESD. Endoscopic control after the index procedure was available for 86.5% patients. Among these patients, 80% had a second follow-up colonoscopy. The overall recurrence rate was 13.2, 0 and 6.1% for EPMR, ESD and H-ESD respectively, with a significant difference between EPMR and ESD. All recurrences were endoscopically treated during follow-up procedures. Risk of complications was not significantly different between the three groups. CONCLUSIONS: EPMR, ESD and H-ESD are effective and safe procedures. Recurrence rate in EPMR was higher but can be managed endoscopically with high success rates. EPMR is faster and technically simpler so should be considered a potential first-line therapy for colorectal superficial neoplastic lesions.

Outpatient ESD for challenging colorectal lesions: Is it feasible and safe for western countries?

Background and study aims The need for hospital beds during the COVID-19 pandemic almost overwhelmed the health care systems all over the world. Therefore, elective non-life-saving procedures were postponed. We decided to perform all colorectal endoscopic mucosal dissections (ESDs) for challenging lesions as outpatient procedures, organizing an ad hoc path to management of any delayed post-procedural complications. The aim of the present study was to retrospectively evaluate the feasibility and safety of outpatient ESD for colorectal tumors. Patients and methods From March 2020 to May 2020, outpatient colorectal ESDs were performed for 15 challenging lesions. We retrospectively investigated feasibility and safety of the procedures, rates of en bloc resection, and complications rates. Results The mean age of the patients was 66.5 years and 40 % of the them were on antiplatelet/anticoagulation therapy. Median size of removed lesions was 45 mm (range 32-77) and 38 mm (range 24 to 55) Five patients (33 %) had rectal tumors extending to the dentate line and four (26.6 %) were recurrences on a scar of previous endoscopic or surgical local resections. All complications, such as bleeding or visible microperforation, were managed endoscopically and no delayed perforations occurred. One patient had fever (37.5 °C), while three patients complained of anal pain after ESD for a rectal tumor that extended to the dentate line (RTDL); all patients were managed conservatively. Conclusion Outpatient colorectal ESD is feasible and safe for challenging lesions. It reduces costs of hospitalization but direct access to the endoscopy service to manage potential post-ESD complications should always be guaranteed.

Switching from IFX originator to biosimilar CT-P13 does not impact effectiveness,safety and immunogenicity in a large cohort of IBD patients.

BACKGROUND: Switching from IFX originator to CT-P13 is safe; however, little data on immunogenicity exists. RESEARCH DESIGN AND METHODS: Consecutive IBD patients on IFX originator were switched to CT-P13 and followed-up for 12 months. Clinical activity, infliximab trough levels (ITLs), anti-drug antibodies (ATIs), and adverse events were recorded at predefined timepoints (baseline, second CT-P13 infusion, 6 and 12 months). The outcomes investigated were immunogenicity, pharmacokinetics, effectiveness and safety. RESULTS: 119 patients were switched to CT-P13 after a median time with IFX of 5.8 years. No changes in mean ITLs were observed. ATIs were detected in 30 patients (25.2%): 14 before and 16 after switch. Mean persistent ATIs were significantly higher compared to mean transient ones (109.74 ng/mL ±84.70 vs 18.22 ng/mL ±11.37, p < 0.001), with significantly lower ITLs associated (mean 0.32 µg/mL ±0.6 vs 3.08 µg/mL ±3.22, p < 0.001). A significant decrease of patients in steroid-fee clinical remission was observed after the switch (p = 0.004), with subsequent improvement at 6 months (p = 0.005). Eighteen patients (15.1%) discontinued IFX, only 6 (5%) for loss of response. CONCLUSIONS: Switching from infliximab originator to CT-P13 seems safe and effective, without differences in immunogenicity. A temporary reduction of clinical benefit after switching could be potentially explained by a 'nocebo-effect response'.

Clinical management of rheumatologic conditions co-occurring with inflammatory bowel diseases.

INTRODUCTION: Spondyloarthritis (SpA) is the most common extra-intestinal manifestation in patients with inflammatory bowel diseases (IBD). Articular disorders may also appear as 'paradoxical' effects during biologic therapy with anti-tumor necrosis factor (TNF). Areas covered: In this narrative review, we report the current knowledge about the pathogenesis, the diagnosis and the therapeutic management of articular diseases occurring in patients with IBD. Expert commentary: Evidence-based recommendations for the management of IBD-associated SpA and paradoxical arthritis are lacking. Then, collaboration between gastroenterologists and rheumatologists is mandatory to guarantee the best outcomes for these patients, from a prompt diagnosis to an appropriate therapeutic strategy. Among therapies currently available, steroids, sulfasalazine, methotrexate and anti-TNFs are recommended for both gastrointestinal and articular diseases, whereas non-steroidal anti-inflammatory drugs (NSAIDs) and etanercept are contraindicated in IBD. Thiopurines are not effective for the treatment of articular symptoms. Several agents have been recently introduced for the treatment of IBD, such as vedolizumab, a gut-selective anti-α4ß7integrin, and ustekinumab, an anti-interleukin 12/23. Their effects on SpA still need to be clarified; however, the possible contemporary administration of biologics with different molecular targets is becoming an intriguing option to cover multiple inflammatory manifestations in the same patient and is worthy of further investigation.

Adalimumab in active ulcerative colitis: a "real-life" observational study.

BACKGROUND AND AIMS: The effectiveness of adalimumab in the treatment of ulcerative colitis is under debate. Although controlled trials have shown that adalimumab is significantly better than placebo, the absolute clinical benefit is modest. We report data on the effectiveness of adalimumab in a cohort of ulcerative colitis patients treated in 22 Italian centres. METHODS: All patients with active disease treated with adalimumab were retrospectively reviewed. Co-primary endpoints were clinical remission at weeks 4, 12, 24 and 54. Secondary endpoints were sustained clinical remission, steroid discontinuation, endoscopic remission and need for colectomy. RESULTS: Eighty-eight patients were included. Most patients had received previous infliximab treatment. Clinical remission rates were 17%, 28.4%, 36.4% and 43.2% at 4, 12, 24 and 54 weeks respectively. Twenty-two patients required colectomy. Clinical remission and low C-reactive protein at week 12 predicted clinical remission at week 54 (OR 4.17, 95% CI 2.36-19.44; OR 2.63, 95% CI 2.32-14.94, respectively). Previous immunosuppressant use was associated with a lower probability of clinical remission at week 54 (OR 0.67, 95% CI 0.08-0.66) and with a higher rate of colectomy (HR 9.7, 95% CI 1.46-9.07). CONCLUSION: In this large "real-life" experience adalimumab appears effective in patients with otherwise medically refractory ulcerative colitis. Patients achieving early remission can expect a better long-term outcome.

Randomized controlled trials in steroid dependent and in severe colitis.

Intravenous steroids are considered the mainstay of treatment in patients with severe ulcerative colitis. Several randomized controlled trials have been designed to evaluate drugs that, as an adjunct to intravenous steroids, could obtain a clinical response and avoid colectomy in patients who do not respond to corticosteroids. For steroid refractory patients, cyclosporine and infliximab seem to be an effective alternative to colectomy in the short term, but more data are needed to evaluate if they can prevent colectomy also in the long term. Although there is no evidence from the published trials that antibiotics as adjunctive therapy may have an additional benefit, therapeutic protocols for severe ulcerative colitis generally include antibiotics for patients with signs of toxicity, or with worsening of symptoms despite the medical treatment. No additional benefit over steroids has been shown from bowel rest. Moreover, as bowel rest deprives the colonic enterocytes of the short-chain fatty acids vital to their metabolism and repair, it may even be harmful. Conflicting results have been published on heparin as primary treatment of severe ulcerative colitis; at the present time there is no evidence supporting its use. Although "steroid-free" clinical remission is, at this time, the most important end point of clinical studies in inflammatory bowel disease, only few data are available in steroid dependent colitis patients. Azathioprine seems to be effective in inducing steroid-free remission.

Upper gastrointestinal involvement of Crohn's disease: a prospective study on the role of upper endoscopy in the diagnostic work-up.

BACKGROUND: Prevalence of upper gastrointestinal (GI) tract involvement in adult Crohn's disease (CD) has been reported to be very low (0.3-5%). In routine practice, upper endoscopy is recommended only in CD patients with upper GI symptoms. Available data concerning the prevalence of asymptomatic upper GI lesions in CD patients are controversial. The aim of this study was to prospectively evaluate the prevalence of upper GI CD involvement in CD patients, irrespective of upper GI symptoms. METHODS: A series of 119 consecutive CD patients underwent clinical assessment, including occurrence and score of upper GI symptoms, and upper endoscopy with biopsy samples for histological assessment and Helicobacter pylori (Hp) infection detection. In an attempt to further recognize the upper GI tract lesions as CD or other form of inflammation, in a subgroup of CD patients, the histological and endoscopic evaluation was repeated following 12 weeks of anti-TNF-α or other treatments in association with proton-pump inhibitors. RESULTS: Upper CD involvement was found in 19/119 (16%) patients. Hp infection was detected in 10/119 (8.4%) CD patients. Hp-negative focally active chronic gastritis was found in 34/119 (28.6%) CD patients. At presentation, 12/19 patients (63%) showing upper CD involvement were asymptomatic and 7 (37%) symptomatic. CONCLUSION: A high prevalence of upper GI tract involvement has been observed in CD patients, irrespective of upper symptoms. This finding suggests the usefulness of routine upper endoscopy in the diagnostic work-up of CD patients in order to correctly classify the distribution and extent of the disease.