Reporting Quality of Endoscopic Colorectal Cancer Screening Randomized Controlled Trials: Adherence to Recommendations and Interventions.

Background and Aims: In 2013, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) steering group published recommendations to standardize reporting quality in randomized controlled trials (RCTs). We aim to assess adherence to SPIRIT reporting guidelines in RCTs on endoscopic colorectal cancer (CRC) screening and participants' adherence to trial protocols. Methods: We searched databases for RCTs evaluating flexible sigmoidoscopy or colonoscopy for CRC screening published in English language through September 2023. Each eligible study was evaluated using the 8 core SPIRIT statement areas, totaling 51 points. Each item received 1 point if it met the criteria and 0 points if it did not. Adherence to SPIRIT items was calculated, and participant adherence to RCT protocols was assessed as the proportion of participants screened compared to those invited. Results: Five RCTs, including 4 on flexible sigmoidoscopy and 1 on colonoscopy, were analyzed. Adherence to SPIRIT guidance ranged from 82.4% to 92.2%. The most missed recommendation was item 2b (trial registrations), scored 0 across all studies. Additionally, item 32 (informed consent materials) scored 20%, and items 17a & b (blinding) scored 40% each. In total, 587,572 participants were randomized across the 5 RCTs. Of these, 37% (200,610) underwent CRC screening, with 69.8% (139,983/200,610) adhering to the protocol. The Nordic-European Initiative on Colorectal Cancer (NordICC) trial, employing a unique invitation method, had a lower adherence rate of 42%. Excluding this trial would raise the adherence rate to 74.3% (128,050/172,390). Conclusion: The published CRC screening trials have acceptable adherence to the SPIRIT reporting guidelines. However, reporting appended consent form materials and disclosing all WHO trial registration data can be improved.

A randomized controlled trial of efficacy and safety of Fecal Microbiota Transplant for preventing recurrent Clostridioides difficile infection.

BACKGROUND: Clostridioides difficile infection (CDI) is the most common cause of healthcare-associated infections in US hospitals with 15%-30% of patients experiencing recurrence. The aim of our randomized, double-blind clinical trial was to assess the efficacy of capsule-delivered fecal microbiota transplantation (FMT) versus placebo in reducing recurrent diarrhea and CDI recurrence. The secondary aim was FMT safety assessment. METHODS: Between 2018 and 2022, Veterans across the Veterans Health Administration system with recurrent CDI who responded to antibiotic treatment were randomized in a 1:1 ratio to oral FMT or placebo capsules. Randomization was stratified by number of prior CDI recurrences (1 or ≥2). The primary endpoint was clinical recurrence by day 56, defined as >3 unformed stools daily for ≥2 days with or without laboratory confirmation of C. difficile, or death within 56 days. RESULTS: The study was stopped due to futility after meeting pre-specified criteria. Of 153 participants (76 FMT, 77 placebo) with an average age of 66.5 years, 25 participants (32.9%) in the FMT arm and 23 (29.9%) in the placebo arm experienced the primary endpoint of diarrhea and possible or definite CDI recurrence or death within 56 days of capsule administration (absolute difference 3.0%; 95% CI [-11.7%, 17.7%]). Stratification by number of recurrences revealed no statistically significant differences. There were no clinically important differences in adverse events. CONCLUSIONS: FMT therapy vs. placebo did not reduce CDI recurrence or death at 56 days. There were no meaningful differences in adverse events between treatment groups.

Severe Polypharmacy Increases Risk of Hospitalization Among Older Adults With Inflammatory Bowel Disease.

INTRODUCTION: As the inflammatory bowel disease (IBD) patient population is aging, the prevalence of polypharmacy is rising. However, data exploring the prevalence, risk factors, and clinical outcomes associated with polypharmacy among older adults with IBD are limited. The aim of the study is to determine (i) prevalence of polypharmacy (≥5 medications) and potentially inappropriate medication (PIM) utilization in older adults with IBD, (ii) changes in medications over time, (iii) predictors of polypharmacy, and (iv) the impact of polypharmacy/PIMs on 1-year hospitalization rates. METHODS: We conducted a retrospective single-center study of older adults with IBD from September 1, 2011, to December 31, 2022. Wilcoxon-signed rank and McNemar tests were used to assess changes in polypharmacy between visits, with ordinal logistic regression and Cox proportional hazards models used to determine risk factors for polypharmacy and time to hospitalization, respectively. RESULTS: Among 512 older adults with IBD, 74.0% experienced polypharmacy at the initial visit, with 42.6% receiving at least one PIM. In addition, severe polypharmacy (≥10 medications) was present among 28.6% individuals at the index visit and increased to 38.6% by the last visit ( P < 0.01). Multivariable analysis revealed that age ≥70 years, body mass index ≥30.0 kg/m 2 , previous IBD-related surgery, and the presence of comorbidities were associated with polypharmacy. Moreover, severe polypharmacy ( adj hazard ratio 1.95, 95% confidence interval 1.29-2.92), as well as PIM use ( adj hazard ratio 2.16, 95% confidence interval 1.37-3.43) among those with polypharmacy, was significantly associated with all-cause hospitalization within a year of the index visit. DISCUSSION: Severe polypharmacy was initially present in more than 25% of older adults with IBD and increased to 34% within 4 years of the index visit. Severe polypharmacy, as well as PIM utilization among those with polypharmacy, were also associated with an increased risk of hospitalization at 1 year, highlighting the need for deprescribing efforts in this population.

Sarcopenia Is a Risk Factor for Postoperative Complications Among Older Adults With Inflammatory Bowel Disease.

BACKGROUND: Sarcopenia has been associated with adverse postoperative outcomes in older age cohorts, but has not been assessed in older adults with inflammatory bowel disease (IBD). Further, current assessments of sarcopenia among all aged individuals with IBD have used various measures of muscle mass as well as cutoffs to define its presence, leading to heterogeneous findings. METHODS: In this single-institution, multihospital retrospective study, we identified all patients aged 60 years and older with IBD who underwent disease-related intestinal resection between 2012 and 2022. Skeletal Muscle Index (SMI) and Total Psoas Index (TPI) were measured at the superior L3 endplate on preoperative computed tomography scans and compared through receiver operating characteristic curve. We then performed multivariable logistic regression to assess risk factors associated with an adverse 30-day postoperative outcome. Our primary outcome included a 30-day composite of postoperative mortality and complications, including infection, bleeding, cardiac event, cerebrovascular accident, acute kidney injury, venous thromboembolism, reoperation, all-cause rehospitalization, and need for intensive care unit-level care. RESULTS: A total of 120 individuals were included. Overall, 52% were female, 40% had ulcerative colitis, 60% had Crohn's disease, and median age at time of surgery was 70 years (interquartile range: 65-75). Forty percent of older adults had an adverse 30-day postoperative outcome, including infection (23%), readmission (17%), acute kidney injury (13%), bleeding (13%), intensive care unit admission (10%), cardiac event (8%), venous thromboembolism (7%), reoperation (6%), mortality (5%), and cerebrovascular accident (2%). When evaluating the predictive performance of SMI vs TPI for an adverse 30-day postoperative event, SMI had a significantly higher area under the curve of 0.66 (95% CI, 0.56-0.76) as compared to 0.58 (95% CI, 0.48-0.69) for TPI (P = .02). On multivariable logistic regression, prior IBD-related surgery (adjusted odds ratio [adjOR] 6.46, 95% CI, 1.85-22.51) and preoperative sepsis (adjOR 5.74, 95% CI, 1.36-24.17) significantly increased the odds of adverse postoperative outcomes, whereas increasing SMI was associated with a decreased risk of an adverse postoperative outcome (adjOR 0.88, 95% CI, 0.82-0.94). CONCLUSIONS: Sarcopenia, as measured by SMI, is associated with an increased risk of postoperative complications among older adults with IBD. Measurement of SMI from preoperative imaging can help risk stratify older adults with IBD undergoing intestinal resection.

Sarcopenia has been associated with adverse postoperative outcomes in older adult populations but data among older adults with inflammatory bowel disease are limited. In our study, sarcopenia was significantly associated with adverse postoperative outcomes in older adults undergoing disease-related intestinal resection.

The Effects of Aspirin Intervention on Inflammation-Associated Lingual Bacteria: A Pilot Study from a Randomized Clinical Trial.

Several bacterial taxa enriched in inflammatory bowel diseases and colorectal cancer (CRC) are found in the oral cavity. We conducted a pilot study nested within a six-week aspirin intervention in a randomized placebo-controlled trial to test their response to aspirin intervention. Fifty healthy subjects, 50-75 years old, were randomized to receive 325 mg aspirin (n = 30) or placebo (n = 20) orally once daily for six weeks. Oral tongue swabs were collected at baseline and week six. We estimated the association between aspirin use and the temporal changes in the relative abundance of pre-specified genus level taxa from pre- to post-treatment. The temporal change in relative abundance differed for eight genus level taxa between the aspirin and placebo groups. In the aspirin group, there were significant increases in the relative abundances of Neisseria, Streptococcus, Actinomyces, and Rothia and significant decreases in Prevotella, Veillonella, Fusobacterium, and Porphyromonas relative to placebo. The log ratio of Neisseria to Fusobacterium declined more in the aspirin group than placebo, signaling a potential marker associated with aspirin intervention. These preliminary findings should be validated using metagenomic sequencing and may guide future studies on the role of aspirin on taxa in various oral ecological niches.

Cold snare polypectomy versus cold endoscopic mucosal resection for small colorectal polyps: a meta-analysis of randomized controlled trials.

Background/Aims: Cold snare polypectomy (CSP) is routinely performed for small colorectal polyps (≤10 mm). However, challenges include insufficient resection depth and immediate bleeding, hindering precise pathological evaluation. We aimed to compare the outcomes of cold endoscopic mucosal resection (CEMR) with that of CSP for colorectal polyps ≤10 mm, using data from randomized controlled trials (RCTs). Methods: Multiple databases were searched in December 2023 for RCTs reporting outcomes of CSP versus CEMR for colorectal polyps ≤10 mm in size. Our primary outcomes were rates of complete and en-bloc resections, while our secondary outcomes were total resection time (seconds) and adverse events, including immediate bleeding, delayed bleeding, and perforation. Results: The complete resection rates did not significantly differ (CSP, 91.8% vs. CEMR 94.6%), nor did the rates of en-bloc resection (CSP, 98.9% vs. CEMR, 98.3%) or incomplete resection (CSP, 6.7% vs. CEMR, 4.8%). Adverse event rates were similarly insignificant in variance. However, CEMR had a notably longer mean resection time (133.51 vs. 91.30 seconds). Conclusions: Our meta-analysis of seven RCTs showed that while both CSP and CEMR are equally safe and effective for resecting small (≤10 mm) colorectal polyps, the latter is associated with a longer resection time.

The Role of Tumor Location on Endoscopic and Surgical Management of Malignant Colon Polyps.

BACKGROUND: Endoscopic polypectomy could be an appropriate, definitive treatment for pathologic T1 (pT1) colon polyps without high-risk features. Prior studies suggested worse prognosis for proximal versus distal advanced-stage colon cancers following curative treatment. However, there is limited evidence on the prognostic impact of tumor location for pT1s. PATIENTS AND METHODS: This was a retrospective cohort study using the Surveillance, Epidemiology, and End Results database to identify adults with T1NxMx or T1N0-3M0/x colon adenocarcinoma from 2000 to 2019. RESULTS: A total of 3398 patients underwent endoscopic polypectomy (17% proximal) and 28,334 had a partial colectomy (49% proximal) for pT1 adenocarcinoma. Following endoscopic polypectomy, 5-year overall and cancer-specific survival rates were 64% and 91% for proximal versus 83% and 96% for distal polyps, compared with 82% and 95% for proximal versus 88% and 97% for distal tumors after colectomy. In multivariable models, there was a greater difference in overall survival between proximal and distal polyps for those who underwent endoscopic versus surgical resection [hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.49-2.02 vs. HR 1.13, 95% CI 1.08-1.18]. Patients with proximal versus distal polyps who underwent polypectomy also exhibited increased cancer-specific mortality (HR 1.94, 95% CI 1.37-2.75). However, cancer-specific survival variations based on tumor location were no longer observed in patients undergoing partial colectomy (HR 1.09, 95% CI 0.98-1.21). CONCLUSIONS: Proximal tumor location was independently associated with worse overall and cancer-specific survival following endoscopic polypectomy. However, after colectomy, the cancer-specific disparity based on tumor laterality was mitigated. These findings suggest that proximal location may be considered a high-risk feature in endoscopic polypectomy.

Patient and procedural factors associated with true histology rates in patients undergoing colonoscopy with computer-aided detection of polyps.

BACKGROUND AND AIMS: Computer-aided detection (CADe) devices have been shown to increase adenoma detection rates and adenomas per colonoscopy compared to standard colonoscopies. Questions remain about whether CADe colonoscopies are mainly increasing the detection of small, nonneoplastic lesions or if they are detecting more pathologically meaningful polyps. In this analysis, we compare the true histology rate (defined as polyps with confirmation of clinically relevant histopathology) of CADe-identified polyps with polyps identified during standard colonoscopies. METHODS: Using data from the SKOUT trial, we compared the true histology rate (THR) between CADe and standard colonoscopies. We also conducted a subgroup analysis by patient, procedural, and endoscopist factors. To account for multiple testing of comparisons, we used the false discovery rate. RESULTS: A total of 1423 participants were included (CADe, n = 714; standard, n = 709). Overall, THR was similar between the CADe and standard colonoscopy arms for adenomas, sessile serrated lesions, and large hyperplastic polyps. Higher THR with CADe colonoscopy was observed in some subgroups for adenomas. Endoscopists with 11 to 20 years of experience and procedures occurring after 12 pm had significantly higher adenoma THRs in the CADe cohort. Patients younger than 65 years, male patients, and procedures with a withdrawal time of ≥8 minutes had borderline significance in the CADe device adenoma THR subgroup. CONCLUSIONS: CADe colonoscopies may hold the key to improving endoscopic quality measures, provided that the polyps identified by the CADe device are those of clinical relevance. Although the benefit and significance in the CADe group were demonstrated in this analysis, further research is warranted to ensure that the true histology is maintained when applied in real-world applications.

Rationalizing polyp matching criteria in colon capsule endoscopy: an international expert consensus through RAND (modified DELPHI) process.

Background: Colon capsule endoscopy (CCE) has gained momentum as an alternative modality for the investigation of the lower gastrointestinal tract. Of the few challenges that remain, the comparison and - eventually - matching of polyps at different timestamps leads to the potential for double reporting and can contribute to false-positive findings and inaccuracies. With the impending artificial intelligence integration, the risk of double reporting the same polyp due to the lack of information on spatial orientation underscores the necessity for establishing criteria for polyp matching. Objectives: This RAND/University of California, Los Angeles (modified Delphi) process aims to identify the key factors or components used to match polyps within a CCE video. This involves exploring the attributes of each factor to create comprehensive polyp-matching criteria based on international expert consensus. Design: A systematic qualitative study using surveys. Methods: A panel of 11 international CCE experts convened to assess a survey comprised of 60 statements. Participants anonymously rated statement appropriateness on a 1-9 scale (1-3: inappropriate, 4-6: uncertain and 7-9: appropriate). Following a virtual group discussion of the Round 1 results, a Round 2 survey was developed and completed before the final analysis. Results: The factors that were agreed to be essential for polyp matching include (1) timestamp, (2) polyp localization, (3) polyp vascular pattern, (4) polyp size, (5) time interval of the polyp appearance between the green and yellow camera, (6) surrounding tissue, (7) polyp morphology and (8) polyp surface and contour. When five or more factors are satisfied, it was agreed that the comparing polyps are likely the same polyp. Conclusion: This study has established the first complete criteria for polyp matching in CCE. While it might not provide a definitive solution for matching difficult, small and common polyps, these criteria serve as a framework to guide and facilitate the process of polyp-matching.

Creating criteria and standards for matching polyps (abnormal growth in the bowels) on colon capsule video analysis: an international expert agreement using the RAND (modified Delphi process) process Background: Doctors often use colon capsule endoscopy (CCE), a high-tech capsule with two cameras, to record and check for diseases in the small and large bowels as the capsule travels through the intestines. One of the most common conditions in the large bowel is polyps, which are abnormal growths in the lining of the bowel. Comparing and matching polyps in the same video from the capsule can be tricky as they look very similar, leading to the possibility of incorrectly reporting the same polyp twice or more. This can lead to wrong results and inaccuracies. The literature did not have any criteria or standards for matching polyps in CCE before. Aim: Using the RAND/UCLA (modified Delphi) process, this study aims to identify the key factors or components used to match polyps within a CCE video. The goal is to explore each factor and create complete criteria for polyp matching based on the agreement from international experts. Method: A group of 11 international CCE experts came together to evaluate a survey with 60 statements. They anonymously rated each statement on a scale from 1 to 9 (1-3: inappropriate, 4-6: uncertain, and 7-9: appropriate). After discussing the Round 1 results virtually, a Round 2 survey with the same but revised questions was created and completed before the final analysis of their agreement. Results: The main factors for matching polyps are 1) the timing when the polyp was seen, 2) where it is in the bowel, 3) its blood vessel pattern, 4) size, 5) the timing of its appearance between cameras, 6) surrounding tissue features, 7) its shape, and 8) surface features. If five or more of these factors match, the compared polyps are likely the same. Conclusion: This study establishes the first complete criteria for matching polyps in CCE. While it may not provide a definitive solution for matching challenging and small polyps, these criteria serve as a guide to help and make the process of polyp matching easier.

Increased Risk of Breakthrough SARS-CoV-2 Infections in Patients with Colorectal Cancer: A Population-Based Propensity-Matched Analysis.

Background/Objectives: This study aimed to investigate the association between colorectal cancer (CRC) and the risk of breakthrough respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vaccinated patients with CRC. Methods: This retrospective cohort study used the TriNetX research network to identify vaccinated patients with CRC. Patients were matched using propensity score matching (PSM) and divided into patients with CRC and control (without history of CRC) groups. The primary outcome was the risk of breakthrough SARS-CoV-2 in vaccinated patients. The secondary outcome was a composite of all-cause emergency department (ED) visits, hospitalization, and death during the follow-up period after the diagnosis of COVID-19. Results: A total of 15,416 vaccinated patients with CRC were identified and propensity matched with 15,416 vaccinated patients without CRC. Patients with CRC had a significantly increased risk for breakthrough infections compared to patients without CRC (aOR = 1.78; [95% CI: 1.47-2.15]). Patients with CRC were at increased risk of breakthrough SARS-CoV-2 infections after two doses (aOR = 1.71; [95% CI: 1.42-2.06]) and three doses (aOR = 1.36; [95% CI: 1.09-1.69]) of SARS-CoV-2 vaccine. Vaccinated patients with CRC were at a lower risk of COVID-19 infection than unvaccinated CRC patients (aOR = 0.342; [95% CI: 0.289-0.404]). The overall composite outcome (all-cause ED visits, all-cause hospitalization, and all-cause death) was 51.6% for breakthrough infections, which was greater than 44.3% for propensity score-matched patients without CRC (aOR = 1.79; [95% CI: 1.29-2.47]). Conclusions: This cohort study showed significantly increased risks for breakthrough SARS-CoV-2 infection in vaccinated patients with CRC. Breakthrough SARS-CoV-2 infections in patients with CRC were associated with significant and substantial risks for hospitalizations.