Colon Cancer Screening and the End of Life: Is Age Just a Number?

Age is the strongest risk factor for colorectal cancer. Although there is updated guidance for the age at which to start screening, there is little guidance for individuals or their medical teams on how to decide when to stop. Current recommendations from the US Preventive Services Task Force and other societies focus primarily on age. For patients older than 85 years, guidelines discourage screening because the harms largely outweigh benefits. Although at a population level, the overall benefit of screening in older individuals decreases, one must individualize the recommendation based on comorbidities, functional status, screening history, and gender-not solely base it on age. Patient and caregiver preferences must also be thoroughly explored. Current models struggle with incorporating other colorectal cancer risk factors such as family history, previous adenomas, and modality of previous screening into recommendations and simulations, but are likely to improve with machine learning and whole electronic health record prediction-based approaches.

Microbiota or placebo after antimicrobial therapy for recurrent Clostridioides difficile at home: A clinical trial with novel home-based enrollment.

INTRODUCTION: Clostridiodes difficile infection is the leading cause of infectious diarrhea in the United States, with substantial morbidity and mortality. Recurrent infection is especially challenging, with each recurrence increasing the likelihood of a successive recurrence, leading to cycles of prolonged symptoms, frequent antimicrobial use, and decreased quality of life. Fecal microbiota transplantation to prevent recurrent infection is a promising intervention with a large effect size in observational studies, but with conflicting results from randomized controlled trials. We are conducting a Veterans Affairs-wide randomized controlled trial utilizing centralized case identification, with enrollment and fecal microbiota transplant administration occurring at the participant's home. This type of trial design significantly improves trial efficiency, greatly decreases trial cost, increases consistency of trial administration, and most importantly makes nationwide clinical trials in less-common diseases possible. METHODS: This is a randomized comparison of capsule-delivered fecal microbiota transplant for the prevention of recurrent Clostridiodes difficile infection, administered after successful initial treatment of recurrent C. difficile infection with standard therapy. The primary endpoint is the incidence of recurrent C. difficile infection or death. Cases are identified by searching the Veterans Affairs Corporate Data Warehouse, with central study coordinators then reaching out to potential participants. Individuals meeting inclusion criteria and interested in participation are scheduled for in-home consent, randomization, and capsule administration, followed by telephone follow-up for 6 months. To mitigate risks of COVID-19, enrollment via video visits has been implemented. RESULTS: A total of 102 participants have been enrolled through January 2021. Centralized case identification and in-home enrollment has facilitated enrollment from 34 unique states, with 38% being from rural or highly rural areas. DISCUSSION: Centralized case identification and in-home enrollment is a feasible and innovative method of conducting randomized controlled trials in the Veterans Affairs system, improving access to clinical research for populations who may have difficulty engaging with the traditional model of clinical trials where enrollment is based at large hospitals in major metropolitan areas.

Immunophenotypic Comparison of Neoplasms of the Appendix, Right Colon, and Left Colon in Search of a Site-Specific Phenotypic Signature.

Aims. The proximal colon derives from the midgut endoderm, the distal one third derives from the hindgut endoderm, and the distal anal canal is of ectodermal origin. At least 5 molecular subtypes of colorectal carcinomas (CRC) have been identified, and some have a marked preferential right-sided location. Histologically, some CRC are much more common in the appendix. We hypothesized that these findings suggest the existence of diverse molecular genetic colonic subregions and compared the expression of classic and recently discovered colorectal markers in tumors at various locations to determine if a site-specific immunophenotypic signature could be identified. Methods and Results. Immunostains for CK7, CK20, MUC2, MUC5AC, MUC6, SATB2, DCR3/TNF6B, CDX2, Ki-67, and MMR proteins were performed on 17 appendiceal low-grade mucinous neoplasms and 6 crypt cell adenocarcinomas of the appendix, 15 right-sided and 15 left-sided mucinous adenocarcinomas, 17 right-sided and 15 left-sided conventional adenocarcinomas, and 5 signet ring cell adenocarcinomas (SRCCA). Statistically significant differences in the expression of MUC2, MUC5AC, MUC6, CK7, and SATB2 by site and/or histologic type were documented. MMR deficiency showed a significant correlation with MUC5AC and MUC6 expression. DCR3, CDX2, and CK20 expression was consistent throughout the colon. A CK7+/CK20+ phenotype was most common in appendiceal tumors and SRCCA. Conclusions. Statistically significant differences in the expression of some markers by histologic type and site were documented, supporting the existence of regional molecular genetic heterogeneity in the colon that result in site-specific epigenetic susceptibilities, tumor phenotypes, and immunophenotypes.

Differentiating Clostridium difficile Colitis from Clostridium difficile Colonization in Ulcerative Colitis: A Role for Procalcitonin.

BACKGROUND/AIMS: Clostridium difficile infection (CDI) frequently complicates ulcerative colitis (UC) and can mimic disease flare. Differentiating UC flare from CDI remains a clinical challenge, particularly due to C. difficile colonization. Procalcitonin (PCT) is a serum biomarker for bacterial infections. We hypothesized that PCT would differentiate acute CDI from UC flare and C. difficile colonization. METHODS: A single-center prospective cohort study was conducted from 2013 to 2016. All UC patients with a stool sample for C. difficile testing were eligible. A total of 117 patients were enrolled, while 20 were excluded. Chart review was performed. RESULTS: Among 27 patients with CDI, median PCT was 60.7 (range 26-560.6) pg/mL, while among 90 patients without CDI, median PCT was 56.7 (range 25.1-2,252) pg/mL (p = 0.9). It was found that 14 patients with CDI responded completely to C. difficile treatment (CDI-R), while 8 patients did not and were diagnosed with UC flare (CDI-NR). For CDI-R, median PCT was 104.5 (range 26.3-560.6), compared to 40.3 (range 26.0-116.3) for CDI-NR (p = 0.036). CONCLUSIONS: In UC patients presenting with diarrhea, serum PCT was not significantly higher in UC patients with positive C. difficile testing. However, PCT was significantly elevated in CDI-R versus CDI-NR, suggesting that PCT may have utility in making this discrimination.

Endoscopic Mucosal Healing Predicts Favorable Clinical Outcomes in Inflammatory Bowel Disease: A Meta-analysis.

BACKGROUND: Mucosal healing (MH) in inflammatory bowel disease has been associated with improved long-term clinical outcomes. Uncertainty remains as to the magnitude of this effect and to how this association changes with time and degree of healing. METHODS: PubMed, EMBASE, and Web of Science searches identified 1570 citations. Screening of abstracts identified 155 articles for full-text review, of which 19 met inclusion criteria. For 3 outcomes of interest (surgeries, hospitalizations, remission), weighted random-effects meta-analysis was performed. RESULTS: In pooled analysis, MH predicted fewer major abdominal surgeries (relative risk [RR], 0.34; 95% confidence interval [CI], 0.26-0.46), increased remission (RR, 1.84; 95% CI, 1.43-2.36), and fewer hospitalizations (RR, 0.58; 95% CI, 0.42-0.78). Complete MH and partial MH both showed significantly higher rates of favorable outcomes. Separate analyses for Crohn's disease and ulcerative colitis showed identical patterns for surgeries and remission. When subjects with no healing were excluded, and complete versus partial healing was compared, rates of surgery were not significantly different (RR, 0.82; 95% CI, 0.46-1.44). However, complete healing was superior in predicting corticosteroid-free remission (RR, 1.71; 95% CI, 1.24-2.34). Meta-regression found that the predictive power of this complete versus partial healing distinction was strongly associated with the duration of follow-up after endoscopy. CONCLUSIONS: MH is a strong predictor of fewer surgeries, long-term clinical remission, and fewer hospitalizations. Complete healing is not significantly more favorable than partial healing for predicting surgeries or hospitalizations, but it did predict higher rates of clinical remission. This benefit of complete MH over partial healing increases with follow-up time.

Factors associated with poor outcomes in adults with newly diagnosed ulcerative colitis.

It is a challenge to accurately identify patients with early stage ulcerative colitis (UC) who are at highest risk for a poor outcome and therefore might require salvage therapy. Several epidemiologic and clinical studies have analyzed factors associated with poor prognosis and increased risk for colectomy. We review prognostic factors for adults with newly diagnosed UC and discuss which patients might benefit from rapid and progressive therapy. Patients with poor prognoses tend to be young nonsmokers with high levels of inflammatory biomarkers, low levels of hemoglobin, and extensive disease, based on colonoscopy. We examine these risk factors in 2 hypothetical patients who have been newly diagnosed with UC.