Search

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.

Background and study aims Adenomas per colonoscopy (APC) and adenomas per positive patient (APP) have been proposed as additional quality indicators but their association with adenoma detection rate (ADR) is not well studied. The aim of our study was to evaluate the variability in APC and APP, their association with ADR, and associated risk factors in screening colonoscopies from a community practice. Patients and methods We calculated the APC, APP, and ADR from all screening colonoscopies performed over 5 years. We used adjusted hierarchical logistic regression to assess the association of factors with APC, APP, and ADR. Results There were 80,915 screening colonoscopies by 60 gastroenterologists. The median (Q1-Q3) APC, APP, and ADR were 0.41 (0.36 – 0.53), 1.33 (1.23 – 1.40), and 0.32 (0.28 – 0.38), respectively. Despite the high correlation between APC and ADR, 47.6 % of endoscopists with the lowest APC had a higher ADR, and no endoscopists with the highest APC had a lower ADR. Of endoscopists with the lowest APP, 74.3 % had a higher ADR and 5.6 % of endoscopists with the highest APP had a lower ADR. Factors associated with higher APC after multivariable adjustment included: older patients age (OR 1.003; 95 % CI 1.002 – 1.005), male patients (OR 1.123; 95 % CI 1.090 – 1.156), younger endoscopist age (OR 0.943; 95 % CI 0.941 – 0.945), and longer withdrawal time (OR 3.434; 95 % CI 2.941 – 4.010). Factors associated with higher APP were male sex, younger endoscopist age, and longer withdrawal time. Conclusion APC and APP provides additional information about endoscopist performance. Younger endoscopist age and longer withdrawal time are associated with colonoscopy quality.

Many gastrointestinal disorders, autoimmune diseases, and pregnancy-related conditions preferentially impact women. This issue of The American Journal of Gastroenterology focuses on women's health in the context of gastrointestinal and liver disease. This editorial highlights the current issue's contents and seeks to spark the conversations to bring awareness to the many issues faced by women as both patients and practitioners.

Prior studies have reported the prevalence of colorectal cancer (CRC) in average-risk screening population ages 50-75 to be 0.7%-1.0%.sup1,2/supHowever, no estimates from studies enrolling individuals undergoing screening colonoscopy have been reported. The experience of ongoing studies enrolling average-risk individuals is that the prevalence rates are substantially lower. A 2020 study from a community-based cohort undergoing CRC screening with fecal immunochemical testing followed by diagnostic colonoscopy reported a CRC prevalence rate of 1.46 per 1000, or 0.15%.sup3/supThe aim of our study is to report the screen-detected prevalence of CRC and advanced neoplasia in average-risk asymptomatic individuals from selected academic and community medical centers in the United States, Canada, and Germany and describe associated risk factors.

Accurate sizing of polyps and improving adenoma detection rates (ADR) are important goals for high-quality colonoscopy. Surveillance intervals are based on accurate sizing of polyps. There are no clinical tools or interventions that have demonstrated improvement in both these metrics. We investigated the efficacy of a simple, low-cost intervention, based on use of polyp sizing posters to improve measurements of polyps and increase ADRs during colonoscopy at a large gastroenterology community practice.We collected data on polyp measurements and ADRs by 62 gastrointestinal endoscopists at a large multi-site community practice, from January to November 2015 (baseline). In a prospective study, endoscopy units were given a polyp sizing poster to be hung above the endoscopy video monitor (intervention group, for 33 endoscopists) or for usual care (control group, for 29 endoscopists) in December 2015, and we collected data on polyp measurements and ADRs over the following 6 months (January-June 2016). We compared the endoscopists' assessment of polyp size and their ADRs before and after the intervention using a mixed effects proportional odds model, controlling for provider age and sex and patient and indication for colonoscopy. Our primary aim was to assess the effect of the snare and forcep-based polyp sizing poster on change in polyp size. The secondary aim was to study the effect of the polyp sizing poster on ADR.Our final analysis included 85,657 polyps from 38,307 colonoscopies. The characteristics of patients who underwent colonoscopy were similar between the control and intervention group (median age, 61 years; 48.1% female; 53.9% undergoing screening; 31.4% undergoing surveillance; 14.7% receiving a diagnostic colonoscopy). The endoscopists' median age was 51 years (range, 33-76) years, and 15 were women (24.2%). During the baseline period, male endoscopists were more likely to size polyps larger than measurements made by female endoscopists (odds ratio [OR], 1.78; 95% CI, 1.24-2.55; P = .002). For the intervention group, 78.6% of polyps were assigned to the 1-5 mm category during the baseline period compared to 76.0% after the intervention, whereas the proportions of polyps assigned to the 6-10 mm category increased from 16.9% during the baseline period to 18.3% after the intervention. In the control group, 78.9% of polyps were assigned to the 1-5 mm category during the baseline period and 78.3% were assigned to this group in the prospective study; 16.5% of polyps were assigned to the 6-10 mm during the baseline period and 17.5% were assigned to this group in the prospective study. The interaction between intervention group and timing (baseline vs after the intervention) was statistically significant, with an increase in the odds of larger polyp sizing after the intervention (OR, 1.15; 95% CI, 1.08-1.23; P.001). The odds of larger polyp measurement during the intervention period, compared to the baseline period, increased for male endoscopists (OR, 1.17; 95% CI, 1.09-1.27; P.001) and female endoscopists (OR, 1.18; 95% CI, 1.01-1.36; P = .04), as well as for younger physicians (50 years; OR, 1.32; 95% CI, 1.20-1.46; P .001) but not for older physicians (50 years; OR, 0.96; 95% CI, 0.88-1.06; P = .44). The average ADR for male and female endoscopists combined during the baseline period was 42%. The change in ADR from the baseline vs the post-intervention was an increase of 2.6% in the control group compared to 5.7% in the intervention group (P = .39) CONCLUSIONS: Placement of a polyp sizing poster above the endoscopy video monitor increases the odds of polyps being assigned a larger size but does not affect ADRs.

BACKGROUND & AIMS: Randomized trials have shown that biennial fecal occult blood test (FOBT) screening reduces mortality from colorectal cancer (CRC), but not overall mortality. Differences in benefit for men vs women, and by age, are unknown. We sought to evaluate long-term reduction in all-cause and CRC-specific mortality in men and women who comply with offered screening, and in different age groups, using individual participant data from 2 large randomized trials of biennial FOBT screening, compared with an intention to treat analysis.METHODS: We updated the CRC and all-cause mortality from the Danish CRC screening trial (n=61,933) through 30 years of follow up and pooled individual participant data with individual 30-year follow-up data from the Minnesota Colon Cancer Control trial (n=46,551). We compared the biennial screening groups to usual care (controls) in individuals 50-80 years old using Kaplan Meier estimates of relative risks and risk differences, adjusted for study differences in age, sex, and compliance.RESULTS: Through 30 years of follow up, there were 33,478 (71.9%) and 33,479 (72.2%) total deaths and 1023 (2.2%) and 1146 (2.5%) CRC deaths in the biennial screening (n=46,553) and control groups (n=46,358), respectively. Among compliers, biennial FOBT screening significantly reduced CRC mortality by 16% (relative risk [RR], 0.84; 95% CI, 0.74-0.96) and all-cause mortality by 2% (RR, 0.98; 95% CI, 0.97-0.99). Among compliers, the reduction in CRC mortality was larger for men (RR, 0.75; 95% CI, 0.62-0.90) than women (RR, 0.91; 95% CI, 0.75-1.09). The largest reduction in CRC mortality was in compliant men 60-69 years old (RR, 0.59; 95% CI, 0.42-0.81) and women 70 years and older (RR, 0.53; 95% CI, 0.30-0.94).CONCLUSIONS: Long-term CRC mortality outcomes of screening among compliers using biennial FOBT are sustained, with a statistically significant reduction in all-cause mortality. The reduction in CRC mortality is greater in men than women-the benefit in women lags that of men by about 10 years.

Background Aspirin is associated with decreased risk of colorectal cancer (CRC), potentially by modulating the gut microbiome. Aims To evaluate the effect of aspirin on the gut microbiome in a double-blinded, randomised placebo-controlled pilot trial. Methods Healthy volunteers aged 50-75 received a standard dose of aspirin (325 mg, N = 30) or placebo (N = 20) once daily for 6 weeks and provided stool samples every 3 weeks for 12 weeks. Serial measurements of gut microbial community composition and bacterial abundance were derived from 16S rRNA sequences. Linear discriminant analysis of effect size (LEfSe) was tested for between-arm differences in bacterial abundance. Mixed-effect regression with binomial distribution estimated the effect of aspirin use on changes in the relative abundance of individual bacterial taxa via an interaction term (treatment × time). Results Over the study period, there were differences in microbial composition in the aspirin vs placebo arm. After treatment, four taxa were differentially abundant across arms: Prevotella, Veillonella, Clostridium XlVa and Clostridium XVIII clusters. Of pre-specified bacteria associated with CRC (n = 8) or aspirin intake (n = 4) in published studies, interactions were significant for four taxa, suggesting relative increases in Akkermansia, Prevotella and Ruminococcaceae and relative decreases in Parabacteroides, Bacteroides and Dorea in the aspirin vs placebo arm. Conclusion Compared to placebo, aspirin intake influenced several microbial taxa (Ruminococcaceae, Clostridium XlVa, Parabacteroides and Dorea) in a direction consistent with a priori hypothesis based on their association with CRC. This suggests that aspirin may influence CRC development through an effect on the gut microbiome. The findings need replication in a larger trial. The study was registered using Clinical Trials Registration NCT02761486.

Hepatitis C treatment has rapidly evolved with the arrival of direct-acting antiviral therapy. Sustained virologic response (SVR) rates in clinical trials are high but it is unknown how this translates to the immigrant community. Data from December 2013 to September 2015 was collected from a Midwest academic and community practice with a large immigrant population. There were 802 patients with an overall SVR rate of 88%. Ledipasvir/sofosbuvir was associated with favorable response among genotype 1 and 4 patients compared to other regimens (p

Colonoscopy vs. Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM): Rationale for Study Design

The relationship between dietary and lifestyle risk factors and long-term mortality from colorectal cancer is poorly understood. Several factors, such as obesity, intakes of red meat, and use of aspirin, have been reported to be associated with risk of colorectal cancer mortality, though these findings have not been replicated in all studies to date. In the Minnesota Colon Cancer Control Study, 46,551 participants 50–80 years old were randomly assigned to usual care (control) or annual or biennial screening by fecal occult blood testing. Colon cancer mortality was assessed after 30 years of follow-up. Dietary intake and lifestyle risk factors were assessed by questionnaire at baseline. Age [hazard ratio (HR) 1.09; 95% CI 1.07, −1.11], male sex (HR 1.25; 95% CI 1.01, 1.57), and higher body mass index (BMI) (HR 1.03; 95% CI 1.00–1.05) increased the risk of CRC mortality, while undergoing screening for CRC was associated with a reduced risk of colorectal cancer mortality (HR 0.76; 95% CI 0.61–0.94 and 0.67; 95% CI 0.53–0.83 for biennial and annual screening, respectively). Intakes of grains, meats, proteins, coffee, alcohol, aspirin, fiber, fruits, and vegetables were not associated with colorectal cancer mortality. Our study confirms the relationship between BMI and long-term colorectal cancer mortality. Modulation of BMI may reduce risk of CRC mortality.

Objective Age, sex, and deprivation are known factors influencing colorectal (bowel) cancer screening uptake. We investigated the influence of these factors on uptake over time. Methods Data from the Scottish Bowel Screening Programme (SBoSP) were collected between 2007 and 2014. End-points for analysis were uptake, faecal occult blood test positivity, and disease detection, adjusted for age, sex, deprivation, and year of screening. Results From 5,308,336 individual screening episodes documented, uptake gradually increased with increasing age up to 65–69 and was lower in men than women (52.4% vs. 58.7%, respectively). Deprivation had a significant effect on uptake by men and women of all age groups, with the most deprived least likely to complete a screening test. Uptake has increased with time in both sexes and across the deprivation gradient. The number needed to screen to detect significant neoplasia was significantly lower in men than women overall (170 vs. 365), and this held over all age and deprivation groups. The number needed to screen was also lower in the more deprived population. Conclusions Although lower age, male sex, and increased deprivation are associated with lower bowel cancer screening uptake in Scotland, uptake has increased since SBoSP introduction in all age groups, both sexes, and across the deprivation gradient. Despite a lower uptake, the number needed to screen to find significant disease was lower in men and in those with higher levels of deprivation.

Sessile serrated lesions (SSLs) are important precursor lesions for the CpG island-methylated pathway to colorectal cancer. The reported detection rates of SSL are highly variable, and national or population-based estimates are not available. Patient-, provider-, and procedure-level factors associated with the detection rates of SSL have not been well described. The aim of our study was to study the detection rates of SSL, variability of rates over time, and factors associated with detection rates of SSL in a national sample of patients undergoing colonoscopy using the GIQuIC registry.We used colonoscopies submitted to the GIQuIC registry from 2014 to 2017 on adults, aged 18-89 years. Only the first colonoscopy record per patient was included. Indications for colonoscopy were categorized as screening, diagnostic, and surveillance. We used the hierarchical logistic models to study the factors associated with the detection rates of SSL. The Cochrane-Armitage test was used to study the significance of trend over time.There were a total of 5,173,211 colonoscopies performed by 3,934 endoscopists during the study period. Among the 2,101,082 screening colonoscopies over the study period in adults older than or equal to 50 years that were complete to the cecum, the average detection rate per endoscopist for SSL was 6.43% (SD 5.18) and 6.25% standardized for the 2010 US population. There was a significant increase in the detection rates of SSLs from screening colonoscopies over the study period from 4.99% in 2014 to 7.09% in 2017 (P trend0.001). Clinically significant factors associated with higher detection rates of SSL were longer withdrawal times (11 minutes vs ≤6 minutes) (odds ratio [OR] 9.61; 9.03-10.24), adequate preparation (OR 1.25; 1.22-1.28), female sex (OR 1.17; 1.16-1.18), and use of a specialized gastrointestinal pathology group (OR 1.12; 95% confidence interval 1.04, 1.19).Population-based estimates of the detection rates of SSL are 6% and have increased over time.

Colorectal cancer (CRC) remains both the third most common and deadly cancer in the United States in 2018 [1]. This is despite overall decreases in incidence and mortality, presumably due to increa...

SUMMARY Patients with Barrett's esophagus (BE) and low-grade dysplasia (LGD) are at increased risk of esophageal adenocarcinoma (EAC), although many regress to nondysplastic BE. This has significant clinical importance for patients being considered for endoscopic eradication therapy. Our aim is to determine the risk for progression in patients with confirmed persistent LGD. We performed a single-center retrospective cohort study of patients with BE and confirmed LGD between 2006 and 2016. Confirmed LGD was defined as LGD diagnosed by consensus conference with an expert GI pathologist or review by an expert GI pathologist and persistence as LGD present on subsequent endoscopic biopsy. The primary outcome was the incidence rate of HGD (high-grade dysplasia)/EAC. Secondary outcomes included risk factors for dysplastic progression. Risk factors for progression were assessed using univariate and multivariate analysis with logistic regression. Of 69 patients (mean age 65.2 years) with confirmed LGD were included. In total, 16 of 69 patients (23.2%) with LGD developed HGD/EAC during a median follow-up of 3.74 years (IQR, 1.24–5.45). For persistent confirmed LGD, the rate was 6.44 (95% confidence interval (CI), 2.61–13.40) compared to 2.61 cases per 100 patient-years (95% CI, 0.83–6.30) for nonpersistent LGD. Persistent LGD was found in only 29% of patients. Persistent LGD was an independent risk factor for the development of HGD/EAC (OR 4.18; [95% CI, 1.03–17.1]). Persistent confirmed LGD, present in only 1/3 of patients, was an independent risk factor for the development of HGD/EAC. Persistence LGD may be useful in decision making regarding the management of BE.

OBJECTIVES: Irritable bowel syndrome (IBS) is a common gastrointestinal condition with a heterogeneous pathophysiology. An altered gut microbiome has been identified in some IBS patients, and fecal microbiota transplantation (FMT) has been suggested to treat IBS. We performed meta-analyses and systematic review of available randomized controlled trials (RCTs) to evaluate the efficacy of FMT in IBS. METHODS: We performed a systematic literature search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science. Selection criteria included RCTs of FMT vs placebo using FMT excipients or autologous FMT in IBS. Meta-analyses were conducted to evaluate the summary relative risk (RR) and 95% confidence intervals (CIs) of combined studies for primary outcome of improvement in global IBS symptoms as measured by accepted integrative symptom questionnaires or dichotomous responses to questions of overall symptom improvement. RESULTS: Among 742 citations identified, 7 were deemed to be potentially relevant, of which 4 studies involving 254 participants met eligibility. No significant difference in global improvement of IBS symptoms was observed at 12 weeks in FMT vs placebo (RR = 0.93; 95% CI 0.48–1.79). Heterogeneity among studies was significant (I(2) = 79%). Subgroup analyses revealed benefits of single-dose FMT using colonoscopy and nasojejunal tubes in comparison with autologous FMT for placebo treatment (number needed to treat = 5, RR = 1.59; 95% CI 1.06–2.39; I(2) = 0%) and a reduction in likelihood of improvement of multiple-dose capsule FMT RCTs (number needed to harm = 3, RR = 0.54; 95% CI 0.34–0.85; I(2) = 13%).Placebo response was 33.7%in nonoral FMT RCTs and 67.8% in capsule FMT RCTs. The Grading of Recommendations Assessment, Development and Evaluation quality of the body of evidence was very low. DISCUSSION: Current evidence from RCTs does not suggest a benefit of FMT for global IBS symptoms. There remain questions regarding the efficacy of FMT in IBS as well as the lack of a clean explanation on the discrepant results among RCTs in subgroup analyses.

43 Background: Blood-based screening tests for colorectal cancer (CRC) with high sensitivity and specificity are needed to improve adherence, facilitate early detection, and ultimately reduce mortality from CRC. Current stool-based tests have a sensitivity of 24-42% for colorectal advanced adenomas (AAs), while blood tests that rely on tumor-derived cell-free DNA (cfDNA) methylation signatures have shown limited sensitivity for AAs. Here we demonstrate the ability to detect AAs from blood using a multiomics test that incorporates both tumor- and immune-derived signatures, and compare it to the performance of a cfDNA methylation-only test. Methods: Participants enrolled in a prospective study (NCT03688906) were included in this analysis. The multiomics test includes signatures for cell-free nucleic acids based on next-generation sequencing, and for plasma proteins based on high-throughput multiplexed assays. Signatures are integrated computationally with a combination of convolutional neural networks and regularized logistic regression. We compared the multiomics test with one based on cfDNA methylation only. Results: This sub-study included 542 participants (AA: n = 122; colonoscopy-confirmed negative controls: n = 420). Participants with AA were 56% male with a mean age of 63 years, and colonoscopy-confirmed negative controls were 54% male with a mean age of 61 years. The multiomics test achieved a sensitivity of 41% (n = 50/122, 95% CI 34-48%) at 90% specificity (377/420). By contrast, the cfDNA methylation-only test achieved a sensitivity of 20% (24/122, 95% CI 15-25%) at 91% specificity (383/420). Performance was also analyzed by histological subtype and location, and superiority of the multiomics test to the cfDNA-methylation-only test was consistently observed. Conclusions: A novel multiomics blood test can detect colorectal AAs at a sensitivity and specificity comparable to existing stool-based tests. Combining signatures from both tumor- and immune-derived sources resulted in AA sensitivity greater than that of cfDNA-methylation alone.

Studies assessing colonoscopic practice have demonstrated variation in adenoma detection rate,1 detection rates of advanced adenomas,2,3 and detection rates of sessile serrated lesions (SSLs).4,5 Our aims were to study the patient-, provider-, and procedure-level variables associated with detection rates of adenoma, SSLs, and advanced neoplasia in screening colonoscopies performed in large community practice.

Withdrawal times and adenoma detection rates are widely used quality indicators for screening colonoscopy. More rapid withdrawal times have been associated with undetected adenomas, which can increase risk for interval colorectal cancer.We analyzed records of 76,810 screening colonoscopies performed between 2004 and 2009, by 51 gastroenterologists practicing in Minneapolis and St Paul, MN. Colonoscopy records were linked electronically to the state cancer registry (Minnesota Cancer Surveillance System) to identify incident interval cancers that were diagnosed within 5.5 years after the screening examination.The physicians' mean ± SD withdrawal time was 8.6 ± 1.7 minutes and adenoma detection rates were 25% ± 9%. Longer mean withdrawal times were associated with higher adenoma detection rates (3.6% per minute; 95% confidence interval: 2.4% to 4.8%; P.0001). We identified 78 cancers during 410,687 person-years of follow-up, for an annual rate of 0.19/1000 person-years. Physicians' mean annual withdrawal times were inversely associated with cancer incidence (P.0001). Compared with withdrawal times ≥6 minutes, the adjusted incidence rate ratio for withdrawal times of6 minutes was 2.3 (95% confidence interval: 1.5-3.4; P.0001).Shorter mean annual withdrawal times during screening colonoscopies were independently associated with lower adenoma detection rates and increased risk of interval colorectal cancer.

Background: Currently, no clinical tools use demographic and risk factor information to predict the risk of finding an adenoma in individuals undergoing colon cancer screening. Such a tool would be valuable for identifying those who would most benefit from screening colonoscopy. Methods: We used baseline data from men and women who underwent screening colonoscopy from the randomized, multicenter National Colonoscopy Study (NCS) to develop and validate an adenoma risk model. The study, conducted at three sites in the United States (Minneapolis, MN; Seattle, WA; and Shreveport, LA) asked all participants to complete baseline questionnaires on clinical risk factors and family history. Model parameters estimated from logistic regression yielded an area under the receiver operating characteristic curve (AUROCC) used to assess prediction. Results: Five hundred forty-one subjects were included in the development model, and 1,334 in the validation of the risk score. Variables in the prediction of adenoma risk for colonoscopy screening were age (likelihood ratio test for overall contribution to model, P < 0.001), male sex (P < 0.001), body mass index (P < 0.001), family history of at least one first-degree relative with colorectal cancer (P = 0.036), and smoking history (P < 0.001). The adjusted AUROCC of 0.67 [95% confidence interval (CI), 0.61–0.74] for the derivation cohort was not statistically significantly different from that in the validation cohort. The adjusted AUROCC for the entire cohort was 0.64 (95% CI, 0.60–0.67). Conclusion: We developed and validated a simple well-calibrated risk score. Impact: This tool may be useful for estimating risk of adenomas in screening eligible men and women Cancer Epidemiol Biomarkers Prev; 24(6); 913–20. ©2015 AACR.

BACKGROUND The role of fecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) is not well-known. PURPOSE To assess the efficacy, comparative effectiveness, and harms of FMT for CDI. DATA SOURCES MEDLINE (1980 to January 2015), Cochrane Library, and ClinicalTrials.gov, followed by hand-searching references from systematic reviews and identified studies. STUDY SELECTION Any study of FMT to treat adult patients with CDI; case reports were only used to report harms. DATA EXTRACTION Data were extracted by 1 author and verified by another; 2 authors independently assessed risk of bias and strength of evidence. DATA SYNTHESIS Two randomized, controlled trials (RCTs); 28 case-series studies; and 5 case reports were included. Two RCTs and 21 case-series studies (516 patients receiving FMT) reported using FMT for patients with recurrent CDI. A high proportion of treated patients had symptom resolution; however, the role of previous antimicrobials is unclear. One RCT comparing FMT with 2 control groups (n = 43) reported resolution of symptoms in 81%, 31%, and 23% of the FMT, vancomycin, or vancomycin-plus-bowel lavage groups, respectively (P < 0.001 for both control groups vs. FMT). An RCT comparing FMT route (n = 20) reported no difference between groups (60% in the nasogastric tube group and 80% in the colonoscopy group; P = 0.63). Across all studies for recurrent CDI, symptom resolution was seen in 85% of cases. In 7 case-series studies of patients with refractory CDI, symptom resolution ranged from 0% to 100%. Among 7 patients treated with FMT for initial CDI, results were mixed. LIMITATION Most studies were uncontrolled case-series studies; only 2 RCTs were available for analysis. CONCLUSION Fecal microbiota transplantation may have a substantial effect with few short-term adverse events for recurrent CDI. Evidence is insufficient on FMT for refractory or initial CDI treatment and on whether effects vary by donor, preparation, or delivery method. PRIMARY FUNDING SOURCE U.S. Department of Veterans Affairs.

The goal of this review is to summarize stool-based testing for colorectal cancer (CRC). The key questions answered in this review were the advantages and limitations of each available stool-based test for CRC and to examine their comparative efficacy. Guaiac-based fecal occult blood testing (gFOBT) is no longer a relevant test for CRC screening. fecal immunochemical testing (FIT) tests, especially quantitative assays, are clearly a reliable stool-based test. Multitarget DNA (mtsDNA) stool testing may represent a viable option as well, although cost and test characteristics are yet fully defined. FIT and mtsDNA represent the options for stool-based CRC screening. In larger screening centers, quantitative FIT assays represent an attractive option for stool-based testing. Qualitative FIT has applicability in smaller centers. Although a large validation trial showed promising results for mtsDNA, further head-to-head trials with FIT will help define the ultimate role of mtsDNA. Ultimately, however, the best test for CRC screening is the one performed stool-based CRC screening as an initial or alternative option can increase participation in CRC screening.

The majority of the world's adult population and an estimated 80 million Americans are hypolactasic and hence malabsorb ingested lactose. Although lactose malabsorption is easily identified, less readily assessed is the clinically important question of how often does this malabsorption induce symptoms. This review summarizes: (1) knowledge concerning the etiology and diagnosis of hypolactasia and the pathophysiology of the symptoms of lactose malabsorption and (2) the results of well-controlled trials of the symptomatic response of lactose malabsorbers to varying dosages of lactose and the efficacy of therapeutic interventions to alleviate these symptoms. We conclude that the clinical significance of lactose malabsorption has been overestimated by both the lay public and physicians in that commonly ingested doses of lactose (ie, the quantity in a cup of milk) usually do not cause perceptible symptoms when ingested with a meal. Symptoms occur when the lactose dosage exceeds that in a cup of milk or when lactose is ingested without other nutrients. Simple dietary instruction, rather than the use of commercial products to reduce lactose intake, is recommended for the vast majority of lactose-malabsorbing subjects.

APC/β-catenin pathway perturbation is a common early event in colorectal carcinogenesis and is affected by calcium and vitamin D in basic science studies. To assess the effects of calcium and vitamin D on adenomatous polyposis coli (APC), β-catenin, and E-cadherin expression in the normal appearing colorectal mucosa of sporadic colorectal adenoma patients, we conducted a randomized, double-blinded, placebo-controlled 2 × 2 factorial clinical trial. Pathology-confirmed colorectal adenoma cases were treated with 2 g/day elemental calcium and/or 800 IU/day vitamin D3 versus placebo over 6 months (N = 92; 23/group). Overall APC, β-catenin, and E-cadherin expression and distributions in colon crypts in normal-appearing rectal mucosa biopsies were detected by standardized automated immunohistochemistry and quantified by image analysis. In the vitamin D3-supplemented group relative to placebo, the proportion of APC in the upper 40% of crypts (Φh APC) increased 21% (P = 0.01), β-catenin decreased 12% (P = 0.18), E-cadherin increased 72% (P = 0.03), and the Φh APC/β-catenin ratio (APC/β-catenin score) increased 31% (P = 0.02). In the calcium-supplemented group Φh APC increased 10% (P = 0.12), β-catenin decreased 15% (P = 0.08), and the APC/β-catenin score increased 41% (P = 0.01). In the calcium/vitamin D3-supplemented group, β-catenin decreased 11% (P = 0.20), E-cadherin increased 51% (P = 0.08), and the APC/β-catenin score increased 16% (P = 0.26). These results support (i) that calcium and vitamin D modify APC, β-catenin, and E-cadherin expression in humans in directions hypothesized to reduce risk for colorectal neoplasms, (ii) calcium and vitamin D as potential chemopreventive agents against colorectal neoplasms, and (iii) the potential of APC, β-catenin, and E-cadherin expression as modifiable, preneoplastic risk biomarkers for colorectal neoplasms. Cancer Prev Res; 5(10); 1247–56. ©2012 AACR.

Colorectal cancers diagnosed in the interval after a complete colonoscopy may occur due to rapid tumor growth. Interval colorectal cancers are associated with microsatellite instability (MSI).Our aim was to study the association of KRAS mutation with interval colorectal cancers and MSI.We searched our institution's cancer registry for interval colorectal cancers, defined as colorectal cancers that developed within 5 years of a complete colonoscopy. These were frequency matched to patients with non-interval colorectal cancers. Archived cancer specimens were evaluated for KRAS mutations in codons 12 and 13 using sequencing, and MSI by sequencing microsatellite loci. Multivariable logistic regression was used to analyze the association between KRAS mutation status, MSI status and interval colorectal cancers.There were 63 interval and 131 non-interval colorectal cancers. KRAS mutation was present in 12.9% of interval cancers compared to 28.9% of non-interval cancers (P = 0.03). In multivariable logistic regression model, KRAS was inversely associated with interval cancers (OR 0.36; 95% CI 0.15-0.90). In Cox proportional hazards model, adjusting for age, tumor grade, TNM Stage and MSI status, we found no association between KRAS mutation and 5-year survival compared to cancers without KRAS mutation (HR 0.84; 95% CI 0.4-1.46; P = 0.5).KRAS mutation is inversely associated with interval cancers and with MSI, suggesting that it is a marker of the chromosomal instability pathway associated with slow tumor growth, and distinct from MSI rapidly growing cancers. Molecular characterization of colorectal cancers is helpful in determining underlying pathway and may determine therapy.

While ulcerative colitis (UC) is a risk factor for colorectal cancer, the association of UC with survival after colorectal cancer has not been studied in an older population.The objective of our study was to compare the survival of colorectal cancer between persons with and without UC.All cases of colorectal cancer (CRC) in persons 67 and older residing in a SEER catchment area and enrolled in the Medicare between 1993 and 1999 were assessed. We identified diagnosis of UC using ICD-9 codes on Medicare outpatient, office, and inpatient claims in the 2 years prior to the date of diagnosis. We used Cox proportional hazards model and Kaplan-Meier curves to compare survival between individuals with UC and CRC (UC-CRC) and sporadic CRC RESULTS: We identified 47,543 cases of colorectal cancer. Cases with UC-CRC tend to be diagnosed at earlier stages compared to sporadic CRC (42 vs. 37% local (TNM stage 1 and 2) and 11 vs. 17% distant spread (TNM stage 4), respectively; P value = 0.04). Controlling for age, gender, race and stage, diagnosis of UC did not affect the 3-year survival for CRC.Colorectal cancers tend to be diagnosed at earlier stages among persons with UC, but there is no difference in 3-year survival rates for colorectal cancer among individuals with and without UC.

Background: Intake of aspirin is associated with reduction in risk of colorectal adenoma and carcinoma. Some plants contain salicylates, and individuals not taking aspirin may have measurable salicylate levels. However, the association between serum salicylate level and recurrence of adenoma in nonusers of aspirin has not been studied. Methods: We measured serum salicylate levels in participants in a randomized controlled trial with calcium supplementation for the prevention of colorectal adenomas. Generalized linear models were used to assess the association between serum levels and adenoma risk during the follow-up period of the trial. Results: We did not find an association with recurrence of adenomas or advanced adenomas with serum salicylate levels at year 1 among nonusers of aspirin. There was no effect modification of the chemopreventive effect of calcium supplementation in reducing risk of recurrent adenomas or advanced adenomas. Conclusions: Among nonusers of ASA, serum salicylate levels are not associated with risk of recurrence of adenomas. Impact: Serum salicylate levels can be detected in individuals not taking aspirin, but the levels may be too low to confer protection from risk of recurrent adenomas. Cancer Epidemiol Biomarkers Prev; 20(4); 679–82. ©2011 AACR.

While ulcerative colitis (UC) and Crohn’s disease (CD) are thought to predispose to colorectal cancer (CRC), the association has not been well studied in an older population. The objective of our study was to evaluate the association of ulcerative colitis and Crohn’s disease and colorectal cancer in a population-based, case–control study. We also wished to estimate the incidence rates of colorectal cancer among older individuals with UC/CD. All cases of colorectal cancer in persons 67 and older in the SEER catchment area and in the Medicare claims database were compared with cancer-free controls residing in the same geographic area. We used multivariable logistic regression models adjusted for demographic and other factors. We identified 47,543 cases of CRC and 142,273 controls. We found a modest association between UC and CRC (OR 1.93; 95% CI 1.54–2.49; P-value