Faculty Bibliography

Background/Purpose: The relationship between gout and cancer remains unclear. Whereas some studies have reported possible anti-cancer benefits of uric acid and monosodium urate crystals, others have found an increased risk of cancer in gout patients. Our study aimed to clarify the relationship between gout and colon metaplasia, including cancer and polyps. Methods: We conducted a retrospective study of patients in a VA hospital system using two distinct approaches. To obtain a historical, cross-sectional view of colon cancer prevalence, we assessed the presence of physiciancoded diagnoses of colon cancer and/or polyps in gout patients, versus patients with osteoarthritis (OA) but no gout, with active records in our computerized patient record system (CPRS) between 2007 and 2008. Lung and prostate cancer prevalence were recorded for comparison. In the second approach, we included only patients with documented colonoscopy reports in CPRS, and performed a retrospective cohort study of colon cancer and polyp incidences in gout versus OA patients over a ten-year period (2001-2010). In addition, colon cancer and polyp incidences were compared between patients who had undergone screening versus diagnostic colonoscopy, those who used aspirin or NSAIDs and those who did not, and between gout patients who used allopurinol and/or colchicine and those who did not. Results: 1287 gout patients and 1287 OA patients were included. Gout and OA patients were similar in age, ethnicity, BMI and smoking history. Gout patients had a lower physician-coded prevalence of all colonic lesions (cancer or polyp: 1.8 versus 9.6%, p<0.001), and a lower prevalence of colon cancer (1.0 versus 1.9%, p<0.001), than OA patients (Figure A). Lung and prostate cancer were similar between the two groups. Among 581 gout patients and 598 OA subjects with documented colonoscopies, the ten-year incidence of colon cancer was lower in gout patients than in patients with OA (0.8 versus 3.7%, p=0.0008) (Figure B). This difference in colon cancer incidence remained significant after accounting for NSAID and/or aspirin use. Among gout patients, the use of colchicine and/or allopurinol, as well as the presence or absence of concomitant of OA, did not appear to influence colon cancer prevalence. Differences in colon cancer incidence were significant between gout and OA patients undergoing diagnostic colonoscopy (0.5% in gout patients versus 4.6% in OA patients, p<0.001) but not those undergoing screening colonoscopy (0.9% in gout patients versus 1% in OA patients, p=1.0). No protective effect of gout was observed for prostate or lung cancer. Conclusion: Patients with gout had decreased physician-reported prevalence, and colonoscopy-documented incidence of colon cancer compared to patients with OA, suggesting a possible protective effect of gout or a goutassociated clinical, epidemiological or genetic factor. (Figure Presented)

This review is an update to the American College of Gastroenterology (ACG) Committee on Minority Affairs and Cultural Diversity's paper on colorectal cancer (CRC) in African Americans published in 2005. Over the past 10 years, the incidence and mortality rates of CRC in the United States has steadily declined. However, reductions have been strikingly much slower among African Americans who continue to have the highest rate of mortality and lowest survival when compared with all other racial groups. The reasons for the health disparities are multifactorial and encompass physician and patient barriers. Patient factors that contribute to disparities include poor knowledge of benefits of CRC screening, limited access to health care, insurance status along with fear and anxiety. Physician factors include lack of knowledge of screening guidelines along with disparate recommendations for screening. Earlier screening has been recommended as an effective strategy to decrease observed disparities; currently the ACG and American Society of Gastrointestinal Endoscopists recommend CRC screening in African Americans to begin at age 45. Despite the decline in CRC deaths in all racial and ethnic groups, there still exists a significant burden of CRC in African Americans, thus other strategies including educational outreach for health care providers and patients and the utilization of patient navigation systems emphasizing the importance of screening are necessary. These strategies have been piloted in both local communities and Statewide resulting in notable significant decreases in observed disparities.

Kidney stones are a disease of worldwide prevalence with significant public health implications. About 60-80 % of stones are composed of calcium oxalate (CaOx). Hyperoxaluria is a major risk factor. Oxalobacter formigenes (OF), a member of the human colonic microbiota, plays a major role in net colonic oxalate absorption and secretion. We now report OF colonization rates in a young healthy population, the stability of colonization, the effects of antibiotic treatment, and OF colonization on urinary oxalate (Uox) excretion. We followed 64 healthy subjects tested for Helicobacter pylori (HP), who were treated with antibiotics (amoxicillin and clarithromycin for 2 weeks) for HP eradication. Using species-specific PCR, we tested for OF colonization at baseline and at follow-up. Urine samples 3 h after a low oxalate standard meal were analyzed for Uox, factored for urine creatinine (Cr). Of the 65 subjects (M/F: 23/42; mean age 25.2 +/- 5.7 years) tested for OF, 28 (43 %) were positive at baseline. Of 7 OF + subjects at baseline, subject to HP elimination, 6 became OF-negative at 12 wks, only 2 reverted to positive at week 24, and 4 patients remained negative at follow up (Mean 22.5 +/- 4.2 weeks). Of 18 untreated positive people with follow assessments, 16 (89 %) remained positive at follow up (Mean 23.0 +/- 4.2 week), but of 24 untreated negative subjects, only 3 (12 %) were positive at follow up (mean 20.2 +/- 6.8 weeks), significantly fewer than the untreated positives (p = 0.001 by Fisher exact test). We tested Uox/Cr in 137 samples from 46 subjects with no antibiotic exposure at different time points. We found that the presence of OF was associated with 14 % lower Uox/cr as compared with its absence (17.0 +/- 0.0 vs 19.4 +/- 0.1 mg/g, p = 0.04). We conclude that OF colonization status remains stable over a follow- up period of several months, with antibiotics suppressing colonization in the majority of people in the short term. The differences in urinary oxalate levels with respect to OF status is consistent with its protective effects for the prevention of calcium oxalate kidney stones

Gastroesophageal reflux disease (GERD) is a frequently encountered disorder. Obesity is an important risk factor for GERD, and there are several pathophysiologic mechanisms linking the two conditions. For obese patients with GERD, much of the treatment effort is focused on weight loss and its consistent benefit to symptoms, while there is a relative lack of evidence regarding outcomes after novel or even standard medical therapy is offered to this population. Physicians are hesitant to recommend operative anti-reflux therapy to obese patients due to the potentially higher risks and decreased efficacy, and these patients instead are often considered for bariatric surgery. Bariatric surgical approaches are broadening, and each technique has emerging evidence regarding its effect on both the risk and outcome of GERD. Furthermore, combined anti-reflux and bariatric options are now being offered to obese patients with GERD. However, currently Roux-en-Y gastric bypass remains the most effective surgical treatment option in this population, due to its consistent benefits in both weight loss and GERD itself. This article aims to review the impact of both conservative and aggressive approaches of obesity treatment on GERD.

BACKGROUND: Accumulating evidence shows that Helicobacter pylori protects against some metabolic and immunological diseases in which the development of these diseases coincide with temporal or permanent dysbiosis. The aim of this study was to assess the effect of H. pylori eradication on the human gut microbiome. METHODS: As part of the currently on-going ESSAY (Eradication Study in Stable Adults/Youths) study, we collected stool samples from 17 H. pylori-positive young adult (18-30 years-old) volunteers. The same cohort was followed up 6, 12 and 18 months-post H. pylori eradication. The impact of H. pylori on the human gut microbiome pre- and post-eradication was investigated using high throughput 16S rRNA gene (V3-V4 region) sequencing using the Illumina Miseq followed by data analysis using Qiime pipeline. RESULTS: We compared the composition and diversity of bacterial communities in the fecal microbiome of the H. pylori-positive volunteers, before and after H. pylori eradication therapy. The 16S rRNA gene was sequenced at an average of 150,000-170,000 reads/sample. The microbial diversity were similar pre- and post-H. pylori eradication with no significant differences in richness and evenness of bacterial species. Despite that the general profile of the gut microbiome was similar pre- and post-eradication, some changes in the bacterial communities at the phylum and genus levels were notable, particularly the decrease in relative abundance of Bacterioidetes and corresponding increase in Firmicutes after H. pylori eradication. The significant increase of short-chain fatty acids (SCFA)-producing bacteria genera could also be associated with increased risk of metabolic disorders. CONCLUSIONS: Our preliminary stool metagenomics study shows that eradication of H. pylori caused perturbation of the gut microbiome and may indirectly affect the health of human. Clinicians should be aware of the effect of broad spectrum antibiotics used in H. pylori eradication regimen and be cautious in the clinical management of H. pylori infection, particularly in immunocompromised patients.

BACKGROUND: Hospital care on weekends has been associated with delays in care, reduced quality, and poor clinical outcomes. OBJECTIVE: The purpose of this study was to evaluate the impact of a weekend hospital intervention on processes of care and clinical outcomes. The multifaceted intervention included expanded weekend diagnostic services, improved weekend discharge processes, and increased physician and care management services on weekends. DESIGN AND PATIENTS: This was an interrupted time series observational study of adult non-obstetric patients hospitalized at a single academic medical center between January 2011 and January 2014. The study included 18 months prior to and 19 months following the implementation of the intervention. Data were analyzed using segmented regression analysis with adjustment for confounders. MAIN MEASURES: The primary outcome was average length of stay. Secondary outcomes included percent of patients discharged on weekends, 30-day readmission rate, and in-hospital mortality rate. KEY RESULTS: The study included 57,163 hospitalizations. Following implementation of the intervention, average length of stay decreased by 13 % (95 % CI 10-15 %) and continued to decrease by 1 % (95 % CI 1-2 %) per month as compared to the underlying time trend. The proportion of weekend discharges increased by 12 % (95 % CI 2-22 %) at the time of the intervention and continued to increase by 2 % (95 % CI 1-3 %) per month thereafter. The intervention had no impact on readmissions or mortality. During the post-implementation period, the hospital was evacuated and closed for 2 months due to damage from Hurricane Sandy, and a new hospital-wide electronic health record was introduced. The contributions of these events to our findings are not known. We observed a lower inpatient census and found differences in patient characteristics, including higher rates of Medicaid insurance and comorbidities, in the post-Hurricane Sandy period as compared to the pre-Sandy period. CONCLUSIONS: The intervention was associated with a reduction in length of stay and an increase in weekend discharges. Our longitudinal study also illuminated the challenges of evaluating the effectiveness of a large-scale intervention in a real-world hospital setting.

OBJECTIVES: Annual fecal occult blood testing (FOBT) is often continued in patients who have had a recent negative colonoscopy, despite recommendations to the contrary. This prospective study aimed to determine the proportion of patients with a positive FOBT who had adenomas and cancers on colonoscopy stratified according to the duration of time since the last negative colonoscopy. METHODS: A total of 1,119 asymptomatic average-risk patients >/=50 years of age referred for a positive FOBT were prospectively identified and stratified by the duration of time since the last colonoscopy (never, >10 years, 5-10 years, or <5 years). The proportion of patients in each category with adenomas of any size, adenomas >/=10 mm, advanced neoplasms, and cancers was assessed. RESULTS: The mean age (68.9+/-9.6 years), sex (95.2% male), and race (48.1% white, 32.1% black, 15.6% Hispanic, and 4.2% other) did not differ between the four groups. Overall, adenomas of any size were detected in 42.8% of patients, adenomas >/=10 mm in 14.7%, advanced neoplasms in 20.7%, and cancers in 7.3%. Advanced neoplasms were detected in 30.4% of patients who have never had a colonoscopy, 27% in those who have had one greater than 10 years prior, 10.0% in 5-10 years prior, and 1.1% in less than 5 years prior. CONCLUSIONS: In asymptomatic average-risk patients with a negative colonoscopy within the last 5 years, the prevalence of adenomas is low, and no patient was diagnosed with cancer. These findings support the CDC recommendations to suspend annual FOBT for up to 5 years after a negative colonoscopy.Am J Gastroenterol advance online publication, 4 August 2015; doi:10.1038/ajg.2015.234.

BACKGROUND: More than half of the world's adults carry Helicobacter pylori. The eradication of H. pylori may affect the regulation of human metabolic hormones. The aim of this study was to evaluate the effect of H. pylori eradication on meal-associated changes in appetite-controlled insulinotropic and digestive hormones, and to assess post-eradication changes in body mass index as part of a currently on-going multicentre ESSAY (Eradication Study in Stable Adults/Youths) study. METHODS: We enrolled 29 H. pylori-positive young adult (18-30 year-old) volunteer subjects to evaluate the effect of H. pylori eradication on meal-associated changes on eight gastrointestinal hormones, using a multiplex bead assay. Changes in body mass index and anthropometric measurements were recorded, pre- and post-eradication therapy. RESULTS: Pre-prandial active amylin, total peptide YY (PYY) and pancreatic polypeptide (PP) levels were significantly elevated 12 months post-eradication compared with baseline (n = 18; Wilcoxon's signed rank test, p<0.05). Four of the post-prandial gut metabolic hormones levels (GLP-1, total PYY, active amylin, PP) were significantly higher 12 months post-eradication compared to baseline (n = 18; p<0.05). Following H. pylori eradication, the BMI and anthropometric values did not significantly change. CONCLUSIONS: Our study indicates that H. pylori eradication was associated with long-term disturbance in three hormones (active amylin, PP and total PYY) both pre- and post-prandially and one hormone (GLP-1) post-prandially. Longer post-eradication monitoring is needed to investigate the long-term impact of the observed hormonal changes on metabolic homeostasis.