[Show abstract][Hide abstract]ABSTRACT: Background
Selenium supplementation may help to prevent colorectal cancer; as precursors of colorectal cancer, colorectal adenomas are a surrogate for colorectal cancer. Selenium supplementation may increase risk of type 2 diabetes (T2D).
The Selenium and Celecoxib (Sel/Cel) Trial was a randomized, placebo controlled trial of selenium 200 µg daily as selenized yeast and celecoxib 400 mg once daily, alone or together, for colorectal adenoma prevention. Men and women between age 40 and 80 years were eligible following colonoscopic removal of colorectal adenomas. The primary outcome was adenoma development. Celecoxib was suspended because of cardiovascular toxicity in other trials, but accrual continued to selenium and placebo. A total of 1621 participants were randomly assigned to selenium or placebo, of whom 1374 (84.8%) were available for analysis. All statistical tests were two-sided.
In the respective placebo and selenium arms of 689 and 685 participants, adenoma detection after medians of 33.6 (range = 0.0–85.1 months) and 33.0 months (range = 0.0–82.6 months) were 42.8% and 44.1% (relative risk [RR] = 1.03, 95% confidence interval [CI] = 0.91 to 1.16, P = .68). In participants with baseline advanced adenomas, adenoma recurrence was reduced by 18% with selenium (RR = 0.82, 95% CI = 0.71 to 0.96, P = .01). In participants receiving selenium, the hazard ratio for new-onset T2D was 1.25 (95% CI = 0.74 to 2.11, P = .41), with a statistically significantly increased risk of selenium-associated T2D among older participants (RR = 2.21; 95% CI = 1.04 to 4.67, P = .03).
Overall, selenium did not prevent colorectal adenomas and showed only modest benefit in patients with baseline advanced adenomas. With limited benefit and similar increases in T2D to other trials, selenium is not recommended for preventing colorectal adenomas in selenium-replete individuals.
Full-text available · Article · Dec 2016 · JNCI Journal of the National Cancer Institute
[Show abstract][Hide abstract]ABSTRACT: Background
Cyclooxygenase (COX)-2 inhibitors such as celecoxib were designed to preserve anti-inflammatory activity without inhibiting COX-1. Downregulation of COX-2 inhibits colorectal carcinogenesis.
The Selenium and Celecoxib Trial was a randomized, placebo-controlled trial of once-daily selenium 200 µg and celecoxib 400 mg, alone or together, for colorectal adenoma prevention. Men and women between age 40 and 80 years were eligible following colonoscopic removal of adenomas. The primary outcome was development of new adenomas. Celecoxib was suspended early because of cardiovascular toxicity in other trials. Accrual to selenium or placebo continued. Before suspension, 824 participants were randomly assigned to celecoxib or placebo, of whom 712 (86.4%) were available for analysis. All statistical tests were two-sided.
In the placebo and celecoxib arms of 356 participants each, adenoma detection was 47.5% and 49.7% (relative risk [RR] = 1.04, 95% confidence interval [CI] = 0.90 to 1.21, P = .58), respectively, after median periods of 13.6 and 14.2 months on intervention. Among participants colonoscoped within 12 months of discontinuing intervention (n = 244), overall adenoma recurrence (RR = 0.69, 95% CI = 0.48 to 0.98, P = .04) and recurrence with advanced adenomas (RR = 0.23, 95% CI = 0.07 to 0.80, P = .02) were reduced with celecoxib. Reduction of adenoma recurrence was greatest in participants with previous advanced adenomas. Celecoxib increased risk of hypertension in participants with pre-existing cardiovascular risk factors compared with placebo (hazard ratio = 2.19, 95% CI = 1.07 to 4.50, P = .03).
Limited-duration celecoxib prevents adenoma recurrence in patients with prior high-risk adenomas, in whom strategies to minimize cardiovascular toxicity might be feasible.
Full-text available · Article · Dec 2016 · JNCI Journal of the National Cancer Institute
[Show abstract][Hide abstract]ABSTRACT: Background: IBD is a chronic illness that can have a variable course of disease progression. Studies show up to 11% IBD patients receive care that not recommended in guidelines and is potentially harmful. Hence there is need to improve quality by standardizing care, that can be quantified. AGA/CCFA has endorsed a set of IBD-specific process-measures that are currently incorporated into the Physician Quality Reporting System (PQRS). In the year 2012 to 2013, our IBD group adopted a standardized worksheet based on 10 highest yielding QMs recommended by AGA/CCFA (sample worksheet Figure1). This worksheet was available in electronic medical system (EMR) and was filled annually by our nurse practitioner from responses obtained on routine follow-up patient visit. This worksheet itemized applicable quality indicators and allowed us the opportunity to quantify not only improvement in documentation of QMs but also improved clinical outcomes. Our aims were (1) An electronic health maintenance worksheet improves documentation of quality indicators; (2) The worksheet improves quality care in IBD patients. Methods: All consecutive patients with established IBD, who had a health maintenance worksheet filled during return visits in the year 2012 and 2013 were included. To measure improvement in documentation of quality indicators, clinical notes from 12 months prior to filling of the worksheet were reviewed and all quality indicators mentioned in any of those notes were recorded. Patients who did not have an encounter with a health care provider in 12 months prior, were excluded. Patients who had a new diagnosis of IBD were also excluded. To measure if completion of worksheet actually translated to better care and not just improved documentation, we recorded every time a medical intervention was performed, when any QM was identified lacking on the worksheet. Statistical analysis was done using means and standards deviations (SD). Pre and post intervention data was analyzed using paired t-test with alpha level 0.05. Results: Ninety-five patients were identified with mean age of 47 years (SD 17) and 63% were men. 65% had CD and 35% UC with a mean length of disease of 12 years (Range 1-25 years). Mean QM indicators recorded in 12 months prior to filling the worksheet were 2 per patient (SD 1.4). Mean QM indicators identified for the same cohort of patients after completing worksheet was 5.8 (SD 1.22). For each patient the paired data of pre and post intervention showed mean improvement in recorded quality indicators was 3.9 items per patient (SD 0.16), which was statistically significant, P-value <0.001 (Figure 2). A deficiency identified by the worksheet resulted in medical intervention in 76% of patients (N = 73). In 10% of patients, 3 or more interventions were done. Common interventions included orders for bone density scans, vaccinations, colonoscopy for dysplasia surveillance and dermatology referral for skin exam for patients on immune suppression. Conclusions: A standardized QM worksheet when incorporated into clinical practice as a part of EMR, improved documentation of quality measures and resulted in improved quality care for patients with known IBD.
[Show abstract][Hide abstract]ABSTRACT: Factitious disorder is a rare psychiatric illness characterized by the willful and deceptive induction of illness for the purpose of assuming the sick role. It presents a substantial diagnostic challenge, as patients often go to great lengths to conceal their deception. Accordingly, its presence in the full spectrum of gastrointestinal diseases is likely underappreciated. While factitious gastrointestinal bleeding, abdominal pain and diarrhea are relatively common, factitious non-gastrointestinal symptoms in the setting of gastrointestinal illness have been infrequently reported. We present the case of a patient with Crohn's disease with recurrent pancytopenia attributed to the surreptitious ingestion of 6-mercaptopurine. In patients with possible access to immunomodulatory drugs, a high suspicion for and early identification of factitious disorder may improve patient outcomes and avoid invasive and costly diagnostic evaluations.
Full-text available · Article · May 2015 · Case Reports in Gastroenterology
[Show abstract][Hide abstract]ABSTRACT: Eosinophilic granulomatosis with polyangiitis (EGPA), formerly named Churg-Strauss syndrome, is a rare systemic small- and medium-sized-vessel vasculitis, characterized by the presence of severe asthma as well as blood and tissue eosinophilia. Gastrointestinal (GI) symptoms, like diarrhea and abdominal pain, are common; however, there are few reports of histologic evidence of GI involvement. We report the case of a patient on treatment for EGPA who presented with recurrent small bowel obstruction and choledocholithiasis. Biopsies of the esophagus, small bowel and common bile duct showed diffuse eosinophilia, with clear EGPA in the GI tract. Improved awareness of GI EGPA may allow for timely management of this disorder.
Full-text available · Article · Oct 2014 · Case Reports in Gastroenterology
[Show abstract][Hide abstract]ABSTRACT: Patients with familial adenomatous polyposis (FAP) are known to have an increased risk for gastric adenomas. The clinical features of gastric adenomas in FAP have not been well characterized, and there is a lack of standardized approaches to the management of these lesions.
To study the endoscopic appearance, risk factors, clinical course, and response to therapy of gastric adenomas in patients with FAP.
We retrospectively reviewed the records of 97 patients with FAP who underwent esophagogastroduodenoscopy (EGD) at Mayo Clinic (Florida, Rochester and Arizona) between 2004 and 2013.
Nine patients (9%) had biopsy-proven gastric adenomas. Adenomas were located in the antrum (five patients), in the body and fundus in the setting of background fundic gland polyps (FGP) (three patients), and in the body not associated with FGP (one patient). Adenoma size was 3-40 mm and the number of adenomas per patient ranged from one to 20. Adenomas in the antrum were flat and subtle, whereas those in the gastric body or fundus were polypoid and difficult to differentiate from the cystic FGPs seen in patients with FAP. The performing endoscopists reported difficulty with identifying adenomas, and six patients had at least one EGD within the previous three years where gastric adenomas were not reported. Adenomas were classified as tubular in eight patients and tubulovillous in one patient. High grade dysplasia was noted in one patient. After a median follow-up of 63 months (interquartile range: 20-149 months), no patient in our entire cohort (with or without gastric adenomas) developed gastric cancer. The patients in whom gastric adenoma developed, compared to those without gastric adenoma, were more likely to be younger [36 +/- 12 vs. 48 +/- 15 years, p = 0.02], have concomitant chronic gastritis [22% vs. 0%, p = 0.008], and have desmoid tumors [5(56%) vs. 19(22%), p 0.04]002E CONCLUSIONS: Gastric adenomas are not uncommon in patients with FAP and are often difficult to identify endoscopically. Endoscopists should have a high degree of suspicion for gastric adenomas in these patients and a low threshold to biopsy. Given the benign clinical course, recommended initial management is conservative with endoscopic therapy and periodic surveillance.
Full-text available · Article · Feb 2014 · Hereditary Cancer in Clinical Practice
[Show abstract][Hide abstract]ABSTRACT: Objectives:
Precursors to 1/3 of colorectal cancer (CRC), serrated polyps have been under-detected by screening due to their inconspicuous, non-hemorrhagic, and proximal nature. A new multi-target stool DNA test (multi-target sDNA) shows high sensitivity for both CRC and advanced adenomas. Screen detection of serrated polyps by this approach requires further validation. We sought to assess and compare noninvasive detection of sessile serrated polyps (SSP) ≥ 1 cm by sDNA and an occult blood fecal immunochemical test (FIT).
In a blinded prospective study, a single stool sample used for both tests was collected from 456 asymptomatic adults prior to screening or surveillance colonoscopy (criterion standard). All 29 patients with SSP ≥ 1 cm were included as cases and all 232 with no neoplastic findings as controls. Buffered stool samples were processed and frozen on receipt; Exact Sciences performed sDNA in batches using optimized analytical methods. The sDNA multi-marker panel targets methylated BMP3 (mBMP3) and NDRG4, mutant KRAS, β-actin, and hemoglobin. FIT (Polymedco OC-FIT Check) was performed in separate lab ≤ 2 days post defecation and evaluated at cutoffs of 50 (FIT-50) and 100 ng/ml (FIT-100).
MEDIAN AGES: cases 61 (range 57-77), controls 62 (52-70), p = NS. Women comprised 59% and 51%, p = NS, respectively. SSP median size was 1.2 cm (1-3 cm), 93% were proximal, and 64% had synchronous diminutive polyps. Among multi-target sDNA markers, mBMP3 proved highly discriminant for detection of SSP ≥ 1 cm (AUC = 0.87, p<0.00001); other DNA markers provided no incremental sensitivity. Hemoglobin alone showed no discrimination (AUC = 0.50, p = NS). At matched specificities, detection of SSP ≥ 1 cm by stool mBMP3 was significantly greater than by FIT-50 (66% vs 10%, p = 0.0003) or FIT-100 (63% vs 0%, p<0.0001).
In a screening and surveillance setting, SSP ≥ 1 cm can be detected noninvasively by stool assay of exfoliated DNA markers, especially mBMP3. FIT appears to have no value in SSP detection.
Full-text available · Article · Jan 2014 · PLoS ONE
[Show abstract][Hide abstract]ABSTRACT: BACKGROUND & AIMS: Colorectal cancer (CRC) and advanced pre-cancers can be detected non-invasively by analyses of exfoliated DNA markers and hemoglobin in stool. Practical and cost-effective application of a stool DNA-based (sDNA) test for general CRC screening require high levels of accuracy and high-capacity throughput. We optimized an automated sDNA assay and evaluated its clinical performance. METHODS: In a blinded, multi-center, case-control study, we collected stools from 459 asymptomatic patients before screening or surveillance colonoscopies and from 544 referred patients. Cases included CRC (n=93), advanced adenoma (AA, n=84), or sessile serrated adenoma ≥1 cm (SSA, n=30); controls included non-advanced polyps (n=155) or no colonic lesions (n=641). Samples were analyzed using an automated multi-target sDNA assay to measure β-actin (a marker of total human DNA), mutant KRAS, aberrantly methylated BMP3 and NDRG4, and fecal hemoglobin. Data were analyzed by a logistic algorithm to categorize patients as positive or negative for advanced colorectal neoplasia (CRC, advanced adenoma, and/or, sessile serrated adenoma ≥ 1 cm.). RESULTS: At 90% specificity, sDNA analysis identified individuals with colorectal cancer with 98% sensitivity. Its sensitivity for stage I cancer was 95%, for stage II cancer was 100%, for stage III cancer was 96%, for stage IV cancer was 100%, and for stages I-III cancers was 97% (non-significant P-value). Its sensitivity for advanced pre-cancers (AA and SSA) ≥1 cm was 57%, >2 cm was 73%, and >3 cm was 83%. The assay detected AA with high-grade dysplasia with 83% sensitivity. CONCLUSIONS: We developed an automated, multi-target, sDNA assay that detects CRC and premalignant lesions with levels of accuracy, previously demonstrated with a manual process. This automated high-throughput system could be a widely accessible non-invasive approach to general CRC screening.
Article · Apr 2013 · Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association
[Show abstract][Hide abstract]ABSTRACT: Sarcina ventriculi is a Gram positive organism, which has been reported to be found rarely, in the gastric specimens of patients with gastroparesis. Only eight cases of Sarcina, isolated from gastric specimens have been reported so far. Sarcina has been implicated in the development of gastric ulcers, emphysematous gastritis and gastric perforation. We report a case of 73-year-old male, with history of prior Billroth II surgery and truncal vagotomy, who presented for further evaluation of iron deficiency anemia. An upper endoscopy revealed diffuse gastric erythema, along with retained food. Biopsies revealed marked inflammation with ulcer bed formation and presence of Sarcina organisms. The patient was treated with ciprofloxacin and metronidazole for 1 wk, and a repeat endoscopy showed improvement of erythema, along with clearance of Sarcina organisms. Review of reported cases including ours suggests that Sarcina is more frequently an innocent bystander rather than a pathogenic organism. However, given its association with life threatening illness in two reported cases, it may be prudent to treat with antibiotics and anti-ulcer therapy, until further understanding is achieved.
Full-text available · Article · Apr 2013 · World Journal of Gastroenterology
[Show abstract][Hide abstract]ABSTRACT: Background and Study Aims. The presence of an implantable electromechanical cardiac device (IED) has long been considered a relative contraindication to the performance of video capsule endoscopy (CE). The primary aim of this study was to evaluate the safety of CE in patients with IEDs. A secondary purpose was to determine whether IEDs have any impact on images captured by CE. Patients and Methods. A retrospective chart review of all patients who had a capsule endoscopy at Mayo Clinic in Scottsdale, AZ, USA, or Rochester, MN, USA, (January 2002 to June 2010) was performed to identify CE studies done on patients with IEDs. One hundred and eighteen capsule studies performed in 108 patients with IEDs were identified and reviewed for demographic data, method of preparation, and study data. Results. The most common indications for CE were obscure gastrointestinal bleeding (77%), anemia (14%), abdominal pain (5%), celiac disease (2%), diarrhea (1%), and Crohn's disease (1%). Postprocedure assessments did not reveal any detectable alteration on the function of the IED. One patient with an ICD had a 25-minute loss of capsule imaging due to recorder defect. Two patients with LVADs had interference with capsule image acquisition. Conclusions. CE did not interfere with IED function, including PM, ICD, and/or LVAD and thus appears safe. Additionally, PM and ICD do not appear to interfere with image acquisition but LVAD may interfere with capsule images and require that capsule leads be positioned as far away as possible from the IED to assure reliable image acquisition.
Full-text available · Article · Apr 2013 · Gastroenterology Research and Practice
[Show abstract][Hide abstract]ABSTRACT: BACKGROUND: Turnaround time is an important component of endoscopy unit efficiency. Any reduction in the total time from patient arrival in the endoscopy room to departure from the recovery area may translate into better endoscopy unit efficiency. OBJECTIVE: To evaluate the effects on endoscopy unit efficiency of a change in narcotic choice for moderate sedation in patients undergoing EGD at an ambulatory surgery center. DESIGN: Prospective, comparative, quality-improvement project. SETTING: Endoscopy unit of a tertiary-care academic medical center. PATIENTS: We enrolled consecutive patients (n = 1963) who underwent outpatient EGD by 1 of 5 endoscopists between November 2008 and November 2010. INTERVENTION: Moderate sedation with midazolam plus fentanyl versus meperidine. MAIN OUTCOME MEASUREMENTS: Sedation-dependent endoscopy unit efficiency and total procedure time (induction-to-intubation, intubation-to-extubation, and extubation-to-discharge). RESULTS: Fentanyl was associated with reduced total procedure time by 10.1 minutes resulting from both shorter induction-to-intubation time and extubation-to-discharge time (P < .001). The mean (± SD) sedation-dependent endoscopy unit efficiency was 3.2 (± 1.9) procedures per hour for the meperidine group and 3.9 (± 2.7) procedures per hour for the fentanyl group (P = .012); this would translate into possibly increasing the endoscopy suite efficiency by 22%. Based on dosage equivalency conversion, equal doses of fentanyl and meperidine were used. No sedation-related complications or need for reversal agents were recorded. LIMITATIONS: No randomization was performed. CONCLUSION: Compared with meperidine, fentanyl in combination with midazolam was associated with significantly shorter total procedure time. By improving the turnaround time, sedation-dependent endoscopy unit efficiency may be improved by 22%.
[Show abstract][Hide abstract]ABSTRACT: Cyclooxygenase (COX) inhibitors reduce colorectal adenoma recurrence by up to 45% and selenium supplementation may prevent colorectal cancer. Following colonoscopic adenoma resection, 1,600 men and women aged 40-80 years were randomized to celecoxib (400 mg daily), a selective COX-2 inhibitor, and/or selenium (200 µg daily as selenized yeast), or double placebo. The trial was initiated in November, 2001. The primary trial endpoint is adenoma recurrence in each intervention group compared to placebo, as determined by surveillance colonoscopy performed 3-5 years after baseline. Randomization was stratified by use of low-dose aspirin (81 mg) and clinic site. Following reports of cardiovascular toxicity associated with COX-2 inhibitors, the celecoxib arm was discontinued in December, 2004 when 824 participants had been randomized. Accrual continued with randomization to selenium alone or placebo. Randomization of the originally planned cohort (n=1,621) was completed in November, 2008. A further 200 patients with 1+ advanced adenomas (denoting increased risk for colorectal cancer) were accrued to enhance statistical power for determining intervention efficacy in this higher-risk subgroup. Accrual of the total cohort (n=1,824) was completed in January, 2011. Baseline cohort characteristics include: mean age 62.9 years; 65% male; BMI 29.1 ±5.1; 47% taking low-dose aspirin while on trial; 20% with 3+ adenomas; and 38% with advanced adenomas. Intervention effects on adenoma recurrence will be determined, and their modification by genetic background and baseline selenium level. The effect of selenium supplementation on risk for type 2 diabetes will also be reported (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00078897.).
Full-text available · Article · Oct 2012 · Cancer Prevention Research
[Show abstract][Hide abstract]ABSTRACT: The patency capsule (PC) is used before capsule endoscopy (CE) in patients with known or suspected small-bowel (SB) strictures or obstruction (SBO) to avoid CE retention. False-positive PC examination results can occur in patients with delayed transit without obstruction, precluding the use of CE. Radiological tests are another option to evaluate the presence of SBO before CE.
Comparison of the PC and radiological examinations to detect clinically significant SB strictures.
Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the PC, and radiological tests for detecting significant strictures.
Forty-two patients underwent a PC study and radiological examinations. Both of the examinations showed similar sensitivity (57% vs 71%; P = 1.00) and specificity (86% vs 97%; P = .22). The receiver-operating characteristic curves evaluating combined sensitivity and specificity were also similar in both the PC and radiological examinations (0.71 vs 0.84, respectively; P = .46). Pooling results from both the PC and radiological tests had the highest sensitivity and NPV (100%, 100%). False-positive results occurred in 5 PC examinations and 1 radiological examination. The PC examination had 3 false-negative results (9%), whereas radiological tests had 2 (6%).
The NPV for the PC and radiological tests were not significantly different, suggesting that if findings on either test are negative before CE, the patient will most likely pass the capsule without incident. Radiological tests can be used to minimize PC study false-positive results by confirming or excluding the presence of a significant stricture suspected by the PC and to localize the PC if passage is delayed.
[Show abstract][Hide abstract]ABSTRACT: Eosinophilic enteritis is a rather rare condition that can manifest anywhere from esophagus to rectum. Its description in the literature is sparse, but associations have been made with collagen vascular disease, malignancy, food allergy, parasitic or viral infections, inflammatory bowel disease, and drug sensitivity. We present the case of a 41-year-old male diagnosed with ulcerative colitis who underwent proctocolectomy with ileal pouch anal anastomosis and loop ileostomy formation utilizing Seprafilm®, who later developed eosinophilic enteritis of the loop ileostomy site. This is the first report of eosinophilic enteritis and its possible link to the use of bioabsorbable adhesion barriers.
Full-text available · Article · May 2011 · Case Reports in Gastroenterology
[Show abstract][Hide abstract]ABSTRACT: Afternoon colonoscopies have recently been reported to be associated with lower adenoma detection rate (ADR), which was attributed to physician fatigue resulting from the same endoscopist performing procedures throughout the day. The aim of our study was to assess ADR in morning compared with afternoon colonoscopy performed in half-day blocks with different physicians. We evaluated the primary hypothesis that morning and afternoon ADRs would not differ significantly when performed in half-day blocks by different endoscopists.
Data on all colonoscopies performed between January 2009 and December 2009 were obtained from our endoscopy database. All patients who underwent colonoscopies in 2009 for screening, surveillance, and family history of colon cancer/polyps were included in the study. Morning colonoscopies were defined as those that were performed from 0800 to 1200 hours. Afternoon colonoscopies were defined as those that were performed from 1300 to 1700 hours. Colonoscopies in each block were performed either by different endoscopists working in half-day (morning or afternoon) block schedules or by the same endoscopist working a full-day schedule.
A total of 4,665 patients were included in the study. For endoscopists working the full-day, the afternoon ADR was significantly lower than the morning ADR (21 vs. 26.1%; odds ratio (OR)=0.75; 95% confidence interval (CI) 0.59, 0.96; P=0.02). Conversely, in the half-day group, there was no significant difference in ADR between afternoon and morning (27.6 vs. 26.6%; OR=1.05; 95% CI 0.88, 1.26; P=0.56).
Performing colonoscopies in half-day blocks by different endoscopists increases the detection of adenomas in afternoon procedures, probably by reducing physician fatigue.
Full-text available · Article · Apr 2011 · The American Journal of Gastroenterology