Low Incidence of Aerodigestive Cancers in Patients With Negative Results From Colonoscopies, Regardless of Findings From Multitarget Stool DNA Tests.

BACKGROUND & AIMS: We aimed to compare the incidence of aerodigestive cancers in persons with negative results from colonoscopies and positive vs negative results from multitarget stool DNA tests for colorectal cancer and vs expected incidence. METHODS: We performed a retrospective cohort study of 1216 subjects with comprehensive patient records and/or cancer registry data from 3 medical centers in North America. Subjects had no neoplasia or only nonadvanced adenomas, based on screening colonoscopy, and either negative results (concordant with colonoscopy, n = 1011) or positive results (discordant colonoscopy, n = 205) from the multitarget stool DNA test. Outcomes included aerodigestive cancers in discordant vs concordant groups and comparison of observed aerodigestive cancer incidence between the groups and compared with expected incidence for the population, based on the Surveillance, Epidemiology, and End Results (SEER) data. RESULTS: Median follow-up times were comparable between subjects in the discordant (5.3 y; interquartile range, 3.5-5.8 y) and concordant (5.4 y; interquartile range, 3.7-5.8 y) groups. Aerodigestive cancers developed in 5 subjects in the discordant group vs 11 subjects in the concordant group (crude risk ratio, 2.3; 95% CI, 0.8-6.6; adjusted risk ratio, 2.2; 95% CI, 0.8-6.2; P = .151). The incidence of aerodigestive cancer was lower in the concordant group than the expected incidence based on SEER data (risk ratio, 0.4; 95% CI, 0.2-0.6; P = .0008). The incidence of aerodigestive cancer was not significantly greater in the population in the discordant group than the expected incidence based on SEER data (risk ratio, 0.8; 95% CI, 0.3-1.9; P = .599). CONCLUSIONS: In a retrospective study with a median follow-up time of 5.4 years, incident aerodigestive cancers were uncommon among subjects with negative findings from colonoscopies, regardless of discordant or concordant results from multitarget stool DNA tests. Patients with negative results from high-quality colonoscopies therefore should not undergo further testing.

Gastric adenomas in familial adenomatous polyposis are common, but subtle, and have a benign course.

BACKGROUND: 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. AIMS: To study the endoscopic appearance, risk factors, clinical course, and response to therapy of gastric adenomas in patients with FAP. METHODS: 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. RESULTS: 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]. 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.

Clinical performance of an automated stool DNA assay for detection of colorectal neoplasia.

BACKGROUND & AIMS: Colorectal cancer (CRC) and advanced precancers can be detected noninvasively 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 requires high levels of accuracy and high-capacity throughput. We optimized an automated sDNA assay and evaluated its clinical performance. METHODS: In a blinded, multicenter, 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 nonadvanced polyps (n = 155) or no colonic lesions (n = 641). Samples were analyzed by using an automated multi-target sDNA assay to measure ß-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 SSA ≥1 cm). RESULTS: At 90% specificity, sDNA analysis identified individuals with CRC with 98% sensitivity. Its sensitivity for stage I cancer was 95%, for stage II cancer it was 100%, for stage III cancer it was 96%, for stage IV cancer it was 100%, and for stages I-III cancers it was 97% (nonsignificant P value). Its sensitivity for advanced precancers (AA and SSA) ≥1 cm was 57%, for >2 cm it was 73%, and for >3 cm it 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 noninvasive approach to general CRC screening.

Impact of fentanyl in lieu of meperidine on endoscopy unit efficiency: a prospective comparative study in patients undergoing EGD.

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%.

Adenoma detection rate is not influenced by the timing of colonoscopy when performed in half-day blocks.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Performing colonoscopies in half-day blocks by different endoscopists increases the detection of adenomas in afternoon procedures, probably by reducing physician fatigue.

Performance of the patency capsule compared with nonenteroclysis radiologic examinations in patients with known or suspected intestinal strictures.

BACKGROUND: 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. OBJECTIVES: Comparison of the PC and radiological examinations to detect clinically significant SB strictures. MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the PC, and radiological tests for detecting significant strictures. RESULTS: 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%). LIMITATIONS: Retrospective study. CONCLUSIONS: 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.

Capsule endoscopy has a significantly higher diagnostic yield in patients with suspected and established small-bowel Crohn's disease: a meta-analysis.

OBJECTIVES: Capsule endoscopy (CE) has demonstrated superior performance compared with other modalities in its ability to detect early small-bowel (SB) Crohn's disease (CD), especially when ileoscopy is negative or unsuccessful. The aim of this study was to evaluate the diagnostic yield of CE compared with other modalities in patients with suspected and established CD using a meta-analysis. METHODS: A thorough literature search for prospective studies comparing the diagnostic yield of CE with other modalities in patients with CD was undertaken. Other modalities included push enteroscopy (PE), colonoscopy with ileoscopy (C+IL), SB radiography (SBR), computed tomography enterography (CTE), and magnetic resonance enterography (MRE). Data on diagnostic yield among various modalities were extracted, pooled, and analyzed. Data on patients with suspected and established CD were analyzed separately. Weighted incremental yield (IYW) (diagnostic yield of CE-diagnostic yield of comparative modality) and 95% confidence intervals (CIs) of CE over comparative modalities were calculated. RESULTS: A total of 12 trials (n=428) compared the yield of CE with SBR in patients with CD. Eight trials (n=236) compared CE with C+IL, four trials (n=119) compared CE with CTE, two trials (n=102) compared CE with PE, and four trials (n=123) compared CE with MRE. For the suspected CD subgroup, several comparisons met statistical significance. Yields in this subgroup were CE vs. SBR: 52 vs. 16% (IYw=32%, P<0.0001, 95% CI=16-48%), CE vs. CTE: 68 vs. 21% (IYw=47%, P<0.00001, 95% CI=31-63%), and CE vs. C+IL: 47 vs. 25% (IYw=22%, P=0.009, 95% CI=5-39%). Statistically significant yields for CE vs. an alternate diagnostic modality in established CD patients were seen in CE vs. PE: 66 vs. 9% (IYw=57%, P<0.00001, 95% CI=43-71%), CE vs. SBR: 71 vs. 36% (IYw=38%, P<0.00001, 95% CI=22-54%), and in CE vs. CTE: 71 vs. 39% (IYw=32%, P=or<0.0001, 95% CI=16-47%). CONCLUSIONS: Our meta-analysis demonstrates that CE is superior to SBR, CTE, and C+IL in the evaluation of suspected CD patients. CE is also a more effective diagnostic tool in established CD patients compared with SBR, CTE, and PE.

A retrograde-viewing device improves detection of adenomas in the colon: a prospective efficacy evaluation (with videos).

BACKGROUND: Colonoscopy may fail to detect neoplasia located on the proximal sides of haustral folds and flexures. The Third Eye Retroscope (TER) provides a simultaneous retrograde view that complements the forward view of a standard colonoscope. OBJECTIVE: To evaluate the added benefit for polyp detection during colonoscopy of a retrograde-viewing device. DESIGN: Open-label, prospective, multicenter study evaluating colonoscopy by using a TER in combination with a standard colonoscope. SETTING: Eight U.S. sites, including university medical centers, ambulatory surgery centers, a community hospital, and a physician's office. PATIENTS: A total of 249 patients (age range 55-80 years) presenting for screening or surveillance colonoscopy. INTERVENTIONS: After cecal intubation, the disposable TER was inserted through the instrument channel of the colonoscope. During withdrawal, the forward and retrograde video images were observed simultaneously on a wide-screen monitor. MAIN OUTCOME MEASUREMENTS: The number and sizes of lesions (adenomas and all polyps) detected with the standard colonoscope and the number and sizes of lesions found only because they were first detected with the TER. RESULTS: In the 249 subjects, 257 polyps (including 136 adenomas) were identified with the colonoscope alone. The TER allowed detection of 34 additional polyps (a 13.2% increase; P < .0001) including 15 additional adenomas (an 11.0% increase; P < .0001). For lesions 6 mm or larger, the additional detection rates with the TER for all polyps and for adenomas were 18.2% and 25.0%, respectively. For lesions 10 mm or larger, the additional detection rates with the TER for all polyps and for adenomas were 30.8% and 33.3%, respectively. In 28 (11.2%) individuals, at least 1 additional polyp was found with the TER. In 8 (3.2%) patients, the polyp detected with the TER was the only one found. Every polyp that was detected with the TER was subsequently located with the colonoscope and removed. For all polyps and for adenomas, the additional detection rates for the TER were 9.7%/4.1% in the left colon (the splenic flexure to the rectum) and 16.5%/14.9% in the right colon (the cecum to the transverse colon), respectively. LIMITATIONS: There was no randomization or comparison with a separate control group. CONCLUSIONS: A retrograde-viewing device revealed areas that were hidden from the forward-viewing colonoscope and allowed detection of 13.2% additional polyps, including 11.0% additional adenomas. Additional detection rates with the TER for adenomas 6 mm or larger and 10 mm or larger were 25.0% and 33.3%, respectively. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00657371.).

Use of an electromagnetic colonoscope to assess maneuvers associated with cecal intubation.

BACKGROUND: Safe and effective colonoscopy is aided by the use of endoscopic techniques and maneuvers (ETM) during the examination including patient repositioning, stiffening of the endoscope and abdominal pressure. AIM: To better understand the use and value of ETM during colonoscopy by using a device that allows real-time imaging of the colonoscope insertion shaft. METHODS: The use of ETM during colonoscopy and their success was recorded. Experienced colonoscopists and endoscopy assistants used a commercially available electromagnetic (EM) transmitter and a special adult variable stiffness instrument with 12 embedded sensors to examine 46 patients. In 5 of these a special EM probe passed through the instrument channel of a standard pediatric variable stiffness colonoscope was used instead of the EM colonoscope. RESULTS: Thirty-nine men and 7 women with a mean age of 64 years (range 33-90) were studied. The cecum was intubated in 93.5% (43/46). The mean time to reach the cecum was 10.6 minutes (range 3-25). ETM were used a total of 174 times in 41 of the patients to assist with cecal intubation. When ETM were required to reach the cecum, and the cecum was intubated, an average of 3.82 ETM/patient was used. While ETM were used most often when the tip of the colonoscope was in the left side of the colon (rectum 5.0%, sigmoid colon 20.7%, descending colon 5.0%, and splenic flexure 11.6%), when the instrument was in the transverse colon (14.8%), hepatic flexure (20.7%) and ascending colon (19.8%) the use of ETM was also required. When the colonoscope tip was in the transverse colon, hepatic flexure and ascending colon, ETM success rates were less (61.1%, 52.0%, and 41.7% respectively) compared to the left colon success rates (rectum 83.3%, sigmoid colon 84.0%, descending colon 100%, and splenic flexure 85.7%). CONCLUSION: The EM colonoscope allows imaging of the insertion shaft without fluoroscopy and is a useful device for evaluating the efficacy of ETM. ETM are important tools of the colonoscopist and are used most often in the left colon where they are most effective.

Patient preference and acceptance with sodium phosphate tablet preparation for colonoscopy.

BACKGROUND: Colonoscopy is considered the primary procedure for colorectal cancer screening and prevention. However patient acceptance of this procedure has been poor. A major deterrent for patients is the need for a large-volume (4-l) preprocedure colonic preparation (polyethylene glycol [PEG] solution) that can be associated with a bad taste. AIM: To determine patient preference and acceptance of the NaP tablet preparation in patients who have previously used PEG solutions for their prior colonoscopy exams. METHODS: Patients who had used a standard 4-l PEG solution preparation for a colonoscopy within the past 12 months and who were scheduled for a repeat colonoscopy were invited to participate in this study. A preprocedural questionnaire was administered to the patients. The primary outcome measure was whether the patient indicated a preference for the NaP tablet preparation over the previous PEG solution. RESULTS: Thirty-five of 53 participants (66%) who completed the study preferred the NaP tablet preparation over 4-l PEG. A majority of patients also indicated that they would use the NaP tablet preparation again and would like to have a choice of preparation for their next colonoscopy. CONCLUSIONS: Among patients who previously used a 4-l PEG preparation for colon cleansing and participated in this study, 66% of patients preferred the NaP tablet preparation over the PEG preparation for their colonoscopy.

Rural-urban differences in colorectal cancer screening capacity in Arizona.

Colorectal cancer can be prevented via screening by the detection and removal of colorectal adenomas. Few data exist on screening capacity by rural/urban areas. Therefore, the aims of this work were to evaluate current colorectal cancer endoscopy screening capacity and to estimate potential volume for rural and urban regions in Arizona. Gastroenterologists and colorectal surgeons practicing in Arizona completed a survey (n = 105) that assessed current colonoscopy and sigmoidoscopy screening and estimated future capacity. Resources needed to increase capacity were identified, and differences between rural and urban regions were examined. Responders were more likely to practice in an urban region (89.5%). Physicians reported performing 8,717 endoscopic procedures weekly (8,312 in urban and 405 in rural regions) and the vast majority were colonoscopies (91% in urban and 97% in rural regions). Urban physicians estimated being able to increase their capacity by 35.7% (95% confidence interval 34.7-35.7) whereas rural physicians estimated an increase of 53.1% (95% confidence interval 48.1-58.0). The most commonly cited resource needed to increase capacity was a greater number of physicians in urban regions (52.1%); while the top response in rural areas was appropriate compensation (54.6%). Lastly, 27.3% of rural physicians noted they did not need additional resources to increase their capacity. In conclusion, Arizona has the ability to expand colorectal cancer screening endoscopic capacity; this potential increase was more pronounced in rural as compared to urban regions.

Retention of the capsule endoscope: a single-center experience of 1000 capsule endoscopy procedures.

BACKGROUND: Retention of the video capsule is the most significant complication associated with capsule endoscopy (CE). There are limited data on incidence, risk factors, and outcomes of capsule retention. OBJECTIVE: We aimed to determine the incidence of capsule retention and to investigate the causes and clinical outcomes of capsule retention. SETTING: Single tertiary referral medical center. PATIENTS: All patients who underwent CE for suspected small bowel disease from June 2002 to March 2006. METHODS: Retrospective case series. RESULTS: Capsule retention occurred in 1.4% of our patients (14/1000). Eleven patients failed to pass the capsule because of nonsteroidal anti-inflammatory drug (NSAID) enteropathy (diaphragm disease). One patient had capsule retention from an obstructing carcinoid tumor. Metastatic ovarian cancer with invasion of the ileum was the cause of retention in another patient. One patient who did not have surgical removal of the capsule because of loss of follow-up had retention caused by a small-bowel tumor suspicious for carcinoid tumor on CT enterography. All patients remained "asymptomatic" from the retained capsules. Thirteen patients underwent elective partial small-bowel resection and capsule removal. No deaths were associated with these surgeries. Eleven patients recovered promptly, whereas 2 patients had mild postoperative ileus. LIMITATION: Retrospective study. CONCLUSION: Retention of the capsule endoscope appears to be infrequent. The most common cause is diaphragm disease resulting from NSAIDs in this study population. In most cases, capsule retention is asymptomatic, and it usually leads to surgical removal, which appears safe and also identifies and treats the underlying small-bowel condition.

A multicenter randomized comparison of the Endocapsule and the Pillcam SB.

BACKGROUND: Video capsule endoscopy has been shown to be the single most effective endoscopic procedure for identifying the source of obscure GI bleeding (OGIB). OBJECTIVE: Our purpose was to report on the Food and Drug Administration pivotal trial in which the Endocapsule (EC) (Olympus America, Allentown, Pa) was compared with the Pillcam SB (PSB) (Given Imaging, Yoqneam, Israel) in patients with OGIB. DESIGN: A novel trial design was used in which the EC and the PSB were swallowed by the same patient 40 minutes apart, in randomized order. SETTING: Four academic medical centers. PATIENTS: Patients with OGIB aged 18 to 85 years who had either been transfused or who had a hematocrit of <31% in males or <28% in females. INTERVENTIONS: Both video capsules were swallowed in random order. Videos from the PSB were read locally for patient management. All videos were then read by at least 2 independent readers for normal versus abnormal categorization, a diagnosis, capsule transit time, reading time, and a subjective assessment of image quality. MAIN OUTCOME MEASUREMENT: Categorization of videos as either normal or abnormal. RESULTS: Data from 51 of 63 enrolled patients were analyzed. Nine patients were excluded for technical reasons and 3 for protocol violations. Twenty-four videos were read as normal and 14 as abnormal from both capsules. Disagreement occurred in 13. No adverse events were reported for either capsule. Overall agreement was 38 of 51 (74.5%) with a kappa of 0.48, P = .008. LIMITATIONS: Although ingestion order was randomized, the videos could not be read blind owing to a different shape of the image margin. CONCLUSIONS: (1) Both devices were safe and had a comparable diagnostic yield within the range previously reported. (2) There was a subjective difference in image quality favoring the EC. (3) This study design provided unique information about capsule movement in the small intestine and the lack of electromechanical interference between 2 different capsules.

Using CT enterography to monitor Crohn's disease activity: a preliminary study.

OBJECTIVE: The purpose of our study was to determine whether imaging changes of Crohn's disease at sequential CT enterography examinations correlate with disease progression or regression. MATERIALS AND METHODS: Forty CT enterography examinations in 20 patients (12 women, eight men; mean age, 55.5 years) with known Crohn's disease were retrospectively evaluated by a radiologist who was blinded to the clinical history. One radiologist determined whether imaging findings of Crohn's disease were present and, if so, whether the findings progressed, regressed, or remained stable between examinations. CT enterography findings were then compared with disease progression or regression based on symptoms and clinical follow-up. Direct comparison of CT enterography and endoscopy was also performed when available. RESULTS: Disease progression or regression by CT enterography correlated with symptoms in 16 of 20 (80%) patients. Specifically, CT enterography and symptoms agreed in 12 patients with clinical disease progression, two patients with clinical regression, and two with clinically stable disease. In four of 20 (20%) patients, symptoms progressed although CT enterography findings were negative (n = 2) or improved (n = 2). No treatment change was initiated; and at follow-up, three of four patients were improved and the remaining patient was stable symptomatically. Sixteen ileoscopies were attempted in 12 patients; however, four examinations did not reach the ileum. In the remaining examinations, endoscopy correlated with CT enterography in all cases (12/12, 100%) and with symptoms in nine of 12 (75%) cases. The weighted kappa statistic, which measures the chance-adjusted agreement between CT enterography and symptoms, was 0.57 (95% CI, 0.20-0.94). CONCLUSION: This preliminary study indicates that imaging changes between CT enterography examinations have excellent potential for reliably monitoring Crohn's disease progression or regression.

Severe Diarrhea in the Setting of Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICPIs) are novel therapeutic agents targeting a variety of cancers by enhanced T cell activation. Immune-related adverse events (irAEs) commonly occur with ICPI use and can affect multiple organ systems including the gastrointestinal tract. Due to irAEs, the use of ICPIs is limited in autoimmune diseases. We present a case of microscopic colitis diagnosed after the initiation of nivolumab and a case of ipilimumab colitis and Clostridium difficile in the setting of Crohn's colitis.

Comparison of morning versus afternoon cecal intubation rates.

BACKGROUND: Many factors impacting cecal intubation rates have been examined in detail; however, little information exists regarding the effect of the timing of the procedure. We sought to examine any difference in cecal intubation rates between morning and afternoon colonoscopies and identify factors contributing to a discrepancy. METHODS: Retrospective, single-center study comparing cecal intubation rates for colonoscopies performed in the morning (begun prior to 12 noon) and colonoscopies performed in the afternoon (begun after 12 noon) over an approximately 12 month period. Univariate and multivariate analyses were performed evaluating patient demographics, procedure indication(s), endoscopist, bowel preparation type and quality, and participation by a gastroenterology fellow. RESULTS: 6087 colonoscopies were evaluated in this study. Colonoscopies (n = 3729) performed in the morning were compared to colonoscopies performed in the afternoon (n = 2358). The crude completion rate to the cecum was 95.0% in the morning group while the completion rate to the cecum was 93.6% of the afternoon exams (p = 0.02). The morning colonoscopies had better bowel preparation quality (p < 0.001). The multivariate analyses demonstrated that gender, age, and bowel preparation quality impacted completion rates. After correcting for these factors, there was no significant difference in completion rates in the morning versus afternoon. CONCLUSION: Uncorrected cecal intubation rates were lower in the afternoon compared to the morning in outpatients undergoing colonoscopy. Bowel preparation quality was worse in the afternoon compared with the morning. Efforts at improving afternoon bowel preparation may improve the outcome of afternoon colonoscopies.

Long-term Follow-up of Patients Having False-Positive Multitarget Stool DNA Tests after Negative Screening Colonoscopy: The LONG-HAUL Cohort Study.

Background: Studies of colorectal cancer screening by multitarget stool DNA (MT-sDNA) show false-positive (FP) rates of 7% to 13%. It is unclear whether FP patients are at increased long-term risk of adverse outcomes.Methods: We compared subsequent clinical events among patients with apparent FP MT-sDNA with those in patients reported as true negative (TN). This was a retrospective cohort study of participants in pre-FDA approval MT-sDNA studies having nonadvanced or negative baseline colonoscopy findings from a single referral center. Per-protocol and calibrated cutoffs defined FP and TN groups. From the time of stool collection, we measured differences between FP and TN groups in time to death, subsequent cancer diagnosis, and onset of alarm symptoms.Results: Of 1,050 eligible patients, only 6 were lost to follow-up. Median age was 65.6 years [interquartile range (IQR), 56.8-72.3]; 54% were female. Median follow-up time was 4 years (IQR, 3.5-5.3). Eight aerodigestive (lung and gastrointestinal tract) cancers occurred. FP status by calibrated, but not per-protocol, cutoffs was associated with subsequent aerodigestive cancer; however, cumulative incidence did not exceed SEER expectations from the general population. By any cutoff method, FP status was not associated with mortality or alarm symptoms.Conclusions: Although FP status was associated with long-term aerodigestive cancers, new cases were not temporally related and did not exceed incidence estimates from general population.Impact: These observations do not justify aggressive follow-up evaluation for patients with FP MT-sDNA at this time. Larger studies are needed to confirm these early findings. Cancer Epidemiol Biomarkers Prev; 26(4); 614-21. ©2016 AACR.

Celecoxib for the Prevention of Colorectal Adenomas: Results of a Suspended Randomized Controlled Trial.

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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Limited-duration celecoxib prevents adenoma recurrence in patients with prior high-risk adenomas, in whom strategies to minimize cardiovascular toxicity might be feasible.

Selenium Supplementation for Prevention of Colorectal Adenomas and Risk of Associated Type 2 Diabetes.

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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Imaging of small bowel disease: comparison of capsule endoscopy, standard endoscopy, barium examination, and CT.

Capsule endoscopy is a revolutionary new diagnostic tool for the detection of small bowel disease. As the name implies, capsule endoscopy makes use of a swallowable video capsule; as such, it is the only technique that allows noninvasive endoscopic examination of the entire small bowel without sedation. Obscure gastrointestinal bleeding is the most common indication for capsule endoscopy, which commonly depicts arteriovenous malformations, small bowel tumors, and ulcers missed at standard endoscopy and imaging examinations. However, capsule endoscopy is not optimal for the localization of small bowel lesions. In addition, lesions can be missed due to poor bowel preparation, rapid or delayed small bowel transit, or orientation of the camera away from a lesion. Computed tomography and barium examinations are useful for detecting these missed lesions and for localizing lesions detected at capsule endoscopy. Other limitations of capsule endoscopy are the inability to treat lesions and its limited use in patients with small bowel strictures or obstruction. Nevertheless, this new technique is easy to perform, is well tolerated by patients, and, for the first time, allows noninvasive endoscopic evaluation of the entire small bowel.