Almost One-Third of Large Sessile Serrated Polyps Are Missed on CT Colonography.

BACKGROUND: Nearly one-third of colorectal cancers (CRC) arise via the serrated pathway. CT colonography (CTC) is a CRC screening examination. Endoscopic detection of sessile serrated polyps (SSPs) varies widely; it is unknown whether CTC effectively detects SSPs. The aim of this study is to determine whether CTC detects SSPs at an institution that performs a large volume of CTC. METHODS: We conducted a search of pathology records to identify serrated polyps (SPs) from 2005 to 2012. We extracted demographic data from the electronic health records (EHRs) of subjects with an SSP and examined endoscopy reports for location and size of each SSP. We identified subjects with a CTC within 1 year prior to the colonoscopy that found an SSP, and determined if the CTC identified the SSP. RESULTS: Our search found 3978 subjects with SP over the 7-year period. Seven hundred thirty-two subjects had at least 1 SSP. Eightytwo subjects had CTC done within 1 year prior to the colonoscopy that identified SSP. Seventy-nine subjects' polyps were identified on CTC. CT colonography was done an average of 38 ± 54 days prior to colonoscopy. One hundred fifteen SSPs were identified endoscopically. A total of 48.7% of all SSPs were identified via CTC; larger SSPs were more likely to be seen on CTC (P < .001), and 69.6% of SSPs larger than 10 mm were found via CTC. Proximal SSPs were more often identified than distal SSPs (P = .005). CONCLUSION: Given the miss rate for SSPs on CTC, endoscopists should be vigilant about examining the proximal colon in subjects referred after CTC, even if the imaging does not reveal a proximal polyp.

Lower Annual Rate of Progression of Short-Segment vs Long-Segment Barrett's Esophagus to Esophageal Adenocarcinoma.

BACKGROUND & AIMS: European guidelines recommend different surveillance intervals of non-dysplastic Barrett's esophagus (NDBE) based on segment length, as opposed to guidelines in the United States, which do recommend surveillance intervals based on BE length. We studied rates of progression of NDBE to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in patients with short-segment BE using the definition of BE in the latest guidelines (length ≥1 cm). METHODS: We collected demographic, clinical, endoscopy, and histopathology data from 1883 patients with endoscopic evidence of NDBE (mean age, 57.3 years; 83.5% male; 88.1% Caucasians) seen at 7 tertiary referral centers. Patients were followed for a median 6.4 years. Cases of dysplasia or EAC detected within 1 year of index endoscopy were considered prevalent and were excluded. Unadjusted rates of progression to HGD or EAC were compared between patients with short (≥1 and <3) and long (≥3) BE lengths using log-rank tests. A subgroup analysis was performed on patients with a documented Prague C&M classification. We used a multivariable proportional hazards model to evaluate the association between BE length and progression. Adjusted hazards ratios were calculated after adjusting for variables associated with progression. RESULTS: We found 822 patients to have a short-segment BE (SSBE) and 1061 to have long segment BE (LSBE). We found patients with SSBE to have a significantly lower annual rate of progression to EAC (0.07%) than of patients with LSBE (0.25%) (P = .001). For the combined endpoint of HGD or EAC, annual progression rates were significantly lower among patients with SSBE (0.29%) compared to compared to LSBE (0.91%) (P < .001). This effect persisted in multivariable analysis (hazard ratio, 0.32; 95% CI, 0.18-0.57; P < .001). CONCLUSION: We analyzed progression of BE (length ≥1 cm) to HGD or EAC in a large cohort of patients seen at multiple centers and followed for a median 6.4 years. We found a lower annual rate of progression of SSBE to EAC (0.07%/year) than of LSBE (0.25%/year). We propose lengthening current surveillance intervals for patients with SSBE.

Increasing prevalence of high-grade dysplasia and adenocarcinoma on index endoscopy in Barrett's esophagus over the past 2 decades: data from a multicenter U.S. consortium.

INTRODUCTION: Data on time trends of dysplasia and esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE) during the index endoscopy (ie, prevalent cases) are limited. Our aim was to determine the prevalence patterns of BE-associated dysplasia on index endoscopy over the past 25 years. METHODS: The Barrett's Esophagus Study is a multicenter outcome project of a large cohort of patients with BE. Proportions of patients with index endoscopy findings of no dysplasia (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and EAC were extracted per year of index endoscopy, and 5-yearly patient cohorts were tabulated over years 1990 to 2010+ (2010-current). Prevalent dysplasia and endoscopic findings were trended over the past 25 years using percentage dysplasia (LGD, HGD, EAC, and HGD/EAC) to assess changes in detection of BE-associated dysplasia over the last 25 years. Statistical analysis was done using SAS version 9.4 software (SAS, Cary, NC). RESULTS: A total of 3643 patients were included in the analysis with index endoscopy showing NDBE in 2513 (70.1%), LGD in 412 (11.5%), HGD in 193 (5.4%), and EAC in 181 (5.1%). Over time, there was an increase in the mean age of patients with BE (51.7 ± 29 years vs 62.6 ± 11.3 years) and the proportion of males (84% vs 92.6%) diagnosed with BE but a decrease in the mean BE length (4.4±4.3 cm vs 2.9±3.0 cm) as time progressed (1990-1994 to 2010-2016 time periods). The presence of LGD on index endoscopy remained stable over 1990 to 2016. However, a significant increase (148% in HGD and 112% in EAC) in the diagnosis of HGD, EAC, and HGD/EAC was noted on index endoscopy over the last 25 years (P < .001). There was also a significant increase in the detection of visible lesions on index endoscopy (1990-1994, 5.1%; to 2005-2009, 6.3%; and 2010+, 16.3%) during the same period. CONCLUSION: Our results suggest that the prevalence of HGD and EAC has significantly increased over the past 25 years despite a decrease in BE length during the same period. This increase parallels an increase in the detection of visible lesions, suggesting that a careful examination at the index examination is crucial.

Emphysematous Gastritis in a Patient with Untreated Cyclic Vomiting Syndrome.

Emphysematous gastritis (EG) is an uncommon and potentially fatal disease characterized by gastric pneumatosis in the setting of infection. While this disease has been described in the literature, it has not previously been identified as a potential complication of cyclic vomiting syndrome. We describe a patient with a history of cyclic vomiting syndrome who presented acutely ill and was found to have radiographic, endoscopic, and histologic evidence of EG. This case illustrates how an untreated functional bowel disorder can lead to severe and potentially fatal complications.

Factors influencing decisions about a career in hepatology: A survey of gastroenterology fellows.

Despite an unmet need for hepatologists in the United States, every year transplant hepatology (TH) fellowship positions remain unfilled. To address this, we investigated factors that influence trainee decisions about pursuing a career in hepatology. We invited current gastroenterology (GI) and TH fellows from all Accreditation Council for Graduate Medical Education-accredited programs for the academic year 2014-2015 to participate in an online survey about factors influencing decisions to train in hepatology. The same paper-based survey was distributed at a nationally recognized GI board review course. The survey was completed by 180 participants of which 91% were current GI or TH fellows and 24% were not aware of the pilot 3-year combined GI and TH training program. A majority of respondents (57%) reported that a shorter time (3 versus 4 years) to become board certification eligible would influence their decisions to pursue TH. The most common reasons for not pursuing hepatology were less endoscopy time (67%), additional length of training (64%), and lack of financial compensation (44%). Personal satisfaction (66%), management of complex multisystem disease (60%), and long-term relationships with patients (57%) were the most attractive factors. Sixty-one percent of participants reported having a mentor, and 94% of those with mentors reported that their mentors influenced their career decisions. Conclusion: We have identified several factors that affect fellows' decision to pursue TH. Shorter training, increased financial compensation, and increased endoscopy time are potentially modifiable factors that may increase the number of trainees seeking careers in hepatology and help alleviate the deficit of hepatologists. (Hepatology Communications 2017;1:347-353).

Esophagogastric Fistula Caused by an Angelchik Antireflux Prosthesis.

The Angelchik prosthesis is an antireflux device that was popular in the 1980s for treatment of refractory gastroesophageal reflux disease (GERD). We present a patient who developed a gastroesophageal fistula 17 years after Angelchik prosthesis placement. The incidence of late complications continues to grow, and clinicians should consider device malfunction in patients with history of Angelchik placement presenting with abdominal symptoms.

Clinical outcomes in patients with a diagnosis of "indefinite for dysplasia" in Barrett's esophagus: a multicenter cohort study.

BACKGROUND AND STUDY AIM: Data are limited on the natural history of patients with Barrett's esophagus with a diagnosis of "indefinite for dysplasia" (IND). The aims of this study were to: (i) determine rates of progression to high grade dysplasia (HGD) or esophageal adenocarcinoma, and compare these with rates for low grade dysplasia (LGD); and (ii) determine the proportion of patients whose histological IND diagnosis changed on follow-up endoscopy. PATIENTS AND METHODS: Demographic, endoscopic, and histologic information of patients with diagnoses of IND and LGD and at least 12 months of follow-up were extracted from the database of a multicenter Barrett's esophagus study. Rates and times for progression to HGD and esophageal adenocarcinoma and regression to nondysplastic epithelium were calculated. Proportions of diagnoses upgraded to HGD/esophageal adenocarcinoma or downgraded to nondysplastic epithelium at first follow-up endoscopy were evaluated. RESULTS: Amongst 2264 patients, 83 with a diagnosis of IND (mean age 60 years, 95 % men, 95 % white; mean follow-up 5.6 years) and 79 with diagnosis of LGD were identified. In the IND group, annual incidences of esophageal adenocarcinoma and HGD were 0.21 % and 0.64 %, respectively, representing a combined incidence of 0.8 %. Mean time to progression was 4.72 years. Within the IND group 55 % patients showed regression to nondysplastic epithelium at first follow-up endoscopy and the overall regression rate was 80 %. Corresponding rates in LGD patients were similar. CONCLUSIONS: Lesions diagnosed as IND and LGD show similar biological behavior and can be treated as a single category with respect to surveillance and follow-up.

Barrett's oesophagus length is established at the time of initial endoscopy and does not change over time: results from a large multicentre cohort.

OBJECTIVE: It is unclear whether Barrett's oesophagus (BO) length changes over time or whether the full length of the segment is established at the onset of disease recognition. The objectives of this study were to evaluate the association of age and BO length and to evaluate the changes in BO length over time. DESIGN: This is a prospective, multicentre cohort study involving patients with BO from five centres. Patients were divided into groups based on the decade of initial diagnosis of BO. The mean BO length and the mean change in BO length were calculated for each age decade. The mean change in BO length was also calculated between the index endoscopy and the last surveillance endoscopy. RESULTS: 3635 patients with BO were included in the study: 87.8% men, 92.8% Caucasians, mean age 60.9 years and mean BO length 3.5 cm. The mean change in BO length was 0.9 cm. The mean BO length did not significantly change for each age category: <30 years (4.6 cm), 30-39.9 years (3.2 cm), 40-49.9 years (3.1 cm), 50-59.9 years (3.1 cm), 60-69.9 years (3.6 cm), 70-79.7 (4.0 cm) and >80 years (4.5 cm), p=0.47. On subgroup analysis of patients with non-dysplastic BO who had at least 1 year of endoscopic follow up, there was a significant decrease in mean change in BO length across age categories ranging from +1.7 to -0.8 cm, p=0.03. CONCLUSIONS: There was no significant difference in BO length by age category in decades. In addition, the change in BO length from index to follow-up endoscopy was similar among patients >30 years. These findings suggest that a patient's BO segment length attains its full extent by the time of the initial endoscopic examination.

Influence of provider discussion and specific recommendation on colorectal cancer screening uptake among U.S. adults.

OBJECTIVES: It is unclear if provider recommendations regarding colorectal cancer (CRC) screening modalities affect patient compliance. We evaluated provider-patient communications about CRC screening with and without a specific screening modality recommendation on patient compliance with screening guidelines. METHODS: We used the 2007 Health Information National Trends Survey (HINTS) and identified 4283 respondents who were at least 50 years of age and answered questions about their communication with their care providers and CRC screening uptake. We defined being compliant with CRC screening as the use of fecal occult blood testing (FOBT) within 1 year, sigmoidoscopy within 5 years, or colonoscopy within 10 years. We used survey weights in all analyses. RESULTS: CRC screening discussions occurred with 3320 (76.2%) respondents. Approximately 95% of these discussions were with physicians. Overall, 2793 (62.6%) respondents were current with CRC screening regardless of the screening modality. Discussion about screening (odds ratio (OR)=8.83; 95% confidence interval (CI): 7.20-10.84) and providers making a specific recommendation about screening modality rather than leaving it to the patient to decide (OR=2.04; 95% CI: 1.54-2.68) were associated with patient compliance with CRC screening guidelines. CONCLUSION: Compliance with CRC screening guidelines is improved when providers discuss options and make specific screening test recommendations.

Early detection of colorectal cancer recurrence in patients undergoing surgery with curative intent: current status and challenges.

Despite advances in neoadjuvant and adjuvant therapy, attention to proper surgical technique, and improved pathological staging for both the primary and metastatic lesions, almost half of all colorectal cancer patients will develop recurrent disease. More concerning, this includes ~25% of patients with theoretically curable node-negative, non-metastatic Stage I and II disease. Given the annual incidence of colorectal cancer, approximately 150,000 new patients are candidates each year for follow-up surveillance. When combined with the greater population already enrolled in a surveillance protocol, this translates to a tremendous number of patients at risk for recurrence. It is therefore imperative that strategies aim for detection of recurrence as early as possible to allow initiation of treatment that may still result in cure. Yet, controversy exists regarding the optimal surveillance strategy (high-intensity vs. traditional), ideal testing regimen, and overall effectiveness. While benefits may involve earlier detection of recurrence, psychological welfare improvement, and greater overall survival, this must be weighed against the potential disadvantages including more invasive tests, higher rates of reoperation, and increased costs. In this review, we will examine the current options available and challenges surrounding colorectal cancer surveillance and early detection of recurrence.

Global changes in gene expression of Barrett's esophagus compared to normal squamous esophagus and gastric cardia tissues.

BACKGROUND: Barrett's esophagus (BE) is a metaplastic precursor lesion of esophageal adenocarcinoma (EA), the most rapidly increasing cancer in western societies. While the prevalence of BE is increasing, the vast majority of EA occurs in patients with undiagnosed BE. Thus, we sought to identify genes that are altered in BE compared to the normal mucosa of the esophagus, and which may be potential biomarkers for the development or diagnosis of BE. DESIGN: We performed gene expression analysis using HG-U133A Affymetrix chips on fresh frozen tissue samples of Barrett's metaplasia and matched normal mucosa from squamous esophagus (NE) and gastric cardia (NC) in 40 BE patients. RESULTS: Using a cut off of 2-fold and P<1.12E-06 (0.05 with Bonferroni correction), we identified 1324 differentially-expressed genes comparing BE vs NE and 649 differentially-expressed genes comparing BE vs NC. Except for individual genes such as the SOXs and PROM1 that were dysregulated only in BE vs NE, we found a subset of genes (n = 205) whose expression was significantly altered in both BE vs NE and BE vs NC. These genes were overrepresented in different pathways, including TGF-ß and Notch. CONCLUSION: Our findings provide additional data on the global transcriptome in BE tissues compared to matched NE and NC tissues which should promote further understanding of the functions and regulatory mechanisms of genes involved in BE development, as well as insight into novel genes that may be useful as potential biomarkers for the diagnosis of BE in the future.

Association between length of Barrett's esophagus and risk of high-grade dysplasia or adenocarcinoma in patients without dysplasia.

BACKGROUND & AIMS: It is not clear whether length of Barrett's esophagus (BE) is a risk factor for high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in patients with nondysplastic BE. We studied the risk of progression to HGD or EAC in patients with nondysplastic BE, based on segment length. METHODS: We analyzed data from a large cohort of patients participating in the BE Study-a multicenter outcomes project comprising 5 US tertiary care referral centers. Histologic changes were graded as low-grade dysplasia, HGD, or EAC. The study included patients with BE of documented length without dysplasia and at least 1 year of follow-up evaluation (n = 1175; 88% male), and excluded patients who developed HGD or EAC within 1 year of their BE diagnosis. The mean follow-up period was 5.5 y (6463 patient-years). The annual risk of HGD and EAC was plotted in 3-cm increments (≤3 cm, 4-6 cm, 7-9 cm, 10-12 cm, and ≥13 cm). We calculated the association between time to progression and length of BE. RESULTS: The mean BE length was 3.6 cm; 44 patients developed HGD or EAC, with an annual incidence rate of 0.67%/y. Compared with nonprogressors, patients who developed HGD or EAC had longer BE segments (6.1 vs 3.5 cm; P < .001). Logistic regression analysis showed a 28% increase in risk of HGD or EAC for every 1-cm increase in BE length (P = .01). Patients with BE segment lengths of 3 cm or shorter took longer to develop HGD or EAC than those with lengths longer than 4 cm (6 vs 4 y; P = nonsignificant). CONCLUSIONS: In patients with BE without dysplasia, length of BE was associated with progression to HGD or EAC. The results support the development of a risk stratification scheme for these patients based on length of BE segment.

Persistence of nondysplastic Barrett's esophagus identifies patients at lower risk for esophageal adenocarcinoma: results from a large multicenter cohort.

BACKGROUND & AIMS: Recent population-based studies have shown a low risk of esophageal adenocarcinoma (EAC) in patients with nondysplastic Barrett's esophagus (NDBE). We evaluated whether persistence of NDBE over multiple consecutive surveillance endoscopic examinations could be used in risk stratification of patients with Barrett's esophagus (BE). METHODS: We performed a multicenter outcomes study of a large cohort of patients with BE. Based on the number of consecutive surveillance endoscopies showing NDBE, we identified 5 groups of patients. Patients in group 1 were found to have NDBE at their first esophagogastroduodenoscopy (EGD). Patients in group 2 were found to have NDBE on their first 2 consecutive EGDs. Similarly, patients in groups 3, 4, and 5 were found to have NDBE on 3, 4, and 5 consecutive surveillance EGDs. A logistic regression model was built to determine whether persistence of NDBE independently protected against development of cancer. RESULTS: Of a total of 3515 patients with BE, 1401 patients met the inclusion criteria (93.3% white; 87.5% men; median age, 60 ±17 years). The median follow-up period was 5 ± 3.9 years (7846 patient-years). The annual risk of EAC in groups 1 to 5 was 0.32%, 0.27%, 0.16%, 0.2%, and 0.11%, respectively (P for trend = .03). After adjusting for age, sex, and length of BE, persistence of NDBE, based on multiple surveillance endoscopies, was associated with a gradually lower likelihood of progression to EAC. CONCLUSIONS: Persistence of NDBE over several endoscopic examinations identifies patients who are at low risk for development of EAC. These findings support lengthening surveillance intervals or discontinuing surveillance of patients with persistent NDBE.

Colonoscopy for colorectal cancer screening.

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Many, if not most, cases arise from premalignant lesions (adenomas) which may be identified and removed prior to becoming frankly malignant. For over a decade, colonoscopy has been the preferred modality for both CRC screening and prevention in the US. Early reports suggested that colonoscopic screening imparted a 90% risk reduction for colorectal cancer. Subsequent studies showed that estimate to be overly optimistic. While still an outstanding CRC screening and detection tool, colonoscopy has several important limitations. Some of these limitations relate to the mechanics of the procedure such as the risk of colonic perforation, bleeding, adverse consequences of sedation, and the inability to detect all colonic polyps. Other limitations reflect issues with patient perception regarding colonoscopy which, at least in part, drive patient non-adherence to recommended testing. This review examines the literature to address several important issues. First, we analyze the effect of colonoscopy on CRC incidence and mortality. Second, we consider the patient-based, periprocedural, and intraprocedural factors which may limit colonoscopy as a screening modality. Third, we explore new techniques and technologies which may enhance the efficacy of colonoscopy for adenoma detection. Finally, we discuss the short and long-term future of colonoscopy for CRC screening and the factors which may affect this future.

Probiotics for the treatment of inflammatory bowel disease.

Probiotics are organisms which provide a desired and beneficial effect on human health. With recent evidence implicating a disruption in the balance of the gastrointestinal microbiome and intestinal immunity as a potential trigger for inflammatory bowel disease (IBD), there has been growing interest in using probiotics as an adjunct to standard anti-inflammatory and immune suppressing therapy. Animal models describe potential and plausible mechanisms of action for probiotics to counter inflammation of colonic mucosa. Although there are insufficient data to recommend probiotics in ulcerative colitis or Crohn's disease, good evidence supports the use of specific probiotics for maintenance of remission in pouchitis. Although there are limited regulatory standards for the agents, probiotics are relatively safe with minimal reported side effects or contraindications. More rigorous studies need to be published supporting efficacy and safety of these agents before they become a mainstay of IBD medical treatment.