Interobserver reliability of methods to determine complete resection of adenomas in colonoscopy.

BACKGROUND: Forceps margin biopsy and polypectomy specimen margins have both been used to assess for polypectomy resection adequacy. The interobserver reliability of the two methods has not been well described. METHODS: The interpretability of polypectomy specimens for presence of residual neoplasia at the margin was assessed by two blinded pathologists. Next, the concordance of forceps margin biopsy interpretations between three blinded pathologists was evaluated by calculation of interobserver κ. RESULTS: Rates of polypectomy specimen margin interpretability were low: 24/92 (26 %) for pathologist A, 28/92 (30.4 %) for pathologist B. Concordance of forceps margin biopsy interpretations (n = 129) between pathologists was high. Two internal pathologists showed substantial agreement in margin biopsy interpretations (κ 0.779; 95 %CL 0.543, 0.912). The concordance remained strong after biopsies were reviewed by a third, external pathologist (κ 0.829; 95 %CL 0.658, 0.924). There was complete agreement on 123/129 (95.3 %) between all three pathologists for presence of neoplasia. CONCLUSION: The majority of polypectomy specimen margins were uninterpretable by pathologists for presence of residual neoplasia. Forceps margin biopsy shows strong interobserver reliability in adenomatous lesions.

Alternative approaches to polyp extraction in colonoscopy: a proof of principle study.

BACKGROUND AND AIMS: A limitation of determination of the completeness of resection in polypectomy is polyp fragmentation. When a polyp fragments, the pathologist cannot determine resection completeness. Alternative approaches to reduce polyp fragmentation include reducing shearing forces on the polyp or removing polyps through the instrument channel. The primary aim of this study was to assess fragmentation of polyps extracted using different approaches from conventional polyp retrieval. METHODS: Polyps (5-15 mm) resected by cold snare or cautery by 3 colonoscopists were extracted from the colonoscope using 1 of 4 techniques. Method I was the conventional method of pressing the suction valve button and retrieving the polyp through a trap. Method II involved removing the suction valve, covering the open suction valve cylinder with a finger. Method III used a Roth Net polyp retriever placed through the instrument channel. Method IV involved connecting a polyp trap to suction onto the instrument channel port. Fragmentation was defined as multiple pieces of the specimen in formalin, as grossly described by the pathologist. Alternative approaches (methods II, III, and IV) were all compared with the conventional method (method I). RESULTS: The method I fragmentation rate of polyps was 60.3% (123/204). Method II extraction reduced fragmentation to 43.0% (52/121, P = .003), proving that fragmentation occurs with passage through the suction valve channel. Method III had a lower fragmentation rate of 23.1% (6/26, P < .001). Method IV likewise showed a reduced fragmentation rate of 18.5% (5/27, P < .001). CONCLUSIONS: Polyp fragmentation is reduced by removal of the suction valve button. There is also a decrease in fragmentation rates in removing the polyp by connecting the polyp trap to the instrument port. Our study suggests that decreasing polyp fragmentation and improving pathology margin interpretability is possible through methods that extract polyps through the instrument port with currently available devices.

A compartmentalized type I interferon response in the gut during chronic HIV-1 infection is associated with immunopathogenesis.

OBJECTIVE(S): Type I interferon (IFN-I) responses confer both protective and pathogenic effects in persistent virus infections. IFN-I diversity, stage of infection and tissue compartment may account for this dichotomy. The gut is a major site of early HIV-1 replication and microbial translocation, but the nature of the IFN-I response in this compartment remains unclear. DESIGN: Samples were obtained from two IRB-approved cross-sectional studies. The first study included individuals with chronic, untreated HIV-1 infection (n = 24) and age/sex-balanced uninfected controls (n = 14). The second study included antiretroviral-treated, HIV-1-infected individuals (n = 15) and uninfected controls (n = 15). METHODS: The expression of 12 IFNα subtypes, IFNß and antiviral IFN-stimulated genes (ISGs) were quantified in peripheral blood mononuclear cells (PBMCs) and colon biopsies using real-time PCR and next-generation sequencing. In untreated HIV-1-infected individuals, associations between IFN-I responses and gut HIV-1 RNA levels as well as previously established measures of colonic and systemic immunological indices were determined. RESULTS: IFNα1, IFNα2, IFNα4, IFNα5 and IFNα8 were upregulated in PBMCs during untreated chronic HIV-1 infection, but IFNß was undetectable. By contrast, IFNß was upregulated and all IFNα subtypes were downregulated in gut tissue. Gut ISG levels positively correlated with gut HIV-1 RNA and immune activation, microbial translocation and inflammation markers. Gut IFN-I responses were not significantly different between HIV-1-infected individuals on antiretroviral treatment and uninfected controls. CONCLUSION: The IFN-I response is compartmentalized during chronic untreated HIV-1 infection, with IFNß being more predominant in the gut. Gut IFN-I responses are associated with immunopathogenesis, and viral replication is likely a major driver of this response.

Effect of cytomegalovirus and Epstein-Barr virus replication on intestinal mucosal gene expression and microbiome composition of HIV-infected and uninfected individuals.

BACKGROUND: HIV-infection is associated with dramatic changes in the intestinal mucosa. The impact of other viral pathogens is unclear. METHODS: One hundred and eight (108) biopsies from left and right colon (n = 79) and terminal ileum (n = 29) were collected from 19 HIV-infected and 22 HIV-uninfected participants. Levels of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNA were measured by droplet digital PCR. Mucosal gene expression was measured via multiplex-assay. Microbiome analysis was performed using bacterial 16S-rDNA-pyrosequencing. The effect of CMV and EBV replication on the microbiome composition and mRNA-expression of selected cytokines (IL-6, IFN-γ, IL-1ß, CCL2, IL-8, and IFN-ß1) was evaluated. RESULTS: Overall, CMV and EBV were detected in at least one intestinal site in 60.5 and 78.9% of participants, respectively. HIV-infected individuals demonstrated less detectable CMV (PB = 0.02); CMV was more frequently detected in terminal ileum than colon (PB = 0.05). Detectable EBV was more frequent among HIV-infected (P B= 0.04) without differences by intestinal site. The number of operational taxonomic units did not differ by CMV or EBV detection status. Among HIV-infected participants, higher CMV was only associated with lower relative abundance of Actinobacteria in the ileum (P = 0.03). Presence of CMV was associated with upregulated expression of all selected cytokines in the ileum (all P < 0.02) and higher expression of IL-8 and IFN-ß1 in the colon (all P < 0.05) of HIV-uninfected participants, but not among HIV-infected. EBV had no effect on cytokine expression or microbiome composition whatsoever. CONCLUSION: These results illustrate a complex interplay among HIV-infection, intestinal CMV replication, and mucosal gut environment, and highlight a possible modulatory effect of CMV on the microbial and immune homeostasis.

The Effects of Bowel Preparation on Microbiota-Related Metrics Differ in Health and in Inflammatory Bowel Disease and for the Mucosal and Luminal Microbiota Compartments.

OBJECTIVES: Bowel preparations (BPs) taken before colonoscopy may introduce a confounding effect on the results of gastrointestinal microbiota studies. This study aimed to determine the effect of bowel preparation on the mucosa-associated and luminal colonic microbiota in healthy subjects (HC) and inflammatory bowel disease (IBD) patients. METHODS: Biopsy samples (n=36) and fecal samples (n=30) were collected from 10 HC and 8 IBD subjects pre- and post-BP. 16S rRNA gene was pyrosequenced using 454 Titanium protocols. We compared the differences between the pre- and post-BP samples (i.e., comparisons-across-bowel-prep); we examined the effect of BP on the expected separation of the mucosal vs. the luminal compartments (i.e., comparisons-across-compartments). Last, we compared the baseline differences between the HC vs. IBD groups (a secondary analysis), and examined whether the differences between the HC vs. IBD changed after BP. RESULTS: In comparisons-across-bowel-prep, the Shannon's index (SI) decreased only in the biopsy samples of IBD subjects post-BP (P=0.025) and phylogenetic diversity-whole tree (PD-WT) metric decreased in biopsy samples of HC subjects post-BP (P=0.021). In secondary comparisons, the subtle differences between the fecal samples of the HC vs. IBD groups, in terms of evenness and the SI, were not apparent post-BP. In terms of ß-diversity, in comparisons-across-bowel-prep, the proportion of shared operational taxonomic units (OTUs) in pre- and post-BP samples was low (~30%) and unweighted Unifrac distances between pre- and post-BP specimens ranged from 0.52 to 0.66. HC biopsies were affected more than IBD biopsies with BP (P=0.004). In comparisons-across-compartments, the proportion of shared OTUs between biopsy and fecal samples increased and Unifrac distances decreased post-BP in IBD subjects, reducing the differences between the mucosal and luminal compartments of the gut microbiota. Interindividual differences in Unifrac distances were preserved even with BP effects, although the effects were greater on weighted Unifrac distances. Bacteroidetes and its subtypes increased post-BP in both the luminal and mucosal compartments. CONCLUSIONS: Bowel preparations affect the composition and diversity of the fecal and luminal microbiota in the short term, introducing potential bias into experiments examining the gut microbiota. The magnitude of the effect of BP is not greater than that of interindividual variation. Both the luminal and mucosal compartments of the gut microbiota get affected, and samples from controls and IBD subjects may get affected differently. Studies of the colonic microbiota should take into account the direction and the magnitude of the change introduced by BP during the design stage of the experiments, and consider sample sizes so that potential bias is minimized.

Patient Non-adherence and Cancellations Are Higher for Screening Colonoscopy Compared with Surveillance Colonoscopy.

BACKGROUND: A significant proportion of the eligible population is non-adherent to colonoscopy for colorectal cancer (CRC) screening. AIMS: To define the demographic and clinical variables associated with non-adherence and multiple cancellations to scheduled colonoscopy within 1 year in a CRC screening and adenomatous polyp surveillance population. METHODS: This was an observational cohort study of 617 consecutive patients scheduled to undergo colonoscopy at an outpatient academic tertiary care center for CRC screening or adenomatous polyp surveillance from January 2012 to September 2012. RESULTS: Overall, 551 patients (89.3%) were adherent and 66 (10.7%) were non-adherent to scheduled colonoscopy at 1 year. The relative risk for non-adherence was 5.42 [95% confidence interval (CI) 2.74-10.75] in patients undergoing colonoscopy for screening compared to those for surveillance (16.7 vs. 3.5% non-adherence, respectively, P < 0.001). An indication of screening in comparison with surveillance was associated with non-adherence [odds ratio (OR) 12.69, 95% CI 4.18-38.51] and multiple cancellations (OR 2.33, 95% CI 1.27-4.31) by multiple regression analysis. CONCLUSIONS: Patients undergoing colonoscopy for CRC screening are significantly less likely to attend their scheduled procedure within a year and have more procedure cancellations than those undergoing surveillance colonoscopy.

HIV-associated mucosal gene expression: region-specific alterations.

OBJECTIVE: Despite the use of HAART to control HIV, systemic immune activation and inflammation persists with the consequence of developing serious non-AIDS events. The mechanisms that contribute to persistent systemic immune activation have not been well defined. The intestine is the major source of "sterile" inflammation and plays a critical role in immune function; thus, we sought to determine whether intestinal gene expression was altered in virally controlled HIV-infected individuals. DESIGN AND METHODS: Gene expression was compared in biopsy samples collected from HIV-uninfected and HIV-infected individuals from the ileum, right colon (ascending colon), and left colon (sigmoid). Affymetrix gene arrays were performed on tissues and pathway analyses were conducted. Gene expression was correlated with systemic markers of intestinal barrier dysfunction and inflammation and intestinal microbiota composition. RESULTS: Genes involved in cellular immune response, cytokine signaling, pathogen-influenced signaling, humoral immune response, apoptosis, intracellular and second messenger signaling, cancer, organismal growth and development, and proliferation and development were upregulated in the intestine of HIV-infected individuals with differences observed in the ileum, right, and left colon. Gene expression in the ileum primarily correlated with systemic markers of inflammation (e.g., IL7R, IL2, and TLR2 with serum TNF) whereas expression in the colon correlated with the microbiota community (e.g., IFNG, IL1B, and CD3G with Bacteroides). CONCLUSION: These data demonstrate persistent, proinflammatory changes in the intestinal mucosa of virally suppressed HIV-infected individuals. These changes in intestinal gene expression may be the consequence of or contribute to barrier dysfunction and intestinal dysbiosis observed in HIV.

Hepatitis B vaccination in patients with inflammatory bowel disease.

AIM: To determine the prevalence for hepatitis B virus (HBV) and HBV screening and vaccination practices for inflammatory bowel disease (IBD). METHODS: This study is a retrospective, cross-sectional observational study. A retrospective chart review was performed in 500 patients who have been consecutively treated for IBD between September 2008 and January 2013 at the Rush University Medical Center Gastroenterology section. The patients were identified through the electronic medical record with the criteria that they attended the gastroenterology clinic, and that they had a diagnosis of IBD at the time of visit discharge. Once identified, each record was analyzed to determine whether the subject had been infected with HBV in the past, already been vaccinated against HBV, or advised to get vaccinated and followed through with the recommended vaccination. RESULTS: About 254 out of 500 patients (51%) had HBV screening ordered. Among those ordered to have screening tests, 86% followed through with HBV serology. Gastroenterology physicians had significantly different screening ratios from each other (P < 0.001). There were no significant differences in the ratios of HBV screening when IBD specialists were compared to other gastroenterology physicians (0.505 ± 0.023 vs 0.536 ± 0.066, P = 0.66). Of those 220 patients screened, 51% of IBD patients were found not to be immune against HBV. Approximately 50% of gastroenterology physicians recommended HBV vaccinations to their patients in whom serology was negative for antibodies against HBV. IBD specialists recommended vaccinations to a higher percentage of their patients compared to other gastroenterology physicians (0.168 ± 0.019 vs 0.038 ± 0.026, P = 0.015). Present and/or past HBV infection was found in 3.6% of the patients who had serology checked. There was no statistically significant difference in the prevalence of hepatitis B surface antigen (HBsAg) between our study and that reported in previous studies done in Spain (4/220 vs 14/2076 respectively, P = 0.070); and in France (4/220 vs 3/315 respectively, P = 0.159). But, the prevalence of anti-HBcAb in this study was less than that reported in the study in Spain (7/220 vs 155/2076 respectively, P = 0.006); and was not significantly different from that reported in the study in France (7/220 vs 8/315 respectively, P = 0.313). CONCLUSION: The prevalence of HBsAg in our IBD patients was not higher than previously reported European studies. Most IBD patients are not routinely screened or vaccinated against HBV at a tertiary referral center in the United States.

A compositional look at the human gastrointestinal microbiome and immune activation parameters in HIV infected subjects.

HIV progression is characterized by immune activation and microbial translocation. One factor that may be contributing to HIV progression could be a dysbiotic microbiome. We therefore hypothesized that the GI mucosal microbiome is altered in HIV patients and this alteration correlates with immune activation in HIV. 121 specimens were collected from 21 HIV positive and 22 control human subjects during colonoscopy. The composition of the lower gastrointestinal tract mucosal and luminal bacterial microbiome was characterized using 16S rDNA pyrosequencing and was correlated to clinical parameters as well as immune activation and circulating bacterial products in HIV patients on ART. The composition of the HIV microbiome was significantly different than that of controls; it was less diverse in the right colon and terminal ileum, and was characterized by loss of bacterial taxa that are typically considered commensals. In HIV samples, there was a gain of some pathogenic bacterial taxa. This is the first report characterizing the terminal ileal and colonic mucosal microbiome in HIV patients with next generation sequencing. Limitations include use of HIV-infected subjects on HAART therapy.

Inpatient capsule endoscopy leads to frequent incomplete small bowel examinations.

AIM: To examine the predictive factors of capsule endoscopy (CE) completion rate (CECR) including the effect of inpatient and outpatient status. METHODS: We identified 355 consecutive patients who completed CE at Rush University Medical Center between March 2003 and October 2005. Subjects for CE had either nothing by mouth or clear liquids for the afternoon and evening of the day before the procedure. CE exams were reviewed by two physicians who were unaware of the study hypotheses. After retrospective analysis, 21 cases were excluded due to capsule malfunction, prior gastric surgery, endoscopic capsule placement or insufficient data. Of the remaining 334 exams [264 out-patient (OP), 70 in-patient (IP)], CE indications, findings, location of the patients [IP vs OP and intensive care unit (ICU) vs general medical floor (GMF)] and gastrointestinal transit times were analyzed. Statistical analysis was completed using SPSS version 17 (Chicago, IL). Chi-square, t test or fisher exact-tests were used as appropriate. Multivariate logistic regression analysis was used to identify variables associated with incomplete CE exams. RESULTS: The mean age for the entire study population was 54.7 years. Sixty-one percent of the study population was female, and gender was not different between IPs vs OPs (P = 0.07). The overall incomplete CECR was 14% in our study. Overt obscure gastrointestinal bleeding (OGB) was significantly more common for the IP CE (P = 0.0001), while abdominal pain and assessment of IBD were more frequent indications for the OP CE exams (P = 0.002 and P = 0.01, respectively). Occult OGB was the most common indication and arteriovenous malformations were the most common finding both in the IPs and OPs. The capsule did not enter the small bowel (SB) in 6/70 IPs and 8/264 OPs (P = 0.04). The capsule never reached the cecum in 31.4% (22/70) of IP vs 9.5% (25/ 264) of OP examinations (P < 0.001). The mean gastric transit time (GTT) was delayed in IPs compared to OPs, 98.5 ± 139.5 min vs 60.4 ± 92.6 min (P = 0.008). Minimal SB transit time was significantly prolonged in the IP compared to the OP setting [IP = 275.1 ± 111.6 min vs OP = 244.0 ± 104.3 min (P = 0.037)]. CECR was also significantly higher in the subgroup of patients with OGB who had OP vs IP exams (95% vs 80% respectively, P = 0.001). The proportion of patients with incomplete exams was higher in the ICU (n = 7/13, 54%) as compared to the GMF (n = 15/57, 26%) (P = 0.05). There was only a single permanent SB retention case which was secondary to a previously unknown SB stricture, and the remaining incomplete SB exams were due to slow transit. Medications which affect gastrointestinal system motility were tested both individually and also in aggregate in univariate analysis in hospitalized patients (ICU and GMF) and were not predictive of incomplete capsule passage (P > 0.05). Patient location (IP vs OP) and GTT were independent predictors of incomplete CE exams (P < 0.001 and P = 0.008, respectively). CONCLUSION: Incomplete CE is a multifactorial problem. Patient location and related factors such as severity of illness and sedentary status may contribute to incomplete exams.

Laparoscopic repair of a recurrent chronic traumatic diaphragmatic hernia.

Traditionally the approach to a long-standing traumatic diaphragmatic hernia has been a closure of the diaphragmatic defect via a thoracotomy. The evolution of minimally invasive surgery has allowed surgeons to challenge many of the traditional approaches. Herein we describe the first reported case of laparoscopic repair of recurrent chronic traumatic diaphragmatic hernia as well as review the current literature on minimally invasive surgery for traumatic diaphragmatic hernia. With proper advanced laparoscopic skills and techniques laparoscopic diaphragmatic herniorrhaphy for a chronic and recurrent defect is a safe and viable option.

Endoscopy in eosinophilic esophagitis: "feline" esophagus and perforation risk.

BACKGROUND & AIMS: Idiopathic eosinophilic esophagitis is an underdiagnosed disease with typical endoscopic findings, which have not been well described. METHODS: Charts and pathology reports at two tertiary care centers from June 1993 to April 2002 were reviewed to describe the endoscopic findings of this disease and to correlate them with clinical characteristics. Eight patients were identified as having eosinophilic esophagitis based on clinical symptoms and pathology reports. RESULTS: Soft and subtle ring(s) in the esophagus were found in 7 of 8 patients. In 3 of 8 patients, the esophagus appeared rigid. Mucosal rents occurred with simple passage of the endoscope in 5 of 8 patients. One patient developed a perforation after simple passage of the endoscope. Endoscopic findings can be normal or very subtle in these patients, and the findings can easily be missed during endoscopy. Tearing of the esophagus can occur with simple passage of the endoscope or biopsy even in the absence of overt rings. A minimum of 8 weeks of medical therapy (proton pump inhibitor, histamine antagonists, immunosuppressants) should be undertaken before considering dilation because of the high risk involved with the procedure and the good response to medical therapy. CONCLUSIONS: We recommend considering dilation only in patients with eosinophilic esophagitis who do not respond to medical therapy and have rings that appear to be obstructing the lumen.