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Our aim was to examine the humoral immune response against Streptococcus gallolyticus subspecies gallolyticus antigens in individuals subjected to a routine colonoscopy in which colon adenomatous polyps were present or not. Serum samples from 133 individuals with adenomatous polyps and serum samples from 53 individuals with a normal colonoscopy were included. Western blot was performed in all subjects using a whole cell antigen from S. gallolyticus ATCC 9809, and rabbit antisera against the whole cell bacteria was prepared as a control. By analyzing the immune profile of the rabbit-immunized sera by Western-blot, at least 22 proteins were identified as immunogenic in S. gallolyticus. When we evaluated sera from human subjects, two proteins of approximately 30 and 22 kDa were most prominent. Based on this 2-protein band pattern, Western-blot profiles from human subjects were compared. The detection of a protein band of 22 kDa was associated with the presence of adenomatous polyps in colon [odds ratios (OR) 7.98, 95% confidence intervals (CI): 3.54-17.93], p < 0.001. When the presence of the 30 kDa protein alone or both the 22 and 30 kDa proteins were analyzed, the OR increased to 22.37 (95% CI: 3.77-131.64), p < 0.001. The specificity was 84.9 for the presence of the 22 kDa protein, and 98.1 for the presence of the 30 kDa protein alone or both 22 and 30 kDa bands. Serum from individuals with adenomatous polyps recognized two proteins from S. gallolyticus. This result confirmed the possible association of S. gallolyticus with adenomatous polyps in the colon.

Background Appetite and energy expenditure are regulated in part by ghrelin and leptin produced in the gastric mucosa, which may be modified by H. pylori colonization. We prospectively evaluated the effect of H. pylori eradication on meal-associated changes in serum ghrelin and leptin levels, and body weight. Methods Veterans referred for upper GI endoscopy were evaluated at baseline and ≥8 weeks after endoscopy, and H. pylori status and body weight were ascertained. During the first visit in all subjects, and during subsequent visits in the initially H. pylori-positive subjects and controls, blood was collected after an overnight fast and 1 h after a standard high protein meal, and levels of eight hormones determined. Results Of 92 enrolled subjects, 38 were H. pylori-negative, 44 H. pylori-positive, and 10 were indeterminate. Among 23 H. pylori-positive subjects who completed evaluation after treatment, 21 were eradicated, and 2 failed eradication. After a median of seven months following eradication, six hormones related to energy homeostasis showed no significant differences, but post-prandial acylated ghrelin levels were nearly six-fold higher than pre-eradication (p = 0.005), and median integrated leptin levels also increased (20%) significantly (p < 0.001). BMI significantly increased (5 ± 2%; p = 0.008) over 18 months in the initially H. pylori-positive individuals, but was not significantly changed in those who were H. pylori-negative or indeterminant at baseline. Conclusions Circulating meal-associated leptin and ghrelin levels and BMI changed significantly after H. pylori eradication, providing direct evidence that H. pylori colonization is involved in ghrelin and leptin regulation, with consequent effects on body morphometry.

To determine the expression and clinical significance of transcriptional intermediary factor 1 gamma (TIF1γ), Smad4 and transforming growth factor-beta (TGFβR) across a spectrum representing colorectal cancer (CRC) development.Tissue microarrays were prepared from archival paraffin embedded tissue, including 51 colorectal carcinomas, 25 tubular adenomas (TA) and 26 HPs, each with matched normal colonic epithelium. Immunohistochemistry was performed using antibodies against TIF1γ, Smad4 and TGFβRII. The levels of expression were scored semi-quantitatively (score 0-3 or loss and retention for Smad4).Overexpression of TIF1γ was detected in 5/26 (19%) HP; however, it was seen in a significantly higher proportion of neoplasms, 15/25 (60%) TAs and 24/51 (47%) CRCs (P0.05). Normal colonic mucosa, HP, and TAs showed strong Smad4 expression, while its expression was absent in 22/51 (43%) CRCs. Overexpression of TGFβRII was more commonly seen in neoplasms, 13/25 (52%) TAs and 29/51 (57%) CRCs compared to 9/26 (35%) HP (P0.05). Furthermore, there was a correlation between TIF1γ overexpression and Smad4 loss in CRC (Kendall tau rank correlation value = 0.35, P0.05). The levels of TIF1γ overexpression were significantly higher in stage III than in stage I and II CRC (P0.05).The findings suggest that over-expression of TIF1γ occurs in early stages of colorectal carcinogenesis, is inversely related with Smad4 loss, and may be a prognostic indicator for poor outcome.

Esophageal adenocarcinoma (EA), the type of cancer linked to heartburn due to gastroesophageal reflux diseases (GERD), has increased six fold in the past 30 years. This cannot currently be explained by the usual environmental or by host genetic factors. EA is the end result of a sequence of GERD-related diseases, preceded by reflux esophagitis (RE) and Barrett’s esophagus (BE). Preliminary studies by Pei and colleagues at NYU on elderly male veterans identified two types of microbiotas in the esophagus. Patients who carry the type II microbiota are >15 fold likely to have esophagitis and BE than those harboring the type I microbiota. In a small scale study, we also found that 3 of 3 cases of EA harbored the type II biota. The findings have opened a new approach to understanding the recent surge in the incidence of EA.Our long-term goal is to identify the cause of GERD sequence. The hypothesis to be tested is that changes in the foregut microbiome are associated with EA and its precursors, RE and BE in GERD sequence. We will conduct a case control study to demonstrate the microbiome disease association in every stage of GERD sequence, as well as analyze the trend in changes in the microbiome along disease progression toward EA, by two specific aims. Aim 1 is to conduct a comprehensive population survey of the foregut microbiome and demonstrate its association with GERD sequence. Furthermore, spatial relationship between the esophageal microbiota and upstream (mouth) and downstream (stomach) foregut microbiotas as well as temporal stability of the microbiome-disease association will also be examined. Aim 2 is to define the distal esophageal metagenome and demonstrate its association with GERD sequence. Detailed analyses will include pathway-disease and gene-disease associations. Archaea, fungi and viruses, if identified, also will be correlated with the diseases. A significant association between the foregut microbiome and GERD sequence, if demonstrated, will be the first step for eventually testing whether an abnormal microbiome is required for the development of the sequence of phenotypic changes toward EA. If EA and its precursors represent a microecological disease, treating the cause of GERD might become possible, for example, by normalizing the microbiota through use of antibiotics, probiotics, or prebiotics. Causative therapy of GERD could prevent its progression and reverse the current trend of increasing incidence of EA.

Objective To qualitatively evaluate the views of Haitian immigrants on cancer and the influence of cultural and socio-ecological factors on cancer screening behavior. Methods Six focus groups, consisting of 4–10 individuals each, were conducted among Haitian adults at average risk for colorectal cancer. The interviews were conducted in Haitian Creole and featured questions that addressed beliefs and attitudes about general health, access to health care, colon cancer, and screening practices. Results The focus groups provided insight into the health service utilization patterns in the Haitian community, as well as the factors driving them including language and the pattern of accessing healthcare only for emergencies. Conclusions Many misconceptions regarding cancer and its development were evident in the discussions. However participants were willing to follow the recommendations of a physician. This highlighted the importance in this community of disseminating information at every opportunity about preventative care, including colorectal cancer screening.

This paper presents the results oj a jollow-up evaluation conducted to assess the impact oj a community-wide stop smoking contest conducted in Buffalo, lVew York in January 1988. The contest challenged smokers to make a pledge to quit jar 30 days to have a chance to win $1,000 cash, a vacation trip, or other prizes. Finalists were randomly selected and chemically tested to verify abstinence. Telephone jollow-up interviews were conducted on a sample oj 411 contestants six weeks and eight months ajter the quit date. A total oj 2,565 smokers enrolled in the contest. Compared to smokers in the general population, contestants were more likely to be jemale, white, under age 40, and smoke 25 or more cigarettes daily. Over 90 percent oj contestants attempted to stop smoking, 51 percent quit jar the 3D-day contest period, and 32 percent were not smoking ajter eight months.

Although many patients with human immunodeficiency virus (HIV) infection are now living well beyond 50 years of age, there are no data available on colorectal cancer screening in this population. The aim of this study was to determine the utility of screening flexible sigmoidoscopy in patients with HIV.Consecutive patients at average risk for colorectal cancer who were referred for screening flexible sigmoidoscopy were prospectively identified. A detailed medical history was obtained from all patients before flexible sigmoidoscopy, and colonoscopy was recommended for all subjects with positive sigmoidoscopic findings.A total of 2382 patients were enrolled in the study; 165 were HIV positive. The prevalence of neoplastic lesions (adenomas or adenocarcinomas) in the distal colon was significantly higher in HIV-infected patients than in control subjects (25.5% vs 13.1%, P.001), and the odds of HIV-infected patients having a neoplastic lesion was significantly higher even after adjustment for potential confounding variables (odds ratio, 2.34; 95% confidence interval, 1.60-3.44). The prevalence of adenomas of any size (25.5% vs 12.9%, P.001) and advanced neoplasia (7.3% vs 3.8%, P = .03) in the distal colon was significantly higher in HIV-infected patients. Among individuals with positive results on flexible sigmoidoscopy, proximal colonic neoplastic lesions on follow-up colonoscopy were more common in HIV-infected patients after adjustment for age, sex, and race/ethnicity (odds ratio, 1.88; 95% confidence interval, 1.02-3.46).Patients infected with HIV are more likely to have colonic neoplasms on screening flexible sigmoidoscopy than those without HIV, and these individuals should be offered colorectal cancer screening.

Although the association between distal neoplasia on sigmoidoscopy and proximal colonic pathology on follow-up colonoscopy has been well-described, it is not known if these findings are consistent across ethnic groups. The aim of this study was to evaluate ethnic variations in the prevalence of proximal neoplasia on follow-up colonoscopy after a neoplastic lesion is found on sigmoidoscopy.Consecutive asymptomatic patients at average-risk for colorectal cancer who were referred for screening flexible sigmoidoscopy were prospectively enrolled. Colonoscopy was recommended for all patients with a polyp on flexible sigmoidoscopy, regardless of size. Advanced neoplasms were defined as adenomasor = 10 mm in diameter or any adenoma, regardless of size, with villous histology, high-grade dysplasia, or cancer.Among the 2,207 patients who had sigmoidoscopy, 970 were Caucasian, 765 were African American, 395 were Hispanic, and 77 were Asian. The prevalence of neoplasia in the distal colon was 12.6% in Caucasians, 11.2% in African Americans, 15.9% in Hispanics, and 24.7% in Asians (p = 0.002). Of the 290 patients with neoplastic lesions on sigmoidoscopy, follow-up colonoscopy identified neoplasms in the proximal colon in 63.9% of Caucasians, 59.3% of African Americans, 66.7% of Hispanics, and 26.3% of Asians (p = 0.01). Advanced neoplasms in the proximal colon were highest in African Americans (34.9%) and lowest in Asians (10.5%).In our study population, Asians demonstrated a higher prevalence of distal colonic neoplasia and a lower prevalence of proximal colonic neoplasia compared to non-Asians. Future studies should explore ethnic variation in colonic neoplasia prevalence and location since ethnic variation could lead to tailored colorectal cancer screening strategies.

The microbiota of the human stomach and the influence of Helicobacter pylori colonization on its composition remain largely unknown. We characterized bacterial diversity within the human gastric mucosa by using a small subunit 16S rDNA clone library approach and analyzed 1,833 sequences generated by broad-range bacterial PCR from 23 gastric endoscopic biopsy samples. A diverse community of 128 phylotypes was identified, featuring diversity at this site greater than previously described. The majority of sequences were assigned to the Proteobacteria , Firmicutes , Actinobacteria , Bacteroidetes , and Fusobacteria phyla. Ten percent of the phylotypes were previously uncharacterized, including a Deinococcus -related organism, relatives of which have been found in extreme environments but not reported before in humans. The gastric clone libraries from 19 subjects contained H. pylori rDNA; however, only 12 of these subjects tested positive for H. pylori by conventional laboratory methods. Statistical analysis revealed a large degree of intersubject variability of the gastric ecosystem. The presence of H. pylori did not affect the composition of the gastric community. This gastric bacterial rDNA data set was significantly different from sequence collections of the human mouth and esophagus described in other studies, indicating that the human stomach may be home to a distinct microbial eco-system. The gastric microbiota may play important, as-yet-undiscovered roles in human health and disease.

The esophagus, like other luminal organs of the digestive system, provides a potential environment for bacterial colonization, but little is known about the presence of a bacterial biota or its nature. By using broad-range 16S rDNA PCR, biopsies were examined from the normal esophagus of four human adults. The 900 PCR products cloned represented 833 unique sequences belonging to 41 genera, or 95 species-level operational taxonomic units (SLOTU); 59 SLOTU were homologous with culture-defined bacterial species, 34 with 16S rDNA clones, and two were not homologous with any known bacterial 16S rDNA. Members of six phyla, Firmicutes , Bacteroides , Actinobacteria , Proteobacteria , Fusobacteria , and TM7 , were represented. A large majority of clones belong to 13 of the 41 genera (783/900, 87%), or 14 SLOTU (574/900, 64%) that were shared by all four persons. Streptococcus (39%), Prevotella (17%), and Veilonella (14%) were most prevalent. The present study identified ≈56–79% of SLOTU in this bacterial ecosystem. Most SLOTU of esophageal biota are similar or identical to residents of the upstream oral biota, but the major distinction is that a large majority (82%) of the esophageal bacteria are known and cultivable. These findings provide evidence for a complex but conserved bacterial population in the normal distal esophagus.

We hypothesized that laparoscopic adjustable gastric banding (LAGB) reduces weight and modulates ghrelin production, but largely spares gastrointestinal endocrine function. To examine this hypothesis, we determined plasma concentrations of appetite-control, insulinotropic, and digestive hormones in relation to LAGB.Twenty-four patients undergoing LAGB were prospectively enrolled. Body mass index (BMI) was measured and blood samples obtained at baseline and 6 and 12 months post-surgery. Plasma concentrations of leptin, acylated and total ghrelin, pancreatic polypeptide (PP), insulin, glucose-dependent insulinotropic peptide (GIP), active glucagon-like peptide-1 (GLP-1), gastrin, and pepsinogens I and II were measured using enzyme-linked immunoassays.Median percent excess weight loss (%EWL) over 12 months was 45.7% with median BMI decreasing from 43.2 at baseline to 33.8 at 12 months post-surgery (p0.001). Median leptin levels decreased from 19.7 ng/ml at baseline to 6.9 ng/ml at 12 months post-surgery (p0.001). In contrast, plasma levels of acylated and total ghrelin, PP, insulin, GIP, GLP-1, gastrin, and pepsinogen I did not change in relation to surgery (p0.05). Pepsinogen II levels were significantly lower 6 months after LAGB but returned to baseline levels by 12 months.LAGB yielded substantial %EWL and a proportional decrease in plasma leptin. Our results support the hypothesis that LAGB works in part by suppressing the rise in ghrelin that normally accompanies weight loss. Unchanged concentrations of insulinotropic and digestive hormones suggest that gastrointestinal endocrine function is largely maintained in the long term.

BACKGROUND: GERD is a prevalent condition that encompasses bothersome symptoms or mucosal injury. It remains challenging to diagnose the condition in individuals with the most common presentation of non-erosive reflux disease. The current diagnostic tools include symptom assessment, endoscopy, and pH-metry. Few studies have evaluated the utility of combining these factors with histology to diagnose GERD in the general population. This study aimed to assess the diagnostic yield of a model with predefined criteria in diagnosing GERD among those with non-erosive disease. METHODS: Individuals presenting for upper endoscopy were prospectively enrolled, and the presence of upper GI symptoms was assessed via a standardized questionnaire. All subjects underwent EGD with lower esophageal biopsies 2 cm above the squamocolumnar junction. A blinded GI pathologist reviewed all biopsies. Esophageal acid exposure and symptom association were assessed off acid suppression therapy via 48-hour pH-metry. Subjects were categorized as GERD if at least two of the following criteria in this model were present: 1) positive symptoms reported on presentation 2) any endoscopically identified LA grade esophagitis 3) histologic pathology 4) esophageal pH ,4 for more than 4.5% of the time. RESULTS: Among the 292 subjects enrolled 26% were women and 74% were men, while the majority were either Caucasian (43%) or African American (27%). Mean age (59 ± 9 years) did not differ according to gender or race/ethnicity. The prevalence of GERD symptoms was 62% and erosive esophagitis was 20%. Data for all diagnostic criteria was complete for 113 subjects and as expected, the prevalence of positive pH studies (pH+) was highest for those with endoscopic esophagitis compared to those without endoscopic esophagitis (65% vs. 41%, p=0.03). However the sensitivity of EGD alone for pH+ was 29% with a specificity of 87%. Regardless of endoscopic findings, no difference in pH+ studies was found based on symptoms or histology alone. Among the 90 subjects with a normal endoscopy who still met the predefined criteria the prevalence of pH+ was significantly higher compared to those who did not meet the criteria (71% vs. 15%, p,0.001). The positive likelihood ratio for this diagnostic approach among individuals with non-erosive disease was 3. In multivariate logistic regression analysis, the model remained significant for GERD with pH+ after controlling for age, gender, BMI, tobacco and alcohol (OR 11, 95% CI 3.0-39; p,0.001). CONCLUSIONS: Among individuals presenting for general endoscopic evaluation the prevalence of erosive disease is low. A predictive model that includes histology allows for a clinically useful approach in diagnosing GERD in non-erosive disease and can help predict and potentially obviate the need for pH testing. Further assessment should be conducted in diverse populations.

Background The incidence of colorectal cancer can be decreased by appropriate use of screening modalities. Patients with a family history of colon cancer and of African-American ethnicity are known to be at higher risk of developing colorectal cancer. We aimed to determine if there is a lack of physician knowledge for colorectal cancer screening guidelines based on family history and ethnicity. Between February and April 2009 an anonymous web-based survey was administered to a random sample selected from a national list of 25,000 internists, family physicians and gastroenterologists. A stratified sampling strategy was used to include practitioners from states with high as well as low CRC incidence. All data analyses were performed following data collection in 2009. Results The average knowledge score was 37 ± 18% among the 512 respondents. Gastroenterologists averaged higher scores compared to internists, and family physicians, p = 0.001. Only 28% of physicians correctly identified the screening initiation point for African-Americans while only 12% of physicians correctly identified the screening initiation point and interval for a patient with a family history of CRC. The most commonly cited barriers to referring high-risk patients for CRC screening were "patient refusal" and "lack of insurance reimbursement." Conclusions There is a lack of knowledge amongst physicians of the screening guidelines for high-risk populations, based on family history and ethnicity. Educational programs to improve physician knowledge and to reduce perceived barriers to CRC screening are warranted to address health disparities in colorectal cancer.

We have characterized the nature and pattern of cell death during regression of the pupillary membrane, a developmentally transient capillary network found in the anterior chamber of the eye. This analysis has revealed that the cellular components of the pupillary membrane include vascular endothelial cells in an intricate network of fine capillaries as well as attendant macrophages. The capillaries are situated on the anterior surface of the lens and held in relative position by a cobweb-like meshwork of extracellular matrix fibres that regress along with the cellular components of this structure. Cell death during regression of the pupillary membrane is characteristic of apoptosis. Specifically, apoptotic bodies containing condensed chromatin can be observed in vascular endothelial cells and genomic DNA isolated from the pupillary membrane shows the nucleosomal fragmentation pattern typical of apoptotic cells. Using a method for labelling fragmented DNA in tissue preparations (TUNEL), we have assessed the overall pattern of apoptotic cell death during pupillary membrane regression. We find that apoptosis occurs either in single cells in healthy vessels or synchronously along the entire length of a capillary segment. Both morphological and TUNEL analysis indicate that capillary regression occurs from junction to junction one segment at a time. We propose a model to explain the pattern of capillary regression observed and conclude from these and previous experiments (Lang and Bishop (1993)Cell 74, 453-462), that during regression of the pupillary membrane, the macrophage elicits target cell death by inducing apoptosis.

Background and Aims: The incidence of colorectal cancer (CRC) can be decreased by appropriate screening. Given limited resources, strategies based on established guidelines may increase screening efficacy particularly by targeting high risk populations. Our aim was to assess physician knowledge of CRC screening guidelines based on family history and ethnicity, and perceived adherence barriers. Methods: Using a stratified sampling strategy of states with high and low incidence of CRC, a random sample of internists (IMs), family medicine physicians (FMPs) and gastroenterologists (GIs) was established from the American Medical Association registry. The study cohort was electronically invited to anonymously complete a web-based 19-item survey (tested for face and content validity) assessing knowledge, and adherence barriers. Responses were evaluated based on established guidelines from the US Multisociety Task Force and American College of Gastroenterology. Results: Among 25,000 invitees, 512 (2%) representing 29 states (55% from high and 45% from low CRC states) completed the survey and served as the study cohort. Reflecting the sampled cohort 38.3% were IMs, 30.1% FMPs, and 28.3% GIs. The majority (76%) had been in practice for >5 years and saw >50 patients per week. Among the participants, 49.6% were in group practice, 27% in academics, 14.6% in solo practice, and 8.8% were hospital based. The overall mean correct score for knowledge of screening guidelines was only 37± 18%. The mean score for GIs (50±19%) was higher compared to IMs (34±15%), and FMPs (31±14%); P=0.003. Private Practitioners scored higher than academicians (49±19% vs. 33±15%; P

The work by De Francesco and colleagues showing the enhanced efficacy of sequential therapy is a timely advance for patients with peptic ulcer disease or mucosa-associated lymphoid tissue lymphoma,...

Obesity Increases the Risk for Colon Polyps in an Immigrant Minority Colorectal Cancer Screening Population Fritz Francois, Richard M. Lin, Renee Williams, Michael Huang, Michael A. Poles Background: The prevalence of obesity in the U.S. has increased more than twofold in the past decade, and is higher among ethnic minorities compared to whites. Obesity is associated with adverse health outcomes, including cancers of the breast, endometrium, and prostate, although this has not been well defined in minority groups. The aim of this study was to evaluate the relationship of body mass index (BMI) to the prevalence of polyps in a minority population undergoing colorectal cancer screening. Methods: Consecutive patients referred for screening colonoscopy at a municipal hospital were prospectively enrolled. A detailed medical history was obtained prior to colonoscopy and BMI was calculated based on measured height and weight. Patients were classified as normal (BMI 18-24.9), overweight (BMI 25-29.9), or obese (BMIO Z 30). The number, size, as well as location of all polyps was documented. Advanced colonic neoplasms were defined as adenomas R10 mm or any adenoma, regardless of size, with villous histology, high-grade dysplasia, or adenocarcinoma. Results: A total of 206 patients were enrolled of which 93 (45%) were Hispanic, 68 (33%) were Asian, 28 (13.6%) were African American, and 15 (7.3%) were Caucasian. A total of 75 (38.1%) individuals were normal weight, 72 (36.5%) were overweight, while 50 (25.4%) were obese. Non-Caucasians were significantly more likely to be overweight or obese when compared to Caucasians (64.8% vs. 21.4%, p Z 0.001). The prevalence of one or more polyps on colonoscopy (hyperplastic or adenomatous) was 13.3% in normal weight individuals, 13.9% in overweight, and 26.0% in obese subjects. When compared to normal weight individuals the obese group was at significantly higher risk for colon polyps in logistic regression analysis after adjusting for age, sex, race, and diabetes (OR 2.97; 95% CI 1.06 to 8.3; p Z 0.038). Neither the location of polyps nor the prevalence of advanced adenomas differed significantly between weight groups. Conclusions: In this ethnically diverse screening population, the prevalence of obesity was highest among Non-Caucasians and was associated with an increased risk for colon polyps. Further studies are warranted among obese underrepresented populations to define the risk for colorectal cancer.