A Comparative Clinical Study of a Novel Pre-colonoscopy Bowel Capsule Preparation Against Two Commercially Available Liquid Preparations.

Background and Aims: Colonoscopy surveillance depends on effective bowel preparation. Inadequate bowel preparation can lead to inaccurate clinical diagnosis, insufficient visualization of the colon and increased risk of missed diagnosis. This study aimed to compare the efficacy and safety of a novel Capsule Bowel Preparation (RitePrep), high-volume (2L) polyethylene glycol electrolyte solution (MoviPrep®) and low-volume (1L) polyethylene glycol electrolyte solution (Plenvu™). Methods: Patients (n = 120) were divided into three groups and were administered either RitePrep, MoviPrep® or Plenvu™ as a pre-colonoscopy bowel preparation followed by a colonoscopy at a single center. Validated Boston Bowel Preparation Score (BBPS) and bubble score were used to evaluate bowel cleanliness. Blood tests were also evaluated. The scores and the blood results were analyzed using Kruskal-Wallis and Chi-squared tests. Results: A total of 120 patients (median age of 55; 57 males) [RitePrep (n = 40), MoviPrep® (n = 40) and Plenvu™ (n = 40)] were included in the study. RitePrep was the most effective method for cleansing the bowel, with a significantly higher median BBPS compared to MoviPrep® and Plenvu™ (p = 0.006 and 0.024, respectively). Nearly 50% of the patients in Plenvu™ group showed increased serum osmolality disturbance. Nausea and vomiting were higher in Plenvu™ and MoviPrep® groups than RitePrep group. Conclusions: RitePrep was demonstrated to be a more effective and safe preparation than the other two preparations. RitePrep was not only well-tolerated by all patients; the preparation sufficiently cleared the ascending, transverse, and descending colon, enabling optimal visualization for the clinician. RitePrep was also much safer than the comparators, with no alteration in electrolytes measured. For both the clinician and the patient, RitePrep was the preferred preparation.

Novel Aberrations Uncovered in Barrett's Esophagus and Esophageal Adenocarcinoma Using Whole Transcriptome Sequencing.

Esophageal adenocarcinoma (EAC) has one of the fastest increases in incidence of any cancer, along with poor five-year survival rates. Barrett's esophagus (BE) is the main risk factor for EAC; however, the mechanisms driving EAC development remain poorly understood. Here, transcriptomic profiling was performed using RNA-sequencing (RNA-seq) on premalignant and malignant Barrett's tissues to better understand this disease. Machine-learning and network analysis methods were applied to discover novel driver genes for EAC development. Identified gene expression signatures for the distinction of EAC from BE were validated in separate datasets. An extensive analysis of the noncoding RNA (ncRNA) landscape was performed to determine the involvement of novel transcriptomic elements in Barrett's disease and EAC. Finally, transcriptomic mutational investigation of genes that are recurrently mutated in EAC was performed. Through these approaches, novel driver genes were discovered for EAC, which involved key cell cycle and DNA repair genes, such as BRCA1 and PRKDC. A novel 4-gene signature (CTSL, COL17A1, KLF4, and E2F3) was identified, externally validated, and shown to provide excellent distinction of EAC from BE. Furthermore, expression changes were observed in 685 long noncoding RNAs (lncRNA) and a systematic dysregulation of repeat elements across different stages of Barrett's disease, with wide-ranging downregulation of Alu elements in EAC. Mutational investigation revealed distinct pathways activated between EAC tissues with or without TP53 mutations compared with Barrett's disease. In summary, transcriptome sequencing revealed altered expression of numerous novel elements, processes, and networks in EAC and premalignant BE.Implications: This study identified opportunities to improve early detection and treatment of patients with BE and esophageal adenocarcinoma. Mol Cancer Res; 15(11); 1558-69. ©2017 AACR.

Changes in gene expression of neo-squamous mucosa after endoscopic treatment for dysplastic Barrett's esophagus and intramucosal adenocarcinoma.

BACKGROUND: Endoscopic therapy, including by radiofrequency ablation (RFA) or endoscopic mucosal resection (EMR), is first line treatment for Barrett's esophagus (BE) with high-grade dysplasia (HGD) or intramucosal cancer (IMC) and may be appropriate for some patients with low-grade dysplasia (LGD). OBJECTIVE: The purpose of this study was to investigate the molecular effects of endotherapy. METHODS: mRNA expression of 16 genes significantly associated with different BE stages was measured in paired pre-treatment BE tissues and post-treatment neo-squamous biopsies from 36 patients treated by RFA (19 patients, 3 IMC, 4 HGD, 12 LGD) or EMR (17 patients, 4 IMC, 13 HGD). EMR was performed prior to RFA in eight patients. Normal squamous esophageal tissues were from 20 control individuals. RESULTS: Endoscopic therapy resulted in significant change towards the normal squamous expression profile for all genes. The neo-squamous expression profile was significantly different to the normal control profile for 11 of 16 genes. CONCLUSION: Endotherapy results in marked changes in mRNA expression, with replacement of the disordered BE dysplasia or IMC profile with a more "normal" profile. The neo-squamous mucosa was significantly different to the normal control squamous mucosa for most genes. The significance of this finding is uncertain but it may support continued endoscopic surveillance after successful endotherapy.

High Expression of Cathepsin E in Tissues but Not Blood of Patients with Barrett's Esophagus and Adenocarcinoma.

BACKGROUND: Cathepsin E (CTSE), an aspartic proteinase, is differentially expressed in the metaplasia-dysplasia-neoplasia sequence of gastric and colon cancer. We evaluated CTSE in Barrett's esophagus (BE) and cancer because increased CTSE levels are linked to improved survival in several cancers, and other cathepsins are up-regulated in BE and esophageal adenocarcinoma (EAC). METHODS: A total of 273 pretreatment tissues from 199 patients were analyzed [31 normal squamous esophagus (NE), 29 BE intestinal metaplasia, 31 BE with dysplasia (BE/D), 108 EAC]. CTSE relative mRNA expression was measured by real-time polymerase chain reaction, and protein expression was measured by immunohistochemistry. CTSE serum levels were determined by enzyme-linked immunosorbent assay. RESULTS: Median CTSE mRNA expression levels were ≥1,000-fold higher in BE/intestinal metaplasia and BE/D compared to NE. CTSE levels were significantly lower in EAC compared to BE/intestinal metaplasia and BE/D, but significantly higher than NE levels. A similar expression pattern was present in immunohistochemistry, with absent staining in NE, intense staining in intestinal metaplasia and dysplasia, and less intense EAC staining. CTSE serum analysis did not discriminate patient groups. In a uni- and multivariable Cox proportional hazards model, CTSE expression was not significantly associated with survival in patients with EAC, although CTSE expression above the 25th percentile was associated with a 41 % relative risk reduction for death (hazard ratio 0.59, 95 % confidence interval 0.27-1.26, p = 0.17). CONCLUSIONS: CTSE mRNA expression is up-regulated more than any known gene in Barrett intestinal metaplasia and dysplasia tissues. Protein expression is similarly highly intense in intestinal metaplasia and dysplasia tissues.

Durable alteration of the colonic microbiota by the administration of donor fecal flora.

GOALS: To determine whether fecal bacteriotherapy results in a durable beneficial change in the colonic microbiota of patients with flora-related disorders. BACKGROUND: Earlier studies have implicated the colonic microbiota in a number of conditions. Administration of a fecal suspension from a healthy individual to an ill individual (fecal bacteriotherapy) can cure Clostridium difficile infection and potentially other diseases. Oral probiotics do not work in this condition, yet there has been no study to determine whether fecal bacteriotherapy results in prolonged implantation. STUDY: Fecal samples were collected from 10 patients undergoing fecal bacteriotherapy. Patients completed an antibiotic schedule and bowel lavage before the infusion of healthy donor feces. Using a molecular approach, the bacterial populations in patient fecal samples were followed from pretreatment to 24 weeks post-initial infusion and compared with the initial infused donor fecal suspension. RESULTS: At intervals of 4, 8, and 24 weeks after the procedure, the bacterial populations in the patients' fecal samples consisted predominantly of bacteria derived from the healthy donor samples. Comparisons of similarity at 4, 8, and 24 week samples to the donor-infused sample were made and each recipient's baseline sample was statistically significant with Friedman test. CONCLUSIONS: This study demonstrates a durable beneficial change in the patients' bacterial populations of the colon to represent those of the healthy donor's microbiota. Manipulation of the colonic microbiota to improve its protective and beneficial role represents a promising field of new therapeutic strategies for the treatment of gastrointestinal conditions.

Early studies on the safety and efficacy of thalidomide for symptomatic inflammatory bowel disease.

BACKGROUND AND AIM: Thalidomide is clinically effective in the treatment of graft versus host disease in bone marrow transplantation and aphthous ulceration in HIV infection. It appears to exert a selective effect on tumor necrosis factor-alpha (TNF-alpha) production. Tumor necrosis factor-alpha is implicated in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to assess the efficacy and safety of thalidomide in symptomatic IBD. METHODS: Eleven patients (nine males, mean age 33 years, range 20-77 years) with chronic inflammatory bowel disease (six Crohn's disease (CD), four ulcerative colitis (UC), one indeterminate colitis (IC)) who were symptomatic despite standard medical therapy were administered a daily dose of thalidomide for 12 weeks in an open-labeled protocol. Their response was assessed by using clinical, colonoscopic, histological, and immunological methods. RESULTS: Two patients withdrew at 3 weeks because of mood disturbances. Of the remaining nine patients, eight (five CD, two UC and one IC) had a marked clinical response, while one patient with CD had no response. The mean stool frequency decreased from 4.3 to 2.3 per day (P = 0.0012), and the stool consistency increased from 2.1 to 1.2 (P = 0.02). The mean Crohn's Disease Activity Index decreased from 117 to 48 (P = 0.0008). Endoscopic inflammatory and histological grade, C-reactive protein and erythrocyte sedimentation rate (ESR) all decreased significantly (P = 0.011, P = 0.03, P = 0.023 and P = 0.044, respectively). However, the serum TNF-alpha levels did not change. Side-effects included mild sedation, xerostomia and skin dryness in all, constipation in three, and minor abnormalities in nerve conduction in one patient. CONCLUSION: These data strongly suggest that thalidomide is an effective short-term treatment for symptomatic IBD.