The following on histology and immunohistology of Barrett's esophagus (BE) includes commentaries on the various difficulties remaining in reaching a consensus on the definition of BE; the difficulties in the characterization of intestinal and cardiac mucosa, and in the role of submucosal glands in the development of BE; the importance of a new monoclonal antibody to recognize esophageal intestinal mucosa; the importance of pseudo goblet cells; the best techniques for the endoscopic detection of Barrett's epithelium; and the biomarkers for identification of patients predisposed to the development of BE.
Non-erosive reflux disease (NERD) has assumed increasing prominence in studies of gastroesophageal reflux disease (GERD), but it remains a challenge to define NERD precisely and to define its place in the investigation and treatment of GERD. Most simply, NERD may be defined as GERD in an individual who has no evidence of erosions at endoscopy. Unfortunately, the characteristic symptoms of GERD – heartburn and regurgitation – are insufficient to identify all GERD patients and, hence, the diagnosis of NERD is hampered by the lack of clear criteria for the symptomatic diagnosis of GERD. The diagnosis of NERD is hampered further by limited interobserver agreement on the endoscopic diagnosis of erosive esophagitis and by the fact that endoscopy is often performed soon after patients have discontinued therapy. Improvements in endoscopic technology will increase the likelihood of identifying small erosions or other reflux-related lesions; however, this will increase the proportion of patients considered to have erosive esophagitis without defining precisely what constitutes NERD. It is important to recognize that NERD is but one manifestation of GERD and that it, like other manifestations of GERD, is associated with a marked diminution in patients’ quality of life. However, this recognition apart, there seems to be little practical benefit or understanding to be gained in clinical practice or clinical research from considering NERD as a distinct entity or from studying NERD patients in isolation. Advances in understanding the pathogenesis of GERD and its symptoms may be better served by categorizing GERD with respect to the spectrum of its histologic, functional, endoscopic and symptomatic manifestations rather than by studying NERD, a manifestation that is characterized solely by the absence of esophageal erosions.
Despite recommendations that patients rating their own health using utility and preference measures such as the feeling thermometer (FT) and standard gamble (SG) should also rate hypothetical marker states, little evidence supports marker state use. We evaluated whether the administration of marker states improves measurement properties of the FT and SG.We randomized 217 patients with gastroesophageal reflux disease to complete the FT (self-administered) and SG with marker states (FT+ / SG+, n = 112) or without marker states (FT- / SG-, n = 105) before and after 4 weeks of treatment with a proton pump inhibitor, esomeprazole. Patients also completed other health-related quality of life instruments.The use of marker states did not influence baseline utility scores (FT+ 0.66, FT- 0.68; SG+ 0.77, SG- 0.78, on a scale from 0 [dead] to 1.0 [full health]). Improvement after therapy was 0.21 in FT+ and 0.15 in FT- (both P < 0.001; difference between FT+ and FT- = 0.06, P = 0.02). Improvement in SG+ was 0.07 (P < 0.001) and 0.06 in SG- (P = 0.003) (difference between SG+ and SG- = 0.01, P = 0.63). Correlations with other health-related quality of life scores were generally stronger, with some statistically significant differences in correlations, for FT+ compared with FT-, but tended to be weaker for SG+ compared with SG-.The administration of marker states improved the responsiveness and validity of the FT but not of the SG. Decisions about administering marker states should depend on whether the FT and SG is of primary interest and the importance of optimal validity and responsiveness relative to competing objectives such as efficiency.
High Amplitude Pressure Waves (HAPWs) are the only motor pattern routinely assessed in human colonic manometry. High-Resolution Colonic Manometry is able to provide more information and shows HAPW associated motor patterns that may have clinical relevance. Our aim was to characterize the HAPW associated rhythmic motor pattern, its myogenic basis based on its frequency pattern, its physiological significance and its potential diagnostic value. High-resolution manometry was performed using an 84 sensor water-perfused catheter in 7 healthy subjects. Pressures were recorded at baseline, after a meal, in response to balloon distension and bisacodyl administration. The most consistent motor pattern that followed HAPWs in healthy adults was a characteristic rhythmic motor pattern with distinct frequency components of 6, 9,12 and 15 cpm, clearly distinguishable from the breathing frequency. This pattern had an average duration of 78.1 ± 49.6 s (24 to 165), occurring over a section of the colon of 11.5 ± 5.9 cm (6 to18) length, which is about 2 or 3 haustra. The motor pattern ended 24.0 ± 7.0 cm above the anal verge; hence it is a characteristic of the sigmoid colon. Individual pressure transients within the pattern occurred almost exclusively instantaneous. To quantify, HAPWs were evoked by balloon distention, a 1000 kcal meal, and 10 mg luminal bisacodyl. Using balloon distention, 31 HAPWs were evoked, 16.1% were followed by quiescence and 48.4% by the rhythmic motor pattern; other HAPWs were associated with spontaneous pressure waves without the occurrence of this rhythmic motor pattern. In response to a meal, 30 HAPWs were evoked, 10.0 % were followed by quiescence and 33.3 % by the rhythmic motor pattern. In response to bisacodyl, 39 HAPWs were evoked, 5.1 % were followed by quiescence and 46.2 % by the rhythmic motor pattern. This motor pattern also occurred independently of the HAPWs with dominant frequencies of 3 and 6 cpm at baseline condition, indicating the motor pattern was in a less excited state with more retrograde propagation. A rhythmic motor pattern characteristically follows the HAPW in the sigmoid colon. Its occurrence after an HAPW suggests that this rhythmic motor pattern shares neural excitation with the HAPWs. Its frequency spectrum (3,6,9,12,15 cpm) and very fast propagation (or instantaneous appearance) suggest orchestration by a network of interstitial cells of Cajal (ICC). The frequency spectrum is identical to that in previous electrical recordings of the human colon (2). The occurrence of this motor pattern in healthy adults suggests that it may not be a biomarker of constipation in adults (1) and suggests that it may be a signature of intrinsic ICC activity. 1. Giorgio et al. Neurogastr. Mot. 2013. 2. Sarna et al. Gastroenterology 1981. High-Resolution Colonic Manometry: a High Amplitude Pressure Wave is followed by a Rhythmic Motor Pattern in the distal colon. CIHRHamilton Academic Health Sciences Organization
Teduglutide is a synthetic glucagon-like peptide-2 analogue approved for the treatment of short bowel syndrome associated with chronic intestinal failure (SBS-IF) in adult patients. Clinical trials have demonstrated its ability to reduce parenteral support (PS) requirement. This study aimed to describe the effect of 18-month treatment with teduglutide, evaluating PS and factors associated with PS volume reduction of ≥20% from baseline and weaning. Two-year clinical outcomes were also assessed.This descriptive cohort study collected data prospectively from adult patients with SBS-IF treated with teduglutide and enrolled in a national registry. Data were collected every 6 months and included demographics, clinical, biochemical, PS regimen, and hospitalizations.Thirty-four patients were included. After 2 years, 74% (n = 25) had a PS volume reduction of ≥20% from baseline, and 26% (n = 9) achieved PS independency. PS volume reduction was significantly associated with longer PS duration, significantly lower basal PS energy intake, and absence of narcotics. PS weaning was significantly associated with fewer infusion days, lower PS volume, longer PS duration, and lower narcotics use at baseline. Alkaline phosphatase was significantly lower in weaned patients after 6 and 18 months of treatment. During the 2-year study duration, patients who had PS volume reduction of ≥20% had significantly fewer yearly hospitalizations and hospital-days.Teduglutide reduces PS volume and promotes weaning in adults with SBS-IF. Lack of narcotics and longer PS duration were associated with PS volume reduction and weaning, and lower baseline PS volume and fewer infusion days were favorable in obtaining enteral autonomy.
Corticosteroids (CS) have been used extensively to induce remission in Crohn's disease (CD); however, they are associated with severe side effects. We hypothesized that the administration of an exclusive enteral nutrition (EEN) formula to CS would lead to increased CD remission rates and to decreased CS-related adverse events. We proposed to undertake a pilot study comparing EEN and CS therapy to CS alone to assess decrease symptoms and inflammatory markers over 6 weeks.The overall aim was to assess study feasibility based on recruitment rates and acceptability of treatment in arms involving EEN.The pilot study intended to recruit 100 adult patients with active CD who had been prescribed CS to induce remission as part of their care. The patients were randomized to one of three arms: (i) standard-dose CS; (ii) standard-dose CS plus EEN (Modulen 1.5 kcal); or (iii) short-course CS plus EEN.A total of 2009 CD patients attending gastroenterology clinics were screened from October 2018 to November 2019. Prednisone was prescribed to only 6.8% (27/399) of patients with active CD attending outpatient clinics. Of the remaining 372 patients with active CD, 34.8% (139/399) started or escalated immunosuppressant or biologics, 49.6% (198/399) underwent further investigation and 8.8% (35/399) were offered an alternative treatment (e.g., antibiotics, surgery or investigational agents in clinical trials). Only three patients were enrolled in the study (recruitment rate 11%; 3/27), and the study was terminated for poor recruitment.The apparent decline in use of CS for treatment of CD has implications for CS use as an entry criterion for clinical trials.
