Safety of Pneumatic Dilation in Older Adults with Achalasia: An International Multicenter Cross-Sectional Study.

BACKGROUND: Pneumatic dilation (PD) is an effective first line treatment option for many patients with achalasia. PD use may be limited in adults with achalasia who are older than 65 because of concern for adverse events (AE), and less efficacious therapies are often utilized. We explored the periprocedural safety profile of PD in older adults. METHODS: An international real world cross-sectional study of patients undergoing PD between 2006-2020 in two tertiary centers. Thirty-day AEs were compared between older adults (65 and older) with achalasia and younger patients. RESULTS: A total of 252 patients underwent 319 PDs. In 319 PDs, 18 (5.7%) complications occurred: 6 (1.9%) perforations and 12 (3.8%) emergency department referrals with benign (non-perforation) chest pain, of which 9 (2.8%) were hospitalized. No bleeding or death occurred within 30 days. Perforation rates were similar in both age groups and across achalasia subtypes. Advanced age was protective of benign chest pain complications in univariate analysis, and the limited number of AEs precluded multivariable analysis. CONCLUSIONS: The safety of PD in older adults is at least comparable to that of younger patients and should be offered as an option for definitive therapy for older patients with achalasia. Our results may affect informed consent discussions.

Data From a One-Stop-Shop Comprehensive Cancer Screening Center.

PURPOSE: Cancer is the second leading cause of death globally. However, by implementing evidence-based prevention strategies, 30%-50% of cancers can be detected early with improved outcomes. At the integrated cancer prevention center (ICPC), we aimed to increase early detection by screening for multiple cancers during one visit. METHODS: Self-referred asymptomatic individuals, age 20-80 years, were included prospectively. Clinical, laboratory, and epidemiological data were obtained by multiple specialists, and further testing was obtained based on symptoms, family history, individual risk factors, and abnormalities identified during the visit. Follow-up recommendations and diagnoses were given as appropriate. RESULTS: Between January 1, 2006, and December 31, 2019, 8,618 men and 8,486 women, average age 47.11 ± 11.71 years, were screened. Of 259 cancers detected through the ICPC, 49 (19.8%) were stage 0, 113 (45.6%) stage I, 30 (12.1%) stage II, 25 (10.1%) stage III, and 31(12.5%) stage IV. Seventeen cancers were missed, six of which were within the scope of the ICPC. Compared with the Israeli registry, at the ICPC, less cancers were diagnosed at a metastatic stage for breast (none v 3.7%), lung (6.7% v 11.4%), colon (20.0% v 46.2%), prostate (5.6% v 10.5%), and cervical/uterine (none v 8.5%) cancers. When compared with the average stage of detection in the United States, detection was earlier for breast, lung, prostate, and female reproductive cancers. Patient satisfaction rate was 8.35 ± 1.85 (scale 1-10). CONCLUSION: We present a proof of concept study for a one-stop-shop approach to cancer screening in a multidisciplinary outpatient clinic. We successfully detected cancers at an early stage, which has the potential to reduce morbidity and mortality as well as offer substantial cost savings.[Media: see text].

Integrase-derived peptides together with CD24-targeted lentiviral particles inhibit the growth of CD24 expressing cancer cells.

The integration of viral DNA into the host genome is mediated by viral integrase, resulting in the accumulation of double-strand breaks. Integrase-derived peptides (INS and INR) increase the number of integration events, leading to escalated genomic instability that induces apoptosis. CD24 is a surface protein expressed mostly in cancer cells and is very rarely found in normal cells. Here, we propose a novel targeted cancer therapeutic platform based on the lentiviral integrase, stimulated by integrase-derived peptides, that are specifically delivered to cancerous cells via CD24 antigen-antibody targeting. INS and INR were synthesized and humanized and anti-CD24 antibodies were fused to the lentivirus envelope. The activity, permeability, stability, solubility, and toxicity of these components were analyzed. Cell death was measured by fluorescent microscopy and enzymatic assays and potency were tested in vitro and in vivo. Lentivirus particles, containing non-functional DNA led to massive cell death (40-70%). Raltegravir, an antiretroviral drug, inhibited the induction of apoptosis. In vivo, single and repeated administrations of INS/INR were well tolerated without any adverse effects. Tumor development in nude mice was significantly inhibited (by 50%) as compared to the vehicle arm. In summary, a novel and generic therapeutic platform for selective cancer cell eradication with excellent efficacy and safety are presented.

Low Risk of Neoplasia and Intraprocedural Adverse Events in Gastric Hyperplastic Polypectomy.

GOALS: Assess neoplasia and polypectomy-related adverse event (AE) rates in gastric hyperplastic polyps (GHPs). BACKGROUND: GHPs carry a risk of neoplastic transformation. The rate of neoplastic transformation and the risk of polypectomy-related bleeding are unclear in the West, as data are derived from Asian or small studies. The authors aimed to determine the rate of dysplasia and intraprocedural AEs in GHP polypectomies in a western cohort. STUDY: A retrospective study of 591 GHPs >1 cm resected in 491 patients in a single referral center on the occurrence of neoplasia and intraprocedural AEs. RESULTS: The mean age was 74.9±11.1 years, 57% female individuals. The mean polyp size was 2±0.8 cm. There were 11 neoplastic polyps (1.9%) with low-grade dysplasia, high-grade dysplasia, and cancer in 7 (1.3%), 2 (0.3%), and 2 (0.3%), respectively. Neoplasia was associated with age [9 (3.2%) for more than 75 years vs. 2 (0.7%) for less than 75 years; P=0.035], but not with polyp size or gender. Fifty patients (8.5%) had intraprocedural bleeding (IPB) requiring endoscopic intervention, with 3 hospitalizations. There were no perforations or procedure-related deaths. IPB was associated with polyp size and neoplasia. The adjusted odds ratio (95% confidence interval) for IPB was 1.63 (1.2-2.2) for a 1 cm increase in polyp size, and 7.4 (1.9-29.6) for the presence of neoplasia. CONCLUSIONS: The neoplasia rate in GHPs was 1.9%, lower than most previous reports, with no major intraprocedural AEs. Physicians may consider biopsy and follow-up in frail elderly patients, but the safety of this strategy needs further confirmation.

Burnout, but not job strain, is associated with irritable bowel syndrome in working adults.

OBJECTIVE: Although stress is an important component of irritable bowel syndrome (IBS) pathophysiology, the possibility that work-related stress is implicated in the pathophysiology of IBS has not been widely studied. This study aimed to examine whether job strain (a combination of high job demands and low control at work) and/or burnout, the outcome of a gradual depletion of energetic resources resulting from chronic exposure to work-related stress, are associated with IBS. METHODS: Fifty-five patients fulfilling the Rome III criteria for IBS and 214 matched healthy controls (HC) participated in this cross-sectional study. All participants completed a job strain measure, the Shirom - Melamed Burnout Measure (SMBM), and dietary and health questionnaires. RESULTS: There was no significant difference in the prevalence of job strain between IBS patients and HC (25.5% vs. 23.0%, respectively). Job strain was not associated with increased IBS prevalence (adjusted OR = 1.99, 95% CI: 0.54-7.33). In contrast, the mean burnout score in the IBS group was significantly higher than in HC (2.9 ± 1.1 vs. 2.1 ± 0.8, p < .001). Burnout was associated with a 2.41-fold elevated prevalence of IBS (95% CI: 1.16-5.02), after adjusting for potential confounding variables including job strain. Moreover, the odds of having IBS increased in patients with a high burnout level (adjusted OR = 3.3, 95% CI:1.09-10.03). CONCLUSION: Burnout, but not job strain, is associated with the prevalence of IBS in working adults.

Clinical outcomes of endoscopic balloon dilatation of intestinal strictures in patients with Crohn's disease.

Intestinal strictures are common complications of Crohn's disease (CD). Endoscopic balloon dilatation (EBD) constitutes an alternative therapy to surgery, but associated factors of procedure success are inconclusive. Therefore, we aimed to evaluate the EBD success rate and its associated factors in CD patients.This is a retrospective cohort study of consecutive EBDs that were conducted between 2006 and 2014 among patients with CD with lower gastrointestinal tract strictures. Patients' and stricture characteristics, short term procedure success and related complications at 1 week follow-up, and long-term clinical endpoints were documented.A total of 138 dilatations were performed on 64 CD patients. The overall dilatation success rate was 84.8%, with no difference between primary or anastomotic strictures, or between first or recurrent dilatation procedures. Long strictures (≥4 cm) were negatively associated with successful EBDs, but not with perforations. A multivariate analysis adjusting for age, sex, smoking, and disease duration revealed that a maximal dilatation diameter of ≥15 mm was positively associated with a successful EBD, while an inflamed stricture was negatively associated with procedure success. Strictures which were both long and inflamed were associated with the lowest EBD success rates compared with other strictures. Only 32.8% of patients required surgery during the follow-up period. Long-term prevention of surgery was negatively associated with stricture length and with a successful EBD.EBD is highly successful in treating intestinal strictures and in prevention of surgery in CD patients. Although EBD of long strictures is safe, it will not prevent surgery in the majority of cases.

Pancreatic cancer in bloom syndrome.

Bloom syndrome is a rare autosomal recessive disorder characterized by distinct physical features, such as short stature, genomic instability, and predisposition to numerous cancers. The BLM gene encodes for the RecQ helicase that plays an important role in genome editing, maintenance, and stability. Mutations in the BLM gene cause genomic instability that exposes the carriers to a variety of cancers, and in particular hematological and gastrointestinal cancers. Herein, we report the first case of pancreatic cancer in a 32-year-old patient with bloom syndrome.

Serum cholinesterase activity is elevated in female diarrhea-predominant irritable bowel syndrome patients compared to matched controls.

BACKGROUND: Micro-inflammation is involved in the pathogenesis of irritable bowel syndrome (IBS). The parasympathetic nervous system, via acetylcholine (ACh), and its hydrolytic enzymes, plays a role in regulating inflammation. Increased serum cholinesterase activity, named cholinergic Status (CS), is associated with decreased inflammatory inhibition (ie, pro-inflammation). We assessed the association between IBS diarrhea-predominant (IBS-D) symptoms, CS, and inflammatory biomarkers. METHODS: Women with IBS-D were prospectively recruited. Serum acetylcholinesterase (AChE), CS, and high-sensitivity C-reactive protein (hs-CRP) levels were analyzed and fecal calprotectin (FC) in a subgroup of patients. The control group included women attending routine health checkups (matched by age and BMI). KEY RESULTS: Ninety-four women with IBS-D were compared to matched controls (1:1). Serum CS, AChE, and the AChE/butyrylcholinesterase (BChE) ratios were significantly increased in the IBS-D group compared to matched controls (P = 0.018, P = 0.001, and P = 0.004, respectively). Using a multiple logistic regression model, IBS-D was almost twice as likely in women with high CS compared to women with low CS (adjusted OR=1.84 (95% CI: 1.01-3.33), P = 0.045). Furthermore, IBS-D patients with higher hs-CRP levels demonstrated lower CS and BChE activity and elevated AChE and AChE/BChE ratios compared to patients with lower hs-CRP levels (P = 0.026, P = 0.036, P = 0.002; and P = 0.0007, respectively). CS was not correlated with the IBS symptoms score. CONCLUSIONS AND INFERENCES: This is the first study to explore the potential role of serum CS in IBS-D. The findings emphasize the possible role of the autonomic nervous system and its anti-inflammatory properties in IBS.

The effect of a multispecies probiotic on microbiota composition in a clinical trial of patients with diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Although probiotics are increasingly used in irritable bowel syndrome (IBS), their mechanism of action has not been elucidated sufficiently. We aimed to evaluate the impact of a multispecies probiotic on enteric microbiota composition in women with diarrhea-predominant-IBS (IBS-D) and to determine whether these effects are associated with changes in IBS symptoms or inflammatory markers. METHODS: In a double-blind, placebo-controlled study, Rome III IBS-D women completed a two-week run-in period and eligible women were assigned at random to a probiotic capsule (BIO-25) or an indistinguishable placebo, twice daily for 8 weeks. IBS symptoms and stool consistency were rated daily by visual analogue scales and the Bristol stool scale. High sensitivity C-reactive protein, fecal calprotectin and microbial composition were tested at baseline and at 4 and 8 weeks. Microbial sequencing of the 16S rRNA was performed and data were analyzed to compare patients who responded to treatment with those who did not. KEY RESULTS: 172 IBS-D patients were recruited and 107 eligible patients were allocated to the intervention (n = 54) or placebo (n = 53) group. Compared to placebo, BIO-25 did not result in changes in microbial diversity or taxa proportions, except for higher relative proportions of Lactobacillus in the BIO-25 group (P = 0.002). Symptomatic responders to BIO-25 showed a reduction in the proportion of Bilophila(P = 0.003) posttreatment. Patients with beneficial inflammatory-marker changes had higher baseline proportions of Faecalibacterium(P = 0.03), Leuconostoc (P = 0.03), and Odoribacter (P = 0.05) compared to corresponding non-responders. CONCLUSIONS & INFERENCES: Identifying patients with a more amenable microbiome at treatment initiation may result in better treatment response.

The use of psychotropic drugs in irritable bowel syndrome.

INTRODUCTION: Irritable bowel syndrome (IBS), the most common functional gastrointestinal disorder, is manifested by chronic abdominal pain associated with irregular bowel movements. Although not life threatening, IBS is associated with impaired quality of life that ranges from mild to severe. AREAS COVERED: The pathogenesis of IBS is not completely understood, but involves dysfunction of the "brain-gut axis" including peripheral visceral hypersensitivity and central maladaptive processing of visceral pain input. Stress and concomitant psychopathologies such as somatization, anxiety and depression are thought to play a major role in the development, clinical course and response to treatment. Psychopharmacological agents such as selective serotonin/serotonin-norepinephrine receptor antagonists, tricyclic antidepressants as well as other agents are commonly used in treating moderate to severe IBS. This review will provide the pathophysiological rationale for the use of psychopharmacological agents in IBS, review the main classes of drugs and evidence for their use in IBS and offer a practical approach to the use of these drugs. EXPERT OPINION: Psychotropic drugs can play a pivotal role in the treatment of IBS patients, so doctors should be familiar with their use. Further research with these drugs is needed to solidify our current knowledge and increase our therapeutic options.

Irritable Bowel Syndrome and Co-morbid Gastrointestinal and Extra-gastrointestinal Functional Syndromes.

The irritable bowel syndrome (IBS) is the best known of the functional gastrointestinal tract disorders. Many IBS patients have at least one co-morbid somatic complaint and many meet diagnostic criteria for other functional disorders. Patients with IBS and another functional disorder, in comparison with patients with IBS only, have more severe IBS symptoms, a higher rate of psychopathology, greater impairment of quality of life, and more illness-related work absenteeism. Estimates of the prevalence of IBS in patients with fibromyalgia range from 30-35% to as high as 70%. Studies of IBS among patients with chronic fatigue syndrome have reported a prevalence ranging from 35-92%. The prevalence of IBS among patients with chronic fatigue syndrome is reported to be 14%. IBS patients with other co-morbid functional disorders appear to manifest a greater degree of somatization. It has been suggested that the presence of multiple co-morbid disorders may be a marker for psychological influences on etiology. This raises the question of whether the functional syndromes represent the same pathophysiological process, i.e., are the same entity that has been separated into different clinical entities because of medical sub-specialization, or are indeed separate disorders. While the answer to this question awaits further research, it would appear that most functional patients who meet formal diagnostic criteria for more than one functional disorder manifest one disorder clinically more that the others and seek consultation differentially for that set of symptoms.

Relationships between sleep quality and pH monitoring findings in persons with gastroesophageal reflux disease.

BACKGROUND: Nighttime reflux has been shown to be associated with esophageal mucosal injury, complications, and extra-esophageal manifestations. However, few studies have assessed the impact of gastroesophageal reflux on reported quality of sleep and quality of sleep on gastroesophageal reflux. AIMS: The aims of this study were (1) to determine the correlation between the severity of gastroesophageal reflux disease (GERD) symptoms and esophageal acid contact time and subjects' perceived quality of sleep; (2) to investigate the correlation between reported quality of sleep of the night prior and severity of GERD symptoms and esophageal acid contact time the following day; and (3) to define in a sleep laboratory the correlation between acid reflux events and sleep architecture. METHODS: Subjects with typical GERD symptoms > or =3 times a week underwent upper endoscopy and pH monitoring. These subjects subsequently completed the GERD Symptom Assessment Score (GSAS), and the Sleep Heart Health Study Sleep Habits (SHHS) Questionnaire to assess baseline sleep symptoms and GERD symptoms, including an index of GERD symptom severity (GERD symptom index). Before and after the pH test, the patients completed a different instrument, the Sleep Quality Questionnaire, utilized specifically to assess the quality of each subject's sleep before and after pH testing. Fifteen randomly selected subjects also underwent a polysomnographic study during the pH test. RESULTS: Forty-eight (33 males/15 females, mean age 48.8 +/- 17.1 y) subjects were prospectively recruited. Using data from the GSAS and SHHS questionnaires, disorders of initiating and maintaining sleep were found to be positively associated with greater severity of the GERD symptom index (r = 0.33, p <0.05). More frequent awakenings also correlated with a higher GERD symptom index (r = 0.4, p <0.01). Correlations between the Sleep Quality Questionnaire on the night before sleep testing and pH monitoring data showed that subjects with poorer sleep quality had longer acid reflux events (r=-0.34, p<0.05). More perceived awakenings also were correlated with the number of supine acid reflux events > 5 min (r=0.31, p<0.05) and the duration of the longest supine acid reflux event (r = 0.28, p = 0.05). Inverse correlations were observed between overall sleep quality on the pH testing night and a higher percentage of time spent with pH<4 supine (r=-0.432, p <0.002), and the duration of the longest acid reflux event during the entire night (r = -0.38, p <0.01) and supine (r=-0.37, p<0.02). CONCLUSIONS: Persons with worse GERD symptoms report poorer subject sleep quality. Poor sleep quality on the night prior to pH testing was associated with more acid exposure the following day. Greater acid exposure at night was related to a worse perception of sleep quality the next day. These findings suggest important interactions between GERD and sleep quality.

Low-dose naltreoxone for the treatment of irritable bowel syndrome: a pilot study.

Preclinical studies have shown that a very low dose of naltreoxone hydrochloride (NTX), an opiate antagonist, can block excitatory opioid receptors without affecting inhibitory opioid receptors, resulting in analgesic potency without side effects. The present study assessed the efficacy and safety of PTI-901 (low-dose NTX) treatment in Irritable bowel syndrome (IBS) patients. Forty-two IBS patients participated in an open-label study. Participants received 0.5 mg PTI-901/day for 4 weeks and were evaluated during baseline, during treatment, and at 4-week follow-up. Patients recorded degree of abdominal pain, stool urgency, consistency, and frequency. Primary outcomes were number of pain-free days and overall symptom relief, evaluated by a global assessment score. Data were analyzed per protocol. Global assessment improved in 76% of 42 patients. During treatment, the mean weekly number of pain-free days increased from 0.5+/-1 to 1.25+/-2.14 (P=0.011). There were no significant adverse reactions. PTI-901 improves pain and overall feeling, and is well tolerated by IBS patients. A large, randomized, double-blind, placebo-controlled study is justified.

The relationship between the esophageal tissue content of neurotensin and the presence or absence of esophageal inflammation.

Neurotensin (NT) decreases lower esophageal sphincter pressure and impedes gastric emptying, thus exacerbating gastroesophageal reflux. The aim was to determine the content of esophageal tissue NT in patients with erosive esophagitis compared to those with normal endoscopy with or without abnormal acid exposure. Consecutive patients (N = 21) with gastroesophageal reflux disease symptoms underwent an upper endoscopy, at which two biopsies from opposite walls were obtained from normal-appearing mucosa. Patients with normal upper endoscopy underwent a pH test. NT tissue content was determined using radioimmunoassay. Six patients had erosive esophagitis, seven normal endoscopy but abnormal acid exposure, and eight both normal upper endoscopy and normal acid exposure. The NT/protein ratio was significantly higher in patients with normal upper endoscopy and normal or abnormal pH test compared to those with erosive esophagitis (8.7 +/- 1.4 and 8.0 +/- 1.2 vs. 3.8 +/- 0.5, respectively; P < 0.01). There was no significant difference in NT/protein ratio in patients with normal upper endoscopy with versus those without abnormal acid exposure (P = 0.7). There was no correlation between the extent of acid exposure and the NT/protein ratio. We suggest that the lower tissue content detected in patients with erosive esophagitis may represent a local protective mechanism against gastroesophageal reflux.

The role of proton pump inhibitors in gastro-oesophageal reflux disease.

The proton pump inhibitors (PPIs) are the most successful class of drugs that have been introduced for the treatment of gastro-oesophageal reflux disease (GORD) because of their profound and consistent effect on gastric acid secretion. The PPIs have demonstrated an excellent adverse effect profile after approximately 18 years of clinical use. Healing rates in erosive oesophagitis surpass 90%. Complete symptom resolution is achievable in close to 80% of patients with Barrett's oesophagus. Complications of these conditions, such as oesophageal stricture, ulceration and others, are becoming less frequent because of PPI treatment. In non-erosive reflux disease, PPIs provide 50-65% symptom response rate, which is the highest amongst all currently available anti-reflux interventions. PPIs have also helped to improve success rates in treating patients with atypical/extra-oesophageal manifestations of GORD. The use of PPI treatment as a diagnostic tool for GORD is well accepted. However, PPIs have changed the face of GORD in the new millennium as the focus in gastroenterology practice has shifted to primarily treating patients who fail PPI therapy.

Evaluation of symptom index in identifying gastroesophageal reflux disease-related noncardiac chest pain.

BACKGROUND: Symptom index (SI), which represents the percentage of perceived gastroesophageal reflux-related symptoms that correlate with esophageal acid reflux events (pH <4), has been suggested as a measure to improve diagnosis of gastroesophageal reflux (GER)-related noncardiac chest pain (NCCP). Because no study has evaluated the value of the symptom index in NCCP patients, data to support this claim have yet to be elucidated. AIM: To evaluate the value of SI in identifying gastroesophageal reflux disease (GERD)-related NCCP patients. METHODS: Patients enrolled in this study were referred by a cardiologist after a comprehensive work-up excluded a cardiac cause for their chest pain. All patients underwent upper endoscopy to determine esophageal inflammation and 24-hour esophageal pH monitoring to assess esophageal acid exposure. Patients were instructed to record all chest pain episodes during the pH test. Patients with a positive SI (> or =50%) underwent the proton pump inhibitors (PPI) test, which is a therapeutic trial using a short course of high dose PPI. RESULTS: A total of 94 patients with NCCP were included in this study. Forty-seven (50%) had either a positive upper endoscopy or an abnormal pH test and were considered GERD-Positive. Forty-seven patients (50%) had both tests negative and were considered GERD-Negative. Total number of reflux episodes and percent total, supine and upright time pH less than 4, were significantly higher in the GERD-Positive group as compared with the GERD-Negative group (P < 0.0001, P < 0.0001, P = 0.0045, and P < 0.0001 respectively). Only 9 (19.1%) patients in the GERD-Positive group and 5 (10.6%) patients in the GERD-Negative group had a positive SI (p = ns). Eight (89%) out of the 9 patients who had a positive SI in the GERD-Positive group and 2 (40%) out of 5 patients in the GERD-Negative group responded to the PPI test. CONCLUSION: Positive SI is relatively uncommon in NCCP patients, regardless if GERD is present or absent. Hence, symptom index provides very little improvement in diagnosing GERD-related NCCP.

Progression or regression of Barrett's esophagus--is it all in the eye of the beholder?

OBJECTIVES: Accurate measurements of Barrett's esophagus length are important in clinical follow-up as well as in studies of therapeutic intervention in Barrett's esophagus. Our aim was to evaluate both the inter- and intraobserver reliability in measuring Barrett's length during two consecutive endoscopies by either the same or different experienced endoscopists. The relationship between Barrett's mucosa length and the absolute change in Barrett's length measurements on a follow-up endoscopy was also evaluated. METHODS: A total of 96 Barrett's patients underwent two consecutive endoscopies. The diagnosis of Barrett's esophagus was confirmed by the presence of intestinal metaplasia on biopsy. The Barrett's esophagus length was carefully measured and recorded during the two endoscopies. Procedures were performed by only two experienced endoscopists, who were not aware of previous endoscopic measurements. Only patients with long-segment (> or =3 cm) Barrett's esophagus were included in this study. RESULTS: The 55 patients who had their consecutive endoscopies performed by the same endoscopist had a mean 1.6-cm difference between the two measurements as compared to 1.4 cm in the 41 patients who had their endoscopies performed by different endoscopists (p = 0.3). The agreement between the two Barrett's length measurements was high in both groups, although it was slightly higher for endoscopies performed by the same endoscopist (r = 0.79 vs r = 0.67). Linear regression analysis of the absolute change in Barrett's length between the two endoscopic measurements and Barrett's mucosa length demonstrated a significant relationship (r = 0.28, p = 0.005). For every 1-cm increase in the mean length of Barrett's mucosa, a 0.15-cm increase in the absolute difference between two consecutive endoscopic measurements of Barrett's length was observed. CONCLUSIONS: Consecutive measurements of Barrett's length performed by different experienced endoscopists or by the same experienced endoscopist demonstrated a high degree of agreement. A range of variability in Barrett's length measurement was determined (+/-1.4-1.6 cm). True regression or progression of Barrett's mucosa should be considered only if the change is greater than the range of variability. In addition, endoscopists should be well aware that the longer the Barrett's mucosa the greater the absolute difference in Barrett's length measurement on follow-up endoscopy.

Gliotoxin ameliorates development of fibrosis and cirrhosis in a thioacetamide rat model.

Activation of hepatic stellate cells causes most of the pathological changes in cirrhosis. The fungal metabolite gliotoxin was shown to induce apoptosis of hepatic stellate cells in vitro. We examined whether gliotoxin may prevent or reverse liver fibrosis in a rat model of thioacetamide-induced cirrhosis, and whether gliotoxin administration in vivo causes apoptosis of activated stellate cells. Gliotoxin treatment resulted in a significant decrease in liver fibrosis in rats, but did not improve liver functions. We observed a significant reduction in the numbers of activated hepatic stellate cells in the gliotoxin-treated rats. Gliotoxin administration also resulted in parenchymal apoptosis of hepatocytes and hepatic stellate cells. In conclusion, gliotoxin reduces hepatic fibrosis, an effect accompanied by reduction of the numbers of activated hepatic stellate cells in the liver.

Current perspectives on the diagnosis and treatment of functional esophageal disorders.

Among the functional gastrointestinal disorders, functional disorders of the esophagus are second in prevalence only to irritable bowel syndrome. Progress has been made in recent years in our understanding of the pathophysiology of functional esophageal disorders. In this review we focus on recent advances in their diagnosis and treatment. Additionally, we critically appraise the current understanding of the various clinical aspects of each esophageal disorder. Finally, we highlight unanswered questions and areas of controversy.