Future aspects of plant derived bioactive metabolites as therapeutics to combat benign prostatic hyperplasia.

ETHNOPHARMACOLOGICAL RELEVANCE: Benign prostatic hyperplasia (BPH), characterized by prostate enlargement due to cell proliferation, is a common urinary disorder in men over 50, manifesting as lower urinary tract symptoms (LUTS). Currently, several therapeutic options are accessible for treating BPH, including medication therapy, surgery and watchful waiting. Conventional drugs such as finasteride and dutasteride are used as 5α-reductase inhibitors for the treatment of BPH. However long-term use of these drugs is restricted due to their unpleasant side effects. Despite the range of available medical therapies, the effective treatment against BPH is still inadequate. Certain therapeutic plants and their phytochemicals have the aforementioned goals and work by regulating this enzyme. AIM OF THE STUDY: This review aims to provide a comprehensive insight to advancements in diagnosis of BPH, modern treatment methods and the significance of ethnobotanically relevant medicinal plants as alternative therapeutics for managing BPH. MATERIAL AND METHODS: A thorough and systematic literature search was performed using electronic databases and search engines such as PubMed, Web of Science, NCBI and SciFinder till October 2023. Specific keywords such as "benign prostatic hyperplasia", "medicinal plants", "phytochemicals", "pharmacology", "synergy", "ethnobotany", "5-alpha reductase", "alpha blocker" and "toxicology". By include these keywords, a thorough investigation of pertinent papers was assured, and important data about the many facets of BPH could be retrieved. RESULTS: After conducting the above investigation, 104 herbal remedies were found to inhibit Phosphodiesterase-5 (PDE-5) inhibition, alpha-blockers, or 5α -reductase inhibition effects which are supported by in vitro, in vivo and clinical trial studies evidence. Of these, 89 plants have ethnobotanical significance as alpha-blockers, alpha-reductase inhibition, or PDE-5 inhibition, and the other fifteen plants were chosen based on their ability to reduce BPH risk factors. Several phytocompounds, including, rutaecarpine, vaccarin, rutin, kaempferol, ß-sitosterol, quercetin, dicaffeoylquinic acid, rutaevin, and phytosterol-F have been reported to be useful for the management of BPH. The use of combination therapy offers a strong approach to treating long-term conditions compare to single plant extract drugs. Furthermore, several botanical combinations such as lycopene and curcumin, pumpkin seed oil and saw palmetto oil, combinations of extracts from Funtumia africana (Benth.) Stapf and Abutilon mauritianum (Jacq.) Medik., and Hypselodelphys poggeana (K.Schum.) Milne-Redh. and Spermacoce radiata (DC.) Sieber ex Hiern are also supported through in vitro and in vivo studies for managing BPH through recuperation in patients with chronic long-term illnesses, as measured by the International Prostate Symptom Score. CONCLUSION: The review proposes and endorses careful utilization of conventional medications that may be investigated further to discover possible PDE-5, 5 alpha-reductase, an alpha-blocker inhibitor for managing BPH. Even though most conventional formulations, such as 5 alpha-reductase, are readily available, systemic assessment of the effectiveness and mechanism of action of the herbal constituents is still necessary to identify novel chemical moieties that can be further developed for maximum efficacy. However, there exist abundant botanicals and medicinal plants across several regions of Africa, Asia, and the Americas, which can be further studied and developed for utilization as a potential phytotherapeutic for the management of BPH.

Ethnobotanical significance of medicinal plants: Beta-amyloid and tau aggregation inhibitors against Alzheimer's disease.

Among the various neurodegenerative disorders, Alzheimer's disease (AD) is identified as one of primary causes of dementia in the elderly, which progresses slowly leading to cognitive decline and ability to function independently. Although various pathological mechanisms have been proposed, the exact mechanism is not yet elucidated. Numerous processes such as old age, mitochondrial dysfunction, and genetics lead to the aggregation of beta-amyloid (Aß) as amyloid plaques and tau proteins as neurofibrillary tangles in the neurons leading to their death and destruction, finally leading to AD. The current treatment measures can only temporarily improve the symptoms, slowing cognitive decline without any effect on AD pathology for better therapeutic effect. Furthermore, the high failure rates of a number of drugs during clinical trials due to their side effects has led the researchers to focus on alternative sources for drug development. As natural ingredients were considered the primary line of treatment in the olden days, and as several medicinal plant products are also proven as effective AD targets, it will be wise to investigate those with significant ethnobotanical value as potential neuroprotectives, nootropics or memory boosters. Throughout the study, propanoids, glycosides, iridoids, carotenoids and flavonoids that show potential anti-inflammatory, antioxidant, and anti-cholinesterase were also found to be inhibitors of Aß and tau aggregation, where Saikosaponin C, Fisetin, and Morin can act as dual inhibitors. The review provides an insight in the need for proper and complete scientific evaluation of these ethnobotanically useful medicinal plants to be identified as potential leads in AD therapy.

Morphology of human fetal enteric neurons: A comparative study of different segments of the colon.

OBJECTIVES: The Enteric Nervous System (ENS) present in the wall of the gut is currently being explored because of its influence on the gut and beyond. In this context, the morphology of developing ENS has not been completely understood in humans due to lack of adequate literature. The aim of the present study was to observe the morphology of the enteric neurons in the human fetal colon and compare the findings in ascending colon a midgut derivative and descending colon a hindgut derivative at various weeks of gestation (WG). MATERIAL AND METHODS: Tissue samples from 15 aborted fetuses (11 WG to 2 months postnatal) were processed for Cresyl violet, H & E staining, and NADPH Diaphorase histochemistry. The morphometric analysis was done by calculating the neuronal number density and neuronal fractional area. The Student t-test; Mann-Whitney test and Wilcoxon signed-rank test were used to analyze the data. RESULTS: The muscularis externa with two distinct layers was visible as early as 13 WG and the muscularis mucosae was first observed at 18 WG. The size of the myenteric neurons appeared to be larger with increasing weeks of gestation suggesting a process of neuronal maturation. The neuronal number density and neuronal fractional area seemed to be reduced with advancing fetal age. There was no marked difference between the ascending and sigmoid colon. At 23 and 26 WG, a mature pattern of nitrergic innervation was observed. CONCLUSION: This study is done on human fetal tissue samples unlike previous studies on animal samples to comprehend the morphology of developing ENS. It will aid in understanding the effect of ENS on various neurological disorders.

Neuromuscular variations in the gluteal region - Embryological basis and clinical significance.

ABSTRACT: Piriformis, is a key muscle in the gluteal region. Under its lower border sciatic nerve and inferior gluteal nerves exit. During routine educational dissection of the lower limb, bilateral gluteal regions in fifteen cadavers (30 gluteal regions) focusing on the variations of inferior gluteal nerve and sciatic nerve with respect to piriformis muscle were observed in the department of anatomy, All India Institute of Medical Sciences, New Delhi, India. In one of the left sided specimens, inferior gluteal nerve had an abnormal course, piercing superior belly of piriformis muscle instead of emerging through the lower border of it along with variation of the sciatic nerve. The common peroneal component of the sciatic nerve was coming out between the two anomalous tendinous slips of the piriformis muscle, whereas the tibial component, emerged along lower border of the piriformis muscle bilaterally in the same cadaver. In the remaining cadavers, there were no variations of the inferior gluteal nerve with respect to the piriformis muscle. But in another cadaver, there was a similar variation of the sciatic nerve bilaterally. Inferior gluteal and sciatic nerves, when compressed by muscle belly or tendinous slips of the piriformis muscle, may cause lurching gait and sciatica respectively. Knowledge of the different variations of these peripheral nerves with respect to the piriformis muscle is important to clinicians and surgeons for the accurate diagnosis and intervention.

Morphology of enteric glia in colorectal carcinoma: A comparative study of tumor site and its proximal normal margin.

OBJECTIVE: Colorectal carcinoma (CRC) is the third most common cancer in the world and fifth most common cancer in India. To understand the extent of perineural invasion (PNI) in CRC it is essential to study the morphology of enteric glial cells (EGCs). The aim of the study was to analyze the numerical density of EGCs and area of myenteric ganglia (MG) in the colonic tissue samples collected from CRC patients. MATERIAL AND METHODS: Fifteen intraoperative tissue specimens were collected from the tumor site and 2cm proximal to the upper extent of tumor. The samples were divided into four groups: group 1 (n=15): proximal tumor free colonic tissue; group 2 (n=3): well-differentiated; group 3 (n=8): moderately differentiated; group 4 (n=4): poorly differentiated adenocarcinoma. After processing the tissues were subjected to hematoxylin and eosin staining. The anti-S100ß and anti-GFAP antibodies were used to observe the EGCs. RESULTS: In the H&E stained sections the number of myenteric ganglia appeared to be decreasing with increasing grade of adenocarcinoma. Immunostaining showed significant decreasing pattern in the numerical density of EGCs per myenteric ganglion and mean area of myenteric ganglia in relation to the thickness of circular muscle, corresponding to the increasing grades of adenocarcinoma. The morphology of the EGCs remained unaltered in the colonic tissue adjacent to the tumor site. CONCLUSION: Significant loss of EGCs and neurodegeneration corresponded with the grade of tumor emphasizing on its prognostic value. The PNI was not seen in the clear margin proximal to the tumor site.

Medicinal plants as a potential source of Phosphodiesterase-5 inhibitors: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: The prevalence and distress caused by erectile dysfunction (ED) to both male and female partners are increasing at a steady rate. ED has now become the most treated sexual disorder for men among young and old age groups due to varying physical and psychological factors. The treatment with synthetic Phosphodiesterase-5 (PDE5) inhibitors are cost-effective but due to adverse effects such as priapism, loss of vision, heart attack and syncope, the daily life patterns of these patients are distressed and hence the need for alternative medicaments or sources are of utmost important. Therefore, the exploration of medicinal plants as PDE5 inhibitors will be worthwhile in tackling the problems as many plant extracts and fractions have been long used as aphrodisiacs and sexual stimulants which may be found to be active against PDE5 enzyme. AIM OF THE STUDY: To provide a review on the different medicinal herbs traditionally used as natural aphrodisiacs, libido or sexual enhancers which are proven for their PDE5 inhibitory effect. MATERIALS AND METHODS: Ethnobotanical and scientific information was procured, reviewed and compiled from the literature search of electronic databases and search engines. RESULTS: A total of 97 medicinal plants exhibiting PDE5 inhibitory effect are reviewed in this paper which is supported by preclinical experimental evidence. Among them, 77 plants have been selected according to their traditional and ethnobotanical uses as aphrodisiacs and the rest are screened according to their effectiveness against predisposing factors responsible for ED and sexual dysfunction such as diabetes and hypertension or due to the presence of phytochemicals having structural similarity towards the identified natural PDE5 inhibitors. In addition, sixteen alkaloids, sixty-one phenolics and eight polycyclic aromatic hydrocarbons have been isolated or identified from active extracts or fractions that are exhibiting PDE5 inhibitory activity. Among them, isoflavones and biflavones are the major active constituents responsible for action, where the presence of prenyl group for isoflavones; and the methoxy group at C-5 position of flavones are considered essential for the inhibitory effect. However, the prenylated flavonol glycoside, Icariin and Icariside II isolated from Epimedium brevicornum Maxim (hory goat weed) are the most effective inhibitor, till date from natural sources. Traditional medicines or formulations containing extracts of Ginkgo biloba L., Kaempferia parviflora Wall. ex Baker, Clerodendrum colebrookianum Walp., Eurycoma longifolia Jack and Vitis vinifera L. are also found to be inhibitors of PDE5 enzyme. CONCLUSION: The review suggests and supports the rational use of traditional medicines that can be further studied for the development of potential PDE5 inhibitors. Many traditional medicines are still used in various regions of Africa, Asia and South America that are poorly characterized and experimented. Despite the availability of a vast majority of traditional formulations as aphrodisiacs or sexual stimulants, there exists a need for systemic evaluation on the efficacy as well as the mechanism of action of the herbal constituents for the identification of novel chemical moieties that can be further developed for maximum efficacy.

Mitral valve repair in an octogenarian with symptomatic severe mitral regurgitation: First use of MitraClip in India.

Percutaneous mitral valve repair is an accepted treatment of choice in Europe and North America for severe primary or secondary mitral regurgitation, in highly symptomatic patients for whom surgical repair is prohibitively high risk. We describe the first use of the MitraClip in India in a frail elderly female with symptomatic heart failure from severe primary mitral regurgitation who was considered high risk for surgical repair. She had substantial improvement in her symptoms as well as quality of life following the procedure.

Enterotoxigenic Escherichia coli heat labile enterotoxin inhibits intestinal ascorbic acid uptake via a cAMP-dependent NF-κB-mediated pathway.

Vitamin C is an antioxidant and acts as a cofactor for many enzymatic reactions. Humans obtain vitamin C from dietary sources via intestinal absorption, a process that involves the sodium-dependent vitamin C transporters-1 and -2 (SVCT1 and SVCT2). Enterotoxigenic Escherichia coli (ETEC) infection impacts intestinal absorption/secretory functions, but nothing is known about its effect on ascorbic acid (AA) uptake. Here we demonstrate that infection of Caco-2 cells with ETEC led to a significant inhibition in intestinal AA uptake. This inhibition was associated with a marked reduction in hSVCT1 and hSVCT2 protein, mRNA, and heterogeneous nuclear RNA (hnRNA) expression levels as well as significant inhibition in the activity of both the SLC23A1 and SLC23A2 promoters. Similarly, exposure of mice to ETEC led to a significant inhibition in intestinal AA uptake and reduction in mSVCT1 and mSVCT2 protein, mRNA, and hnRNA expression levels. Inhibition was caused by the action of heat labile enterotoxin (LT), since infecting Caco-2 cells with LT-deficient ETEC (ΔLT) failed to impact AA uptake. Because LT activates adenylate cyclase, we also examined the effect of dibutyryl-cAMP in AA uptake by Caco-2 cells and observed a significant inhibition. Furthermore, treating the cells with celastrol, a specific NF-κB inhibitor, significantly blocked the inhibition of AA uptake caused by ETEC infection. Together, these data demonstrate that ETEC infection impairs intestinal AA uptake through a cAMP-dependent NF-κB-mediated pathway that regulates both SLC23A1 and SLC23A2 transcription. NEW & NOTEWORTHY Our findings demonstrate that heat-labile enterotoxin produced by enterotoxigenic Escherichia coli inhibits AA uptake in intestinal epithelial cells and mouse intestine. This effect is mediated through transcriptional repression of SLC23A1 (SVCT1) and SLC23A2 (SVCT2) via a cAMP-dependent NF-κB signaling pathway.

Tumor necrosis factor alpha reduces intestinal vitamin C uptake: a role for NF-κB-mediated signaling.

Sodium-dependent vitamin C transporter-1 (SVCT-1) is the major transporter mediating intestinal vitamin C uptake. Intestinal inflammation and prolonged infection are associated with increased serum and intestinal mucosa levels of tumor necrosis factor-α (TNF-α), which also exerts profound effects on the intestinal absorption process. Elevated levels of TNF-α have been linked to the pathogenesis of inflammatory bowel disease (IBD) and malabsorption of nutrients, and patients with this condition have low levels of vitamin C. To date, little is known about the effect of TNF-α on intestinal absorption of vitamin C. We studied the impact of TNF-α on ascorbic acid (AA) transport using a variety of intestinal preparations. The expression level of human SVCT-1 mRNA is significantly lower in patients with IBD. TNF-α treated Caco-2 cells and mice showed a significant inhibition of intestinal 14C-AA uptake. This inhibition was associated with significant decreases in SVCT-1 protein, mRNA, and heterogeneous nuclear RNA levels in TNF-α treated Caco-2 cells, mouse jejunum, and enteroids. Also, TNF-α caused a significant inhibition in the SLC23A1 promoter activity. Furthermore, treatment of Caco-2 cells with celastrol (NF-κB inhibitor) blocked the inhibitory effect caused by TNF-α on AA uptake, SVCT-1 protein, and mRNA expression, as well as the activity of SLC23A1 promoter. Treatment of TNF-α also led to a significant decrease in the expression of hepatocyte nuclear factor-1-α, which drives the basal activity of SLC23A1 promoter, and this effect was reversed by celastrol. Together, these findings show that TNF-α inhibits intestinal AA uptake, and this effect is mediated, at least in part, at the level of transcription of the SLC23A1 gene via the NF-κB pathway. NEW & NOTEWORTHY Our findings show that tumor necrosis factor-α inhibits intestinal ascorbic acid uptake in both in vitro and in vivo systems, and this inhibitory effect is mediated, at least in part, at the level of transcription of the SLC23A1 (sodium-dependent vitamin C transporter-1) gene via the NF-κB pathway.

Pharmacological treatments for acute respiratory distress syndrome: systematic review.

BACKGROUND: Our objective was to systematically review the effect of pharmacological therapies on mortality in patients with acute respiratory distress syndrome (ARDS), focusing on randomized controlled trials (RCTs) published since a previous review in 2004. METHODS: We updated previous searches and searched OVID versions of MEDLINE, EMBASE and CENTRAL (to January 2013) and proceedings from conferences and bibliographies of included studies. We included RCTs of pharmacologic therapies compared with placebo or no therapy for adult patients with ARDS, using authors' definitions, which reported on mortality (≤ 3 months after randomization). We excluded subgroups of patients with ARDS reported in RCTs enrolling other populations and RCTs of therapies to prevent ARDS, nutritional or fluid interventions, inhaled nitric oxide, therapies coupled to a mechanical ventilation strategy, or oxygen. Two reviewers independently screened citations, selected articles for inclusion, and abstracted clinical and methodological data from included studies with disagreements resolved by a third reviewer. Mortality data were pooled using random-effects models. RESULTS: From 13461 citations, 58 trials (6635 patients) of 21 classes of medications met selection criteria; 26 trials (3880 patients) were published after 2003. Meta-analyses showed reduced 28-day mortality with a 48-hour infusion of cis-atracurium in early ARDS (relative risk 0.66, 95% confidence interval 0.50 to 0.87; 431 patients, 138 deaths). There was no effect on mortality with granulocyte-macrophage colony stimulating factor, late low-dose methylprednisolone, neutrophil elastase inhibitors, intravenous salbutamol, surfactant, or N-acetylcysteine; each meta-analysis included ≥ 1 trial published after 2003. Seven single trials of other treatments published after 2003 showed no effect. Meta-analysis of older trials of prostaglandin E1 also showed no effect. CONCLUSION: Effective pharmacotherapy for ARDS remains extremely limited. Cis-atracurium is a promising treatment for early moderate-severe ARDS (using Berlin definition nomenclature) and merits further investigation in a large RCT.

The risk of endoscopic mucosal resection in the setting of clopidogrel use.

Objective. Guidelines on antiplatelet medication use during endoscopy are based on limited evidence. We investigate the risk of bleeding and ischemic events in patients undergoing endoscopic mucosal resection (EMR) of esophageal lesions in the setting of scheduled cessation and prompt resumption of clopidogrel. Design. Single centre retrospective review. Patients. Patients undergoing EMR of esophageal lesions. Interventions. Use of clopidogrel before EMR and resumption after EMR. Patients cease antiplatelets and anticoagulants 7 days before EMR and resume clopidogrel 2 days after EMR in average risk patients. Main Outcomes. Gastrointestinal bleeding (GIB) and ischemic events (IE) within 30 days of EMR. Results. 798 patients underwent 1716 EMR. 776 EMR were performed on patients on at least 1 antiplatelet/anticoagulant (APAC). 17 EMR were performed following clopidogrel cessation. There were 14 GIB and 2 IE. GIB risk in the setting of recent clopidogrel alone (0%) was comparable to those not on APAC (1.1%) (P = 1.0). IE risk on clopidogrel (6.3%) was higher than those not on APAC (0.1%) (P = 0.03). Limitations. Retrospective study. Conclusions. Temporary cessation of clopidogrel before EMR and prompt resumption is not associated with an increased risk of gastrointestinal bleeding but may be associated with increased ischemic events.

Endoscopic ultrasound-guided abscess drainage.

Abdominal and pelvic abscesses have traditionally been drained by percutaneous techniques or surgery. While surgical drainage is associated with considerable morbidity and mortality, percutaneous techniques are associated with the need for multiple interventions, increased length of hospital stay, and an indwelling external catheter for prolonged periods. Endoscopic ultrasound (EUS) is a minimally invasive but highly effective technique that enables internal drainage of the abscess. Although data are limited, evidence supporting its clinical efficacy is increasing rapidly. This article summarizes the current status of EUS-guided approach for drainage of gastrointestinal abscess collections.

Distribution of body fat and its influence on esophageal inflammation and dysplasia in patients with Barrett's esophagus.

BACKGROUND & AIMS: Increased waist circumference and visceral fat are associated with increased risk of Barrett's esophagus (BE) and esophageal adenocarcinoma. This association might be mediated by mechanical and endocrine mechanisms. We investigated the distribution of fat in subjects with BE and its association with esophageal inflammation and dysplasia. METHODS: We collected data from 50 BE cases and 50 controls (matched for age and sex, identified from a radiology trauma database) seen at the Mayo Clinic in 2009. Abdominal (subcutaneous and visceral) and gastroesophageal junction (GEJ) fat area was measured using computed tomography with standard techniques. Esophageal inflammation (based on a histologic score) and dysplasia grade were assessed from esophageal biopsies of BE cases by a gastrointestinal pathologist. Conditional logistic regression was used to assess the association of body fat depot area with BE status, esophageal inflammation, and dysplasia. RESULTS: All BE subjects had controlled reflux symptoms without esophagitis, based on endoscopy. The GEJ fat area (odds ratio [OR], 6.0; 95% confidence interval [CI], 1.3-27.7; P = .02), visceral fat area (OR, 4.9; 95% CI, 1.0-22.8; P = .04), and abdominal circumference (OR, 9.1; 95% CI, 1.4-57.2; P = 0.02) were associated with BE, independent of body mass index (BMI). The subcutaneous fat area was not associated with BE. Visceral and GEJ fat were significantly greater in BE subjects with esophageal inflammation (compared with those without, P = .02) and high-grade dysplasia (compared with those without, P = .01), independent of BMI. CONCLUSIONS: GEJ and visceral fat are associated with BE, and with increased esophageal inflammation and high-grade dysplasia in BE subjects, independent of BMI. Visceral fat therefore might promote esophageal metaplasia and dysplasia.

High-grade dysplasia and intramucosal adenocarcinoma in Barrett's esophagus: the role of endoscopic eradication therapy.

PURPOSE OF REVIEW: Endoscopic eradication therapy is considered a well tolerated and effective alternative to esophagectomy for a select patient population with high-grade Barrett's esophagus and intramucosal adenocarcinoma. This review highlights the available eradication techniques (resection and ablation) with emphasis on factors that influence the choice of therapy. RECENT FINDINGS: Long-term follow-up of patients treated with endoscopic eradication therapies demonstrates high rates of complete remission of dysplasia and intestinal metaplasia with overall survival comparable to patients treated surgically. Cohort studies also report that recurrence following successful ablation occurs in a significant proportion of patients, making careful surveillance an indispensable component following successful endoscopic therapy. Endoscopic eradication therapy is also effective for the treatment of recurrent dysplasia and intestinal metaplasia. Ablative therapies may lead to buried metaplasia in a small proportion of patients. The long-term clinical implications of buried metaplasia are unclear. SUMMARY: Patients undergoing endoscopic eradication therapy should be enrolled in a comprehensive surveillance and staging program that offers both resection and ablative techniques. Complete remission of dysplasia and intestinal metaplasia can be achieved in the vast majority of patients undergoing endoscopic therapy. Surveillance should continue after treatment with close monitoring for recurrent dysplasia.

Safety of prior endoscopic mucosal resection in patients receiving radiofrequency ablation of Barrett's esophagus.

BACKGROUND & AIMS: Radiofrequency ablation (RFA) is safe and effective treatment for flat dysplasia associated with Barrett's esophagus (BE). However, there are limited data on the safety of RFA in patients who had prior endoscopic mucosal resection (EMR), which might increase the risk of complications. We compared complications and histologic outcomes between patients who had EMR before RFA and those who received only RFA. METHODS: We performed a retrospective analysis of data collected from patients treated for BE, associated with dysplasia or intramucosal cancer, at the Mayo Clinic in Rochester, Minnesota, from 1998-2009. Patients were divided into groups that had RFA after EMR (group 1, n = 44) or only RFA (group 2, n = 46). We compared the incidence of complications (strictures, bleeding, and esophageal perforation) and histologic features (complete resolution of dysplasia and complete resolution of intestinal metaplasia [CR-IM]) between groups. Logistic regression analysis was performed to assess predictors of stricture formation. RESULTS: Stricture rates were 14% in group 1 and 9% in group 2 (odds ratio, 1.53; 95% confidence interval [CI], 0.26-9.74). The rates of CR-IM were 43% in group 1 and 74% in group 2 (odds ratio, 0.33; 95% CI, 0.14-0.78). The rates of complete resolution of dysplasia were 76% in group 1 and 71% in group 2 (odds ratio, 1.28; 95% CI, 0.39-4.17). The adjusted odds ratio for CR-IM in group 1 (adjusting for age, segment length, and grade of dysplasia) was 0.50 (95% CI, 0.15-1.66). CONCLUSIONS: Stricture rates among patients who receive only RFA are comparable to those of patients who had prior EMR. EMR appears safe to perform prior to RFA.

Population screening for barrett esophagus: a prospective randomized pilot study.

OBJECTIVE: To assess the feasibility of unsedated transnasal endoscopy (uTNE) and video capsule endoscopy (VCE) as alternatives to sedated endoscopy (sEGD) as screening tools for Barrett esophagus (BE) and to obtain preliminary estimates of participation rates for sEGD, uTNE, and VCE when used for community BE screening in a population cohort. PATIENTS AND METHODS: From February 1, 2009, to May 31, 2010, patients from Olmsted County, Minnesota, who were older than 50 years and had no history of known BE were randomized (stratified by age, sex, reflux symptoms noted in a validated questionnaire) into 3 groups for esophageal evaluation with sEGD, uTNE, or VCE. Participation rates and safety profiles were estimated. RESULTS: We contacted 127 patients to recruit 20 for each procedure arm (60 total). The probability of participation was 38% (95% confidence interval [CI], 26%-51%) for sEGD, 50% (95% CI, 35%-65%) for uTNE, and 59% (95% CI, 42%-74%) for VCE. Both uTNE and VCE were well tolerated without adverse effects. BE was identified in 3 patients and esophagitis in 8. CONCLUSION: Unsedated techniques may be acceptable, feasible, and safe alternatives to sEGD to screen for BE in the community. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00943280.

Outcomes of T1b esophageal adenocarcinoma patients.

BACKGROUND: Esophagectomy is usually recommended for patients with submucosal esophageal adenocarcinoma (T1b EAC) because of the potential for lymph node metastasis (LNM). Endoscopic management often differs based on the risk of metastasis. There is limited information on the difference in outcomes for T1b-EAC with and without esophagectomy. OBJECTIVES: To investigate (1) the outcomes of T1b EAC treatments with and without esophagectomy and (2) the percentage of LNM at esophagectomy for T1b-EAC. DESIGN: Retrospective cohort. SETTING: A tertiary Barrett's esophagus unit. PATIENTS: Sixty-eight T1b EAC patients based on EMR histology. INTERVENTIONS: Esophagectomy and endoscopic therapies. MAIN OUTCOME MEASUREMENTS: Survival duration and mortality rate. RESULTS: A total of 68 patients had T1b EAC; cumulative mortality rate was 30.9% and median survival duration was 39.5 months. Thirty-nine underwent esophagectomy and 29 did not. Among patients who underwent esophagectomy, 13 (33.3%) had LNM, and the mortality rate was 50.0% and 11.1% for those with and without LNM, respectively (P < .01). For those with and without esophagectomy, the cumulative mortality rates were 25.6% and 37.9%, and median survival duration was 48.9 and 34.8 months, respectively. There was no statistical difference in Charlson comorbidity index, number of EMRs, mortality rate, or survival duration. In Cox proportional hazard model analysis, the hazard ratio for esophagectomy was 0.5 (P = .21). LIMITATIONS: Retrospective, nonrandomized small sample size cohort. CONCLUSION: Among the patients with T1b EAC found in EMR specimens who underwent esophagectomy, one third had regional LNM. In our small series, patients who underwent esophagectomy did not have a significantly different survival duration from that of those who did not, indicating that these patients may have similar outcomes [corrected].

Epidemiology and natural history of intestinal metaplasia of the gastroesophageal junction and Barrett's esophagus: a population-based study.

OBJECTIVES: Population-based data on the epidemiology and outcomes of subjects with intestinal metaplasia of the gastroesophageal junction (IMGEJ) and Barrett's esophagus (BE) are limited. The objectives of this study were to (i) estimate the incidence of IMGEJ and BE diagnosed from clinically indicated endoscopy in Olmsted County, MN, over three decades (1976-2006) and prevalence as of 1 January 2007, (ii) compare baseline characteristics of subjects with IMGEJ and BE, and (iii) study the natural history and survival of both cohorts. METHODS: This was a population-based cohort study. The study setting was Olmsted County, MN. Patients with BE (columnar segment >1 cm with intestinal metaplasia) and IMGEJ (intestinal metaplasia in biopsies from the gastroesophageal junction) from 1976 to 2006 in Olmsted County, MN, were identified using Rochester Epidemiology Project resources. Demographic and clinical data were abstracted from medical records and pathology confirmed by gastrointestinal pathologists. The association of baseline characteristics with overall and progression-free survival was assessed using proportional hazards regression models. Outcome measures were baseline characteristics and overall survival of subjects with IMGEJ compared to those with BE. RESULTS: In all, 487 patients (401 with BE and 86 with IMGEJ) were identified and followed for a median interval of 7 (BE subjects) to 8 (IMGEJ subjects) years. Subjects with BE were older, heavier, reported reflux symptoms more often, and had higher prevalence of advanced neoplasia than those with IMGEJ. No patient with IMGEJ progressed to esophageal adenocarcinoma (EAC) in contrast to BE subjects who had a cumulative risk of progression of 7% at 10 years and increased risk of death from EAC (standardized mortality ratio 9.62). The overall survival of subjects with BE and IMGEJ did not differ from that expected in similar age- and sex-distributed white Minnesota populations. CONCLUSIONS: Subjects with IMGEJ appear to have distinct clinical characteristics and substantially lower cancer progression risk compared to those with BE.

Prevalence of esophageal eosinophils in patients with Barrett's esophagus.

OBJECTIVES: Recent studies have demonstrated high esophageal eosinophil counts in patients with GERD similar to eosinophilic esophagitis (EoE) yet the frequency of esophageal eosinophilia in GERD is unknown. Our aim was to determine the prevalence of dense esophageal eosinophilia in patients with Barrett's esophagus as a manifestation of GERD. METHODS: The Mayo Clinic pathology database was reviewed for patients diagnosed with Barrett's esophagus from January to December 2008 with squamous mucosa obtained during endoscopic surveillance. Clinical, endoscopic, and histologic findings were reviewed. Patients with ≥15 eosinophils per high powered field were identified and compared to those without esophageal eosinophilia. RESULTS: Two hundred patients with Barrett's esophagus and squamous tissue obtained at the time of biopsy were identified. Fourteen of the 200 patients (7%) had ≥15 eosinophils per high powered field. Demographics, symptoms, and proton pump inhibitor therapies were similar between those with and without esophageal eosinophilia. Endoscopic features suggestive of EoE were found in the squamous mucosa of 2 patients with and 7 patients without esophageal eosinophilia. Use of photodynamic, radiofrequency ablation, or monopolar electrocoagulation therapy for ablation of Barrett's mucosa was not associated with a higher rate of esophageal eosinophilia. Basal cell hyperplasia, papillary elongation, and spongiosis occurred frequently in association with esophageal eosinophilic infiltration. CONCLUSIONS: High esophageal eosinophil counts were found in 7% of this cohort of 200 patients with Barrett's esophagus and likely underestimates prevalence. The finding of esophageal eosinophilia in this cohort was independent of proton pump inhibitor use, features of EoE, or endoscopic therapy for Barrett's esophagus. Further studies are needed to assess if these findings are applicable to all patients with GERD.