Nutcracker esophagus: GERD or an esophageal motility disorder

A retrospective study was performed to determine the frequency of acid-related esophageal dysfunction in an unselected group of patients with nutcracker esophagus (NE). Five hundred seventy-two consecutive patients who underwent esophageal manometry and pH testing at one institution were evaluated. Forty-one percent were referred for evaluation of chest pain, 39% for reflux symptoms, and 20% for dysphagia, nausea, or epigastric pain. Esophageal manometry and 24-h pH monitoring were performed using standard methods. NE was defined as amplitude of phasic contractions of ≥180 mm Hg in any manometric tracing at any level of the esophagus. Abnormal total reflux was defined as >4% of the time with the esophageal pH < 4. A positive symptom index was defined as >50% of periods with pH < 4 coinciding with symptoms of chest pain or heartburn. Esophagitis was defined as an unequivocal mucosal defect if esophagogastroduodenoscopy was performed.
Forty-five patients met criteria for NE, with acid-related abnormalities found in 77%. Forty-nine percent had abnormal acid exposure time, 16% had positive symptom indexes with normal acid exposure, and 5% had endoscopic esophagitis. An additional 7% had only an increased number of reflux episodes with normal acid exposure and symptom indexes. The prevalence of NE was significantly higher in patients referred for chest pain than for typical reflux symptoms (14.3% vs 4.5%). Seventy-four percent of the patients with NE and chest pain did not have classic reflux symptoms. Seventy-six percent of 34 evaluable subjects who had been started on acid suppression were either improved or symptom free at an average of 10.7 months of follow-up.     

Medical therapy or coronary artery bypass graft surgery for chronic stable angina: an update using decision analysis

PURPOSE: Randomized trials comparing medical and surgical therapies for the treatment of chronic stable angina were completed in the early 1980s. Therapies developed since then have decreased mortality and myocardial infarction rates from coronary artery disease. Using decision analysis and incorporating current recommendations for treatment, we simulated a trial comparing coronary artery bypass graft surgery and medical therapy. METHODS: A Markov decision analysis model was constructed to compare the 5-year and 10-year outcomes of a simulated trial of medical therapy versus bypass surgery for stable chronic angina. Baseline data were obtained from a meta-analysis of trials comparing the two treatments. Data on risk reduction from contemporary therapies were obtained from randomized trials and meta-analyses. RESULTS: All subgroups experienced modest gains in survival with current therapies. At 5 years, the survival rate was 90% in the medical group (an absolute gain of 6%) and 94% in the surgical group (an absolute gain of 4%). Similar results were obtained for patients with triple-vessel disease. Among patients with a low ejection fraction, the 5-year survival rate was 85% for medical patients and 92% for surgical patients. Sensitivity analyses did not substantially affect the conclusions. CONCLUSION: Advances in the treatment of chronic stable angina have improved the outcome both for patients treated initially with surgery and for those treated initially with medical therapy. The improvements were of similar magnitude in both groups, so the fundamental conclusions of the bypass trials are unchanged.     

Gastroesophageal reflux disease symptoms on antisecretory therapy: acid, non-acid, or no GERD

A clinically important subset of patients with erosive esophagitis will not attain adequate symptom relief and healing on once-a-day proton pump inhibitor therapy. This is especially true in patients with frequent and nocturnal heartburn and in those with Los Angeles Grades C and D erosive esophagitis. The approach to evaluation and management of cases of refractory or difficult gastroesophageal reflux disease is the subject of this state-of-the-art review.     

Motion--Helicobacter pylori causes or worsens GERD: arguments against the motion.

Data from large epidemiological studies show that Helicobacter pylori is less prevalent in patients with gastroesophageal reflux disease (GERD) than in control subjects. The more virulent cagA-positive strains of the organism are also less commonly seen in patients with erosive esophagitis and in those with Barrett's esophagus than in those with less severe forms of GERD. Although the relationship between H pylori and gastric physiology is complex, the organism has little effect on acid secretion in most North American or Western European subjects, and has a net suppressive effect, especially in elderly subjects, in other parts of the world. Thus, the organism has a potential protective effect against GERD, which is exacerbated by gastric acidity. H pylori has no proven effect on other gastric factors that might provoke reflux, including delayed gastric emptying or inappropriate relaxation of the gastric fundus. Two well-designed interventional studies have found that eradication of H pylori either provoked GERD or had no effect. A third smaller study, which seemed to demonstrate that persistent infection was associated with GERD, was flawed, in that the two treatment groups were not comparable. The evidence thus does not support the idea that H pylori infection provokes or aggravates GERD.     

Medical therapy for acromegaly.

Both somatostatin analogues, which bind to the somatostatin receptor subtypes 2 and 5, and dopamine agonists, which are specific for the D2 receptor, have been used to treat acromegaly. Each of these classes of drugs contains several compounds that vary in duration of action, efficacy, and side effect profile. Although somatostatin analogues reduce GH levels and alleviate symptoms in most patients and restore IGF-1 levels to normal in 60% to 65% of patients, tumor shrinkage is limited to 40% of patients. evidence in the literature supports the use of these medications as secondary therapy in patients with acromegaly who have had surgery and who continue to have elevated GH levels (above 2 ng/mL during an oral glucose tolerance test) with or without IGF-1 concentrations that are above the upper limit of normal for age. In addition, medical therapy indicated in patients who refuse surgery and in patients who are poor surgical candidates. The controversial question is whether medical therapy should be an option for primary treatment of the acromegalic patient. Currently, ther are no data from prospective randomized trials comparing the effects of surgery versus somatostatin analogues as first-line therapy for for newly diagnosed acromegalic patients. Limited data from nonrandomized studies demonstrate that somatostatin analogues are effective long-term in suppressing GH and reducing IGF-1 into the normal range in approximately two-thirds of patients who have never undergone previous treatment. It is still the consensus that patients with GH-secreting microadenomas should undergo surgical resection, because the likelihood of complete cure by an experience neurosurgeon is high, at least 70% or greater. Successful surgical treatment has the advantage of completely removing the tumor in contrast to medical therapy, which rarely produces shrinkage greater than 50% despite the fact that IGF-1 and GH levels may be normal. In patients with macroadenomas of a size and location that suggest that the chance of complete resection is 40% or less, primary treatment with a somatostatin analogue should be considered as one option in the initial management of the patient. Another option in such an individual would be surgical debulking followed by medical therapy, because it is theoretically possible that biochemical cure with medical therapy after surgical debulking might be achieved with lower doses. The cost-effectiveness of these approaches has not yet been determined. Once the decision has been made to begin medical therapy, a choice must be made between dopamine agonists and somatostatin analogues. Most evidence suggests that somatostatin analogues are more effective than dopamine agonists and therefore would be the therapy of choice. In select patients, dopamine agonists, particularly the long-acting agonist cabergoline, may be preferred initially if the patient is unwilling to take injections or if the GH elevations are relatively modest (< 10 ng/mL). Biochemical cure should be assessed by measurement of GH (which can be performed 2 hours after an octreotide injection) and IGF-1 concentrations. The goal of treatment include reduction of of GH below 2 ng/mL and reduction of IGF-1 into the normal range. In patients who do not reach these goals, the dose or frequency of injection of the somatostatin analogue or both should be increased. If such measures are unsuccessful, a dopamine agonist may be added to the medical regimen because some studies suggest that combination therapy may be more effective in select cases than octreotide therapy alone. If such measures are still unsuccessful, other options should be considered, including surgery, pituitary radiation, and medical treatment with investigational drugs.     

Esophageal reflux hypersensitivity: Non-GERD or still GERD?

The most recent iteration of the classifications for functional esophageal disorders, Rome IV, proposed relevant modifications of the previous definitions for Rome III. They specifically considered increased esophageal acid exposure as the marker of gastroesophageal reflux disease (GERD), including the remaining part of non-erosive reflux disease patients with normal acid in the group with functional alterations, considering both reflux hypersensitivity and functional heartburn. However, recent pathophysiological and therapeutic data suggest the need for a return to including reflux hypersensitivity in the GERD spectrum. Indeed, physiologic alterations in esophageal mucosal integrity and chemical clearance, the presence of microscopic esophagitis, and strict symptom-reflux association support the concept that reflux hypersensitivity pertains to GERD. Surgical anti-reflux therapy has resulted in positive outcomes, even in the long term, in patients with reflux hypersensitivity and not in those with functional heartburn. Moreover, clinical trials using neuromodulators have been scarce and provided conflicting results. As a result, the real progress of the Rome IV classifications is in dispute. This article aims to summarize the most recent knowledge of non-erosive reflux disease and reflux hypersensitivity to discuss the utility of Rome IV criteria in the identification and management of functional esophageal disorders.     

Cytokines in immunodeficient patients with invasive fungal infections: an emerging therapy.

Immune response is the major contributor to host defense against opportunistic fungal infections such as candidiasis, aspergillosis and other rare infections. A number of cytokines have been developed and studied in vitro for activity against fungal pathogens. The most studied among them in relation to fungal infections are granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) and interferon-gamma (IFN-gamma). The fields where these cytokines have been predominantly studied or where they may need more study are primary immunodeficiencies of the phagocytic cells, neonatal age, human immunodeficiency virus infection and cancer-related conditions such as neutropenia and hemopoietic cell transplantation. In this review, the in vitro, experimental animal and clinical data of cytokines are summarized in relation to invasive candidiasis, aspergillosis and emerging fungal infections. Cytokine administration to patients together with antifungal agents, as well as transfusion of cytokine-upgraded phagocytes, are promising immunotherapeutic modalities for further research.     

Advanced therapy for prostatitis: Minimally invasive and invasive therapies

The clinical syndromes of chronic prostatitis range from well-defined chronic bacterial infections to poorly defined chronic pelvic pain syndrome, previously referred to as prostatodynia and abacterial prostatitis. Faced by the obscure nature of the disease, its protracted course, and the poor response to oral medication, urologists have considered alternative treatment options. This article reviews the indications and outcomes of minimally invasive and invasive therapies for chronic prostatitis syndromes and discusses their potential use and benefits.     

Medical therapy for Cushing's disease.

Various drugs have been employed in the management of pituitary-dependent Cushing's disease. The neuromodulatory compounds used thus far have demonstrated true clinical efficacy only occasionally when employed as sole treatment. Steroid synthesis inhibitors are effective in the majority of cases in a dose-dependent manner. By their ability to correct hypercortisolism and its severe complications quickly, they are suitable for critical cases and in preparation for surgery. The clinical experience with the only glucocorticoid receptor antagonist that can be administered to humans is still too limited to assess its therapeutic validity. No medical strategy can be standardized for this complex condition. Different therapeutic tools should be selected according to the form of disease to be treated (hypothalamic/pituitary) and the peculiar clinical situation of each patient. Combined treatments may achieve better therapeutic efficacy.     

High-resolution manometry of the EGJ: an analysis of crural diaphragm function in GERD

AIM: High-resolution manometry (HRM) provides a spatially enhanced, dynamic representation of the esophagogastric junction (EGJ) high-pressure zone making it possible to isolate the crural diaphragm (CD) contraction from expiratory lower esophageal sphincter (LES) pressure. This study compared CD function of subjects with and without gastroesophageal reflux disease (GERD). METHODS: A total of 75 asymptomatic controls and 156 GERD patients (EGD or pH monitoring positive) underwent HRM. The EGJ axial pressure profile was analyzed over five respiratory cycles to quantify the position and contractile vigor of the CD relative to the LES. Correlations between EGJ HRM attributes and GERD status were examined. RESULTS: GERD patients had significantly greater CD-LES separation compared with either controls or EGD-/pH- patients. GERD patients also had significantly less inspiratory augmentation of EGJ pressure (EGD-/pH+, 11.5 +/- 1.9 mmHg; EGD+, 10.0 +/- 1.2 mmHg) compared with controls (16.9 +/- 1 mmHg) or EGD-/pH- patients (16.7 +/- 0.2 mmHg). Using a logistic regression model that simultaneously examined expiratory LES pressure, LES-CD separation, and inspiratory EGJ augmentation while controlling for age and BMI, only inspiratory augmentation had a significant independent association with GERD. CONCLUSIONS: HRM characterization of EGJ morphology correlates with the objective demonstration of GERD. Although both LES pressure and LES-CD separation are associated with GERD, the strongest association and the only independent predictor of GERD as a categorical outcome in a logistic regression analysis was impaired CD function as indicated by reduced inspiratory augmentation of EGJ pressure.     

Proton pump inhibitor step-down therapy for GERD: a multi-center study in Japan

AIM:To investigate the predictors of success in stepdown of proton pump inhibitor and to assess the quality of life(QOL).METHODS:Patients who had heartburn twice a week or more were treated with 20 mg omeprazole(OPZ) once daily for 8 wk as an initial therapy(study 1).Patients whose heartburn decreased to once a week or less at the end of the initial therapy were enrolled in study 2 and treated with 10 mg OPZ as maintenance therapy for an additional 6 mo(study 2).QOL was in-vestigated using the gastrointesti...     

Motion--Helicobacter pylori worsens GERD: arguments for the motion.

There are several reasons for eradicating Helicobacter pylori in patients with chronic gastroesophageal reflux disease (GERD). Perhaps the most compelling is the evidence that chronic acid suppression therapy can lead to the development of atrophic gastritis, a premalignant condition, in patients with H pylori infection. Epidemiological data that suggest that H pylori is less prevalent in GERD patients than in control subjects may be susceptible to publication bias, and confounding social and environmental factors may also be involved. Although it has been thought that eradication of the organism might lead to increased esophageal acid exposure, this has not been demonstrated in practice. Studies that appeared to show that GERD could be provoked by antimicrobial therapy of duodenal ulcers also have methodological weaknesses. Underlying GERD symptoms might be unmasked after withdrawal of acid-suppression therapy, for reasons that are unrelated to H pylori. In fact, eradication of the organism has been shown to decrease heartburn in patients with peptic ulcer disease. When H pylori is successfully eradicated in patients with GERD, relapse rates are not increased, and the disease-free interval seems to be prolonged. Eradication of the organism is a wise policy in patients who face long term acid-suppression therapy for GERD.     

Evaluation of GERD symptoms during therapy. Part II. Psychometric evaluation and validation of the new questionnaire ReQuest in erosive GERD

BACKGROUND/AIMS: Evaluation of the response of gastroesophageal reflux disease (GERD) symptoms to treatment would be facilitated by a brief, valid, reliable and responsive, self-assessed GERD-sensitive scale. We therefore developed the Reflux Questionnaire (ReQuest). This publication describes the psychometric evaluation and validation of ReQuest. METHODS: This second phase of development was based on data from a clinical trial of patients with erosive GERD who received pantoprazole 20 or 40 mg daily for 28 days and completed weekly the long, and daily the short version of ReQuest. The psychometric analyses of ReQuest included internal consistency, test-retest reliability and responsiveness. Construct validity was evaluated by comparison with the Gastrointestinal Symptom Rating Scale (GSRS) and the Psychological General Well-Being (PGWB) scale. RESULTS: Validation of ReQuest indicated very high internal consistency (Cronbach's alpha = 0.90) and test-retest reliability (intraclass correlation coefficient 0.94 (long-long) and 0.86 (short-short)). This was also the case for the two subscales ReQuest-GI and ReQuest-WSO with Cronbach's alpha coefficients of 0.84 and 0.81. Responsiveness was high with a responsiveness index of >0.8 at day 28. Construct validity was good. CONCLUSION: ReQuest is a highly reliable, valid and responsive self-assessment tool for evaluating treatment response in patients with erosive GERD, and can be applied daily.