The Montreal Definition and Classification of Gastroesophageal Reflux Disease: A Global Evidence-Based Consensus

Tumors reprogram pathways of nutrient acquisition and metabolism to meet the bioenergetic, biosynthetic, and redox demands of malignant cells. These reprogrammed activities are now recognized as hallmarks of cancer, and recent work has uncovered remarkable flexibility in the specific pathways activated by tumor cells to support these key functions. In this perspective, we provide a conceptual framework to understand how and why metabolic reprogramming occurs in tumor cells, and the mechanisms linking altered metabolism to tumorigenesis and metastasis. Understanding these concepts will progressively support the development of new strategies to treat human cancer.

Fundamentals of cancer metabolism

Prolactinomas account for approximately 40% of all pituitary adenomas and are an important cause of hypogonadism and infertility. The ultimate goal of therapy for prolactinomas is restoration or achievement of eugonadism through the normalization of hyperprolactinemia and control of tumor mass. Medical therapy with dopamine agonists is highly effective in the majority of cases and represents the mainstay of therapy. Recent data indicating successful withdrawal of these agents in a subset of patients challenge the previously held concept that medical therapy is a lifelong requirement. Complicated situations, such as those encountered in resistance to dopamine agonists, pregnancy, and giant or malignant prolactinomas, may require multimodal therapy involving surgery, radiotherapy, or both. Progress in elucidating the mechanisms underlying the pathogenesis of prolactinomas may enable future development of novel molecular therapies for treatment-resistant cases. This review provides a critical analysis of the efficacy and safety of the various modes of therapy available for the treatment of patients with prolactinomas with an emphasis on challenging situations, a discussion of the data regarding withdrawal of medical therapy, and a foreshadowing of novel approaches to therapy that may become available in the future.

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Advances in the treatment of prolactinomas.

Association of depression with medical illness: does cortisol play a role?

Background
Approximately 25% of adults regularly experience heartburn, a symptom of gastro-oesophageal reflux disease (GORD). Most patients are treated empirically (without specific diagnostic evaluation e.g. endoscopy. Among patients who have an upper endoscopy, findings range from a normal appearance, mild erythema to severe oesophagitis with stricture formation. Patients without visible damage to the oesophagus have endoscopy negative reflux disease (ENRD). The pathogenesis of ENRD, and its response to treatment may differ from GORD with oesophagitis.

Objectives
Summarise, quantify and compare the efficacy of short-term use of proton pump inhibitors (PPI), H2-receptor antagonists (H2RA) and prokinetics in adults with GORD, treated empirically and in those with endoscopy negative reflux disease (ENRD).

Search methods
We searched MEDLINE (January 1966 to November 2011), EMBASE (January 1988 to November 2011), and EBMR in November 2011.

Selection criteria
Randomised controlled trials reporting symptomatic outcome after short-term treatment for GORD using proton pump inhibitors, H2-receptor antagonists or prokinetic agents. Participants had to be either from an empirical treatment group (no endoscopy used in treatment allocation) or from an endoscopy negative reflux disease group (no signs of erosive oesophagitis).

Data collection and analysis
Two authors independently assessed trial quality and extracted data.

Main results
Thirty-four trials (1314 participants) were included: fifteen in the empirical treatment group, fifteen in the ENRD group and four in both. In empirical treatment of GORD the risk ratio (RR) for heartburn remission (the primary efficacy variable) in placebo-controlled trials for PPI was 0.37 (two trials, 95% confidence interval (CI) 0.32 to 0.44), for H2RAs 0.77 (two trials, 95% CI 0.60 to 0.99) and for prokinetics 0.86 (one trial, 95% CI 0.73 to 1.01). In a direct comparison PPIs were more effective than H2RAs (seven trials, RR 0.66, 95% CI 0.60 to 0.73) and prokinetics (two trials, RR 0.53, 95% CI 0.32 to 0.87).

In treatment of ENRD, the RR for heartburn remission for PPI versus placebo was 0.71 (ten trials, 95% CI 0.65 to 0.78) and for H2RA versus placebo was 0.84 (two trials, 95% CI 0.74 to 0.95). The RR for PPI versus H2RA was 0.78 (three trials, 95% CI 0.62 to 0.97) and for PPI versus prokinetic 0.72 (one trial, 95% CI 0.56 to 0.92).

Authors' conclusions
PPIs are more effective than H2RAs in relieving heartburn in patients with GORD who are treated empirically and in those with ENRD, although the magnitude of benefit is greater for those treated empirically.

Short‐term treatment with proton pump inhibitors, H2‐receptor antagonists and prokinetics for gastro‐oesophageal reflux disease‐like symptoms and endoscopy negative reflux disease

Plummer-Vinson syndrome is characterized by dysphagia, iron-deficiency anemia, and esophageal webs. The webs are best diagnosed by cineradiography. Iron repletion often improves the dysphagia, although some patients require esophageal dilatation or bougienage. The syndrome is associated with an increased incidence of postcricoid carcinoma, and surveillance endoscopy is recommended. (Arch Intern Med. 1995;155:2008-2011) The Plummer-Vinson syndrome has be¬ come increasingly rare with the availabil¬ ity of iron supplements, but nonetheless it should be suspected in the setting of dysphagia and iron deficiency. The follow¬ ing case illustrates the clinical, radiographic, and endoscopie presentation of this syndrome.

A case report and literature review

The Plummer-Vinson syndrome is characterized by dysphagia, iron-deficiency anemia, and esophageal webs. The webs are best diagnosed by cineradiography. Iron repletion often improves the dysphagia, although some patients require esophageal dilatation or bougienage. The syndrome is associated with an increased incidence of postcricoid carcinoma, and surveillance endoscopy is recommended.

Plummer-Vinson Syndrome: A Case Report and Literature Review

Background: Many otherwise healthy individuals with episodic heartburn self-medicate with overthe-counter antacids. We evaluated clinical characteristics of subjects who had never been medically diagnosed as having any upper gastrointestinal tract disorder and who used antacids for symptomatic relief of heartburn. Subjects and Methods: Subjects with at least 3 months of frequent heartburn relieved by antacids, and with heartburn on at least 4 of 7 days during the week prior to study entry, had their medical history and gastrointestinal pathological characteristics recorded. Tests included esophagogastroduodenoscopy, esophageal motility and sensitivity studies, and 24-hour pH monitoring. Results: Of 178 subjects screened, 13 were excluded on the basis of other gastrointestinal diseases at baseline, including diffuse esophageal spasm, peptic ulcer disease, dysplastic columnar metaplasia of the esophagus (Barrett’s esophagus), and adenocarcinoma. Ten subjects were ineligible because of insufficient baseline heartburn. The remaining 155 eligible subjects had heartburn for an average of 11 years. Forty-seven percent had daily symptoms and 70% described heartburn severity as moderate, even though on endoscopy most (53%) had normal-appearing esophageal mucosa (grade 0 or 1). Esophageal acid sensitivity was present in 86% of subjects. Mean lower esophageal sphincter pressures and esophageal contractile amplitudes were at the lower limits of normal and total esophageal acid contact time was slightly increased. Conclusions: Chronic heartburn can reflect a wide range of diagnostic findings, including important underlying pathological features, and may warrant a full medical examination to detect such abnormal conditions and to permit selection of appropriate therapy. Arch Intern Med. 1998;158:2373-2376

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/210441/ioi71161.pdf

Philip E. Jaffe

Papers

A case report and literature review

Plummer-Vinson Syndrome: A Case Report and Literature Review

Heartburn requiring frequent antacid use may indicate significant illness.