Claudia Coppo

Epidemiology and natural history of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is highly prevalent in Western countries, particularly when considering its most classic symptom that is heartburn. This symptom is very frequent in the community and ranges from 10% to more than 30%, according to the various population-based studies. This disease is much more represented in Europe and USA than in Asiatic countries. It has been shown that GERD prevalence increases in parallel with the remarkable growth of obesity, as this condition is able to favor all the pathogenetic mechanisms leading to it. Current information regarding the phenotypic presentation of GERD shows that there are two main phenotypic manifestations, that are erosive reflux disease (ERD) and non-erosive reflux disease (NERD) and the latter includes the majority of patients (up to 70%). The major complication of GERD is the development of Barrett esophagus, a pre-malignant lesion potentially leading to esophageal adenocarcinoma. Data from medical literature on the natural history of this disease are scant and mainly retrospective, so the interpretation of them is very difficult. However, they seem to suggest that both NERD and mild esophagitis tend to remain as such overtime and the progression from NERD to ERD, from mild to severe ERD and from ERD to Barretts esophagus may occur only in a small number of cases, ranging from 0% to 30%, 10-22% and 1-13%, respectively. Future studies should help us in elucidating better the real transition from one category to another and to do this, we have to exclude from the world of GERD all the functional conditions that nowadays can be easily recognized by means of impedance-pH monitoring.

Proton pump inhibitors: use and misuse in the clinical setting

ABSTRACT Introduction: The introduction of proton pump inhibitors (PPIs) into clinical practice has greatly improved our therapeutic approach to acid-related diseases for their efficacy and safety. Areas Covered: The following evidence-based indications for PPI use are acknowledged by many scientific societies: treatment of the various forms and complications of gastroesophageal reflux disease, eradication of H. pylori infection in combination with two or more antibiotics, short- and long-term therapy of H. pylori-negative peptic ulcers, healing, and prevention of NSAID/COXIB-associated gastric ulcers, co-therapy with endoscopic procedures to control upper digestive bleeding and medical treatment of Zollinger Ellison syndrome. Expert Commentary: Despite the above well-defined indications, however, the use of PPIs continues to grow every year in both western and eastern countries and the endless expansion of the PPI market has created important problems for many regulatory authorities for two relevant features: the progressive increase of the costs of therapy and the greater potential harms for the patients. The major reasons for the misuse of PPIs are the prevention of gastro-duodenal ulcers in patients without risk factors and the stress ulcer prophylaxis in non-intensive care units, steroid therapy alone, anti-platelet or anti-coagulant treatment in patients without risk of gastric injury and the overtreatment of functional dyspepsia.

Complexity and diversity of gastroesophageal reflux disease phenotypes

Gastroesophageal reflux disease (GERD) is defined as a condition which develops when the reflux of gastric contents causes troublesome symptoms, impairs quality of life, or leads to mucosal damage or complications. There are two main phenotypic presentations of GERD, the erosive (ERD) and non-erosive reflux disease (NERD), with the latter one representing up to 70% of GERD spectrum. Moreover, patients with GERD can be clinically subdivided into two distinct syndromes: patients with esophageal and extraesophageal symptoms. The diagnosis of NERD should be supported by the evidence that symptoms are due to reflux episodes on the basis of an excess of acid into the esophagus or a positive correlation between symptoms and acid and/or weakly acidic reflux episodes as evidenced by 24-hour impedance-pH monitoring. Patients with normal esophageal acid exposure and no correlation between heartburn and any kind of chemical reflux are considered affected by functional heartburn and do not pertain to the realm of NERD. They do not usually respond to PPI therapy as further empirical criterion and are included in the large group of functional digestive disorders with the expression of altered generation or perception of symptoms at the esophageal level and can often overlap with functional dyspepsia and irritable bowel syndrome.

Drugs for improving esophageal mucosa defense: where are we now and where are we going?

In the past, the attention of physiologists and doctors has been mainly focused on the key role of acid in the pathogenesis of gastroesophageal reflux disease (GERD), but increasing evidence that 20-40% of reflux patients respond not at all or only partially to proton pump inhibitors (PPIs) has underlined the concept that factors other than acid are implicated in its development and the elicitation of symptoms. Among these, impaired mucosal integrity, particularly in most patients with non-erosive reflux disease, has recently been reincluded and the reinforcement of defensive mechanisms and/or its protection has been reappointed as a renewed therapeutic target for the management of GERD patients. In this review we will summarize the existing knowledge of the old and novel compounds able to produce this therapeutic effect, including sucralfate, alginate-based drugs, and a new medical device consisting of hyaluronic acid and chondroitin sulfate dispersed in a bioadhesive carrier, together with the potential indications for their use. It is to be stressed, however, that, although these compounds may represent a real alternative to PPI therapy in GERD, the combination of mucosal protection with acid suppression may help manage many cases with a partial or unsatisfactory response to PPIs alone.

Hepatobiliary and Pancreatic: A rare cause of portal hypertension

A 64-year-old gentleman presented with hematemesis and melena. Laboratory tests showed a hemoglobin level of 3 g/dL, normal white blood cells count (9 × 10/L), normal platelet count (386 × 10/L), elevated lactate dehydrogenase levels (308 IU/L, normal values <225 IU/L) and normal liver enzymes. The patient has no known co-morbidity and was no on any regular medication, including herbal medication. Physical examination revealed a large palpable mass in the left hemi-abdomen, without stigmata of chronic liver disease. The patient was transfused and, once hemodinamically stable, underwent upper digestive endoscopy, which found non-bleeding, medium-sized varices (Fig. 1a) and large gastric varices fund (Fig. 1b), abdominal computed tomography scan showed a homogeneous, mildly enlarged liver, and a massive (maximum longitudinal diameter, 21 cm) (Fig. 1c). There was no ascites or lymphoadenomegaly. Complete work-up for common and rare causes of chronic liver disease and portal hypertension were negative. Liver transient elastography result was 19.1KPa. Because of the presence of elevated platelet count despite the presence of a massively enlarged spleen, bone marrow biopsy and assessment of Janus Kinase (JAK) 2 gene mutation were performed, which showed the presence of V617F JAK2 mutation and bone marrow histology diagnostic of primary myelofibrosis (Fig. 2a,b). A transjugular intra-hepatic portosystemic shunt was placed to reduce the patient’s risk of re-bleeding. During angiography, a transjugular liver biopsy was performed, and showed the presence t

A rare cause of portal hypertension

A 64-year-old gentleman presented with hematemesis and melena. Laboratory tests showed a hemoglobin level of 3 g/dL, normal white blood cells count (9 × 10/L), normal platelet count (386 × 10/L), elevated lactate dehydrogenase levels (308 IU/L, normal values <225 IU/L) and normal liver enzymes. The patient has no known co-morbidity and was no on any regular medication, including herbal medication. Physical examination revealed a large palpable mass in the left hemi-abdomen, without stigmata of chronic liver disease. The patient was transfused and, once hemodinamically stable, underwent upper digestive endoscopy, which found non-bleeding, medium-sized varices (Fig. 1a) and large gastric varices fund (Fig. 1b), abdominal computed tomography scan showed a homogeneous, mildly enlarged liver, and a massive (maximum longitudinal diameter, 21 cm) (Fig. 1c). There was no ascites or lymphoadenomegaly. Complete work-up for common and rare causes of chronic liver disease and portal hypertension were negative. Liver transient elastography result was 19.1KPa. Because of the presence of elevated platelet count despite the presence of a massively enlarged spleen, bone marrow biopsy and assessment of Janus Kinase (JAK) 2 gene mutation were performed, which showed the presence of V617F JAK2 mutation and bone marrow histology diagnostic of primary myelofibrosis (Fig. 2a,b). A transjugular intra-hepatic portosystemic shunt was placed to reduce the patient’s risk of re-bleeding. During angiography, a transjugular liver biopsy was performed, and showed the presence t