Dyspepsia is a common term used for a heterogeneous group of abdominal symptoms. Functional dyspepsia (FD) is the focus of this review. The 2006 Rome III criteria defined FD and its subgroups, postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). FD is a very common condition with a high prevalence throughout the world, adversely affecting the quality of life of patients. The pathophysiology of FD has been under investigation during the past two decades. Multiple mechanisms such as abnormal gastric emptying, visceral hypersensitivity, impaired gastric accommodation, and central nervous system factors are likely involved. Several tests are available for the assessment of various physiologic functions possibly involved in the pathogenesis of FD, and some of these could be used in clinical practice, helping to understand the abnormalities underlining patients' complaints. Currently, the possibilities of pharmacological therapy for FD are still limited, however, experience of using prokinetics, tricyclic antidepressants, selective serotonin-reuptake inhibitors (SSRIs), proton-pump inhibitors (PPIs), and several alternative techniques has been accumulated. The different combinations of alterations in physiologic gastrointestinal and central nervous system functions result in the very heterogeneous nature of FD so combined approaches to these patients could be beneficial in challenging cases.

Abstract:The wireless motility capsule (WMC) is an ambulatory noninvasive and nonradioactive diagnostic sensor that continuously samples intraluminal pH, temperature, and pressure as it moves through the gastrointestinal (GI) tract. This review summarizes the data obtained in clinical trials with the WMC and discusses its role in clinical practice. The United States Food and Drug Administration has approved the SmartPill GI monitoring system for the evaluation of gastric emptying time in patients with suspected gastroparesis, the evaluation of colonic transit time in patients with suspected chronic constipation, and for the characterization of pressure profiles from the antrum and duodenum. Clinical studies have shown that WMC-measured GI transit times can distinguish patients with motility abnormalities similarly to conventional testing. However, the WMC offers the advantage of providing a full GI-tract profile, enabling the detection of multiregional GI transit abnormalities in patients with suspected upper or lower GI dysmotility. The WMC also characterizes pressure profiles of the GI tract and impaired pressure profile limits are reported for the antrum and duodenum. In comparison with manometry, interpretations of pressure measurements obtained by the WMC are limited by an inability to detect a peristaltic pressure wave front, and further investigation is required to develop clinical applications. Clinical studies with the WMC indicated that it should be considered for the evaluation of regional and whole gut transit time in patients with suspected upper or lower dysmotility, particularly if there are concerns about multiregional dysmotility.

Background Data for Israel from the Rome Foundation Global Epidemiology Study on the disorders of gut‐brain interaction (DGBI) were used to assess the national prevalence of all 22 DGBI, the percentage of respondents meeting diagnostic criteria for at least one DGBI, and the impact on burden of disease in Israel. Methods The survey was conducted through the Internet with multiple built‐in quality‐assurance techniques and included the Rome IV diagnostic questionnaire and an in‐depth supplemental questionnaire. Key Results 2012 Israeli participants completed the survey nationwide: mean age 44.6 ± 16.4 years, 50% females. The national distribution was very close to the latest Israeli census. 36.4% (95% CI 34.3, 38.4) met diagnostic criteria for at least one DGBI, with 4.4% for any esophageal disorder, 6.5% for any gastroduodenal disorder, 30.8% for any bowel disorder, and 5.3% for any anorectal disorder. The rates were higher for women. Having any DGBI was associated negatively with psychosocial variables (including quality of life, somatization, and concern about digestive problems), and healthcare utilization (including doctor visits, use of medications, and abdominal surgeries). Conclusions & Inferences The results of this study provide the first in‐depth assessment of the prevalence and burden of Rome IV DGBI in Israel and facilitate comparisons with other countries. As 36.4% of the 2,012 participants met diagnostic criteria for at least one DGBI, and 23.5% of those met criteria for more than one DGBI, the burden of DGBI in Israel is high, indicating a need to focus on research and training for patient care.

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Enzymatic activity responsible for the cleavage of heparan sulfate, commonly known as heparanase, is abundant in tumor-derived cells. Heparanase cleaves heparan sulfate side chains, presumably at sites of low sulfation, thus facilitating structural alterations of the extracellular matrix and basement membrane underlying epithelial and endothelial cells. Traditionally, heparanase activity was correlated with the metastatic potential of tumor-derived cells, attributed to enhanced cell dissemination as a consequence of heparan sulfate cleavage and remodeling of the extracellular matrix barrier. More recently, heparanase upregulation was documented in an increasing number of human carcinomas and hematological malignancies, correlating with increased tumor metastasis, vascular density, and shorter post-operative survival of cancer patients. Although heparanase upregulation and its pro-malignant features are well documented, the instance of its induction in the course of tumor development was less investigated. Here, we used immunohistochemical analysis to investigate heparanase expression in normal esophagus, Barrett's esophagus without dysplasia, Barrett's esophagus with low-grade dysplasia, Barrett's esophagus with high-grade dysplasia, and adenocarcinoma of the esophagus. We report that heparanase expression is already induced in Barrett's epithelium without dysplasia, and is further increased during progression through distinct pathological stages, namely, low-grade dysplasia, highgrade dysplasia, and adenocarcinoma. Notably, heparanase induction correlated with increased cell proliferation index revealed by Ki-67 staining. These findings suggest that heparanase function is not limited to the process of tumor metastasis, but rather is engaged at the early stages of esophagus carcinoma initiation and progression. Modern Pathology ( Keywords: heparanase; Barrett's epithelium; esophageal; adenocarcinoma; staining; localization Heparanase is an endo-b-D-glucuronidase, the predominant enzyme that degrades heparan sulfate side chains of heparan sulfate proteoglycans. 1,2 These complex macromolecules are highly abundant in the extracellular matrix and are thought to have an important structural role, contributing to extracellular matrix integrity and insolubility. 3,4 Traditionally, heparanase activity was correlated with the metastatic potential of tumor-derived cells, attributed to enhanced cell dissemination as a consequence of heparan sulfate cleavage and remodeling of the extracellular matrix barrier. 1,2 A proof-of-concept to this notion has been established by using specific anti-heparanase ribozyme and siRNA methodologies, clearly implicating heparanase-mediated heparan sulfate cleavage as a critical requisite for metastatic spread. 5 Similarly, heparanase activity was implicated in cell dissemination associated with inflammation and angiogenesis. 5,6 More recently, heparanase upregulation was documented in an increasing number of human carcinomas and hematological malignancies. 7,8 In many cases, heparanase ind...