Challenges to Unravel Mechanisms of GERD

Gastroesophageal reflux disease (GERD) encompasses a spectrum of disorders caused by a reflux of gastric contents into the esophagus or complications of gastroesophageal reflux. Although depending on the definition, the prevalence of GERD is higher in the West than in the East, and the prevalence has been slightly increasing, so that the clinicians, even though they are not gastroenterologists, must encounter GERD patients and treat them. However, the clinicians do feel difficulty in treating GERD patients, since prescription of acid neutralizing agents, such as proton pump inhibitors (PPIs), sometimes fail to resolve their complaints. This may be partly explained by the discrepancies between clinical complaint and endoscopic findings; some patients present endoscopic esophagitis while some do not, and be partly explained by the potentially wide spectrum of pathophysiological etiologies than has been thought. This chapter describes current knowledge on heterogeneous mechanisms of GERD development. Clarifying the mechanisms of GERD on the individual basis may realize conceptual shift from uniform prescription of acid neutralizing agents to establishment of patient-oriented therapies

Molecular Targeting Therapy for Gastric Cancer: Current Advances and Obstacles

Although the incidence of gastric cancer (GC) has declined steadily in recent years, GC remains a major cancer burden. Multimodal therapies have been developed and first-line chemotherapy for advanced GC patients, even they have good performance status, could provide only modest efficacy. Furthermore, treatment outcomes after failure of first-line chemotherapy remain poor. In order to provide a solution to this unmet clinical need, since the management of various types of cancer has progressed rapidly into the molecular era, biomarker-targeted therapy for GC has received enormous attention in recent years. This review focuses on the current treatment achievement of molecular targeting agents for GC, such as trastuzumab, pertuzumab, trastuzumab emtansine, lapatinib, cetuximab, panitumumab, nimotuzumab, mammalian target of rapamycin, bevacizumab, ramucirumab, sunitinib, sorafenib, apatinib, rilotumumab, and onartuzumab. However, problems are also emerged with regard to resistance and refractoriness. This chapter also focuses on the current obstacles concerning resistance and refractoriness, as well as provides discussions concerning future directions with regard to molecular categorization to predict response and toxicities leading to select patients most likely to benefit

Tortuosity of the brachiocephalic artery complicated with arterial injury after tracheotomy: a case report

Tracheotomy is an operation of the airway performed even on critical care patients. Surgical complications of tracheotomies are fatal. In this study, tortuosity of the brachiocephalic artery complicated with arterial injury was observed in a patient after tracheotomy. A 95-year-old woman in coma was admitted to our medical center. The patient needed airway management, and tracheal intubation was performed. The cause of the coma was extensive cerebral infarction of the right middle cerebral artery. It was expected that the coma would be prolonged, and a tracheotomy was performed after 7 days. Tortuosity of the brachiocephalic artery was confirmed with cervical computed tomography before surgery. The patient bled through the tracheostomy after 30 days. To arrest bleeding from the right common carotid artery, a vascular repair surgery was performed. There was no recurrent bleeding after surgery. After 37 days, the patient died of deteriorating primary disease. Although tracheotomy is a common operation, attention should be paid to abnormalities of blood vessels including tortuosity of the brachiocephalic artery

Pharmacogenetics of irinotecan: An ethnicity-based prediction of irinotecan adverse events

Irinotecan is now regarded as the most active drug for the treatment of colorectal cancer. However, one of the most difficult issues oncologists face is deciding the optimal dose for an individual patient, as each individual shows different outcomes even at the same dose with regard to treatment related adverse events, ranging from no toxicity to a lethal event. Inherited genetic polymorphism of a single gene or multiple genes (haplotype or linkage disequilibrium) involved in SN-38 glucuronidation, a predominant route of irinotecan detoxification, is now recognized as a significant factor that can alter the incidence of side effects. Attempts to explore such inherited genetic variability have been focused on elucidating interindividual as well as interethnic differences. Genotyping studies in relation to adverse events in an individual or in a group of similar ethnicity should contribute to establishing individual-oriented or ethnicity-oriented irinotecan treatment regimens. This review highlights current single- or multi-tired approaches for the elucidation of genetic predispositions of patients to severe toxicities, especially among Asians. The purpose of this is to contribute to minimizing toxicity by dose modifications, with the consequent aim of maximizing dose intensity and efficacy, an ultimate goal of irinotecan-individualized therapy

Successful type-oriented endoscopic resection for gastric carcinoid tumors: A case report

The standard treatment in Japan for gastric carcinoid has been gastrectomy with lymphadenectomy. This report describes the possibility of endoscopic treatment as an appropriate option for gastric carcinoid fulfilling certain conditions. A 46 year old woman underwent endoscopic mucosal resection for two 3 mm gastric carcinoids. The patient had hypergastrinemia with pernicious anemia and type A chronic atrophic gastritis, suggesting that the tumors were type I in Rindi's classification. Both tumors were located in the mucosal layer with no cellular polymorphism and were chromogranin A positive. Neither tumor recurrence in the stomach nor distant metastases have been documented during the 5 years of follow-up. Although many type I gastric carcinoids may be clinically indolent, reports on successful endoscopic treatment for this carcinoid have been scanty in the literature in Japan, presumably because of the hitherto surgical treatment stance for the disease. This report discusses how the size, number, depth and histological grading of the type I gastric carcinoid could allow the correct identification of a benign or malignant propensity of an individual tumor and how endoscopic resection could be a treatment of choice when these factors render it feasible. This stance could also obviate unnecessary surgical resection for more benign tumors

A substantial incidence of silent short segment endoscopically suspected esophageal metaplasia in an adult Japanese primary care practice

AIM: To determine the incidence and characteristics of endoscopically suspected esophageal metaplasia (ESEM) in a primary adult care institution