Personalized targeted therapy for esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma continues to heavily burden clinicians worldwide. Researchers have discovered the genomic landscape of esophageal squamous cell carcinoma, which holds promise for an era of personalized oncology care. One of the most pressing problems facing this issue is to improve the understanding of the newly available genomic data, and identify the driver-gene mutations, pathways, and networks. The emergence of a legion of novel targeted agents has generated much hope and hype regarding more potent treatment regimens, but the accuracy of drug selection is still arguable. Other problems, such as cancer heterogeneity, drug resistance, exceptional responders, and side effects, have to be surmounted. Evolving topics in personalized oncology, such as interpretation of genomics data, issues in targeted therapy, research approaches for targeted therapy, and future perspectives, will be discussed in this editorial.

Gastroesophageal reflux disease and morbid obesity: To sleeve or not to sleeve?

Laparoscopic sleeve gastrectomy(LSG) has reached wide popularity during the last 15 years, due to the limited morbidity and mortality rates, and the very good weight loss results and effects on comorbid conditions. However, there are concerns regarding the effects of LSG on gastroesophageal reflux disease(GERD). The interpretation of the current evidence is challenged by the fact that the LSG technique is not standardized, and most studies investigate the presence of GERD by assessing symptoms and the use of acid reducing medications only. A few studies objectively investigated gastroesophageal function and the reflux profile by esophageal manometry and 24-h p H monitoring, reporting postoperative normalization of esophageal acid exposure in up to 85% of patients with preoperative GERD, and occurrence of de novo GERD in about 5% of cases. There is increasing evidence showing the key role of the surgical technique on the incidence of postoperative GERD. Main technical issues are a relative narrowing of the mid portion of the gastric sleeve, a redundant upper part of the sleeve(both depending on the angle under which the sleeve is stapled), and the presence of a hiatal hernia. Concomitant hiatal hernia repair is recommended. To date, either medical therapy with proton pump inhibitors or conversion of LSG to laparoscopic Rouxen-Y gastric bypass are the available options for the management of GERD after LSG. Recently, new minimally invasive approaches have been proposed in patients with GERD and hypotensive LES: the LINX? Reflux Management System procedure and the Stretta? procedure. Large studies are needed to assess the safety and long-term efficacy of these new approaches. In conclusion, the recent publication of p H monitoring data and the new insights in the association between sleeve morphology and GERD control have led to a wider acceptance of LSG as bariatric procedure also in obese patients with GERD, as recently stated in the 5^(th) International Consensus Conference on sleeve gastrectomy.

Development and validation of a registry-based definition of eosinophilic esophagitis in Denmark

AIM:To develop and validate a case definition of eosinophilic esophagitis(EoE) in the linked Danish health registries.METHODS:For case definition development,we queried the Danish medical registries from 2006-2007 to identify candidate cases of EoE in Northern Denmark.All International Classification of Diseases-10(ICD-10) and prescription codes were obtained,and archived pathology slides were obtained and re-reviewed to determine case status.We used an iterative process to select inclusion/exclusion codes,refine the case definition,and optimize sensitivity and specificity.We then re-queried the registries from 2008-2009 to yield a validation set.The case definition algorithm was applied,and sensitivity and specificity were calculated.RESULTS:Of the 51 and 49 candidate cases identified in both the development and validation sets,21 and 24 had EoE,respectively.Characteristics of EoE cases in the development set [mean age 35 years;76% male;86% dysphagia;103 eosinophils per high-power field(eos/hpf)] were similar to those in the validation set(mean age 42 years;83% male;67% dysphagia;77 eos/hpf).Re-review of archived slides confirmed that the pathology coding for esophageal eosinophilia was correct in greater than 90% of cases.Two registrybased case algorithms based on pathology,ICD-10,and pharmacy codes were successfully generated in the development set,one that was sensitive(90%) and one that was specific(97%).When these algorithms were applied to the validation set,they remained sensitive(88%) and specific(96%).CONCLUSION:Two registry-based definitions,one highly sensitive and one highly specific,were developed and validated for the linked Danish national health databases,making future population-based studies feasible.