Current state of prognostication, therapy and prospective innovations for Barrett’s-related esophageal adenocarcinoma: a literature review

Abstract

Objective: Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC), which has one of the lowest 5-year survival rates in oncology. The reasons for poor survival are twofold: the large majority of diagnoses are in advanced stages (~80%) and limited treatment options, with a deficit of biology-guided therapies. As a rapidly growing public health concern with poor prognosis, research into the molecular progression for BE and novel therapeutics for EAC currently has high clinical utility. Review of the literature reveals that innovative analysis of metaplastic progression from BE to EAC at a molecular level can shed light on the underlying transformative probabilities of BE into malignant pathologies and may impact current of future therapeutic modalities for management of these diseases.Background: EAC is the fastest increasing cancer in the United States with a 600% increase over the past 25 years. This cancer arises from dysplastic tissue of BE, a complication of gastroesophageal reflux disease (GERD). Chronic acid and bile reflux in the distal esophagus initiates a metaplastic conversion of normal squamous epithelium to premalignant intestinalized columnar epithelium. Patients with BE have a 125-fold higher risk of cancer compared to the general population.Methods: We critically reviewed the current status of BE monitoring, and subsequent therapeutic strategies being used in patients who have progressed to cancer. Also, new diagnostic tools and therapeutic candidates for BE-related EAC are discussed. Highly-targeted searches of databases containing recent original peerreviewed papers were utilized for this review.Conclusions: Novel and well-described biomarkers analyzed in the patient's diseased tissue will provide for more powerful diagnostics, but also possess the potential to develop strategies for personalized management and identify targets for intervention to either cease disease progression or treat BE and/or EAC. Since millions of Americans develop BE without progressing to cancer, there is a critical need to identify the small percentage of Barrett's patients who possess hallmarks of disease progression or carcinogenesis with novel screening techniques. Incorporation of such tools into standard screening protocols for BE surveillance and/or therapy would be critical to detect malignant transformations before clinically obvious cancer ever develops.Mittal et al. Barrett's-related EAC management

Variation in Fatty Acid Synthase, Ki67 and p53 Esophageal Mucosa Expressions in Barrett’s Esophagus Patients Treated for One Year with Two Esomeprazole Different Regimens

“…Although esophageal intestinal metaplasia and adenocarcinoma are strictly associated, the overall risk of cancer in BE patients is estimated to be approximately 0.5% per year, and the risk of neoplasia including HGD to be 1.3% per year [ 49 , 50 , 51 ]. The aim of this study was to evaluate if, after one year of treatment, continuous or discontinuous administration of Esomeprazole 40 mg/day affected the expression of proliferation and metabolic cellular markers activities in comparison to the initial expression, in two groups of BE patients.…”

Biomarkers for Early Detection, Prognosis, and Therapeutics of Esophageal Cancers

“…Notably, overexpressed DAD1 protein levels contribute to cisplatin resistance, which is striking since 95% of EC patients treated after esophagectomy were placed on cisplatin by their community oncologist in the first-line setting [ 93 ]. S100P expression has been found to increase resistance to 5-FU in colorectal cancer [ 94 ], and 5-FU was prescribed to >70% of EC patients, so if there is innate resistance to the two most prescribed drugs for esophageal cancer then alternative patient management strategies are needed [ 95 ].…”

Students and physicians differ in perception of quality of life in patients with tumors of the upper gastrointestinal tract

“…Historically, tumors of the upper gastrointestinal (GI) tract ensue heavy reduction of HRQoL due to the tumor itself, the restricted food intake and the aggressive therapeutic approach 1 , 2 . Recently, developments in the therapeutic approach including neoadjuvant chemotherapy have led to improved long-term survival 3 – 7 . Consequently, attention has been directed on patients’ HRQoL during and after therapy, as HRQoL is known to decrease significantly after surgery 8 , 9 .…”