Esophageal and gastric cancers represent tumors with poor prognosis. Unfortunately, radiotherapy, chemotherapy, and targeted therapy have made only limited progress in recent years in improving the generally disappointing outcome. Immunotherapy with checkpoint inhibitors is a novel treatment approach that quickly entered clinical practice in malignant melanoma and renal cell cancer, but the role in esophageal and gastric cancer is still poorly defined. The principal prognostic/predictive biomarkers for immunotherapy efficacy currently considered are PD-L1 expression along with defects in mismatch repair genes resulting in microsatellite instability (MSI-H) phenotype. The new molecular classification of gastric cancer also takes these factors into consideration. Available reports regarding PD-1, PD-L1, PD-L2 expression and MSI status in gastric and esophageal cancer are reviewed to summarize the clinical prognostic and predictive role together with potential clinical implications. The most important recently published clinical trials evaluating checkpoint inhibitor efficacy in these tumors are also summarized.
The prognosis of esophageal cancer (EC) is poor, despite considerable effort of both experimental scientists and clinicians. The tri-modality treatment consisting of neoadjuvant chemoradiation followed by surgery has remained the gold standard over decades, unfortunately, without significant progress in recent years. Suitable prognostic factors indicating which patients will benefit from this tri-modality treatment are missing. Some patients rapidly progress on the neoadjuvant chemoradiotherapy, which is thus useless and sometimes even harmful. At the same time, other patients achieve complete remission on neoadjuvant chemoradiotherapy and subsequent surgery may increase their risk of morbidity and mortality. The prognosis of patients ranges from excellent to extremely poor. Considering these differences, the role of drug metabolizing enzymes and transporters, among other factors, in the EC response to chemotherapy may be more important compared, for example, with pancreatic cancer where all patients progress on chemotherapy regardless of the treatment or disease stage. This review surveys published literature describing the potential role of ATP-binding cassette transporters, the genetic polymorphisms, epigenetic regulations, and phenotypic changes in the prognosis and therapy of EC. The review provides knowledge base for further research of potential predictive biomarkers that will allow the stratification of patients into defined groups for optimal therapeutic outcome.
Metastases of esophageal carcinoma to the skeletal muscle are rare, but the incidence may be increasing because of better diagnosis resulting from widespread use of positron emission tomography/computed tomography (PET/CT). A cohort of 205 patients with esophageal carcinoma treated at our center who had PET/CT between 2006 and 2010 was retrospectively evaluated for the presence of skeletal muscle metastases. Four patients had skeletal muscle metastases of esophageal carcinoma, including two patients with squamous cell carcinoma. In another patient with squamous cell carcinoma of the esophagus and synchronous skeletal muscle metastases, muscle metastases were subsequently shown to be related to second primary pancreatic adenocarcinoma. In all cases, skeletal muscle metastases were the first manifestation of systemic disease. In three patients palliation was obtained with the combination of external beam radiation therapy, systemic chemotherapy or surgical resection. Skeletal muscle metastases are a rare complication of esophageal carcinoma.
The use of biodegradable covered stents for the treatment of anastomotic leaks or esophageal perforations is technically feasible and safe. The initial results are promising; however, larger number of patients will be required to evaluate the capability of these biodegradable stents in the future. The use of biodegradable material for coverage of the stent is essential.
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