Nonoperative management of gastrointestinal malignancies in era of neoadjuvant treatment

Cancers derived from the gastrointestinal(GI)tract are often treated with radical surgery to achieve a cure.However,recent advances in the management of GI cancers involve the use of a combination of neoadjuvant radiation and chemotherapy followed by surgical intervention to achieve improved local control and cure.Interestingly,a small proportion of patients with highly sensitive tumors achieved a pathological complete response(pCR)(no residual tumor cells in the resected specimen)to neoadjuvant chemoradiation therapy(nCRT).The desire for organ preservation and avoidance of surgical morbidity brings the idea of a nonoperative management(NOM)strategy.Because of the different nature of tumor biology,GI cancers present diverse responses to nCRT,ranging from high sensitivity(anal cancer)to low sensitivity(gastric/esophageal cancer).There is an increasing attention to NOM of localized GI cancers;however,without the use of biomarkers/imaging parameters to select such patients,NOM will remain a challenge.Therefore,this review intends to summarize some of the recent updates from the aspect of current nCRT regimens,criteria for patient selection and active surveillance schedules.We also hope to review significant sequelae of radical surgery and the complications of nCRT to clarify the directions for optimization of nCRT and NOM for oncologic outcomes and quality of life.

Is endoscopic ultrasound examination necessary in the management of esophageal cancer?

Despite substantial efforts at early diagnosis, accurate staging and advanced treatments, esophageal cancer(EC) continues to be an ominous disease worldwide. Risk factors for esophageal carcinomas include obesity, gastroesophageal reflux disease, hard-alcohol use and tobacco smoking. Five-year survival rates have improved from 5% to 20% since the 1970 s, the result of advances in diagnostic staging and treatment. As the most sensitive test for locoregional staging of EC, endoscopic ultrasound(EUS) influences the development of an optimal oncologic treatment plan for a significant minority of patients with early cancers, which appropriately balances the risks and benefits of surgery, chemotherapy and radiation. EUS is costly, and may not be available at all centers. Thus, the yield of EUS needs to be thoughtfully considered for each patient. Localized intramucosal cancers occasionally require endoscopic resection(ER) for histologic staging or treatment; EUS evaluation may detect suspicious lymph nodes prior to exposing the patient to the risks of ER. Although positron emission tomography(PET) has been increasingly utilized in staging EC, it may be unnecessary for clinical staging of early, localized EC and carries the risk of false-positive metastasis(over staging). In EC patients with evidence of advanced disease, EUS or PET may be used to define the radiotherapy field. Multimodality staging with EUS, crosssectional imaging and histopathologic analysis of ER, remains the standard-of-care in the evaluation of early esophageal cancers. Herein, published data regarding use of EUS for intramucosal, local, regional and metastatic esophageal cancers are reviewed. An algorithm to illustrate the current use of EUS at The University of Texas MD Anderson Cancer Center is presented.

Medical management of gastric cancer:A 2014 update

Gastric cancer represents a serious health problem on a global scale. It is the second leading cause of cancer-related death worldwide. Novel therapeutic targets are desperately needed because the meager improvement in the cure rate of about 10% realized by adjunctive treatments to surgery is unacceptable as > 50% patients with localized gastric cancer succumb to their disease. Either postoperative chemoradiotherapy(United States),pre-and post-operative chemotherapy(Europe),and adjuvant chemotherapy after a D2 resection(Asia) can all be regarded as standards of care in the localized gastric cancer management. In metastatic disease the addition of trastuzumab to chemotherapy is standard of care in Her2 positive disease. In the HER2 negative population,the treatments remain limited.In the first line setting,the standard of care is a combination of fluoropyrimidine and platinum containing chemotherapy,with or without epirubicin or docetaxel.The results of targeted therapy trials have by and large been disappointing,but none of these trials looked at an appropriately enriched population.Finally there is a meager overall survival benefit in treating patients with metastatic disease in the second line setting,with either irinotecan,docetaxel or ramucirumab however none of these drugs have been compared head to head in a well-powered randomized controlled trial.

Endoscopic management of esophageal cancer

Esophageal cancer(EC)generally consists of squamous cell carcinoma(which arise from squamous epithelium)and adenocarcinoma(which arise from columnar epithelium).Due to the increased recognition of risk factors associated with EC and the development of screening programs,there has been an increase in the diagnosis of early EC.Early EC is amenable to curative therapy by endoscopy,which can be performed by either endoscopic resection or endoscopic ablation.Endoscopic resection consists of either endoscopic mucosal resection(preferred in cases of adenocarcinoma)or endoscopic submucosal dissection(preferred in cases of squamous cell carcinoma).Endoscopic ablation can be performed by either radiofrequency ablation,cryotherapy,argon plasma coagulation or photodynamic therapy,amongst others.Endoscopy can also assist in the management of complications post-esophageal surgery,such as anastomotic leaks and perforations.Finally,there is a growing role for endoscopy to manage end-of-life palliative symptoms,especially dysphagia.The growing use of esophageal stents,debulking therapy and dilation can assist in improving a patient’s quality of life.In this review,we examine the multiple roles of endoscopy in the management of patients with EC.

Trimodality treatment in gastric and gastroesophageal junction cancers:Current approach and future perspectives

Gastric and gastroesophageal junction(GEJ)cancers represent an aggressive group of malignancies with poor prognosis even when diagnosed in relatively early stage,with an increasing incidence both in Asia and in Western countries.These cancers are characterized by heterogeneity as a result of different pathogenetic mechanisms as shown in recent molecular analyses.Accordingly,the understanding of phenotypic and genotypic correlations/classifications has been improved.Current therapeutic strategies have also advanced and moved beyond surgical extirpation alone,with the incorporation of other treatment modalities,such as radiation and chemotherapy(including biologics).Chemoradiotherapy has been used as postoperative treatment after suboptimal gastrectomy to ensure local disease control but also improvement in survival.Preoperative chemoradiotherapy/chemotherapy has been employed to increase the chance of a successful R0 resection and pathologic complete response rate,which is associated with improved long-term outcomes.Several studies have defined various chemotherapy regimens to accompany radiation(before and after surgery).Recently,addition of immunotherapy after trimodality of gastroesophageal cancer has produced an advantage in disease-free interval.Targeted agents used in the metastatic setting are being investigated in the early setting with mixed results.The aim of this review is to summarize the existing data on trimodality approaches for gastric and GEJ cancers,highlight the remaining questions and present the current research effort addressing them.