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Jaffer A. Ajani

Approximately 38,000 new patients will be diagnosed with gastroesophageal cancer in 2008.1 Although this number may be trivial compared with more common cancers, the incidence of esophageal and gastroesophageal junction adenocarcinoma has been steadily climbing over the past 20 years (www.cancer.org; accessed June 10, 2008). Although obesity, gastroesophageal reflux, and Barrett's metaplasia may contribute some or great extent to this alarming increase, some of the reasons for this increase remain elusive.2 The global health burden imposed by gastroesophageal cancer parallels that imposed by lung cancer, with approximately 1.4 million new cases and 1.1 million deaths per year.3 Furthermore, the mortality is likely to remain high because early detection of gastroesophageal cancer is not commonly practiced in most countries. Nevertheless, we have witnessed some definite progress in staging and therapy of patients with gastroesophageal cancer. For localized gastroesophageal cancer, progress has been made with the implementation of multidisciplinary approaches that lead to better selection of therapy for a specific patient, formulation of long-term strategies, and emergence of new standards.4–6 Multidisciplinary interactions can lead to new research strategies and improved understanding of the philosophies used by individual disciplines for treatment decisions. Progress in the treatment of early gastroesophageal carcinomas using endoscopic therapies is also worth mentioning.7-10 Endoscopic therapy of early cancer seems to be spreading in non-academic centers as well. In addition to these improvements, progress in imaging techniques can improve patient selection. Despite these improvements, considerably more progress must be made. To reduce mor-bidity and mortality, gastroesophageal surgeries should be performed...
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Prajnan Das, Norio Fukami and Jaffer A. Ajani

Gastric and esophageal cancers continue to be a significant health problem. The incidence of proximal gastric and distal esophageal cancers has been increasing, especially in white men. Gastric and esophageal cancers have high rates of locoregional and distant failure, resulting in poor overall survival. Therefore, patients with gastric and esophageal cancer may benefit from combined modality therapy. Adjuvant chemoradiation has been shown to improve survival in gastric and gastroesophageal cancers in a phase III trial. In esophageal cancer, most randomized trials have not shown a survival benefit for preoperative chemotherapy or chemoradiation, although these approaches are widely used. This article reviews the role of staging, surgery, and adjuvant and preoperative therapies in the management of localized gastric and esophageal cancers.

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Yixing Jiang, Heath Mackley, Hua Cheng and Jaffer A. Ajani

Use of definitive chemoradiation as primary therapy for locoregional squamous cell carcinoma of the anal canal has been the standard approach in the United States since the 1980s. Over the past several years, phase III studies have shown that combination mitomycin C (MMC) and 5-fluorouracil (5-FU) concurrent with radiotherapy had better outcomes than radiotherapy alone or 5-FU with radiotherapy. Two recent phase III studies using diverse treatment strategies showed that cisplatin and 5-FU were not superior to 5-FU and MMC; in one of the trials, use of cisplatin-based chemoradiation resulted in a higher rate of colostomy compared with mitomycin-based chemoradiation. MMC and 5-FU concurrent with radiotherapy remains standard care. Further improvement is likely depending on an increased understanding of the molecular biology of anal carcinoma and the addition of relevant biologic agents to chemoradiation to overcome chemoradiation resistance.

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Mariela A. Blum Murphy, Takashi Taketa, Kazuki Sudo, Jeffrey H. Lee and Jaffer A. Ajani

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Vivian E. Strong, Thomas A. D’Amico, Lawrence Kleinberg and Jaffer Ajani

The 7th edition of the AJCC Cancer Staging Manual has attempted to harmonize gastric and esophageal cancers, including management of gastroesophageal junction (GEJ)-type tumors. The treatment of complex tumor types is best guided by a staging classification that reliably groups patients according to prognosis and therapy. This article reviews and discusses these changes with the goal of elucidating key features of the staging system and outlining how these changes relate to the NCCN Clinical Practice Guidelines in Oncology with regard to the care and treatment of patients. The 7th edition of the AJCC Cancer Staging Manual has certainly improved harmonization of gastric and distal esophageal/GEJ-type adenocarcinomas, although issues persist, particularly regarding the optimal neoadjuvant treatment for the management of GEJ carcinomas.

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Robert E. Glasgow, David H. Ilson, James A. Hayman, Hans Gerdes, Mary F. Mulcahy and Jaffer A. Ajani

The clinical spectrum of esophageal cancer has changed dramatically over the past couple of decades. Most notably, a profound rise in esophageal adenocarcinoma and decrease in the incidence of squamous carcinomas have occurred. An understanding of the factors that influence survival for patients with localized esophageal cancer has evolved concomitantly with these changes in epidemiology. Significant advancement in endoscopic and radiographic staging allows for more selective use of treatment modalities. The treatment of localized esophageal cancer mandates a multidisciplinary approach, with treatment tailored to disease extent, location, histology, and an accurate assessment of pretreatment staging. Despite these improvements in the staging and use of multimodality therapy, only modest improvements in patient survival have been observed. This article summarizes these modern approaches to localized cancer of the esophagus.

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Prajnan Das, Yixing Jiang, Jeffrey H. Lee, Manoop S. Bhutani, William A. Ross, Paul F. Mansfield and Jaffer A. Ajani

Most patients with localized gastric cancer require multimodality therapy. Surgery is the primary treatment for localized gastric cancer, although controversy exists about the optimal extent of lymphadenectomy in these patients. Recent studies have evaluated the role of laparoscopic surgery and endoscopic mucosal resection in selected patients. Multimodality treatment options for these patients include post-operative chemoradiation and perioperative chemotherapy. The Intergroup 0116 trial demonstrated that patients treated with surgery and post-operative chemoradiation had significantly higher overall survival compared to patients treated with surgery alone. The MAGIC trial showed that patients treated with perioperative epirubicin, cisplatin, and 5-fluorouracil had significantly higher overall survival compared to patients treated with surgery alone. Other recent trials have evaluated the roles of preoperative chemoradiation and adjuvant chemotherapy. Multidisciplinary evaluation plays a crucial role in the management of these patients.

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Elena Elimova, Roopma Wadhwa, Hironori Shiozaki, Kazuki Sudo, Jeannelyn S. Estrella, Brian D. Badgwell, Prajnan Das, Aurelio Matamoros Jr, Shumei Song and Jaffer A. Ajani

Gastric cancer (GC) represents a serious health problem on a global scale. Despite some recent advances in the field, the prognosis in metastatic GC remains poor. Even in localized disease the adjunctive therapies improve overall survival (OS) by only approximately 10%. A better understanding of molecular biology, which would lead to improved treatment options, is needed and is the basis for this review. Many potential biomarkers of prognostic significance have been identified, including ALDH, SHH, Sox9, HER2, EGFR, VEGF, Hippo/YAP, and MET. However, inhibition of only HER2 protein has led to a modest survival benefit. A new approach to GC treatment, which is a disease influenced by inflammation, is the exploitation of the immune system to fight disease. Two interesting targets/prognostic markers that bear further investigation in GC are PD1 and PDL, particularly given their success in the treatment of other inflammation/immune-associated malignancies.