The Digestive Endoscopy and Gastrointestinal Oncology Division conducts research in various fields: endoscopic diagnosis and treatment, chemotherapy, and palliative care for head and neck, esophageal, gastric, and colorectal cancer patients. Many of the research projects of the Division are conducted as prospective studies either in a single institution or in collaboration with other institutions. Presently, the research activities of the Division are mainly focused on the development of new instruments for endoscopic diagnosis, novel endoscopic treatment modalities, new anticancer agents, as well as new combinations of anticancer agents with/without radiation therapy (8-26).
A new instrument, namely, a narrow band imaging (NBI) system combined with magnifying endoscopy, has greatly influenced the field of endoscopic diagnosis. Through this system, it is possible to visualize a unique image that emphasizes the capillary pattern and structure of the mucosal surface. The Division has contributed greatly to the clinical development of this system with support from a Grant for Scientific Research Expenses for Health and Welfare Programs, Japan. Indications for the use of this system currently include the diagnosis of head and neck, esophageal, gastric, and colorectal cancers. In 2008, many articles regarding endoscopic diagnosis, endoscopic treatment, or complications of such treatments were published. Based on the promising results of this system, prospective multi-institutional studies to confirm its efficacy for screening of head and neck, esophageal, gastric, and colorectal cancers are currently in progress. Diagnosis of colorectal neoplastic lesions is routinely performed in conventional and magnifying NBI observations. Furthermore, pit pattern on the surface of these lesions are also diagnosed. NBI findings are significantly correlated with histologic findings in early colorectal neoplasia. Moreover, NBI colonoscopy was demonstrated to be a useful diagnostic tool for predicting histological grade (9, 10). In addition, the efficacy of pit pattern for the diagnosis of mucosal and submucosal cancers was also elucidated (11).
Currently, endoscopic submucosal dissection is routinely indicated not only for early gastric cancer (12) but also for esophageal and colorectal cancers. Some new approaches for endoscopic treatment of esophageal and head and neck cancers have also been demonstrated. Presently, salvage endoscopic mucosal resection (EMR) and photodynamic therapy (PDT) after chemoradiotherapy are routinely being performed for local residual/recurrent tumors, and a prospective study to evaluate the feasibility and efficacy of salvage PDT is presently in progress. Long-term results of salvage EMR after chemoradiotherapy were shown (13).
Furthermore, molecular biological analysis of esophageal, head and neck, and colorectal cancers is presently being performed. Importantly, analysis of genetic polymorphisms in the genes coding for alcohol and aldehyde dehydrogenases for determining the risk factors for cancer of the upper aerodigestive tract including esophageal and head and neck cancers could be a useful novel strategic approach to the prevention of these cancers in Japanese. In the examination of esophageal precursor lesions, risk factors for low-grade dysplasia were shown to be different from those for high-grade dysplasia.
Many prospective clinical trials in the field of oncology that are mainly targeted at Investigational New Drug (IND) registration are currently in progress. The final results of several studies were published in 2008 (14, 15, 16, 17, 18, and 19). Based on the results of the above registration trials, the INDs were approved in Japan, and several new trials targeting different types of solid tumors as an indication expansion process has been on-going or planned. Sorafenib, a novel multikinase inhibitor, has been approved for renal cell carcinoma in Japan in mid-2008. Moreover, a phase I trial of sorafenib in combination with S-1 plus cisplatin for advanced gastric cancer has been on-going, and whose accruals have already been completed (15). Cetuximab, a novel monoclonal antibody against the epidermal growth factor receptor, was also approved for colorectal cancer in Japan in the late 2008. A phase II trial for cetuximab concurrent with radiotherapy for head and neck cancer as an indication expansion trial will be started in early 2009 (16). Imatinib mesylate, a novel c-kit inhibitor, has also been approved for gastrointestinal stromal tumors in Japan (17).
In addition, the Division has analyzed retrospectively several manuscripts and a review article published in 2008. In the field of head and neck cancer, nonplatinum-based chemotherapy with irinotecan plus docetaxel for advanced or metastatic olfactory neuroblastoma was retrospectively investigated (20). In the field of esophageal cancer, patients receiving chemotherapy with or without radiotherapy were retrospectively analyzed (21, 22, 23). A review article on systemic chemotherapy for advanced gastric cancer has been published (8). Furthermore, the efficacy of gemcitabine as a second-line treatment after chemoradiotherapy and maintenance 5-fluorouracil chemotherapy for locally advanced pancreatic cancer was retrospectively investigated (24). The safety and efficacy of the FOLFIRI regimen for advanced colorectal cancer in the Japanese population has also been retrospectively evaluated, as well as the clinical significance of baseline sum of the longest diameter of target lesions by RECIST for advanced colorectal cancer (25, 26).
● K. Kaneko, T. Yoshino, A. Ohtsu ●
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