Digestive Endoscopy and Gastrointestinal Oncology Division
Introduction
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 are conducted as prospective studies either in a single institution or in collaboration with other institutions. Presently, research activities of the Division have mainly been focused on the development of new instruments for endoscopic diagnosis, new endoscopic treatment modalities, new anticancer agents, and new combinations of anticancer agents with/without radiation therapy.
Research Activities in Digestive Endoscopy
A new instrument, namely, a narrow band imaging system (NBI) combined with magnifying endoscopy, has greatly influenced the field of endoscopic diagnosis. Using this system, it is possible to visualize a unique image that emphasizes the capillary pattern and the 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 2007, many articles regarding endoscopic diagnosis, endoscopic treatment, or complications of such treatments have been published (4, 5-14, 15-18). Based on the promising results of this system, prospective multiinstitutional studies to confirm its efficacy for screening of head and neck, esophagus, gastric, and colorectal cancers are currently in progress. Endocytoscopy enables in vivo observation of cell nuclei in the GI tract with a considerably high magnification. A potential limitation of endocytoscopy in the diagnosis of esophageal squamous cell carcinoma was confirmed (6).
Currently, endoscopic submucosal dissection (ESD) is routinely indicated not only for early gastric cancer but also for esophageal and colorectal cancer. In a retrospective analysis regarding ESD for large superficial colorectal tumors, ESD was shown to be feasible and less invasive than surgical resection (16). Some new approaches for endoscopic treatment of esophageal and head and neck cancers have been demonstrated. Currently, salvage EMR and photodynamic therapy (PDT) after chemotherapy 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.
Furthermore, molecular biological analysis of cancers of the esophagus, head and neck, and colorectum is being performed. Analysis of the 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 (19, 20) could be a useful novel strategic approach to the prevention of these cancers in the Japanese. In the examination of the p53 tumor suppressor gene mutations in relation with the precursor of esophageal cancer, genetic alterations were found in Lugol-unstained lesions without dysplasia (18).
Research Activities in Gastrointestinal Oncology
Many prospective clinical trials in the field of oncology that are mainly targeted at IND registration are currently in progress. The final results of several studies have been published in 2007 (21, 22, 23). One such noteworthy study was the biological study of patients with gastric cancer that clarified the impact of VEGF status on treatment outcomes (21, 24). Evaluation of FDG-PET in chemotherapy with tyrosine kinase dual inhibitors (ErbB1 and ErbB2) revealed that FDG-PET was clinically beneficial (25). The feasibility of the FOLFOX4 regimen in advanced colorectal cancer in the Japanese population has been prospectively evaluated, and the details of the long-term outcomes of S-1 monotherapy for gastric cancer were retrospectively investigated (22, 26). Several pharmacogenetic variations/polymorphisms have been reported in Japanese patients (27, 28, 29, 30). Review articles regarding the disparities in chemotherapy for advanced gastric cancer between Japan and the Western countries have been published (31). In the field of head and neck cancer, patients receiving chemoradiotherapy were retrospectively analyzed (32,123). Since the number of elderly patients is increasing in Japan, the efficacy and toxicity of chemoradiotherapy with 5-FU and CDDP were retrospectively compared between the elderly and nonelderly patients (33). A new category of cancer involving the esophagogastric junction has been reported on the basis of the lymph node compartments that are involved (34). Furthermore, 5-FU is frequently combined with other drugs including new molecular targeting agents. To examine fatal toxicity to 5-FU, genetic variations of DPYD encoding DPD were searched for (27).
● K. Kaneko, T. Doi, A. Ohtsu ●
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