Message from the Chairman

Toshiyoshi Fujiwara
Toshiyoshi Fujiwara,
M. D., Ph. D.

Welcome to the website of the Department of Gastroenterological Surgery at Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.

I assumed the Chairmanship of the Department of Gastroenterological Surgery on April 1, 2010.Our Department was founded in 1922 as the First Department of Surgery at Okayama Medical Science University. It has a long history and the tradition, and consists of more than 1100 surgeons with various specialties. I am very much honored to be a Chairman and Professor of this large Department, and feels a strong responsibility for the management of the community.

The Department of Gastroenterological Surgery is comprised of two divisions: Gastrointestinal Surgery and Hepato-Biliary-Pancreatic Surgery. There are three groups in each division: Esophageal, Gastric, and Colorectal teams in GI Surgery, and Liver, Biliary-Pancreatic, and Transplantation teams in HBP Surgery. In intimate communications, these teams are working independently. Rotating these teams enables the fellows and residents to obtain the broad knowledge regarding patient care as well as the advanced surgical techniques.

Currently, our Department has 23 full time faculty members participating in teaching, research and clinical activities. More than 15 graduate students are investigating oncology, immunology, and transplantation.

In addition to our commitment to provide the clinical activities in patient care, we place a major emphasis on research and education. We have promoted the Translational Medicine, in which the knowledge of basic science is utilized to solve clinical problems with the ultimate goal of improving patient care.

We will continue to strengthen our academic activities and research efforts on molecular-based anticancer therapies, genetic diagnosis and molecular imaging for cancer, and immunology supporting transplantation. We will create a new surgical technique with an innovation.

The environment that surrounds surgery is now severe because the number of new surgeons is decreasing; however, we believe that young medical students will be interested in surgery again. We should tell them the surgeon’s motivation by showing the smiles of the patients and by training them to feel accomplishments.

We will establish an attractive Department where young medical students can feel gentle atmosphere and new hope to work together. We will train young surgeons who work for community health as well as for improvement of medical levels in the world.

The Department of Gastroenterological Surgery at Okayama University is dedicated to providing the most innovative surgical care, performing basic science and translational research, and serving premier educational programs for the training of next generation's surgeons.

April 1, 2010

Toshiyoshi Fujiwara, M. D., Ph. D.

 

Overview

The Department of Gastroenterological Surgery at Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences provides exceptional patient care and outstanding surgical education through innovative basic science and clinical research.

The tradition of the Department was established by the first Chair, Dr. Hachiro Akaiwa, in 1922, continues through the 9th Chairman, Dr. Toshiyoshi Fujiwara, and the work of more than 1100 affiliated member surgeons.

The Department of Gastroenterological Surgery provides diagnostic procedures and surgical therapies using state-of-the-art techniques. Divisions within the Department include:

 

Mission Statement

The Department of Gastroenterological Surgery shares hope and impression with people who struggle with illness.

 

 

Our Goals

 

Clinical medicine

 

Research Projects

Molecular Therapy

Gene Therapy

Gene and vector-based molecular therapies for cancer encompass a wide range of treatment types that all use genetic material to modify cancer cells and/or surrounding tissues to exhibit antitumor properties. One of the most common approaches to emerge from the concept of gene therapy is the introduction of foreign therapeutic genes into target cells.
We have completed a clinical trial of a replication-deficient adenoviral vector (Ad5CMV-p53, Advexin) that delivers normally functioning p53 tumor suppressor gene to patients with advanced non-small cell lung cancer (NSCLC). Fifteen patients with histologically confirmed NSCLC and p53 dysfunction were enrolled into this phase I trial. Nine patients received escalating dose levels of Advexin as monotherapy once every 4 weeks. Six patients were treated on a 28-day schedule with Advexin in combination with intravenous administration of cisplatin.
Fifteen patients received a total of 63 intratumoral injections of Advexin without dose-limiting toxicity. The most common treatment-related toxicity was a transient fever. Specific p53 transgene expression was detected using reverse-transcriptase polymerase chain reaction in biopsied tumor tissues throughout the period of treatment despite of the presence of neutralizing anti-adenovirus antibody. Distribution studies revealed that the vector was detected in the gargle and plasma, but rarely in the urine. Thirteen of 15 patients were assessable for efficacy; one patient had a partial response (squamous cell carcinoma at the carina), 10 patients had stable disease, with three lasting > 9 months, and 2 patients had progressive disease.
Multiple courses of intratumoral Advexin injection alone or in combination with intravenous administration of cisplatin were feasible and well tolerated in advanced NSCLC patients, and appeared to provide clinical benefit.

Oncolytic Virotherapy

Replication-selective tumor-specific viruses present a novel approach for treatment of neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. For targeting cancer cells, there is a need for tissue- or cell-specific promoters that can express in diverse tumor types and are silent in normal cells.
Telomerase activation is considered to be a critical step in carcinogenesis through the maintenance of telomeres, and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. We constructed an attenuated adenovirus 5 vector, in which the hTERT promoter element drives expression of E1 genes (Telomelysin). Since only tumor cells that express telomerase activity would activate this promoter, the hTERT proximal promoter allows for preferential expression of viral genes in tumor cells, leading to selective viral replication and oncolytic cell death.
A phase I clinical trial was conducted to determine the clinical safety of Telomelysin in patients with advanced solid tumors. Patients with histologically confirmed advanced solid tumors were enrolled into this phase I trial. A single intratumoral injection of Telomelysin was administered to three cohorts of patients (1 x 1010, 1 x 1011, 1 x 1012 viral particles). Safety, response and pharmacodynamics were evaluated. Virus shedding was monitored in the saliva, sputum, urine, and plasma by a quantitative DNA-PCR assay.
Sixteen patients with a variety of solid tumors were enrolled. Intratumoral injection of Telomelysin was well tolerated at all dose levels. Common grade 1 and 2 toxicities included injection site reactions (pain, induration) and systemic reactions (fever, chills). Viral DNA was transiently (<6 hours after injection) detected in plasma in 13 of 16 patients. Three patients demonstrated evidence of prolonged viral replication through detection of plasma viral DNA at days 7 and 14. One of these 3 had disappearance of the injected malignant lesion and loco-regional uninjected satellite nodules, fulfilling a definition of complete response at day 28. Seven patients fulfilled RECIST definition for stable disease day 56 after treatment, although 6 patients showed 6.6 to 43% tumor size reduction.
No dose-limiting toxicity, or maximally tolerated dose were identified. Telomelysin was well tolerated. Evidence of antitumor activity was suggested and warrants further clinical studies for solid cancer.

Clinical Trial of Telomelysin in a Patient with Esophageal Cancer Started in Japan

 

Fluorescent Molecular Imaging

Circulating Tumor Cells (CTC)

The presence of circulating tumor cells (CTC) in the peripheral blood is associated with short survival and, therefore, the detection of CTC is clinically useful as prognostic factors of disease outcome and/or surrogate markers of treatment response. Recent technical advances in immunocytometric analysis and quantitative real-time PCR have made possible to detect a few CTC in the blood; however, there is no sensitive assay for detecting viable CTC. We developed a new approach to visually detect live CTC among millions of peripheral blood leukocytes using telomerase-specific replication-selective adenovirus expressing green fluorescent protein (GFP). We constructed a GFP-expressing attenuated adenovirus, in which the telomerase promoter regulates viral replication (OBP-401, TelomeScan). We used TelomeScan to establish a simple ex vivo method for detecting viable human circulating tumor cells in the peripheral blood. The detection method involves a three-step procedure including the lysis of red blood cells, the subsequent addition of TelomeScan to the cell pellets, and the automated scan under the fluorescent microscope. TelomeScan infection increases the signal-to-background ratio as a tumor-specific probe, because the fluorescent signal can be amplified only in viable human tumor cells by viral replication. This GFP-expressing virus-based method is simple and allows precise enumeration of CTC.

Surgical Navigation System

Currently available methods for detection of tumors in vivo such as computed tomography and magnetic resonance imaging are not specific for tumors. We developed a new approach for visualizing tumors whose fluorescence can be detected using telomerase-specific replication-competent adenovirus expressing green fluorescent protein (GFP) (OBP-401, TelomeScan). When TelomeScan was intratumorally injected into HT29 tumors orthotopically implanted into the rectum in BALB/c nu/nu mice, para-aortic lymph node metastasis could be visualized at laparotomy under a three-chip color cooled charged-coupled device camera. Our results indicate that TelomeScan causes viral spread into the regional lymphatic area and selectively replicates in neoplastic lesions, resulting in GFP expression in metastatic lymph nodes. This technology is adaptable to detect lymph node metastasis in vivo as a preclinical model of surgical navigation.

 

Staff

Toshiyoshi Fujiwara
Professor & Chairman
Toshiyoshi Fujiwara, M. D., Ph. D.
Takahito Yagi
Professor(Univ. Hospital)
Takahito Yagi, M. D., Ph. D.
Takuo Noda
Professor(Univ. Hospital)
Takuo Noda, M. D., Ph. D.
Hiroshi Sadamori
Associate Professor
Hiroshi Sadamori, M. D., Ph. D.
Yasuhiro Shirakawa
Lecuturer
Yasuhiro Shirakawa, M. D., Ph. D.
香川 俊輔
Assistant Professor
Shunsuke Kagawa, M. D., Ph. D.
西崎 正彦
Assistant Professor
Masahiko Nishizaki, M. D., Ph. D.
篠浦 先
Assistant Professor
Susumu Shinoura, M. D., Ph. D.
永坂 岳司
Assistant Professor
Takeshi Nagasaka, M. D., Ph. D.
田澤 大
Assistant Professor
Hiroshi Tazawa, M. D., Ph. D.
Hiroyuki Kishimoto
Assistant Professor
Hiroshi Tazawa, M. D., Ph. D.
Takayuki Motoki
Assistant Professor
Takayuki Motoki, M. D., Ph.D.
楳田 祐三
Assistant Professor
Yuzo Umeda, M. D., Ph. D.
尾山 貴徳
Assistant Professor
Takanori Oyama, M. D., Ph. D.
野間 和広
Assistant Professor
Kazuhiro Noma, M. D., Ph. D.
吉田 龍一
Assistant Professor
Ryuichi Yoshida, M. D., Ph.D.
岩本 高行
Takayuki Iwamoto, M. D., Ph.D.

信岡 大輔
Daisuke Nobuoka, M. D.
黒田 新士
Shinji Kuroda, M. D., Ph.D.
田辺 俊介
Assistant Professor
Shunsuke Tanabe, M. D., Ph.D.
近藤 喜太
Assistant Professor
Yoshitaka Kondo, M. D.

大原 利章
Toshiaki Ohara, M. D., Ph.D.
内海 方嗣
Assistant Professor
Masashi Utsumi, M. D.
Yoshiko Mori
Yoshiko Mori, M. D.
Takashi Kuise
Takashi Kuise, M. D.
Satoru Kikuchi
Satoru Kikuchi, M. D.
前田 直見
Naoaki Maeda, M. D.
稲田 涼
Ryo Inada, M. D.
Takeshi koujima
Takeshi Koujima, M. D.

Tetsushi Kubota
Tetsushi Kubota, M. D.
Kenjiro Kumano
Kenjiro Kumano, M. D.