What are your research goals?

The Graduate School of Medicine, Department of Gastroenterological Surgery II conducts surgery and carries out clinical and basic research on malignant diseases including cancer of the upper gastrointestinal tract, biliary tract, and pancreas, as well as other tumorous and non-tumorous diseases.

In treatment of the multidisciplinary advanced cancers, just surgery is not enough. Development of "multidisciplinary therapy" that is combined also with chemotherapy and radiotherapy is required.

Our department performs aggressive extended radical surgery for ultra-advanced cancers, appropriate organ-preserving surgery for low-grade lesions, and offers minimally invasive endoscopic surgery as an early cancer treatment strategy. Among these, we consider esophageal cancer, gallbladder cancer, and pancreatic cancer as intractable cancers, which have especially high malignancy and tend to recur, and are therefore difficult to treat even through surgery. In treating such refractory advanced cancers, surgery alone is not enough. Development of a "multidisciplinary therapy" that combines other treatments given before and after surgery (adjuvant treatment), such as chemotherapy using anticancer drugs, or radiation therapy, is required.

Surgery after chemotherapy for advanced cancer

One of our projects for this "multidisciplinary therapy" development is a clinical trial of pre-surgery (neo-adjuvant) chemotherapy for pancreatic cancer. The goal of this project is to lower cancer recurrence rates by adding neo-adjuvant chemotherapy in order to improve treatment results. This project is unique in that it broke down the institutional barriers between the three medical universities in Hokkaido, merging the internal medicine departments and surgery departments from 38 institutions across Hokkaido. This large-scale clinical trial is quite literally being conducted by “all of Hokkaido.” In addition, there is a new project underway for advanced pancreatic cancer patients and biliary tract cancer patients that could not undergo surgery at the time of diagnosis. We reported for the first time in the world that in cases where chemotherapy and/or radiotherapy is effective, and no advancement of the cancer lesion is observed for more than a half year, it is possible to achieve good results through aggressive surgery. This surgical therapy involves the combined resection and reconstruction of multiple blood vessels such as the hepatic artery, or in other words, extended resection, which is not usually performed. In addition to the above, we have also started clinical research on immunotherapy, and basic research into genetic treatments and molecular targeted treatments, which apply state-of-the-art molecular biological methods in order to develop adjuvant treatments with less side effects for patients of advanced or recurring cancer, for which standard therapy such as surgery, chemotherapy, or radiotherapy is no longer effective. The next paragraph introduces some research results from our department’s clinical research on cancer immunotherapy.

 

What challenges do you face?

Tumor antigens appear only on the surface of cancer cells, and do not appear on normal cells. Since 2005, our department has conducted clinical research into immunotherapy used on tumor antigens appearing in a wide variety of carcinomas, producing research such as "Cancer vaccine phase I trial with HER2 protein CHP complex pulsed dendritic cells" and "Cancer vaccine phase I trial with NY-ESO-1 cancer antigen protein / CpG / liposome complex.”

"Basic research" in the lab

These are new adjuvant treatments, and place less burden on the patient by strengthening the immunity that originally exists in a living organism in order to improve anti-tumor activities. Clinical trials for patients with advance / recurring cancer have revealed that cancer immunotherapy induces specific immune reactions in high frequency, and there are cases where only immunotherapy can stop the progression of disease for a relatively long time.

It has been found that, in this way, the cancer vaccine induces tumor-specific immune response in vivo. However, no definitive clinical effects have been obtained solely through the application of the vaccine as of present. The reasons for this, such as the presence of tumor immune evasion mechanisms and immunosuppressive cells, are known. We consider our future challenges to be the development of biomarkers that can detect good reactions to a cancer vaccine, in order to indicate cases to be selected for vaccine therapy. We also hope to develop and validate adjuvant treatments that can induce stronger immunoreactions.

 

What is your next goal?

It is difficult to develop a truly effective treatment for patients, applicable in clinical practice, with data obtained under limited conditions solely in a laboratory. "Basic research" conducted in a lab, and "clinical research" as applied to real patients, are two prongs in medical research, also referred to as "translational research.” Hokkaido University Hospital was specified as one of the core clinical research hospitals by the Ministry of Health, Labour, and Welfare in 2012, and is equipped with systems to promote such research. Our clinical department is also developing a wide variety of translational research into overcoming intractable cancers and recurring cancers. We are looking to establish evidence of the effectiveness of multidisciplinary therapy that has surgery as a core treatment.