Cross-boundary Cancer Studies
The Road toward Asia Well-being
Cross-boundary Cancer Studies
The Road toward Asia Well-being
TITLE
Closing lectures by lecture series partners
SPEAKER
Nobuhisa MATSUHASHI, MD, PhD
Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine
Kazushige SASAKI, PhD
Associate Professor, The University of Tokyo
- Profile -
Nobuhisa MATSUHASHI received his MD from Osaka Medical College, School of Medicine, subsequently earning his PhD from Gifu University. Starting his career in 1996 as a resident in surgery at Gifu University, he has worked at several major hospitals in Gifu Prefecture, specializing in surgery. From 2001 to 2004 he was a research fellow at the Department of Surgical Oncology, Gifu University, and from 2004 to 2006 he served as Assistant Professor at the Gifu University Hospital Advanced Critical Care Center. He subsequently worked at other institutions, including Gifu Prefectural General Medical Center. From 2013 to 2019 he was a Specially Appointed Associate Professor, Frontier Science for Surgical Oncology at Gifu University Hospital. Before taking up his current position, from 2019 to 2022 he was an Associate Professor, Department of Surgical Oncology, Gifu University. He is a member of various councils and academic societies, including Japanese Society of Gastrointestinal Surgery, Japanese Society of Endoscopic Surgery, Japan Society of Clinical Oncology, and Japan College of Surgeons.
Kazushige SASAKI received his PhD from the University of Tokyo and is currently an Associate Professor at the Graduate School of Arts and Sciences, the University of Tokyo. He is an expert in exercise physiology, conducting research primarily on human skeletal muscle, with a particular focus on age-related and training-induced changes, as well as their relationships with physical performance and health. He and the graduate students under his supervision have published impactful papers in leading journals in the fields of physiology and sports science, including The Journal of Physiology. In addition, he serves as a core member of UTokyo Sports Science Initiative (UTSSI), a university-wide organization, holding the concurrent position of Project Associate Professor in two endowed research sections affiliated with UTSSI, where he is engaged in research activities aimed at translating basic research findings into societal applications.
SUMMARY
Norie KAWAHARA noted that the lecture course is part of the official graduate program at the University of Tokyo, and is open to students across the entire university. She noted that from this year, graduate students from Gifu University’s School of Medicine have also joined the course.
At the end of the lecture series, Dr. Kawara welcomed guest lecturers from professors of each university to give short lectures.
The first speaker was Professor Nobuhisa Matsuhashi of Gifu University’s School of Medicine. Professor Matsuhashi is a leading expert in colorectal cancer, and is also deeply involved in medical collaboration across Asia. What is more, Gifu University has a strong partnership with Malaysia. Professor Matsuhashi would be sharing insights not only about cancer care, but also about a topic that gained attention at this year’s largest cancer conference in the United States—ASCO—namely the connection between exercise and cancer prognosis.
Professor Kazushige Sasaki from the University of Tokyo would also be giving a lecture as an expert in exercise science. Professor Sasaki’s specialization is in muscle physiology, and he plays an essential role in advancing research on how exercise and cancer are physiologically connected. Prof. Sasaki would be talking about the benefits of physical activity from a scientific perspective.
Dr. Kawahara noted that both professors would speak from their respective fields about the value of exercise— especially important in Asian healthcare systems where medical resources are limited. This topic is expected to become even more important for healthcare in Asia, and it will continue to be discussed in the fall lecture series.
Dr. Kawahara noted that the highlight of this lecture series is that over the course of 11 lectures it has brought together insights from various fields, creating a foundation for interdisciplinary research. Through the lecture series students had learned about the current situation where Asian cancer patients face fragmented support systems that exist in isolation, preventing them from receiving integrated support. Due to these circumstances, many people hold the image that cancer equals the end of life and are too afraid to undergo screening. Now that cancer medicine has advanced in Asia and cancer has become a disease from which one can survive after treatment rather than succumbing to a fatal illness, social inclusion to support the lives of cancer patients as survivors has become an extremely important issue.
In closing her comments, Dr. Kawahara noted that the lectures today, from lecture series collaborators would become the beginnings of new possibilities. Triggered by these lectures, the respective approaches of cancer treatment physicians, exercise physiology researchers, medical sociologists, and community-based business practitioners will become the starting point for developing rehabilitation work programs for cancer survivors, in order to further open up the future of cancer care in Asia. This represents a new approach to solving social issues, and one that has been inspired by this interdisciplinary research.
Dr. Matsuhashi presented a short lecture on new advances in colorectal cancer treatment, covering the four areas of: 1) advances in robotic surgery, 2) immune checkpoint inhibitors for MSI-high rectal cancer, 3) limitations of adjuvant therapy after surgery, and 4) importance of exercise therapy.
In terms of advances in robotic surgery, the “da Vinci” was originally commissioned by the US Army in the 1990s for military use. The aim was to allow surgeons based in the continental United States or aboard US Navy aircraft carriers to remotely perform necessary surgeries on injured soldiers.
However, because the Gulf War ended sooner than expected, development shifted away from military oversight. Civilian development continued thereafter, and in 1999 the “da Vinci” system was completed.
In July 2000, it received approval from the US FDA. It has been developed and manufactured by Intuitive Surgical and other companies. In 2019, key patents expired, which has since accelerated global adoption and further development in various countries.
It is evident that the proportion of robotic surgery has been increasing year by year. While there is no statistically significant difference in prognosis, robotic surgery trends to show relatively better outcomes, however, a key issue moving forward is that, despite use of expensive equipment, this improvement has not translated into a clear survival benefit,
With regard to immune checkpoint inhibitors for MSI-high rectal cancer, immune checkpoint inhibitors led to remission in rectal cancer. Microsatellite instability -high (MSI-H) colorectal cancer is generally difficult to treat until now, but a new method, known as CheckMate 8HW has seen better outcomes, Even in patients with unresectable disease, treatment outcomes are comparable to those of cured patients.
With regard to limitations of adjuvant therapies after surgery, oxaliplatin-based chemotherapy has been found to improve prognosis.
With regard to the importance of exercise therapy for cancer care, a recent article in the New England Journal of Medicine on Structured Exercise after Adjuvant Chemotherapy for colon cancers was cited. The background to this paper was the for patients with stage three or high risk stage two colorectal cancer, adjuvant chemotherapy is considered the standard of care. However, if after completion of standard treatment, the recurrence rate remains between 20% and 40% and improvement in long term outcomes continue to be a challenge. Pre-clinical and observational studies have suggested that exercise interventions may have positive impact on the prognosis of the colorectal cancer. To date, no randomized control trials have demonstrated that postoperative exercise interventions improve outcomes in colorectal cancer. This raises the question does a structured exercise program after completion of adjuvant therapy improve disease-free survival, or overall survival in patients with stage III or high-risk stage II colon cancer?
In patients with stage III or high-risk stage II colon cancer after curative resection, two to six months following the completion of adjuvant therapy, a fitness test was implemented and a three-year structured exercise intervention program combined with health education materials was compared to a regimen of only health education materials. The study was split into three phases, including behavior support, supervised PA and PA goals. At the end of the third phase 77% of patients were still reporting to the study.
The study found that exercise prevented one recurrence or new cancer for every 16 participants. The improvement in overall survival is attributable to a reduction in colon cancer-specific mortality. Exercise prevented one death for every 14 participants.
The study suggests that the era of exercise oncology has arrived. Patients could collaborate with exercise specialists, and engage in stepwise programs during and after treatment, receiving exercise “prescriptions” following cancer care.
Colorectal cancer is one of the most prevalent forms of cancer in Japan, both in terms of mortality and by incidence. The risk of developing cancer increases sharply after the age of 50. In Japan the country is entering a super-aged society ahead of the rest of the world and it is evident that Japan’s younger population is decreasing.
In terms of Japan’s contribution to cancer care in Asia, Japan has well-established cancer screening programs with high quality control. Japan also offers cutting-edge cancer treatment, including endoscopic resection, laparoscopic and robotic surgery, radiation therapy, chemotherapy and palliative care.
In terms of palliative and end-of-life care support, Japan can provide educational and policy support for pain management, end-of-life care, and holistic support for patients and families.
In terms of development of cancer registries and epidemiological data, Japan’s population based cancer registry system plays a vital role in policy planning and program evaluation.
In terms of international collaborative research and clinical trials, Japan can lead or participate in collaborative research and clinical trials on cancers common in Asia.
Gifu University is currently planning to use a joint system to provide telemedicine support in cancer care.
With regard to support for cancer policy and system development, Japan’s Basic Act for Cancer Control provides a comprehensive national framework, including the designation of cancer centers and regional coordination systems. Japan can assist other Asian nations in formulating national cancer control plans and designing sustainable systems.
Dr. Sasaki noted that he would be taking about the role of muscle and physical activity in maintaining and promoting health as a supplement to the lecture series.
Muscles play a diverse role in the human body. Muscle is an essential organ or tissue for generating force and body movement. However, recent research has revealed that muscles play a much wider role than previously thought. Among these two roles in particular, consuming energy to produce heat and screening hormones are considered to be closely related to maintaining our overall health.
Among the total amount of energy we expand in a day, in the portion used for physical activity, there is great difference between individuals, but it is mostly consumed by skeletal muscles. In addition, muscles consume a considerable amount of energy, even at rest. In terms of reducing energy consumption, skeletal muscle runs just behind the liver and the brain.
For example, when we eat, our energy expenditure increases. This is known as diet induced thermogenesis. During eating, we use muscles around the mouth and tongue, so part of that energy expenditure also comes from muscle activity. Metabolic rate refers to the minimum amount of energy required to sustain life.
This includes the energy used for heat production to maintain body temperature. Because skeletal muscles are distributed throughout the entire body, they play a key role in maintaining body temperature through heat production.
Physical activity and energy expenditure can be divided into two categories. One is energy for intentional exercise, and the other is energy for daily activities that are not used for the purpose of exercising, such as doing housework or walking to school. The latter is known as known non-exercise activity thermogenesis (NEAT).
Individuals with obesity tend to spend more time sitting and less time standing or walking compared to lean individuals. This difference in lifestyle results in a range variations in daily physical activity levels among individuals. The negative correlation has been observed between variations in physical activity and body fat percentage. Obesity is well known as a major risk factor for lifestyle diseases such as diabetes and cardiovascular disease. Therefore, if increasing NEAT can lead to weight loss, it may also help prevent or slow the progression of various diseases, including some types of cancer.
It has also become increasingly clear in recent years that the skeletal muscle functions as an endocrine organ by secreting various bioactive substances. There are at least several dozen such substances secreted by muscle, and they are collectively referred to as myokines. Most myokines are carried through the bloodstream to various organs and tissues throughout the body where they exert specific biological effects.
In this sense, they function as almost the organs and tissues that receive these myokines are called target organs or target tissues. Interestingly, many of these targets can also secrete hormones themselves. For example, adipose tissue and digestive organs are both known to release several types of hormones just like skeletal muscles.
Some of these hormones are secreted more actively during physical activity. In recent years, these exercise responsive hormones, including myokines, have come to be known collectively as exerkines. In this way, various organs and tissues in the body are constantly communicating with each other. However, when the secretion myokines or exerkines are insufficient, it may lead to physical dysfunction or accelerated aging.
As an example, one of the myokines, known as SPARC, were shown to suppress the proliferation of colon cancer cells. SPARC levels increased significantly both immediately after and three hours after exercise. Moreover, when SPARC was applied to cultured muscle cancer cells, the number of cancer cells decreased in a dose dependent model. Colon cancer has long been known as one of the cancers most responsive to physical activity. However, the mechanisms behind this effect have not been fully understood the discovery of SPARC shed light on part of this previously unclear mechanism and has received considerable attention in the research community.
In another study, researchers investigated the effects of a muscle agent, which is designed to promote muscle growth on cancer cachexia in mice. Cachexia is a condition in which systemic information caused by cancer progression leads to severe weight loss even without physical activity. When colon cancer cells are transplanted subcutaneously into mice, signs of cachexia typically appear within two weeks waiting to rapid weight loss and ultimately death.
However, when the mice were treated with a muscle agent to increase their muscle mass, the tumor itself did not shrink, but the treated mice maintained greater body weight and showed a clear extension in survival compared to untreated mice. While the precise mechanism remains unclear, it is possible that myokines, such as SPARC mentioned earlier, may play a role.
In conclusion, with regard to the types of exercise that are effective in preventing and surviving cancer, the best option is a combination of endurance exercise and resistance exercise, which can lead to synergistic effects.
Typical examples of endurance exercise include working, jogging, but in fact, any activity that can be sustained continuously for 10 or 20 minutes without rest can be considered endurance exercise. These activities tend to increase energy expenditure, and from a myokine perspective, they are valuable because they increase the opportunities for myokine secretion.
On the other hand, resistance exercise is generally prone to increase muscle strength, including exercises like weight lifting using barbells or dumbbells. However, recent studies have shown that even body weight exercises when done properly can be effective in gaining muscle mass. Since myokine secretion is considered to be proportional to muscle mass, increasing muscle mass or regular resistance exercise may enhance the capacity for myokine secretion.
Therefore, performing endurance exercise helps increase the opportunities for myokine secretion. This combination forms the core concept of exercise from long-term health and disease prevention. Doing both endurance and resistance exercises may sound difficult or impractical, but endurance exercise doesn't always require setting aside time. It can be inter integrated into daily life, for example, by walking faster than usual or choosing the stairs instead of the elevator.
Resistance exercise is also very time efficient. Just doing one type of exercise per day, like sports or pushups to the point of fatigue or failure can take only one or two minutes, and that alone can produce significant benefits, especially for beginners.
Details of the final assignment were provided, as detailed below:
Purpose of the Assignment
As a culminating task of this course, students are required to prepare a concise but impactful policy brief aimed at key decision-makers and stakeholders in healthcare across Asia, particularly those attending the Malaysia NCDs Summit.
The brief should address the following key questions:
What are the pressing challenges currently hindering the realization of well-being in Asia?
What innovative strategies, programs, or policies are required to address these challenges effectively?
Assignment Guidelines
Policy brief should be based on insights and knowledge gained from the course lectures and discussions.
Students are encouraged to adopt an interdisciplinary approach, drawing on public health, social policy, economics, and regional context.
The format is flexible, but the tone should be professional and oriented toward policy impact.
Think of the audience as policymakers, practitioners, and civil society leaders shaping the future of healthcare and well-being in Asia.
Students are free to choose their own topic within the broader framework of Asia and well-being. While cancer may be your point of departure, the scope of your analysis can-and should-expand to encompass the social, economic, cultural, and policy dimensions of health and well-being in Asia.
Your submission may take any format you feel most effectively conveys your proposal. One suggested model is the policy brief format, such as those introduced on the World Bank's Policy Briefs portal (above), but this is only one example. The key is to communicate your message persuasively and accessibly to real-world audiences, particularly to participants of the upcoming Asia Health and Well-being Summit.
Evaluation Criteria (Positive factors will be awarded additional points)
Depth of Issue Analysis:
Does your report accurately identify and analyze the current challenges related to your theme? Are data, case studies, or relevant literature incorporated to support your argument? Analytical rigor and evidence-based insights are essential.
Specificity and Feasibility of Proposals:
Are your proposed solutions clearly articulated in the form of concrete actions or policies? Are they grounded in real-world constraints and opportunities? Proposals should consider implementation challenges and identify the necessary institutional or stakeholder collaborations.
Originality and Innovation:
Does your report offer novel perspectives or creative solutions that can contribute to the future of health in Asia?
Multi-dimensional Approach:
Does your work integrate knowledge across multiple fields (e.g., medicine, social sciences, technology, public policy)? We value submissions that demonstrate an ability to synthesize diverse perspectives-such as connecting technological innovation with cultural acceptance, or health policy with economic viability.
Logical Structure and English Expression:
Is your argument well-structured and coherent, with a clear introduction, development, and conclusion? Is your English clear, persuasive, and appropriate for an academic and policy-oriented readership?
This assignment is not merely an academic report. It is an opportunity to shape real-world policy discourse. Your voice as part of the next generation of researchers and practitioners matters. Let us bring your ideas to the global stage, and help shape a more inclusive and sustainable future for health in Asia.