近畿大学医学部・病院50周年史
Survey or Interview光冨 徹哉

外科も内科も重なり合う
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A lung cancer specialist bridging both surgery and internal medicine.
MITSUDOMI Tetsuya

Specially Invited Professor

The patient must always be at the center. Even surgeons need not only surgical skills but also knowledge of pharmacological treatments.

In the field of medicine, the division between internal medicine and surgery is said to have originated in medieval Europe. Physicians who studied at universities were responsible for medical theory and internal medicine, while surgical operations were performed by barber-surgeons, who also worked as barbers. At the time, internal medicine was regarded as more academic and thus ranked “higher” than surgery.
Of course, such a “hierarchy” no longer exists today. However, differences in temperament between the two fields remain.
MITSUDOMI Tetsuya, now a Specially Invited Professor at Kindai University Faculty of Medicine, reflects with a wry smile, “Everyone seemed surprised that I went into surgery.”
MITSUDOMI was born in 1955 at Kyushu University Hospital, where his father was working. His father was a physician in the First Department of Internal Medicine, specializing in tuberculosis.
“There was a time when I disliked the way people around me assumed I would also become a doctor. Still, I suppose it was my father’s influence. The idea of saving lives, of helping people, had a certain appeal. That’s what led me to enter medical school.”
When the time to choose a career path upon graduating from the Kyushu University Faculty of Medicine, two options were before him: the First Department of Internal Medicine, where his father had belonged, and the Second Department of Surgery.
“I could sense that the professors of the First Department of Internal Medicine naturally expected me to join them, being the son of Dr. Mitsudomi. I think my classmates also took it for granted that I would go into internal medicine,” he recalls.
As for the difference between surgeons and internists, he laughs, “It’s often said half-jokingly that surgeons move their hands before thinking, while internists think carefully but are slow to act. I think people saw me as the latter.”
“But,” he adds, “the captain of the soccer club was a professor in the Second Department of Surgery, and many of my seniors had gone there. I agonized over the choice, but in the end, my club activities tipped the scales.”
The Second Department of Surgery at Kyushu University Faculty of Medicine, founded in 1904, was a historic department that primarily treated gastrointestinal diseases. As for why he specialized in thoracic surgery—lung cancer in particular—it was not so much a recommendation as an order from his professors.
“When it came time to choose my specialty in my ninth year after graduation, many were already working on gastric cancer. I said I wanted to tackle something more unusual, like the liver or esophagus. But they told me, ‘Thoracic surgery is the way to go,’ and that was that.”

Translational research is the ‘bridge’ between basic science and clinical practice.

Lung cancer arises from the cells of the bronchi or alveoli. It is broadly divided into two types: non-small cell lung cancer, which tends to progress relatively slowly, and small cell lung cancer, which grows quickly and tends to metastasize. Both are strongly associated with smoking. Surgical treatment is primarily indicated for non-small cell lung cancer.
“It may not be the most incurable cancer,” MITSUDOMI explains, “but compared with other cancers, overall, it is indeed difficult to treat. Even when surgery seems to go well, recurrence and metastasis often occur soon after. It is, I think, a cancer with a particularly strong tendency to spread.”
In 1989, MITSUDOMI traveled to the United States, to the National Cancer Institute (NCI) at the National Institutes of Health (NIH) in Maryland. What struck him first was the sheer abundance of resources.
“Perhaps it was because the U.S. economy was booming at the time, but whenever I needed laboratory equipment or reagents, they bought them without hesitation. Researchers of my generation had gathered there from all over the world, and it was incredibly exciting,” he recalls.
At NCI, great emphasis was placed on what today is called translational research—bridging basic science with clinical applications. MITSUDOMI’s primary focus was using PCR to investigate genetic abnormalities in lung cancer. PCR, short for polymerase chain reaction, is a technique used to selectively amplify specific DNA sequences.
“Until then, examining whether cancer cells carried genetic mutations was an arduous process. With the advent of PCR, however, it became possible to obtain data from a large number of samples in a short period of time. This allowed us to investigate the clinical significance of abnormalities in genes such as KRAS and P53,” he explains.
The KRAS gene, one of the RAS genes located on human chromosome 12, functions as an accelerator for cell proliferation. When mutations occur, the switch is stuck in the ‘on’ position, driving uncontrolled proliferation that leads to cancer. In lung cancer, KRAS mutations are thought to be the cause in 15–30 percent of cases.
The P53 gene, on the other hand, is often referred to as a tumor suppressor gene. In contrast to KRAS, it acts as a brake on cell proliferation. When P53 undergoes mutation, that brake fails, leading to uncontrolled cell growth. Today, it is understood that more than half of all cancers involve mutations in the P53 gene.
Though a surgeon by training, MITSUDOMI’s involvement in this kind of “internal medicine”-like research profoundly influenced the course of his life.
After returning to Japan, he served as Associate Professor of Thoracic Surgery at Kyushu University Faculty of Medicine, and in 1995 he became Director of the Department of Thoracic Surgery at the Aichi Cancer Center Hospital.

The beginning of my connection with Kindai University was through ‘Iressa.’

MITSUDOMI Tetsuya’s deep attraction to translational research was sparked by the advent of the EGFR inhibitor gefitinib (trade name Iressa). Gefitinib is a molecularly targeted cancer drug designed to block the activity of proteins and enzymes involved in carcinogenesis and cancer cell proliferation. In 2002, Japan became the first country in the world to approve gefitinib for the treatment of “unresectable, advanced, or recurrent non-small cell lung cancer.”
“Iressa produced striking responses in some patients, while showing no effect at all in others,” MITSUDOMI recalls. At the time, it was observed that non-smokers, women, patients with adenocarcinoma, and Asian populations tended to respond better, but the mechanism behind this was completely unknown.”
Drawing on his experience in the United States, MITSUDOMI had continued preserving surgical specimens from lung cancer patients and subjecting them to genetic analysis. Then, in May 2004, a groundbreaking paper was published showing that “a subset of non-small cell lung cancer patients harbor EGFR mutations, and these mutations may predict responsiveness to EGFR inhibitors such as Iressa.”
“After that paper came out, we conducted our own analyses and found a striking correlation between EGFR mutations and treatment response,” MITSUDOMI recalls.
It was around this time that his ties with Kindai University began to take shape.
“We conducted experimental testing and observed that when gefitinib was administered to patients with EGFR gene mutations, its effects correlated remarkably well. At one point, Dr. NAKAGAWA Kazuhiko from Kindai University Hospital contacted me, asking if I could test the specimen of a female patient in her 40s. At that time, Kindai University did not yet have the capability to perform such testing.”
“The patient had been treated for what was believed to be advanced uterine cancer, with ascites and pleural effusion. But the treatments brought little effect, and she was struggling with severe shortness of breath due to the fluid in her lungs. Her father carried the specimen to the Aichi Cancer Center, where I was working, and when we examined it, we discovered an EGFR mutation. Since EGFR mutations are almost specific to lung cancer, we realized it was not uterine cancer after all, but lung cancer. We contacted Kindai to say that Iressa would likely work. Once she began taking Iressa at the Department of Medical Oncology there, her breathing improved dramatically. Later, I even received a New Year’s card from her. I still remember how grateful she was, and how deeply it moved me. For the first time, I felt my research had truly helped a person.”
Thanks in part to MITSUDOMI and his colleagues’ work, the drug label for Iressa was revised in 2010: instead of being indicated for “unresectable lung cancer in general,” its use was restricted to “patients with EGFR mutation–positive lung cancer.” This change reduced the risk of severe side effects and marked the beginning of what is now called personalized medicine, in which genetic testing is paired with tailored therapy.
“Today, in lung cancer surgery, research has shifted from the old style of cutting 30-centimeter incisions across the back, to minimally invasive approaches using endoscopes or robot-assisted surgery. These minimize both the incision size and the portion of lung removed. But let’s be honest—such innovations do not suddenly make incurable cancers curable. I have always aspired to be a physician for lung cancer patients, and in that sense, there is no strict boundary between surgery and internal medicine. Surgeons not only operate, but we can also administer drugs. And when I give a patient medicine and see them improve—that brings me joy,” he adds with a quiet smile.

What matters most is that the patient remains at the center, while people from various fields exchange their views.

“At the Aichi Cancer Center, residents are regularly dispatched from universities. Some of them are very capable, and just when I thought they should be sent abroad for further training, they would return after only two years. Over time, I felt a stronger desire not only to pursue clinical practice and research myself, but also to pass on my experience to the next generation within a university setting.”
It was around this time that MITSUDOMI was approached by NAKAGAWA Kazuhiko, then Chief Professor of the Department of Medical Oncology at Kindai University Faculty of Medicine.
“He told me that a new Division of Thoracic Surgery would be established within the Department of Surgery. At the time, I was 55 years old. I thought, with ten years left before retirement, I would still have enough time to train young people.”
In 2012, he was appointed Chief Professor of the Division of Thoracic Surgery in the Department of Surgery at Kindai University Faculty of Medicine.
From 2014 to 2018, he served as President of the Japan Lung Cancer Society, and from 2019 to 2021, as President of the International Association for the Study of Lung Cancer (IASLC)— taking on leadership roles not only in Japan but also on the global stage.
When asked what kind of person is best suited for thoracic surgery, MITSUDOMI answered:
“First, someone who is genuinely interested in cancer. Cancer remains the leading cause of death, and lung cancer is the most common of all. It is where the need is greatest. If you want to tackle lung cancer and are aiming to be a surgeon, then naturally, thoracic surgery is the natural choice.”
He also stressed the importance of collaboration with internal medicine.
“Medical oncology is, of course, centered on drug therapy. But even surgeons can no longer rely solely on surgery—they must also acquire knowledge of pharmacological treatments. In recent years, the concept of the multidisciplinary team, or MDT, has gained prominence. Medical oncologists, pulmonologists, thoracic surgeons, radiation oncologists, radiologists, pathologists, nurses, and physical therapists all come together to discuss the best approach for each patient. What matters most is that the patient is at the center, while professionals from diverse disciplines exchange their views.”
At the end of March 2022, MITSUDOMI stepped down from his professorship. Today, he continues to serve as President of the Izumi City General Medical Center and as a Specially Invited Professor at the Department of Innovative Medicine, Kindai University Faculty of Medicine, among other roles.
When asked in closing whether there was anything he had left undone at Kindai University, he laughed lightly and replied, “Perhaps only that I never had the chance to work in the new hospital.”