Leading Doctors Discuss Modern Longevity

The Benefits of PDT—
Hopes for the Early Discovery and Conquest of Lung Cancer

Doctor Harubumi Kato, Thoracic Surgeon
Niizashiki Central General Hospital

Theme:Treating Central Lung Cancer

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PROFILE

Doctor Harubumi Kato

Professor, International University of Health and Welfare Graduate School
Professor Emeritus, Tokyo Medical University
Honorary Director, Niizashiki Central General Hospital

Harubumi Kato was born in 1942. After graduating from Tokyo Medical University in 1969, he studied at the Karolinska Institutet in Sweden from 1974. He became an assistant professor at Tokyo Medical University in 1988 and a senior professor in 1990. In 1991 he was appointed as Deputy Director of the Tokyo Medical University Hospital and Deputy President of Tokyo Medical University in 1991. His current post dates from 2008. Other posts held include President of International Association for the Study of Lung Cancer, Chairman of the General Meeting of the Japan Lung Cancer Society, President of the International Photodynamic Association, and President of the International Academy of Cytology.

Did you know that there’s a painless way to cure early-stage lung cancer in just 30 minutes using an endoscope? Known as “Photodynamic Therapy” (PDT), this method was developed by Doctor Harubumi Kato as an inexpensive and minimally invasive treatment for lung cancer. Although 70 years old, he continues to play a leading role in efforts to perfect early discovery and treatment methods.

Report: JQR Medical editorial staff / Photos: Satoru Naito

“The treatment will start soon. This is an anesthetic spray.” As he speaks, the doctor repeatedly sprays Xylocaine into the throat of the patient, who is sitting near the entrance to the operating theater. Xylocaine is a common local anesthetic that is applied during endoscopic examinations of the esophagus and stomach.
The patient, a man in his 60s, is about to undergo PDT for early-stage central lung cancer. Laser PDT is the most minimally invasive treatment for this type of lung cancer and is also regarded as a highly effective method.

Cancer Obliterated in Just 30 Minutes

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We generally think of laser treatment as a method that uses powerful lasers beams to burn away lesions. In fact, PDT uses a low-output laser. Far from being able to burn away lesions, the laser is so weak that you feel almost no heat even if you put your hand in front of the beam.
About four hours before the procedure, the patient receives an intravenous injection of an oncotropic photosensitizer, which is a photosensitive preparation with an affinity for tumors. This substance has properties that cause it be absorbed in high concentrations in cancerous tissue. This ensures that laser irradiation selectively destroys the cancer cells without damaging normal tissue.
Dr. Kato, who developed PDT, watches closely as a 5 mm diameter bronchoscope (endoscope) slides smoothly through a mouthpiece and into the mouth of the patient. The camera on the tip of the bronchoscope quickly reaches the disease site, which is visible on the monitor as a shining red area because of the concentration of photosensitizer in the tissue. Someone says “Begin irradiation”, and the laser beam comes on, filling the screen with dazzling light. A soft beeping noise can be heard, indicating that irradiation is in progress.
From time to time Dr. Kato gives instructions. “Apply the beam more to the front…move toward the 12 o’clock direction.” He repeatedly adjusts the angle and repeats the irradiation, each time checking the affected area. This continues for less than 20 minutes, and the treatment is complete.
“That wasn’t so hard, was it? Your cancer has gone,” says Dr. Kato, grinning at the patient.

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The patient walked unaided into the operating theater for this PDT procedure, which was performed at Niizashiki Central General Hospital in October 2015. Apart from a therapeutic laser system, the equipment is identical with a conventional bronchoscope. Even during laser irradiation, the patient feels no pain or heat. Look closely at the picture and you will see that Dr. Kato is holding the patient’s hand to comfort him. The eyes that watch the monitor so intently are filled with gentleness when they turn toward the patient. The procedure was completed successfully in just 30 minutes.

Early-stage central lung cancer
obliterated by PDT

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The lump in the middle of the photograph on the left is early-stage central lung cancer (squamous cell carcinoma). The photograph on the right shows the same area after PDT. The cancer has completely disappeared.

Suitable Only for Central Lung Cancer

In terms of incidence rates, lung cancer has moved into second place in Japan after being overtaken by colorectal cancer in 2015. However, it remains the number one cause of cancer deaths, killing approximately 80,000 people every year.
Lung cancers can broadly be divided into two types. Central lung cancer is found in the large bronchi, while peripheral lung cancer occurs near the pulmonary alveoli. Central lung cancer is difficult to detect using chest X-rays because the area is obscured by the heart, and in many cases cancer of this type is not diagnosed until a cytodiagnosis is performed following the appearance of bloody sputum, or when the patient exhibits pneumonia or other conditions. Peripheral lung cancer is often asymptomatic and is commonly detected by means of X-rays or CT scans of the chest.
In terms of the types of tissue involved, the four main types of lung cancer are adenocarcinoma, squamous cell carcinoma, small-cell carcinoma and large-cell carcinoma. This is a major difference from other types of cancer, which occur in a single type of tissue. Central lung cancer usually involves squamous cell or small-cell carcinomas, while peripheral lung cancer more commonly involves adenocarcinomas.
PDT, which is the focus of this article, is effective against early-stage central lung cancer.

PDT the Only Hope for a Patient with Serious Emphysema

The patient mentioned at the start of the article was diagnosed with lung cancer after he was examined in the respiratory department at Kanagawa Hospital five years ago for severe emphysema. Also known as chronic obstructive pulmonary disease (COPD), emphysema causes breathing difficulties by impairing lung function in a variety of ways. It is most often seen in elderly people with a history of smoking. Despite the discovery of early-stage cancer, the doctor concluded that surgery was not an option because the examination revealed that emphysema had already destroyed almost 90% of both of the patient’s lungs. The doctor also ruled out radiotherapy, which stresses the lungs, and chemotherapy, because of the serious side-effects. Dr. Kato was then asked to carry out PDT, which was seen as the only way to save the patient. The results were excellent. Although early-stage lung cancer was again detected during a regular medical examination, it was limited to one location, and the area previously treated had remained completely cancer-free. This time the procedure was completed in less than 30 minutes.
It seems incredible that lung cancer can be cured in 30 minutes, using just local anesthetic, and with no bleeding, and that the patient can stand up and walk briskly out of the hospital immediately afterwards. There is almost a sense of disappointment and anticlimax.

The PDT Method

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① About four hours before the start of treatment, the patient receives an intravenous injection of an oncotropic photosensitizer. ② After the patient’s throat has been sprayed with Xylocaine, a bronchoscope is inserted into the bronchus. ③ The cancer site is irradiated with red laser light through the bronchoscope, selectively destroying the cancer. On average, the procedure takes around 30 minutes.

Saving an Area of Lung Excised to Eliminate a Carcinoma a Million Times Smaller

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Professor Kato established the Clinical Proteome Center in 2003 while working as a professor at Tokyo Medical University. He was assisted by Dr. Koichi Tanaka (front row, center), winner of the Nobel Prize for Medicine. A proteome analysis is a comprehensive method for investigating proteins. Protein abnormalities are involved in the onset or progress of many diseases.

Japan can be proud of Dr. Kato’s achievements as one of the world’s leading authorities on lung cancer treatment. His involvement in the treatment of over 10,000 lung cancer cases has earned him the nicknames “Superdoctor” and “Hand of God.” The Tokyo Medical University Hospital, where Dr. Kato previously worked, has built an excellent track record as one of the best cancer treatment facilities in the Tokyo Metropolitan Area, while Dr. Kato has achieved international prominence through the development of PDT. With an amazing recovery rate of 85%, PDT has already become a standard method for the treatment of early-stage lung cancer.
The Path to the Development of PDT—
In the mid-1970s Dr. Kato returned to Japan after studying at the Karolinska Institutet in Sweden, where he completed studies on lung cancer carcinogenesis and DNA analysis. After returning to his alma mater, Tokyo Medical University, he worked to apply the results of his research to the early detection and localization of lung cancer. In 1976, Dr. Kato achieved the early detection of in situ lung cancer for the first time in Japan and performed successful surgery.
“I was confronted by a serious contradiction. Early surgical removal of in situ cancer would result in a full recovery, but we had to remove two-thirds of the lung. The price of life was the excision of an area a million times bigger than the in situ carcinoma. That seemed totally crazy, and I wanted to develop a different method that would cure the cancer while also preserving lung functionality.”

Childhood Inventor Driven by Intense Curiosity

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(Left) Dr. Kato performs lung cancer surgery. In 2007, the year before Dr. Kato stepped down from his professorial role, 270 primary lung cancer operations were performed at Tokyo Medical University. This is the second highest total in Tokyo after the National Cancer Center.

 Although Dr. Kato was born into a family of doctors, as the fifth of sixth brothers he was given the freedom to choose his own career. Filled with curiosity from an early age, he was a keen inventor, and while still in sixth grade he devised a timer that would turn a radio on at a specific time. His habit of devoting himself wholeheartedly to anything that took his interest caused him to fail the entrance exam for the engineering school of a national university. However, the spirit that had evolved in him since childhood eventually took him into medicine, and he achieved his full potential by struggling with things that he found inconsistent and illogical.
“The first person to report the clinical use of PDT was a veterinarian in the United States. I thought that PDT had potential for both diagnosis and treatment, so I went to the United States to carry out joint research with that veterinarian. After returning to Japan, I worked with an optical equipment manufacturer to verify the effectiveness and safety of the method, and in 1980 I attempted to treat early-stage lung cancer using PDT for the first time in the world. The patient made a full recovery.”

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(Top) Dr. Kato gives a presentation on his research at the World Conference of the International Association for the Study of Lung Cancer in September 2015. (Lower) Dr. Kato has won numerous awards, including the Maurice Goldblatt Cytology Award presented by the International Academy of Cytology.

China Entering the PDT Era as Central Lung Cancer Continues to Spread

of all therapies. That’s because it’s also covered by insurance. There’s been a lot of interest in immunotherapy in recent years, but the drugs cost ¥1.5-2 million per month, which means that the yearly cost per patient is about ¥20 million. PDT costs less than ¥2 million at most, and one treatment is enough. The only complication is excessive sensitivity to light due to the use of photosensitizers, so patients become more vulnerable to sunburn and need to avoid exposure to direct sunlight for a couple of weeks after treatment. However, this causes absolutely no problems provided that patients remain indoors, and in Europe and the United States the treatment is performed on an outpatient basis.”
Dr. Kato emphasizes the benefits of PDT, but he is frustrated that currently only one or two hundred patients a year are benefiting from the treatment in Japan. Of the 135,000 new lung cancer cases each year, about 10-30% are classified as central lung cancer. Simple arithmetic shows that over 10,000 patients could be completely cured by PDT. The reasons for this are as follows.
First, lung cancer is difficult to discover early, since few lung cancer patients have medical checks. Second, not enough is being done to raise awareness, with the result that few people are even aware of the existence of PDT.
“Another issue may be the fact that we can’t treat adenocarcinomas, which are the most common type of lung cancer. Unlike central lung cancer, which is caused primarily by smoking, there’s little causal linkage between smoking and adenocarcinomas, which are becoming more common in Japan despite progress on anti-smoking measures. There’s been little growth in the use of PDT in Japan. Globally, vast numbers of people are developing lung cancer because of the smoking population and the effects of air pollution. In many countries the real need for PDT may be in the future.”

Another World-First Discovery Helping to Detect Cancer

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Dr. Kato believes that doctors should follow the philosophy of the 19th century Japanese educator Issai Sato, who said that one should be “as gentle as a spring breeze with others and as strict as an autumn frost with oneself.” Harubumi Kato continues to move forward one step at a time along the path of lung cancer research.

At 73, Dr. Kato is at an age when most people would have retired from front-line work, but he is still one of the world’s leading researchers in his field. In addition to his efforts to develop and promote the PDT method, he has also made major contributions to the design of tools for the early discovery and diagnosis of lung cancer. One of Dr. Kato’s ideas is the TMDU Tube, a diagnostic kit for sputum cytodiagnosis. Sputum cytodiagnosis is effective in the early detection of lung cancer, and the kit allows patients to undergo testing by mail. In September 2015, Dr. Kato astounded the world with his discoveries at the World Conference on Lung Cancer in the United States.
“Almost all ground-glass opacity (GGO) shadows discovered in CT scans can be assumed to be early-stage cancers. Treatment at this stage generally results in a full recovery. There are various GGO patterns, so our research team decided to investigate which of those patterns could be treated effectively with PDT by excising GGOs with an endoscope and subjecting them to protein analysis.
“We were surprised to find that although the tissue around sites that were thought to be GGOs appeared completely normal under a microscope, the proteins were already showing signs of abnormality. This led us to hypothesize that the onset of cancer begins with protein abnormalities in the pre-cancerous stage. If this is true, it will be easy to predict the onset or metastasis of cancer, and we will be able to treat the disease much earlier than was previously possible. There was intense interest when I spoke about these findings. This discovery also has potential for use in drug development.”
Dr. Kato remains extremely active. Apart from his research into protein analysis, he is also working on a method to use PDT in the treatment of adenocarcinomas, which have until now been regarded as incurable.
“In addition to lung cancer, PDT is also effective and eligible for insurance cover as a method for the early treatment of esophageal cancer, stomach cancer and cervical cancer. I am confident that as lung cancer screening becomes more common and various challenges are overcome, PDT will play an increasingly important role. I’d like to leave this work to the next generation, including younger colleagues from my alma mater, but I feel that I have to carry on for the sake of the patients.” Dr. Kato laughs as he speculates that advances in medicine might extend the average lifespan to 100. If that happens, he would have another 30 years to spend on his work. The world still needs Dr. Kato.

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