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  • Yuzo Endo, M.D., Ph.D.
  • Masahito Hitosugi, M.D., Ph.D.
  • John E. Lewis, Ph.D.

Doctor’s Health Advice

Doctor’s Health Advice

Pathologist’s advice on how to combat cancer

No.14

Strategies for the treatment of advanced cancer in adult 2

Anticancer Drugs or Surgery?

If I were informed that I had advanced cancer in my body wherever it is, and that its metastatic area was limited, I would choose surgical intervention without any intention of anti-cancer drugs. Even if there were its metastasis in the liver, I would prefer to select surgery by a certain team of excellent doctors. The liver has strongly regenerative powers, and removing a part of it will not cause serious health problems. Although surgery of the liver is extremely difficult, it is still better than systemic or oral administration of chemotherapy, which must influence by all means adverse effects to the whole body and yet cannot kill cancer cells completely.

In place of general administration of anti-cancer drugs, one method of administration for anticancer drugs was selected, so-called hepatic arterial infusion (chrono-fuser treatment), which entails infusing anticancer drugs selectively into the liver slowly over several hours. For some reason, it is believed that infusing anticancer drugs at night might be more effective in terms of killing the cancer cells. Although there is no direct evidence whether cancer cell could grow faster in the night than in the daytime, I guess it has something to do with the speed of cancer proliferation. In another method, the catheter is induced into the liver through the artery, which is plugged by the substances of anti-cancer drugs leading to the obstruction of arterial vessels supplying nourishment to cancer cells. There are some other methods, such as collapsing blood vessels around the cancer to block the supply of nutrition to the cancer tissue. These methods are now disappointing to kill cancer cells completely. Surgical removal of metastatic foci no matter how many they might be.

Cancer cells that have metastasized to the lungs are extremely troublesome, because lung tissue doesn’t regenerate like the liver tissue. Removing even a portion of the lung consequently results in the decreased breathing capacity. It depends on where the cancer cells are located, but one method is to make a small incision in the lung and remove the metastasis by using small holes for endoscopes through the chest wall without cutting ribs or muscles.

By the way, there are some patterns of cancer metastasis. Rectal cancer will mainly metastasize to lung on the way of the inferior main vein to the heart and lung. On the contrary, cancer of the stomach and colon metastasize commonly to the liver in terms of portal vein stream. This tendency is dependent upon blood stream. In cases when metastasis to the brain is expected, it is difficult to decide whether preventive radiation should be delivered to the brain. If any, Gamma knife treatment in terms of target-oriented radiation may be also available for the treatment of brain metastasis. Therefore, surgery should be selected in the first place without intention of preferring of chemotherapy.

What and for what are tumor markers?

Generally speaking, methods of cancer treatment consist of surgery, radiation, and anticancer drugs. If early cancer is detected and removed surgically, it may be curable. As for advanced cancer, whether cancer cells remain or not is the critical issue for necessity of further treatment.

If cancer cells remain and secrete specific substances as its characteristics of production, they are called tumor makers which may be practical parameters to be surveyed and used as targets for efficacy of killing tumor cells. For example, increased PSA (prostate- specific antigen) in the blood sometimes provides an indication for early stage of prostate cancer. Also, in two-thirds of cases of large bowel cancer, CEA (carcino-embryonic antigen) is secreted from the cancer cells into the blood. Hepatocellular carcinoma, which is one of the liver cancer, often shows increase of  AFP (alpha-fetoprotein) in the blood. These substances are called tumor markers.

In the early stages of cancer, almost all tumor markers except for PSA can not be detected by the blood test. However, they are sometimes useful and practical for detection of advanced cancer only by the blood test. Furthermore, if each cancer had its own tumor marker, checking the tumor marker in the blood would be helpful to evaluate the efficacy of the treatment for killing the cancer cells. It takes for granted that outcome is mainly judged by the size of the cancer masses which are measured with CT scanning and magnetic resonance imaging, and so forth.

What is the ultimate treatment for cancer?

The ultimate treatment for cancer is to selectively destroy and eliminate only the cancer cells, by utilizing the premise of enhancing immune function to induce rejection of non-self like cancer cells, which unfortunately are self-derived cells.

The human body are composed of cells whose cell membrane has numerous “self” molecules, for example, human leukocyte antigens (HLA molecules). Blood type such as A, B, and O are dependent only upon cell wall of red blood cells. These are also materials for self-recognition. If cancer cells become “non- self” or “less-self”, then “self” white blood cells must try to eliminate the non-self cells in terms of immunological rejection. Immunological rejection must be the ultimate method of cancer treatment.  Cancer cells were originally derived from self cells and later transformed into cancer cells. They have changed only slightly, so they are not such fundamental changes as to cause non-self rejection. Gene therapy, in which non-self genes are inserted into self cancer cells, was developed by applying this concept. Some cancer cells have abnormalities in their genes related to proliferation or suppressing proliferation of the cells. Therefore, corrective therapy done by inducing normal genes into cancer cells may normalize cancer cells. These methods have been attempted for over 10 years, but they still require further improvement.

Immunological response is an extremely complicated phenomenon, and how it can be applied is the key in cancer treatment. In this method, immune cell function plays a major role, and therapies that promote slow rejections should be developed. Although it is a compromising position, methods that enable patients to coexist with cancer should also be developed and practical.

Research on non-self antigens for cancer cells has been conducted over the past 20 to 30 years, but tumor antigens, except for some specific cancers, have not been found yet. I have explained cancer development as one’s own self-cell changes gradually to become a cancer cell. Cancer cells continuously change but can stay in a patient without becoming non-self. I suppose that progressing cancer cells are becoming more and more less-self to non-self, but there is no evidence.

It has been revealed that antigenic substances on a cell membrane can change into non-self, with only slight changes of sugar chain antigenic substances. Research and development on tumor antigens are facing a deadlock, but on the other hand, the discoveries below have accumulated.

Many research results have been reported on immuneostimulatory functions of the sugar chain. Arabinoxylan from BioBran, Arabinomannan of Specific Substance MARUYAMA, Arabinogalactan of BCG, and Arabinogalactan of Mannatech are shown to have immunostimulatory actions. I suppose those immunostimulatory functions can be verified by the ability of T lymphocytes to produce interferon gamma. Activation of macrophages as well as NK cells would be considered a part of this immunostimmulatory function. Great attention should be paid to whether those immunotherapies are showing effectiveness.

Treatment effects of Specific Substance MARUYAMA on advanced cancer were reported in 2006. Nearly 200 stomach or bowel cancer patients, in stage 3 or 4, survived more than 10 years with only Specific Substance MARUYAMA, although it was regrettably not a double-blind experiment.

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Literature 1

Iwaki H, Iida, Nagatsumi, Endo: Reports on progressing bowel cancer cases with the use of Specific Substance MARUYAMA (SSM) more than a decade 2004-2005 : Japan Medical Journal 2006, No.4291, 67-72. (in Japanese)

Iwaki H, Iida, Nagatsumi, Endo: Reports on progressing bowel cancer cases (stage Ⅲ-Ⅳ) with the use of Specific Substance MARUYAMA (SSM) more than a decade, from chart s of 2004~2005 : Japan Medical Journal 2006, No.4314, 63-68 (in Japanese)

This series is coming close to the end. I would like to talk about multiple myeloma on the next essay because I have received many inquiries on this illness. I will talk about this topic based on my treatment experiences as a clinical immunologist at Tranomon Hospital.

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Yuzo Endo, M.D., Ph.D.

Yuzo Endo, M.D., Ph.D.
Hamamatsu University School of Medicine

1969.9: Graduated from Medical School, University of Tokyo Consultant pathologist in Hamamatsu University, Medical School, and Fujimoto General Hospital. Medical Consultant in conventional and integrative medicine.

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