SUMMARY REPORTS OF EXCHANGE SCIENTISTS

1) JACOB FURTH,
Columbia University Presbyterian Medical Center Division of Health Sciences

Host Institution:
Dr. Kenjiro Yokoro, Professor, Pathology Hiroshima University
Dates of Visit: Hiroshima Univ. May 21-24, Nagoya Univ. May 25-26 Osaka Univ. May 27-28, 1979

Summary of Activities:
Participation at meetings of the International Association on Late Effects of Ionizing Radiation (IALE) and Cancer Research Programs. I discussed Experimental radiation carcinogenesis, Implication of virus in leukemogenesis, Mammary carcinogenesis, Differences between the different types of radiations. As I pioneered in these areas, I could participate in the respective seminars. I also amplified the presently prevailing concepts on related topics, on which I worked during the past few years. These include: induction of functional transplantable pituitary tumors of all pituitary cell types; their hormonal interrelationship; stages of carcinogenes from dependent to autonomous; mutagenesis vs. carcinogenesis; carcinogenesis without carcinogens (by unrepaired replication error of DNA). Discussed the mechanism of carcinogenesis by estrogens; induction of pituitary tumors by birth control pills and their conceivable prevention.

Additional Information
These International Symposia in Hiroshima on late effects on ionizing radiation and neoplasia were organized and excellently managed by Dr. K. Yokoro. Dr. A. Ito, his associate (also my former trainee and co-worker in N.Y.C.) met me in Tokyo on arrival and remained my guide and translator until I departed from Tokyo to Nagoya. The visits to Nagoya and Osaka were not in the original plan. Dr. A. Kunii, Professor of Experimental Pathology at the university of Nagoya, having learned of my projected trip to Hiroshima, invited me to delay my return to the USA by stopping at Nagoya. He organized a symposium for May 25 on “Cancer as viewed by Experimental Pathologists” The chairman of the conference was Dr. R. Akazaki (Honorable Director of the Aichi Cancer Institute). Here, a historical revue was given (in Japanese) by the chairman of the Department of Pathology, followed by discussions (translated for me by Dr. Kunii).
On the session, Dr. Kunii asked me to lecture on “Recollections of my life in Cancer Research.” This session was introduced and chaired by Dr. Hibino (Honorable President of the Nagoya National Hospital and Professor at Nagoya University).
May 26. Dr. Kunii took me to see Nagoya’s Scientific Institutions and brought me together with medico-biologic scientists. In Osaka, May 27 similar arrangements were made by Dr. Ueda. His invitation followed that of Kunii (The Universities in Nagoya and Osaka are modern, next in size and scientific standing to that of Tokyo).
My discussions at all seminars in Japan were ad hoc, since I was not preinformed about the subject of their presentation except that on ionizing radiation. Altogether, my trip to Japan was a joyous occasion which cemented supernational understanding and friendship both, scientific and cultural.


2) ROBERT H. YONEMOTO, M.D.,
City of Hope National Medical Center, 1500 East Duarte Road, Duarte, Callf. 91010

Host Institution:
Prof. Haruo Sugano, Cancer Institute Kami-Ikebukuro 1-37-1, Toshima-ku, Tokyo 170, Japan
Dates of Visit: May 31-July 7, 1979

Summary of Activities:
The object was to secure first hand information regarding the present status of breast cancer in Japan and how it relates to the situation in U.S. Ten institutions were visited and approximately twenty some sessions were held to exchange current status of research as well as clinical progress by exchanging information. In addition to these individual small sessions, formal lectures were given by me on the topic of “Present Status of Breast Cancer in U.S., “Immune Monitoring of Breast Cancer Patients” “Application of Transfer Factor as Immuno-therapeutic Agent in Breast Cancer” “A New Microslide Leukocyte Migration Inhibitaion Assay to Monitor Cell Mediation Immunity in Breast Cancer Patients.”
The information I secured was invaluable from a standpoint of getting insight into the changing epidemiological picture of breast cancer in Japan which directly leads one to the understanding of causitive agents in breast cancer.
Publication resulting from this visit is “Breast Cancer in Japan and U.S.A.” submitted to Archives of Surgery in January 1980. This same paper was also presented to the Southern California Chapter of the American College of Surgeons.

Abstract of “Breast Cancer in Japan and U.S.A.”
Cancer of the breast represents the most common cancer (27% of all malignancies) among U.S. women, whereas in Japan it ranks third behind stomach and uterus in its frequency. In spite of the relative low incidence of breast cancer in Japan, a sharp increase in the frequency has been noted since 1966, which is decidedly related to change in dietary patterns in the Japanese women. An increase in over 250% of fat dietary intake has been noted during the past 15 years, mostly in the form of pork. Cancer is detected at an earlier stage in Japan as compared wit the U.S. and consequently, the end result is significantly better. But the improved results could not be totally explained on the basis c early detection, since stage for stage the Japanese series appears to be consistently better than the U.S. series by 10% in their 10 year survival rates. The effect of Atomic bomb radiation prevails even to this date. Women 10-30 years of age at time of A-bomb exposure show a continuous increase in the cumulative risk of breast cancer.


3)-5) BREAST CANCER PATHOLOGY STUDY GROUP
Members of the Study Group:
Dr. Donald E. Henson, Laboratory of Pathology, DCBD, NCI, National Cancer Institute, Bethesda, Md.
Dr. William Hartmann, Department of Pathology Vanderbilt University Nashville, Tenn.
Dr. Robert V.P. Hutter, St. Barnabas Medical Center, Livingston, NJ.

Sponsor: Dr. Haruo Sugano
Hosting Institute: Radiation Effects Research Foundation (RERF) Hiroshima and Nagasaki, Japan
Dates of Visit: November 23 to December 5, 1979

Summary of Activities:
“Report of Visit to Nagasaki and Hiroshima, November 24 thru December 5, to Review Histologic Material on Breast Cancer Patients Exposed to Atomic Irradiation”
Reported by Dr. Donald E. Henson, Laboratory of Pathology, DCBD, NCI

Left U.S. on Saturday, November 24, along with Drs. Hutter and arrived at Nagasaki on Monday, November 27 at 2:00 p.m. after an overnight in Tokyo. We were met at the airport by Dr. Asano, Pathologist at RERF in Nagasaki, and Dr. Tokuoka, Pathologist from Hiroshima University, and taken to the RERF building to organize our work. We spent the entire next day, Tuesday, November 28, reviewing case material from women exposed to atomic irradiation in Nagasaki. The plan of the study was to review the cases blind; that is, the three pathologists did not know in advance which case represented a control (non-exposed), or irradiated patient. In addition, the diagnoses were recorded independently so that one pathologist did not know the diagnoses of the other two. Seventy cases were reviewed in Nagasaki.
The following morning we traveled by train to Hiroshima and started our work on the afternoon of arrival. Our study which included 246 cases followed the same format used in Nagasaki. In Hiroshima, Wednesday, Thursday and Friday were required for the review. We were assisted by Dr. Tokunaga who helped with the clerical work and organization. On Friday afternoon, the U.S. pathologists reviewed the case material as a group in order to resolve any disagreements in diagnosis.
On Sunday, December 2, the five Japanese pathologists who had reviewed the cases in November prior to the arrival of the U.S. pathologists, assembled at RERF in Hiroshima. Included in the group were Dr. Yamamoto from RERF and Dr. Sakamoto from Tokyo, in addition to Dr. Asano, Dr. Tokuoka and Dr. Tokunaga.
On Monday, December 3, pathologists from both countries met together in order to review the diagnoses and resolve any differences in diagnosis and classification that might exist. There was surprisingly little disagreement; only two cases were not resolved. In both cases, however, there was complete agreement that the diagnosis was cancer. The disagreement involved the particular histologic type. We attributed our general success to the fact that a preliminary meeting was held by the participating pathologists in Nashville, Tennessee in July, which afforded us the opportunity to become familiar with the classification scheme and diagnostic criteria used by the different pathologists. The classification scheme that we adopted was a combination of the World Health Organization’s histologic classification of breast cancer modified to include the Japanese classification. By including the WHO classification, studies conducted in other parts of the world could be readily compared with our studies in Japan.
On Tuesday, December 4, the results of our work were presented in preliminary form to the staff of RERF including Dr. Sugano, Director of the Cancer Institute in Japan, who attended. Of 70 cases reviewed in Nagasaki, 63 were considered to be definitely cancer. In 6 cases, organs containing metastases were available but sections from the primary breast lesion could not be located. In these cases, a diagnosis of breast cancer was considered presumptive based on the appearance of the metastatic tumor. Of these 63 cases, 42 were from irradiated patients and 21 controls. Of 246 cases reviewed at Hiroshima, 240 were definitely considered to be cancer. This figure included 107 exposed and 133 non-exposed patients. It should be noted that a case of primary lymphoma of the breast was discovered in the control group. Again, 6 cases were not diagnosed as cancer, but considered presumptive since sections from the primary breast lesion were not available.
In addition to the women with breast cancer, a pilot study was conducted which consisted of reviewing breast material from 56 women who were exposed to 100 rads or more, but who did not have a diagnosis of breast cancer. The purpose of the review was to search for precancerous lesions that did not progress to neoplasia or persistent atypical hyperplasia. Our results showed no hyperplasia or atypical lesions, but atrophy, some degeneration of fat, and a peculiar fibroelastotic degeneration of the stroma, a change that is known to be associated with irradiation. These findings were thought by the pathologists to warrant further studies on the potential effects of irradiation on breast tissue.
There was general agreement that the bi-national study was a successful one. A list of patients indicated by master file numbers along with the final diagnoses will be submitted to RERF. In addition, results of the study will be published in a scientific journal.
During the general summation on December 4, and during informal discussions that followed, there was a consensus that the work should be pursued. It was decided to expand the pilot study to include appropriate controls and a larger number of patients because of the unexpected finding of fibrosis and severe atrophy. There was some discussion but no consensus regarding the extent these lesions occur in the normal breast of Japanese women. Furthermore, Dr. Sugano was enthusiastic about the possibility of RERF sponsoring a symposium on the acute, chronic and long-term effects of radiation on breast tissue. The symposium seems timely in view of the increase in our knowledge concerning the affects of irradiation on breast tissue. Finally, it should be noted that Dr. Tokunaga, one of the participating pathologists, will work in the U.S. as a Visiting Scientist for three months beginning in February. He will review, as one task, breast material removed from women who had a diagnosis of cancer and who received large therapeutic doses of irradiation prior to mastectomy. In addition, a number of cases have been collected concerning women who had a diagnosis of chronic mastitis and who were treated by irradiation and subsequently developed cancer. It is hoped that Dr. Tokunaga will be able to review these cases while in the U.S.
On behalf of the participating U.S. pathologists, I would like to thank the staff at RERF both in Hiroshima and in Nagasaki as well as the Japan Society for the Promotion of Science and the NCI for approving and supporting this work. We hope to be able to obtain additional support for future studies related to radiation and the breast.


6) MASAYOSHI TOKUNAGA, M.D.,
IInd Department of Pathology, Faculty of Medicine, Kagoshima University

Host Institution:
Dr. Donald E. Henson, Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Md.
Dates of Visit: January 15 to May 4, 1980

Summary of Activities:
A series of epidemiological studies have indicated a significantly greater incidence in the occurrence of breast cancer in Japanese women exposed to atomic irradiation than comparable women not exposed. The purpose of this study is to compare the histological differences of breast cancer cases exposed and non-exposed. There were 303 breast cancer cases, 149 irradiated and 155 non-irradiated, among the extended LSS sample of RERF. Five Japanese and three American pathologists reviewed the slides.
The results of the study showed no significant difference in the distribution of the histological type between exposed and non-exposed groups or between two cities, Nagasaki and Hiroshima. There is no significant difference in either group in the distribution of histological types according to age of diagnosis or from the time of age at bombing to diagnosis. The age distribution of breast cancer cases at the time of bombing for the exposed and non-exposed groups show significant different among these two groups.