INTERDISCIPLINARY PROGRAM AREA

ADMINISTRATIVE REPORT

SEMINARS AND MEETINGS

At last year's annual meeting we noted that binational research programs are especially suited to study of diseases that differ substantially in frequencies between the two countries--the more so if the diseases are approached in a novel way.

WORKSHOPS

The Interdisciplinary Program Area convened a workshop on "Differences in Lymphocytic Diseases Between the United States and Japan." Participants included epidemiologists, clinicians, and laboratory scientists from the U.S. mainland, Hawaii, and Japan. The workshop was held in Honolulu on March 11 and 12, 1981; a list of the participants and the agenda appear later in this report.
The rationale for the meeting was based on the observation that high rates for lymphoproliferative disorders are associated with low rates of autoimmune diseases. Among U.S. whites, lymphoma is more frequent in males, and autoimmune diseases in females (e.g., systemic lupus erythematosus-SLE, M:F=1:9; and Hashimoto's thyroiditis M:F=1:20). A reciprocal relation between the two categories of disease is also found when data from the United States and Japan are compared. Certain lymphoid neoplasms are rare in Japan, and certain autoimmune diseases are known or suspected to be substantially more frequent in orientals than in caucasians.
Deficiencies of Certain Diseases in Japan

1. Hodgkin's Disease: Absent first age-peak at 25 to 29 years, in contrast to all other countries studied to date.
   
2. Chronic Lymphocytic Leukemia: Frequency is near zero in Japan versus 30 percent of all leukemia in U.S. adults.
   
3. Follicular (non-Hodgkin's) Lymphoma: Almost absent in Japan as revealed at the meeting (based on a recent careful pathology review by Dr. Namba of the Mutual Relief Hospital in Kure, Japan).
   
4. Clinical Apparent Infectious Mononucleosis: Rare, perhaps because abortive infectious mononucleosis occurs early in infancy before the immune system has matured fully.

Excesses of Certain Diseases in Japan

1. Adult T Cell Leukemia Clusters: In eastern Kyushu and Okinawa (mapped in recent years), rarely if ever seen in western countries.
   
2. Kawasaki's Disease (Mucocutaneous Lymph Node Syndrome): First became epidemic in Japan and then appeared in other countries.
   
3. Subacute Necrotizing Lymphadenitis Clusters in Hokkaido: Seventy percent of the patients are women 20 to 35 years old; etiology unknown.
   
4. Takatsuki's Disease: Plasma cell dyscrasia with polyneuropathy of Guillain-Barre type and endocrine disorders, similar to Castleman's angiofollicular lymphoid hyperplasia in the United States, but apparently more common in Japan.
   
5. Kimura's Disease: A benign T cell lynphadenopathy with peripheral blood eosinophilia and elevated IgE levels, predominantly in males. It is similar to a very rare angiofollicular hyperplasia with eosinophilia in the United States.
   
6. Extranodal Non-Hodgkin's Lymphoma of the Stomach: In Japan with a lower frequency in the small intestine as compared with the United States.
   
7. Stomach Cancer Among Persons with Dermatomyositis: Among 155 Japanese with dermatomyositis, 22 had stomach cancer as compared with only 1 of 234 persons who had scleroderma.
   
8. Takayasu's Aortitis: Thirty-one new cases among Japanese males and 244 among females in a multi-hospital survey in 1975 (M:F=1:7.8). Prevalent cases for the year in 15 hospitals numbered 2,148. The corresponding numbers in the United States are unknown.
   
9. Hashimoto's Thyroiditis: 1,784 cases in a multi-hospital study in 1974 (M:F=1:12.4). In 15 hospitals, 1973 to 1975, 20.4 percent of 8,033 patients with thryoid disease had Hashimoto's thyroiditis. The corresponding frequency in the United States is 9 percent of thyroid operations (M:F=1:4).
   
10. Systemic Lupus Erythematosus (SLE): About four times more common in Japanese and other Asians than in caucasians in Hawaii.

With these ethnic differences in lynphocyte-related diseases in mind, the following collaborations were suggested:

1. Clinicians and epidemiologists in Honolulu extend their ethnic comparisons of the frequency of SLE to other relatively common autoimmune diseases (systematic arthritis, thyroiditis, and possibly rheumatoid arthritis).
   
2. Diagnosticians in the two countries determine if rare cases of Adult T Cell Leukemia in the United States differ from cases that cluster in Japan.
   
3. Clinicians and epidemiologists in Japan study the distribution and determinants of subacute necrotizing lymphadenitis in Hokkaido.
   
4. Epidemiologists and laboratory scientists in both countries develop a hypothesis concerning ethnic differences in T cell function to account for the excesses and deficiencies in the lymphocytic diseases listed above.

A "Symposium on Recent Topics in Cancer Research" was held in Osaka, June 12 and 13, 1980, in conjunction with the annual meeting of the Steering Committee for the binational cancer program. The Symposium was co-sponsored by the Japan Cancer Association. The agenda and list of participants are included later in this report.
From November 26 until December 4, 1979, three U.S. pathologists worked in Hiroshima and Nagasaki to provide U.S. collaboration with five Japanese pathologists in a review of 313 cases of breast cancer on file at the Radiation Effects Research Foundation (formerly the Atomic Bomb Casualty Commission). The purpose was to standardize and agree upon the classification of the cancer by subtype. The pathologists' contribution is a keystone for further epidemiologic studies, which can now be made with confidence as to the most precise diagnosis possible. The provisional report has been prepared by Donald E. Henson, M.D., on behalf of the United States pathologists.

EXCHANGE OF SCIENTISTS

Dr. Kasumi spent six months in Dr. Fortner's group studying recent advances in diagnosis and treatment of pancreatic cancer, especially in regard to Regional Pancreatectomy (RP) as advocated by Dr. Fortner in 1973. Dr. Kasumi witnessed four cases treated in this fashion: one by conventional pancreato-duodenectomy and 12 palliative treatments; and some with implantation of I¹²⁵ seeds. The RP-treated cases had severe complications of surgery. Dr. Kasumi wrote in his report, "I heartily appreciate his philosophy on Surgery of Regional Pancreatectomy and believe that this procedure must overcome the pessimistic pancreatic surgery at the present time, but the real surgical maneuvers and postoperative care are not so easy as to be imagined. It seems to be the most important in the Regional Pancreatectomy to keep a good teamwork among skillful surgeons and tight relationship between surgeons and anesthesiologists, hematologists, endocrinologists and other technicians during and after operation."