REPORTS ON SEMINARS

(1) Seminar on "Lymphoproliferative Diseases in the U.S. and Japan"

The recent widespread use of surface marker analysis in studies of lymphoid tumors has made possible the confirmation of the different frequencies of lymphoid disorders in Japan and in Western countries. The relatively increased frequency of T-cell malignancies has been demonstrated in Japan, where certain B-cell tumors-including nodular lymphoma and chronic lymphocytic leukemia- are uncommon. In certain regions of Japan, the T-cell malignancies are associated with a type C retrovirus that is suspected of having a causative role. Recently, some cases of T-cell leukemia/lymphoma similar or identical to Japanese cases have been discovered in the United States and other Western countries. A better understanding of the similarities and differences between lymphoid disorders in Japan and the West was the subject of a recent conference sponsored by the U.S.-Japan Cooperative Cancer Research Program.
The following is a summary of this conference that was held in Seattle, Washington, on September 6 and 7, 1982; at this conference data on diseases in the United States and Japan were compared. The conference was made possible by the close cooperation and friendship of scientists of both countries. In addition, valuable contributions were made by distinguished investigators from England and Germany. The conference addressed issues of the etiology, epidemiology, and pathology of lymphoid malignancies as well as related benign disorders of the immune system. Special attention was focused on the immunologic phenotype, function, and ultrastructure of malignant lymphoid cells. Several unique lymphadenopathies (necrotizing lymphadenitis, multicentric lymphadenopathy resembling Castleman's disease, and immunoblastic lymphadenopathy-like T-cell lymphoma) were described.
Clinical differences between B- and T-cell lymphomas of immunoblastic and mixed (large and small cell) types were emphasized. New insights into Hodgkin's disease included attention to the difficulty of distinguishing Hodgkin's disease from certain peripheral T-cell lymphomas and the proposal of a new "candidate" cell for precursor of the Reed-Sternberg cell. An electron immunoperoxidase technique was used to demonstrate immunoglobulin synthesis in neoplastic cells from most cases of hairy cell leukemia. Newly made monoclonal antibodies were found to be useful to develop a hypothetical model of B-cell malignancies. Possible mechanisms by which B-cell malignancies develop in persons with congenital or acquired immune deficiencies were presented. Advances in the treatment of leukemia and lymphoma that were discussed included the advantages and limitations of bone marrow transplantation and the treatment of terminal deoxynucleotidyl transferase (TdT)-positive malignancies with inhibitors of TdT.
We conclude that an improved understanding of leukemia and lymphoma has resulted from a comparison of lymphocytic disorders in Japan and Western countries.

(2) Seminar on "Human Hepatocarcinogenesist"

The seminar was attended by seven Japanese and seven U.S. investigators. In addition, three Japanese observers who were present also made presentations. The seminar organizers were Drs. Wataru Mori and Hans Popper.
In the first session, Dr. W. Mori (University of Tokyo), as chairman, gave an overview emphasizing epidemiology and stressing the fact that the incidence of hepatocellular carcinoma has increased in recent years in Japan and possibly in the United States. Dr. R.L. Peters (University of Southern California) presented a new classification of hepatocellular carcinoma based primarily on gross appearance of the common tumors, and then described rare types, such as fibrolamellar carcinomas having a better prognosis. Dr. E. Farber (University of Toronto, Canada) discussed chemical carcinogenesis, following an approach more mechanism than agent oriented; it is a multistep process in which the initial several stages and the late processes are better understood than the long intervening period. Dr. T. Kitagawa (Cancer Institute, Japan) presented experimental studies identifying specific stages in hepatocarcinogenesis where transfer to cultures is possible, and also the effect of promoters on the cultures, which are different from skin carcinogenesis.
In the second session, Dr. H. Kurata (National Institute of Hygienic Sciences, Japan) described studies in the Philippines on man and in Japan on rats in which ethanol had synergistic effects with aflatoxin. Dr. G.N. Wogan (Massachusetts Institute of Technology) stressed that biostatistic studies of the available dose-response curves do not permit reliable extrapolation to the putative risk of very low aflatoxin exposures. He therefore introduced new methods to determine DNA adducts from aflatoxin B1 administration which may provide this information in man. Dr. H. Popper (Mount Sinai School of Medicine, New York) discussed the similarities of vinyl chloride-induced sequences in man and rodents, a model lesion assisting in regulatory action, particularly since the vinyl chloride-associated angiosarcoma is, because of its rarity otherwise, an important "signal tumor." Dr. M. Okudaira (Kitasato University, Japan) presented Japanese experiences with vinyl chloride exposure in man. Dr. C. Kido (Aichi Cancer Center, Japan) reported extensive experience with Thorotrast in Japan, where cholangiocarcinoma was the most frequent tumor.
In the third session, Dr. Okudaira described the relation of the carcinoma to alcoholic liver disease in Japan, where alcohol consumption has risen remarkably. Dr. S.W. French (Veterans Administration Medical Center, LMartinez, California) discussed alcohol abuse-associated hepatocellular carcinoma worldwide, and considered Mallory's hyalin as a preneoplastic marker. Drs. T. Nakashima and M. Kojiro (Kurume University, Japan) dealt with the relation of the carcinoma to schistosomiasis japonica; while hepatitis B infection is the important factor, schistosomiasis acts as promoter. Dr. S. Goldfarb (University of Wisconsin) described the relation of sex steroids to hepatic tumors and ascribed them a promoting effect in carcinogenesis.
In the fourth session, Dr. M.A. Gerber (Mount Sinai Medical Center, New York) reviewed the evidence for a causal relation between hepatitis B virus infection and hepatocellular carcinoma and then described morphometric studies of precursor lesions. Drs. O. Hino and T. Kitagawa (Cancer Institute, Japan) presented apparently the first hepatitis B virus DNA hybridization studies in Japan. They confirmed integration of viral DNA in hepatocellular carcinoma, but did not find it in hepatitis B marker negative hepatocellular carcinoma. Drs. T. Shikata and T. Uchida (National Institute of Hygenic Sciences, Japan) developed a non-A, non-B antigen/antibody system, and identified the antigen, which they demonstrated by immunoperoxidase techniques in hepatocytes around and sometimes in the cancer, suggesting that hepatitis non-A, non-B plays a role in hepatocellular cancer. Dr. Hans Popper (summarizing as co-chairman) emphasized the many new observations presented, and delineated unresolved problems as the possible subject of a future seminar. The participants strongly endorsed such repetition.



SEMINAR AGENDA AND PARTICIPANTS

(1) Second Seminar on Lymphoproliferative Diseases in
the U.S. and Japan
Fred Hutchinson Cancer Research Center, Seattle, Washington
September 6-7, 1982

AGENDA

PARTICIPANTS

UNITED STATES
E. Farber
Professor, Dept. of Pathology
Banting Institute
University of Toronto

S.W. French
Chief, Laboratory Service
Veterans Administration Center-Martinez

M.A. Gerber
Director of Laboratories
Mount Sinai Services
City Hospital Center at Elmherst

S. Goldfarb
Professor, Dept. of Pathology
Medical School
University of Wisconsin

R.L. Peters
Chief Pathologist
Ranchos Los Amigos Hospital

H. Popper
Mount Sinai Medical Center New York

G. N. Wogan
Dept. of Nutrition and Food Science
Massachusetts Institute of Technology

JAPAN
C. Kido
Aichi Cancer Center
Nagoya

T. Kitagawa
Dept. of Pathology
Cancer Institute
Tokyo

T. Nakashima
Kurume University
Kurume

M. Okudaira
Kitasato University
Tokyo

H. Kurata
National Institute of Hygenic Sciences
Tokyo

W. Mori
Professor of Pathology
University of Tokyo
Tokyo

T. Shikata
National Institute of Hygenic Sciences
Tokyo