SUMMARY REPORTS OF EXCHANGE SCIENTISTS

(1) Mitsuru Mori
Department of Public Health
Sapporo Medical College

Sponsor and Host Institute:
Professor Brian E. Henderson
Department of Preventive Medicine
University of Southern California School of Medicine
Dates of Visit October 24 - December 23, 1986

Summary of Activities:
The survey of the case-control study on ovarian cancer had been conducted from 1981 to 1985 in Hokkaido, Japan. The data collected through this survey were brought to the University of Southern California (USC) in the form of IBM punch cards. Those data were analyzed by the sophisticated software package for epidemiological researches, namely the “EPILOG,” which was originally established by Dr. J. Buckley of the USC. The risk factors of ovarian cancer were statistically evaluated by the multivariate analyses such as the conditional logistic regression method as well as the univariate analyses such as the maximum likelihood estimation of relative risks. The results obtained by those analyses were as followed: Ovarian cancer risk was increased in single women (P<0.01) and in women with a family history of breast, uterine, or ovarian cancer in a mother or sister (P<0.001). Conversely, risk was decreased in women who had experienced a live-birth (P<0.001), an induced abortion (P<0.05) or who had had permanent sterilization by tubal ligation (P<0.05). Each of these factors remained significant when adjusted for each other using logistic regression analysis. The odds ratio for ovarian cancer decreased significantly with increasing number of live-births (P 0.001). Furthermore, a significant negative association between anovulatory periods and ovarian cancer risk was noted (P<0.01). The discussions about those results were carried out with the epidemiologists not only at USC but also at the National Cancer Institute (Bethesda) and at the University of Washington (Seattle), where I visited under this program. Dr. J.T. Casagrande of USC has proposed that incessant ovulation provides the stimulus for the division of epithelial ovarian cells, and that ovarian cancer risk is directly related to the frequency of such periods of active cell division. Under this hypothesis, total duration of anovulatory periods would be expected to reduce the risk. Total anovulatory period was significantly shorter among ovarian cancer patients than among the controls, and this finding would suggest that the number of live-births directly reduces the incidence of ovarian cancer Moreover, some significant reports of familial associations of breast, uterine, and ovarian cancer were notified through the discussions. Thereafter, the manuscript concerning this case-control study on ovarian cancer has been developed, which is ready to be submitted to one of the appropriate journals.



(2) Okio Hino
Department of Pathology
Cancer Institute. Tokyo

Sponsor and Host Institution:
Dr. Charles E. Rogler
Albert Einstein College of Medicine
Liver Research Center, New York.
Dates of Visit: August 13-September 27, 1988

Summary of Activities:
I visited at Albert Einstein College of Medicine, Liver Research Center, New York, and worked on a collaborative research project with Dr. C. E. Rogler. We extracted RNA from hepatocelluiar carcinoma cells and did a Northern blot analysis using flanking cellular sequences of HBV DNA integrations as probes. We could not detect any transcription from them.
I attended the Cold Spring Harbor Conference of HBV and gave two presentations: “HBV integration and rearrangement sites implicate the DRI sequence in the viral DNA integration mechanism” and “Formation of transgenic mice constructed obtained from human hepatocellular carcinoma.” (August 22, 1986)
I visited at the Pennsylvania Zoo, Penrose Institute, Philadelphia. I examined microscopically the histology of liver specimens from WHV carrier woodchuck. (August 22, 1986)
I visited at Baylor College of Medicine, Department of Virology and Epidemiology, Houston, and gave a seminar on “Hepatitis B virus infection and hepatocellular carcinoma.” (September 11-16, 1986)
I visited at the National Cancer Institute laboratory of Viral Carcinogenesis, and gave a seminar on “Hepatocarconogenesis and hepatitis B virus.” (September 18-20, 1986)
I visited at the Fox Chase Cancer Center and discussed hepatitis viruses with Drs. Blumberg, Feitelson, London, O’Connell and Mason. (September 24, 1986)

Comments for JSPS
The JSPS fellowship program is a very valuable program. The interactions and collaborations I was able to develop during my stay in USA were valuable for me.



(3) Isamu Kino, M.D.
First Department of Pathology
University of Hamamatsu School of Medicine

Sponsor and Host Institute:
Dr. Leslie H. Sobin, M.D.
Department of Fastrointestinal Pathology
Armed Forces Institute of Pathology
Dates of Visit: November 25-December 24, 1986

Summary of Activities:
Review of Gastric Cancer in Minneapolis, Minnesota
Resected cases (including biopsy and resection) and biopsy cases of stomach cancer in University of Minnesota Hospital and Methodist Hospital in Minneapolis were examined histologically. Two cases of early cancer were excluded. The cases of gastric cancer following gastrectomy were also omitted.
There were 67 cases, including 42 resected cases, between 1978 and 1983 in University of Minnesota Hospital, consisting of 44 males with a mean age of 64.4 years and 23 females with a mean age of 68.8 years. There were 70 cases, including 51 resected cases, between 1980-1985 in Methodist Hospital, comprising 50 males with a mean age of 68.3 years and 20 females with a mean age of 75.8 years.
In both hospitals, out of 71 males, in whom the location of cancer was described, 21(29.6%) were located in the antrum (A), 14(19.7%) in the mid-portion(M) and 46(64.8%) in the proxical portion (Prox). Especially in the University Hospital, in 18 cases out of 35 males the lesions were located in the cardia (gastroesophageal junction). Out of 33 females in both hospitals, 17(51.5%) were located in A,4(12.1%) in M and 11(36.4%) in Prox.
Regarding histological grading in both hospitals, out of 50 males, in whom histological typing could be made, 12 were classified as well differentiated adenocarcinoma (W) (Broders 1-2; papillary and tubular, well differentiated, according to Japanese Research Society for Gastric Cancer), 34(36.1%) as moderately differentiated (M) (Broders 3; tubular, moderately differentiated), 22 (51.2%) as poorly differentiated adenocarcinoma (P)(Broders 4; signet-ring cell carcimona and poorly differentiated adenocarcinoma) and 2(2.1%) as mucinous adenocarcinoma (Muc). Out of 43 females in both hospitals, 8(18.6%) were classified as W, 9(20.9%) as M, 22(51.296) as P and 4(9.3%) as Muc.
A Comparative Study in Shizuoka, Japan, and Minnesota
Based on the above data, in Japan stomach cancers, excluding early, multiple and rest-stomach cancers, were classified with the same method as the Minnesota cases.
There were 395 resected cases in Hamamatsu University Hospital and Fujieda City General Hospital, both of which are situated in Shizuoka Prefecture, between 1978 and 1983, comprising 234 males with a mean age of 62.2 years and 161 females with a mean age of 59.2 years.
Out of 224 males, in whom the location could be determined (i.e., too advanced cases to localize the lesions were excluded), 113 (50.4%) were located in A, 58(25.9%) in M and 53 (23.7%) in Prox. In these, 17 cases (7.6%) were located in the cardia. These figures clearly showed a predominance in the proximal portion of the stomach, especially in the cardia in Minnesota, while there was a predominance in the antrum in Shizuoka.
In 153 females, 57 (37.2%) were located in A, 46 (30.1%) in M and 50 (32.7%) in Prox. Thus, there was no predominance in the proximal part in Minneapolis.
Regarding histological classification, out of 233 males, in whom histological typing was made, 47 (20.2%) were classified as W, 73 (31.3%) as M, 103 (44.2%) as P and 10 (4.3%) in Muc. These figures disclosed no definite difference in the histological pattern between Minnesota and Shizuoka.
In 159 females 24 (15.1%) were classified as W. 42 (26.4%) as M, 89 (56.0%) as P and 4 (2.5%) in Muc. These figures did not demonstrate a significant difference between Minnesota and Shizuoka either.
According to the Atlas of Cancer Mortality for U.S. Counties published by NIH, kindly provided by Dr. Miller, NIH. Minnesota is one of the states where mortality of gastric cancer is the highest in the United States. Therefore, the figures regarding the location and histological grading in Minnesota do not necessarily represent the figures in the United States in general. In addition, standardization of age distribution is necessary for further analysis because there was some difference between Minnesota and Shizuoka.
The frequency of the “fundamental” type of gastric cancer is similar in Japan to that in Minnesota. The “supplementary” type, environmentally influenced, predominates in the gastric antrum in Japan, and may be related to the extent of intestinal metaplasia.
Standard of Histological Diagnosis of Gastric Cancer in the United States and Japan
Discussion was held with the pathologists who specialize in gastrointestinal pathology, particularly on the standard of histological diagnosis of gastric cancer.
Dr. H. Goldman: Beth Israel Hospital in Boston, agreed to the diagnosis of malignancy in about half cases of very well differentiated adenocarconoma of the stomach brought from Japan. However, he disagreed in the other half and diagnosed them as severe dysplasia.
Dr. Si-Chi Ming, Temple University in Philadelphia, agreed with the diagnosis of malignancy in most cases of very well differentiated adenocarcinoma of the stomach. In the rest of the cases he favored the diagnosis of carcinoma in situ. Dr. L.H. Sobin, AFIP in Washington, also favored the diagnosis of carcinoma in situ in cases of what Japanese pathologists call focal carcinoma in adenoma of the colon.
A meeting between several American and Japanese specialists in gastrointestinal pathology is proposed to discuss possible differences in the standard for diagnosing gastric cancer, carcinoma in situ, adenoma and dysplasia.