For the purpose to know whether the annual increase of leukemia incidence in Japan is due to some leukemogenic factors or due to the increased detection
rate, the authors made some statistical survey of autopsy cases in which the
diagnosis is reliable and not any type of leukemias escape the detection. The
results showed that acute leukemias, which are found mostly in younger age, is
actually increasing. In addition, it has been deduced that among the suspected
factors the increase in ionizing radiation will be one of the most probable factors
for the increase in leukemia incidence</p

Asakura, Hikaru

Hamada, Hisao

Hayashi, Kenji

Katano, Takashi

Matsuoka, Kenichi

Monden, Hisashi

Nakatsuka, Ayako

Seki, Shuji

Seno, Satimaru

Shibata, Takashi

Toyama, Yuki

English

Okayama University Digital Information Repository

Leukemia autopsies in Japan

Okayama University Scientific Achievement Repository

Acta Medica OkayamaVolume 18, Issue 1 1964 Article 5FEBRUARY 1964Leukemia autopsies in JapanSatimaru Seno, Okayama UniversityHisashi Monden, Okayama UniversityTakashi Shibata, Okayama UniversityShuji Seki, Okayama UniversityHikaru Asakura, Okayama UniversityHisao Hamada, Okayama UniversityKenichi Matsuoka, Okayama UniversityYuki Toyama, Okayama UniversityTakashi Katano, Okayama UniversityKenji Hayashi, Okayama UniversityAyako Nakatsuka, Okayama UniversityCopyright c©1999 OKAYAMA UNIVERSITY MEDICAL SCHOOL. All rights reserved.Leukemia autopsies in Japan∗Satimaru Seno, Hisashi Monden, Takashi Shibata, Shuji Seki, Hikaru Asakura,Hisao Hamada, Kenichi Matsuoka, Yuki Toyama, Takashi Katano, KenjiHayashi, and Ayako NakatsukaAbstractFor the purpose to know whether the annual increase of leukemia incidence in Japan is due tosome leukemogenic factors or due to the increased detection rate, the authors made some statisticalsurvey of autopsy cases in which the diagnosis is reliable and not any type of leukemias escapethe detection. The results showed that acute leukemias, which are found mostly in younger age, isactually increasing. In addition, it has been deduced that among the suspected factors the increasein ionizing radiation will be one of the most probable factors for the increase in leukemia incidence∗PMID: 14201062 [PubMed - indexed for MEDLINE] Copyright c©OKAYAMA UNIVERSITYMEDICAL SCHOOLActa Med. Okayama 18, 45-52 (1964)LEUKEMIA AUTOPSIES IN JAPANSatimaru SENO, Hisashi MONDEN, Takashi SHIBATA,Shuji SEKI, Hikaru ASAKURA, Hisao HAMADA,~enichi MATSUOKA, Yuki TOYAMA, Takashi KATANO,Kenji HAYASHI and Ayako NAKATSUKADepartment of Pathology, Okayama University Medical SchoolOkayama, Japan (Director: Prof. S. Seno)Received for publication, February 15, 1961The incidence of leukemia is now increasing gradually year by year inseveral countries of the world as can be seen from the statistical investigationsreportedl - 6• This is also the case in Japan6 - 1\ This increase may be due tothe increased detection rate by the improvement of diagnostic methods andby the development of the social security system, but there seems to be anactual increase in the number of the cases. According to the opinion of DoLL16,the number of leukemia is increasing also in England and leukemia seems tobe actually increasing at least in younger age, though the increase in older ageappears to be indirect one, that is, due to the increased detection rate justmentioned. If the leukemia incidence is actually on the increase, it is a veryserious social problem and the cause of it must urgently be attacked for findingthe way to eradicate the very cause of this disease. In order to eliminate theindirect factors, which may lead to an erroneous judgment of the statisticaldata, autopsy cases have been observed, because in autopsy leukemias whichare difficult to detect clinically can never be missed and the diagnosis is veryreliable. From this standpoint, in this paper the observations on the autopsycases in the past five years are reported for the purpose to get more reliableinformation whether leukemias have actually increased or not. Observationswere also made with respect to sex, age and type of leukemias.OBSERVATIONSPrior to the demonstration of the detailed statistical works on autopsy casesit may be worthwhile to introduce. briefly the population of Japan, its annualincrease in recent years, and mortality rate. The population in Japan wasabout 91,000,000 in 1957 and it has increased by about 800,000 a year but thenumber of annual deaths has remained almost unchanged, about 700,000 peryear16• The incidence of leukemia in 1958 was 2.64 per 100,000 population,which is 1.7 times that in 1951 and this means about 2,400 to 2,500 leukemic451Seno et al.: Leukemia autopsies in JapanProduced by The Berkeley Electronic Press, 196446 S. SENO et al.Table 1 Changes in mortality from leukemia andlymphosarcoma for the period of years from 1951to 1958. Mortality per 100,000 population.I"::~I Leukemia I LymphsarcomaI 1951 1.58 0.521952 1.67 0.52I1953 1.90 0.611954 2.12I0.721955 2.28 0.791956 2.47 I 0.731957 2.43 0.811958 2.64 0.82'51/'58I1: 1.7 I 1: 1.6deaths per year in Japan (Table 1).In the last five years (1957-1961)2,475 of autopsy leukemias inclu-ding the leukemic and aleukemictumors of hematopoietic organshave been reported17• Consequently,about 1/7 of the total leukemicdeaths has been autopsied and thisnumber will be enough to makesome statistical observations.In autopsy cases, too, both ofactual autopsy number and the rateof leukemic numbers to the totalautopsies have increased year byyear (Table 2). Observations divided into each type of leukemias revealed thatthe increase is solely in acute leukemias while the other types of leukemia showTable 2 The number of total and leukemia autopsy cases duringthe five years from 1957 to 1961.I II I I IYearI1957 1958 1959 1960 1961LeukemiaIIIi II IAutopsies 273 I 445 510 ! 598 I 649i(LA)I! III iI I IITotal autopsy I 6,391 i 9,586I10,427 i 11,113I 12,483Inumber (TA)III IIIILA/TA (%) I 4.3 I 4.9 I 4.9 I 5.4 5.2III\ IIalmost no increasing tendency both in actual number and in the rate to the totalautopsy number (Fig. 1). Among acute leukemias, acute myeloid leukemia hasa decidedly high incidence in Japan. Consequently, the increase in acutemyeloid leukemia is mainly responsible for the increase of acute leukemias (Fig.1).The age distribution shows a higher rate of acute leukemia in younger ageas in other countries18, and acute myeloid leukemia is also high in incidence inyounger age (Fig. 2). This signifies that the increase in acute leukemias as awhole is mainly attributable to the increase in leukemia in younger age.The difference in the incidence as to sex has been observed and theleukemia incidence in male proved to be higher than that in female (Table 3).This coincides with the observations of leukemic deaths in Japan6 as well as in2Acta Medica Okayama, Vol. 18 [1964], Iss. 1, Art. 5http://escholarship.lib.okayama-u.ac.jp/amo/vol18/iss1/5262422201616141210e642Leukemia Autopsies in Japan~~_ CMl... - ... --------------- ALLAlU-- --------------------- Cll1957 1956 1959 1960 196147Fig. 1 Yearly change of the rate of autopsy number of leukemia in each typeto the total autopsies. AL: Acute leukemia, AML: Acute myeloid leukemia, SL:Specific type of leukemia, ALL: Acute lymphatic leukemia, ALU: Acute leukemiaof undifferentiated type, CLL: Chronic lymphatic leukemia, CML: Chronic myelo-genous leukemiaTable 3 Autopsy number of leukemia (L), total autopsy number(A) and the ratio L/A in male and female (1957-1961)I--~-I IYear 1957 1958 1959 1960 1961 MeanL 187 280 332 397 406 320Male A 4,026 5, 771 6.015 6,904 7,694 6,082I L/A 4.6 4.9 5.5 5.8 5.3 5.3I (%)IL 86 165 178 201 239 174Female A 2,365 3,329 3, 785 3,987 4,588 3,610L/A 3.6 5.0 4.7 5.0 5.2 4.8(%)other countries19• Further observations in detail by dividing into each leukemictype has revealed that acute myeloid leukemia is not concerned with the diffe-rence in sex. The main difference has been recognized in leukemia of specifictype which is mainly composed of the leukemic and aleukemic tumors of hema-3Seno et al.: Leukemia autopsies in JapanProduced by The Berkeley Electronic Press, 196448 S. SENO et al.topoietic organs, e. g. lymphosarcoma, reticulosarcoma, chloroma, myeloma,etc. (Table 4). These are rather low in incidence in younger age, and theyAL.' '""SiJ ~",- .. _ •• -----'",/\,i" '\., ,I ',I,-,,,. ,", ', , I: .I",,,,I,I,,I80" ........., ..,'2) 10 3'5------ .., ." '''''......-- ...............ALLALU "o ) 10 151020%305040708060Fig. 2 Age distribution of acute, chronic and specific type of leukemias autopsiedduring five years (1957-1961). Each curve shows the percentage of the number ofleukemia to the total number of leukemia autopsies in the corresponding age. ForAL, AML, SL, ALL, ALU, and CL see Fig.!.Table 4 Incidence of each type of leukemia in male and female (1957-1961)~I IAL AML AFL ALU I CL CML CLL I MoL I SLI~~---=:::!-N-O-.-,'-1----=-1::-:97;;;--1-5-9--2-8----10--1-----:3:-"8:----3-2----6- --U-I-WTMale I <:) 1-0-.6-5--0=-.5-c"2--0-='.0"-9--0-.-'-03-1--0.-1-2--0-.1-0--0-.-02-1--0-.-04- -0-.-54-1FemaleNo.R(%)1190.64940.52110.06110.06250.14200.1150.0380.0490I----I0.49 I4Acta Medica Okayama, Vol. 18 [1964], Iss. 1, Art. 5http://escholarship.lib.okayama-u.ac.jp/amo/vol18/iss1/5MaleFemaleLeukemia Autopsies in Japan 49II SLI R L C M 0I No. ! 373 152 28 110 46j---II R iI 1.23 0.50 0.08 0.36 0.15I (%) III No. I 198 48 9 52 21I--I R I 1.09 0.26 0.23 0.28 0.12I (%)increase with advance in age (Fig. 2). Thus, it can be said that there is hardlyany difference in the incidence of acute leukemia between male and female atleast in the autopsy cases observed.COMMENTAs just demonstrated the observations on the autopsy cases showed thatthe autopsy number of leukemic deaths is increasing year by year20• This coin-cides with the annual increase of leukemic incidence as observed in leukemicdeaths in 100,000 population6• And yet the observations on the autopsy casesgive a reliable information for the actual increment of leukemia. Data showthat leukemia is increasing certainly by some unknown factor or factors. Incontrast to observation in U. S. A.1,2 where the leukemia in older age is increas-ing, the leukemia that is on the increase in Japan is acute leukemia in youngerage both in male and female. In England the incidence of acute leukemia isincreasing, though in adult ages. As the acute myeloid leukemia is extremelyhigh in incidence among acute leukemias in Japan, the annual increase is mainlyattributable to the increase in this type of leukemia in younger age. In the ob-servations of autopsy cases the increased incidence of leukemia by the increaseddetection rate cannot be accounted as the factor misleading to an erroneousjudgment is minimized. Nor is there any possibility that leukemias are antopsiedin an especially higher rate in recent years than in the other diseases. Besidesthis, the decrease in deaths from other diseases that had been formerly thehighest causative factors for death like tuberculosis and other infectious diseases,may be an indirect factor responsible for the increase in leukemic deaths as inother malignant neoplasms. This will be true in the death of adult to older age,but in younger age the situation is completely different from leukemia in thoseof older age, because the probability of suffering from leuk~mia in those whosurvived through the diseases will be less.Therefore, it is reasonable to deduce that the leukemia incidence in childrenis actually increasing. Consequently, the annual increase of leukemia in Japan5Seno et al.: Leukemia autopsies in JapanProduced by The Berkeley Electronic Press, 196450 S. SENO et al.will be an actual increase by unknown causative factors.Among suspected factors leukemogenic virus may possibly be included. Insome cases of animal leukemias, viruses are concerned but in human leukemiathere seems to be no definitive evidence of virus involvement though someauthors claim virus to be a causative factor21, 22. Besides virus, the ionizingradiation is concerned with the onset of leukemia in animal and it is also in-,criminated in human leukemia. A high incidence of leukemia among thosehandling X-rays suggests2S that ionizing radiation should be an importantfactor for the induction of human leukemia. The higher incidence of leukemiaamong those exposed to the atomic bombs in Hiroshima and Nagasaki and thehighest rate of acute myeloid leukemia also support this view24- 28• The ionizingradiation in atmosphere will probably be increasing by repeated fission explo-sions.Observations conducted on the incidence of leukemias by dividing theperiods into the ones before and after the fission explosions may contribute to.clarify whether or not the ionizing radiation would be a prbable cause, if thefactors responsible for the increase of the detection rate are taken into considera-tion. The curve of leukemia incidence in Japan shows an incessant increaseof the incidence but it shows a refraction at the Second World War into the age-of nuclear fission6• In the former the increasing tendency was slow and gradualbut in the latter it has been rather steep in the increasing curve. In the periodbefore the War and the gradual improvement in the diagnostic method mighthave been concerned with the increase. But after the \Var the social securitysystem has been set up widely, especially in the last several years, so that theincreasing rate of detection of leukemias will not appreciably affect the statistical<lata. In spite of this the leukemia incidence has increased from about 2,200 casesto 2,700 in these five years. This means that an increase of 24.5 to 28.5 per100,000 population. Indeed, the incidence of leukemias in Japan in 1957 wasabout 2.5 times that in 1947. During the same decade there was an increase ofthe leukemia incidence of about 1.6 times in the U. S. A. and Canada, and about1.4 times in England and Denmark6• These data amply disclose how great isthe increase in the incidenee of leukemias in Japan. All of these data togetherwith those obtained from the observations on autopsied leukemias suggest thatthe increase in ionizing radiation in atmosphere is the most probable factorresponsible for the rapid increase of leukemia incidence in recent years in Japan.This coincides with the view of CURT-BROWN and DOLLS.SUMMARYFor the purpose to know whether the annual increase of leukemia incidence6Acta Medica Okayama, Vol. 18 [1964], Iss. 1, Art. 5http://escholarship.lib.okayama-u.ac.jp/amo/vol18/iss1/5Leukemia Autopsies in Japan 51in Japan is due to some leukemogenic factors or due to the increased detectionrate, the authors made some statistical survey of autopsy cases in which thediagnosis is reliable an& not any type of leukemias escape the detection. Theresults showed that acute leukemias, which are found mostly in younger age, isactually increasing. In addition, it has been deduced that among the suspectedfacto~s the increase in ionizing radiation will be one of the most probable factorsfor the increase in leukemia incidence.ACKNOWLEDGEMENTWe gratefully acknowledge the kind cooperation of staffs of pathological laboratories ofuniversities and colleges by supplying us with the necessary data for the completion of thisreport.REFERENCES1. COOKE, J. v.: The occurrence of leukemia. Blood 9, 340, 19542. GUNZ, F. W. and HOUGH, R. F.: Acute leukemia over the age of fifty, A study of itsincidence and natural history. Blood 11, 882, 19563. CURT BROWN, W. M. and DOLL, R.: Adult leukemia. Trend in mortality in relation toaetiology. Brit. med. f. 1, 1063, 19594. TING, N. and HWANG, T.: Leukemias in Chinese armed forces. Incidence and clinico-pathological study. Acta Haem. fap. 21 (2) Suppl. 311, 19585. SACKS, M. S. and SEEMAN, I.: A statistical study of mortality from leukemia. Blood 2,1, 19476. WAKISAKA, G.: Leukemia, a statistical investigation. Nippon Ketsuekigaku Zensho (Hand-book of Hematology in Japanese) 5, 596, 19627. TAKEDA, K.: Geographical pathology of leukemia in Japan. Acta 16, 1629, 19608. WAKISAKA, G.: Clinical and statistical research of leukemia in Japan, especially in theKinki district. Acta Haem. fap. 21, (2) Supple. 240, 19589. SHIRAISHI, T.: Clinical and statistical research of leukemia in Hokkaido over the 7 yearperiod 1931-1957, Ibid. 21 (2) Supple. 259, 195810. NAKAJIMA, A.: Statistical and clinical studies on leukemia of Kanto area, especially aroundTokyo. Ibid. 269, 1958.11. OTA, K.: Clinical and statistical studies of leukemia in the Tokai district. Ibid. 279, 195812. HIRAKI, K.: Clinical and statistical research of leukemia occurring in Chugoku-Shikokudistrict of Japan. Ibid. 286, 195814. WAKISAKA, G., UCHINO, H., YASUNAGA, K., NAKAMURA, T., SAKURAI, M., MIYAMOTO,K., YOSHINO, T and MORIGA, M.: Statistical investigations of leukemia in Japan, ActaHaemat. in press15. DOLL, R.: Paper read at VII International Congress for Geographical Pathology, 1963.Acta hemat, in press16. KOseinO Shihyo (Statistics of Public Health) Special issue in 1962 (in Japanese)17. Annual of the Pathological Autopsy Cases in Japan, Ed. Japan. Soc. Pathol. Tokyo 1958-196218. WINTROBE, M. M.: Clinical Hematology, Lea and Febiger, Philadelphia, 196219. GILLIAN, A. G.:' Age, sex and race selection at death from leukemia and the lymphomas.Blood 8, 693, 195320. SENO, S.: Statistical 'investigations of leukemia autopsies in Japan. Acta Haemat, in7Seno et al.: Leukemia autopsies in JapanProduced by The Berkeley Electronic Press, 196452 S. SENO et al.press21. DMOCHOWSKI, L.: Studies on submicroscopic structure of known or suspected origin, areview. Blood 13, 1017, 195822. BRAUNSTEINER, H. and PAKESCH, F.: Electron microscopic observations on leukemic cells,Acta haemat. 24, 64, 196023. WAKISAKA, G.: The effect of radiation on hematopoietic tissues with special reference toleukemia induced by radi~tion. Hiroshima Igaku 14, 916, 1961 (in Japanese)24. BRILL, A. B., TOMONAGA, M., and HEYSSL, R. M.: Leukemia in man following exposureto ionizing radiation, a summary of findings in Hiroshima and Nagasaki and a comparisonwith other human experience. Annals Intern. Med. 56, 590, 196225. WATANABE, 5.: On the incidence of leukemias in Hiroshimas during the past fifteen yearsfrom 1946-1960, ]. Rad. Res. 2. 131, 196126. WATANABE, S., Ito,1., and MATSUBAYASHI, Y.: Statistical observations on leukemias inHiroshima during the past fourteen years (1946-1959)27. TOMONAGA, M.: Leukemia in Nagasaki atomic bomb survivors from 1945 through 1959.Bull. Org. mond. Sante. Bull. Wld. Hlth. Org. 26, 619, 196228. WATANABE,S., HIROSE. F., and MATSUBAYASHI, Y.: The incidence of leukemia in Hiro-shima during the years from 1946 to 1960, Proc. 2nd Congo Asia and Pacific Soc. Hematol.81. 1962 .8Acta Medica Okayama, Vol. 18 [1964], Iss. 1, Art. 5http://escholarship.lib.okayama-u.ac.jp/amo/vol18/iss1/5

A statistical study of mortality from leukemia.

Acute leukemia over the age of fifty, A study of its incidence and natural history.

Adult leukemia. Trend in mortality in relation to aetiology.

Clinical and statistical research of leukemia

Clinical and statistical research of leukemia in Hokkaido over the 7 year period 1931-1957,

Clinical and statistical research of leukemia occurring in Chugoku-Shikoku district of Japan.

Clinical Hematology, Lea and Febiger,

Electron microscopic observations on leukemic cells,

Geographical pathology of leukemia in Japan.

KOseinO Shihyo (Statistics of Public Health)

Leukemia in man following exposure to ionizing radiation, a summary of findings in Hiroshima and Nagasaki and a comparison with other human experience.

Leukemia in Nagasaki atomic bomb survivors from 1945 through

Leukemia, a statistical investigation. Nippon Ketsuekigaku Zensho (Handbook of Hematology

Leukemias in Chinese armed forces. Incidence and clinicopathological study.

On the incidence of leukemias in Hiroshimas during the past fifteen years from 1946-1960,

Paper read at VII International Congress for Geographical Pathology,

sex and race selection at death from leukemia and the lymphomas.

Statistical 'investigations of leukemia autopsies in Japan. Acta Haemat,

Statistical and clinical studies on leukemia of Kanto area, especially around Tokyo.

Statistical investigations of leukemia in Japan, Acta Haemat.

Statistical observations on leukemias in Hiroshima during the past fourteen years

Studies on submicroscopic structure of known or suspected origin, a review.

The effect of radiation on hematopoietic tissues with special reference to leukemia induced by radi~tion.

The incidence of leukemia in Hiroshima during the years from

The occurrence of leukemia.

Leukemia autopsies in Japan

Abstract

Similar works

Full text

Available Versions

Okayama University Digital Information Repository

Okayama University Scientific Achievement Repository