By endolymphatic injection of radioisotope 131I.Lipiodol, so.called endolymphatic radiotherapy, we treated 10 cases with malignant lymphoma and found a marked tumor reduction to normal size in all the 10 cases we tried. It seems that this method is one of the most effective therapeutic methods for malignant lymphoma, espe.
cially invading into the retroperitoneal lymph nodes.</p

Irino, Shozo

Oka, Akira

Tanji, Tameyo

Uno, Junichiro

English

Okayama University Scientific Achievement Repository

Acta Medica OkayamaVolume 28, Issue 2 1974 Article 5APRIL 1974Clinical evaluation of endolymphaticradiotherapy in malignant lymphomaShozo Irino∗ Tameyo Tanji†Junichiro Uno‡ Akira Oka∗∗∗Okayama University,†Okayama University,‡Okayama University,∗∗Okayama University,Copyright c©1999 OKAYAMA UNIVERSITY MEDICAL SCHOOL. All rights reserved.Clinical evaluation of endolymphaticradiotherapy in malignant lymphoma∗Shozo Irino, Tameyo Tanji, Junichiro Uno, and Akira OkaAbstractBy endolymphatic injection of radioisotope 131I.Lipiodol, so.called endolymphatic radiother-apy, we treated 10 cases with malignant lymphoma and found a marked tumor reduction to normalsize in all the 10 cases we tried. It seems that this method is one of the most effective therapeuticmethods for malignant lymphoma, espe. cially invading into the retroperitoneal lymph nodes.∗PMID: 4368508 [PubMed - indexed for MEDLINE] Copyright c©OKAYAMA UNIVERSITYMEDICAL SCHOOLActa Med. Okayama 28, HI-H8 (1974)CLINICAL EVALUATION OF ENDOLYMPHATICRADIOTHERAPY IN MALIGNANTLYMPHOMAShozo IRINa, Tameyo T ANJI, Junichiro UNO and Akira OKADepartment of Internal Medicine, Okayama University Medical School,Okayama, Japan (Director: Prof. K. Hiraki)Received for publication, July 9, 1973Abstract: By endolymphatic injection of radioisotope 131I.Lipiodol,so.called endolymphatic radiotherapy, we treated 10 cases with malig-nant lymphoma and found a marked tumor reduction to normal sizein all the 10 cases we tried. It seems that this method is one of themost effective therapeutic methods for malignant lymphoma, espe.cially invading into the retroperitoneal lymph nodes.It was FISCHER and ZIMMERMAN (1) who first suggested a possibility ofapplying lymphography for the treatment, and WALLACE et al, (2, 3) attemptedfirst to inject therapeutic materials into the lymph vessels for treatment.Subsequently, there appeared many reports by CHIAPPA et al, (4-7) whotreated malignant lymphoma and metastatic lymph nodes by injecting 1311_Lipiodol into the lymphatics, the so-called endolym,phatic radiotherapy.Simultaneously ARIEL (8, 9), SEITZMAN (10), BETOULIERES et al, (11), LIEBNER(12), zum WINKEL et al, (13) have reported the efficacy of this therapeuticmethod on malignant lymphoma. Despite these clinical studies carried outusing endolymphatic isotopes, there is still controversy on the importance andlimitations of this method in the treatment of malignant lymphoma. In addi-tion, there is as yet no report on study concerning this therapy in Japan.In our experimental study on dogs, we reported that this method hadlittle side-effect and it showed the irradiation effect selectively on lymphnodes (14). Since then we have applied this therapeutic method to patientswith malignant lymphoma and observed a marked reduction of tumors in allthe cases we treated. Here we present our clinical results.PATIENTS AND METHODSThe patients on whom endolymphatic radiotherapy was attempted were10 cases as shown in Table I ; consisted of 3 cases of Hodgkin's disease, 4 reti-culum cell sarcomas, one lymphosarcoma and two chronic lymphatic leukemia.The isotope used was intralymphatic injection iodinated triolein 1311 inLipiodol U. -F. (a product of the Radiochemical Center, England and abbre.viated as 131I.Lipiodol in this report). To each case 4.5 ml 131I-Lipiodol con·1111Irino et al.: Clinical evaluation of endolymphatic radiotherapy in malignantProduced by The Berkeley Electronic Press, 1974112 S. IRINO, T. TANJI. J. UNO and A. OKATABLE 1 PATIENTS TREATED WITH ENDOL YMPHA TIC RADIOTHERAPYSurvival timeCase Sex Age Histological Dead or After the onset After 1311diagnosis* alive** administrationYears Months Years Months1 M 55 RCS dead 2 1 1 32 M 33 CLL alive 5 10 3 43 M 39 RCS dead 10 74 M 51 Hodgkin dead 9 95 M 49 Hodgkin alive 5 2 86 M 28 Hodgkin alive 4 9 2 67 M 42 CLL alive 3 1 2 II8 M 68 RCS alive 1 II 1 39 M 68 LS dead 2 110 M 24 RCS dead 6* RCS: Reticulum Cell SarcomaCLL: Chronic Lymphatic LeukemiaLS: Lymphosarcoma** on the 31 March, 1973taining specific radioactivity of 10 mCi/ml was used. The total volume of 1311.Lipiodol on each side was adjusted before injection to 7-10 ml by mixing withLipiodol Ultrafluide not containing isotope.Following the method of KINMONTH, the mixture of 0.5 ml patent blue andan equal volume of 1-2% xylocaine was subcutaneously injected on the dorsumof both feet, then incision was made for 1. 5-2 cm along the visible lymphaticstained blue to expose the lymph vessel, needle was inserted into the lymphaticand physiological saline was injected through the needle. After confirmingthe saline flow into the lymph vessel, isotope was simultaneously injectedbilaterally into the exposed dorsal lymph vessels.In order to limit the uptake of free 1311 by the thyroid, 10 ml (50 mg)iodinated sodium solution was given orally to the patient the night before theinjection.Immediately thereafter and 24 hours after the injection periodically atintervals of about one week, abdominal and chest X.rays (anterior.posterior,lateral and oblique pictures) were taken. The plane scanning, linear scanning,and the scintillation camera were also used to detect the organ distribution ofthe isotope. In addition, to check the excretion of 1311 into feces and urine,the amounts of 1311 excreted into urine and feces were measured every twodays for two weeks.For determining of therapeutic effects, the size of lymph node wasmeasured by planimetery on the lymphograms taken periodically after theisotope injection, and was calculated by the degree of shrinkage expressed interms of percentage by the following formula: A~B_x100 (where A: the total2Acta Medica Okayama, Vol. 28 [1974], Iss. 2, Art. 5http://escholarship.lib.okayama-u.ac.jp/amo/vol28/iss2/5Endolymphatic Radiotherapy for Malignant Lymphoma 113area of the lymph node before the isotope injection, B: the total area of lymphnode at given days after the injection); we studied the efficacy from the so-called tumor shrinkage curves, and also took the improvement of subjectivesymptoms and changes of humoral factors into consideration.20102080(,,)o~oE.2 60RESULTS1. Effect on lymphoma with endolymphatic radiotherapyFig. 1 shows the results of endolymphatic radiotherapy conducted on thepatients being determined by thetumor shrinkage. This was mea-sured with lapse of time and wasexpressed in percentage, indicat-ing a marked shrinkage of tumorsin all the cases treated; theshrinkage of 20-50%, (35% inaverage) 2 weeks later and 50%in average one month later. Tworepresentative cases are describ-ed as follows.Case 1. A 55-year old fe·male with main complaint ofsystemic lymph node swelling.case 1 Marked lymph node swellingswere observed at each side ofneck, the left clavicular fossa,and especially the right inguinalDays after 13lJ administration . h' f" BregIOn reac mg 1st-sIze. yFig,!. The tumor shrinkage curves of patients b' h' d' dtreated with endolymphatic radiotherapy. IOPSY t IS was lagnose asreticulum cell sarcoma. Afterendolymphatic injection of 35mCi 131I-Lipiodol from the dorsum of both feet,on the third day the right inguinal lymph node, which was as big as a fist,was somewhat softened and began to shrink, by one week it became clearlysmaller, and within two weeks it grew as small as the tip of thumb. Fig. 2and Fig. 3 illustrate the lymphograms taken 24 hours and one month after the131I-Lipiodol injection respectively. As shown in these lymphograms theswollen inguinal and the retroperitoneal lymph nodes are markedly reducedin sizes. Studying the case by the lymph node shrinkage curves, the rate ofshrinkage is 50% by two weeks, and 60% by three weeks as shown in Fig. 1.By the scanning (Fig. 4) and the scintillation camera (Fig. 5) it is obvious that131I-Lipiodol has been distributed homogeneously to lymph nodes. By the3Irino et al.: Clinical evaluation of endolymphatic radiotherapy in malignantProduced by The Berkeley Electronic Press, 1974114 S. IRINO, T. TANJI. J. UNO and A. OKAFig. 2. Lymphogram' taken 24 hours afteradministration of 131I·Lipiodol (Case I)Fig. 3. Lymphogram taken one month later(Case I). Note remarkable shrinkage of lymphnodes.linear scanning conducted at intervals of 2 hours and one week after 131ILipiodol injection as shown in Fig. 6, the isotope is distributed quite denselyand selectively in the inguinal and retroperitoneal lymph nodes. And it wasdemonstrated that the isotope is retained in the lymph nodes over a longperiod of time as observed in animal experiments. 131I-distribution in thelung is clearly observable, but it was diminished markedly and quite rapidly.In thyroid gland its distribution was not detected by the linear or planescanning. Treatment with Bleomycin was started on this patient 3 weeks after131J·Lipiodol injection. The superficial lymph nodes became hardly detect-able, the retroperitoneal lymphogram returned practically normal, generalconditions were also improved, and she was discharged after 3 months oftreatment. There could be observed no marked change of peripheral bloodpicture and bone marrow picture, nor was there any abnormality of thethoracic X-ray picture and functions of liver and thyroid gland.Case 2. A 33-year old male, with chief complaint of bilateral swellingof the neck. There were somewhat hard lymph nodes of a pea to a hen's eggsize palpable bilaterally under the jaw, on the both sides of neck, in theclavicular fossa and in the inguinal region. There was no fusion nor severe4Acta Medica Okayama, Vol. 28 [1974], Iss. 2, Art. 5http://escholarship.lib.okayama-u.ac.jp/amo/vol28/iss2/5Endolymphatic Radiotherapy for Malignant Lymphoma 115Fig. 4. Scintigram after administration of13lJ-Lipiodol (case 1). Note retention of theisotope throughout the pelvic and periaorticlymph nodesFig. 5. Scinticamera of Case 1. upper:chest. middle: abdomen. lower: in-guinalFig. 6. Linear scan of Case 1.pain. By biopsy and other laboratoryfindings this case was diagnosed as chroniclymphatic leukemia. The retroperitoneallymph nodes revealed a moderate swellingpresenting the picture characteristic ofmalignant lymphoma by the lymphogramwith Lipiodol Ultrafluide not containing1311. The Iymphograms taken periodicallydid not show any clear-cut shrinkage evenat the termination of Bleomycin (15mgjday,twice a week to the total of 300 mg).Therefore, the endolymphatic therapy of131I-Lipiodol was commenced, and pursuedthe size of lymphoma by the X-ray picturestaken with lapse of time. Three weeks<""'m IJh..A-.'- _Z weeks later3 weeks later4 weeks later1 week 1.ter ~--)\'---~.A...."tl ...I<: '"III U Q)Q) Q)..c:..c: s:: UI I IZ hour s after13 11 injection5Irino et al.: Clinical evaluation of endolymphatic radiotherapy in malignantProduced by The Berkeley Electronic Press, 1974116 S. IRINO, T. TANJI. J. UNO and A. OKAlater the shrinkage was over 50% and one month later over 60%, clearlyshowing the improvement as in Case 1 (Fig. l). The uptake of 1311 into thelymph nodes is extremely marked by scintigram or scinticamera. By the linearscanning conducted with lapse of time the 131I-distribution in. the inguinaland retroperitoneal lymph nodes is marked.2. The excretion of 13 11 into urine and feces in the cases receiving endolymphaticradiotherapy.Figs. 7 and 8 show the amounts of 131I excreted into urine and fecesrespectively. The excreted amounts vary considerably with cases; in general2 4 6 8 /0 /2 /4-Days after 1311 administrationFig. 8. Excretion of 1311 into feces in thepatients given endolymphatic radiotherapy2 4 6 8 ~ n uDays after 1311 administrationFig. 7, Excretion of 13 11 into urine inthe patients given endolymphatic radio-therapyex) (%)50 /.045 ,~.. ~,'/ ~c' /40 0.8 ...~ ./... / .I~_o", c' / ... ",.. /.,.35 ,;';? .' .,.1"·1/"'0 "'0 .:' /~.,/..t"'~ Cl) ri /,Ii?Cl) 30 t 0.6:',tl///... ...u u>( >< '... ' ·'1Cl) Cl) /'" //1til 2S til <f'o'II~Cl) Cl) /c" /., 1til til0 0';/ / 1,./-"'0 20 "'0 0.4 .. .,//y.;;... ,//. ,/IS I I ,'/ /"/ WII ,:1'.....-'!j10 0.2.Y.I. ///j"S /, ,---to- if'the excretion into urine for two weeks was 5 to 40% showing an inverserelation to the swelling of the inguinal and retroperitoneal lymph nodes.Excretion into feces was under I % in all the cases.DISCUSSIONAdvantages of the 131I-Lipiodol injection into the lymphatics, so-calledendolymphatic radiotherapy, can be pointed out as follows; I) the treatmentcan be accomplished by a single injection into the lymph vessel and, if6Acta Medica Okayama, Vol. 28 [1974], Iss. 2, Art. 5http://escholarship.lib.okayama-u.ac.jp/amo/vol28/iss2/5Endolymphatic Radiotherapy for Malignant Lymphoma 117necessary, repeated injections can be done. 2) By lymphograms, scintiscann-ing, and scinticamera it is possible to observe the 131I-distribution in thelymph nodes. And by taking roentgenograms with lapse of time we canobtain the lymph node shrinkage curves, by which the shrinkage effect canbe determined objectively. 3; As the radiation range of p-emitter from 13 11is about 2 rom, a strong radioactivity is directly gathered onto the pathologicfocus, although it hardly gives any injurious effect on the organs around thepathological lymph nodes. 4) Other than a transient or a slight lYmphocyto-penia (15) there is no inhibitory effect at all on the hematopoietic organs in-cluding the bone marrow.It has been said that in the endolymphatic injection of 131I-Lipiodol fromthe dorsum of feet the retroperitoenal lymph nodes receive 200-800 rads(Siegel), 333-1, 000 rads (Picard), 700 rads in average (Dargent, Romeiu) per1 mCi of 131I-Lipiodol (13). Therefore, for the cases with malignant lym-phoma showing the lymph nodes swelling in the inguinal, iliac and retro-peritoneal regions this method seems to be of the first choice. Also in our10 cases the lymph node shrinkage was marked. Especially, Case 2, who wastreated with Bleomycin 2 months prior to the 131I-Lipiodol injection, showedno clear-cut shrinkage of lymph nodes. When the 131I-Lipiodol treatment wasgiven, the shrinkage of lymph nodes was observed in about the same degree aswith the other cases, and this case suggested a possibility of the shrinkageeffect by 13lJ-Lipiodol even in the malignant lymphoma whereby Bleomycinalone does not induce the shrinkage.As for side-effects, oil embolism of the lung by the contrast medium hasbeen pointed out, but it is extremely rare to see any case raising clinicalproblems. 131 I, that has entered into the lung and has been distributed, isexcreted more rapidly than in lymph nodes and cause little irradiation damage.By histological observations of the lung in animal experiments, likewise, nofibrosis nor any other injurious effects could be seen (14). And by the X-raypictures there were no findings suggestive of fibrosis and other abnormalities.It is also reported that in 16% of the patients treated amenorrhea occurred, twocases showed disorders of liver function due to 131 r-Lipiodol, and hemolyticanemia occurred in one case (7). We did not, however, encounter such sideeffects in our cases. As obvious from the results of the 10 cases whom wetreated, endolymphatic radiotherapy seems to be an extremely useful therapyfor malignant lymphoma with the involvement of retroperitoneal lymph nodesas an ajunct of ordinary radiotherapy and chemotherapy.Acknowledgement: The authors wish to thank Prof. K. HIRAKI for valuable advice and forreviewing the manuscript.7Irino et al.: Clinical evaluation of endolymphatic radiotherapy in malignantProduced by The Berkeley Electronic Press, 1974118 S. IRINO, T. TANJI, J. UNO and A. OKAREFERENCES1. FISCHER, H. W. and ZIMMERMAN, G. R.: Roentgenologic visualization of lymph nodes andlymphatic channels. 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An appraisal of radioactive therapeutic lymphography.

Chemotherapy by intralymphatic infusion.

Endolymphatic radiotherapy in malignant lymphomas. A clinical evaluation of 258 patients.

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Lymphadenography with radioactive contrast medium in retroperitoneal localization of malignant lymphogranuloma.

Lymphangiograms: their diagnostic and therapeutic potential.

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Radioactive lymphangiograpy as a therapeutic adjunct.

Roentgenologic visualization of lymph nodes and lymphatic channels.

Selective lymphopenia in man after intralymphatic injection of radioactive 131I-Lipiodol.

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The role of endolymphatic radiotherapy in the treatment of chronic lymphatic leukemia.

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Clinical evaluation of endolymphatic radiotherapy in malignant lymphoma

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Clinical evaluation of endolymphatic radiotherapy in malignant lymphoma

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