前立腺ガンにたいするThio-TEPA(TESPAMIN)の前立腺組織内 注射療法

稲田, 務, 片村, 永樹, 本郷, 美弥

This report deals with our satisfactory result in o u r conservative treatment of carcinoma of the prostate, injecting Tespamin in the prostatic tissue. In 1953T hio-TEPAw as found to be an antileuk e m ic agent clinically used by Drs. Shay, Zarafonetis, Smith, Woldow and Sun for 49 leukemic patients. This medicine can be administrered in any way of intravenous, intramuscular, intracavital, intratumorous and oral. Thio-TEPAi s a powerful alkylating agent which combine with the nucleoprotei n o f the cell, followed by cell destruction especially inhibiting mitotic activity of immature cells resulting in nuclear pyknosis and destruction. Therfore, spermatogenesis becomes suppressed resulting in clinical castration. Method of Administration 1) Under local anesthesia in the perineum , occasionally epidural anesthesia, patient is placed in lithotomy position. 2) Thio-TEPA i s mixed with some hyaluronidase and given 20 or 30 mg. (0.5 mg/kg). 3) With the 10 ml. Luer-Syringe and gauge 17 or 15 long needle, the prostate is punctured, simultaneously being palpated rectally. Solution is injected to the several sites 1 or 2 cc each times. When the needle hits the carcinomatous tissue, we feel some resistance . 4) Patient receives the injection every 5 days to 7 days, or every 2 weeks . Tot a l doses ranged 150 to 300 mg. 5) Hematologic a lly, white cell count 4, 000 and platelet count 100 , 000 are the standard for terminating this treatment. Presentation of Cases Case 1 : Y.U. A 64-year-old male had frequency since May 1958 and was seen in acute urinary retention June 1960. Rectal examination revealed enlarged prostate of egg-s, =- -hard , irregular especiallerly on the right. Urethrocystography showed intravesical protrusion of the prostate without abnormality of the urethra (Fig. 1). Residual urine amounted 300 cc. Cystoscopy revealed chronic cystitis. Blood chemistry : Acid phosphatase 1.6 (normal title 0 to 3) ; Alkali phosphatase 1.4 (normal 1 to 4); Normal electrolytes level. Needle biopsy of prostate was repo r ted to be adenocarcinoma (Fig. 2 and 3). Laboratory examination : Examination of the blood ; white cell count 3, 400 , with 68% of neutrophils and 20% of lymphocytes. Blood pressue was 108/64 mmHg. Treatment and course : Bilateral orchiectomy a nd administration of estrogen did not improve dysuria and unpleasment feeling in his perineum. Thio-TEPA (Tespamin ) 25 mg was first injected in the prostate weekly, biweekly later, amounting total dose of 200 mg. After initial injection of 25 m g Thio-TEPA, patient became free from dysuria ; and unpleasant feeling in the perineum also disappeared after injection of 75 mg. He also gained his weight and general condition much improved. After injection of Thio-TEPA 200 mg during 3 months, the prostate decreased in size, and induration became small-finger-sized, which was 1 year later noted as only flat, slightly indurated lesion. Phosphatase and hematology were normal. Histological change after injection of 25 mg of T e spamin was that tumor cells were polymorph, not uniform in size and irregularly arranged with nuclei abundant in chromatin. After injection of 125 mg, tissue developed remarkable fibrosis and narrowin g glandular lumen where tumor cells were only scattered. After injection of 200 mg, this tendency became remarkable with more poorly stained carcinoma cells and vacuole formation. The nuclei were atrophic. Tissue was mostly replaced to fibrous connective tissue of poor vascularity (Fig. 4 and 5). Case 2 : T.T. 75-year-old male first noticed frequency and dy s uria in September 1958. In May 1959, dysuria got worse with unpleasant perineum. He was admitted in October 1959. 1) Digital examination revealed egg-sized, enlarged, fixed prostate of bony hardness and irregular surface. 2) Ur o graphy. Urethrocystography (Fig. 6) showed elongated, irregular prostatic urethra with marked protrusion of prostate into the bladder on the left side. 3) Cystoscopy was performed with feeling of fixed cystoscope. Irregular bladder neck at IV to VIII o'clock was found. Residual urine amounted 400 cc. 4) Blood chemistry Acid phosp h atase 4.4 u. (normal level 0 to 4 u.), alkali phosphatase 2.1 u. (normal level 1 to 4 u.), 17 KS 6.12 mg/day (normal). Other electrolytes were normal. 5) Perineal needle biopsy of ;the prostate disclosed undiffer e ntiated adenocarcinoma of the prostate (Fig. 7 and 8). 6) Hematology : R.B.C. 365 x 104, Hb. 10.8 g/dl, color index 0.86, W.B.C. 5, 400. neutrophils 68.0%, lymphocyte 29.7%, monocyte 4.5%. Treatment and Course : After bilateral orchiect o my, Thio-TEPA (Tespamin) was injected, as mentioned, 25 mg every 5 days or weekly into the prostate gland, amounting 200 mg in total dose. After Thio-TEPA 50 mg was injected, dysuria much improved ; and freq u ency disappeared after 75 mg injection. However, burning, unpleasant perineum, and cloudy urine were still present. A f ter 200 mg was injected, rectal examination showed that prostate became smaller in size with increased firmness. Periprostatic infiltration also seemed to have disappeared. Residual urine was 20 cc. Acid phosphatase also dropped to 2.5 u. and 17KS also decreased to 3.7 mg/day. Ur e t hrocystography showed the regular prostatic outline and much less protorusion into the urinary bladder (Fig. 9). Histologically, prostate showed remarkable fibrosis and smaller glandular lumen. Carcinoma cells seldom formed nest but exsisted in spotted way except for very few nests surrounded by fibrous tissue. Each carcinoma cell possessed prominent necleus with rich chromatin and showed protoplasmic destruction (Fig. 10, 11, 11, 12, 13). Case 3 : A.S. 60-year-old male with bony meta s tasis (Fig. 14). No remarkable improvement was obtained by orchiectomy and administration of Honvan. Dysuria and untoward feeling in the perineum disappeared after injection of Thio-TEPA (Tespamin) 150 mg. Seven months later, pubis appeared normal on x-ray (Fig. 15), acid phosphatase returned to normal. Needle biopsy of prostate showed adenocarcinoma (Fig. 16 and 17). After i n jection of 250 mg, histologically, tissue developed remarkable fibrosis and smaller glandular lumen (Fig. 18, 19, 20). Ca s e 4: S.N. 72-year-old male with history of simple prostatectomy 7 years previously, developed a big carcinoma of the prostate which became much smaller with disappearence of all troubles but dysuria after 300 mg of injected dose. Case 5 : K.K. 82-year-old. Big carcinoma of the prostate and bony metastasis. 300 mg of Thio-TEPA (Tespamin) injection gave no remarkable regression in size and slight improvement in dysuria. No side effects seen in all cases.

前立腺ガンにたいするThio-TEPA(TESPAMIN)の前立腺組織内注射療法

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