芳彰 山田’s scientific contributions

愛知医科大学附属病院にて経験した睾丸腫瘍について臨床的観察をおこなった.1) 1974～1983年までの10年間に19例を経験した.この期間中の男子外来患者数は6,097名,男子入院患者数は1,097名で,睾丸腫瘍の割合は,それぞれ0.31%と1.73%であった.2)年齢は,10歳以下の小児期と20～40歳代にピークがみられ,平均年齢は27.8歳であった.3)患側は左11例,右側8例であった.4)主訴としては,睾丸の無痛性腫脹が17例(89.4%)を占めた.5)停留睾丸および外傷の既往を持ったものはなかった.6)組織学的分類では,1型9例,2型4例,3型1例,4型4例,malignant lymphoma 1例であった.7)実測生存率は3年および5年ともに81.8%であった.8)治療は全例に高位除睾術を施行,ただし後腹膜リンパ節郭清術はおこなっていない.術後の補助療法としては放射線療法,化学療法の単独あるいは併用をおこなった The 19 cases of testicular tumors treated at our Hospital between 1974 and 1983, were reviewed retrospectively. The incidence of testicular tumors among the male outpatients in our urologic clinic was 0.31%. The patients ranged in age from 1 to 76 years old (average: 27.8 years old). The affected side was the left side in 11 and the right side in 8 cases. The most frequent symptom was a painless mass of the testis. Histopathological diagnosis according to the classification by Dixon and Moore was type I in 9 cases, type II in 4 cases, type II in 1 case, type IV in 4 cases. Thus germinal tumors accounted for 18 (94.7%) of the cases. One case (5.3%) of malignant lymphoma was non-germinal. As for the age distribution, two peaks were noted in testicular tumors, especially in cases with potential embryonal carcinoma, between 1 and 2 years and between 19 and 32 years. On the other hand, the cases with potential seminoma showed one peak between 25 and 44 years. The treatment consisted of high orchiectomy alone, orchiectomy with radiation, orchiectomy with chemotherapy or orchiectomy with radiation and chemotherapy. Retroperitoneal lymphadenectomy was not done in any case. The over-all 3-year and 5-year actual survival rates were both 92%.

ヌードマウス実験系を用い,ヒト腎細胞癌株(AM-RC-3)に対し行った制癌剤感受性試験の実験結果をもとに,腎細胞癌に対するHLBI単独投与あるいはUFTとの併用投与による術後治療と再発予防効果および進行癌に対する治療効果について78例を対象に検討した。1)術後補助療法としてのHLBIの投与は再発予防効果を示す可能性があると考えられる。2)進行癌に対しては,CR 3例,PR 2例,MR 1例でMR以上の奏効率は,24%であった。効果の認められた6例中4例がUFTとの併用例であり,併用療法の有用性が示唆された Previously, we reported the effects of human lymphoblastoid interferon (HLBI), using a transplantable human renal cell carcinoma strain (AM-RC-3) in nude mice established in our laboratory. An overall anticancer effect was found from its combination with UFT (Ft-207t uracil). In the present investigation, we examined the clinical effectiveness when HLBI was administered alone or in combination with UFT to the patients. Seventy-three patients who had undergone curative surgery were divided into 3 groups, according to the type of adjuvant therapy. The HLBI group consisted of 38 patients, including those administered the agent alone over 50 times for more than six months, and or those to whom it was given in combination with UFT. The second group of 23 patients had been treated with hormones, radiotherapy, or with an anticancer drug (Fluoride pyrimidine group), while the last group of 17 patients underwent no postoperative adjuvant therapy. The survival rate calculated by the Kaplan-Meier method revealed no significant effects of HLBI on the survival period, but a significant difference (p < 0.05) was found in the HLBI group compared to the other groups in terms of much higher non-recurrence rate. When HLBI was administered alone or in combination with UFT, a definite anticancer effect was seen in 6 (complete response 3, partial response 2, minor response (MR) 1, no change 5, progression of disease 14) of the 25 treated patients. Fourteen of the 25, treated patients had postoperative recurrence, and 11 patients had distant metastases, at the time of diagnosis which were considered to be progressive and measurable lesions. In 6 patients the response was better than MR, with the effective rate being 24%. Four of the 6 patients had received HLBI in combination with UFT, which suggests a clinical effect in this combination. However, the effectiveness was limited to the lung lesions, more effective treatment of the lesions in other sites is required.

1)TUR-P患者においてCDZMは,静脈内投与で速やかな前立腺内組織移行性を示した。2)CDZM 1gと2g投与間にdose responseが認められた。3)CDZMは,泌尿器科領域感染症の起炎菌に対するMICに比して,十分な組織移行性を示した。細菌性前立腺炎および前立腺疾患術後の感染予防に対し,CDZMは,有効な薬剤である Twenty-four patients suffering from prostate hyperplasia were given venous injections of CDZM of either 1 or 2 g at specific intervals (30 min, 1, 2 and 4 hr) before surgery. Blood samples from the injected vein and tissue samples from the prostate were subsequently taken. In this study, the concentrations of CDZM in the prostate tissue (P) and in serum (S), as well as the ratio of the tissue to serum concentrations (P/S) were determined. In patients given 1 g injections, P ranged from 5.26-48.10 micrograms/g, while S ranged from 25.40-130.00 micrograms/ml and P/S ranged from 12.6-37.0%. In the patients given 2 g injections, P ranged from 9.40-49.20 micrograms/g, S ranged from 62.30-234.00 micrograms/ml and P/S ranged from 9.3-29.1%. CDZM exhibited excellent transmigration to the prostate tissue. Inflammatory bacteria present in prostatitis and urinary tract infections are generally those of E. coli, Proteus sp., but because the P range was much higher than the ratio of MIC, CDZM is expected to be useful against infections in the field of urology.

1983～1987年,愛知医大泌尿器科受診患者を対象とした.外来由来株5,725株の内訳はS. epidermidis (S.e.)(23.8%),Enterococcus sp. (E.s.)(16.5%),E. coil (E.c)(14.7%),Streptococcus sp. (S.s.)(12.6%),Proteus sp. (P.s.)(5.3%)の順であった.特に年次的変化は認められなかった.入院由来株4,748株では,E.s. (23.1%),S.e. (18.7%),真菌(12.9%),P. aeruginosa (P.a.)(8.0%),他のグラム陰性桿菌(GNR)(6.8%)の順であった.年次的変化としてはS.s.の減少とS. aureusの増加,P.s., P.a.の減少,E.c.の増加が認められた.分離菌の感受性としてStaphylococcusはminocycline (MINO)に,E.s.はampicillin, MINOに良好な感受性を示し,E.c.は検討したがすべての抗生物質に良好な感受性を示した.P.a.はNorfloxacinとgentamycin以外は耐性を示す株が多かった Statistical studies were performed on bacterial strains isolated from the urine of patients with various urological disease in our Urological Department between January, 1983 and December, 1987. In 1987, sensitivity tests of antibiotics to various pathogens were carried out. From the outpatients, 5,725 bacterial strains were isolated. S. epidermidis was isolated most frequently (23.8%), followed by Enterococcus species (16.5%), E. coli (14.7%), Streptococcus species (12.6%), Proteus species (5.3%), other GNR (4.6%), P, aeruginosa (4.5%), Klebsiella species (4.4%), and others. From the inpatients, 4,747 bacterial strains were isolated. Enterococcus species was isolated most frequently (23.1%), followed by S. epidermidis (18.7%), Fungi (12.9%), P. aeruginosa (8.0%), other GNR (6.8%), Streptococcus species (5.4%), Enterobacter species (4.8%), E. coli (4.1%), S. aureus (4.1%) and others. Annual change of distribution of organisms indicated that S. aureus from outpatients had a tendency to increase and Streptococcus species had a tendency to decrease. Whereas from inpatients, E. coli, other GNR, Pseudomonas species and Enterobacter species had a tendency to increase, and Streptococcus species, P. aeruginosa, Proteus species and Klebsiella species had a tendency to decrease. S. epidermidis showed a high sensitivity to minocycline and cephalothin, and Enterococcus showed a high sensitivity to ampicillin and minocycline, but did not show good sensitivity to cefoperazone and latamoxef. E. coli showed a high sensitivity to all drug we tested. P. aeruginosa showed a high sensitivity to gentamycin and norflaxacin, but did not show good sensitivity to other many drugs we tested.

1)ヒト原発性尿管移行上皮癌(grade 2, stage B)からヌードマウス可移植株(AMUT-1)を樹立した.2) AMUT-1は,5代以降ほぼ100%の生着率を示し,安定した一定の増殖を示した.3) AMUT-1は,継代を繰り返しても原腫瘍の形態学的および生物学的性格をよく維持した.4)本腫瘍はCEA産生腫瘍と考えられた The tumor line in nude mice is one of the most important experimental animal models for oncodevelopmental studies. We implanted a human ureteral tumor into nude mice, established the tumor line, AM-UT-1, and maintained it by serial transplantation. The characteristics of this tumor line in nude mice are reported. Histologically, the original tumor was a transitional cell carcinoma (grade II, stage B). The transplanted tumor grew locally and had a constant growth pattern during serial passage until the 13th passage in nude recipients and maintained the basic histological, immunohistochemical findings of the original tumor. Both original tumor and serial transplanted tumor had carcinoembryonic antigen (CEA)-producing activity. A high level of serum CEA was also recognized in nude mice.

A case of asynchronous triple cancer in an 88-year-old male is reported. Six years ago, he had received left radical nephrectomy for renal cell carcinoma, and 2 years ago partial hepatectomy for hepatocellular carcinoma detected by follow-up computed tomography (CT). During the post-operative follow-up, no metastasis of either the renal or hepatic carcinoma was detected. On February 12, 1997 he presented with macroscopic hematuria. Cystoscopy revealed a tumor emerging from the left ureteral orifice, while CT and magnetic resonance imaging (MRI) revealed a tumor mass in the left exterior of bladder. Diagnosis of residual ureter tumor, we performed both left ureterectomy and partial cystectomy. Histological diagnosis revealed transitional cell carcinoma of the residual ureter (G2 > G3, pT1, pV0, pL0, pR0). Convalescence was uneventful and 10 months after the operation, he is alive with no recurrence or metastasis. We stress the importance of careful follow-up not only to perceive the recurrence or metastasis of renal cancer but also to detect cancer in other parts of the body.

A total of 518 bacterial strains isolated from the urine of patients with various urological diseases in our Urological Department between November, 1987 and February, 1989 were studied for their beta-lactamase production and susceptibility to various antimicrobial agents was determined. beta-lactamase activity was determined by the acidometry disc method. There were 241 gram-positive cocci, 276 of gram-negative rods and 1 Neisseria gonorrhoeae. Thirty-four percent of the gram positive and 76.3% of gram negative rods produced beta-lactamase. S. aureus (81.3%), S. epidermidis (65.1%) in gram-positive cocci, E. cloacae (100%), S. marcescens (100%), C. freundii (100%), P. aeruginosa (97.2%), P. Rettgeri (88.9%), E. gergoviae (85.7%), K. oxytoca (84.6%), M. morganii (81.8%) and E. coli (69.0%) in gram-negative rods produced beta-lactamase at a higher rate. beta-lactamase produced by gram-positive cocci was entirely penicillinase, and that produced by gram-negative rods only penicillinase in 4.0%, only cephalosporinase in 44.2% and both in 25.4%. In S. aureus and S. epidermidis, the isolated rate of strains resistant to ampicillin (p less than 0.01) and piperacillin (p less than 0.05) in the beta-lactamase producing strains was significantly higher than that in the beta-lactamase non-producing strains. In E. coli, the isolation rate of strains resistant to ampicillin and piperacillin in the penicillinase-producing strains was significantly higher than in the penicillinase non-producing strains (p less than 0.01). But both cephalosporinase-producing strains and beta-lactamase non-producing strains showed high susceptibility to cephalothin. These results suggest that the penicillinase might present a clinical problem in the treatment of urinary tract infections by S. aureus, S. epidermidis and E. coli.

Two cases of primary female urethral carcinoma are presented and discussed. The patients were 70 years old and 65 years old, and the pathological diagnoses were squamous cell carcinoma and adenocarcinoma, respectively. The patient with squamous cell carcinoma had metastasized inguinal lymph nodes at the first consultation, despite the administration of bleomycin, and the tumor had widely metastasized to skin of the lower extremities. She died of cachexia and disseminated intravascular coagulopathy (DIC). The other patient with adenocarcinoma was treated by postoperative cobalt radiation therapy in a total dose of 6,000 rads. After 18 months, she had recurrence of tumor in urethra, and developed Virchow's node metastasis, she died of acute renal failure. Both patients died within two years.

Sultamicillin, a new semisynthetic oral beta-lactam antibiotic, was evaluated for its antibacteria susceptibility and clinical efficacy against urinary tract infection (UTI), and the following results were obtained. The sensitivity of sultamicillin (SBTPC) on 518 strains of clinical isolates from the urine were tested and compared to ampicillin (ABPC). S. aureus, S. epidermidis, Enterococcus sp., Streptococcus sp., E. coli, K. pneumoniae, K. oxytoca, P. mirabilis, M. morganii and Acinetobacter sp. showed high sensitivity to SBTPC. The antibacterial activity of SBTPC was superior to that of ABPC in most strains and especially more superior in beta-lactamase producing strains. The clinical effectiveness rate on a total of 15 patients with acute uncomplicated cystitis was 93.3% and the eradication rate of causative organisms was 93.3%. On 15 patients with chronic complicated UTI, the clinical effectiveness rate was 73.3% and eradication rate was 76.5%. Side effects (diarrhea) were observed in 3 cases, but this symptom was not severe and soon disappeared. Abnormal laboratory data due to the drug were not observed.

A 67-year-old man was admitted for complaint of gross hematuria on April 9, 1986. Cytoscopic examination was revealed broad-base tumor, its size was thumb's head, at the right lateral wall of the bladder. Ultrasonography and computed tomographic scan of the bladder demonstrated no evidence of invasion to adjacent organs. The biopsy showed signet-ring cell carcinoma. Radiography of the digestive organs showed no abnormality. A partial cystectomy was performed. Histologically the tumor was limited up to submucosa, that is pT1b. The localization of carcinoembryonic antigen (CEA) on tissue of our case, using the peroxidase-antiperoxidase (PAP) method, was evidenced.