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OBJECTIVE This prospective and randomized clinical study was initiated to compare the efficacy and safety of combined androgen blockade with combination with UFT in patients with untreated prostate cancer. METHODS A total of 142 patients were entered in this study between April 1990 and December 1992. All patients received bilateral orchiectomy and 200 mg/day of diethylstilbestrol diphosphate. Of these patients, 70 patients were administered an additional 400 mg/day of UFT after randomization. Either treatment was continued for at least 1 year or until objective progression occurred if the initial response was equal to or better than no change. The endpoints of this study were progression-free survival, cancer-specific survival and change of QOL scores. RESULTS A total of 136 patients were evaluable and 131 patients (96.3%) could be followed up with a median follow-up period of 1469 days. Both groups showed similar initial treatment response at 12 weeks, adverse effect and change of quality of life score during the first year after initiation of the treatment. There was a significantly longer progression-free survival and better but not significant cancer-specific survival in the endocrine chemotherapy group. The patients with earlier stage and initial serum prostate-specific antigen values

Objective The clinical utility of the determination of serum prostate-specific antigen-alpha1-antichymotrypsin complex (PSA-ACT) for the diagnosis of prostate cancer, especially in cases in the diagnostic gray zone, is still unclear. Material and methods With the use of a newly approved enzyme immunoassay for the detection of PSA-ACT, 907 sera, including those from non-urological benign and malignant diseases, were analysed. Results Serum values of PSA-ACT in non-prostate cancer males increased according to age from the 40s to 70s. The serum values were high only in the patients with prostatic diseases and, in prostate cancer patients, the values became high as the clinical stage progressed. By receiver-operating characteristic analysis significantly better results in PSA-ACT than total PSA were observed. In the group with a total PSA of 2-20 ng/ml, the detection of PSA-ACT showed better results, although not significantly so, than the free-to-total PSA ratio. Conclusions The detection of PSA-ACT showed a high clinical utility in the diagnosis of prostate cancer. Therefore, it may replace total PSA determination.

In allogeneic tumor or skin transplantation, the rejection process that destroys the allogeneic cells leaves syngeneic cells intact by discrimination between self and nonself. Here, we examined whether the cells infiltrating into the allografts could be cytotoxic against syngeneic immortal cells in vitro and in vivo. The leukocytes (i.e., macrophages (Mφ; 55–65% of bulk infiltrates), granulocytes (20–25%), and lymphocytes (15–20%)) infiltrating into allografts, but not into autografts, in C57BL/6 mice were cytotoxic against syngeneic tumor cells and cell lines, whereas the cytotoxic activity was hardly induced in allografted, IFN-γ−/− C57BL/6 mice. Among the leukocytes, Mφ were the major population of cytotoxic cells; and the cytotoxic activity appeared to be cell-to-cell contact dependent. When syngeneic tumor cells were s.c. injected into normal C57BL/6 mice simultaneously with the Mφ-rich population or allogeneic, but not syngeneic, fibroblastic cells, tumor growth was suppressed in a cell number-dependent manner, and tumor cells were rejected either with a Mφ:tumor ratio of about 30 or with an allograft:tumor ratio of ∼200. In the case of IFN-γ−/− C57BL/6 mice, however, the s.c. injection of the allograft simultaneously with tumor cells had no effect on the tumor growth. These results suggest that allograft or allograft-induced Mφ may be applicable for use in cancer treatment and that IFN-γ induction by the allograft may be crucial for the treatment.

Background: The ratio of free PSAin total PSA(fit) has been reported to improve the diagnostic accuracy of prostate cancer in the groupwith slightly elevated serum PSA values. In Japanese cases, the clinical significance of fit is still controversial. Methods: The diagnostic significance of fit in serum for prostate cancer was evaluated in a cooperative study. A total of 77 cases with prostate cancer and 224 with non-prostate cancer showing less than 20 ng/ml of total PSAwere evaluated. Results: Serum total and free PSA values were not affected by storage at 25°C for 2 days. The determination of fit was useful in the cases with a serum total PSA of 5.1-10 ng/ml; the specificity was 60% with a sensitivity of 90% at an fit of 0.148. The positive predictive value for diagnosis of prostate cancer also increased to 54%from 34% of that in total PSA alone. In the range of 4.1-10 ng/ml, the cut-off value of fit was 0.155 for obtaining relatively high specificity; sensitivity was 85% and specificity was 56.5%. Conclusions: Thus, thedetermination offit wasconsidered to beaneffective tool fordiscriminating the non-prostate cancer cases from those of prostate cancer.

Background. It has been generally assumed that CD8 + T cells mediate direct lysis of allografts and that their growth, differentiation, and activation are dependent upon cytokine production by CD4 + T cells. However, both the generation of CD4- or CD8-deficient mice and adoptive transfer experiments with CD4 + T cells from CD8-deficient mice demonstrate that non-cytotoxic CD4 + T cells alone are sufficient to induce skin or organ allograft rejection. Furthermore, we have reported that the major effector cells responsible for allografted-tumor (e.g., Meth A) rejection are allograft-induced macrophages (AIM) with MHC haplotype specificity. Methods. We characterized the macrophages migrating into the rejection site of allografted skin by immunohistochemical and in situ hybridization analyses using an antibody (K16.5) specific for AIM and a cDNA (pK30) encoding the antigen. To determine the in situ effector cells responsible for the rejection, we prepared both effector cells and target cells from the graft-graft bed border. Results. The macrophages seemed to be morphologically (monocytic), phenotypically (K16.5 + /pK30 + ), and functionally (cytotoxic against Meth A cells) AIM. The AIM population in bulk infiltrates taken from the rejection site was cytotoxic against allografted, but not self, skin components (e.g., fibroblasts, myocytes, endothelial cells, and epithelial cells). In contrast, other types of infiltrating cells including lymphocytes and granulocytes were virtually inactive toward these targets, and NK-1.1+ cells hardly infiltrated into the rejection site. Conclusions. These data suggest that the major effector cells mediating allografted skin rejection are AIM and not T cells.

Objective To evaluate the oxidative metabolism of polymorphonuclear leukocytes (PMNL) in continuous ambulatory peritoneal dialysis (CAPD) patients compared with those of hemodialysis (HD) patients, chronic renal failure (CRF) patients not yet on dialysis, and healthy controls; and to discover factors contributing to the oxidative function in CAPD patients. Patients Thirty-five CAPD, 22 HD, 11 CRF patients were assessed; all were free from infections at the time of examination. Thirty-one healthy volunteers served as controls. Methods The oxidative metabolism was estimated by the production of superoxide anion, which was detected by luminol-dependent zymosan stimulated chemiluminescence (CL) with whole blood assessment. The volume of superoxide production equivalent to 1 mL of circulating blood (T-CL), that equivalent to 104 neutrophils (CL/N) and the velocity of superoxide production (V-CL), were measured as parameters for the oxidative function of PMNL. Results There were no differences in all CL parameters between CAPD and HD patients. T -CL and CL/N of dialysis patients were equal to controls but those of CRF patients were significantly decreased. V-CL of dialysis patients, as well as CRF patients, was smaller than that of controls but the difference was not significant. Among nutritional status, degree of anemia, dialytic efficacy and duration of dialysis in CAPD patients, only serum albumin concentration (Alb) correlated well to all CL parameters. Hypoalbuminemic patients(Alb Conclusions Oxidative metabolism of PMNL in CAPD patients was maintained with respect to superoxide productive volume, while the oxidative velocity was relatively impaired. Furthermore, it seems that albumin has a great influence on the oxidative metabolism of PMNL in CAPD patients.

To study the function of leukocyte in urinary tract infection (UTI), the effect of granulocyte colony-stimulating factor (G-CSF) and various osmolarities on the function were studied. The superoxide production of blood leukocytes increased by treatment of G-CSF with its dose dependency. This effect was not observed in urinary leukocytes. This increased function was well preserved even in higher osmotic atmosphere when previously treated by the G-CSF. Therefore, urinary leukocyte activated by G-CSF and migrating from the blood through the tissue may still have its function and work in the patients with UTI.

血液透析患者における細菌尿の実態を知る目的で, 尿路感染症の急性症状を示さない時期に, 尿検査を実施し分離菌種を検討した.複数菌種の細菌が分離される割合が過半数を占め, また女性の方が複数菌種分離の程度が高かった. 分離菌種は, グラム陽性球菌, 特にStaphylococcus属の頻度が高かった. これらは103CFU/ml以下の低菌数で分離される検体が多く, 採尿時の汚染が示唆されたが, 菌数104CFU/ml以上の単独菌分離の67%がEnterococcus faecalis, Streptococcus属をはじめとするグラム陽性球菌であるなど, 一般の尿路感染症と異なる傾向も見られた.乏尿など特異な病態下にある血液透析患者の細菌尿の解釈には注意が必要であると考えられた.

We report 2 cases of persistent ureteral infolding in a fourmonth-old infant and an eight-year-old boy, both presenting with hydronephrosis. Initial diagnostic evaluation showed multiple pleats in the upper ureter. Endoscopic incision of the pleats relieved hydronephrosis. The concept of persistent ureteral infolding seems to apply to these cases.

昭和61年11月から平成3年3月までの間に29例 (男性16例, 女性13例) の続発性副甲状腺機能亢進症に対し副甲状腺全摘術および前腕筋肉内への自家移植術を施行した. 我々は異所性の副甲状腺や微小腺による本症の再発を防止する目的で, 全例に対し通常の4腺摘出に加えて頸部リンパ節郭清と両側胸腺舌区切除を同時に行ってきた. その結果29例中3例 (10.3%) の摘出リンパ節および胸腺の中から甲状腺癌の転移 (すべて乳頭癌) を発見し, うち2例に甲状腺葉切除を行い微小癌 (大きさ各々2.5×1.0mm, 1.0×1.5mm) を発見した. 更に追加切除を行わなかった残りの1例は後に顕性癌へ進行した. 本症の外科的治療に際しこの手術方法をとった結果, 甲状腺癌の転移を発見した場合は更に追加手術を行ったほうがよいと思われる.

CAPD施行時に肉眼的血性排液を認めることは, 女性の生理に起因するものを除き比較的稀である. 今回我々は, 特発性腎破裂の腹腔内穿破により血性排液をきたし, 腎動脈塞栓術によりCAPDを中断することなく保存的に治癒せしめた1例を経験したので報告する. 症例は, CAPD歴1年2か月の30歳男性である. 打撲などの誘因はなく, 突然に左腰背部痛が出現し, 来院した. 受診時, 著明な貧血を呈し, CTにて巨大な左後腹膜血腫を認めた. 安静および輸血にても貧血は進行し, 同夜にはCAPD排液が血性となり, 左腎破裂の腹腔内穿破と診断された. 翌日施行した選択的左腎動脈造影にて, 左腎下極の腎内動脈末梢部の破裂を認めたため, スポンゼルによる腎動脈塞栓術 (TAE) を行い, 十分な止血効果が得られた. 術後は, ヘパリン入りの頻回バッグ交換にて, 凝血塊によるカテーテル閉塞を防ぎ, 腹膜クリアランス値や除水量などの腹膜機能に低下を認めることなくCAPDを維持することが可能であった. 血性排液の原因は多岐にわたり, 必ずしもCAPDや腎不全に直結するわけではないことを念頭において治療を進めることが肝要であると考えられた.

We reported a case of juxtaglomerular cell tumor, which excessively produced renin, resulting in secondary hypertension. A 25-year-old woman complained of headache and nausea. Hypertension and elevation of plasma renin activity were found by physical and laboratory examination. US and CT showed a space occupying lesion at upper pole of the right kidney. Angiography showed a hypovascular area at the corresponding area of the right kidney. Renin-secreting renal tumor of the right kidney was diagnosed and right nephrectomy was performed. Postoperatively, blood pressure and plasma renin activity became normalized and symptoms ameliorated. The juxtaglomerular cell tumor was pathologically confirmed and localization renin in the tumor cells was shown by immunohistochemical study. Forty one cases of juxtaglomerular cell tumor have been reported, since Robertson reported the first case. We discussed the clinical and pathological characteristics of the disease in this report.

CAPDに関連した腹膜炎起炎菌として検出されやすいS. epidermidis, S. aureusの増殖動態を1.5% DianealTM液および同液を使用してCAPDを継続中の1例から得られたCAPD排液 (peritoneal dialysis effluents) とで比較, 検討した. 両菌種ともDianealTM液中では増殖が抑制されたが, CAPD排液中では生菌数は培養開始6時間目まではほぼ不変であったが, 24時間目ではむしろ増殖傾向を示した. 浸透圧, ブドウ糖, 総タンパク質, pHは, 24時間の検討期間中不変であった. 一方, 6時間目までは生菌数の増加があまりないという結果は毎6時間のCAPD液交換が腹膜炎発症予防には有利であるとも考えられた.

A review of 611 cases of renal pelvic or ureter tumor registered in Tokai Urological Tumor Registry for the past 10 years from 1980 and comparison of results between the first and latter half was made. The number of renal pelvis tumor was 347 and that of ureter tumors was 264. Clinical stages and pathological grades of the tumor were as follows; Ta, 11.9; T1, 31.8; T2, 14.4; T3, 24.3; T4, 17.6% and G1, 10.5; G2, 49.3; G3, 33.0%. Higher stages and grades were observed in the recent 5 years. Of 409 cases (66.9% in total cases) treated by total nephroureterectomy, 28.3% of the first and 49.0% of the latter half were treated adjunctively by chemotherapy. Five years relative survival rates of these two groups were 49.4 and 47.3%, respectively, suggesting no improved results. A new treatment strategy such as neoadjuvant chemotherapy or lymphadenectomy is expected to improve the prognosis.

Extramammary Paget's disease of the vulva (EMPDV) is a rare gynecologic malignancy. We examined two cases of EMPDV in which cytologic study led to early detection of disease recurrence.In case 1, a 71-year-old woman, recurrence was detected with malignant cells from the vaginal Papanicolaou smear a few months after radical surgery for endometrial cancer. An asymptomatic perineal erythematous lesion was identified and diagnosed as EMPDV by biopsy specimen. She underwent curative surgery, but during the follow-up period, malignant cells appeared again in her vaginal Papanicolaou smear, which led to early detection of the recurrent disease that was macroscopically invisible. In case 2, an 80-year-old woman presented with the complaint of perineal pruritus and was diagnosed with EMPDV. Twenty-two months after the curative primary surgery, bilateral groin lymphadenopathies appeared, and the cytologic specimen by fine needle aspiration biopsy from the lymph nodes led to early detection of the recurrence without her experiencing negative side effects such as severe pain.Cytologic examination is a simple but efficient diagnostic measure without major negative side effects, provided the procedures are applied adequately and performed correctly.

透析患者195例中評価可能な115例を対象に, 腎性骨異栄養症 (広義のROD) の疼痛scoreとDEXA骨密度測定の意義を検討するため, 測定部位別骨密度すなわち, 中手骨, 腰椎 (L2-L4), 大腿骨の骨密度と各種骨パラメータ検査値, および中手骨のmicrodensitometry (MD法) のパラメータの相関性と有用性を検討した. 透析歴で5年未満, 10年未満, 15年未満, 15年以上の4群間でDEXAによる骨塩量を中手骨, 腰椎, 大腿骨で測定値を比較すると, 中手骨でのみ群間で有意差を認めた. 10年以上の長期透析群の骨密度の検討では男性では10年未満に比して有意に低値を示したが, 女性群の10年未満の症例ですでに骨密度は低下していて長期透析群と同程度であった. また疼痛scoreによる患者群別でも中手骨の骨密度が群間で有意差を認めたが腰椎では差を認めなかった. DEXAによる各部位の骨塩量を目的変量として多変量解析すると, 中手骨では疼痛score, 透析歴, 年齢の順で寄与率が高く, 大腿骨頸部では, C-PTH, 年齢, Ca×P, calcitoninに, 腰椎ではC-PTH, 年齢に高い結果を得た. DEXAによる骨塩量の測定でも, 透析歴および疼痛scoreを反映する骨塩量の変化は皮質骨主体の中手骨で認められ, 腰椎のDEXA骨密度は治療効果の経過観察に適している可能性があることが示唆された.

症例は透析歴12年の53歳男性. 眼サルコイドーシスの既往がある. 1990年10月四肢末梢の脱力としびれが出現し, 原因不明のままステロイドパルス療法が奏効した. 1991年4月, 胃部不快感, 微熱を, さらに両肩痛を訴えるようになり, やがてせん妄が出現し, 意識混濁に至った. 意識障害の原因として高カルシウム血症が疑われ, プレドニゾロンとエルカトニンの投与により意識障害と高カルシウム血症がともに急速に改善した. 高カルシウム血症の原因としてサルコイドーシスが疑われ, 前斜角筋リンパ節生検の病理組織診断で証明された.本邦ではサルコイドーシスによる高カルシウム血症は稀であり, 血液透析患者に高カルシウム血症, 意識障害をきたしたサルコイドーシスの報告例は我々が調べた限り文献上認めなかった.

血液透析患者における膿尿, 細菌尿の実態を知る目的で, 尿路感染症の急性症状を示さない時期に尿検査を実施した結果を報告する.尿沈渣白血球数は5コ/hpf以上が59.7%, 10コ/hpf以上が43.5%, 細菌尿は104CFU/ml以上が29.8%, 105CFU/ml以上が21.0%と, いずれも高頻度であった. 膿尿, 細菌尿の頻度に有意な性差はなかった. 腎炎群, 糖尿病腎症群間にも有意差は認められなかったが, 多発性嚢胞腎が原疾患である症例では, 膿尿, 細菌尿の程度が高い傾向が認められた.1日尿量と膿尿および1日尿量と細菌尿の分布および統計学的検討より, 少なくとも1日尿量400ml以下の場合には通常の基準を用いて感染尿の決定をすることは好ましくないと考えられた.

A strain of Escherichia coli 06:H-, which was isolated from a patient with acutepyelonephritis, was used to produce ascending pyelonephritis in mice. The histologic features at the early stage of acute pyelonephritis and the pathways of bacterial invasion and distribution in the infected kidneys were studied by using transmission electron microscope. The histologic changes were characterized by degeneration and destruction of renal pelvic and tubular epithelial cells, and a massive infiltration of polymorphonuclear leukocytes. Bacteria invaded the pelvic surface and spread over the renal medulla and cortex by contiguity twelve hours after infection. It was also shown that bacteria ascended the tubules, multiplied in the tubular lamina, destroyed the tubular epithelial cells, and spread over the renal cortex by twelve hours. In addition, bacteria and leukocytes phagocytizing bacteria were present in the capillaries in the renal interstitium twelve hours after infection.

CAPD (continuous ambulatory peritoneal dialysis) は腎不全の治療として血液透析や腎移植と共に重要な治療法の一つである. しかし最大の合併症として腹膜炎があり, これがCAPD継続の鍵を握っている. 最近この腹膜炎の中に無菌性のものがあることが知られている. 特に排液中の好酸球の割合が多く, 自然寛解をみる好酸球性腹膜炎が注目されてきている. 今回我々は3例の好酸球性腹膜炎を経験した. 3症例ともCAPD導入後2-3週間で発症し, 抗生剤を使用せずに1-3週間で自然治癒した. このうち2症例に肝機能障害が出現した. 好酸球性腹膜炎の発症機転はアレルギー反応と推察されているが, 我々の症例においては末梢血の好酸球の増加はなく, カテーテルの滅菌方法をEOGからオートクレーブに変更したところその後の症例においては1例も好酸球性腹膜炎の発症を認めていない. 好酸球性腹膜炎は自然治癒し腹膜機能も低下させないので, 腹膜炎発症時には白血球分画も測定し, 本疾患の診断をつけることが大切であり, 抗生剤治療は無意味である.

Registration of renal pelvic and ureteral tumor was done from 1980 through 1986, in the Tokai Urological Tumor Registry. Among the 404 cases of the carcinoma, 384 cases (210 renal pelvis, 174 ureter) were subjected to the present study. A total of 319 cases (83.1%) showed a complete cure, while 20 cases (5.2%) were considered as partial cure, and 45 cases (11.7%) were classified to progressive disease group. Chemotherapy was performed on 151 patients including systemic administration to 141 patients (33.9%) and 11 patients received combined intravesical instillation therapy. Irradiation was performed on 49 patients (12.8%). Degree of histological and morphological differentiation of renal pelvis and ureter tumor were studied in 341 cases of transitional cell carcinoma (88.8%); G0, 0.3%, G1, 12.9%, G2, 49.3%, Gx, 5.2%. Stage of the tumor were T1, 33.6%; T2, 12.5%; T3, 14.6%; T4, 13.3%; Tis, 0.3%; Tx, 24.7%. Five-year relative survival for carcinoma of the renal pelvis was 46.6%, and for the ureter it was 53.1%. Five-year survival according to histological differentiation of transitional cell carcinoma and according to the stage of the tumor were as follows; G1, 91.6%; G2, 58.5%; G3, 27.2%; Ta, 84.6%; T1. 74.2%; T2, 48.5%; T3, 24.1%, T4, 7.3%. The rate of survival was correlated with histological differentiation of the tumor cells. The survival was poor in cases who had the components of squamous cell carcinoma and/or adenocarcinoma. Overall survived case were 177, 122 patients died of cancer, 20 patients died of other causes than cancer, and 1 patient died from immediate surgical effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: For screening prostate cancer (CAP) using prostate-specific antigen (PSA), the indications of biopsies for patients showing slightly elevated PSA values are still controversial. Furthermore, the dependence of total PSA, free-to-total PSA ratio (FIT) and PSA density (PSAD) on prostatic volume in gray zone cases is unclear. Methods: By analyzing 1913 patients with a serum total PSA ranging from 2.0 to 20 ng/ml, we evaluated the correlation between total PSA and age or prostatic volume and positive predic­ tive value (PPV) in each range for total PSA, c;lge and prostatic volume. Then suitable reference values for total PSA, FIT and PSAD were decided according to prostatic volume. Results: There was no close correlation between PSA and age or volume. The PPV was high in the group with a prostatic volume of 10-30 ml. Prostatic volume was categorized into three groups

Background: Thedetection of prostate-specific antigen (PSA) molecular formssuchasfree PSA and PSA-ACT andthe useof PSAmolecular ratios, especially the percentage of freeto total PSA, have been reported to improve the diagnostic accuracy of prostate cancer in the patients with slightlyelevated serum PSAvalues. However, thecorrelation among thevaluesofserum free PSA or PSA-ACT obtained in various assays remains unclear. Methods: Serum free PSA and PSA-ACT values were detected with the following assays: Hybritech, DPC, EIKEN, Abbott, Roche and Can-Ag for free PSAand Dainippon, Chugai, EIKEN and Bayerfor PSA-ACT. The dataobtained with eachassaywerecompared with Hybritech (free PSA) and Dainippon (PSA-ACT) as standards. Results: The free PSA data obtained with the Hybritech, EIKEN, Abbott and Can-Ag kits were similar. The values obtained with the OPC and Roche kits showed a linear regression of y = ax + b with thoseobtained with the Hybritech, with a b valueof zero and an a valueof 1.20and1.57, respectively. The serum PSA-ACT values detected with the Dainippon and Chugai kits were identical. The equation for converting the dataobtained withthe EIKEN kitsto the Dainippon value was 0.7636x (EIKEN) + 0.1381. Conclusions: Serum free PSA and PSA-ACT values obtained with various assays were not necessarily the same. Somekits for the assay of free PSAand PSA-ACT gave the sameserum values. The free PSA valuesobtained with the other kits could be converted using appropriate equations. The y-Sm values showed wide variations and were not considered suitable as a measurement of free PSA.

BACKGROUND We studied the clinical significance of serum prostate-specific antigen bound to alpha1-antichymotrypsin (PSA-ACT) values determined with a newly developed enzyme immunoassay. METHODS Serum PSA-ACT values were determined in a total of 652 sera. Clinical utility for the diagnosis of prostate cancer was compared to that of Tandem-R PSA and gamma-seminoprotein (gamma-Sm). The new enzyme immunoassay is based on the use of the Stanford reference as an international standard for PSA assays. RESULTS Serum PSA-ACT values ranged from less than 0.10 to 1.4 ng/mL in healthy males (n = 100) while values in patients with benign prostatic hyperplasia (n = 155) averaged 3.4 +/- 3.8 ng/mL (mean +/- SD). In patients with prostate cancer, serum PSA-ACT values increased significantly with progression of the clinical stage and there were statistically significant differences between benign prostatic hyperplasia and each stage of prostate cancer except for stage A. Using BPH levels as controls (4.8 ng/mL for PSA-ACT, 7.2 ng/mL for PSA, 3.8 ng/mL for gamma-Sm, and 2.4 ng/mL for the complexed/free PSA ratio of PSA-ACT/gamma-Sm), specificity was 80%. The sensitivity of prostate cancer detection was 79% for PSA-ACT, 77% for PSA, 57% for gamma-Sm, and 46% for the ratio between PSA-ACT/gamma-Sm. CONCLUSION Although the determination of serum PSA-ACT showed essentially the same utility as that of PSA for the diagnosis of prostate cancer, PSA-ACT may allow prediction of the clinical stage. The PSA-ACT assay may therefore replace PSA in the detection of prostate cancer.

Prostate specific antigen (PSA) levels after total prostatectomy or radiation therapy to localized prostate cancer and also during endocrine therapy are within normal range. Therefore, it is necessary to use hyper sensitive PSA assay kits for early detection of relapse. The present study was undertaken to evaluate two hyper sensitive assay kits (Delfia kit, lower limit 0.1 ng/ml, Kabi Pharmacia Diagnostics Co. and Markit M kit, 0.5 ng/ml, Dainippon Pharmaceutical Co.) and to compare them with conventional PSA kit (Eiken Chemical Co., 1.0 ng/ml). Total of 291 sera were examined: patients consisted of 10 total prostatectomy+endocrine therapy, 9 radiation therapy+endocrine therapy, 5 radiation therapy alone and 44 endocrine therapy alone. Values of endocrine therapy alone were divided into two groups according to duration after start of treatment; more or less than 5 years. The following results were obtained. 1. In non-relapse patients after total prostatectomy+endocrine therapy and radiation+endocrine therapy, PSA showed under lower limit with hyper sensitive kit. On the contrary, conventional kit indicated more than 1.0 ng/ml. 2. Radiation therapy alone kept PSA in detectable range with hyper sensitive kit in spite of no sign of relapse. 3. In non-relapsed patients under endocrine therapy alone, long duration (more than 5 years after start of treatment) decreased PSA in non detectable values with hyper sensitive kits. In this case, conventional kit still showed PSA as more than 1 ng/ml. 4. Doubling time at relapse was estimated similar with Delfia kit and Markit M kit, and much longer with conventional kit. It is concluded that hyper sensitive kit is more useful to manage patients after therapy than conventional kit.

For local control in patients with endocrine-refractory prostate cancer, an intra-arterial chemotherapy regimen comprising methotrexate (MTX), Adriamycin (ADM), and cisplatin (CDDP) was evaluated. A total of 19 patients having a mean age of 66.4 +/- 8.8 years and a mean performance status (PS) of 1.3 +/- 1.0 were enrolled. Of these patients, 3 had proved to be resistant to initial endocrine therapy and the remaining 16 had relapsed from disease stabilization after endocrine therapy. The catheter tip was placed in the internal iliac artery in 16 cases, in the common iliac artery in 2 cases, and in the aorta in 1 case after occlusion of the contralateral feeding artery. The intraarterial chemotherapy was performed mainly using MTX (30 mg/m2), ADM (30 mg/m2), and CDDP (50 mg/m2) as one course and was repeated for a mean of 2.9 +/- 2.3 courses. Then, in an outpatient clinic, 5-fluorouracil (5-FU), ADM, or MTX was given intra-arterially as maintenance chemotherapy until re-relapse. As based on the criteria for evaluation of nonsurgical therapy in prostate cancer proposed by the Japanese Urological Association, the prostatic lesion showed a partial response (PR) in 9 cases and no change (NC) in 10 cases. As judged from the response of prostate-specific antigen (PSA), a complete response (CR) was obtained in 6 cases, a PR, in 3 cases; and NC and progressive disease (PD), in 2 cases each. Therefore, the overall response rate was 63%. Improvement in the symptoms was observed in 83% of patients. The duration of the response was 15.1 +/- 10.5 months for the PR cases and 7.4 +/- 5.7 months for the NC cases. Furthermore, the mean survival time observed in the PR group was 38.9 months, which was better than that seen in the NC (16.4 months) and PD (10.5 months) groups. These results suggest that intra-arterial chemotherapy may become an option for the treatment of locally advanced and endocrine-refractory prostate cancers. Using a reservoir, this chemotherapy can be easily given in an outpatient clinic.

Serum prostate-specific antigen (PA) values detected by a newly developed enzyme immunoassay (EIA, MARKIT-M PA) as a successor of MARKIT-F PA, which has been a leading kit in Japan, were evaluated for its role in the diagnosis of cancer of the prostate and follow-up of the patients afflicted with the disease. The system is one-step sandwich type EIA using horseradish peroxidase as a tracer and has 0.50-100 ng/ml of detectable range with small amount of sample volume (25 microliters) and reliable quality control data. Furthermore, serum PA values detected by the assay were almost equivocal to those detected by MARKIT-F PA. Serum PA values in prostate cancer patients (n = 122) were statistically higher than those in normal males (n = 90), urological malignancies other than prostate cancer (n = 48) or benign prostatic hypertrophy (BPH, n = 73). Even in the patients with stage A and B prostate cancer, serum PA values were observed to be statistically higher than those in BPH cases. If 3.6 ng/ml was used, which is normal value in MARKIT-F PA, as a cut-off value and BPH cases as a control, the sensitivity, specificity and efficacy for diagnosis of prostate cancer were 77.9, 91.8 and 83.1%, respectively, which showed the best results during the range examined. Serially determined serum PA values in following up the patients with prostate cancer were confirmed to be highly effective to evaluate treatment responses. These results suggest that MARKIT-M PA is thought to be one of the best tool for determination of serum PA values.

Clinical usefulness of a newly developed assay kit for ACB (SD-8828) which detects urinary bacteria coating IgG was evaluated and compared to the enzyme antibody plate method. A total of 48 patients including 20 patients with acute simple cystitis and 28 patients with acute or chronic pyelonephritis, who were shown to have pyuria of at least 5 cells/HPF, bacteriuria of at least 10(4) CFU/ml were enrolled in this study. By enzyme antibody method. ABC was positive in 92.9% of patients with upper urinary tract infection and negative in 100% of patients with lower UTI, this difference being statistically significant (p < 0.02). By SD-8828, 85% of positive coincidence rate and 100% of negative coincidence rate, compared to the enzyme antibody technique, was obtained. The overall coincidence rate was high (91.7%). This SD-8828, a new simple assay for ACB, which detects IgG alternating the plate method, may be used as a convenient method in clinical practice.

A silver colloid technique for the staining of nucleolar organizer regions (NORs) was applied to paraffin sections of 52 clinical prostate cancers, 5 incidental carcinomas of the prostate, 12 benign prostatic hypertrophy (BPH) specimens and 7 normal prostates. The mean numbers of silver-stained NORs (AgNORs) in these lesions were 3.12±0.52 in clinical cancer, 2.65±0.64 in incidental cancer, 1.66±0.16 in BPH, and 1.76±0.22 in normal prostate. There was a statistically significant difference in agNORs numbers between cancer and benign prostatic tissues (p

A 59-year-old man presented with a four-month history of almost painless bilateral scrotal swellings. Histological examination of a biopsy specimen confirmed sarcoidosis. He was well two months later, the mass had not increased, and he was receiving no treatment. This is the nineteenth reported case to our knowledge, and the eighth with bilateral disease.

As neoadjuvant chemotherapy for advanced bladder cancer, the intra-arterial administration of methotrexate (MTX), Adriamycin (ADM), and cisplatin (CDDP; IA-MAC) was evaluated. A total of 48 patients with bladder cancer (greater than or equal to T2 or CIS) were selected and received 30.1 mg MTX, 34.5 mg ADM, and 89.1 mg CDDP as an average course. The mean tumor-regression rate after 2 or 3 weeks was 52.3%, and patients with grade 3 transitional-cell carcinoma showed the best results, achieving a 69.6% regression rate. In 30 cases (63%), downstaging was observed. Among the 46 patients who underwent subsequent surgical therapy, the bladder could be preserved in 26 cases by transurethral resection or segmental resection. According to the criteria of the Japanese Association of Cancer Therapy, a histological effect of GIII or better was obtained in 15 cases (29%). The histological effect correlated well with the tumor-regression rate. As compared with intravenous therapy with MTX, vinblastine, ADM, and CDDP (M-VAC), IA-MAC treatment was well tolerated due to its lower degree of bone marrow suppression, and it resulted in a longer disease-free interval and better survival. In addition, the period prior to surgical therapy was shortened in this study. These results suggest that IA-MAC chemotherapy can be useful as an arm of multidisciplinary treatment of advanced bladder tumors.

Prostate-specific antigen (PA) and gamma-seminoprotein (gamma-Sm) were compared by immunocytochemical, immunodiffusion and immunoblotting methods using rabbit anti-PA antibody and rabbit anti-gamma-Sm antibody. Enzyme immunoassays (EIAs) were developed for measurements of PA and gamma-Sm to determine a correlation between serum PA and gamma-Sm levels in patients with prostate cancer. The patterns of localization and distribution of PA and gamma-Sm were identical in prostate tissue sections, including benign and cancerous human prostates. The immunodiffusion study showed that the antigens with which anti-PA antibody and anti-gamma-Sm antibody reacted in seminal plasma and prostate tissue homogenates were identical to each other. In the immunoblotting study, anti-PA antibody and anti-gamma-Sm antibody recognized a single antigen corresponding to a molecular weight of approximately 33,000 both in seminal plasma and prostate tissue homogenates. The EIAs developed in this study were sensitive, specific, and reproducible, and the correlation between serum PA and gamma-Sm values determined by these EIAs was highly significant (r = 0.99, P less than 0.001). These results indicated that PA and gamma-Sm were immunologically identical and that serum PA and gamma-Sm determined by immunoassays using anti-PA antibody and anti-gamma-Sm antibody should be evaluated as identical tumor markers for serodiagnosis of prostate cancer.

Fluoroquinolones have a broad spectrum of antimicrobial activity and they have been shown to be highly effective in curing urinary tract infection. Tosufloxacin is a fluoroquinolone developed in Japan. We report on a patient in whom tosufloxacin was associated with the formation of bladder stones. CASE REPORT

A reverse enzyme-linked immunosorbent assay (ELISA) modified from a prostate antigen (PA) assay previously reported has been developed to measure circulating PA-binding globulin (PABG). Serum specimens taken from normal males, normal females, male patients with nonprostatic cancers, patients with benign prostatic hypertrophy, and patients with various stages of prostate cancer were analyzed for PABG. Results revealed that only patients with an advanced stage of prostatic cancer exhibited an elevated level of PABG. PABG was then isolated from prostatic cancer patients' serum by PA affinity chromatography. Upon immunodiffusion and immunoelectrophoresis, this PABG preparation reacted with purified PA, anti-PA xenoantibodies and anti-human IgG. By the immunoperoxidase technique, PABG stained positively in prostatic ductal epithelial cells and negatively in all other tissues examined. An additional PABG preparation, which reacted with anti-PA and anti-human IgG and not with purified PA, was also isolated by an anti-PA affinity chromatography. These PABG preparations were separately subjected to high-performance liquid chromatography for further purification. Three major protein peaks at Mr of greater than 240K, 150K, and 34K were obtained. These results demonstrated that circulating IgG antibody reactive with PA was present in patients with metastatic cancer of the prostate, and this in part was in complexed form with PA and was specifically reactive with ductal epithelial elements of the prostate.

A pancreas cancer-associated antigen (PCAA) was identified and isolated from ascites fluid of human pancreatic cancer. Purified PCAA was homogeneous as determined by polyacrylamide gel electrophoresis. PCAA was a glycoprotein with a molecular weight of approximately 1,000,000 and consisted of 20% carbohydrates and 80% peptides, had an isoelectric point of 4.7, and migrated to alpha 2-beta region. It possessed a sedimentation coefficient of 14S and appeared to be a fibrous or fibroglobular protein. Immunoreactivity of PCAA was sensitive to proteolytic enzymes, perchloric acid, KSCN, glycine-HCl at pH 2.5, urea and lithium diiodosalicylate; and insensitive to neuraminidase or beta-glucosidase. Immunohistochemical technique revealed that PCAA was located in the cytoplasm of ductal epithelial cells of malignant pancreas. Using heteroantiserum raised against purified PCAA, horseradish peroxidase and CNBr-activated Sepharose 4B, an enzyme-immunoassay (EIA) for circulating PCAA has been developed. From a group of 40 healthy blood donors, an upper limit of 16.2 micrograms of PCAA/ml of serum has been tentatively determined. An elevated PCAA was shown in 67% (29/43) of patients with pancreas cancer, as well as in 30% (11/36) of lung cancer patients, 27% (10/37) of colonic cancer patients, and in 16% (6/36) of breast cancer patients. The reactive antigen in sera of these cancers was shown to be immunologically identical. PCAA also was detected in extracts of various human tissues, particularly pancreatic tumors, colonic tumors, and in a normal colon. Further, PCAA exhibited heterogeneity in molecular weight, isoelectric point, and electrophoretic mobility.

A 17-year-old patient with mixed gonadal dysgenesis (MGD) showing ambiguous genitalia and hypergonadotropic hypogonadism was described. By intraabdominal exploration, a poorly developed uterus with a fallopian tube and a streak gonad was found on the right side and a poorly developed testis with epidydimis and vas deferens on the left. Chromosomal analysis on cultured peripheral lymphocytes and bone marrow cells showed 45, X karyotype, while among the majority of 45, X + cells small numbers of 46, X + mar cells (3-23%) were found in cultured fibroblasts from the abdominal skin and various organ tissues. We compared our patient with the Japanese patients with MGD reported in the literatures.