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Aim To evaluate the effects of early (≤6 months after starting any medical treatment [baseline] for benign prostatic hyperplasia [BPH]), intermediate (between >6 months and 2 years from baseline) and late (2 years after baseline) initiation of add-on dutasteride therapy on the incidence of acute urinary retention (AUR) and BPH-related surgery in Japanese patients with moderate-to-severe BPH. Methods This multicentre, observational, retrospective chart review study used anonymised data from Japanese medical records. Eligible patients (≥50 years) were followed from baseline until first AUR, BPH-related surgery or Year 4. Results Overall, 1206 patients were included (early initiation: n = 793; intermediate: n = 233; late: n = 180). Early dutasteride initiation was not superior to late initiation in reducing the risk of first AUR or BPH-related surgery from baseline (hazard ratio [HR] 0.733; 95% confidence interval [CI] 0.468-1.150) but was superior in reducing the risk of first AUR alone (HR 3.449; 95% CI 1.796-6.623). One year after initiation, the cumulative incidence of first AUR rose rapidly in the late vs early and intermediate initiation groups. Incidences of all parameters (first AUR/BPH-related surgery, first AUR alone and BPH-related surgery alone) in patients undergoing BPH-related surgery in low incidence sites (ie clinical sites with ≤ 16% incidence of first AUR or BPH-related surgery) were significantly lower in the early vs late initiation groups. Conclusion Early dutasteride initiation reduced the risk of AUR in a Japanese real-world setting. A randomised controlled trial is warranted to evaluate the benefit of early initiation in preventing BPH-related surgery in Japanese patients.

The authors conducted this retrospective study to evaluate the efficacy of radiotherapy (RT) for high-risk patients with adenocarcinoma (AC) compared with chemotherapy (CT) after radical hysterectomy.There were 263 patients with AC and 58 with adenosquamous cell carcinoma (ASCC). Of these 321 patients, 151 received adjuvant treatment. Of these 151 patients, 69 received radiotherapy (RT) alone, including concurrent chemoradiotherapy (CCRT) with weekly cisdiamminedichloroplatinum (CDDP), 64 patients received CT alone, and 18 patients received concomitant RT and CT (RT + CT).The five-year overall survival (OS) was 70.9% for patients receiving RT, 79.2% for CT, and 66.2% for RT + CT. Adjuvant treatment did not affect the incidence or the pattern of recurrence. The incidence of lymph node involvement was 9.0% in Stage Ib1, 23.9% in Stage Ib2, 30.8% in Stage IIa, and 41.2% in Stage IIb.Adjuvant CT may be effective for high-risk patients with cervical adenocarcinoma.

The authors report a case study of a 54-year-old male admitted to our hospital with severe chest pain and ST depression in II, III and aVf lead on the electrocardiogram. The chest X-ray showed an enlarged superior mediastinum. An enhanced computed tomography (CT) was performed and confirmed the diagnosis of acute type A aortic dissection. The patient underwent emergency surgical repair with the replacement of the ascending aorta. The patient recovered without complication until the fifteenth postoperative day, when another severe chest pain appeared. Emergency coronary angiography revealed a remaining dissection in both the left anterior descending artery (LAD) and the left circumflex artery (LCx). Implantation of Elite stents to the LAD and the LCx was performed. The patient recovered uneventfully after this operation. Remaining coronary artery dissection after the replacement of the ascending aorta is very rare. In this case coronary intervention with Elite stents was effective.

Deletions and point mutations of the p16 gene are detectable in more than 50% of ovarian cancer cells. In this study, we examined the effect of p16 gene transduction on the growth of ovarian cancer cells and on the effect of anti-cancer agents.p16-null human ovarian cancer cell lines, SKOV-3 and OVCAR-5, were used in this study. We transduced the full-length human p16 gene using recombinant adenovirus (AxCA-hp16).The spontaneous growth of these cells was significantly inhibited by hp16 transduction. MTT assay revealed that AxCA-hp16 infection induced chemoresistance in both cell lines. Flow cytometric analysis revealed that only hp16 -transduced SKOV-3, were arrested at the G1-phase for 3 days whereas those infected with AxCA-mock and OVCAR-5 infected with both recombinant viruses did not. Western blot analysis showed increased microtubule-associated proteins 4 (MAP4) in both cell lines.These results suggest that in SKOV-3 cells, G1-arrest induced by p16-transduction prevents paclitaxel- and vindesine-induced cell death, and in OVCAR-5 cells, the other unknown mechanisms play a role of chemoresistance.

This study was performed to assess the feasibility of weekly paclitaxel (TXL) and cisplatin (CDDP) in patients with recurrent ovarian cancer. Ten of eleven patients experienced recurrence after more than 6 months after first line CDDP-based chemotherapy. TXL and CDDP were given at initial doses of 60 mg/m2 and 30 mg/m2 on days 1, 8, and 15 in 2 patients and an increase in the respective dose level was planned to 60/35 in 5 patients, 70/35 in 2 patients, and 70/40 in 2 patients. Toxicities were well tolerated. None of the patients suffered from neurotoxicity or myalgia of more than grade 2. Gastrointestinal disorder was recognized as grade 1-2, and grade 3-4 hematological toxicity included leucocytopenia (64%), anemia (36%), and thrombocytopenia (9%). We set the recommended dose of TXL at 70 mg/m2 and that of CDDP at 35 mg/m2, considering toxicity and performed planned schedule. Of eleven patients, nine were assessable by computed tomographic scan. The overall response rate was 67% (CR: 1, PR: 5, NC: 1, PD: 2). One of two patients with standard TXL/CDDP therapy showed PR by switching to a weekly schedule. The median follow-up duration was 490 days and the median response duration was 371 days. From the results presented here, it is suggested that this regimen with increased DI might be quite effective and well tolerated in patients who experience relapse after CDDP-based chemotherapy.

A clinico-pathological study was performed retrospectively on 62 patients who underwent surgery for renal cell carcinoma between January 1992 and October 1998 at Himeji National Hospital to clarify the prognostic determinants for survival. The median follow-up period was 32 months and the cause-specific survival rates at 1, 3 and 5 years were 86.7, 81.3, 81.3%, respectively. Of the 62 patients, 11 (17.7%) patients died of renal cell carcinoma and 2 (3.2%) patients died of unrelated causes. Of the variables related to survival, presenting symptoms, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), tumor size, pathological tumor grade, infiltration pattern, pathological tumor stage, N classification and M classification were significant risk factors for survival by univariate analysis. However, ALP, N classification and M classification were significant for survival as determined by the step-wise procedure and M classification was the most significant factor according to Cox's proportional hazard model analysis.

We evaluated the feasibility of high-dose CEP (cyclophosphamide 750 mg/m2, epirubicin 90 mg/m2, cis-platinum 70 mg/m2) therapy, with granulocyte colony-stimulating factor support every 21 days, in 18 patients with advanced and recurrent ovarian cancer. Ten patients (56%) received 6 cycles of this regimen as planned. Toxicities more than grade 3/4 on' the WHO scale of neutropenia and thrombocytopenia were observed in all cases. Nausea, vomiting, mucositis, malaise, alopecia, hepatotoxicity, and fever were common adverse effects. The average relative dose intensity of cyclophosphamide, epirubicin, cis-platinum was 0.77, 0.77, 0.79 respectively, and each RDI decreased in the last two cycles. These data suggest that this regimen could be performed safely with careful consideration on hepatotoxicity and thrombocytopenia.

Central catecholamines, particularly dopaminergic and noradrenergic systems, have affected the appetitive behavior in patients with anorexia nervosa (AN). The purpose of this study is to distinguish the characteristics of contingent negative variation (CNV) and postimperative negative variation (PINV), which may reflect the level of catecholamine in children with AN.Eight children with AN aged 10 to 15 years and 23 age-matched healthy children were recruited. Contingent negative variation was recorded from the frontal midline (Fz), central midline (Cz) and parietal midline (Pz) referenced to linked earlobes during 30 trials consisting of a warning stimulus and an imperative stimulus with an interstimulus interval of 2 s and an intertrial interval of 10 s. The imperative stimulus of each trial required a button press.Children with AN had a diminished amplitude of the CNV. They had a significantly more attenuated early CNV and late CNV amplitude at Cz than normal children. No significant differences were observed between AN children and normal children in the amplitude of PINV at all three electrode sites. No difference could be found between the two groups in the frequencies of normal and abnormal duration of PINV.These findings suggest that early CNV may be diminished by norepinephrine deficiency and late CNV may be attenuated by dopaminergic deficiency in children with AN. Reduced CNV may represent impaired cognitive processes which reflect impaired appetitive behavior in AN children.

We conducted a multi-site late phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical cancer in cooperation with 32 institutes. Fifty mg/body of oral etoposide was administered daily for 21 consecutive days. Treatment cycles were to be repeated at 4- to 5-week intervals. Eighty patients were enrolled and 70 patients were evaluated. The overall response rate (95% CI), including one complete response patient and 18 partial response patients, was 27.1% (19/70). The most commonly observed toxicity was myelosuppression such as leukopenia, neutropenia, hemoglobin decrease and thrombocytopenia. Other adverse effects were gastrointestinal toxicities such as anorexia, nausea, stomatitis and vomiting, as well as fatigue and alopecia. These adverse effects were well tolerated and controlled with medications. From these results we concluded oral etoposide administered for 21 consecutive days was an effective drug against cervical cancer.

We report a case of a non-Hodgkin's lymphoma (NHL) patient treated successfully with combination chemotherapy during pregnancy who delivered a full-term baby. A 29 year-old patient with cervical and inguinal lymphadenopathy in the 27th week of gestation was referred to our hospital. The diagnosis of lymph node biopsy was NHL (diffuse, large cell type with B-cell phenotype). Three courses of CHOP regimen (adriamycin, cyclophosphamide, vincristine and prednisolone) were given before delivery. The patient has been in complete remission for three years and her baby has been in normal development. Our case supports previous reports that chemotherapy in the third trimester may be given safely on NHL patients.

A 36-year-old woman with early recurrence of uterine cervical cancer had received radiotherapy and a CDDP-containing chemotherapy regimen. She was treated with oral etoposide by administration of 50 mg/day for 21 consecutive days at 14-day intervals. After two courses, complete remission was demonstrated by disappearance of the cervical tumor mass and pelvic lymph node enlargement on MRI. Leukopenia (grade 3) occurred after five courses, as well as alopecia (grade 2) and gastrointestinal discomfort (grade 1) after two courses. The patient has shown no sign of recurrence for 1.5 years. This method might be quite effective for patients with recurrent cervical cancer as well as allowing outpatient treatment and improving the quality of life.

For the clinical application of the cytokine gene therapy, the antitumor effects of systemic administration of Interferon-gamma (IFN-gamma) and those of in vivo direct IFN-gamma gene transfer to the tumors of mouse bladder carcinoma (MBT2) were compared. After the subcutaneous inoculation of MBT2 cells into mice, 10(2), 10(3) or 10(4) units of IFN-gamma were injected intraperitoneally (i.p.) or subcutaneously (s.c.). Neither i.p. nor s.c. injection of IFN-gamma resulted in tumor suppression or prolonged the survival time of tumor-bearing mice. The effect of in vivo direct IFN-gamma gene transfer by a retrovirus vector to MBT2 tumors was also evaluated. After the subcutaneous inoculation of MBT2 cells into mice, a virus culture supernatant containing IFN-gamma gene was injected into the same tumor site once a day for 3 days. In 50% of the mice in the treatment groups with IFN-gamma gene induction, no tumor formation was observed. Tumor-free survival and actuarial survival in the treatment groups were significantly longer than those in the control group. These results showed the possibility of in vivo direct IFN-gamma gene transfer into tumors and were encouraging for the execution of tumor cell-targeted IFN-gamma gene therapy against human bladder cancer.

Two cases of renal artery embolism treated by selective intra-arterial infusion of tissue plasminogen activator (t-PA) are reported. A 74-year-old woman with atrial fibrillation presented with left flank pain of 54-hour duration. Selective renal angiography revealed embolic obstruction of multiple segmental arteries in the left kidney. She was treated by one-shot intra-arterial t-PA infusion (8,000,000 units) and intravenous heparinization (25,000 units/3 days). Although fibrinolysis was successful except for most distal arterial branches, complete recovery of renal function was not obtained. A 66-year-old man presented with complete obstruction of left main renal artery. He had hyperthyroidism and atrial fibrillation. At 75 hours after onset of left flank pain, he was treated by one-shot intra-arterial t-PA infusion (18,000,000 units) and intravenous heparinization (4,000 units/24 hours). His renal function was recovered completely. Selective intraarterial t-PA infusion is considered an effective treatment for renal artery embolism.

Slower growing and peculiar colonies, "fried egg" appearance, of different sizes were temporally grown on a sheep blood agar plate from a clinical blood sample obtained from a patient with mediastinitis due to infection by methicillin-resistant Staphylococcus aureus (MRSA) following the graft replacement of thoracic aorta. The organisms revealed morphologically characteristic "fried egg" appearance, mainly Gram-positive cocci including some Gram-negative cells and cell-debris, catalase test positive and coagulase test positive as well as having the identical profiles for S. aureus on biochemical examination with VITEK Systems. The rough surfaced cell walls with unequal thickness of the organisms were observed in an electronmicroscope. According to these bacteriological studies, the organisms were identified as a mutant of S. aureus which had many similarities to staphylococcal L-form. Being resistant to oxacillin, instead of methicillin susceptibility test, and possessing a mecA gene, the organisms were confirmed to belong to MRSA. It is likely that this mutant of S. aureus was induced by a long term medication of sulfamethoxazole-trimetoprim, since the patient had been receiving the drug during 5 weeks when the colonies were first detected.

A new therapeutic strategy for advanced ovarian cancer is to administer ultra-high doses of anticancerous drugs, followed by peripheral blood stem cell transplantation (PBSCT) to recover normal marrow functions. There are, however, no clear regimens to induce mobilization of peripheral blood stem cells (PBSCs). We therefore used three different chemotherapies and granulocyte colony-stimulating factor (G-CSF) to produce a rebound increase in PBSCs during myelosuppression by apheresis. Eleven patients with advanced ovarian cancer (FIGO Stage; IIc-1, IIIc-5, IV-4, Recurrence-1) received chemotherapy with CEP (cyclophosphamide: 500-750mg/m2, epirubicin: 50-70mg/m2, cisplatin: 70mg/m2), CEE (cyclophosphamide: 2,000mg/m2, epirubicin: 50mg/m2, etoposide: 300mg/m2, and PEC salvage (cisplatin: 75mg/m2, etoposide: 300mg/m2, cyclophosphamide: 1,000mg/m2) followed by lenograstim (G-CSF; 2 micrograms/kg subcutaneous injection daily for 14-18 days) to mobilize PBSCs. A range of 0-38.2 x 10(4) (mean +/- S.D.; 11.1 +/- 5.0 x 10(4) colony forming unit granulocyte-macrophage (CFU-GM)/kg in the CEP regimen (n = 15), 1.6-40.8 x 10(4) (mean +/- S.D.; 12.3 +/- 3.6 x 10(4) CFU-GM/kg in the CEE regimen (n = 11), and 8.6-11.4 x 10(4) (mean +/- S.D.; 10.0 +/- 2.0 x 10(4) CFU-GM/kg in the PEC salvage regimen (n = 2) were recruited by a single apheresis. Although the CEE regimen to mobilize PBSCs was much more efficient than the CEP regimen, a large number of PBSCs showing 38.2 x 10(4) CFU-GM/kg were mobilized by the CEP regimen with a dose-escalation of cyclophosphamide 750mg/m2 and epirubicin 70mg/m2. The number of CFU-GM/kg correlated well with that of CD34+ (r = 0.693).(ABSTRACT TRUNCATED AT 250 WORDS)

We analyzed the sensitizing activity of five agents, which have been assumed to be MDR-overcoming drugs, in two human renal cell carcinoma cell lines expressing the MDR1 gene at high levels. In addition, we studied the sensitizing activity of cepharanthin, an MDR-overcoming agents, to vinblastine, adriamycin, epirubicin, cisplatin, mitomycin C and etoposide. Based on the results, we treated 6 patients with metastatic renal cell carcinomas (4: bones, 2: contralateral kidneys) by intraarterial injection of vinblastine and adriamycin (or epirubicin) in combination with cepharanthin. Two of the 4 bone metastasis cases responded markedly to the treatment. Renal tubular impairment was observed in one patient who was treated for the contralateral kidney metastasis.

Tumour cell-targeted cytokine gene therapy of cancer has been proposed using various cytokine genes including interferon (IFN)-gamma gene. In the course of the experimental approach using IFN-gamma gene, we established two IFN-gamma gene-transferred clonal sublines, IFN-gamma producer and non-producer, from a murine bladder tumour line MBT-2 via retroviral transfer of mouse IFN-gamma cDNA, and studied the influence of local secretion of IFN-gamma on tumour progression. While cell growth in vitro was not affected by gene transfer, expression of major histocompatibility complex (MHC) class I antigens was increased in both sublines. The IFN-gamma producing cells injected subcutaneously into syngeneic mice could not induce tumours but the non-producing cells tended to induce tumours. Thus the increase in MHC class I expression was not enough to cause tumour regression, and IFN-gamma secretion over a certain amount was needed for tumour suppression, probably in addition to MHC class I expression. Mice that rejected IFN-gamma producers established a specific anti-tumour immunity and spleen cells derived from the mice contained populations of CD8+ effector T cells against MBT-2 cells. These results supported previous reports that IFN-gamma gene transfer into tumour cells apparently abrogated the tumorigenicity by augmenting the host anti-tumour immunity, and were encouraging for a promising execution of the tumour cell-targeted IFN-gamma gene therapy against human bladder cancers.

We established constitutively an interferon-gamma (IFN-gamma) producing cell line (MBT2/gamma) from a mouse bladder cancer cell line (MBT2) by retroviral transfer of a mouse IFN-gamma cDNA. Although the in vitro cell growth of these cells was unaffected by the IFN-gamma production, their subcutaneous tumor growth in syngeneic C3H/He mice was different; MBT2/gamma tumor growth was more strongly suppressed (3/20) than that of MBT2 (10/10). MBT2/gamma tumor growth was observed in nude mice (6/6). The mice immunized with MBT2/gamma were resistant to tumor growth of the parental cells (7/9; 77%), but permitted the growth of another kind of C3H/He tumor line. These findings indicate that the reduced tumorigenicity of the IFN-gamma producing line was due to the augmented specific antitumor immunity, probably as a result of the immunomodulatory effects of the IFN-gamma derived from the tumor.

The results of clinical application of a Dornier Lithotripter Compact (Dornier Medical Systems Co., Ltd.) on upper urinary tract stones are presented. Between October 1991 and June 1992, 30 patients with upper urinary tract stones were treated with ESWL in the Department of Urology, Kyoto University. Although 49 sessions for 32 stones in total were carried out without anesthesia, analgesics such as indomethacin and/or pentazocine were required in 37 sessions (76%). Stone-free rate 3 months after the last session was 12/30 cases (40%) and the success rate, the ratio of the patients without residual stone or with residual stones less than 4 mm to total 30 patients, was 18/30 (60%) at the point. Macrohematuria was seen after the treatment in 42/49 (86%) sessions, but it disappeared within 3 days in all instances. Pain necessitating analgesics after the treatment was seen in 16/49 (33%) sessions. Subcutaneous bleeding and fever-up of less than 38 degrees C were seen in 15/49 (31%) and 8/49 (16%) sessions, respectively, but bacteremia after the treatment was not detected in any case. No serious adverse effects were observed in blood chemistry. The Dornier Lithotripter Compact is considered to be useful in the treatment of renal and upper third ureteral stones.

Treatment of guinea pig polymorphonuclear leukocytes (PMNL) with phorbol 12-myristate 13-acetate (PMA) induced an increase in phosphorylation of 46 kDa protein(s) in parallel with activation of NADPH oxidase. In response to PMA stimulation, phosphorylated 46 kDa protein(s) increased markedly in the membrane fraction, accompanied by a decrease in the unphosphorylated form(s) in the cytosol. The results indicate that the 46 kDa protein(s) may be translocated concomitantly with its phosphorylation. On the other hand, in a cell-free activation system reconstituted from the cytosol and plasma membranes of unstimulated PMNL, arachidonic acid caused the translocation of the 46 kDa protein(s) from the cytosol to the plasma membranes concomitantly with an enhancement of NADPH oxidase activity. These results suggest that activation of NADPH oxidase is dependent on an association of 46 kDa protein(s) with the membranes both in intact PMNL and in the cell-free system.

In order to evaluate the clinical significance of multiple tumor markers, plasma levels of carcino-embryonic antigen (CEA), squamous cell carcinoma-related antigen (SCC), tissue polypeptide antigen (TPA) and immunosuppressive acidic protein (IAP) were measured before and after treatment in 136 patients (89 surgery cases and 47 radiotherapy cases). The patients had invasive cervical carcinoma (stages I-IV). The effect of radiotherapy was examined by cytology and biopsies obtained by colposcopy. For CEA, SCC and TPA there was a significant reduction (p less than 0.01) in values between the pretreatment and posttreatment periods, but plasma IAP was transiently increased after operation. Cytology and histology revealed negative rates of 95.6% and 86.7%, respectively, after radiotherapy. Regarding recurrence, for the negative groups and positive groups plasma CEA, SCC, TPA and IAP were determined in 24 patients with stage IIIb before radiotherapy. Only the CEA concentration showed a good correlation with the outcome (p less than 0.01). Effective serial plasma determinations of CEA, SCC and TPA in patients with cervical carcinoma following therapy may often be useful in the evaluation of therapy as well as in the earlier detection of recurrent disease.

Seventy-six patients with cervical cancers underwent preoperative abdominopelvic computed tomography before a pelvic lymphadenectomy to evaluate the efficacy of computed tomography in assessing pelvic lymph node metastases. The sensitivity and the specificity of computed tomography for detecting pelvic lymph node metastases were judged to be 70.6 and 89.8%, respectively. In 54 patients in stage Ib or IIa of the disease, the sensitivity and specificity were 85.7 and 91.5%, respectively. Although inaccuracies could be caused by normal-sized metastasized lymph nodes and by enlarged lymph nodes with reactive hyperplasia, computed tomography was found to be a useful method of detecting a pelvic lymph node metastasis.

A case of an endometrial carcinoma occurring in both horns of a uterus bicornis unicollis in a 50-year-old women is described. This diagnosis can be easily missed unless both endometrial cavities are curetted simultaneously in cases of an either right or left affected fundus of a divided uterus. The correct diagnosis and a prompt definite treatment in this rare combination are emphasized.

Two cases of renal angiomyolipoma without tuberous sclerosis are reported. The first case was of a 35-year-old man with complaints of right upper abdominal and right flank pain. Preoperative diagnosis was right renal angiomyolipoma. Thoracoabdominal radical nephrectomy and lymphadenectomy were performed. The pathological diagnosis was renal angiomyolipoma with lymph node involvement. The second case was of a 46-year-old woman whose left renal mass had been accidentally found by ultrasound study. Preoperative diagnosis was left renal angiomyolipoma. This tumor was enucleated from the left kidney through flank incision.

In order to investigate the kinetics of the synthesis and release of the secretory protein in the STH-secreting cell of the pituitary anterior lobe, studies were made using the electron microscopic autoradiography of 3H-amino acids. Each mouse received an intravenous injection of 2.8 mCi of 3H-amino acids consisting of equal amounts of 3H-leucine, 3H-tyrosine, 3H-lysine, 3H-histidine and 3H-glycine. The animal was sacrificed at 3, 5, 15 and 30 min, 1, 2, 4, 8 and 24 hrs after the injection. Although the whole silver grains are very few 3 min after the injection, half of the grains are recognized over the r-ER (47.1%); the Golgi apparatus already shows a few grains (5.9%). Total silver grains over the STH-cell increase in number with the lapse of time; the ratio of the grain number over the r-ER to the total grains over the whole cell decreases gradually, while the ratio of the grain number over the Golgi apparatus increases to reach a peak about 30 min after the injection (40.1%) and then decreases gradually. The ratio of the number of labelled granules to that of total granules increases slowly until 24 hrs after the injection (3 min: 0%, 5 min: 0.8%, 30 min: 3.9%, 2 hrs: 5.0%, 8 hrs: 8.0%, 24 hrs: 12.3%). It is concluded that the turnover in synthesis and release of exportable protein in the mouse STH-cell is very slow as compared with that of the thyroid and parathyroid cell.

Cisplatin was administered to 11 patients as a continuous infusion, 25 mg/m2/day for 1 to 4 days. Total and filterable platinum in plasma were monitored for 12 courses and a pharmacokinetic study was carried out in 7 patients by computerized nonlinear least-squares analysis. Following interruption of the infusion, the decrease of plasma filterable platinum was biphasic, with initial and terminal half-life of 21.6 +/- 11.4 min and 31.7 +/- 27.1 hr. Filterable platinum was still detectable in plasma 24 hours after the end of infusion. The total AUC exposure of filterable platinum for 24 hrs, 48 hrs and 96 hrs infusion were 3.67 micrograms.hr/ml, 13.68 micrograms.hr/ml and 14.75 micrograms.hr/ml, which were at least 3-fold higher than that observed for the short-term infusion of equal dose in literature. Gastrointestinal toxicity was evaluated and compared with short-term infusion of equal dose. In the continuous-infusion patients, the reduction of vomiting was observed but the duration of nausea was not shortened.

Seventeen solitary renal cysts were punctured with the ultrasound-guided procedure and 26-91% of the cyst volume was replaced with 95% ethanol used as a sclerosing agent of the cyst wall. Ethanol was injected through a 7 F pigtail ureteral catheter, allowed to remain in place for 20 minutes and removed through the catheter. Recovery rate of ethanol was 82.4%. The maximum blood level of ethanol was obtained 30 to 60 minutes after injection, while the maximum urinary excretion rate was observed after 60 to 120 minutes. The maximum blood levels of ethanol ranged from 0.015 to 0.339 mg/ml. There was a positive correlation between injected volume of ethanol and the maximum blood level (r = 0.66) or the total amount of urinary excretion during 12 hours (r = 0.72). Residual ethanol concentrations in the body were calculated from injected volume and recovery rate of ethanol. Only 2.3% of the residual ethanol in the body was excreted in the urine during the first 12 hours after injection. However, urine/blood ratio of ethanol 1 hour after injection was tremendously high with a wide variation between 1.6 and 230.5. Therefore, a large part of the ethanol absorbed from the cyst wall seems to be excreted directly from the kidney, not entering general circulation. From the estimation of the blood and urine levels of ethanol, it is concluded that 95% ethanol can be applied to the renal cyst wall as a sclerosing agent through the percutaneous ultrasound-guided procedure in the case of good recovery of ethanol.

Since reduced antithrombin III (AT III) activity are associated with increased risk of thromboembolism, we have determined it in 39 patients with prostatic carcinoma. Pre-treatment levels were determined in 24 patients, 6 additional patients with prostatic carcinoma on estrogen treatment and 9 patients on chlormadinone acetate (CMA) therapy. In 12 of 24 patients we studied AT III levels before and after estrogen therapy was initiated. A significant decrease in AT III activity of 23.5% was found after one month on estrogen treatment, the patients on low doses of estrogen. Recovery of the levels of AT III was found after 6 months treatment even in in 5 of 6 patients who had shown depression of AT III levels initially. CMA treatment did not cause its depression. AT III levels was not connected with the stage of the disease or age of the patient.

A case of a cervical cancer in a 40-year-old woman with a plasma carcinoembryonic antigen (CEA) level of 29.4 ng/ml was investigated using light and electron microscopy. In addition, the plasma CEA levels before treatment were determined in 168 patients with cervical cancer and in 33 patients with endometrial cancer. CEA was found to be elevated in the plasma of 19% of those with cervical cancer and in 6% of those with endometrial cancer. Effective serial plasma CEA determinations following therapy, in patients whose plasma or tumors initially contain elevated amounts of antigen, might be useful as an adjunctive method in the earlier detection of a recurrent cancer.

A case of rhabdomyosarcoma of the right kidney is presented. A 78-year-old man was admitted with the complaint of abdominal pain and abdominal fullness on March 15, 1985. Radiological examination showed a giant tumor of the right kidney. Radical nephrectomy and right hemicolectomy were performed. Histological findings were embryonal rhabdomyosarcoma of the kidney. Residual tumor in the duodenal area recurred and he died of peri-duodenal abscess 2 months after admission. This case is the 17th case of rhabdomyosarcoma of the kidney in Japan. The literature is reviewed and discussed.

Adjuvant chemotherapy mainly consisting of cisplatin, adriamycin and mitomycin C was administered to 17 patients after cystectomy for bladder tumor (chemotherapy group). Seventeen concurrently treated patients did not receive adjuvant chemotherapy (control group). From the comparison of survival curves of these two groups, the following results were obtained. 1) Survival curves of the patients in all stages did not differ significantly between chemotherapy and control groups. 2) Among patients in stage pT3, pT4 and/or N+, survival of the chemotherapy group seemed to have some advantage over that of the control group, but the survival curves did not differ significantly between these two groups. 3) Among patients in N+, survival of the chemotherapy group was far better than that of the usual cases. Review of the literature on adjuvant chemotherapy after cystectomy for bladder tumor revealed the necessity of randomized study to determine whether adjuvant chemotherapy is effective.

Surgical excision of the indurated penile plaque and tunica vaginalis autografting was done in 3 patients. Preoperatively, their chief complaints had not been impotence but penile angulation or pain. Postoperatively, all of them improved and erectile failure was not seen, although hypesthesia of glans developed in all patients. One patient complained of impotence. The patients had been followed from 2 months to 9 months. As prosthesis is not prevailing in Japan and tunica vaginalis is easy to procure and handle, tunica vaginalis autografting is recommended.

Double-J or double-pigtail ureteral stent was used in 7 cases, 6 cases for ureteral obstruction and 1 case for ureterocutaneous fistula in irradiated patients. In 5 cases ureteral stent failed to drain effectively, in 4 of these 5 cases due to stent obstruction by necrotic tissue which led to percutaneous nephrostomy in 3 cases. In 1 case the ureteral stent drained well and in another case effectiveness of ureteral stent was equivocal. We think that ureteral stent is neither safe nor effective for internal divertion except in short term use postoperatively.

A case of paratesticular rhabdomyosarcoma is presented. An 18-year-old male was admitted with the complaint of giant scrotal swelling and abdominal fullness on September 5, 1986. Left radical orchiectomy was performed with the pathologic diagnosis of alveolar rhabdomyosarcoma. The tumor was paratesticular in location and had invaded a spermatic cord. Radiological examination showed a gross metastatic mass in retroperitoneal lymph nodes, supraclavicular lymph nodes and Douglas pouch. The patient received induction chemotherapy containing vincristine, actinomycin-D, cyclophosphamide, bleomycin, CDDP and VP-16. After 3 courses, he had no mass in Douglas pouch and supraclavicular lesion. He received retroperitoneal lymph node dissection for residual retroperitoneal mass, and postoperative radiotherapy was given. However, recurrent disease was developed in the paraaortic region with malignant ascites. He was treated with salvage chemotherapy, had without any significant effect. He died of liver dysfunction due to progressive mass in hepatic hilum. A review of the current approach of paratesticular rhabdomyosarcoma with the usefulness of combination chemotherapy is given.

The testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin levels were measured by radioimmunoassay up to one year in 21 patients with prostatic carcinoma treated with diethylstilbestrol diphosphate (DESP), 50 mg/day, and chlormadinone acetate (CMA), 100 mg/day. The purpose of this treatment was to reduce the cardiovascular side effects which were believed to occur dose-dependently and to achieve the direct drug action to the prostate gland. The same measurements were made on 9 patients treated with DESP, 50 mg/day, alone. Marked reduction of plasma testosterone and FSH levels with weaker LH suppressions was observed during the first 1-3 months in both groups. The same levels were maintained up to the end of follow-up in DESP and CMA treatment group. In the DESP treatment group, the plasma level of testosterone showed a gradual increase to 1.0 +/- 0.5 ng/ml at the sixth month. Prolactin level increased gradually in both groups. Cardiovascular side-effects were found in 29% of the patients treated with DESP and CMA and in 22% of those treated with DESP alone. In two patients in the former group gynecomastia with lactation was observed.

Between June, 1983 and December, 1988, 40 patients with primary bladder tumor underwent total cystectomy. Of the 40 patients, 33 (82.5%) were treated by total cystectomy at first presentation. Only 7 patients (17.5%) had prior history of bladder tumors. The mean time from the onset of symptoms to consultation was 11.5 months. In 68.5% of the evaluable 35 patients, gross hematuria was the first symptom. In 74.4% of the 39 evaluable patients, preoperative urine cytology was positive. If class III (suspicious) was included, the positive urine cytology rate was 82.1%. The operative mortality rate was 15%. Early complications occurred in 52.5% of the 40 patients. Late complications occurred in 35.3% of the 34 patients. The 1-, 2- and 3-year actual survival rates of the 40 patients were 69.6%, 65.5% and 65.5% respectively. The 2-year survival rate according to pathologic stage was 14.3% for patients in pT4, 43.8% in pT3b, 75% in pT3a, 100% in pT2, 78.8% in pT1 and 100% in pT0 + pTis. Of the 28 patients who underwent pelvic lymphadenectomy, 8 (28.6%) had positive nodes, including 1 of 1 (100%) in pT4, 5 of 7 (71.4%) in pT3b, 1 of 6 (16.7%) in pT3a, 1 of 4 (25%) in pT2 and 0 of 10 (0%) in pT1 + pT0 + pTis. The prognosis of the 7 patients who had prior history of bladder tumor was poor. The selection of initial therapy and the clinical follow-up should be done carefully.

Kinetics of protein synthesis in the human granulosa lutein cell during pregnancy were investigated using the electron microscopic autoradiography of 3H-leucine. The corpus luteum of early pregnancy was chased at 10 and 30 min, 1, 3, 6, 12, 24 and 48 h after pulse labelling (10 min) with 100 microCi of 3H-leucine. Although the whole silver grains were very few at 10 min postpulse, silver grains were localized mainly over the rough endoplasmic reticulum (r-ER, 34.3%) and there were no silver grains over the smooth endoplasmic reticulum (s-ER). At 30 min postpulse, the ratio of the grain number to r-ER is decreased (18.7%) and silver grains begin to appear over the s-ER (5.4%). The total number of silver grains over the cell increases with the lapse of time, the ratio of the grain number over the r-ER slightly increases and then decreases afterwards, while that over the s-ER continues to increase gradually. From these facts, it is felt that some protein synthesized on the r-ER might be transported to the s-ER in the human granulosa lutein cell during pregnancy showing steroidogenic activity.

A case of a virilizing ovarian Leydig cell tumor in a 38 year-old woman with a markedly elevated plasma testosterone level was investigated using light microscopic dry-mounting radioautography and electron microscopic cytochemistry. Following total abdominal hysterectomy and bilateral salpingo-oophorectomy, the plasma testosterone level fell abruptly. Light microscopic dry-mounting radioautography for 3H-cholesterol showed silver grains mainly localized over the cytoplasm of the tumor cells. In the Leydig cell tumor there were three different cell types: Fibroblast-like cells, Leydig cells (steroid-secreting cells) and transitional cells (partially or incompletely differentiated Leydig cells). Reaction products for 3 beta-hydroxysteroid dehydrogenase activity were localized on tubular or lamellar cristae and inner membranes of the mitochondria, and on the membranes of smooth endoplasmic reticulum in the transitional cell as well as in the Leydig cell. From these facts, it is suggested that the Leydig cell tumor is derived from the fibroblast-like cell and the Leydig cell, already has a steroidogenic activity in secreting testosterone.

A 51-year-old man was admitted with the complaint of left scrotal swelling (11 x 5 x 5 cm). He had undergone left nephrectomy and removal of tumor thrombus in inferior vena cava due to renal cell carcinoma. Nine months after the nephrectomy, left scrotal enlargement was noticed. Left high orchiectomy was performed on January 20, 1988. A clear cell carcinoma was present in spermatic cord and pampiniform plexus histologically but testis and epididymis were intact. Renal cell carcinoma seemed to disseminate retrograde through the spermatic vein to spermatic cord. The metastatic tumor of spermatic cord from renal cell carcinoma is very rare and this case is the fifth case in the Japanese literature.