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To evaluate the relationship between dentists' demographic changes and their uneven geographical distribution.Secondary analysis of nationwide government surveys, to assess trends in the geographical distribution of dentists by gender and age from 1996 to 2014 in Japan.The Gini-coefficient for the number of dentists per population from 47 prefectures decreased from 0.084 in 1996 to 0.069 in 2014. The coefficients for female (0.124-0.144) were higher than for male dentists (0.058-0.081). Coefficients for dentists aged 60 and older were lower than those for dentists younger than 40 in 2014 (male: 0.060 vs. 0.112; female: 0.107 vs. 0.169).The geographical maldistribution of dentists in Japan has improved. Demographic changes among dentists, including the increasing number of female dentists, could moderate this improvement.

Background:Rapidly destructive coxopathy (RDC) is an unusual subset of osteoarthritis of the hip characterized by rapid chondrolysis with progressive loss of the joint space as the first manifestation of the disease. Because rapid progression of RDC makes it difficult to obtain sequential radiographs in its early stage, the process of disease progression in the early stage remains unclear. Although the pathogenesis of RDC is still unclarified, the potential causes of RDC include subchondral insufficiency fracture of the femoral head resulting from osteoporosis, pelvic posterior inclination in RDC as a mechanical factor, and increased serum levels of matrix metalloproteinase (MMP)-3 as a biological factor.Objectives:This study aimed to differentiate the process of disease progression in the early stage of RDC and provide its new classification system.Methods:This monocentric retrospective study included 42 female patients who met the criteria of RPOH, chondrolysis >2 mm during 12 months from the onset of hip pain based on a series of radiographs and computed tomography (CT). This study also included 9 female patients with osteoarthritis secondary to developmental dysplasia of the hip (DDH), who demonstrated chondrolysis >2 mm during 12 months from the onset of hip pain. Cortical thickness index (CTI) correlated with bone mineral density of the hip, pelvic tilt, and serum concentrations of matrix metalloproteinase (MMP)-3 were analyzed.Results:RDC were classified into two types based on the absence (type 1, n=17) and presence (type 2, n=25) of subsequent femoral head destruction shown by CT within 12 months after the onset of hip pain. MMP-3 significantly increased in RDC type 2 compared with type 1 and DDH. Increased posterior pelvic tilt was found in RDC type 2 compared with DDH. Logistic regression and receiver operating characteristic curve analyses indicated that MMP-3 may be associated with differentiation between RDC types 1 and 2. No difference was found in CTI between RDC types and DDH.RDC type 2 hips developed partial (type 2A) and massive (type 2B) femoral head destruction within the first 12 months. Whereas partial destruction showed 40% collapse ratio. Increased posterior pelvic tilt was found in massive destruction. Femoral head destruction started earlier within the first 6 months in massive destruction compared with that in partial destruction. From receiver operating characteristic curve analysis, pelvic tilt differentiated the femoral head destruction types using the initial radiograph at the onset before first demonstration of femoral head destruction. No difference was found in CTI or MMP-3 between the two subtypes.Conclusion:Disease progression of RDC during 12 months after the onset of hip pain could be classified into two distinct types based on the absence (type 1) and presence (type 2) of femoral head destruction in association with MMP-3 and pelvic tilt as biological and mechanical factors, respectively. MMP-3 may be helpful to differentiate those two types in the early stage of RPOH. The extent of femoral head destruction could further differentiate RDC type 2 into two subtypes based on pelvic tilt.Acknowledgments :This study was supported by the Japan Hip Joint Foundation.Disclosure of Interests:None declared

Aim The purpose of this study was to detect Slackia exigua from root canal samples using a sensitive PCR amplification method. Mogibacterium timidum and Eubacterium saphenum were also included because of their culture-difficult properties. Methodology The species-specific PCR primers were prepared according to 16S rDNA sequence analysis data, and confirmed to be effective for PCR amplification as species-specific, respectively. A total of 36 clinical samples were obtained during the first visit of root canal treatment. Results The sensitivity of detection was a minimum of 10 organisms for S. exigua and five organisms for M. timidum and E. saphenum, respectively. In seven cases of pulpitis, S exigua was detected in two cases (29%), and M. timidum in two cases (29%), but E. saphenum was not detected. In 17 cases of root canal treatment, S.exigua was detected in seven cases (41%), M. timidum in 12 cases (71%) and E. saphenum in four cases (24%). In 12 cases of root canal retreatment, S. exigua was detected in three cases (25%), M. timidum in three cases (25%) and E. saphenum in two cases (17%). Conclusions S. exigua, M. timidum and E. saphenum were present in root canal systems, and may be associated with pulpal and periradicular pathosis.

A new genus, Mogibacterium, is proposed for anaerobic, non-spore-forming, Gram-positive, rod-shaped bacteria which have been isolated from the periodontal pockets of adult human patients with periodontal disease and infected root canals. The novel isolates, strains D2-18T, BA11a-f and D5-2T, were inert in most of the conventional biochemical tests and phenotypically resemble asaccharolytic Eubacterium species. The protein profiles of whole cells on SDS-PAGE gels and Western immunoblotting reaction analysis distinguished these organisms from type strains belonging to the previously described Eubacterium species. The G + C content of the DNA is 45-46 mol% for Mogibacterium pumilum and 46 mol% for Mogibacterium vescum. The levels of DNA-DNA relatedness of these new species to other Eubacterium species, including Eubacterium limosum, Eubacterium brachy, Eubacterium lentum, Eubacterium nodatum, Eubacterium saphenum, and the more recently proposed Eubacterium minutum and Eubacterium exiguum (reclassified as Slackia exigua), are less than 2%. The DNA-DNA hybridization value between M. pumilum and M. vescum was 30%. Eubacterium timidum exhibited DNA homologies with Mogibacterium species which were low (17 and 18%) but clearly higher than with all the other Eubacterium species. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the closest phylogenetic neighbour of Mogibacterium species was E. timidum, and that these three species represent a novel lineage distinct from the previously described genera of Gram-positive, rod-shaped bacteria. On the basis of phenotypic characteristics and 16S rRNA gene sequence comparisons, it is also proposed that E. timidum is transferred to the genus Mogibacterium gen. nov. as Mogibacterium timidum gen. nov., comb. nov. (type strain ATCC 33093T).

A miniaturized X-band MMIC T/R module for conformal array antenna has been developed based on a newly designed cylindrical package concept aiming at easier assembly of the package and the array. The overall package measures 19 mm in diameter excluding the base flange and 15 mm in height and weighs 18 g. The module provides 2W output power in X band.

A conformal active phased array antenna the shape of which is an elliptical cylinder was developed. Features of this antenna and transceiver/receiver module, digital beam forming (DBF) architecture developed for conformal antenna, and measured antenna patterns both in transmitting and in receiving, are described. The validity of the two-dimensional DBF with the maximum S/N weight design architecture confirmed through an experiment are also presented.

A conformal antenna, which is regarded as promising airborne antenna in the future, has been experimentally manufactured and tested with regard to its radiation characteristics. On the realization of the antenna, down-sizing of transmit/receive modules, thinning of RF feed networks and development of the radiation pattern synthesis method which is applicable to whatever shape of the array antennas are performed. The antenna array aperture has a doubly-curved surface of the curvature radius of 0.6 meter on the left side and 0.9 meter on the right side in the elevation plane and 5 meter in the azimuth plane. The operating frequency is in the X-band and digital beam forming (DBF) technique is adopted for the elevation plane beam forming in the receive mode. The measured radiation patterns showed a good agreement with the calculated ones.

The purpose of this study was to detect Slackia exigua from root canal samples using a sensitive PCR amplification method. Mogibacterium timidum and Eubacterium saphenum were also included because of their culture-difficult properties.The species-specific PCR primers were prepared according to 16S rDNA sequence analysis data, and confirmed to be effective for PCR amplification as species-specific, respectively. A total of 36 clinical samples were obtained during the first visit of root canal treatment.The sensitivity of detection was a minimum of 10 organisms for S. exigua and five organisms for M. timidum and E. saphenum, respectively. In seven cases of pulpitis, Sexigua was detected in two cases (29%), and M. timidum in two cases (29%), but E. saphenum was not detected. In 17 cases of root canal treatment, S. exigua was detected in seven cases (41%), M. timidum in 12 cases (71%) and E. saphenum in four cases (24%). In 12 cases of root canal retreatment, S. exigua was detected in three cases (25%), M. timidum in three cases (25%) and E. saphenum in two cases (17%).S. exigua, M. timidum and E. saphenum were present in root canal systems, and may be associated with pulpal and periradicular pathosis.

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.

A 19-year-old man sustained a fracture of the left ischial rami and disruption of the membranous urethra when a car hit him against a wall. A suprapubic tube was placed and was used for reconstruction of the disrupted urethra 3 months later. Eighty days after the injury, an 11.5 F ureteral resectoscope was inserted through the open cystostomy tract. Simultaneously, a 11 F pediatric cystoscope was inserted via urethra. Using the "cut to the light" procedure, the scar tissue was incised with sharp strokes of the ureteral resectoscope revealing the distal urethral lumen. Sequentially, urethral dilatation to 24 F was performed over a 0.038 Teflon-coated guide wire following insertion of a 24 F urethral catheter. The urethral catheter was removed 22 days after the operation. Direct vision urethroscopy was performed at 1- to 2-week intervals for 3 months. At present 13 months after the operation, he performs 18 F urethral self-dilation and has been free of voiding complaints. The ureteral resectoscope is useful for endoscopical reconstruction of urethral disruption.

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.

We report a case of uretero-aortic fistula. A 69-year-old man with rectal cancer underwent a pelvic exenteration and a double--barreled cutaneous ureterostomy in the right lower abdomen. Stomal stenosis necessitated continuous indwelling of double J stents in the two ureters. Two years postoperatively, massive bleeding occurred during exchange of double J catheters. Occlusive ureterogram demonstrated a uretero-aortic fistula at the crosspoint between the left ureter and the aorta. The surgical repair consisted of closure of the aortic fistula, ligation of the left ureter proximal to the fistula and percutaneous left nephrostomy.

A 69-year-old man complained of a painless left scrotal swelling. The scrotal mass was enlarged to a hen's egg size with a smooth surface. The scrotal ultrasonogram showed diffuse hypoechogenicity. A testicular tumor was suspected and left high orchiectomy was performed. Histopathological diagnosis was granulomatous orchitis.

A 77-year-old woman with a previous history of pelvic fracture had suffered from recurrent cystitis. In the excretory urography, post-void upright film revealed the bladder hernia associated with the bladder diverticulum. Transurethral incision and fulguration of the bladder diverticulum and left inguinal herniography was performed. There has been no recurrence since then.

Between May 1990 and August 1992, 5 patients with advanced seminoma were treated with single agent carboplatin at Kyoto University. The mean follow-up period of all patients was 23 months. The clinical stage was IIA: 1, IIB: 1, IIIA: 2, IIIB1: 1. Three to 4 courses of carboplatin at 400 mg/m2, were administered intravenously over 1 hour without hydration every 3 to 4 weeks. One patient achieved complete response (CR). Four patients with a residual mass were observed, in two of them the mass disappeared and they remained free of disease. Two of the 4 patients with a residual mass relapsed 11 and 19 months after the start of treatment, and were successfully salvaged with surgery and adjuvant EP (etoposide and cisplatin) therapy. Subsequently, the overall CR rate was 60% and overall survival rate was 100%. The side effects of carboplatin were compared with those of VAB6 (vinblastine, actinomycin-D, bleomycin, cisplatin and cyclophosphamide), with which another 5 patients were previously treated at our hospital. Leukopenia and alopecia were observed in the VAB6 group with a significant difference (p0.05). Severe thrombocytopenia, dyspnea, skin rash, tinnitus and numbness were observed in 4 patients in the VAB6 group. However, no other symptoms but nausea and vomiting were observed in the carboplatin group. It was concluded that single agent carboplatin therapy for advanced seminoma was effective and less toxic, and it would be beneficial for the quality of life of patients, but the residual mass should be treated with surgery, cisplatin-based chemotherapy, or radiotherapy because it possibly has a recurrent potential; otherwise it should be carefully observed.

A 68-year-old man visited his home doctor with the chief complaint of left flank pain. Abdominal ultrasonography revealed left hydronephrosis and space occupying lesion in the right kidney. He was referred to our hospital because of suspected left ureteral stone and for further examination. Drip infusion pyelography revealed a left ureteral stone and retrograde pyelography showed extrinsic compression and deformation of the right pyelogram. A computed tomography showed a heterogeneous solid mass, 7 x 4 cm in size, compressing the pelvicocalyceal system and growing out of the kidney. Right radical nephrectomy was performed under the diagnosis of renal cell carcinoma. The pathological diagnosis was leiomyosarcoma. Seventy-five cases of renal leiomyosarcoma have been reported in the Japanese literature and this is the third case as an incidental tumor. Because of the absence of the characteristic diagnostic signs, this malignant tumor can present diagnostic difficulty. The diagnostic problems and clinical features of renal leiomyosarcoma are discussed.

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.

We report three cases of renal or perirenal malignant lymphoma. The patients were a 69-year-old woman presenting with lumbago, a 43-year-old man with fever and erythema, and a 69-year-old woman with general malaise. In each case, renal or perirenal tumor was discovered by abdominal ultrasound. Biopsy and microscopic examination revealed the diagnosis of non-Hodgkin's malignant lymphoma. The computerized tomography patterns of the cases were different from each other; "direct invasion" in the first case, "solitary nodule" in the second case, and "engulfment" in the third case. Chemotherapy and/or radiation therapy were performed. Only the third case is still alive at present. The computerized tomography pattern of renal or perirenal malignant lymphoma was classified into five groups; I) multiple nodules, II) solitary nodule, III) engulfment, IV) direct invasion, V) diffuse infiltration. This classification should be useful in making an accurate and early diagnosis.

To improve the quality of life (QOL) of patients requiring urinary diversion, various surgical techniques including those employing a continent urinary reservoir (CUR), such as Kock pouch or Indiana pouch, and those using the conventional ileal conduit have been advocated. In this study we asked patients who had undergone a CUR operation to complete a questionnaire, consisting of 106 questions relating to the QOL during the disease-free period. A total of 81 questionnaires were sent out, and 60 (74.1%) CUR patients responded. The average age was 61 and the male to female ratio was 49 to 11. The time elapsed from the operation was 42 months. Twenty-nine questions addressed the patients physical condition and on the whole it was kept in good quality. Because they were unwilling to show their stoma, they were reluctant to bathe together with family members. However, 59% of them went to a public bathhouse (common in Japan). Other physical abilities related to exercise were not significantly hampered by this operation. Eighty per-cent of them were not bothered by having a stoma. Twenty four questions were related to social life. The operation had a bad influence in 20-30% of them concerning their interaction with friends and hobbies. Twenty two percent of the patients who had a job prior to the operation stopped working. Only a few patients abandoned travelling. Concerning their sex life (7 questions), males suffered impotence at a very high rate, but only 26% of the patients lost interest in sex. Symptoms related to the operation (41 questions) were mild. Overall, 94% of the patients would choose the same operation again if it were required.(ABSTRACT TRUNCATED AT 250 WORDS)

A 41-year-old man was referred to our clinic for gross hematuria. Cystoscopy revealed a 6 x 5 x 5 cm wide-based tumor located at the dome of the bladder. Pathological diagnosis of the biopsy was pseudosarcomatous fibromyxoid tumor. Microscopically this tumor was composed of spindle cells and myxoid stroma, and immunohistochemical and ultrastructural studies showed benign characteristics of this tumor. Therefore partial cystectomy was performed. It is important to recognize the histological characteristics of this essentially benign condition so that total cystectomy can be avoided.

Most of renal cell carcinomas (RCCs) are refractory at the start of chemotherapy. We have demonstrated that the frequently elevated expression of the multidrug resistance gene (MDR) in RCCs is associated with the intrinsic vinca alkaloids and anthracyclines resistance. The preliminary clinical trials using verapamil or amiodarone in combination with vinblastine or doxorubicin to overcome multidrug-resistant (MDR) tumors could not achieve satisfactory results owing to severe cardiovascular toxicities of such reversing agents. In the present study, we studied the sensitizing ability of bis-benzyl-isoquinoline (cepharanthine) and SDB-ethylenediamine (N-1379) in natural MDR kidney cancer cells. Cepharanthine remarkably sensitized vinblastine and doxorubicin sensitivities in those cells with high MDR RNA levels. From a clinical point of view, cepharanthine seems to be a potent and less toxic agent to treat natural MDR kidney cancers.

Sacral agenesis is an uncommon disease. About 50 cases have been reported in Japan since 1929. Neurogenic bladder is often accompanied with the disease. The patient was a 26-year-old man who had suffered from persistent urinary incontinence since his childhood. Kidney-ureter-bladder (KUB) revealed Type IV sacral agenesis according to the classification by Renshaw. The upper urinary tract remained normal. Urodynamics study showed a low compliance bladder with low urethral pressure. Pharmacotherapy failed to improve his continence. Augmentation sigmoid-cystoplasty was undertaken to enlarge vesical capacity and it has successfully overcome his urinary incontinence. Clinical aspects of sacral agenesis are discussed focusing on urological problems.

DWA2114R (DWA) is a new derivative of platin compounds. Eleven patients with rapidly progressive, endocrine-resistant stage D carcinoma of the prostate were treated with infusion of DWA (800-1,000 mg/m2) every 3 to 4 weeks. A partial objective response was observed in 3 of 11 patients (27%). This response lasted from 5 to 11 months with an average of 7.7 months. Six patients (55%) had a significant decrease or disappearance of bone pain and five became ambulatory and asymptomatic. Four patients (36%) showed no change, and four patients (36%) did not respond to the treatment and showed progression of their disease. There were no patients with severe leukopenia (less than 1,000/mm3). No significant renal toxicity was observed in any of the patients and gastrointestinal toxicity was tolerable. DWA appears to be an effective drug available for the treatment of endocrine-resistant advanced carcinoma of the prostate.

We analyzed the clinico-pathological features of the initial tumors in 205 patients with superficial bladder cancer, admitted to Kyoto University Hospital between 1974 and 1988, to investigate the prognostic factors for progression to the muscle invasive disease or metastasis. Of 205 patients, 35 (17%) exhibited muscular invasion alone (12 patients) and/or metastasis (23 patients). Tumor multiplicity, higher grade and positive urinary cytology were the significant risk factors for later malignant progression. Expression of A, B, H-blood group isoantigens in the bladder tumor were significantly decreased from the onset in the patients with initially T1 tumor but not in those with Ta tumor. Significant loss of expression was also found at the time of progression in the initially Ta cases. Thus, loss of A, B, H-blood group antigen expression seems to be correlated with the malignant potential of superficial bladder cancer. However, more feasible and reliable diagnostic markers such as molecular genetical and biochemical markers remain to be developed to predict the malignant potential of the superficial bladder cancer.

Cisplatin has played a major role in the treatment of germ cell tumors. However, it causes renal damage, severe nausea and vomiting. It is also neurotoxic and ototoxic. Carboplatin is an analog of cisplatin which, does not cause renal damage at therapeutic doses. It is not neurotoxic or ototoxic and it produces less gastrointestinal toxicity than cisplatin. We used carboplatin alone as an initial chemotherapy in a 36-year-old man with stage IIB seminoma. Following left radical orchiectomy the patient received 4 courses of carboplatin chemotherapy. After the first course of chemotherapy, tumor markers (LDH, beta-HCG) returned to the normal range. After 4 courses, the size of the retroperitoneal metastases was significantly reduced. The toxicity of 4 courses of carboplatin chemotherapy was generally milder than that of cisplatin-based combination chemotherapies such as PVB or VAB-6. There were no episodes of septicemia, thrombocytopenic bleeding or renal deterioration. The patient did not suffer from alopecia, neuropathy, symptomatic hearing loss, severe nausea or vomiting. Nine months after the completion of carboplatin chemotherapy, the patient remains well and free from disease progression. This case strongly suggests that single agent carboplatin therapy could be an effective and less-toxic treatment for advanced seminoma.

Stereotactic radiosurgery with linear accelerator requires accurate localization of target and accurate spatial delivery of radiation. In phantom study, geometric accuracy of radiosurgery was assessed in combination of CT simulation system (CTSS), which had been developed in our institute, and linear accelerator with supplemental collimator. After determination of target and its isocenter with CTSS, phantom was placed on treatment table so that isocenter meet at the intersection of mechanical axes (gantry, turn table). Displacement of the isocenter from the center of the radiation field was 1 mm in average. It was concluded that this combination could be applied to radiosurgery.

Quantitative analysis of the malignant potential in cancer cells is a method currently under discussion. Recently the stereological estimation of cancer cells has been utilized in making an objective and quantitative pathological diagnosis. In this study, we estimated the mean nuclear volume (MNV) of untreated bladder carcinomas in 128 patients by stereological methods and attempted to quantitatively analyze the malignant potential of the carcinoma. The MNV was significantly enlarged as the tumor advanced in grade and stage. MNV was largest in grade 3 tumors (340.2 +/- 100.1 microns3) followed by grade 2 tumours (206.2 +/- 90.6 microns3) (P less than 0.01), and grade 1 tumors (130.6 +/- 46.7 microns3) (P less than 0.01). MNV was larger in pT1 tumors (278.2 +/- 126.9 microns3) than in pTa tumors (156.9 +/- 60.5 microns3) (P less than 0.01). MNV was also larger in invasive tumors (T2, T3 and T4: 318.2 +/- 104.0 microns3) than in superficial tumors (Ta and T1: 203.5 +/- 109.2 microns3) (P less than 0.01). Patients were then divided into two subgroups, one with large nuclei (MNV greater than or equal to 197.3 microns3), and the other with small nuclei (MNV less than 197.3 microns3). Survival and disease-free rates in patients with small nuclei (5-year survival rate: 92.9%, 5-year disease-free rate: 24.4%) were significantly better than in patients with large nuclei (5-year survival rate: 58.0%, 5-year disease-free rate: 12.5%). For patients with grade 2 tumors, those with small nuclei had a good survival rate (5-year survival rate: 95.5%), similar to that of patients with grade 1 tumors (5-year survival rate: 95.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

Combination chemotherapy with methotrexate, etoposide, adriamycin and cisplatin (M-EAP regimen) was administered to 4 patients with advanced epithelial cancer of the urinary tract (Methotrexate 30 mg/M2 day 1, 15 and 22; Etoposide 100 mg/M2 day 1, 2, 15 and 22; Adriamycin 30 mg/M2 day 2; Cisplatin 70 mg/M2 day 2, every 4 weeks). In an attempt to improve the anti-cancer effect of the M-VAC regimen, etoposide was substituted for vinblastine. This series comprised 3 males and 1 female ranging in age from 54 to 68 years (mean age: 63), with a performance status of 1 to 2. The site of the primary lesion was bladder in 3, and left ureter in 1. The clinical response was assessed in 3 of the 4 patients: one achieved complete response and two had partial response. Two of the four died of disease 5 months after chemotherapy. Two of them have been alive for 10 and 8 months with no evidence of disease after chemotherapy. Toxicity included moderate or severe myelosuppression in two patients, and mild to moderate anorexia, vomiting, alopecia, and hiccups in all patients. These preliminary results suggest that the M-EAP regimen is effective against advanced epithelial carcinoma of the urinary tract. However, myelosuppression was a dose-limiting factor.

Forty-six lung cancer patients received radiotherapy from 1982 to 1987 were reviewed to analyze the incidence of radiation pneumonitis and the factors which were related to it. The incidence of which evaluated with plain chest X-ray was 54% at 1 month, 78% at 3 months and 89% at 6 months after radiotherapy. The relationship between severity of pneumonitis and several parameters were studied. As a result, six parameters consisting of pre-radiotherapy granulocyte counts, tumor location, T-factor, radiation dose, radiation field size and the combination timing of chemotherapy were found to be contributing factors.

From May 1982 to Nov. 1987, 33 patients with bladder carcinoma were treated with preoperative radiotherapy (20 Gy/5fr) and total cystectomy. The over all 3-year survival rate was 70%. For T1 and T2, 3-year survival rate was 100%, but only 55% and 0% for T3 and T4 respectively. In 23 out of 33 patients, preoperative T-stage was confirmed by TUR-BT. Down-Staging was recognized in 7 out of 23 patients (30%). They were 0 out of 1 patients for Tcis (0%), 2 of 3 for T1 (67%), 3 of 6 for T2 (50%), 2 of 11 for T3 (18%) and 0 of 2 for T4 (0%). This protocol of preoperative radiotherapy is thought to be favorable for T1 and T2 bladder carcinoma, but inadequate for T3 and T4 tumors. Consequently, it is considered that higher dose radiotherapy and postoperative chemotherapy are necessary for T3 and T4 bladder carcinoma.

A case of extramedullary plasmacytoma in the radix linguae was reported. Although immunological parameters rapidly normalized during the treatment, tumor size slowly reduced to minimal lesion 11 months after radiotherapy combined with chemotherapy. The management and the availability of MRI for this tumor was discussed reviewing the literature.

Primary bladder tumor is the most frequent malignant tumor in the field of urology, whereas the incidence of secondary bladder tumor from a distant organ is quite rare. We report here a 21-year-old female patient with metastatic bladder tumor from gastric cancer. She came to our hospital with a complaint of only bladder irritability. Cystoscopical and cytological examinations revealed rhabdomyosarcoma of the bladder. She did not respond to radiation therapy and combined chemotherapy, consisting of actinomycin D, vincristine and cyclophosphamide, and died 91 days after admission. Autopsy revealed a primary tumor of poorly differentiated scirrhus carcinoma of the stomach. Thus this was a quite rare case of metastatic bladder carcinoma characterized by bladder irritability without gastrointestinal symptoms.

A case of primary localized amyloidosis is reported. The patient was a 73-year-old female who suffered from miction pain and consulted our department. There was a 1.5 x 1.5 cm slightly red, nonpapillary tumor around the right ureteral orifice in cystoscopy. The diagnosis was amyloidosis with cystitis hemorrhagica histopathologically. After the treatment with antibiotics for about one month there were no symptoms and no tumors in the urinary bladder cystoscopically. The clinical course was relatively good. The treatment varies from transurethral resection to total cystectomy with urinary diversion. This case was cured by non-operative treatment, but close follow-up of the patient is necessary because of the frequency of multiple recurrence.

Portopulmonary venous anastomosis is a potential channel for systemic arterial embolization during embolization procedures for bleeding esophageal varices. To document the presence of such anastomoses, 15 patients with esophageal varices were studied by real-time contrast echocardiography combined with transhepatic cineportography. Cinefluorographic technique, which was applied for this purpose, occasionally failed to demonstrate the dynamic events in the left atrium because of rapid dilution of contrast medium. Echocardiography after the injection of dextrose solution into the gastric coronary vein allowed two-dimensional real-time images of contrast echoes in the left cardiac chambers. By combining these two methods, more reliable diagnostic information was obtained in five of the 15 patients studied.

In vitro chemosensitivity of lung cancer and other chest tumors was evaluated by human tumor colony assay (HTCA). From 61 specimens 33 (54%) grew more than 30 colonies from which evaluation of chemosensitivity could be performed. Of 41 specimens of lung cancer, 26 (63%) yielded adequate growth for drug testing. Nine out of 26 specimens of non-small cell lung cancer showed more than 50% reduction in colony formation, and in 4 of the 26 specimens, more than 70% reduction was obtained with more than one of the drugs tested. Specimens obtained from metastatic lesions of lung cancer showed higher plating efficiency and drug sensitivity than those from primary lesions. Plating efficiency of non-epithelial tumors was lower than that of epithelial tumors. HTCA has a potential value for screening anticancer agents against lung cancer and other chest tumors. However, the assay still has many problems to be resolved, such as difficulty in obtaining single-cell suspensions and poor plating efficiency.

Lisuride hydrogen maleate (LHM, SH-1072), a dopaminergic agonist and therefore an inhibitor of prolactin (PRL) secretion, were administered to 12 patients with mild to moderate BPH in order to evaluate the clinical effectiveness. LHM was administered 75 or 150 mcg/day, po, for 20 weeks on the average. The status of micturition evaluated by score points and nocturnal frequency of urination was significantly improved, whereas objective responses such as on the amount of residual urine, size of the prostate gland, findings of urethrocystography and the length of prostatic urethra measured on the film were minimal. Serum PRL level have been reduced significantly through the therapy, and testosterone were unchanged. The mechanism of action of the agent on BPH and the surrounding tissue was discussed; reduced androgen effect on the prostate through lowering of PRL and anti-alpha-adrenergic activity or the effect through prostaglandin on the gland, the bladder neck and the posterior urethra would mitigate the symptoms.

Presented is a 69-year-old female who had gigantic leiomyosarcoma showing a pedunculated and exogastric growth. Though the patient had been diagnosed as having a gastric submucosal tumor (SMT) on being given an upper GI series and an endoscopical examination, she did not enter hospital until a year and 4 months later. On admission, a large SMT was suspected after an upper GI series and an endoscopic examination. Computed tomography (CT), ultrasonography (US), and angiography revealed a gastric SMT that had grown exogastrically. Subsequently, this tumor was resected with the gastric wall. Histologically, tumor was determined as being a leiomyosarcoma. CT and US were found useful in demonstrating the SMT with its exogastric growth.

The human tumor colony-forming assay was used to compare chemosensitivity among tumor cells within a primary tumor, between primary tumor and its metastasis, and between different metastases. The results indicate that the reported discrepancies of in vitro and in vivo results in clinical trials with TCFA for predicting of resistance or sensitivity to cytostatic drugs may be due to therapeutic heterogeneity among tumor colony-forming units within a primary tumors and between primary tumor and metastases, and that the results from a metastatic lesion may have more profound implications in planning treatment of other metastatic lesions of the same patient.

An in vitro double soft agar technique was used to culture 91 human urologic tumors including 37 renal cell, 40 uroepithelial, 7 prostatic and 7 testicular cancers. Cells from 31 of 37 renal, 32 of 40 uroepithelial, 3 of 7 prostatic and 4 of 7 testicular cancer specimens grew to the extent that they could be used in chemosensitivity testing in soft agar (greater than or equal to 30 colonies per control plate). With this assay system, a very high growth rate (70/91; 77%) was obtained. The in vitro response rates of greater than or equal to 10% were noted with mitomycin C, 5-fluorouracil, cisplatin, bleomycin and vincristine in renal cell cancers, and with vincristine and cisplatin in uroepithelial cancers. Drug sensitivity studies showed that the rates of in vitro sensitivity of uroepithelial cancers were close to those obtained in general clinical experience, while the rates of the vitro sensitivity of renal cell cancers were considerably higher than the rates found clinically. It is concluded from this study that in vitro chemosensitivity testing by clonogenic assay is likely to be a useful tool in the treatment of urologic cancers, but that a simple definition of sensitivity cannot be applied for all types of tumors.

Recombinant human leukocyte (alpha) interferon was administered i.m. at the initial dose of 3 X 10(6) U/day to 27 patients with measurable metastatic renal cell carcinoma during the past 2 years. The results of 22 of these patients were evaluable. Three patients (13.6%) showed partial response; 3 patients (13.6%), minor response; 7 patients (31.8%), no change; and 9 patients (40.9%), progressive disease. Major toxicity consisted of fever (55.5%), anorexia (44.4%), malaise (22.2%), elevation of GOT/GPT (48.1%), leukopenia (44.4%) and thrombocytopenia (29.6%). When the 3 patients who showed stabilization (S) and the 2 patients who showed mixed effects (ME) among the 7 patients who showed no change are classified into the responded group, half the patients had some response to interferon. Characteristics of these responders (PR + MR + ME + S) were good performance status, relatively longer disease-free interval, metastases limited to the lungs or metastasis to lungs and one other organ excluding the liver, and frequency of interferon-induced thrombocytopenia. Interferon administration is still being continued to 4 patients on an outpatient basis, 5 patients are hospitalized and 13 patients have died. In conclusion, patients with pulmonary metastases seem to be the best responding group for interferon treatment in renal cell carcinoma and further trials, especially combined regimens with chemotherapy and/or other kinds of interferon should be tested.

Using transplantable testicular tumor lines serially passaged in nude mice, the antitumor effect of JM-8, an analogue compound of cisplatin, was evaluated by clonogenic assay and in nude mice. JM-8 exhibited compatible tumor growth inhibition to that of 8 to 10 times the concentration of cisplatin both in vitro and in vivo. In addition, JM-8 had less toxicity than cisplatin in vivo. However, when JM-8 was adopted for treatment of regrowing tumors after repeated manipulations with cisplatin, it exerted less growth inhibition than cisplatin. Apart from this effect, it was considered that JM-8 could be substituted for cisplatin in clinical use.

A single topical application of 7,12-dimethylbenz[a]anthracene (DMBA) followed by twice-weekly 12-O-tetradecanoyl phorbol-13-acetate (TPA) treatment was given to the skin of female CD-1 mice, and soft agar colony formation of the epidermal cells was evaluated periodically during the treatment. From the second week, colony growth was observed and the number of colonies increased with time, reaching a significant level from the fourth week. Colony formation was observed earlier than papilloma development in the mouse skin. Soft agar colony-forming assay might be a useful tool to analyze the early events in carcinogenesis.

Radiation pneumonitis are well recognized as complications of radiotherapy for the thoracic malignancies. However, the pathogenesis of radiation pneumonitis has been poorly understood and prevention of it has not been developed. In this study, to define the mechanisms of radiation pneumonitis biologically, we measured lipid peroxides, the activities of glutathione peroxidase (GSH pex.), leukotriene C4 and D4 (LTC4 and LTD4) in the irradiated lungs of mice. Eight weeks old female ICR mice were sacrificed at various time periods (immediately after to 5 days) following the 10 Gy whole-body irradiation with 60Co gamma rays. The lipid peroxides and the activities of GSH pex. increased immediately after the irradiation, but returned to the control level 1 hour after the irradiation. And then, the lipid peroxides also increased from 1 day after the irradiation, while the activities of GSH pex. decreased below the control level. LTC4 and LTD4 in the irradiated lungs of mice were also significantly higher than those of non-irradiated controls. Furthermore, we investigated effects of Coenzyme Q10 and Azelastine for the prevention of radiation pneumonitis. Lungs of ICR mice after 10 Gy whole-thorax irradiation treated with those drugs were compared with the control lungs pathologically. Intraperitoneal administration of those drugs decreased the damages for endothelium, such as vacuole formation and stripping off the basement membrane which were recognized by electron microscope. Based on these results, it was strongly suggested that initial damage of irradiated lungs might be induced by lipid peroxides and leukotrienes, and that Coenzyme Q10 and Azelastine could reduce radiation pneumonitis.