市川 智彦

遺伝子多型が転移性前立腺癌の予後予測因子となり得るかどうかを検討した.初診時骨転移を有する前立腺癌患者122例を対象とした.13個の遺伝子多型のうち,CYP19の長いアレル(反復数8以上),又はIGF-1の長いアレル(反復数19以上)を有する患者の癌特異的死亡率は有意に高かった.又,CYP19とIGF-1を組み合わせて4群に分けたところ,両多型に長いアレルを有する患者は,他の3群と比べて有意に生存期間が短かった.多変量解析においても,CYP19の長いアレル,又はIGF-1の長いアレルは独立した予後規定因子であり,これらの遺伝子型は転移性前立腺癌の予後規定因子となり得ることが示唆された

OBJECTIVE: Pretreatment serum level of testosterone (T) is a potential prognostic factor for prostate cancer. The present study was conducted to evaluate the clinical significance of pretreatment serum T level in patients with clinically localized prostate cancer. MATERIALS AND METHODS: The subjects were 82 clinically localized prostate cancer patients treated with radical prostatectomy, whose pretreatment T levels were recorded. We investigated clinical and pathological factors such as pretreatment serum T level, age, pretreatment PSA or pathological Gleason score concerning the association with pathological stage and biochemical recurrence. RESULTS: The mean pretreatment T level was significantly lower in patients with non-organ-confined prostate cancer (pT3-T4, N1; 3.44+/-1.19 ng/ml) than in patients with organ-confined cancer (pT2; 4.33+/-1.42 ng/ml) (p=0.0078). Multivariate analysis demonstrated that pathological Gleason score, pretreatment serum T level and pretreatment PSA were significant predictors of extraprostatic disease. When the patients were divided into high and low T level groups according to the median value, pretreatment T levels were not significantly associated with PSA recurrence rates (p=0.7973). CONCLUSIONS: A lower pretreatment T level appears to be predictive of extraprostatic disease in patients with localized prostate cancer.

The molecular and biochemical mechanisms contributing to the development and progression of prostate carcinogenesis are still unknown. Recent technologies such as, real-time PCR, microarray, and laser capture microdissection, have accelerated the study of the molecular events involved in prostate cancer. The expression and function of numerous genes have been shown to be altered in prostate cancer. Such gene regulations are involved in cell cycle, signal transduction pathways, or gene expression. Analysis of the genes during prostate cancer progression has provided a better understanding of the basis of the disease. This review summarises current knowledge of the molecular analysis for prostate cancer.

Prostate cancer is one of the most common cancers in Western men. In Japan, the incidence of this malignancy is increasing. Recent advances in molecular biology brought new biomarkers to prostate cancer diagnosis. In this article, we describe new biomarkers including serum and genetic and histochemical markers for screening, staging and drug selection for the management of prostate cancer patients.

BACKGROUND: The antiangiogenic CXC chemokines interferon gamma (IFN-gamma)-inducible T-cell alpha chemoattractant (I-TAC) and monokine induced by IFN-gamma (Mig) are known as members of IFN-gamma-inducible antiangiogenic CXC chemokines. However, the expression of these chemokines in highly angiogenic tumors remains poorly understood. The authors examined expression of I-TAC, Mig, and their receptor, CXCR3, in tissue samples from patients with renal cell carcinoma (RCC). METHODS: Twenty-one samples of untreated RCC and corresponding normal renal tissues were obtained from surgical specimens. The expression levels of I-TAC, Mig, and CXCR3 were investigated using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, real-time RT-PCR analysis, and Western blot analysis. Immunohistochemistry was carried out to clarify the localization of both chemokines and of CXCR3. RESULTS: RT-PCR analysis showed strong expression levels of I-TAC, Mig, and CXCR3 in RCC tissues and very weak or undetectable expression in normal kidney tissues. Real-time RT-PCR analysis showed that expression levels of I-TAC, Mig, and CXCR3 in RCC tissues were 14.9 times greater, 30.3 times greater, and 9.9 times greater compared with the levels in the corresponding normal kidney tissues, respectively (P < 0.01). Western blot analysis showed up-regulation of I-TAC, Mig, and CXCR3 at the protein level. Immunofluorescence double stainings revealed that I-TAC coincided with pericytes and vascular smooth muscle cells (VSMCs) in tumor angiogenic vessels. Mig was detected in tumor endothelial cells (TECs) and in infiltrating leukocytes. In the corresponding normal kidney tissues, neither VSMCs nor endothelial cells showed positive stainings for these chemokines. CXCR3 was expressed in both tumor cells and infiltrating leukocytes. CONCLUSIONS: The results revealed special feature of vascular mural cells and TECs in RCC. The up-regulated I-TAC and Mig, produced by tumor vessels, may interact with CXCR3 expressed in tumor cells, with possible pathophysiologic significance in RCC progression.

Objective: The present study was conducted to evaluate the clinical significance of pretreatment serum testosterone (T) level in patients with clinically localized prostate cancer. Materials and methods: We investigated clinical and pathological factors such as pretreatment serum T level, age, pretreatment PSA or pathological Gleason score concerning the association with pathological stage and biochemical recurrence. Results: The mean pretreatment T level was significantly lower in patients with non organ-confined prostate cancer than in patients with organ-confined cancer. When the patients were divided into high and low T level groups, pretreatment T levels were not significantly associated with PSA recurrence rates. Conclusions: A lower pretreatment T level appears to be predictive of extraprostatic disease in patients with localized prostate cancer.

Genes encoding the serine proteinase inhibitor B family (SERPINBs) are mainly clustered on human chromosome 18 (18q21). Several serpins are known to affect malignant phenotypes of tumor cells, so aberrant genetic variants in this molecular family are candidates for conferring susceptibility for risk of cancer. We investigated whether eight selected non-synonymous variations within SERPINB loci at 18q21 might be associated with risk of prostate cancer in Japanese men. A case-control study involving 292 prostate-cancer patients and 384 controls revealed significant differences in regard to distribution of four missense variations in genes encoding plasminogen activator inhibitor 2 (PAI2) and SERPINB10. The most significant association was detected for the N120D polymorphism in the PAI2 gene (P = 5.0 x 10(-5)); men carrying the 120-N allele (120-N/N and 120-N/D genotypes) carried a 2.4-fold increased risk of prostate cancer (95% confidence interval 1.45-4.07). Associations were also detected for three other missense polymorphisms in those two genes. Strong linkage disequilibrium in the region encompassing PAI2 and SERPINB10 extended to about 50 kbp. The results suggested that missense variations in one or both of these genes confer important risks for prostate cancer, and may be themselves tumorigenic. Although confirmative replication studies on larger cohorts are awaited, clinical examination of these variations may become useful for identifying individuals at high risk for prostate cancer.

Carcinogenesis of the prostate involves androgen influences, and associations between genetic polymorphisms of androgen receptor and metabolizing enzymes and prostate cancer risk have been reported. Roles for non-androgenic hormones are not well defined, but they also may have an impact judging from epidemiological and animal experimental alphalambda zetaof data. The purpose of the study was to determine whether hormone-related polymorphisms are associated with prostate cancer risk. A case-control study was performed with 147 Japanese prostate cancer patients and 266 urological controls. Polymorphisms of target genes [cytochrome P450 (CYP) 1B1, Leu(432) Val; debrisoquine hydroxylase, (CYP2D6)*4, aromatase (CYP19), Arg(264) Cys; estrogen receptor (ER)alpha-Xx (Xba I) and Pp (Pvu II); ERbeta-Rr (Rsa I); progesterone receptor (PR) Alu in intron 71 were examined by PCR-based methods. The capital and small letters signify the absence and presence of restriction sites, respectively. Odds ratios (OR) were adjusted for age using multiple logistic regression analysis with SPSS Medical Pack. Among the seven examined genetic polymorphisms, significant associations between CYP1B1 Leu(432)Val (OR 4.80; 95% confidence interval (CI), 1.21-19.05) and Alu in intron 7 of PR (OR 4.17; 95%CI, 1.26-13.85) were found. As for combined effects, the CYP1B1 polymorphisms (Leu/Val+Val/Val) together with heterozygosity for Alu in the PR were more frequent among prostate cancer patients (1.45%) than controls (0.41%), although without significance (OR, 3.99; 95%CI, 0.36-44.8). The combination of ERalpha (P/p+p/p) polymorphisms with heterozygosity for Alu in the PR demonstrated an OR of 4.56 (95%CI, 1.01-20.6). This pilot study showed that CYP1B1 and PR polymorphisms, alone or in combination, might be associated with prostate cancer risk. They might, therefore, have potential as a tool for identifying high-risk individuals.

PURPOSE: We studied the efficiency of second or third line hormonal therapy for prostate cancer relapse after hormone therapy. MATERIALS AND METHODS: The study included 70 patients with advanced prostate cancer treated with hormonal therapy, androgen deprivation monotherapy or maximum androgen blockade including surgical or medical castration combined with steroidal antiandrogen, 100 mg chlormadinone acetate daily or nonsteroidal antiandrogens, 375 mg flutamide (FLT) daily or 80 mg bicalutamide (BCL) daily. When the disease relapsed, we discontinued the antiandrogen and evaluated the patient for the antiandrogen withdrawal syndrome (AWS). Thereafter we administrated an alternative antiandrogen and evaluated its effect. RESULTS: The incidence of the AWS after first, second and third line hormonal therapy was 35.8%, 8.0% and 0%, respectively. The efficiency of subsequent hormonal therapy was not related to the occurrence of the AWS. Nonsteroidal antiandrogens as alternative therapies for disease relapse from primary therapy were effective in second line (FLT 38.1%, BCL 44.4%) or in third line (FLT 30.0%, BCL 28.6%) hormonal therapy. Of 5 (80%) patients who responded to second line therapy 4 (80%) had effective third line therapy, while only 1 of 12 (8.3%) second line nonresponders had effective third line therapy (p = 0.003). The survival of second line responders was significantly better than that of nonresponders (5-year survival rate 92.3% vs 23.9%, p <0.001), indicating a potential predictive value for second line responsiveness. No significant clinical factor identified second line responsiveness. CONCLUSIONS: Subsequent nonsteroidal antiandrogen therapies were effective against prostate cancer relapse after hormonal therapy. The response to third line therapy was more effective and survival was improved from the time of first line therapy relapse among second line responders than that in nonresponders. Our data support the notion that second line responders are androgen independent but still hormonally sensitive.

OBJECTIVE: Vasopressin (AVP) is reported to be an important factor for regulating cortisol secretion in patients with Cushing's syndrome due to ACTH-independent macronodular adrenocortical hyperplasia (AIMAH). Recently, there have been several case reports of subclinical Cushing's syndrome due to AIMAH, in which the pathophysiological role of AVP has been unknown. The aim was to conduct an extensive investigation of AVP in the autonomous secretion of cortisol in subclinical Cushing's syndrome due to AIMAH. PATIENTS AND MEASUREMENTS: Five cases of AIMAH with subclinical Cushing's syndrome underwent prospective study including physical examination, imaging (MRI, CT and 131I-adosterol scintigraphy) and endocrinological evaluation that comprised basal plasma cortisol levels and urinary excretions of steroid metabolites, a dexamethasone suppression test and an AVP stimulation test. In case 1, left adrenalectomy was performed and the pathological diagnosis of AIMAH was established. An in vitro experiment using the cultured AIMAH adrenal cells was conducted to investigate cortisol secretion and expression of the V1-AVP receptor, mRNA by RT-PCR. RESULTS: All five cases were discovered incidentally to have bilateral adrenal nodules. Imaging by MRI and CT revealed large multinodular lesions in both adrenal glands, which showed positive uptake on 131I-adosterol scintigraphy. Although the basal values of plasma cortisol and urinary excretions of steroid metabolites were within normal limits, autonomous secretion of cortisol was assumed to occur because of lack of suppression during dexamethasone suppression. The five patients had no overt signs of Cushing's syndrome, and they were therefore diagnosed with subclinical Cushing's syndrome due to AIMAH. In all five patients, AVP stimulated cortisol secretion in vivo, whereas desmopressin acetate failed to affect cortisol secretion. In case 1, AVP stimulated cortisol secretion from cultured AIMAH adrenal cells, but this secretion had no relationship with cAMP production. In addition, over-expression of V1-AVP receptor mRNA in AIMAH tissue was determined by RT-PCR. CONCLUSION: Patients with subclinical Cushing's syndrome due to AIMAH commonly exhibit cortisol responsiveness to AVP, and this is probably mediated through activation of overexpressed V1-AVP receptors.

Based on reviews of the concept of diagnostics and in general and in specific tumour areas it was clear that development of diagnostic procedures involving genomics will allow for much better targeted and tailored treatments in the future. This will result in better efficacy and better tolerability of cancer treatments, but will also allow for progress in prediction, diagnosis and dose selection. Large collaborative projects studying the efficacy and safety of drugs on the genome level is promising to bring important benefits to both patients and the national economy by reducing useless drug therapy. In colorectal cancer there are several genetic defects identified that can act as the target for directed therapy in the future. Expressions of tumour specific antigens open the way for immunological targeted therapies. Developments in the understanding of the genomic basis for resistance to anti-tumour therapy is promising to help targeting patients likely to respond and not develop resistance. A Japanese model is being developed to determine the relative risk of breast cancer of Japanese women. Based on this prevention therapies can be instigated. The last four years have seen the introduction of four novel targeted therapies. If this model should become a standard in the future, much stronger collaboration between academic research and pharmaceutical industry need to develop.

To evaluate the clinical usefulness of power Doppler imaging (PDI), we compared this method to gray-scale transrectal ultrasound (TRUS) in the detection of prostate cancer. A total of 101 men with abnormally high serum prostate specific antigen (PSA) levels and/or abnormal digital rectal examination (DRE) findings were assessed using TRUS and PDI. Random systematic sextant and bilateral far lateral prostate biopsies were performed in all cases. In addition, when TRUS revealed a hypoechoic lesion or PDI revealed a hypervascular lesion (HVL), these lesions were directly biopsied. Of the 101 patients, 48 (47.5%), 42 (41.5%) and 42 (41.5%) were suspicious of having prostate cancer by DRE, TRUS and PDI, respectively. Prostate needle biopsy revealed prostate cancer in 39 patients (38.6%) and benign prostatic diseases in 62 patients (61.4%). If prostate needle biopsy was avoided when PDI was negative, then PDI eliminated the need for biopsy in 59 of the 101 patients (rate of biopsy procedures saved: 58.4%) and missed only 8 (13.6%) prostate cancers. Moreover, in 63 patients with intermediate PSA (3-10 ng/ml), the rate of biopsy procedures saved by DRE, TRUS, and PDI was 60.3%, 65.1%, and 68.3%, respectively, and the rate of cancers missed was 26.3%, 19.5%, and 14.0%, respectively. In a total of 826 specimens of TRUS-guided prostate biopsy, 126 (15.3%) specimens had adenocarcinoma. Site by site based analysis of the present series revealed 34.1% of prostate cancer sites were isoechoic and hypervascular. On a site by site basis, PDI had better sensitivity, specificity, positive predictive value and negative predictive value than TRUS. In 48 patients without abnormal DRE findings, on a site by site basis, the sensitivities of TRUS and PDI were 22.9% and 34.4%, respectively. Gleason score was associated with a positive rate of PDI on both a patient basis and site by site basis. From these results, on a patient basis, we conclude that PDI was helpful in the indication for prostate biopsy for all patients or patients with intermediate PSA level. On a site by site basis, PDI may be able to select prostate cancer sites at biopsy, in particular in patients without abnormal DRE findings.

Degradation of collagen, or gelatinolysis, by tumor cells is one of the most important events in tumorigenesis. We investigate the possible relationship between the in situ gelatinolytic activities exerted by matrix metalloproteinases (MMPs) and clinico-pathological factors in renal cell tumor (RCT) patients. Using the film in situ zymography (FIZ) method, we determined in situ localization of MMP-like gelatinolytic activities in cancerous and normal tissues in the kidney (n = 51). To clarify the MMP(s) responsible for the gelatinolytic activity in RCTs, we examined the expressions of MMP-2 and MMP-9 in the kidney tissues by means of gelatin zymography (GZG). MMP expression was also detected by RT-PCR and Western blotting analysis. We then investigated the associations of MMP expression, as detected by GZG, with the intensity of gelatinolytic activity, as determined by FIZ. We analyzed the possible relationship of FIZ findings to several clinico-pathological factors such as tumor size, grade, vessel invasion, histologic type, stage and metastasis. FIZ demonstrated that all tumor and normal kidney tissues showed in situ gelatinase activities, and that gelatinolytic activities in RCTs were much stronger than those of normal kidney tissues. There was a statistically significant correlation between the intensity of MMP-like gelatinolytic activity and tumor size, tumor grade and vessel invasion (p < 0.05), but not between it and histological type, tumor stage or metastatic status. FIZ showed that tumor tissues in 5 of the 6 patients with fatal outcome exhibited the intense gelatinolytic pattern. Stronger in situ gelatinolytic patterns were documented in cases with higher MMP-2 expression. The molecular species of MMPs detected by GZG were confirmed by RT-PCR and Western blotting analysis. The FIZ technique enables a direct assessment of in situ gelatinolytic activity in RCT tissues. The intensity of the activity seems to affect the biology of RCT tissues. Our results also indicate a major role for MMP-2 in in situ gelatinolysis in RCT tissues.

BACKGROUND: Glucocorticoids may have favorable effects on prostate cancer patients showing clinical and/or biochemical failure after androgen ablation. The efficacy and mechanisms of dexamethasone therapy as possible alternative endocrine therapy were investigated. METHODS: Twenty five patients with prostate cancer treated by androgen ablation and showing a steady increase in serum prostate specific antigen (PSA) were treated with low-dose dexamethasone. RESULTS: Of 25 patients, 11 demonstrated 50% or more decline of serum PSA and 9 showed improvement of pain on dexamethasone therapy. Of 8 patients who responded to dexamethasone therapy, 5 had 80% or more decrease in serum interleukin-6 (IL-6). In contrast, none of 8 non-responders showed remarkable IL-6 suppression. Response of PSA was not correlated to the changes in serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, or androstendione. CONCLUSIONS: Significant suppression of serum IL-6, probably through inhibition of androgen-independent activation of androgen receptor, may be one of the mechanisms for the effect of dexamethasone therapy in prostate cancer patients with progressive disease.

Background and Aims: Testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) is an effective procedure for the treatment of male infertility, obstructive and non-obstructive azoospermia. We have reviewed our experience to investigate the correlation of TESE-ICSI with morphological, biophysical and endocrine profiles in 27 men. Results:  Testicular spermatozoa could be retrieved in 25 of 27 patients who underwent TESE. In two cases, testicular spermatozoa could not be recovered and their serum follicle-stimulating hormone (FSH) levels were significantly higher than those of the former group. However, spermatozoa could be retrieved in sufficient numbers for ICSI, even in the patient with the highest FSH concentration. Johnsen scores evaluated by diagnostic pre-TESE open biopsies were significantly higher in the cases with viable testicular spermatozoa than those in the cases without spermatozoa. However, even in the patient whose Johnsen score was 2.1, testicular spermatozoa could be retrieved with TESE, and pregnancy was achieved by ICSI. Conclusions:  The serum FSH levels and the histological findings of the testes were strong predictors for successful TESE and provided useful information for consultation and making treatment decisions on an individual case. However, whether a patient has enough spermatozoa so that an IVF procedure with ICSI is possible can only be answered by a trial TESE. (Reprod Med Biol 2003; 2: 31-35).

PURPOSE: Bilateral renal cell carcinoma has been reported to occur in 1% to 4% of patients with renal cancer. However, whether bilateral renal cell carcinoma involves metastatic lesions of the contralateral kidney or develops as simultaneous primary tumors remains unclear to date. Thus, we investigated chromosomal losses and von Hippel-Lindau (VHL) gene abnormalities in bilateral tumors from patients with nonfamilial bilateral renal cell carcinoma. MATERIALS AND METHODS: Genomic DNA was exacted from 2 tumors in 8 patients each with nonfamilial bilateral renal cell carcinoma, including clinically asynchronous and synchronous disease in 5 and 3, respectively. The DNA was then subjected to microsatellite analysis on 13 chromosomal loci. In addition, polymerase chain reaction-single nucleotide specific conformation polymorphism analysis and direct sequencing of 3 exons of the VHL gene were performed. RESULTS: All 5 asynchronous cases showed loss of the same allele in bilateral tumors, indicating a common clonal origin. In contrast, 2 of the 3 synchronous cases showed different patterns of chromosomal loss in the right and left renal tumors, suggesting bilateral primary origins. The other synchronous case with loss of the same allele in each tumor involved right stage T3b and left stage T1a neoplasms. No VHL gene mutations were detected in any case. CONCLUSIONS: Except for a small number of cases synchronous and asynchronous bilateral renal cell carcinoma may represent the simultaneous appearance of separate primary tumors and metastatic progression from the contralateral kidney, respectively.

AIM: To evaluate the occurrence and prevalence of microdeletions in the gamma chromosome of patients with azoospermia. METHODS: DNA from 29 men with idiopathic azoospermia was screened by polymerase chain reaction (PCR) analysis with a set of gamma chromosome specific sequence-tagged sites (STSs) to determine microdeletions in the gamma chromosome. RESULTS: Deletions in the DAZ (deleted in azoospermia) loci sgamma254 and sgamma255 were found in three patients with idiopathic azoospermia, resulting in an estimated frequency of deletions of 10.7% in idiopathic azoospermia men. CONCLUSION: We conclude that PCR analysis is useful for the diagnosis of microdeletions in the Y chromosome, which is important when deciding the suitability of a patient for assisted reproductive technology such as testicular sperm extracion-intracytoplasmic sperm injection (TESE-ICSI).

AIM: The metastatic ability of a Dunning R-3327 rat prostate cancer subline (AT6.3) was suppressed by the introduction of human chromosome 10, when these hybrid cancer cells were injected subcutaneously into nude mice (Nihei et al., Genes Chromosomes Cancer 14:112-119, 1995). The present study was undertaken to clarify which step of metastasis was suppressed in the human chromosome 10-containing microcell hybrids (AT 6.3-10 clones). METHODS: Gelatin zymography, an in vitro invasion assay using a Boyden chamber and an intravenous metastasis assay involving the injection of hybrid cells into nude mice were performed. RESULTS: Gelatin zymography revealed that AT6.3-10 microcell hybrid clones expressed the 72 kD type IV collagenase (MMP-2) at an almost equal level as control microcell hybrid clones. Both the invasiveness as measured by the invasion assay and the number of lung metastases as measured by the intravenous metastasis assay of AT6.3-10 hybrid clones were significantly less than those of the AT6.3 parental clone. CONCLUSION: The human chromosome 10 suppresses both the local invasion and the metastatic process after entry into the blood circulation of rat prostate cancer. This decrease in local-invasive ability does not seem to require a decrease in MMP-2 activity.

BACKGROUND: Several investigators have examined the clinical significance of the length of the CAG repeat at the N-terminal region of the androgen receptor in the pathogenesis of prostate cancer. Because the clinical significance of CAG repeat length during the course of prostate cancer in Japanese patients is unknown, the present study analyzed CAG repeat length in relation to several potential clinical factors. MATERIALS AND METHODS: A total of 88 Japanese patients with prostate cancer and a control group of 53 patients with benign prostatic disease were enrolled in this study. The length of the CAG repeat was determined by PCR sequencing and analyzed in relation to several clinical factors. RESULTS: The length of the CAG repeat did not significantly differ between prostate cancer and benign prostatic disease. Although not statistically different with regard to clinical stage and serum PSA level, the CAG repeat length was associated with histological grade and age at diagnosis. In addition, the CAG repeat length in CR and in non CR patients significantly differed at 22.1 +/- 2.4 and 24.4 +/- 3.0, respectively (P = 0.0264), suggesting that the CAG repeat length can act as a molecular marker with which to predict response to endocrine therapy in stage D prostate cancer patients. CONCLUSIONS: A shorter CAG repeat length appears to predict a response to endocrine therapy, showing a positive prognostic value and indicating good prognosis in the metastatic stage of prostate cancer patients.

Thymidine phosphorylase (TP) expression in 100 paired samples of renal cell carcinoma (RCC) and normal adjacent tissue was analyzed by an ELISA method. We also investigated whether TP expression correlates with clinicopathological findings and clinical outcomes of these patients. Median TP expression was 9-fold (range, 0.5-56) higher in primary tumor than in non-cancerous renal tissue (P < 0.0001). There was a significant difference with respect to tumor venous invasion. TP expression was significantly higher in patients with such venous invasion than in those without (P = 0.018). However, there was no correlation between TP level and other clinicopathological findings and the survival curves. These results suggest that ELISA is useful for evaluating TP expression of human RCC and may provide a novel approach to therapy for patients with RCC.

OBJECTIVE: Prostate adenocarcinoma is predominantly a disease of elderly men. This study retrospectively examined prostate adenocarcinoma in Japanese patients 80 years of age or older to determine the natural history and prognosis of this malignancy in the elderly population. METHODS: The medical records of 593 patients were reviewed, with respect to age, histologic grade, clinical and pathological stage, treatment modality and clinical outcome. A variety of possible clinical factors were compared between patient groups > or = 80 and < 80 years old. RESULTS: No significant difference in clinical stage, tumor grade, and performance status (PS) was found between two age groups of patients with prostate cancer. A significant stage migration between pre-PSA era and PSA era was found only in the group < 80 years old. In the series of stage D2 cancer patients, while there was no significant difference in cause-specific and progression-free survival rates between the two groups, the younger group < 80 years old had a better marker response at 3 months from the start of endocrine therapy compared with the older group (P = 0.0048, chi2 analysis). CONCLUSION: These data suggest that patients > or = 80 years with prostate cancer present with similar histologic grade and disease stage as younger patients, although the younger group with stage D2 had a better marker response to endocrine therapy.

To investigate seminal function in patients with mumps orchitis, 16 patients between the ages of 16 and 43 years (average, 30.4) were examined in this study between 1987 and 1999. Deafness was observed in one patient. Bilateral testes were involved in 7 cases, unilateral in 7, and laterality was unclear in 2. Among the 6 unilateral cases who underwent semen analysis, one had oligozoospermia and 5 showed a normal sperm count 3 of those with normal sperm count had decreased sperm motility. Of the 7 patients with bilateral orchitis, 5 showed azoospermia, one had oligozoospermia, and one had normal sperm count and motility. In one azoospermia case, sperm count and motility normalized 18 months after onset of orchitis. Another azoospermia patient had a Johnsen score of 4.6 at testicular biopsy 16 years after the occurrence of bilateral orchitis. For such patients, application of assisted reproductive technology should be considered.