市川 智彦

OBJECTIVES: To evaluate in a retrospective study the improvements in prostate cancer detection rates for patients with a prostate gland larger than 30 cm3 using a systematic 14-core biopsy strategy compared with a systematic 8-core biopsy. METHODS: We retrospectively assessed 273 patients with screened prostate-specific antigen (PSA) levels of 3.0 to 50.0 ng/mL. A total of 204 patients with a prostate volume of 30 cm3 or larger and with normal digital rectal examination findings were enrolled in this study. Of the 204 patients, 110 underwent 8-core biopsy and 94 underwent 14-core biopsy of the prostate. We compared the cancer detection rates of prostate biopsy between the 8 and 14-core groups using total PSA, free/total PSA ratio, PSA density, and PSA density adjusted by transition zone volume. We also analyzed the Gleason grade of the biopsy core and the radical prostatectomy specimens. RESULTS: Of the 204 patients, 40 (19.5%) were identified as having prostate adenocarcinoma. The cancer detection rate for the 8 and 14-core groups was 14.5% (16 of 110 patients) and 24.5% (23 of 94 patients), respectively. The 14-core biopsy had a statistically significant greater cancer detection rate than did the 8-core group in patients with a prostate volume of 30 to 40 cm3 (36.7% versus 11.8%, respectively, P<0.05) and a PSA density adjusted by transition zone volume of 0.38 ng/mL/cm3 or greater (47.8% versus 20.0%, respectively, P <0.05). The difference in tumor grade between the 8 and 14-core biopsy samples was not statistically significant. CONCLUSIONS: The 14-core prostate needle biopsy is a recommended method for detecting prostate cancer in a large-volume prostate gland without increasing the risk of complications.

AIM: To examine the efficiency of alpha1-blocker treatment on disease-specific and generic quality of life (QOL) in men with clinically diagnosed benign prostatic hyperplasia (BPH), the improvement of QOL scores with International prostate symptom score (I-PSS) and Rand Medical Outcomes Study 36-item Health Survey (SF-36) was prospectively analyzed. METHODS: A total of 68 newly diagnosed patients with symptomatic BPH that satisfied all inclusion and none of the exclusion criteria were prospectively recruited. All patients received 0.2 mg/day of tamsulosin for 12 weeks. All patients underwent pretreatment documentation of lower urinary tract symptoms (LUTS) and assessment of symptom-specific QOL. Symptoms and general health-related QOL (HRQOL) were assessed using the I-PSS and SF-36, respectively. Also, other objective variables, such as prostate volume, maximal urinary flow and postvoid residual urine volume, were evaluated. RESULTS: After 12 weeks, decrease in I-PSS was 27% compared with baseline (from 16.4 +/- 7.18 to 11.9 +/- 7.56). All questionnaires in the I-PSS showed improvement after tamsulosin treatment and the I-PSS QOL score was improved from 4.51 +/- 1.14 to 3.17 +/- 1.38 (P < 0.0001) at 12 weeks after tamsulosin administration. In intragroup comparisons of HRQOL scores with age-gender adjusted SF-36 Japanese national norms, three SF-36 subscales (bodily pain, BP; social function, SF; and mental health, MH) were worse in the BPH group aged over 70 years, while younger BPH groups aged <70 had better mean SF-36 physical function (PF) scores compared with age-gender adjusted Japanese national norms. In the BPH group with a prostatic volume > or =20 mL, three mean SF-36 scales (BP, SF and MH) were significantly improved after tamsulosin treatment. It is noteworthy that these SF-36 subscales were identical to those observed to worsen in the older BPH group compared to Japanese national norms. CONCLUSIONS: Treatment with tamsulosin for symptomatic BPH patients is associated with significant improvement in the generic HRQOL, in addition to disease-specific QOL and symptoms, at 3 months after drug administration. In particularly, for generic HRQOL with SF-36, tamsulosin treatment can efficiently improve three mean SF-36 subscales (BP, SF and MH) that are decreased in older BPH patients.

AIM: The clinical significance of the urinary white blood cell (U-WBC) count and serum C-reactive protein (CRP) level was evaluated in an effort to improve the efficiency of prostate biopsies. METHODS: We enrolled 228 consecutive patients with serum prostate-specific antigen (PSA) ranging from 3.0 to 20.0 ng/mL, normal digital rectal examination findings, and who underwent prostate biopsies between January 2001 and August 2004. Of these, 157 patients had histologically confirmed benign prostatic disease and the remaining 71 patients had prostate cancer. Patients with a pretreatment U-WBC count < or =3 or >3/high power field were defined as non-pyuria and pyuria, respectively. The patients were also separated into two groups based on the serum CRP level prior to biopsy. Several clinical factors were compared among these subgroups. RESULTS: Inflammation was histologically detected at rates of 58.1% and 34.1% in the pyuria and non-pyuria groups, respectively (P = 0.0014). The rates of cancer detection were significantly lower in the pyuria, than in the non-pyuria group (P = 0.0384). The cancer detection rates did not significantly differ according to serum CRP levels prior to biopsy. CONCLUSION: The U-WBC count appears to be a reliable indicator of minute prostatic inflammation. The serum PSA level was elevated in patients with asymptomatic prostatitis. Counting U-WBC is a simple, convenient and non-invasive method that should be valuable part of routine urological examinations.

OBJECTIVE: The purpose of this study was to clarify characteristics of baseline health-related quality of life (HRQOL) during the diagnostic process of prostate cancer. METHODS: A prospective study was conducted to measure HRQOL in a cohort of 141 patients in whom prostate cancer was suspected and prostate biopsy was scheduled, using both generic and disease-specific HRQOL measures (SF-36, UCLA-Prostate Cancer Index) at two points: before prostate biopsy (prediagnosis) and after giving biopsy results (postdiagnosis). Seventy-three patients were diagnosed with prostate cancer and 68 were not. RESULTS: Compared to age-gender adjusted population norms, patients demonstrated better physical function (PF) and worse mental health (MH). Characteristic age-related changes were found in PF and sexual function (SXF); however, disease stage exhibited no relevant effects in HRQOL. No significant difference was detected between pre- and postdiagnosis SF-36 and UCLA-PCI scores. CONCLUSION: The present study discovered no relevant impact of the diagnostic process of prostate cancer on baseline HRQOL using SF-36 and UCLA-PCI. Combined with results of previous studies, it is supportive of regarding pretreatment levels of HRQOL as the baseline.

We evaluated the effects of bisphosphonate (BP) treatment in five patients with hormone-refractory prostate cancer (HRPC), experiencing bone pain from metastases to the bone, and assessed changes in serum prostate specific antigen (PSA) levels, bone pain, and quality of life (QOL). Treatment with incadronate disodium (10 mg) in saline was administered at 2-week intervals for a total of 6 times. Evaluation of the treatment included the incidence of adverse events, QOL, bone pain, pain scale, and blood analyses including tumor markers. BP treatment was generally well tolerated by all five patients. The effects of BP treatment on serum PSA values were evaluated as prominent response (PR), no change (NC) and progressive disease (PD) in one, two and two cases of PD, respectively. During BP treatment, serum type I procollagen values decreased in patients, but there was no large change in serum type I collagen values. Only one patient experienced increased pain; pain was well controlled in the others. The QOL evaluation by Short-Form 36 (SF-36), showed no change in scores during BP treatment except for general health. These results suggested that BP treatment is safe and feasible. It may be effective for the treatment of those HRPC patients with bone pain and may become one of the choices for treatment of HRPC.

PURPOSE: The prognosis of metastatic prostate cancer significantly differs among individuals. While various clinical and biochemical prognostic factors for survival have been suggested, the progression and response to treatment of those patients may also be defined by host genetic factors. In this study, we evaluated genetic polymorphisms as prognostic predictors of metastatic prostate cancer. PATIENTS AND METHODS: One hundred eleven prostate cancer patients with bone metastasis at the diagnosis were enrolled in this study. Thirteen genetic polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism or an automated sequencer with a genotyping software. RESULTS: Among the polymorphisms, the long allele (over 18 [CA] repeats) of insulin-like growth factor-I (IGF-I) and the long allele (over seven [TTTA] repeats) of cytochrome P450 (CYP) 19 were significantly associated with a worse cancer-specific survival (P = .016 and .025 by logrank test, respectively). The presence of the long allele of either the IGF-I or CYP19 polymorphisms was an independent risk factor for death (P = .019 or .026, respectively). Furthermore, the presence of the long allele of both the IGF-I and CYP19 polymorphisms was a stronger predictor for survival (P = .001). CONCLUSION: The prognosis of metastatic prostate cancer patients is suggested to be influenced by intrinsic genetic factors. The IGF-I (CA) repeat and CYP19 (TTTA) repeat polymorphisms may be novel predictors in prostate cancer patients with bone metastasis at the diagnosis.

BACKGROUND: Radiation treatment for localized prostate cancer has become a prominent choice of monotherapy, and carbon ion beam is a powerful means for this purpose. METHODS: In total, 37 patients with localized prostate cancer were treated by monotherapy with carbon ion radiation and the outcome, more than 4 years later, was followed. RESULTS: PSA relapse-free survival was overall 85%, 5 years after radiation, and 96% in low-risk patients. Local control was mostly achieved, and no cancer-specific death was obtained. Except in cases of relapse, 1.0 ng/ml or less of PSA was shown in 78%, 3 years after radiation. Half of biopsy specimens out of 12 cases revealed non-viable or no cancer cells after a rather short time from treatment. CONCLUSION: Monotherapy with carbon ion radiation may be an excellent treatment for localized prostate cancer with low risk.

AIM: The objective of the present study was to clarify the indications, usefulness and limitations of ureterorenoscopy. MATERIAL AND METHODS: From January 1998 to June 2004, 72 consecutive patients (48 men and 24 women) with a mean age of 66 years (range, 27-83 years) underwent ureterorenoscopy to diagnose upper urinary tract tumors (UUT). Median follow-up was 24 months (range, 1-73 months). Patients were divided into four subgroups by voided urine cytology and preoperative radiographic findings. Group A (n=11, 15.3%), positive voided urine cytology and positive preoperative radiographic findings; group B (n=5, 6.9%), positive cytology and negative radiographic findings; group C (n=48, 66.7%), negative cytology and positive radiographic findings and group D (n=8, 11.1%), frank hematuria originating from the UUT but negative cytology and negative radiographic findings. We compared the findings of ureterorenoscopic examination and biopsy with the results of retrograde pyelography and cytology of upper tract urine. For each examination, the following diagnostic indices were assessed: sensitivity, specificity, positive-predictive-value (PPV) and negative-predictive-value (NPV) and accuracy. Statistical analysis was performed using McNemar's test. RESULTS: For ureterorenoscopy, sensitivity was 94%, specificity 59%, PPV 72%, NPV 92% and accuracy 76%. For biopsy, sensitivity was 77%, specificity 100%, PPV 100%, NPV 80% and accuracy 88%. Accuracy of ureterorenoscopy tended to be superior to that of retrograde pyelography. Ureterorenoscopy was most useful in the group which consisted of 48 patients (66.7%) with negative voided urine cytology and positive preoperative radiographic findings. This group was the only group in which accuracy of ureterorenoscopic biopsy was superior to that of urine cytology, significantly (P=0.03). CONCLUSION: Results indicated that ureterorenoscopy is most suitable and gives superior accuracy in patients with positive radiographic findings and negative voiding cytology. Ureterorenoscopic biopsy of the upper urinary tract would provide useful information when considering therapeutic strategies, such as nephron-sparing management.

Cystinuria is caused by the inherited defect of apical membrane transport systems for cystine and dibasic amino acids in renal proximal tubules. Mutations in either SLC7A9 or SLC3A1 gene result in cystinuria. The mutations of SLC7A9 gene have been identified mainly from Italian, Libyan Jewish, North American, and Spanish patients. In the present study, we have analyzed cystinuria cases from oriental population (mostly Japanese). Mutation analyses of SLC7A9 and SLC3A1 genes were performed on 41 cystinuria patients. The uptake of 14C-labeled cystine in COS-7 cells was measured to determine the functional properties of mutants. The protein expression and localization were examined by Western blot and confocal laser-scanning microscopy. Among 41 patients analyzed, 35 were found to possess mutations in SLC7A9. The most frequent one was a novel missense mutation P482L that affects a residue near the C-terminus end of the protein and causes severe loss of function. In MDCK II and HEK293 cells, we found that P482L protein was expressed and sorted to the plasma membrane as well as wild type. The alteration of Pro482 with amino acids with bulky side chains reduced the transport function of b 0,+ AT/BAT1. Interestingly, the mutations of SLC7A9 for Japanese cystinuria patients are different from those reported for European and American population. The results of the present study contribute toward understanding the distribution and frequency of cystinuria-related mutations of SLC7A9. © 2006 International Society of Nephrology.

OBJECTIVES: Several nomograms for prostate cancer detection have recently been developed. Because the incidence of prostate cancer is lower among Asian men, nomograms based on Western populations cannot be directly applied to Japanese men. We, therefore, developed a model for predicting the probability of a positive initial prostate biopsy using clinical and laboratory data from a Japanese male population. METHODS: Data were collected from 834 Japanese male referrals who underwent initial prostate biopsies as individual screening. We analyzed age, total prostate-specific antigen (PSA) level, free/total PSA (f/t PSA) ratio, prostate volume, and digital rectal examination findings. Of these data, we randomly reserved 20% for study validation. Logistic regression analysis estimated relative risk, 95% confidence intervals, and P values. RESULTS: Independent predictors of a positive biopsy result included elevated PSA levels, decreased f/T PSA ratio, advanced age, small prostate volume, and abnormal digital rectal examination findings. We developed a predictive nomogram for an initial positive biopsy using these variables. The area under the receiver operating characteristic curve for the model was 81.8%, which was significantly greater than that of the prediction based on PSA alone (area under the receiver operating characteristic curve 67.8%). If externally validated, applying this model could reduce unnecessary biopsy procedures by 32% and reduce the overall need for prostate biopsies by 26%. CONCLUSIONS: In this study of a Japanese population, incorporating clinical and laboratory data into a prebiopsy nomogram significantly improved the prediction of prostate cancer compared with predictions based solely on the individual factors.

Most prostate cancers are androgen-dependent and essentially respond to androgen ablation therapy. However, these tumors eventually become androgen-independent and progress despite androgen ablation. Since the androgen receptor (AR) sequence was determined, numerous studies have shown that AR plays a critical role in the development of androgen-refractory prostate cancer. Amplification of AR, mutations of AR, and deregulation of growth factors, cytokines and AR co-activators, which could be classified as AR-dependent pathways, are frequently observed in this condition. There are other pathways, AR-independent pathways that bypass AR, which involve neuroendocrine differentiation of prostate cancer cells, deregulation of apoptotic genes and unknown mechanisms related to down-regulation of AR. Androgen-refractory prostate cancers with the AR-dependent pathway could be treated by suppressing AR activity, whereas AR-independent tumors would require alternative management strategies. When more cell survival pathways are defined, improvement of patients' survival could be achieved by developing specific gene-targeting therapies that interfere with those pathways.

Background: Ligand-independent activation of the androgen receptor (AR) by cytokines has been implicated in the progression of androgen-independant prostate cancer (PCa). To determine the potential effects of elevated levels of interleukin-4 (IL-4) in patients with PCa, six different cytokines were examined for their ability to activate the AR. Materials and Methods: LNCaP cells were transiently transfected with prostate-specific antigen (PSA) (-630/+12)-luciferase and treated with R1881, six kinds of cytokines including IL-4, or vehicle. Transactivation assays were also performed in LNCaP cells co-transfected with the 5xGalUAS-TATA-luciferase and AR-(1-558)-Gal4DBD prior to incubation with R1881, IL-4, IL-6, or vehicle. Seventy-two patients with pre-treatment PCa, 17 patients with hormone-refractory metastatic PCa receiving androgen ablation therapy, 20 patients with benign prostatic hypertrophy and 10 healthy male volunteers were enrolled in this retrospective study. The concentration of serum IL-4 was measured by chemiluminescence enzyme immunoassay. Results: IL-4 induced androgen-response element-driven reporters and activated the AR N-terminal domain (NTD) in a ligand-independent manner in transiently transfected LNCaP cells. Levels of IL-4 in the serun were significantly elevated in patients with hormone-refractory PCa as compared to the levels in pre-treatment PCa. Conclusion: IL-4 serum levels were demonstrated to be increased in hormone-refractory PCa and IL-4 was shown to enhance PSA reporter gene activity by the activation of AR NTD in human LNCaP cells. These results suggest that the AR can be activated by cytokines, and that this mechanism may play an important role in the transition from androgen-dependent to androgen-independent PCa after patients receive androgen ablation therapy.

AIM: To investigate the prognostic and predictive relevance of p53 protein, Ki-67 antigen, MMP-2 and MMP-9 in patients with transitional cell carcinoma (TCC) of the upper urinary tract. METHODS: The expression of p53 protein, Ki-67 antigen, MMP-2 and MMP-9 was examined by immunohistochemistry in 69 patients with TCC of the upper urinary tract. Correlation of p53, Ki-67, MMP-2 and MMP-9 over-expression with conventional pathological parameters and patient survival was examined. RESULTS: p53 over-expression was significantly correlated with histological grade (P < 0.05), but not with pathological stage, vascular invasion, lymphatic invasion or lymph node metastasis. Ki-67 over-expression was significantly correlated with stage, grade, lymphatic invasion and vascular invasion (P < 0.05). In survival analyses, Ki-67 over-expression was a significant prognostic factor in the univariate analysis (P < 0.05), but it did not have a significant impact on survival in the multivariate analysis. Ki-67 labeling index was a significant prognostic factor in patients with a low p53 labeling index, but not in patients with a high p53 labeling index. CONCLUSION: Ki-67 over-expression is of prognostic value in TCC of the upper urinary tract, while p53, MMP-2 and MMP-9 are of limited value.

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=5.0x10(-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.

We report a multicenter trial with transrectal high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. A total of 72 consecutive patients with stage T1c-2NOM0 prostate cancer were treated using the Sonablate 500TM HIFU device (Focus Surgery, Indianapolis, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and prostate specific antigen (PSA) level were 72 years and 8.10 ng/ml, respectively. The median follow-up period for all patients was 14.0 months. Biochemical disease-free survival rates in all patients at 1 and 2 years were 78% and 76%, respectively. Biochemical disease-free survival rates in patients with stage T1c, T2a and T2b groups at 2 years were 89, 67% and 40% (p = 0.0817). Biochemical disease-free survival rates in patients with Gleason scores of 2-4, 5-7 and 8-10 at 2 years were 88, 72% and 80% (p = 0.6539). Biochemical disease-free survival rates in patients with serum PSA of less than 10 ng/ml and 10-20 ng/ml were 75% and 78% (p = 0.6152). No viable tumor cells were noted in 68% of patients by postoperative prostate needle biopsy. Prostatic volume was decreased from 24.2 ml to 14.0 ml at 6 months after HIFU (p < 0.01). No statistically significant differences were noted in International Prostate Symptom Score, maximum urinary flow rate and quality of life analysis with Functional Assessment of Cancer Therapy. HIFU therapy appears to be minimally invasive, efficacious and safe for patients with localized prostate cancer with pretreatment PSA levels less than 20 ng/ml.

PURPOSE: We investigated the risk factors having an impact on the achievement of stone-free status and on the success rate, as well as on the likelihood of recurrence, in patients undergoing shockwave lithotripsy. PATIENTS AND METHODS: We evaluated the characteristics and outcomes of 3023 patients (3254 renal units) with upper urinary-tract stones who underwent SWL at the Funabashi Clinic over a 13-year period. We assessed the stone-free and success rates for 2844 patients (3061 renal units) 3 months post-SWL. We also determined the recurrence rate for the 1078 patients (1139 renal units) who had achieved stone-free status at that time. RESULTS: Overall, stone-free status was achieved in 65.1% of patients, and the success rate was 85.7%. There were significant differences in the stone-free rates depending on patient age, history of urolithiasis, and presence of pyuria before SWL, as well as the number, location, size, and composition of the stones. Stones recurred in 326 of 1139 renal units (28.6%) during a mean follow-up of 36 months. The recurrence rates were 7.5%, 24.1%, and 33.0% after 1, 3, 5 years, respectively. Multiple stones, a history of urolithiasis, and stones located in the kidney or both kidneys plus the ureter significantly influenced recurrence. Multivariate analysis demonstrated that multiple stones were most significantly related to recurrence. CONCLUSION: Treatment with SWL has a low morbidity and high effectiveness. The number and location of stones and a history of urolithiasis significantly influence recurrence. Further studies of prophylactic therapy are required, especially for patients with these factors.

BACKGROUND: Loss of heterozygosity (LOH) on chromosome 2 is thought to occur only occasionally in prostate cancer (PCa), but allelic losses in this region are frequent in other types of human cancer, such as lung, thyroid, head and neck, and cervix. Here, we show a high-resolution deletion map of markers on chromosome 2 in Japanese patients with PCa. METHODS: Tissue samples were obtained from 66 patients with PCa. DNA from normal, tumor, or metastatic tissue was used as the template for polymerase chain reaction amplification for LOH using 24 microsatellite markers on human chromosome 2. RESULTS: Nineteen of the 66 cases (29%) showed LOH for at least one locus on chromosome 2. LOH on 2p was observed more frequently in cancer death cases than in organ confined and regional diseases (P < 0.001). Paired DNAs were available from both primary and metastatic tumors in the eight cases of cancer death; among those pairs, we detected LOH on 2p in four primary tumors, and in all metastatic foci (P < 0.05). Detailed deletion mapping in these tumors identified four distinct commonly deleted regions on 2p 16.3, 2p 12-cent, 2q 21.3, and 2q 23.1-2q 32.1. CONCLUSIONS: These results suggest that inactivation of putative tumor suppressor genes on chromosome 2 that may play an important role in the progression of Japanese patients with PCa.

INTRODUCTION: The concept of neuroendocrine (NE) differentiation in prostate cancer has become more widely recognized as its diagnostic, prognostic, and therapeutic usefulness. PATIENTS AND METHODS: We enrolled 38 patients with stage D prostate cancer who underwent endocrine therapy by medical or surgical castration and oral antiandrogen. According to PSA response, serum levels of CGA as a marker of NE differentiation were measured at the multiple points of time; (1) pre-treatment, (2) complete response (CR), (3) a nadir level of PSA, (4) PSA failure or hormone independent progression. We compared these serum values in relation to efficacy of endocrine therapy. RESULTS: There was no correlation between serum PSA and CGA values. Patients consisted of 27 with CR and 11 without CR. Serum CGA increased as intervals of endocrine therapy became longer with positive correlation (p < 0.05). Its velocity was higher in patients with PSA failure than in those without it (6.98 vs. 2.09 ng/ml/month, p = 0.011). CONCLUSION: During endocrine therapy in metastatic prostate cancer patients, serum CGA values were not related to serum PSA levels, and increased as treatment periods became longer. It is suggested that CGA velocity has potential to predict androgen independent progression after endocrine therapy.

36歳男.健診にて高血圧を指摘され内服加療されたが血圧コントロール不良で,さらに低K血症と画像所見から右副腎腫瘍を疑われ精査加療目的で紹介入院となった.入院時のホルモン基質値ではニフェジピン60mg・アムロジピン10mg・テルミサルタン40mg服用時に血漿アルドステロン濃度(PAC)390pg/ml・血漿レニン活性(PRA)4.03ng/ml/hrであったが,テルサルミン中止後はPAC320pg/ml・PRA0.31ng/ml/hrとレニンが低下した.血液ガス所見ではアルカローシスを認め,入院後の尿生化学所見では腎機能障害が認められた.腹部単純MRIにて右副腎に径20mm大の腫瘤を認め,カプトリル負荷試験・フロセミド立位負荷試験結果から副腎腫瘍による原発性アルドステロン症と診断したが,腎血管性高血圧症の合併が疑われた.左副腎摘出時の腎生検にて小葉間動脈の内腔狭窄・線維性内膜肥厚を認めたことから中程度の太さの血管病変に伴う異常と考えられた

OBJECTIVE: Androgen ablation has been the initial treatment of choice for men with metastatic prostate cancer, but the disease generally relapses to an androgen-independent state thereafter. To understand which groups respond well or poorly to endocrine therapy is thus important. Several studies have shown that pretreatment serum testosterone (T) levels and the length of the CAG repeat at the N-terminal region of the androgen receptor are significant. However, the relevance of a combination of these factors has not been reported. We therefore investigated the clinical significance of CAG repeat length and pretreatment serum T levels among Japanese patients with metastatic prostate cancer (TxNxM1), and analyzed their relevance to survival. METHODS: Fifty-two Japanese patients with metastatic prostate cancer were enrolled in this study. We determined the length of the CAG repeat by both PCR sequencing and fragment analysis. Pretreatment serum T levels were measured using a radioimmunoassay. We examined the clinical significance of the CAG repeats and T levels individually and in combination with respect to several clinical factors. RESULTS: The pretreatment T level in the responder group was significantly higher than that in the non-responders (p=0.009) and the mean was 4.33+/-2.12 ng/ml. Kaplan-Meier analyses revealed that cause-specific survival was significantly enhanced in patients with higher levels of T (p=0.0489). The length of the CAG repeat was positively associated with age at diagnosis (p=0.032). The mean CAG repeat length was 22.5+/-3.0 and this value was significantly shorter in patients with poorly differentiated, than with well and moderately differentiated tumors (p=0.019). Kaplan-Meier analyses revealed a significantly better cause-specific survival rate as well as progression-free survival rate in patients with longer CAG repeats. Cause-specific survival curves were better in patients with higher T levels and longer CAG repeats than with lower T levels and shorter CAG repeats (p=0.0066). A multivariate analysis showed that the most significant prognostic factor was histological grade, followed by EOD grade, marker response and the combination of T and CAG. CONCLUSION: Pretreatment serum T levels together with the length of the N-terminal CAG repeat of the androgen receptor gene can distinguish responders from non-responders to androgen ablation. These parameters appear to be clinically useful, in that therapies appropriate to individual patients could be selected. Further studies are necessary to confirm these results.