Kenji Ohgaki

Association Between Metabolic Syndrome and Male Lower Urinary Tract Symptoms in Japanese Subjects Using Three Sets of Criteria for Metabolic Syndrome and International Prostate Symptom Score

OBJECTIVES To investigate whether the metabolic syndrome is a risk factor for lower urinary tract symptoms (LUTS), as defined by the International Prostate Symptom Score (IPSS). METHODS A total of 900 men underwent digital rectal examination of the prostate and completed an IPSS questionnaire. These men had visited our hospital for metabolic screening from April 2008 to March 2009. The IPSS includes scores for 3 questions on voiding symptoms, 3 on storage symptoms, and 1 on postmicturition symptoms. The relationships of the LUTS (determined from the IPSS subscores) with the metabolic syndrome diagnosed using the Japan Society for the Study of Obesity, 2005 National Cholesterol Education Program-Adult Treatment Panel III, and 2005 International Diabetes Federation criteria were examined. The severity of LUTS was compared among the younger, middle-age, and older men (<50, 50-64, and ≥65 years old, respectively) with and without the metabolic syndrome. RESULTS A diagnosis of the metabolic syndrome was made in 16.7%, 16.6%, and 11.7% of the men using the Japan Society for the Study of Obesity, 2005 National Cholesterol Education Program-Adult Treatment Panel III, and 2005 International Diabetes Federation criteria, respectively. Regardless of the presence of the metabolic syndrome, aging was significantly associated with an increased rate of moderate or severe LUTS, except for postmicturition symptoms. In the middle-age men, the metabolic syndrome had a significant negative correlation with storage symptoms (odds ratio 0.258-0.426). In the younger and older men, LUTS was observed equally in those with and without the metabolic syndrome. CONCLUSIONS A relationship between age and LUTS was observed; however, the metabolic syndrome did not show a clear association with LUTS. Our results suggest that LUTS is associated with aging, regardless of the presence of the metabolic syndrome.

Localization of tumor suppressor gene associated with distant metastasis of urinary bladder cancer to a 1‐Mb interval on 8p22

To identify the location of one or more putative tumor suppressor genes that may be involved in urinary bladder cancer, we examined 82 such tumors for allelic losses at 19 microsatellite loci on 8p. Loss of heterozygosity was observed in 31 of the cases. Deletion mapping identified a commonly deleted region at 8p22, within the 1‐Mb interval flanked by D8S1135 and AFM177XB10. Allelic loss at 8p22 was associated with higher tumor grade (17/31, 55%, vs. 12/51, 23%; P = 0.0013). Furthermore, no tumor that retained heterozygosity for markers at 8p22 had metastasized to distant organs, whereas a substantial portion of tumors that lost alleles in that region had done so (0/51, 0%, vs. 6/31, 20%; P = 0.001). These data imply that loss or inactivation of tumor‐suppressing activity encoded on 8p contributes to malignancy and to the metastatic potential of bladder cancers. Genes Chromosomes Cancer 25:1–5, 1999.

Association Between Metabolic Syndrome and Male Overactive Bladder in a Japanese Population Based on Three Different Sets of Criteria for Metabolic Syndrome and the Overactive Bladder Symptom Score

OBJECTIVE To investigate whether metabolic syndrome is a risk factor for overactive bladder (OAB) defined by the Overactive Bladder Symptom Score (OABSS). METHODS A digital rectal examination of the prostate and an OABSS questionnaire were conducted in 1031 men who visited our hospital for metabolic screening from April 2009 to March 2010. The OABSS includes scores for daytime frequency, nighttime frequency, urgency, and urgency incontinence. Relationships of OAB (defined as OABSS ≥3 with an urgency score ≥2) with metabolic syndrome diagnosed by Japan Society for the Study of Obesity (JASSO), National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III), and International Diabetes Federation (IDF) criteria were examined. The severity of OAB symptoms was compared among younger, middle-aged, and elderly men (<50, 50-64, and ≥65 years old, respectively) with and without metabolic syndrome. RESULTS Diagnoses of metabolic syndrome were made in 16.4%, 16.9%, and 12.0% of the men using JASSO, NCEP-ATP III, and IDF criteria, respectively. Regardless of the presence of metabolic syndrome, aging was significantly associated with increased rates of moderate or severe OABSS findings and OAB defined by the OABSS. In middle-aged men, metabolic syndrome had a significant negative association with OAB rate. In elderly men, metabolic syndrome had a significant negative association with the total OABSS. CONCLUSION A relationship between age and OAB was observed, but metabolic syndrome did not show a clear association with OAB. Our results suggest that OAB is associated with aging regardless of the presence of metabolic syndrome.

Two Target Regions of Allelic Loss on Chromosome 9 in Urinary-bladder Cancer

Allelic losses on chromosome 9 are common in a wide variety of human tumors; moreover, two predisposing loci for some inherited cancer syndromes, i.e., familial malignant melanoma and Gorlin syndrome, have been identified on this chromosome. To define the location of putative tumor suppressor genes involved in cancer of the urinary bladder, 85 bladder cancers were examined for allelic loss at 18 microsatellite loci on chromosome 9. Correlations were also sought between loss of heterozygosity on chromosome 9 and several clinicopathological parameters. Allelic loss was observed in 54 of the tumors (64%) and deletion mapping identified two target regions; one at an interval on 9p21 flanked by D9S736 and D9S165, and the other at an interval on 9q31‐34 flanked by D9S58 and D9S61. No subtle mutation was detected in the PTCH gene which lies in the latter interval. Allelic loss on chromosome 9 was observed frequently in low grade and non‐invasive tumors as well as in tumors of more advanced phenotype. Inactivation of tumor suppressor genes lying in either of two regions of common deletion identified on chromosome 9 might affect carcinogenic mechanisms at an early stage of tumor development in the urinary bladder.

Definition of a 1-Mb homozygous deletion at 9q32-q33 in a human bladder-cancer cell line

AbstractWe performed detailed molecular analyses of a suspected homozygous deletion on chromosome 9q32-q33 in a bladder-cancer cell line (KYBTDS) derived from a superficial papillary transitional cell carcinoma (TCC). We examined 13 sequence-tagged site (STS) markers mapped along 9q32-q33 by polymerase chain reaction (PCR), and used 13 bacterial artificial chromosome (BAC)/bacteriophage P1-derived artificial chromosome (PAC) genomic clone probes representing these STS markers as probes for dual-color fluorescence in situ hybridization (FISH) analyses to define the deleted region cytogenetically and at the molecular level. Southern blotting confirmed the findings. This combination of techniques revealed that the homozygous deletion in the KYBTDS cell line involved less than 1 megabase of DNA, flanked by markers A003P42 and SGC33380. This interval overlaps part of a common region of deletion observed in a number of primary bladder cancers; moreover, the DNA sequence within the 1-Mb segment corresponds to part of a YAC genomic clone that encompasses a putative tumor suppressor gene, DBCCR1.

Facilitation of expulsion of ureteral stones by addition of α1-blockers to conservative therapy.

Abstract Objective. An antispasmodic agent and a medicine that facilitates stone expulsion are given commonly as conservative therapy for ureteral stones in Japan. The goal of this study was to compare the efficacy of the addition of various α1-blockers to the conservative therapy for spontaneous passage of ureteral stones. Material and methods. The subjects were 132 patients with stones from the upper to the lower ureter who were randomly placed into one of four groups and followed for 1 month to assess spontaneous passage of stones. The control group received daily doses of 240 mg flopropione as an antispasmodic agent and 1350 mg extract of Quercus salicina Blume/Quercus stenophylla Makino as a medicine that facilitates stone expulsion. The other three groups received this therapy and daily doses of 30 mg urapidil, 0.2 mg tamsulosin or 50 mg naftopidil, respectively. The characteristics of the stones and stone expulsion were evaluated by urinalysis, a kidney, ureter and bladder (KUB) X-ray, ultrasound and computed tomography. Results. All patients completed the study and there were no major side-effects. There was no difference in age, stone position or stone size among the groups. Multivariate analysis using a Cox proportional hazards model indicated that the probability of stone expulsion for 1 month was increased 2.38 times (95% confidence interval 1.23–4.61) by naftopidil compared with control therapy alone (p = 0.01). Conclusion. Naftopidil in combination with an antispasmodic agent and a medicine that facilitates stone expulsion produces a significantly increased rate of ureteral stone expulsion.

Nucleotide variations in genes encoding plasminogen activator inhibitor-2 and serine proteinase inhibitor B10 associated with prostate cancer

AbstractGenes 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=5.0×10−5); 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.

Prostate cancer in patients with Hansen's disease.

Hansens disease causes testicular failure secondarily, and because of this, it has been considered that prostate cancer would not be found in association. Three of 14 patients with chronic leprosy in Suruga National Sanatorium Hansens Disease Hospital were found to have prostate cancer. A 72‐year‐old with lepromatous leprosy was diagnosed with stage T3a prostate cancer and treated with radical prostatectomy after hormonal therapy, plus irradiation. An 80‐year‐old with lepromatous leprosy was diagnosed with stage T2 prostate cancer and treated with irradiation and follow up only without hormone therapy and surgery because of his low testosterone level and old age. An 82‐year‐old with borderline leprosy was diagnosed with stage T1c prostate cancer and because of the pathological finding of low Gleason score and his old age, he was treated with hormonal therapy only. Two of the three cases had elevated concentrations of follicle‐stimulating hormone and luteinizing hormone, which suggests that their prostatic cancers might have been equivalent to be under the influence of hormone therapy. Therefore, in aged male patients with Hansens disease, the follicle‐stimulating hormone, luteinizing hormone and testosterone concentrations should be measured, as well as that of prostate‐specific antigen, and a prostate biopsy should be also considered if the prostate‐specific antigen concentration is increased, even with hypogonadism.