Carcinoma of unknown primary origin with isolated adrenal metastasis: a report of two cases.

The adrenal glands are one of the most common sites of malignant tumor metastasis. However, metastatic adrenal carcinoma of unknown primary origin with localized adrenal gland involvement is an extremely rare condition. Herein, we reported two cases of carcinoma of unknown primary origin with isolated adrenal metastasis. In the first case, back pain was the trigger; while in the second case, the triggers were low fever and weight loss. Metabolic abnormalities such as hypertension and obesity were not detected in either case. Neither patient had relevant previous medical histories, including malignancy. However, both had a long-term history of smoking. Systemic imaging studies revealed only adrenal tumors and surrounding lesions. Primary adrenocortical carcinoma was initially suspected, and chemotherapy including mitotane was considered. However, due to difficulty in complete resection of the tumor, core needle tumor biopsies were performed. Histopathological examination of biopsy specimens led to the diagnosis of carcinoma of unknown primary origin with isolated adrenal metastasis. In both cases, additional laboratory testing showed high levels of serum squamous cell carcinoma-related antigen and serum cytokeratin fragment. Malignant lesions confined to the adrenal glands are rare. As in our cases, it could be occasionally difficult to differentiate non-functioning primary adrenocortical carcinoma from metastatic adrenal carcinoma of unknown primary origin localized to the adrenal gland. If the lesion is unresectable and there are elevated levels of several tumor markers with no apparent hormonal excess, core needle tumor biopsy should be considered to differentiate the primary tumor from the metastatic tumor.

The resonance® metallic ureteral stent in the treatment of malignant ureteral obstruction: a prospective observational study.

BACKGROUND: To study the outcomes and experiences of using metallic stents in treating patients with malignant ureteral obstruction (MUO), we examined the effects of metallic ureteral stenting using the Cook Resonance® stent in the treatment of MUO. METHODS: All patients who had a Resonance metallic stent inserted between April 2015 and March 2018 at one of multiple facilities were prospectively observed with a 1-year follow-up. The primary outcome was the patency rate of the metallic ureteral stent. The secondary outcomes included the complications (e.g., infection and fever). RESULTS: Although stent insertion was attempted in 50 patients, the stent could not be inserted as a ureteral stent in three patients due to severe ureteral stricture, and one ureteral cancer patient was excluded from the analysis. The remaining 46 patients' median age was 67 years (range 28-85 years) (16 males, 30 females). Twenty-four patients died during the study; their median survival time was 226 days. The median follow-up period for the censored patients was 355 days (range 16-372 days), and just seven patients were still alive without Resonance failure > 1 year later. The women's IPSS scores tended to be lower than those of the men. Regarding the OABSS score, although the women's total score tended to be low, the difference between the men's and women's scores was nonsignificant. The bacteria detected from urine culture after stent insertion were more gram-positive than gram-negative. CONCLUSION: Metallic ureteric stenting using the Resonance stent is safe and effective for treating MUO. Subjective symptoms were relatively less in the female patients.

Significance of the mucinous component in the histopathological classification of colon cancer.

PURPOSE: Mucinous carcinoma is often independently classified as a histological type of colon cancer, but there are currently no established diagnostic criteria. The relationship between the proportions of mucinous components to the oncological outcomes was examined to determine whether mucinous carcinoma should be classified as an independent histological type. METHODS: The study group comprised 1,038 patients with colon cancer. The relationships between the survival rates and recurrence patterns with the mucinous component area ratio (MC area ratio) and clinical variables were evaluated. RESULTS: Tumors were classified into three groups: Group 1 (MC area ratio, 0 %), Group 2 (1-49 %), and Group 3 (≥50 %). Of the 1038 tumors studied, 877 (84 %) were classified as Group 1, 123 (12 %) as Group 2, and 38 (4 %) as Group 3. The tumor size was significantly larger in Group 3, and an increased MC area ratio was significantly related to a higher proportion of right-sided tumors. Among patients with stage II or III disease, stage III disease, poorly differentiated adenocarcinoma, and no adjuvant chemotherapy were poor prognostic factors. There was no relationship between the MC area ratio and the survival or recurrence pattern. CONCLUSION: Mucinous carcinoma does not need to be classified as a separate histological type from ordinary differentiated adenocarcinoma.

IgE Abs to Der p 1 and Der p 2 as diagnostic markers of house dust mite allergy as defined by a bronchoprovocation test.

BACKGROUND: Limited information is available regarding the clinical usefulness of measuring the levels of IgE to allergen components from house dust mites (HDMs) in the diagnosis of genuine HDM allergy. METHODS: To evaluate the diagnostic usefulness of measuring levels of serum IgE antibodies (Abs) to allergen components from Dermatophagoides pteronyssinus (DP) as a predictor of immediate asthmatic response (IAR) to bronchoprovocation, we studied 55 DP-sensitized asthmatic patients who underwent a bronchoprovocation test using crude DP extract. The levels of IgE Abs to crude DP, nDer p 1, rDer p 2, and rDer p 10 in patients who showed IAR (n = 41) were compared with those in patients who showed no IAR (n = 14). RESULTS: While the frequencies of positivity for IgE Abs to nDer p 1 and rDer p 2 among the entire study population were 89 and 86%, respectively, all patients with IAR tested positive for both of them with high IgE concentrations. The areas under the receiver operating characteristic curves for IgE to nDer p 1 and rDer p 2 as predictors of IAR were 0.913 and 0.906, respectively. The specificity of IgE to nDer p 1 and rDer p 2 was higher than IgE to crude DP even at low cut-off points. CONCLUSIONS: IgE to nDer p 1 and/or rDer p 2 was highly predictive of allergen-induced IAR. These findings validate the clinical usefulness of measuring the levels of IgE to nDer p 1 and rDer p 2 as a diagnostic tool for genuine HDM allergy.

PHYSIOLOGIC AIRWAY RESPONSES TO INHALED HISTAMINE AND ACETYLCHOLINE IN PATIENTS WITH MILD ASTHMA AS ANALYZED BY FORCED OSCILLATION.

BACKGROUND AND AIMS: Asthma is a chronic disease characterized by airway inflammation; it is sometimes difficult to diagnose. For clinical diagnosis, forced oscillation technique (FOT) measures airway reactance and resistance. By FOT, we investigated respiratory resistance and ventilation perfusion ratio inequality in adults with mild asthma. METHODS: We examined 58 adult patients with mild asthma having no inhaled corticosteroid treatment, and 10 adult patients with post-infectious prolonged cough. Using a MostGraph-01 FOT instrument, we evaluated these patients before and after bronchial hyperresponsiveness to acetylcholine (ACh) or histamine (Hist). We measured the following conditions: change of resistance at 5Hz (R5) and 20Hz (R20), R5-R20, reactance at 5Hz, frequency of resonance (Fres), low-frequency reactance area (ALX), and forced expiratory volume in 1 second (FEV1). RESULTS: There were significant changes of R5, R20, R5-R20, X5, Fres, ALX after provocations for ACh or Hist in all patients with asthma, but not in patients with post-infectious prolonged cough. We calculated the percent decrease in FEV1 after provocation with ACh or Hist. For Ach, this decrease in FEV1 correlated with changes in R20 and Fres for all patients. For Hist, the percent decrease in FEV1 correlated with changes in R5, R20, Fres, and ALX for all patients. Furthermore, we investigated these correlations in patients with normalized bronchial hyperresponsiveness to ACh or Hist. For Ach, the percent decrease in FEV1 correlated with changes in Fres or R5-R20. For Hist, this decrease in FEV1 correlated with changes in R5, R20, and Fres. ROC analysis was used to evaluate the diagnostic value of the ratio of change of Fres in BHR to Hist. The area under the curve was 0.7808 (95% CI=0.657-0.904). A reasonably high specificity (100.0%) and a high sensitivity (53.8%) with a cut-off point of 1.5 in the ratio before and after of Fres were obtained. CONCLUSION: The changes in FOT parameters (before and after bronchial airway responses) may detect airway resistance and ventilation perfusion ratio inequality even in adult patients with asthma having normalized bronchial hyperresponsiveness to ACh or Hist. That results may be useful for an early diagnosis of asthma.

Effects of dutasteride on lower urinary tract symptoms and general health in men with benign prostatic hypertroplasia and hypogonadism: a prospective study.

INTRODUCTION: We investigated the effects of the relative increase in testosterone by dutasteride administration in patients with benign prostatic hyperplasia and hypogonadism on urinary symptoms or androgen-responsive general health. METHODS: Seventy-six patients were enrolled, and were taking 0.5 mg dutasteride daily for 52 weeks. Before and after treatment, all participants underwent blood test, and body mass index, prostate volume (PV), bone mineral density (BMD), post-voiding residual (PVR) volume, and muscle volume were measured. All patients responded to the questionnaires: International prostatic symptom score (IPSS), Overactive Bladder Symptom score (OABSS). Patients were divided into two groups according to the increase rate of total testosterone (TT): group A, ≥20% increase in TT level; group B, <20% increase or decrease. RESULTS: Baseline TT and free testosterone (FT) levels were significantly lower in group A than group B. Both groups showed marked improvement in PV and PVR. Group A showed significant improvement in IPSS and OABSS with a significant increase of FT level, whereas group B showed no significant change. Dutasteride treatment contributed to a significant increase in BMD in group A. CONCLUSIONS: Dutasteride treatment significantly improved urinary symptoms and BMD in patients with low baseline serum TT and FT levels.

Plasma free metanephrines in the diagnosis of pheochromocytoma: diagnostic accuracy and strategies for Japanese patients.

Measuring the levels of the plasma free metanephrines (PFMs) represents a recently developed and promising test for the diagnosis of pheochromocytoma in the United States and Europe. As this test has not yet been evaluated in Japan, it is necessary to evaluate the diagnostic efficacy of measuring the levels of PFMs compared with the standard measurement of the urinary excretion of metanephrines (uMNs) whose reliability is well established to detect of pheochromocytoma. A total of 101 Japanese subjects clinically suspected of having pheochromocytoma in were included in this study. Subsequently, we prospectively measured the PFMs levels in all patients, compared with those of biochemical markers of the catecholamine secretion and metabolisms in the plasma and urine. All subjects with adrenal tumors underwent tumor excision. Data were available for 84 of the 101 patients, 47 of whom had histopathologically proven pheochromocytoma and 37 were finally diagnosed with non-pheochromocytoma. The results of comparisons in the accuracy of measurement for diagnosis of pheochromocytoma between PFMs and the urinary excretion of metanephrines (uMNs) were 0.980 VS 0.951 for AUC of receiver operatorating characteristic (ROC) curve, 0.957 VS 0.894 for sensitivity, and 0.973 VS 0.946 for specificity, respectively. Although the differences were small, the results of our study definitely demonstrated that measurement of PFMs was not inferior to standard urinary metanephrines (uMNs) measurement, which is established to be the most reliable biochemical method to detect pheochromocytoma. This study clearly shows measuring the PFMs levels to be a reliable and efficient method for diagnosing pheochromocytoma in Japanese patients, as demonstrated in previous reports.

Comparison of testosterone fractions between Framingham Heart Study participants and Japanese participants.

OBJECTIVES: To determine testosterone fractions in Japanese men and to compare these values with those of Framingham Heart Study participants. METHODS: We enrolled 498 healthy Japanese men. Total testosterone was assayed by liquid chromatography tandem mass spectrometry, sex hormone-binding globulin was assayed by immunoassay and free testosterone was calculated by a laboratory at the Boston Medical Center. Analog-based free testosterone and immunoassay-based total testosterone were determined by immunoassay. We compared mass spectrometry assay-based total testosterone and calculated free testosterone values in the Japanese participants with values in the American Framingham Heart Study third generation cohort. RESULTS: The mean serum mass spectrometry assay-based total testosterone, sex hormone-binding globulin, and calculated free testosterone values were 439.4 ± 167 ng/dL, 65.34 ± 30.61 nmol/L, and 58.75 ± 20.0 pg/mL, respectively. The correlation coefficients with age for mass spectrometry assay-based total testosterone, sex hormone-binding globulin, and calculated free testosterone were 0.0010, 0.5041, and -0.496, respectively. There were no age-related changes in mass spectrometry assay-based total testosterone values in healthy men (P = 0.981), whereas sex hormone-binding globulin and calculated free testosterone levels showed similar age-related changes (P < 0.0001). Serum analog-based free testosterone levels (8.24 ± 2.9 pg/mL) showed age-related changes (P < 0.0001) regardless of immunoassay-based total testosterone levels (P = 0.828). Serum immunoassay-based total testosterone values (486.1 ± 162.5 ng/dL) correlated with serum mass spectrometry assay-based total testosterone values (r = 0.740, 95% confidence interval 0.6965-0.7781, P < 0.0001). Similarly, analog-based free testosterone and calculated free testosterone values showed a highly significant correlation (r = 0.706, 95% confidence interval 0.6587-0.7473, P < 0.0001). The analog-based free testosterone values were approximately 10% of the calculated free testosterone values. CONCLUSIONS: In contrast to the Framingham Heart Study cohort, total testosterone values in Japanese men are not associated with advancing age; thus, they cannot be used to diagnose late-onset hypogonadism in Japan. The analog-based free testosterone value can be considered instead as a suitable biochemical determinant for diagnosing late-onset hypogonadism syndrome.

New molecular diagnostic kit to assess Y-chromosome deletions in the Japanese population.

OBJECTIVES: Deletions in the azoospermia factor regions are the most common known molecular genetic cause of human male infertility involving spermatogenetic failure. Testing for these deletions in Japanese DNA samples using conventional sequence-tagged site probes occasionally lead to considerable non-specific or faint products in the Japanese population. The aim of the present study was to evaluate the sensitivity and specificity of a newly developed kit for the detection of azoospermia factor microdeletions in the Japanese population. METHODS: Sequence-tagged site probes were reselected and the Luminex suspension array assay was carried out. Validation was retrospectively carried out with 2014 DNA sequences with known microdeletions, which were divided into four categories. RESULTS: Category 1 deletions that corresponded to the conventional classification of azoospermia factor deletion were present in 83 men (4.2%), which can result in intrachromosomal homologous recombination. Kit data confirmed the presence of deletions of this type in DNA sequences known to harbor the azoospermia factor deletions. Category 2 deletions involved cytogenetic abnormalities in 28 men (1.4%), whereas category 3 deletions in 759 men (37.7%) were atypical classifications including the gr/gr deletion. As these deletions are thought to be a result of palindromic units and non-homologous recombination, these microdeletions might impact in the interpretation of some clinical findings. The rest of the 1145 cases (56.8%) were assigned to category 4 as normal variants (polymorphism/no deletion). CONCLUSIONS: The present findings show that this new kit offers good sensitivity and specificity with the advantage of saving in terms of cost and time.

[Comparison of exhaled nitric oxide levels measured by two offline methods and the NO breath® method in Japan].

BACKGROUND: The fraction of exhaled nitric oxide (FeNO) is a useful marker of eosinophilic airway inflammation in asthmatics. Clinical application of FeNO measurement in Japan is expected increase because the procedure is now covered through health insurance. However, the measurement system used is known to affect FeNO results, and it remains unknown whether results from offline methods correlate with those from traditional online methods, such as NO breath®. METHODS: The study population comprised 48 patients at our hospital. FeNO levels were measured by using two offline methods (Sievers and CEIS) and a standard online method, NO breath® RESULTS: FeNONO breath levels were significantly correlated with FeNOSievers(r=0.875) and FeNOCEIS(r=0.888) levels. FeNONO breath levels were nearly equal to FeNOSievers results (FeNONO breath=1.05×FeNOSievers), but both of these levels were lower (p=0.02) than FeNOCEIS data (FeNONO breath=0.74×FeNOCEIS). A Bland-Altman plot of values obtained by the NO breath® and Sievers methods revealed that the NO breath® result was lower than the Sievers level when FeNO was low but was higher than the Sievers level when FeNO was high. CONCLUSION: Differences exist in the levels of FeNO measurement by three methods (two offline methods and NO breath®): conversion equations are needed to compare the FeNO levels obtained by using these three methods. In addition, NO breath® may be more useful to distinguish asthmatic patients from non-asthmatics, compared with Sievers method.

Increases in bone turnover marker levels at an early phase after starting zoledronic acid predicts skeletal-related events in patients with prostate cancer with bone metastasis.

OBJECTIVE: To examine whether bone turnover markers could be predictive markers of the probability of newly arising skeletal-related events (SRE) after the start of zoledronic acid treatment in patients with prostate cancer with bone metastasis. PATIENTS AND METHODS: In all, 30 patients with prostate cancer with bone metastasis were treated with zoledronic acid infusion every 4 weeks. Serum C-terminal crosslinking telopeptide of type 1 collagen (1CTP), bone alkaline phosphatase (BAP), and prostate-specific antigen (PSA) levels were measured at the start of zoledronic acid treatment to establish baseline values, and every 4 weeks thereafter. To judge in the early phase whether zoledronic acid is effective in these patients, we retrospectively compared 1CTP, BAP, and PSA levels at 1, 3, and 6 months after starting zoledronic acid treatment with those at baseline. RESULTS: SRE-free survival of patients with increases of 1CTP levels at 1 and 3 months and BAP levels at 3 months were significantly poorer than those of patients with decreases in 1CTP or BAP levels (P = 0.001, P = 0.042, and P = 0.004, respectively). Overall survival of patients with increases of 1CTP levels at 1 and 3 months and of BAP levels at 6 months were significantly poorer than those of patients with decreases of 1CTP or BAP levels (P = 0.013, P = 0.027, and P = 0.035, respectively). CONCLUSION: The measurement of 1CTP and BAP levels at an early phase after starting zoledronic acid treatment may be useful for physicians to inform patients of their prognosis and to determine the subsequent treatment plan.

A case study of human papillomavirus-associated bladder carcinoma developing after urethral condyloma acuminatum.

We report a 35-year-old man with bladder carcinoma developing 2 months after urethral condyloma acuminatum, with an 8-year history of persistent human papilloma virus-58 infection in the urinary tract. DNA was extracted from paraffin-embedded tissue specimens. Human papilloma virus-6 and -58 were detected in the condyloma, whereas human papilloma virus-58 was detected in the carcinoma. In situ hybridization analysis also demonstrated high-risk human papilloma virus-DNA signals in the condyloma and carcinoma tissues. Immunohistochemistry showed that p16-INK4a and mcm-7, surrogate markers of oncogenic human papilloma virus E7 protein, were weakly expressed in the condyloma tissue but were strongly expressed in the carcinoma tissues, suggesting that human papilloma virus-58 was present in the episomal state in the condyloma, whereas human papilloma virus-58 DNA was integrated into the host cells and its infection may have a role in the development of bladder carcinoma. Human papilloma virus-58 was continuously detected in the urethral brushing samples 8 years after treatment for urethral condyloma, and human papilloma virus-58 infection was still persistent in the urethra.

Markers for step-down of inhaled corticosteroid therapy in adult asthmatics.

BACKGROUND: Treatment guidelines recommend the use of inhaled corticosteroids (ICS) as first-line therapy for all stages of persistent asthma. However, it is unknown whether ICS dose reduction in adult asthmatics is compatible with maintaining asthma control. Moreover, there are no predictors of efficacy in maintaining asthma control upon ICS reduction. METHODS: We recruited 90 adult patients with moderate or severe asthma but no clinical symptoms of asthma for at least 6 months. All patients reduced their ICS doses by half but continued taking other asthma-related medications. As a primary outcome, we measured asthma exacerbations during the 12 months following ICS reduction. We also further monitored patients from the above study who had maintained total asthma control for 12 months after ICS reduction and who had continued on their reduced doses of ICS or had further reduced, or stopped, their ICS. RESULTS: Forty of ninety patients (44.4%) experienced exacerbations after ICS reduction (time to first exacerbation: 6.4 ± 3.6 months). Multivariate logistic regression modeling revealed a rank order of predictors of success in ICS reduction while retaining asthma control: acetylcholine (ACh) PC(20) (p < 0.01); length of time with no clinical symptoms before ICS reduction (p < 0.01); FeNO (p = 0.028); and forced expiratory volume in 1 s (FEV(1); % predicted) (p = 0.03). Finally thirty-nine of 50 patients maintained total asthma control for at least 2 years after the initial ICS reduction. CONCLUSIONS: In asthma patients with normalized AChPC(20) of 20mg/mL or 10mg/mL and no clinical symptoms for at least 12 or 24 months it may be possible to successfully reduce ICS without increasing exacerbations for long time.

[Use of forced oscillation technique to detect airflow limitations in adult Japanese asthmatics].

BACKGROUND: The forced oscillation technique (FOT) is a noninvasive method that is used to measure respiratory mechanics, including respiratory resistance and reactance at multiple frequencies. The advantage of FOT over spirometry is that FOT does not require forced expiratory maneuvers. Moreover, a new FOT machine called MostGraph (Chest Co. Ltd., Tokyo, Japan), has been developed in Japan, and can be used clinically to diagnose and monitor asthma. The purpose of this study is to show the standard of FOT measured with MostGraph in adult Japanese asthmatics. METHODS: From our outpatient clinic, we recruited 151 stable asthmatics who were being treated with inhaled corticosteroids at the time of the study. For each subject, we measured the fraction of exhaled nitric oxide (FeNO) by using a chemiluminescent nitric oxide analyzer (Sievers280, GE, Boulder, Co); we determined the levels of forced expiratory volume in 1s (%FEV1) and maximum mid-expiratory flow rate (%MMF) by using spirometory; and we measured resistance at 5 Hz(R5), resistance at 20 Hz(R20), R5-R20, reactance at 5 Hz(X5), frequency of resonance (Fres), and low-frequency reactance area (ALX), by using a MostGraph FOT machine. RESULTS: Each of the FOT parameters measured by using the MostGraph machine was significantly correlated with %FEV1 and %MMF (p<0.001), with Fres showing the strongest association. Three of the FOT parameters, X5, Fres, and ALX, were significantly associated with the subject's age (p=0.01, p<0.001, p<0.001, respectively), and all FOT parameters were significantly associated with the subject's body mass index (BMI) (p<0.001 to p=0.018). The results of multiple regression analyses between FOT parameters and FEV1, age, BMI, and FeNO, showed that Fres was significantly associated with FEV1(p<0.001) and BMI (p<0.001). From the results of the simple linear regression between Fres and FEV1, we estimated that Fres values of 17.5 Hz corresponded to %FEV1 values of 60%; Fres values of 11.3 Hz corresponded to %FEV1 values of 80%; and Fres values of 4.94 Hz corresponded to %FEV1 values of 100%. CONCLUSION: FOT parameters measured by using a MostGraph machine can be used successfully to assess the level of airflow limitation in adult stable asthmatics.

Quality assessment of yellowtail (Seriola quinqueradiata) meat cultured in an offshore floating flexible facility.

Commercial aquaculture of yellowtail (Seriola quinqueradiata) is challenging, owing to deterioration of aquaculture environments. Offshore aquaculture may be a means of overcoming these problems. Here, we assessed the quality of flesh from offshore yellowtail (OY) bred for 1 year in an offshore floating flexible facility compared with coastal yellowtail (CY) cultured simultaneously in a coastal cage facility. The survival rate of the OY group was 94.46%, which was slightly lower than that of CY (98.18%). The feeding rate (feeding weight/fish weight) of CY was 0.4-0.5, whereas that of OY was only 0.3, possibly because poor weather conditions prevented feeding at the offshore facility. However, final fish weights did not differ significantly between both groups. In sensory tests, OY was inferior to CY in terms of oily taste. The lipid content in CY was significantly higher than that in OY. Hardness analysis revealed that OY muscles were harder than those of CY. There were no significant differences between OY and CY in overall sensory evaluations; thus, OY was judged as having equivalent value as a food product with CY. The redness of dark muscles was not significantly different on day 1 of refrigeration. However, the redness value of OY was significantly higher than that of CY on day 2. The inferior fattiness of OY relative to that of CY can be overcome by improving the feeding method. Therefore, offshore aquaculture with negligible environmental pollution may be effective for further development of aquaculture.

Current outcome of patients with ureteral stents for the management of malignant ureteral obstruction.

PURPOSE: We analyzed the prognostic factors associated with overall survival and predictive factors of stent failure in patients treated with an indwelling retrograde ureteral stent for malignant ureteral obstruction. MATERIALS AND METHODS: Among 186 Japanese patients treated with an indwelling retrograde ureteral stent for ureteral obstruction from January 2005 to March 2010, 61 with malignant ureteral obstruction and 95 ureteral units were analyzed retrospectively. RESULTS: Median survival was estimated at 228 days. Unfavorable prognostic factors of overall survival were no treatment after indwelling retrograde ureteral stent placement (p = 0.023) and a serum creatinine before indwelling retrograde ureteral stent placement of 1.2 mg/dl or greater (p = 0.016). Overall survival differed significantly among cancer groups (p <0.001) as did stent failure-free survival (p = 0.011). Overall survival differed significantly among 3 risk groups divided according to the score calculated with regard to prognostic factors (p <0.001). CONCLUSIONS: Gynecologic cancer was a significant favorable predictor of stent failure-free survival. Patients treated with an indwelling retrograde ureteral stent for malignant ureteral obstruction were divided into 3 groups, which showed significant differences in overall survival. This risk classification may help urologists predict survival time.

A novel Y chromosome microdeletion with the loss of an endogenous retrovirus related, testis specific transcript in AZFb region.

PURPOSE: We identified the endogenous retroviruses associated with TTYs (testis specific transcripts linked to the Y) in the AZFb region. We evaluated the relationship between endogenous retroviruses, and TTY expression patterns and function in spermatogenesis. MATERIALS AND METHODS: We identified family members of TTYs in the AZFb region using computational screening. After investigating the relationship between the endogenous retrovirus genome and TTY expression patterns we screened genomic polymerase chain reaction products from TTY13 amplified from 790 Japanese men, including 275 with azoospermia, 285 with oligozoospermia and 230 who were fertile. RESULTS: Computational screening revealed that 3 members of the TTY family, TTY9, 10 and 13, were regulated by endogenous retroviruses in the AZFb region. Homologous recombination between long terminal repeat of the TTY13 associated human endogenous retrovirus-K14C resulted in TTY13 deletion events. These deletions were more common in patients with azoospermia and oligozoospermia than in fertile males. Specifically 15.63% of the azoospermia group, 10.88% of the oligozoospermia group and 0% of fertile controls had only the deletion variant, indicating an association between the homologous recombination rate and the severity of spermatogenesis failure that was statistically significant (p <0.05). CONCLUSIONS: Because of the finding of what are to our knowledge novel microdeletions due to endogenous retrovirus in the AZFb region, our study raises the possibility that specific variations in genomic structure may contribute to some forms of human idiopathic male infertility.

Etiological role of human papillomavirus infection for inverted papilloma of the bladder.

The status of human papillomavirus (HPV) infection in urothelial inverted papilloma was examined in the present study. Formalin-fixed and paraffin-embedded tissues from eight cases of inverted papilloma of the bladder were studied. The presence of HPV-DNA was examined by modified GP5/6+PCR using archival tissue sections by microdissection. HPV genotype was determined with a Hybri-Max HPV genotyping kit. Immunohistochemical analysis for p16-INK4a, mcm7, HPV-E4, and L1, and in situ hybridization for the HPV genome were performed. HPV was detected in seven of eight cases (87.5%) of inverted papilloma. Three cases were diagnosed as inverted papilloma with atypia, while the remaining five were typical cases. HPV-18 was detected in two cases, including one inverted papilloma with atypia, and HPV-16 was detected in four cases, including one inverted papilloma with atypia. Multiple HPV type infection was detected in one typical case and one atypical case. High-risk HPV was present in all HPV-positive cases. Cellular proteins, p16-INK4a and mcm7, which are surrogate markers for HPV-E7 expression, were detected in all HPV-positive cases, and their levels were higher in inverted papilloma with atypia than in typical cases. In contrast, HPV-E4 and L1, which are markers for HPV propagation, were observed in some parts of the typical inverted papilloma tissue. High-risk HPV infection may be one of the causes of urothelial inverted papilloma, and inverted papilloma with atypia may have malignant potential.

Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: a randomised controlled study.

PURPOSE: We performed a randomised controlled study regarding the effects of androgen replacement therapy (ART) on lower urinary tract symptoms (LUTS) in hypogonadal men with benign prostate hypertrophy (BPH). METHODS: Fifty-two patients with hypogonadism and BPH were randomly assigned to receive testosterone (ART group) as 250 mg of testosterone enanthate every 4 weeks or to the untreated control group. We compared International Prostate Symptom Score (IPSS), uroflowmetry data, post-voiding residual volume (PVR) and systemic muscle volume at baseline and 12 months after treatment. RESULTS: Forty-six patients (ART group, n=23; control, n=23) were included in the analysis. At the 12-month visit, IPSS showed a significant decrease compared with baseline in the ART group (15.7 +/- 8.7 vs. 12.5 +/- 9.5; p<0.05). No significant changes were observed in the control group. The ART group also showed improvement in maximum flow rate and voided volume (p<0.05), whereas no significant improvements were observed in the controls. PVR showed no significant changes in either group. In addition, the ART group showed significant enhancement of mean muscle volume (p<0.05), whereas no significant changes were seen in the controls. CONCLUSION: ART improved LUTS in hypogonadal men with mild BPH.

Clinicopathological outcomes of clinical T1a renal cell carcinoma by tumor size.

OBJECTIVE: We performed a retrospective review of clinical T1a renal cell carcinoma patients treated in our institution. The clinicopathological findings and patients' prognoses were analyzed according to tumor size, and risk factors for tumor recurrence were elucidated. METHODS: A total of 140 cases of sporadic renal cell carcinoma with a diameter of 4 cm or less on computed tomography findings for preoperative evaluation were treated as clinical T1a. Patients underwent radical nephrectomy or nephron-sparing surgery, and were evaluated postoperatively every 3-6 months to screen for metastatic disease. Patients' medical records were reviewed retrospectively and the status of each patient was assessed. RESULTS: There were four cases of clinically metastatic disease at diagnosis. There were no correlations between tumor size and pathological stage, Fuhrman nuclear grade or histological type. The rate of cases with microvascular invasion on pathological findings increased according to tumor diameter. Disease recurrence occurred in six patients (5.7%) during a mean postoperative follow-up of 41.7 months. There was a significant difference in the recurrence-free rate between pT1a patients with a tumor diameter of 31 mm or more and other patient groups. In terms of microvascular invasion on histological findings, the probability of non-recurrence at 7 years was 0% for patients with and 92.9% for those without microvascular invasion. CONCLUSIONS: Among T1a renal cell carcinoma, tumors over 30 mm in diameter may have aggressive biological potential, possibly due to microvascular invasion. Long-term follow-up is needed for these tumors.