Correlation of urinary loss rate after catheter removal and long-term urinary continence after robot-assisted laparoscopic radical prostatectomy.

OBJECTIVES: To assess the correlation of urine loss rate after catheter removal with long-term continence after robot-assisted radical prostatectomy. METHODS: We enrolled 163 patients on whom robot-assisted radical prostatectomy was carried out and whose urine loss rate we were able to evaluate after catheter removal. Urinary incontinence was evaluated from immediately after removal of the catheter to the date of discharge, and at 1, 3, 6 and 12 months after surgery. Urine loss rate was defined as the urine loss volume divided by the total urine volume. RESULTS: The continence rates of patients with ≤1% urine loss rate on the day of catheter removal were 100% at 6 and 12 months after surgery. A multivariate analysis proved that ≤10% urine loss rate on the day of catheter removal was a significant predictor of continence at 3 months after surgery. Furthermore, the continence rate at 12 months of patients who did not achieve ≤10% urine loss rate on the day of catheter removal was 79.5%. Among them, the continence rate at 12 months of patients who achieved ≥15% urine loss rate improvement from the day of catheter removal to the next day was 95.2%; the factor differed significantly between the continence and incontinence groups at 12 months after surgery. CONCLUSIONS: The urine loss rate on the day of catheter removal is significantly related to the acquisition of urinary continence. Furthermore, our findings suggest that long-term urinary continence can be expected, even in the event of poor urine loss rate on the day of catheter removal, if it improves on the next day.

BHD-associated kidney cancer exhibits unique molecular characteristics and a wide variety of variants in chromatin remodeling genes.

Birt-Hogg-Dubé (BHD) syndrome is a hereditary kidney cancer syndrome, which predisposes patients to develop kidney cancer, cutaneous fibrofolliculomas and pulmonary cysts. The responsible gene FLCN is a tumor suppressor for kidney cancer, which plays an important role in energy homeostasis through the regulation of mitochondrial oxidative metabolism. However, the process by which FLCN-deficiency leads to renal tumorigenesis is unclear. In order to clarify molecular pathogenesis of BHD-associated kidney cancer, we conducted whole-exome sequencing analysis using next-generation sequencing technology as well as metabolite analysis using liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. Whole-exome sequencing analysis of BHD-associated kidney cancer revealed that copy number variations of BHD-associated kidney cancer are considerably different from those already reported in sporadic cases. In somatic variant analysis, very few variants were commonly observed in BHD-associated kidney cancer; however, variants in chromatin remodeling genes were frequently observed in BHD-associated kidney cancer (17/29 tumors, 59%). Metabolite analysis of BHD-associated kidney cancer revealed metabolic reprogramming toward upregulated redox regulation which may neutralize reactive oxygen species potentially produced from mitochondria with increased respiratory capacity under FLCN-deficiency. BHD-associated kidney cancer displays unique molecular characteristics that are completely different from sporadic kidney cancer, providing mechanistic insight into tumorigenesis under FLCN-deficiency as well as a foundation for development of novel therapeutics for kidney cancer.

Outcomes of treatment for localized prostate cancer in a single institution: comparison of radical prostatectomy and radiation therapy by propensity score matching analysis.

OBJECTIVES: To compare the outcomes of radical prostatectomy (RP), intensity-modulated radiation therapy (IMRT), and low-dose-rate brachytherapy (BT) using propensity score matching analysis in patients with clinically localized prostate cancer. METHODS: A group of 2273 patients with clinically localized prostate cancer between January 2004 and December 2015 at the Yokohama City University hospital were identified. The records of 1817 of these patients, who were followed up for a minimum of 2 years, were reviewed; 462 were treated with RP, 319 with IMRT, and 1036 with BT. The patients were categorized according to the National Comprehensive Cancer Network risk classification criteria, and biochemical outcomes and overall survival rates were examined. Biochemical failure for RP was defined as prostate-specific antigen (PSA) levels > 0.2 ng/ml, and for IMRT and BT as nadir PSA level + 2 ng/ml. Propensity scores were calculated using multivariable logistic regression based on covariates, including the patient's age, preoperative PSA, Gleason score, number of positive cores, and clinical T stage. RESULTS: Median follow-up was 77 months for the RP, 54 months for IMRT, and 66 months for BT patients. After the propensity scores were adjusted, a total of 372 (186 each) and 598 (299 each) patients were categorized into RP vs IMRT and RP vs BT groups, respectively. Kaplan-Meier analysis did not show any statistically significant differences in terms of overall survival rate between these groups (RP vs IMRT: p = 0.220; RP vs BT: p = 0.429). IMRT was associated with improved biochemical failure-free survival compared to RP in all risk groups (high-risk: p < 0.001; intermediate-risk: p = 0.009; low-risk: p = 0.001), whereas significant differences were observed only in the intermediate-risk group (p = 0.003) within the RP vs BT group. CONCLUSION: The results of our propensity score analysis of mid-term localized prostate cancer treatment outcomes demonstrated no significant differences in the overall survival rate. Despite the difference in biochemical failure definition between surgery and radiotherapeutic approaches, the results of this study demonstrate improved biochemical control favoring IMRT and BT as compared to RP.

Extraordinarily long-inactive solitary fibrous tumor transformed to produce big insulin-like growth factor-2, leading to hypoglycemia and rapid liposarcoma growth: a case report.

BACKGROUND: A high-molecular-weight form of insulin-like growth factor-2 (IGF-2), known as "big" IGF-2, is occasionally produced by various tumor types, leading to hypoglycemia. Although solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm, it has been estimated that 4-6% of SFT patients develop hypoglycemia due to circulating big IGF-2. The mean time elapsed from tumor detection until the onset of hypoglycemia is reportedly less than one year (8.5 ± 1.9 months). CASE PRESENTATION: A 68-year-old man was hospitalized for exacerbation of recurring hypoglycemic episodes. He had been diagnosed with an SFT 17 years before the onset of hypoglycemia, and the SFT had already been very large at that time. The tumor, which was non-resectable and refractory to chemotherapies, had slowly increased in size since the initial diagnosis. Half a year before the hypoglycemic episodes manifested, another tumor, adjacent to the left kidney, was newly identified. Fluorodeoxyglucose positron emission tomography-computed tomography scanning, revealed the left peri-renal tumor to show much higher fluorodeoxyglucose uptake than the preexisting SFT, suggesting that it was unlikely to be a metastasis from the SFT. Abundant serum big IGF-2 was detected by western immunoblot analysis, indicating it to be the cause of the hypoglycemia. Since the 17 years between SFT detection and the onset of IGF-2-induced hypoglycemia was an extremely long period as compared with those in previous reports, we initially suspected that the new, peri-renal tumor had produced big IGF-2, but transcatheter arterial embolization of its feeding arteries did not suppress hypoglycemia. Notably, by measuring the tumor volume doubling time, the peri-renal tumor growth was shown to be markedly accelerated in parallel with exacerbation of the hypoglycemia. The patient died of heart failure 21 months after the onset of hypoglycemia. Unexpectedly, autopsy revealed that big IGF-2 had been produced only by the preexisting SFT, not the peri-renal tumor, and that the peri-renal tumor was a dedifferentiated liposarcoma. CONCLUSIONS: We should keep in mind that even a long-inactive SFT can undergo transformation to produce big IGF-2, which then acts on both insulin and IGF-1 receptors, possibly leading to both hypoglycemia and the development/growth of another tumor, respectively.

H255Y and K508R missense mutations in tumour suppressor folliculin (FLCN) promote kidney cell proliferation.

Germline H255Y and K508R missense mutations in the folliculin (FLCN) gene have been identified in patients with bilateral multifocal (BMF) kidney tumours and clinical manifestations of Birt-Hogg-Dubé (BHD) syndrome, or with BMF kidney tumours as the only manifestation; however, their impact on FLCN function remains to be determined. In order to determine if FLCN H255Y and K508R missense mutations promote aberrant kidney cell proliferation leading to pathogenicity, we generated mouse models expressing these mutants using BAC recombineering technology and investigated their ability to rescue the multi-cystic phenotype of Flcn-deficient mouse kidneys. Flcn H255Y mutant transgene expression in kidney-targeted Flcn knockout mice did not rescue the multi-cystic kidney phenotype. However, expression of the Flcn K508R mutant transgene partially, but not completely, abrogated the phenotype. Notably, expression of the Flcn K508R mutant transgene in heterozygous Flcn knockout mice resulted in development of multi-cystic kidneys and cardiac hypertrophy in some mice. These results demonstrate that both FLCN H255Y and K508R missense mutations promote aberrant kidney cell proliferation, but to different degrees. Based on the phenotypes of our preclinical models, the FLCN H255Y mutant protein has lost it tumour suppressive function leading to the clinical manifestations of BHD, whereas the FLCN K508R mutant protein may have a dominant negative effect on the function of wild-type FLCN in regulating kidney cell proliferation and, therefore, act as an oncoprotein. These findings may provide mechanistic insight into the role of FLCN in regulating kidney cell proliferation and facilitate the development of novel therapeutics for FLCN-deficient kidney cancer.

Early assessment with 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography to predict short-term outcome in clear cell renal carcinoma treated with nivolumab.

BACKGROUND: We reported previously the usefulness of 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) to predict prognosis of renal cell carcinoma (RCC) treated with molecular targeted agents. Herein we describe a preliminary research of nine patients who underwent FDG-PET/CT before and after initiation of nivolumab. METHODS: Patients with metastatic RCC who were treated by nivolumab from October 2016 to March 2017 were enrolled in this study. All patients underwent FDG-PET/CT at baseline and 1 month as a first response assessment, and contrast-enhanced or non-contrast-enhanced CT scan at 4 month as a second response assessment. Logistic regression analysis was performed to assess the association of potential predictors, including age, gender, baseline diameter, baseline maximum standardized uptake value (SUVmax), lung or not lung metastasis, elevation of SUVmax at 1st assessment, and decrease in diameter at 1st assessment with the response at 2nd assessment (decrease in the diameter ≥ 30% or not). RESULTS: There were 9 patients and 30 lesions. Mean days of first assessment with FDG-PET/CT and second assessment by CT scan from initiation of treatment were 32.3 ± 6.4, 115.5 ± 14.9, respectively. Lesions whose diameter decreased ≥30% at second assessment were defined as responding, and lesions whose diameter did not decrease ≥30% were defined as non-responding. There were 18 responding lesions, and 12 non-responding lesions. We compared change in diameter and SUVmax at first assessment with FDG-PET/CT, respectively. All lesions with decreased diameter and elevated SUVmax at first assessment with FDG-PET/CT showed responding at second assessment by CT scan, while most lesions with increased diameter and declined SUVmax at first assessment showed non-responding at second assessment. The multivariate logistic regression analyses revealed that only the elevation of SUVmax at 1 month was an independent predictor (P = 0.025, OR: 13.087, 95%CI: 1.373-124.716). CONCLUSION: Our findings suggest that the early assessment using FDG-PET/CT can be effective to predict the response of RCC to nivolumab. However, larger prospective studies are needed to confirm these preliminary results. TRIAL REGISTRATION: Registered in University Hospital Medical Information Network in JAPAN [ UMIN0000008141 ], registration date: 11 Jun 2012.

PD-1 and PD-L1 are more highly expressed in high-grade bladder cancer than in low-grade cases: PD-L1 might function as a mediator of stage progression in bladder cancer.

BACKGROUND: Bladder cancers have been characterized as a tumor group in which the immunological response is relatively well preserved. Programmed death ligand 1 (PD-L1, B7-H1, CD274) has been shown to be expressed in several malignancies, including bladder cancer. However, the clinicopathological impact of this biomarker has not yet been established. In the present study, a quantitative real-time polymerase chain reaction (qPCR) was performed using paired normal and cancerous bladder cancer tissue to investigate PD-1/PD-L1 gene expression. METHODS: We examined the mRNA expression of PD-1/PD-L1 by a qPCR using 58 pairs of normal and cancerous human bladder tissue specimens. We also examined the correlation with the expressions of the STAT1 and NFAT genes, which are thought to be upstream and downstream of the PD-L1 pathway, respectively. RESULTS: There were no significant differences between normal and cancerous tissue in the expression of the PD-1 and PD-L1 genes (p = 0.724 and p = 0.102, respectively). However, PD-1 and PD-L1 were both more highly expressed in high-grade bladder cancer than in low-grade bladder cancer (p < 0.050 and p < 0.010). PD-L1 was positively correlated with the expressions of both the STAT1 (r = 0.681, p < 0.001) and the NFATc1 genes (r = 0.444. p < 0.001). CONCLUSIONS: PD-1 and PD-L1 might be a new biomarker that correlates with the pathological grade of bladder cancer. PD-L1 might function as a mediator of stage progression in bladder cancer and STAT1-NFAT pathway might associate this function.

Genomewide approaches for BACH1 target genes in mouse embryonic fibroblasts showed BACH1-Pparg pathway in adipogenesis.

The transcription repressor BTB and CNC homology 1 (BACH1) represses genes involved in heme metabolism and oxidative stress response. BACH1 also suppresses the p53-dependent cellar senescence in primary mouse embryonic fibroblasts (MEFs). To investigate the role of BACH1 in MEF other than its known functions, we carried out a genomewide mapping of binding site for BACH1 and its heterodimer partner MAFK in immortalized MEFs (iMEFs) using chromatin immunoprecipitation and next-generation sequencing technology (ChIP-sequence). The comparative analysis of the ChIP-sequence data and DNA microarray data from Bach1-deficient and wild-type (WT) iMEF showed 35 novel candidate target genes of BACH1. Among these genes, five genes (Pparg, Nfia, Ptplad2, Adcy1 and Ror1) were related with lipid metabolism. Bach1-deficient iMEFs showed increased expression of mRNA and protein of PPARγ, which is the key factor of adipogenesis. These cells also showed a concomitant increase in ligand-dependent activation of PPARγ target genes compared with wild-type iMEFs. Moreover, Bach1-deficient iMEFs efficiently differentiated to adipocyte compared with wild-type cells in the presence of PPARγ ligands. Our results suggest that BACH1 regulates expression of adipocyte-related genes including Pparg and potentiates adipocyte differentiation capacity.

The acceleration of glucose accumulation in renal cell carcinoma assessed by FDG PET/CT demonstrated acquisition of resistance to tyrosine kinase inhibitor therapy.

BACKGROUND: Tyrosine-kinase inhibitor (TKI) targeting angiogenesis improves the prognosis of patients with metastatic renal cell carcinoma (RCC), but its effect is temporary. In order to understand the mechanism by which RCC acquires resistance to TKI, we investigated the change of glucose accumulation in RCC by FDG PET/CT when they demonstrated progression disease (PD) against TKI. METHODS: We monitored the FDG accumulation in RCC of 38 patients treated with TKI by 162 PET/CT sequentially until they were judged to demonstrate PD. Standardized uptake value (SUV), a simplified index of tissue FDG accumulation rate, was measured, and the sequential changes of max SUVmax (the highest SUV in an individual patient) was analyzed. Additionally, the expression of glucose transporter 1 (GLUT-1) and associated proteins in 786-O cells cultured under hypoxia were analyzed. RESULTS: The 10 patients with RCC which FDG accumulation was accelerated after beginning of TKI treatment demonstrated PD soon. The other 28 patients with RCC which FDG accumulation was suppressed by TKI showed longer progression-free survival (3.6 months vs 6.5 months, P = 0.0026), but this suppression in most cases (96%) was temporary and FDG accumulation was accelerated when tumor demonstrated PD. Interestingly, the FDG accumulation at PD was higher than that before TKI treatment in the half cases. The acceleration of FDG accumulation was suppressed by following treatment by mammalian target of rapamycin (mTOR) inhibitor. Additionally, in vitro assay demonstrated that the expression of GLUT-1 was increased in the RCC cells surviving under hypoxia condition via mTOR pathway. CONCLUSIONS: The acceleration of glucose accumulation dependent on mTOR in RCC assessed by FDG PET/CT demonstrated acquisition of resistance to TKI. FDG PET/CT had potential as an assessment method monitoring not only the initial response but also following status of RCC during TKI treatment. TRIAL REGISTRATION: UMIN0000008141 , 11 Jun 2012. This trial was retrospectively registered.

[Pulmonary Mycobacterium Avium-Complex (MAC) Disease Differentially Diagnosed from Metastasis of Testicular Cancer : A Case Report].

A 45 year-old-man was admitted to our hospital because of discomfort in his left scrotum. He had a left testicular tumor. We performed high orchiectomy and pathological findings revealed testicular cancer. He was treated with bleomycin, etoposide and cisplatin. Computed tomography showed a new mass in the left lung after 3 cycles of the chemotherapy. Because of its rapid growth, the tumor was thought to be a metastasis lesion of testicular cancer or pulmonary infection. Transbronchial lung biopsy showed an invasion of multinucleated giant cells and granuloma. The culture and polymerase chain reaction of the bronchial sputum were positive for myobacterium avium-complex (MAC). From these findings, the left lung tumor was diagnosed as pulmonary MAC disease. He received partial resection of the left lung and the lesion was diagnosed as granuloma. There was no recurrence of testicular cancer or pulmonary disease after the surgery.

Prognostic value of a computer-aided diagnosis system involving bone scans among men treated with docetaxel for metastatic castration-resistant prostate cancer.

BACKGROUND: The bone scan index (BSI), which is obtained using a computer-aided bone scan evaluation system, is anticipated to become an objective and quantitative clinical tool for evaluating bone metastases in prostate cancer. Here, we assessed the usefulness of the BSI as a prognostic factor in patients with metastatic castration-resistant prostate cancer (mCRPC) treated using docetaxel. METHODS: We analyzed 41 patients who received docetaxel for mCRPC. The Bonenavi system was used as the calculation program for the BSI. The utility of the BSI as a predictor of overall survival (OS) after docetaxel was evaluated. The Cox proportional hazards model was used to investigate the association between clinical variables obtained at docetaxel treatment, namely PSA, patient age, liver metastasis, local therapy, hemoglobin (Hb), lactase dehydrogenase (LDH), albumin (Alb), PSA doubling time, and BSI and OS. RESULTS: The median OS after docetaxel therapy was 17.7 months. Death occurred in 22 (53.7%) patients; all deaths were caused by prostate cancer. In multivariate analysis, three factors were identified as significant independent prognostic biomarkers for OS after docetaxel; these were liver metastases (yes vs no; HR, 3.681; p = 0.026), Alb (<3.9 vs ≥ 3.9; HR, 3.776; p = 0.020), and BSI (>1% vs ≤ 1%; HR, 3.356; p = 0.037). We evaluated the discriminatory ability of our models including or excluding the BSI by quantifying the c-index. The BSI improved the c-index from 0.758 to 0.769 for OS after docetaxel. CRPC patients with a BSI >1 had a significantly shorter OS than patients with a BSI ≤ 1 (p = 0.029). CONCLUSIONS: The BSI, liver metastases and Alb were independent prognostic factors for OS after docetaxel. The BSI might be a useful tool for risk stratification of mCRPC patients undergoing docetaxel treatment.

Prognostic value of the bone scan index using a computer-aided diagnosis system for bone scans in hormone-naive prostate cancer patients with bone metastases.

BACKGROUND: The bone scan index (BSI) using a computer-aided diagnosis system for bone scans is expected to be an objective and quantitative clinical tool for evaluating bone metastatic prostate cancer. This study aimed to evaluate the pretreatment BSI as a prognostic factor in hormone-naive prostate cancer patients with bone metastases. METHODS: The study included 60 patients with hormone-naive, bone metastatic prostate cancer that was initially treated with combined androgen blockade therapy. The BONENAVI system was used for calculating the BSI. We evaluated the correlation between overall survival (OS) and pretreatment clinicopathological characteristics, including patients' age, initial prostate-specific antigen (PSA) value, Gleason scores, clinical TNM stage, and the BSI. Cox proportional hazards regression models were used for statistical analysis. RESULTS: The median follow-up duration was 21.4 months. Clinical or PSA progression occurred in 37 (61.7%) patients and 18 (30.0%) received docetaxel. Death occurred in 16 (26.7%) patients. Of these deaths, 15 (25.0%) were due to prostate cancer. The median OS was not reached. In multivariate analysis, age and the BSI were independent prognostic factors for OS. We evaluated the discriminatory ability of our models, including or excluding BSI by quantifying the C-index. The BSI improved the C-index from 0.751 to 0.801 for OS. Median OS was not reached in patients with a BSI ≤ 1.9 and median OS was 34.8 months in patients with a BSI >1.9 (p = 0.039). CONCLUSIONS: The pretreatment BSI and patients' age are independent prognostic factors for patients with hormone-naive, bone metastatic prostate cancer.

FDG PET/CT as a prognostic biomarker in the era of molecular-targeting therapies: max SUVmax predicts survival of patients with advanced renal cell carcinoma.

BACKGROUND: Various molecular-targeting therapies have become available for the treatment of advanced renal cell carcinoma (RCC). Accurate prognostication is desirable for choosing the appropriate treatment for individual patients. (18)F-2-fluoro-2-deoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) is a non-invasive tool for evaluating glucose accumulation, which can be an index of biological characteristics of cancer. We prospectively evaluated FDG PET/CT as a prognostic indicator in patients with advanced RCC. METHODS: A total of 101 patients slated for different systematic therapies for advanced RCC were enrolled between 2008 and 2014. A total of 61 patients had recurrent RCC (58 metastatic and 3 regional) and 40 patients had stage IV RCC (36 metastatic and 4 locoregional). Sixteen patients had not undergone nephrectomy. Pre-treatment FDG PET/CT was performed, and the max SUVmax (the highest SUV measurement in each patient) was recorded. The max SUVmax was compared with different clinical risk factors as prognostic indicators. The median observation period was 18 months (range 1-70 months). RESULTS: The max SUVmax of the 101 subjects ranged from undetectable to 23.0 (median 6.9). Patients with high max SUVmax had a poor prognosis. Multivariate analysis with standard risk factors revealed that max SUVmax was an independent predictor of survival (p < 0.001; hazard ratio 1.265; 95% confidence interval 1.159-1.380). A cutoff of 8.8 for max SUVmax advocated in our previous report was highly significant (p < 0.0001). When we subclassified the max SUVmax values, the median overall survival of subjects with max SUVmax < 7.0 was 41.9 months. That of subjects with max SUVmax between 7.0 and 12.0 was 20.6 months. That of subjects with max SUVmax ≥ 12.0 was 4.2 months. The differences were statistically significant. CONCLUSIONS: Pretreatment max SUVmax assessed by FDG PET/CT is a useful prognostic marker for patients with advanced RCC, providing helpful information for clinical decision making.

Long-term pulmonary complications of chemical weapons exposure in former poison gas factory workers.

CONTEXT: Sulfur mustard (SM) and lewisite are vesicant chemical warfare agents that can cause skin blistering and chronic lung complications. During 1929-1945, a Japanese factory produced poisonous gases, which included SM, lewisite and other chemical weapons. The aim of this study was to investigate the chest computed tomography (CT) findings among long-term survivors who worked at this factory. METHODS: During 2009-2012, we evaluated chest CT findings from 346 long-term survivors who worked at the poison gas factory. Skin lesions were used as an indicator of significant exposure to vesicant agents. RESULTS: Among the 346 individuals, 53 (15%) individuals experienced skin lesions while working at the factory, and chest CT revealed abnormal findings in 179 individuals (52%). Emphysema was the most common CT finding and was observed in 75 individuals (22%), while honeycombing was observed in 8 individuals (2%). Emphysema and honeycombing were more prevalent among individuals with skin lesions, compared to individuals without skin lesions. Multivariate analyses revealed significant associations between the presence of emphysema and skin lesions (p = 0.008). Among individuals who never smoked, individuals with skin lesions (n = 26) exhibited a significantly higher rate of emphysema, compared to individuals without skin lesions (n = 200) (35% versus 7%, respectively; p < 0.001). CONCLUSION: Among the long-term survivors who worked at the poison gas factory, a history of skin lesions was associated with the presence of emphysema, even among never smokers, which suggests that emphysema might be a long-term complication of exposure to chemical warfare agents.

[The Diagnostic Value of Pre-Biopsy Magnetic Resonance Imaging (MRI) for Detecting Prostate Cancer].

We examined the value of pre-biopsy magnetic resonance imaging (MRI) for detecting prostate cancer. We analyzed 267 men with prostate-specific antigen (PSA) levels of 3-10 ng/ml who underwent systematic prostate needle biopsy. From April 2009 to March 2011, a total of 98 male patients underwent 16-core prostatic biopsies without pre-biopsy magnetic resonance imaging (MRI) (nonenforcement group). From April 2011 to March 2013, 169 men underwent pre-biopsy MRI [T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI)] (enforcement group). When MRI findings indicated cancer in the latter group, in addition to the systematic 16-core biopsy one or two targeted biopsies were performed. Patients without suspicious MRI findings underwent only systematic 16-core biopsy. Cancer detection rates in the nonenforcement and enforcement groups were 42.9% (48/92) and 46. 2% (78/169), respectively. The difference did not reach significance (p＝0.612). Although the cancer detection rates were 39.4% (41/104) in the MRI-negative group and 56. 9% (37/65) in the MRI-positive group (p＝0.039), the sensitivity and specificity for cancer detection by MRI were relatively low: 47.4% and 69.2%, respectively. By receiver-operating curve analysis, the area under the curve for cancer detection by MRI was only 0.583. There were two study limitations. First, the patient sample size was small. Second, it is unclear whether an adequate sample of the suspicious lesion was obtained by biopsy. We thus demonstrated that it might be improper to base a diagnosis solely on pre-biopsy MRI (T2WI and DWI) findings in men with serum PSA levels of 3-10 ng/ml.

PHEOCHROMOCYTOMA DURING PREGNANCY-2 CASE REPORTS.

(Introduction) A pheochromocytoma diagnosed during pregnancy is rare, and also its fetal and maternal mortality is high if undiagnosed. We report two cases with successful pregnancy outcome with pheochromocytoma. (Case 1) A 31-years-old previously healthy woman presented at 19 week period of gestation with high blood pressure. High urine catecholamine level and a left adrenal mass recognized by magnetic resonance imaging (MRI) confirmed adrenal pheochromocytoma. The patient had good blood pressure control after we started doxazosin 4 mg daily, and Caesarean section was performed at 35 week period of gestation. Two months after delivery, laparoscopic adrenalectomy was performed and she was discharged in the absence of hypertension. (Case 2) A 31-years-old previously healthy woman presented at 29 week period of gestation with exacerbation of headache and palpitation. High urine catecholamine level and a mass recognized close to the inferior vena cava by MRI confirmed extraadrenal pheochromocytoma. The patient had good blood pressure after we started doxazosin 4 mg daily and labetalol hydrochloride 200 mg daily. Caesarean section was performed at 35 week period of gestation. One month after delivery, laparotomic resection of the tumor was performed. Seven years later, hypertension reoccurred and there was an extraadrenal pheochromocytoma recurrence. We had a laparotomic resection for the recurrent tumor, and now she is in the absence of hypertension. (Conclusion) Pheochromocytoma should be considered as a differential diagnosis in a case of high blood pressure occurred during pregnancy. Early detection and appropriate treatment is crucial to reduce fetal and maternal mortality.

Tumor-suppressive function of protein-tyrosine phosphatase non-receptor type 23 in testicular germ cell tumors is lost upon overexpression of miR142-3p microRNA.

Protein-tyrosine phosphatase non-receptor type 23 (PTPN23) is a candidate tumor suppressor involved in the tumorigenesis of various organs. However, its physiological role(s) and detailed expression profile(s) have not yet been elucidated. We investigated the function and regulation of PTPN23 in the formation of testicular germ cell tumors (TGCTs). Expression of PTPN23 in human TGCT cell lines was significantly lower than that in spermatogonial stem cells in mice. Overexpression of PTPN23 in NEC8, a human TGCT cell line, suppressed soft agar colony formation in vitro and tumor formation in nude mice in vivo. These data indicate that PTPN23 functions as a tumor suppressor in TGCTs. Multiple computational algorithms predicted that the 3' UTR of human PTPN23 is a target for miR-142-3p. A luciferase reporter assay confirmed that miR-142-3p bound directly to the 3' UTR of PTPN23. Introduction of pre-miR-142 in the PTPN23 transfectant of NEC8 led to suppressed expression of PTPN23 and increased soft agar colony formation. Quantitative RT-PCR data revealed a significantly higher expression of miR-142-3p in human seminomas compared with normal testes. No difference in mRNA expression between seminoma and non-seminoma samples was detected by in situ hybridization. Both quantitative RT-PCR and immunohistochemical analyses revealed that PTPN23 expression was significantly lower in TGCTs than in normal testicular tissues. Finally, a lack of PTPN23 protein expression in human TGCTs correlated with a relatively higher miR-142-3p expression. These data suggest that PTPN23 is a tumor suppressor and that repression of PTPN23 expression by miR-142-3p plays an important role in the pathogenesis of TGCTs.

[Pathological diagnosis of renal tumors: up to date].

Renal cell carcinoma (RCC) is composed of heterogenous histological types, with different clinical features and molecular biological characteristics. The "General Rule for Clinical and Pathological Studies on RCC" was revised in 2011, according to the World Health Organization system (WHO) (2004). Although most RCC is clear cell RCC (approximately 70-80% of RCC), papillary and chromophobe RCCs are occasionally encountered (approximately 10 and 5%, respectively). Collecting duct carcinoma is a rare and highly aggressive adenocarcinoma derived from the collecting duct. Additionally, several histological types have been introduced, and "granular RCC" has been omitted as a diagnostic term. For precise diagnosis, careful gross and histological evaluations are required along with immunohistochemical and molecular biological analyses. Additionally, novel histological types have recently been emerging, i.e., 6p21 translocation-associated RCC, dialysis-associated RCC, and tubulocystic carcinoma. Furthermore, mimics of RCC are always considered as differential diagnostic candidates, i.e., metanephric adenoma, epithelioid angiomyolipoma, juxtaglomerular cell tumor, and carcinoid tumor.

[Case of renal cell carcinoma with intertrabecular vertebral metastases detected f-18 fluorodeoxyglucose positron emission tomography and MRI].

We report a case of renal cell carcinoma with intertrabecular vertebral metastases detected by F-18 fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) and magnetic resonance imaging (MRI). The patient was a 40-year-old female, referred to our hospital for fever of ＞ 38°C, and loss of body weight. Examination showed anemia and elevated C-reactive protein (CRP). Abdominal enchanced CT showed a mass 3 cm in diameter, located on left kidney. She was diagnosed with left renal cell carcinoma (cT1aN0M0). Laparoscopic radical nephrectomy with a transabdominal approach was performed. Histological findings showed clear cell renal cell carcinoma G2＞G3. Although after operation, she presented with fever of ＞38°C, anemia, and elevated CRP and alkaline phosphatase. Systemic bone scan could not detect any bone metastases, but FDG-PET/CT and lumber MRI revealed cancer invasion to the bone of the whole body. Histological findings at bone biopsy showed clear cell carcinoma infiltrating the marrow space. We diagnosed the case as bone metastases of intertrabecular vertebral type. She was treated with temsirolimus,but died about five months after her first visit. Intertrabecular vertebral metastases that infiltrate the marrow space without trabecular bone alteration are not visible on radiographs or bone scans. FDG-PET/CT and MRI are more useful for diagnosis of intertrabecular vertebral metastases such as in this case.