INITIAL EXPERIENCE OF THE ENZALUTAMIDE TREATMENT FOR CASTRATION-RESISTANT PROSTATE CANCER.

(Objective) Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with castration-resistant prostate cancer (CRPC). We retrospectively evaluated clinical efficacy and safety of enzalutamide in CRPC. (Patients and methods) We reviewed clinical records of 73 patients who had received enzalutamide for the CRPC at Showa University and affiliated 7 hospitals. Enzalutamide was given at a dose of 160 mg/day, but some patients were treated at lower dose because of there age or poor performance status. Prostrate-specific antigen (PSA) response, prior docetaxel use and the previously administered agents were evaluated retrospectively. (Results) The median patients age was 77 years, the median Gleason score was 9 and the median PSA level at baseline was 26.9 ng/ml. The patients who had prior docetaxel use were 29 (39.7%) and the median of total docetaxel dose was 460 mg/body. The median number of total prior treatments (anti-androgens, Estramustine and steroid) was 3. Twenty seven (61.4%) patients with docetaxel-naïve achieved over 50% reduction of PSA level from baseline, but only 7 (24.1%) in patients previously treated with docetaxel. The most common adverse events included fatigue (24.7%), anorexia (24.7%) and the nausea (16.4%). We found a small proportion of responders to enzalutamide experienced a PSA flare. (Conclusion) Our results of the use of Enzaltamide for CRPC were similar with previous reports. PSA flare was found in some patients with CRPC who responded to enzaltamide. It should be noted that this possible PSA flare phenomenon.

[A Case of Urachal Carcinoma Treated by TS-1/CDDP as Adjuvant Chemotherapy].

A 49-year-old female presented complaining of gross hematuria. Cystoscopy and magnetic resonance imaging revealed a papillary tumor on the bladder dome. At biopsy pathology the tumor was diagnosed as adenocarcinoma. We diagnosed the tumor as urachal adenocarcinoma and performed partial cystectomy of bladder dome with en-bloc resection of the urachal ligament up to the umbilicus. In surgical pathology, the tumor had invaded to the fat tissue around the urachal ligament with metastasis to the lymph node. Therefore the tumor was diagnosed as a stage IVA (Sheldon's category) urachal adenocarcinoma. After surgery, 6 cycles of chemotherapy with TS-1 and cisplatin (CDDP) were performed. There has been no relapse 5 years after surgery. This is the first report of successful adjuvant chemotherapy with TS-1/CDDP for advanced urachal adenocarcinoma.

[A case of mucinous tubular and spindle cell carcinoma of the kidney].

Mucinous tubular and spindle cell carcinoma (MTSCC) is a distinct entity in the World Health Organization classification of kidney tumors since 2004. Herein, we report a case of a patient with MTSCC of the kidney. A 48-year-man visited our hospital with a chief complaint of occult blood in his urine, confirmed by urine occult blood reaction. Computed tomography revealed a solid tumor in the right kidney. The tumor was 40×38 mm in length and was slightly enhanced (cT1aN0M0). Therefore, we performed radical nephrectomy. On analysis of the resected specimen, we found that the number of comparatively small malignant cells had increased markedly, forming branched tubular cuboidal cells. Further more, positive results were obtained on staining the stroma with both PAS and alcian blue stains characteristic of papillary renal cell carcinoma ; however, extracellular mucinous material was found to be depleted. Therefore, we needed to differentiate between papillary renal cell carcinoma and MTSCC. Finally, on the basis of the immunohistochemical staining results-vimentin (＋), CK34ßE12 (-), and CD10 (-)-MTSCC was confirmed.

[A case of vesical endometriosis that worsened during the early pregnancy period].

We report a case of vesical endometriosis that worsened during the early pregnancy period. A 37-year old woman had been under treatment for endometriosis (including vesical endometriosis) by a gynecologist during the past 10 years. She was treated for sterility 1 year ago, and became pregnant through in vitro fertilization. In her 8th gestational week, she complained of gross hematuria at our hospital. Cystoscopic findings revealed some tumors that appeared worse than the last findings two years ago. In order to deny malignancy, transurethral resection of the bladder tumor was performed in her 12th gestational week. The pathologic diagnosis was endometriosis. She was able to stay pregnant, and delivered a girl. After delivery, cystoscopic findings revealed reduction of tumors. In most cases pregnancy cures endometriosis ; however, in this case symptoms became worse during the early stage of pregnancy. The reason for this contrary event is discussed.

[Efficacy and safety of imidafenacin in female patients with urge and mixed urinary incontinence].

The effect of imidafenacin for the treatment of overactive bladder (OAB), in female patients with urge and mixed urinary incontinence was examined. Prior to administration and at 1, 2, 3, 4, 6, 8, 10 and 12 weeks after administration, symptoms and quality of life were assessed using the overactive bladder symptom score (OABSS) and the international consultation on incontinence questionnaire-short form (ICIQ-SF), respectively. After administration, OABSS and ICIQ-SF scores were improved significantly when compared to baseline values. The incidence of adverse events was 7. 9% and none were serious. Imidafenacin was effective in female patients with urge and mixed urinary incontinence. In addition, imidafenacin rapidly improved incontinence one week after administration.

[Limbic encephalitis in the course of testicular lymphoma].

The malignant tumor patient tends to develop various neuropathy by direct invasion, metastasis, secondary infectious disease of tumor, metabolic disorders, vascular damage and adverse drug reactions with a treatment, and, however, it rarely appear by mechanism of autoimmunization. Tumor tissue with paraneoplastic neurological syndrome (PNS) produces an antigen attacking nerve tissue by it's cross reaction, and many studies indicates that there are a few kinds of antineuritic antibodies occurred by the charactor of malignant diseases or the patterns of progression. There is no relationship between the symptoms and the progression of disease. We report a case of malignant testicular tumor presented the paraneoplastic limbic encephalitis which is one of paraneoplastic neurological syndrome.

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

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

Giant retroperitoneal liposarcoma.

Liposarcomas are one of the most common soft tissue sarcomas of adulthood. Liposarcomas are remarkable because of their frequently large size. We report a case with an extremely large dedifferentiated liposarcoma that weighed 18 kg. Although it was capsulated and could be excised en bloc, the patient suffered a relapse 9 months later and died 1 year after the operation.

Papillary cystadenocarcinoma of the prostate.

A giant cystic formation was found behind the prostate of a 69-year-old man who presented with urinary retention. Ultrasonography, computed tomography scans and magnetic resonance imaging revealed a large cystic intrapelvic mass and biopsy of the cyst wall diagnosed papillary cyst adenocarcinoma. Immunohistochemically, the tumor originated from the prostate.

Inguinal hernia of seminal vesicle cyst.

Seminal vesicle cysts are uncommon abnormalities in the pelvis. The case of a seminal vesicle cyst that extended through the inguinal canal is reported. A 35-year-old man presented with left inguinal swelling. He was diagnosed with a left inguinal hernia. However, the interpretative diagnosis was a spermatic cord tumor. The operation was changed to tumor resection. The tumor existed along with the vas deferens from part of the parietal peritoneum outside the inguinal tunnel to the deep pelvic space. The cylinder-shaped tumor was 3 cm in diameter and 20 cm long. Pathological examination revealed a seminal vesicle cyst that extended through the inguinal canal. To the best of our knowledge, this is the first case report of a seminal vesicle cyst inguinal hernia.

Prognostic significance of thrombocytosis in renal cell carcinoma patients.

BACKGROUND: Thrombocytosis has been reported in many types of malignancies and has been studied as a prognostic factor. In the present study, we examined the incidence of thrombocytosis in patients with renal cell carcinoma (RCC) in order to evaluate the prognostic value of thrombocytosis. METHODS: One hundred and ninety-six patients treated by radical nephrectomy for RCC were enrolled in this study. We divided the patients into a normal platelet count group and a thrombocytosis group according to the presurgical platelet count. The two groups were compared pathologically and clinically, including prognosis. RESULTS: Thrombocytosis was present in 16 patients (8.2%). Platelet counts had normalized after nephrectomy in all patients with thrombocytosis. There was no correlation between histological type or grade and thrombocytosis. However, there were correlations between thrombocytosis and tumor size and tumor stage. Patients with thrombocytosis had a worse prognosis than patients without thrombocytosis (P = 0.0028). When adjusted for stage or tumor size, the correlation was limited to low stage (stage 1 + 2: P = 0.0041, stage 3 + 4: P = 0.2983) or small tumors (tumor size: 7 cm, P = 0.8158). CONCLUSION: Thrombocytosis is an inexpensive and easy tool with which to evaluate the prognosis of RCC patients in daily medical practice.

Association of common missense changes in ELAC2 ( HPC2) with prostate cancer in a Japanese case-control series.

The recently identified prostate cancer susceptibility gene ELAC2 ( HPC2) harbors two common missense variants, a serine to leucine substitution at residue 217 (Leu217) and an alanine to threonine substitution at residue 541 (Thr541). We genotyped the two variants in a Japanese cohort consisting of 350 prostate cancer patients 242 male population controls, and 114 male low-risk controls. Both missense alleles, Leu217 and Thr541, were carried at higher frequency in Japanese patients than in the controls (Leu217, P= 0.0012; Thr541, P = 0.0145), and the odds ratios associated with carrying these sequence variants were higher in Japanese than in Caucasians. Although the Leu217 and Thr541 variants of ELAC2 are less common in Japanese than in Caucasians, both variants confer significantly increased risk of prostate cancer in Japanese. Carriage of these variants was not associated with age at diagnosis, tumor stage, or tumor grade in these Japanese prostate cancer patients. The allele-specific pattern of risk observed in Japanese and familial Caucasian patients was qualitatively similar; however, the magnitude of that risk was considerably greater in Japanese than in Caucasians.