Molecular-targeted Therapy and Surgery May Prolong Survival of Renal Cell Carcinoma Patients with Bone Metastasis: A Multi-institutional Retrospective Study in Japan.

AIM: To determine prognostic factors for overall survival (OS) in renal cell carcinoma (RCC) patients with bone metastasis in the targeted-therapy era. PATIENTS AND METHODS: We conducted a retrospective multi-institutional review of the medical records of 149 RCC patients with bone metastasis. Survival was estimated using the Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate Cox proportional hazard regression analyses were performed to identify independent factors associated with OS. RESULTS: The median OS was 13.4 months. In multivariate analysis, molecular-targeted therapy, nephrectomy and surgery for bone metastasis were independent prognostic factors. Bone-modifying agents (BMAs) were not associated with OS. The median OS of patients receiving molecular-targeted therapy after diagnosis of bone metastasis was significantly better than that of those who did not receive targeted therapy. CONCLUSION: Molecular-targeted therapy, nephrectomy and surgery for bone metastasis should be considered for RCC patients with metastasis in the bones.

Efficacy and safety of docetaxel and prednisolone for castration-resistant prostate cancer: a multi-institutional retrospective study in Japan.

OBJECTIVE: Although some new drugs for castration-resistant prostate cancer are available, docetaxel still plays an important role in castration-resistant prostate cancer treatment. In this study, we evaluated the efficacy and safety of docetaxel and prednisolone in patients with castration-resistant prostate cancer. METHODS: We conducted a retrospective chart review of castration-resistant prostate cancer patients who received docetaxel and prednisolone at 14 hospitals in the Sapporo Medical University Urologic Oncology Consortium from August 2004 to December 2011. RESULTS: A total of 140 patients with castration-resistant prostate cancer received docetaxel and prednisolone (median age, 73.8 years; median prostate specific antigen, 54.7 ng/ml). A median of six cycles (range: 1-43) of docetaxel and prednisolone was administered per patient. Median follow-up was 13.7 months. Median overall survival was 22.0 months. The log-rank test revealed that prostate specific antigen before docetaxel and prednisolone (<50 ng/ml) and the prostate specific antigen reduction rate (≥30%) were associated with overall survival (P < 0.001 and P < 0.001, respectively). Eighty patients (57.1%) achieved a prostate specific antigen reduction rate of over 30%. All except two (97.5%) reached 30% prostate specific antigen reduction within five cycles of docetaxel and prednisolone. There were two (1.4%) treatment-related deaths due to adverse events, which were interstitial lung disease, and febrile neutropenia and bacterial pneumonia. Interstitial lung disease occurred in 14 (10.0%) patients within a median of 2.5 cycles of docetaxel and prednisolone. Grade 5 interstitial lung disease was seen after three cycles of docetaxel and prednisolone. CONCLUSIONS: If a prostate specific antigen reduction rate of over 30% is not obtained within five cycles of docetaxel and prednisolone, other treatment options should be considered. Although most patients safely received docetaxel and prednisolone, we must always keep interstitial lung disease in mind as a possible lethal adverse event.

Clinical significance of definite muscle layer in TUR specimen for evaluating progression rate in T1G3 bladder cancer: multicenter retrospective study by the Sapporo Medical University Urologic Oncology Consortium (SUOC).

PURPOSE: To evaluate the clinical impact on progression and recurrence according to presence and absence of a muscle layer, we conducted a retrospective, multicenter study. METHODS: We retrospectively reviewed 247 patients who received transurethral resection (TUR) of bladder tumors and were pathologically diagnosed as having T1G3 bladder cancer from 1990 to 2009. We ruled out 8 patients who received immediate cystectomy and analyzed the remaining 239 T1G3 patients. Patients who had invasion to the prostatic urethra and patients who underwent a second TUR were not included. RESULTS: TUR specimens from 194 patients were confirmed to have a definite muscle layer and those from 45 did not. The median follow-up period was 53 months, ranging from 3 to 181 months. The progression-free survival rates at 5 years after TUR were 91.1 % for patients who had a muscle layer in their specimen and 77.3 % for those who did not (p = 0.005, log-rank test). Multivariate analysis indicated that the absence of a muscle layer was a risk factor for progression (p = 0.006, Cox proportional hazards analysis). CONCLUSIONS: Patients without a muscle layer in the specimen had high risk for progression. The initial TUR must have a muscle layer in the specimen. Variations of progression rates in previous studies might be due to different proportions of patients who had a muscle layer in TUR specimens.

Paclitaxel, ifosfamide, and nedaplatin as second-line treatment for patients with metastatic urothelial carcinoma: a phase II study of the SUOC group.

There is no standard second-line chemotherapy treatment for recurrent or metastatic urothelial cancer (MUC). The purpose of this phase II study was to evaluate the efficacy and toxicity of the three-drug combination of paclitaxel, ifosfamide, and nedaplatin (TIN). Patients with MUC were eligible after treatment failure with methotrexate, vinblastine, doxorubicin, and cisplatin, or gemcitabine and cisplatin. Doses for TIN therapy were paclitaxel 175 mg/m2 on day 1, ifosfamide 1500 mg/m2 on days 1-3, and nedaplatin 70 mg/m2 on day 1, every 4 weeks. Tumor response, the primary efficacy parameter, was assessed according to unidimensional measurements (Response Evaluation Criteria in Solid Tumors criteria, version 1.0). Secondary efficacy parameters were overall survival (OS) and progression-free survival (PFS). Toxicity was assessed according to the National Cancer Institute Common Toxicity Criteria, version 3.0. A total of 45 patients (13 females and 32 males) with MUC were evaluable for response and toxicity. The overall response rate was 40.0%. Median PFS time was 4.0 months (95% confidence interval [CI], 4.6-11.6). Median OS time was 8.9 months (95% CI, 10.5-18.9). Grade 3 or 4 hematologic adverse events were neutropenia (95.6%), anemia (15.6%), and thrombocytopenia (17.8%). The most common grade 3 or 4 non-hematologic adverse events were anorexia (4.4%) and elevated aspartate transaminase/alanine transaminase (2.2%). No toxic death was observed. The main limitation of this study is that only 10 patients (22.2%) who were previously treated with gemcitabine and cisplatin were included. In conclusion, TIN as second-line treatment for MUC is an active regimen with a manageable toxicity profile.

[Surgical site infection by bacillus Calmette-Guerin (BCG) after radical cystectomy, occurring after intravesical bcg therapy: a case report].

A 51-year-old man received 2 courses of intravesical bacillus Calmette-Guerin (BCG) therapy for carcinoma in situ of the bladder. Two years after the therapy, he underwent left radical nephroureterectomy, cystectomy, urethrectomy and construction of an ileal conduit because of left renal pelvic cancer and severe atrophic bladder. The histopathological diagnosis was carcinoma in situ of the left pelvis and ureter, and epithelioid cell granuloma of left kidney, prostate and bladder. After the operation, he developed extensive surgical site infection (SSI) by BCG, the diagnosis of which was delayed. He recovered from the SSI soon after anti-tuberculosis chemotherapy was begun. We discuss the requirements for more prompt diagnosis of SSI by BCG by analysis of this case.

Hypermethylation of an E-cadherin (CDH1) promoter region in high grade transitional cell carcinoma of the bladder comprising carcinoma in situ.

PURPOSE: We elucidated the role of methylation in the promoter region of the 1 gene in bladder carcinogenesis, particularly in those comprising carcinoma in situ. MATERIALS AND METHODS: A total of 49 cases of transitional cell carcinoma of the bladder obtained from transurethral resection were examined. Methylation status of the 1 promoter region was analyzed by methylation specific polymerase chain reaction from chemically modified DNA after Na-bisulfite treatment. Loss of heterozygosity on 16q was examined by blunt end single strand DNA conformation polymorphism using 4 tetranucleotide repeat microsatellite markers assigned on 16q13 to 22.1. E-cadherin expression was evaluated by immunostaining on formalin fixed, paraffin embedded tissue sections using anti E-cadherin murine monoclonal antibody, HECD1 and standard avidin-biotin immunoperoxidase complex technique. RESULTS: Analysis of the 49 bladder transitional cell carcinoma samples showed 1 promoter methylation in 23 (47%). Methylation of the 1 gene did not correlate with tumor stage (p = 0.2097) but with high grade transitional cell carcinoma (p = 0.0416). 1 promoter methylation was observed at a significantly higher frequency in the carcinoma in situ positive group than in the carcinoma in situ negative group (16 of 18 cases or 89% versus 7 of 31 or 23%, p <0.0001) and it strongly correlated with abnormal E-cadherin expression (p <0.0001). We found 16q loss of heterozygosity in 16 of 47 cases (34%), which correlated with higher histological grade (p = 0.0069) but not with the presence of the carcinoma in situ component (p = 0.1235). CONCLUSIONS: This study showed that 1 gene promoter methylation is strongly associated with bladder transitional cell carcinoma comprising carcinoma in situ.

Massive hematuria after cystoscopy in a patient with an internal iliac artery aneurysm.

An unusual case is reported here of a patient with internal iliac artery aneurysm who developed massive hematuria after cystoscopic examination. A 75-year-old man presented with asymptomatic gross hematuria. Cystoscopic examination revealed that the bladder neck was congested and that the right-side wall was being pressed on by an extrinsic mass. Computed tomography showed a right internal iliac artery aneurysm and tortuous perivesical vessels. Three days after the cystoscopic examination the patient suffered massive hematuria. Hemorrhage due to an arteriovesical or arterio-ureteral fistula secondary to rupture of the internal iliac artery aneurysm was suspected, and an emergency operation was performed. At operation the aneurysm had not ruptured but overswelling perivesical vessels were found to have developed, and these fed a high blood flow to the bladder neck. In the present case cystoscopic examination injured the mucosa and led to massive hemorrhage from the bladder neck.

Lymphangioma of the kidney.

Lymphangiomas are rare benign tumors that are congenital malformations of the lymphatic system. Most cases present in children as a soft, cystic mass in the neck and the axilla. Primary renal lymphangioma is exceedingly rare, with only 35 cases reported so far. We report a case of primary lymphangioma arising from the kidney. A 59-year-old man was referred for evaluation of a right renal mass found in an abdominal ultrasonography during a health checkup. Abdominal ultrasonography and computed tomography (CT) revealed a 3.2 x 2.9 cm multiloculated cystic mass in the upper pole of the right kidney. We could not deny malignant disease such as cystic renal cell carcinoma with any diagnostic modalities. The patient was brought to surgery. During the surgical procedure, the tumor was suspected to be lymphangioma of the kidney as a result of a frozen- section histopathological evaluation. Therefore enucleation of the tumor was performed. Pathological evaluation of the specimen revealed lymphangioma arising from the kidney. The patient is free of disease after a 3-month follow-up period.