Remarkable response to abiraterone acetate in castration-resistant prostate cancer patient with aggressive liver metastasis.

INTRODUCTION: The number of treatment options for metastatic castration-resistant prostate cancer has increased in recent years. Abiraterone, which selectively inhibits CYP17 in the androgen synthesis pathway, is widely used. Liver metastasis is one of the worst prognostic factors in metastatic castration-resistant prostate cancer. Only a few case reports have shown abiraterone successfully treated the liver metastasis of metastatic castration-resistant prostate cancer. CASE PRESENTATION: A 62-year-old man with prostate-specific antigen of 16.69 ng/mL was diagnosed with Gleason 8 (3 + 5) poorly differentiated prostate adenocarcinoma. Androgen deprivation therapy and sequential anti-androgen replacement were performed; however, the disease advanced to castration-resistant prostate cancer with liver metastasis. Prior to docetaxel, abiraterone achieved marked improvements in liver metastasis and prostate-specific antigen. CONCLUSION: Metastatic castration-resistant prostate cancer patients with visceral metastasis were excluded from COU-AA-302, which is phase III trial on abiraterone prior to docetaxel. Although docetaxel is the recommended treatment for the visceral metastasis of castration-resistant prostate cancer according to the European Association of Urology guidelines, abiraterone also has potential as a treatment option.

Ureteral Stone in the Distal Blind-ending Branch of a Bifid Ureter.

A bifid ureter with a distal blind-ending branch is a rare congenital anomaly. Most patients are asymptomatic; only patients with complications, such as infection, vesicoureteral reflux, or stone formation, present symptoms. We describe the case of a patient with urinary stone located in the distal blind-ending branch of a bifid ureter diagnosed during transurethral lithotripsy. Preoperative noncontrast-enhanced computed tomography did not reveal a stone in the distal blind-ending branch of the bifid ureter, but a rigid ureteroscope did; however, it could not reach the stone. Therefore, the stone was extracted using a basket catheter under a flexible ureteroscope.

Clinical and molecular characteristics of East Asian patients with von Hippel-Lindau syndrome.

BACKGROUND: Von Hippel-Lindau (VHL) syndrome is a dominantly inherited multisystem cancer syndrome caused by a heterozygous mutation in the VHL tumor suppressor gene. Previous studies suggested that similar populations of Caucasian and Japanese patients have similar genotype or phenotype characteristics. In this comprehensive study of East Asian patients, we investigated the genetic and clinical characteristics of patients with VHL syndrome. METHODS: To create a registry of clinical characteristics and mutations reported in East Asian patients with VHL syndrome, we conducted a comprehensive review of English language and non-English language articles identified through a literature search. Publications in Japanese or Chinese language were read by native speakers of the language, who then performed the data extraction. RESULTS: Of 237 East Asian patients with VHL syndrome, 154 unique kindreds were identified for analysis. Analyzed by kindred, missense mutations were the most common (40.9%, 63/154), followed by large/complete deletions (32.5%, 50/154) and nonsense mutations (11.7%, 18/154). Compared with a previously reported study of both East Asian and non-East Asian patients, we found several key differences. First, missense and frameshift mutations in the VHL gene occurred less commonly in our population of East Asian patients (40.9% vs. 52.0%; P = 0.012 and 8.4% vs. 13.0%; P < 0.001, respectively). Second, large/complete deletions were more common in our population of East Asian patients (32.5% vs. 10.5%; P < 0.001). Third, phenotypically, we observed that, in our population of East Asian patients with VHL syndrome, the incidence of retinal capillary hemangioblastoma was lower, whereas the incidence of renal cell carcinoma was higher. CONCLUSIONS: Evidence suggests that the genotypic and phenotypic characteristics of East Asian patients with VHL syndrome differ from other populations. This should be considered when making screening recommendations for VHL syndrome in Asia.

Effect of Ang-2-VEGF-A Bispecific Antibody in Renal Cell Carcinoma.

The blockade of VEGF pathway has been clinically validated as an initial treatment for renal cell carcinoma (RCC). Angiopoietin-2 (Ang-2) has been indicated as a key regulator for angiogenesis escape. The effect of a novel bispecific antibody (A2V CrossMab) against both Ang-2 and VEGF was investigated in comparison with either factor. A2V CrossMab significantly reduced tumor volume, vessel density, and interstitial fluid pressure compared to either monotherapy of anti-VEGF or anti-Ang-2. Host-derived angiogenesis-related genes have been significantly down-regulated in A2V CrossMab group. These data demonstrate that A2V CrossMab has additive anti-tumor effect for the treatment of RCC.

Inhibition of placental growth factor in renal cell carcinoma.

BACKGROUND/AIM: Placental growth factor (PlGF) is up-regulated in major malignant diseases or following antiangiogenic therapy, although it is present in low levels under normal physiological conditions. TB403, a monoclonal antibody against PlGF, was investigated in clear cell renal cell carcinoma (ccRCC) xenografts since it has been proposed as a potential target in oncology. MATERIALS AND METHODS: Human ccRCCs were implanted in athymic nude mice to evaluate the efficacy of TB403 and to excise xenograft tumors for molecular experiments. RESULTS: TB403 did not significantly inhibit tumor growth in treatment-naïve or sunitinib-resistant ccRCC xenografts. Gene expression profiling resulted in over-expression of the C1orf38 gene, which induced immunoreactivity in macrophages. Angiogenesis PCR arrays showed that VEGFR-1 was not expressed in ccRCC xenografts. CONCLUSION: PlGF blockade did not have a broad antiangiogenic efficacy; however, it might be effective on-target in VEGFR1-expressing tumors. The inhibition of VEGF pathway may induce the activity of tumor-associated-macrophages for angiogenesis escape.

[Myocardial metastasis from renal cell carcinoma treated with sorafenib].

We present a case of myocardial metastasis from renal cell carcinoma (RCC) during the treatment with sorafenib. A 63-year-old male, who had undergone right radical nephrectomy, received interferon-alpha (IFN), interleukin (IL-2) and 5-flurouracil (5-FU) for the treatment of lung and pleural metastases. However, since this metastasis showed progressive disease, we administered sorafenib. Nine months after the introduction of sorafenib, he complained of dyspnea. Chest computed tomography and cardiac ultrasonography revealed a low density mass at the cardiac muscle of the left cardiac ventricle, suggesting myocardial metastasis of RCC. Molecular targeted therapy achieved a longer survival in advanced RCC patients in comparison with the immunotherapy using cytokines. Therefore, in metastasis evaluation, some organs which have been regarded as rare sites should be carefully evaluated.

Single infusion of zoledronic acid to prevent androgen deprivation therapy-induced bone loss in men with hormone-naive prostate carcinoma.

BACKGROUND: Androgen-deprivation therapy (ADT) decreases bone mineral density (BMD) and increases fracture risk in patients with prostate carcinoma. The authors investigated the effectiveness of a single infusion of zoledronic acid initiated subsequent to ADT on BMD with hormone-naive prostate carcinoma. METHODS: Forty men received either a single infusion of zoledronic acid (4 mg intravenously on Day 1) or no infusion during ADT. BMD of the proximal femur and posteroanterior lumbar spine was measured by dual-energy x-ray absorptiometry and urinary N-telopeptide (u-NTx) at 6 and 12 months. RESULTS: At baseline, the overall BMDs demonstrated no significant difference in lumbar spine and hip regions. At 6 months, mean (+/-standard error) BMD of the posteroanterior lumbar spine decreased 4.6%+/-1.0% in control patients and increased 5.1%+/-1.2% in patients receiving zoledronic acid, a significant difference (P=.0002). At 12 months, the change in BMD between the 2 groups was statistically significantly different at the lumbar region (P=.0004), indicating that zoledronate preserved BMD. For u-NTx, bone turnover was statistically significantly decreased in the zoledronate group compared with controls at 6 months (P<.0001), but returned to pretreatment levels at 12 months in the zoledronate group. CONCLUSIONS: Bone loss begins at 6 months with ADT. A single infusion of zoledronic acid in patients receiving ADT reduces bone mineral loss and maintains BMD at least at 12 months during ADT. Further study is needed to determine the best dosing schedule to prevent ADT-induced bone loss in men with hormone-naive prostate carcinoma.