Surgical Management of Organ-Confined Prostate Cancer with Review of Literature and Evolving Evidence.

Prostate cancer is the most common solid organ malignancy in men in the USA with an annual incidence of 105 and an annual mortality rate of 19 per 100,000 people. With the advent of PSA screening, the majority of prostate cancer diagnosed is organ confined. Recent studies including the SPCG-4 and PIVOT trials have demonstrated a survival benefit for those undergoing active treatment for localized prostate cancer. The foremost surgical option has been radical prostatectomy (RP). The gold standard has been open radical retropubic prostatectomy (RRP); however, minimally invasive approaches including laparoscopic and robotic approaches are commonplace and increasing in popularity. We aim to describe the surgical options for the treatment of localized prostate cancer by reviewing the literature. A review of the literature was undertaken using MEDLINE and PubMed. Articles addressing the topic of radical prostatectomy by open, laparoscopic and robotic approaches were selected. Studies comparing the different modalities were also identified. These articles were reviewed for data pertaining to perioperative, oncological and functional outcomes. There is a paucity of randomized studies comparing the three modalities. The published data has demonstrated a benefit in favour of robotically assisted laparoscopic prostatectomy (RALP) over laparoscopic radical prostatectomy (LRP) and traditional open RRP in perioperative outcomes. When reviewing the best-reported outcomes for RALP compared to LRP and RRP, operative times are lower (105 vs. 138 vs. 138 min), estimated blood loss rates are lower (111 vs. 200 vs. 300 ml) and blood transfusion rates are lower as in the length of stay (1 vs. 2 vs. 2.3 days) and overall complication rates (4.3 vs. 5 vs. 20%). Similarly, when reviewing functional outcomes, RALP compared to LRP was not inferior. At 12 months, the reported continence was 97 vs. 94 vs. 89% and potency was 94 vs. 77 vs. 90%. In comparative studies, however, these differences did not always meet statistical significance. With respect to oncological outcomes, there was no clear evidence of superiority of one modality over another. RALP is now the most common modality for surgical treatment of organ-confined prostate cancer. Individual series appear to support better perioperative outcomes and perhaps quicker return to functional outcomes. There does not appear to be a clear advantage to date in oncological parameters; however, RALP does not appear to be inferior to either LRP or RRP. It is anticipated that further high quality randomized studies will shed more light on the clinical and statistical significance in the comparison between these modalities.

Current Concepts of Epigenetics in Testicular Cancer.

Testicular germ cell tumors (GCTs) are characterized into seminomas (SGCTs) and non-seminomatous testicular germ cell tumors (NSGCTs). Serum tumor markers (STMs) play an important role in testicular cancer as they provide useful information for diagnosis, staging, and detection of recurrence. Nonetheless, additional tumor markers for early diagnosis and therapeutic options are required to enhance specificity of serological diagnosis of testes cancers. Epigenetics is defined as inherited changes in gene expression that are not encoded in the DNA structure. Epigenetic changes include DNA methylation, histone modifications, and microRNA (miRNA) regulation. It is through the study of epigenetics that diagnostic methods for early detection and novel therapeutic strategies may be established for testicular cancer. We performed a comprehensive review of the English medical literature in PubMed by combining search terms including DNA methylation, histone modifications, microRNA (miRNA) regulation, epigenetics, and testicular cancer. DNA methylation is the most extensively studied epigenetic modification. It consists of the addition of a methyl group to nucleotide bases. It has been reported that SGCT contain reduced levels of DNA methylation compared to NSGCT. MiRNAs are small non-coding RNAs that regulate posttranscriptional gene expression. It has been suggested that miRNAs may play a role in the pathogenesis of GCT. Specific expression patterns have been displayed by various miRNAs in patients with GCT. Histones are proteins intertwined with coiled, double-stranded genomic DNA that form a structure known as a nucleosome. The most widely studied histone modifications include acetylation, methylation, and phosphorylation. Methylation of histone proteins has been found in all types of NSGCT. Epigenetics may offer an additional and effective tool in establishing a diagnosis of GCT of the testes, including prognostic information and perhaps enabling targeted treatment in patients with testicular GCT.

The role of epigenetics in kidney malignancies.

INTRODUCTION: Renal cell carcinomas (RCC) are collectively the third most common type of genitourinary neoplasms, surpassed only by prostate and bladder cancer. Cure rates for renal cell carcinoma are related to tumor grade and stage; therefore, diagnostic methods for early detection and new therapeutic modalities are of paramount importance. Epigenetics can be defined as inherited modifications in gene expression that are not encoded in the DNA sequence itself. Epigenetics may play an important role in the pursuit of early diagnosis, accurate prognostication and identification of new therapeutic targets. MATERIAL AND METHODS: We used PubMed to conduct a comprehensive search of the English medical literature using search terms including epigenetics, DNA methylation, histone modification, microRNA regulation (miRNA) and RCC. In this review, we discuss the potential application of epigenetics in the diagnosis, prognosis and treatment of kidney cancer. RESULTS: During the last decade, many different types of epigenetic alterations of DNA have been found to be associated with malignant renal tumors. This has led to the research of the diagnostic and prognostic implications of these changes in renal malignancies as well as to the development of novel drugs to target these changes, with the aim of achieving a survival benefit. CONCLUSIONS: Epigenetics has become a promising field in cancer research. The potential to achieve early detection and accurate prognostication in kidney cancer might be feasible through the application of epigenetics. The possibility to reverse these epigenetic changes with new therapeutic agents motivates researchers to continue pursuing better treatment options for kidney cancer and other malignancies.

Resolution of hypercalcemia of malignancy following radical cystectomy in a patient with paraneoplastic syndrome associated with urothelial carcinoma of the bladder.

Hypercalcemia of malignancy is a common finding associated with different types of cancers; however, its association with urothelial carcinoma of the bladder is rare. We report a case of a 69-year-old male with nonmetastatic urothelial carcinoma of the bladder who developed hypercalcemia that failed to respond to medical management, but resolved completely after undergoing resection of the tumor through radical cystectomy.