Vaginal cuff recurrence after radical cystectomy: an under - studied site of bladder cancer relapse

Vaginal cuff recurrence of tumor following radical cystectomy is a rare site of disease recurrence, however it has never been specifically studied. The aim of the study is to evaluate incidence, risk factors, and long-term oncologic outcomes of vaginal cuff recurrence in a cohort of female patients treated with radical cystectomy for invasive urothelial carcinoma of the bladder

Overcoming Drug Resistance and Treating Advanced Prostate Cancer.

Most of the prostate cancers (PCa) in advanced stage will progress to castration-resistant prostate cancer (CRPC). Within CRPC group, 50-70% of the patients will develop bone metastasis in axial and other regions of the skeleton. Once PCa cells spread to the bone, currently, no treatment regimens are available to eradicate the metastasis, and cancer- related death becomes inevitable. In 2012, it is estimated that there will be 28,170 PCa deaths in the United States. Thus, PCa bone metastasis-associated clinical complications and treatment resistance pose major clinical challenges. In this review, we will present recent findings on the molecular and cellular pathways that are responsible for bone metastasis of PCa. We will address several novel mechanisms with a focus on the role of bone and bone marrow microenvironment in promoting PCa metastasis, and will further discuss why prostate cancer cells preferentially metastasize to the bone. Additionally, we will discuss novel roles of several key pathways, including angiogenesis and extracellular matrix remodeling in bone marrow and stem cell niches with their relationship to PCa bone metastasis and poor treatment response. We will evaluate how various chemotherapeutic drugs and radiation therapies may allow aggressive PCa cells to gain advantageous mutations leading to increased survival and rendering the cancer cells to become resistant to treatment. The novel concept relating several key survival and invasion signaling pathways to stem cell niches and treatment resistance will be reviewed. Lastly, we will provide an update of several recently developed novel drug candidates that target metastatic cancer microenvironments or niches, and discuss the advantages and significance provided by such therapeutic approaches in pursuit of overcoming drug resistance and treating advanced PCa

The dog as an animal model for bladder and urethral urothelial carcinoma: comparative epidemiology and histology

Despite the recent approval of several novel agents for patients with metastatic urothelial carcinoma (UC), survival in this setting remains poor. As such, continued investigation into novel therapeutic options remains warranted. Pre clinical development of novel treatments requires an animal model that accurately simulates the disease in humans. The aim of the present study was to evaluate the dog as an animal model for human UC. A total of 260 cases of spontaneous, untreated canine primary urethral and urinary bladder UC, were epide¬miologically and histologically assessed and classified based on the current 2016 World Health Organization (WHO) tumor classification system. Canine data was compared with human data available from scientific literature. The mean age of dogs diagnosed with UC was 10.22 years (range, 4 15 years), which is equivalent to 60 70 human years. The results revealed a high association between UC diagnosis with the female sex [odds ratio (OR) 3.51; 95% confidence interval (CI) 2.57 4.79; P<0.001], surgical neutering (OR 4.57; 95% CI 1.87 11.12; P<0.001) and breed (OR 15.11 for Scottish terriers; 95% CI 8.99 25.41; P<0.001). Based on the 2016 WHO tumor (T), node and metastasis staging system, the primary tumors were characterized as T1 (38%), T2a (28%), T2b (13%) and T3 (22%). Non papillary, flat subgross tumor growth was strongly associated with muscle invasion (OR 31.00; P<0.001). Irrespective of subgross growth pattern, all assessable tumors were invading beyond the basement membrane compatible with infiltrating UC. Conventional, not further classifiable infiltrating UC was the most common type of tumor (90%), followed by UC with divergent, squamous and/or glandular differentiation (6%). Seven out of the 260 (2.8%) cases were classified as non urothelial based on their histological morphology. These cases included 5 (2%) squamous cell carci¬nomas, 1 (0.4%) adenocarcinoma and 1 (0.4%) neuroendocrine tumor. The 2 most striking common features of canine and human UC included high sex predilection and histological tumor appearance. The results support the suitability of the dog as an animal model for UC and confirm that dogs also spontaneously develop rare UC subtypes and bladder tumors, including plasmacytoid UC and neuroendocrine tumor, which are herein described for the first time in a non experimental animal species

Intravesical rAd-IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study.

Purpose Many patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd-IFNα/Syn3 (randomly assigned 1:1 to 1 × 10(11) viral particles (vp)/mL or 3 × 10(11) vp/mL). Patients who responded at months 3, 6, and 9 were retreated at months 4, 7, and 10. The primary end point was 12-month HG recurrence-free survival (RFS). All patients who received at least one dose were included in efficacy and safety analyses. Results Forty patients received rAd-IFNα/Syn3 (1 × 10(11) vp/mL, n = 21; 3 × 10(11) vp/mL, n = 19) between November 5, 2012, and April 8, 2015. Fourteen patients (35.0%; 90% CI, 22.6% to 49.2%) remained free of HG recurrence 12 months after initial treatment. Comparable 12-month HG RFS was noted for both doses. Of these 14 patients, two experienced recurrence at 21 and 28 months, respectively, after treatment initiation, and one died as a result of an upper tract tumor at 17 months without a recurrence. rAd-IFNα/Syn3 was well tolerated; no grade four or five adverse events (AEs) occurred, and no patient discontinued treatment because of an adverse event. The most frequently reported drug-related AEs were micturition urgency (n = 16; 40%), dysuria (n = 16; 40%), fatigue (n = 13; 32.5%), pollakiuria (n = 11; 28%), and hematuria and nocturia (n = 10 each; 25%). Conclusion rAd-IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who were unable or unwilling to undergo radical cystectomy

Predicting prostate cancer treatment choices: The role of numeracy, time discounting, and risk attitudes

Prostate cancer is the most common cancer among males in the United States and there is lack of consensus as to whether active surveillance (AS) or radical prostatectomy (RP) is the best course of treatment. In this study we examined the role of three overlooked determinants of decision making about prostate cancer treatment in a hypothetical experiment—numeracy, time discounting, and risk taking in 279 men over age 50 without a prior prostate cancer diagnosis. Results showed that AS was the most frequently chosen option. Furthermore, numeracy and time discounting significantly predicted participants’ preference for AS, whereas a propensity to take risks was associated with a preference for RP. Such insights into the factors that affects cancer treatment preferences may improve tailored decision aids and help physicians be better poised to engage in shared decision-making to improve both patient-reported and clinical outcomes

Giant growth rate in nano-oxidation of p-silicon surfaces by using ethyl alcohol liquid bridges

We demonstrate that local oxidation nanolithography can be performed in liquid environments different from aqueous solutions with a significant improvement in the aspect ratio of the fabricated motives. Here, we perform a comparative study of noncontact atomic force microscopy oxidation experiments in water and ethyl alcohol. The growth rate of local oxides can be increased by almost an order of magnitude by using oxyanions from ethyl alcohol molecules. We propose that the enhanced growth rate is a consequence of the reduction of the trapped charges within the growing oxide. The present results open the possibility of using local oxidation nanolithography to directly fabricate vertical oxide structures while keeping lateral sizes in the nanometer range.This work was supported by the European Commission (MONA-LISA, G5RD-2000-00349).Peer reviewe

Natural history of ‘second’ biochemical failure after salvage radiation therapy for prostate cancer: a multi‐institution study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142463/1/bju13926.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142463/2/bju13926_am.pd

Collaborative Review: Factors Influencing Treatment Decisions for Patients with a Localized Solid Renal Mass.

CONTEXT: With the addition of active surveillance and thermal ablation (TA) to the urologist\u27s established repertoire of partial (PN) and radical nephrectomy (RN) as first-line management options for localized renal cell carcinoma (RCC), appropriate treatment decision-making has become increasingly nuanced. OBJECTIVE: To critically review the treatment options for localized, nonrecurrent RCC; to highlight the patient, renal function, tumor, and provider factors that influence treatment decisions; and to provide a framework to conceptualize that decision-making process. EVIDENCE ACQUISITION: A collaborative critical review of the medical literature was conducted. EVIDENCE SYNTHESIS: We identify three key decision points when managing localized RCC: (1) decision for surveillance versus treatment, (2) decision regarding treatment modality (TA, PN, or RN), and (3) decision on surgical approach (open vs minimally invasive). In evaluating factors that influence these treatment decisions, we elaborate on patient, renal function, tumor, and provider factors that either directly or indirectly impact each decision point. As current nomograms, based on preselected patient datasets, perform poorly in prospective settings, these tools should be used with caution. Patient decision aids are an underutilized tool in decision-making. CONCLUSIONS: Localized RCC requires highly nuanced treatment decision-making, balancing patient- and tumor-specific clinical variables against indirect structural influences to provide optimal patient care. PATIENT SUMMARY: With expanding treatment options for localized kidney cancer, treatment decision is highly nuanced and requires shared decision-making. Patient decision aids may be helpful in the treatment discussion

The prostate cancer conundrum revisited

BACKGROUND: Prostate cancer mortality rates in the United States declined by >40% between 1991 and 2005. The impact of changes in primary treatment and adjuvant and neoadjuvant hormone therapy on this decline is unknown. METHODS: The authors applied 3 independently developed models of prostate cancer natural history and disease detection under common assumptions about treatment patterns, treatment efficacy, and survival in the population. Primary treatment patterns were derived from the Surveillance, Epidemiology, and End Results registry; data on the frequency of hormone therapy were obtained from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) database; and treatment efficacy was based on estimates from randomized trials and comparative effectiveness studies of treatment alternatives. The models projected prostate cancer mortality without prostate‐specific antigen screening and in the presence and absence of treatment benefit. The impact of primary treatment was expressed as a fraction of the difference between observed mortality and projected mortality in the absence of treatment benefit. RESULTS: The 3 models projected that changes in treatment explained 22% to 33% of the mortality decline by 2005. These contributions were accounted for mostly by surgery and radiation therapy, which increased in frequency until the 1990s, whereas hormone therapies contributed little to the mortality decline by 2005. Assuming that treatment benefit was less for older men, changes in treatment explained only 16% to 23% of the mortality decline by 2005. CONCLUSIONS: Changes in primary treatment explained a minority of the observed decline in prostate cancer mortality. The remainder of the decline probably was because of other interventions, such as prostate‐specific antigen screening and advances in the treatment of recurrent and progressive disease. Cancer 2012. © 2012 American Cancer Society. Three models of prostate cancer natural history are combined with data on patterns of primary treatment, including hormone therapies and trial‐based estimates of treatment efficacy. The results indicate that changes in these treatments explain 22% to 33% of the observed decline in prostate cancer mortality between 1991 and 2005.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94469/1/27594_ftp.pd