Kyle O. Rove

The Role of 3-Dimensional Mapping Biopsy in Decision Making for Treatment of Apparent Early Stage Prostate Cancer

PURPOSEnWe determined the impact of a grid based, transperineal 3-dimensional mapping biopsy on decision making for primary management of early stage prostate cancer.nnnMATERIALS AND METHODSnWe prospectively performed 3-dimensional mapping biopsy on 180 consecutive men who presented to our clinic between 2006 and 2009 with early stage, organ confined prostate cancer based on transrectal ultrasound guided 10 to 12-core biopsy, and on 35 with prior negative transrectal ultrasound biopsies.nnnRESULTSnAt presentation median patient age was 60.5 years (range 43 to 77), median prostate specific antigen was 4.8 ng/ml (range 0.5 to 72.4) and median prostate volume was 35 cc (range 9 to 95). The median number of cores acquired by transrectal ultrasound and 3-dimensional mapping biopsy was 12 and 56, and the median number of positive cores was 1 and 2, respectively. We documented Gleason score upgrade in 49 of 180 cases (27.2%) and up-stage in 82 (45.6%). The incidence of urinary retention catheter requirement of greater than 48 hours was 3.2% and the incidence of transient orthostatic hypotension was 5%. No urinary tract infections were documented. A total of 38 men received radical extirpative therapy, 11 radiation and 45 cryotherapy while 60 enrolled in a targeted focal therapy study, 44 entered active surveillance and 5 underwent other focal investigational treatments. Post-mapping data on 12 men were not available for analysis.nnnCONCLUSIONSnThree-dimensional mapping biopsy revealed that a significant portion of men initially diagnosed with apparently low risk disease harbored clinically significant cancers requiring more aggressive therapy. The technique also enabled a number of men with low risk disease to elect surveillance or another less morbid option.

The computerized rounding report: implementation of a model system to support transitions of care.

OBJECTIVESnIn response to ACGME work-hour restrictions, residency programs that require continuous inpatient clinical care for educational objectives will be forced to increase the proportion of junior resident experience involved in shift work. Maintaining the balance of education over service at these levels will be a challenge, where a considerable amount of time must be spent gathering data for morning rounds and signing out patients at shift change. Patient safety is an issue with this new paradigm. We hypothesized that computerized sign-out would improve resident efficiency.nnnMATERIALS AND METHODSnA multidisciplinary clinical team collaborated to design a computerized rounding and sign-out (CSO) program to automate collection of clinical information in addition to a brief narrative describing ongoing care issues. Residents returned a self-administered questionnaire before (n = 168) and after implementation (n = 83) examining: pre-rounding time, missed patients, handoff quality, and duty hours.nnnRESULTSnResidents reported spending 11 fewer min/d pre-rounding (P = 0.006). After implementation, residents missed fewer patients on rounds (P = 0.01). A majority (70%) of responders stated that the new program helped them with duty hours.nnnCONCLUSIONnThe current study demonstrates the reproducibility of the University of Washington model system for rounding and sign-out at an independent site, using basic infrastructure and leadership common to all residency programs. Developing a CSO was associated with a modest reduction in pre-rounding time and fewer patients missed on rounds. Although automating resident tasks may improve workflow in an increasingly complex hospital environment, structured handoff education and other institutional changes are necessary.

Role of Testosterone in Managing Advanced Prostate Cancer

Androgen deprivation therapy is frequently used to treat patients with advanced prostate cancer. New therapies for metastatic castration-resistant prostate cancer have drawn increased attention to serum and intratumoral testosterone levels. The present review examines the role of testosterone in prostate cancer progression, discusses the nuances and potential pitfalls in measuring serum testosterone using available assays, and summarizes current data relevant to the arguments for and against achieving and maintaining the lowest possible testosterone levels during androgen deprivation therapy, including the adverse effects of such treatment. Incorporating this information, we have made recommendations incorporating testosterone evaluation and its effect on the clinical decision-making process.

Prostate-specific antigen 1.5-4.0 ng/mL: a diagnostic challenge and danger zone.

Study Type – Prognosis (inception cohort)

Potentiation of mitomycin C tumoricidal activity for transitional cell carcinoma by histone deacetylase inhibitors in vitro.

PURPOSEnHistone deacetylase inhibitors represent promising cancer treatments since they offer improved access to target DNA/protein complexes by cytotoxic agents. We hypothesized that histone deacetylase inhibitors would be most effective when combined with DNA damaging agents such as mitomycin C. Valproic acid is a safe, affordable histone deacetylase inhibitor. We examined the effect of the combination of valproic acid and mitomycin C on human bladder cancer cells in vitro and compared this to the effect of valproic acid or mitomycin C alone on the cells.nnnMATERIALS AND METHODSnWe used HTB5 and HTB9 cells derived from low and high grade bladder tumors, respectively. HTB5 and HTB9 cells were grown in modified Eagles and RPMI medium, respectively. Cell growth and proliferation were measured by standard methods. Apoptosis was evaluated microscopically after dual staining of cells with annexin V-fluorescein isothiocyanate/propidium iodide. The change in protein expression was analyzed by Western blot.nnnRESULTSnTreatment of HTB5 and HTB9 bladder cancer cells for 24 to 72 hours with valproic acid and mitomycin C resulted in concentration and time dependent decreases in viability and proliferation. HTB9 cells showed marked sensitivity to mitomycin C with a 48-hour 50% median inhibitory concentration of 1 μg. Cells were less sensitive to valproic acid alone with a 48-hour 50% median inhibitory concentration of 2.5 mM. The chromatin structure relaxation induced by valproic acid pretreatment sensitized the bladder cancer cell lines, augmenting the cytotoxic action of mitomycin C. Valproic acid potentiated the induction of cell death by mitomycin C in each cell line in synergistic fashion. The effect of combining the 2 drugs was greater than the sum effect of each drug alone.nnnCONCLUSIONSnResults indicate that the valproic acid and mitomycin C combination is effective, likely due to synergistic mechanisms. Animal model validation is needed but early results suggest promising intravesical treatments for superficial bladder cancer.

Incomplete testosterone suppression in prostate cancer.

To the Editor: We have witnessed a new renaissance in the treatment of castration-resistant prostate cancer,1 but the progression of this disease beyond a form treatable by means of hormone depriva...

Monitoring and malignancy concerns in patients with congenital bladder anomalies.

Purpose of review There are concerns that patients with congenital bladder anomalies (CBA) may be at higher risk for developing bladder malignancy later in life. To date there is no consensus on how to monitor these patients to prevent this devastating malignancy. We will review the current understanding of bladder malignancy in patients with CBA and the status of surveillance tests. Recent findings Initial reports observed that augmentation cystoplasty in CBA may be an independent risk factor for bladder malignancy. Since that time, studies have identified that the augmented bladder may not be the culprit, but the congenital bladder itself may be at risk. Further, reports determined cystoscopy and cytology are not cost-effective at detecting these malignancies. Bladder cancer in these patients at presentation is typically aggressive and presents at a younger age, high stage with high mortality. Summary Surveillance cystoscopy and cytology of the adult congenital bladder should be discontinued as the evidence shows they are not effective, given the low incidence, high cost, and inability to alter the course of disease. Symptomatic patients should prompt a detailed evaluation for bladder cancer using standard testing.

Androgen annihilation as a new therapeutic paradigm in advanced prostate cancer.

Purpose of review Treatment of all stages of prostate cancer has changed considerably in recent years, as our understanding of its biochemical pathways has improved. Testosterone, true to Huggins original observation, remains a key player not only in newly diagnosed prostate cancer but also in castration-resistant prostate cancer, and our understanding of how to combine and sequence drugs that attack these pathways continues to grow. New US Food and Drugs Administration approved pharmaceutical agents further eliminate testosterone ligand or its activity via inhibition of key synthetic enzymes and through strong inhibition of the androgen receptor. Recent findings This review will briefly examine our knowledge of the complex relationship between testosterone, androgen receptor and advanced prostate cancer, discuss the limits of traditional androgen deprivation therapy in the form of gonadotropin-releasing hormone agonists and newer antagonists, examine combination therapies, including combined androgen blockade and newer studies with 5&agr;-reductase inhibitors, and overview two new therapeutics that target hormonal pathways. Summary This review provides guidance on trials that examine combination therapies in various prostate cancer disease states. Androgens and prostate cancer remain inexorably linked, and this review will shed light on renewed focus on eliminating activity of this trophic ligand.