PURPOSE OF REVIEWRadical treatments for prostate cancer are associated with significant morbidity, including incontinence and erectile dysfunction. Advances in the field of prostate MRI and desire to ...reduce treatment morbidities have led to a rapid growth in focal treatments for prostate cancer. Here, we review novel focal prostate cancer treatments and their associated recent clinical data, with a particular focus on data reported within the last 24 months.
RECENT FINDINGSHigh-intensity focal ultrasound, focal laser ablation, irreversible electroporation, focal cryotherapy, and photodynamic therapy have been used as treatment modalities for localized prostate cancer treatment. Despite the great variety of treatment techniques, each of these modalities is characterized by a significant rate of prostate cancer persistence within treatment zones (6–50%) and the presence of residual cancer within the prostate on rebiopsy (24–49%). These treatments, however, are associated with very low rates of high-grade complications, rare incontinence, and only mild or transient reductions in erectile function. The most common adverse events are urinary tract infections, hematuria, and urinary retention.
SUMMARYProstate cancer focal therapy is an attractive option for well-selected patients because of its low complication profile; however, long-term oncologic outcome is still lacking and early recurrence rates are high, limiting the ability of most urologic associations from endorsing its routine use.
Bladder cancer is a complex disease with variable prognosis. Recent investigations into the molecular landscape of bladder cancer have revealed frequent genetic alterations and molecular subtypes ...with therapeutic implications. Consequently, a shift toward personalized treatment of bladder cancer is underway. To this end, several biomarkers have been developed and tested in their ability to predict response to treatment in patients with bladder cancer and potentially help direct therapy. We performed a search of recently published PubMed articles using terms "biomarker," "bladder cancer," and the respective treatment discussed (i.e., "neoadjuvant" or "BCG"). In this review, we summarize the latest studies on novel biomarkers in bladder cancer with a focus on those intended to improve risk stratification and treatment selection.
Historically, open techniques have been favored over minimally invasive approaches for complex surgeries. We aimed to identify differences in perioperative outcomes, surgical footprints, and ...complication rates in patients undergoing either open or robotic reoperative partial nephrectomy.
A retrospective review of patients undergoing reoperative partial nephrectomy was performed. Patients were assigned to cohorts based on current and prior surgical approaches: open after open, open after minimally invasive surgery, robotic after open, and robotic after minimally invasive surgery cohorts. Perioperative outcomes were compared among cohorts. Factors contributing to complications were assessed.
A total of 192 patients underwent reoperative partial nephrectomy, including 103 in the open after open, 10 in the open after minimally invasive surgery, 47 in the robotic after open, and 32 in the robotic after minimally invasive surgery cohorts. The overall and major complication (grade ≥3) rates were 65% and 19%, respectively. The number of blood transfusions, overall complications, and major complications were significantly lower in robotic compared to open surgical cohorts. On multivariate analysis, the robotic approach was protective against major complications (OR 0.3, p=0.02) and estimated blood loss was predictive (OR 1.03, p=0.004). Prior surgical approach was not predictive for major complications.
Reoperative partial nephrectomy is feasible using both open and robotic approaches. While the robotic approach was independently associated with fewer major complications, prior approach was not, implying that prior surgical approaches are less important to perioperative outcomes and in contributing to the overall surgical footprint.
Nearly all eye drops contain preservatives to decrease contamination. Nonpreservatives such as disodium-ethylene diamine tetra-acetate (EDTA) and phosphate-buffered saline are also regularly added as ...buffering agents. These components can add to the toxicity of eye drops and cause ocular surface disease. To evaluate the potential toxicity of these common components and their comparative effects on the ocular surface, a tissue culture model utilizing immortalized corneal and conjunctival epithelial cells was utilized.
Immortalized human conjunctival and corneal epithelial cells were grown. At confluency, medium was replaced with 100 microL of varying concentrations of preservatives: benzalkonium chloride (BAK), methyl paraben (MP), sodium perborate (SP), chlorobutanol (Cbl), and stabilized thimerosal (Thi); varying concentrations of buffer: EDTA; media (viable control); and formalin (dead control). After 1 h, solutions were replaced with 150 microL of MTT (3-4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazonium bromide). After 4 h, solutions decanted, 100 microL of acid isopropanol added, and the optical density determined at 572 nm to evaluate cell viability.
Conjunctival and corneal cell toxicity was seen with all preservatives. Depending upon concentration, BAK exhibited from 56% to 89% toxicity. In comparison, Cbl exhibited from 50% to 86%, MP from 30% to 76%, SP from 23% to 59%, and Thi from 70% to 95%. EDTA with minimal toxicity (from 6% to 59%) was indistinguishable from SP.
Generally, the order of decreasing toxicity at the most commonly used concentrations: Thi (0.0025%) > BAK (0.025%) > Cbl (0.25%) > MP (0.01%) > SP (0.0025%) approximately EDTA (0.01%). Even at low concentration, these agents will cause some degree of ocular tissue damage.
We aimed to assess post-interventional and 36-month follow-up results of a single-center, single-arm, in-bore phase I trial of focal laser ablation (FLA) guided by multiparametric magnetic resonance ...imaging (mpMRI).
FLA procedures were done in-bore MRI using a transperineal approach. Primary endpoints were feasibility and safety expressed as lack of grade 3 complications. Secondary endpoints were changes in international prostate symptom score (IPSS), sexual health inventory for men (SHIM), quality of life (QoL) scores, and serum prostate specific antigen (PSA) levels. Treatment outcomes were assessed by combined mpMRI-ultrasound fusion-guided and extended sextant systematic biopsy after 12, 24, and optionally after 36 months.
Fifteen participants were included. Seven patients (46.67%) had Gleason 3+3 and 8 patients (53.33%) had Gleason 3+4 cancer. All patients tolerated the procedure well, and no grade 3/4 complications occurred. All grade 1 and 2 complications were transient and resolved completely. There was no significant change in mean IPSS from baseline (-1, p = 0.460) and QoL (0, p = 0.441) scores following FLA but there was a significant drop in mean SHIM scores (-2, p = 0.010) compared to pretreatment baselines. Mean PSA significantly decreased after FLA (-2.5, p < 0.001). Seven out of 15 patients (46.67%) had residual cancer in, adjacent, or in close proximity to the treatment area (1 × 4+3=7, 1 × 3+4=7, and 5 × 3+3=6). Four out of 15 patients (26.67%) underwent salvage therapy (2 repeat FLA, 2 radical prostatectomy).
After 3 years of follow-up we conclude focal laser ablation is safe and feasible without significant complications.
Summary Background Obesity is not only a causative factor for premature mortality, it has also been demonstrated to be associated with an increased postoperative complication rate. As such, it has ...traditionally been considered a relative contraindication to autologous breast reconstruction. The purpose of this study was to assess whether this recommendation is justified. Methods A retrospective study was conducted analyzing the effect of obesity on complication rate after microsurgical autologous breast reconstruction using abdominal tissue. Patients undergoing breast reconstruction between November 2006 and February 2011 were included. In contrast to prior studies, only patients meeting criteria to undergo bariatric surgery were included in the study, thus, representing a particularly high-risk subset of patients (Group 1: BMI greater 40 kg/m2 ; Group 2: BMI greater 35 kg/m2 with co-morbidities). Results A total of 42 breast reconstructions were performed in 28 patients who met inclusion criteria. Surgical complications were seen in a total of 9 patients ( p = 1.00). All complications were successfully managed conservatively and did not prolong hospitalization. No differences were seen among study groups with respect to donor-site ( p = 0.57) and recipient-site complications ( p = 1.00). Of note, no partial or total flap loss was seen in this study. Conclusions Obesity is associated with a relatively high risk of minor complications postoperatively. However, complications can typically be managed non-operatively and on an outpatient basis with fairly minimal patient morbidity. We believe that obesity should not be considered a relative contraindication to autologous microsurgical breast reconstruction. Patients should, however, be informed preoperatively about their higher risk of postoperative complications.
Urinary tract infection (UTI) is a pervasive health problem worldwide. Patients with a history of UTIs suffer increased risk of recurrent infections, a major risk of antibiotic resistance. Here, we ...show that bladder infections induce expression of Ezh2 in bladder urothelial cells. Ezh2 is the methyltransferase of polycomb repressor complex 2 (PRC2)—a potent epigenetic regulator. Urothelium-specific inactivation of PRC2 results in reduced urine bacterial burden, muted inflammatory response, and decreased activity of the NF-κB signaling pathway. PRC2 inactivation also facilitates proper regeneration after urothelial damage from UTIs, by attenuating basal cell hyperplasia and increasing urothelial differentiation. In addition, treatment with Ezh2-specific small-molecule inhibitors improves outcomes of the chronic and severe bladder infections in mice. These findings collectively suggest that the PRC2-dependent epigenetic reprograming controls the amplitude of inflammation and severity of UTIs and that Ezh2 inhibitors may be a viable non-antibiotic strategy to manage chronic and severe UTIs.
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•UTI induces epigenetic remodeling of the bladder•The remodeling exacerbates inflammatory host response to subsequent infections•Targeting the PRC2-dependent epigenetic program reduces inflammatory damage•Ezh2 inhibitors therapeutically alleviate UTIs in mouse models
Health sciences; Molecular mechanism of gene regulation; Epigenetics; Immunology
Conventional staging for prostate cancer (PCa) is performed for men diagnosed with unfavorable-intermediate or higher risk disease. Computed tomography (CT) of the abdomen and pelvis and whole body ...bone scan remains the standard of care for the detection of visceral, nodal, and bone metastasis. The implementation of the 2012 United States Preventive Services Task Force recommendation against routine prostate specific antigen (PSA) screening resulted in a rise of metastatic PCa at the time of diagnosis, emphasizing the importance of effective imaging modalities for evaluating metastatic disease. CT plays a major role in clinical staging at the time of PCa diagnosis, but multi-parametric magnetic resonance imaging (MRI) is now integrated into many prostate biopsy protocols for the detection of primary PCa, and may be a surrogate for CT for nodal staging. Current guidelines incorporate both CT and MRI as appropriate cross-sectional imaging modalities for the identification of nodal metastasis in indicated patients. There is an ongoing debate about the utility of traditional cross-sectional imaging modalities as well as advanced imaging modalities in detection of both organ-confined PCa detection and nodal involvement.
Definitive treatment for local prostate cancer recurrence remains controversial. Early recurrences are often from positive surgical margins or nodal metastases, however other explanations should be ...considered. We present a case of a 79 year-old male with localized prostate cancer and early biochemical persistence after margin-negative robotic-assisted radical prostatectomy. Workup demonstrated a 0.9 cm rectal mass without nodal or distant metastasis, and biopsy revealed prostate adenocarcinoma. A subsequent transanal excision was performed. Post-operatively, his PSA dropped to 0.02 ng/mL. We present a rare case of prostate adenocarcinoma seeding after transrectal prostate biopsy and a review of the literature.
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