Comparative analysis of three vs. four cycles of neoadjuvant gemcitabine and cisplatin for muscle invasive bladder cancer.

PURPOSE: Because the optimal number of cycles of neoadjuvant gemcitabine and cisplatin chemotherapy (GC) is unclear, we aimed to compare disease response and survival outcomes of patients receiving either 3 or 4 cycles of neoadjuvant GC for muscle-invasive bladder cancer (MIBC). METHODS: A total of 166 patients who were treated with neoadjuvant GC and radical cystectomy for clinical stage T2-4N0M0 were identified. Response and effectiveness of different cycle counts were assessed using downstaging (complete pathologic and partial pathologic response), cancer-specific survival (CSS), and overall survival (OS). Response and survival outcomes were examined with adjusted logistic regression and Cox regression models. Statistical significance was defined as P < 0.05. RESULTS: Of 166 patients who received neoadjuvant GC, 107 (64.5%) received 3 cycles and 59 (35.5%) received 4 cycles. Age, insurance, comorbidity, tumor histology (pure urothelial carcinoma, urothelial with divergent differentiation, variant histology), and tumor stage were similar between the 2 treatment groups. Rates of complete response or any downstaging were similar between groups (21.5% and 40.2% in the 3-cycle group and 20.3% and 44.1% in the 4-cycle group, respectively). While disease response was similar (OR 1.03, 95% CI 0.43-2.45), both cancer-specific survival (HR 1.69, 95% CI 0.87-3.26) and overall survival (HR:1.88, 95% CI:1.02-3.48) were more favorable among patients managed with 4 cycles of neoadjuvant chemotherapy compared to those who received 3 cycles in adjusted models. CONCLUSIONS: Our analysis demonstrated that survival outcomes tended to be better among patients who received 4 cycle of neoadjuvant GC compared to those treated with 3 cycles. Although potential benefits of omission of fourth cycle may include expedited time to surgery, reduced chemotherapy-associated toxicity, and lower treatment costs, continuation of treatment with a fourth cycle of neoadjuvant GC chemotherapy may benefit patients with muscle-invasive bladder cancer and further improve disease outcomes.

Clinical indications for necessary and discretionary hospital readmissions after radical cystectomy.

BACKGROUND: To assess predictors, indicators and medical necessity of readmissions after neoadjuvant chemotherapy and radical cystectomy in order to identify opportunities for reducing readmission rates. METHODS: Records for patients treated with cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy between 2007 and 2017 were reviewed for 90-day complications and readmission. Readmissions were classified as necessary vs. discretionary based on independent clinician review. The association between postoperative complications and necessary or discretionary readmission were examined with adjusted regression models. RESULTS: Among a total of 250 patients, 76 patients (30.4%) were readmitted within 90 days of surgery (19 discretionary and 57 necessary). Age, insurance coverage, and comorbidity were similar between readmitted and non-readmitted patients. Readmission was more likely after neobladder than ileal conduit (39% vs. 23%, P = 0.02). Major (grade ≥ 3) complications within 90-day of surgery including index admission and post-discharge period were significantly more common among re-admitted patients compared to patients who were not readmitted (40% in necessary, 21% in discretionary, 3% in none, P < 0.001). Median length of stay on readmission was twice as long in necessary cases compared to discretionary cases (5 vs. 2.5 days, P < 0.001). Gastrointestinal and infectious complications were associated with discretionary readmission in adjusted analyses, while infectious, renal/genitourinary and thromboembolic complications were associated with necessary readmission. CONCLUSIONS: Twenty-five percent of readmissions were categorized as discretionary and were driven primarily by low-grade gastrointestinal complications, marginal oral intake and failure to thrive, suggesting that better coordinated post-discharge supportive care could help avoid a substantial proportion of readmissions.

Focal bipolar radiofrequency ablation for localized prostate cancer: Safety and feasibility.

OBJECTIVES: To evaluate the safety and feasibility of focal bipolar radiofrequency ablation in men with localized prostate cancer. METHODS: A review of 10 patients treated with a novel bipolar radiofrequency ablation probe integrated in a coil design (Encage; Trod Medical, Bradenton, FL, USA) between 2011 and 2017 in two prospective pilot trials. All men had clinical stage T1c prostate cancer, prostate-specific antigen <10 ng/mL and Gleason score ≤7. Ablation was carried out under general anesthesia, and bipolar probes were inserted transperineally under transrectal ultrasound guidance. Treatment-related adverse events, quality of life and negative biopsy rate were evaluated at 6 months after ablation. The Wilcoxon signed-rank test was used to compare baseline and post-treatment symptom scores. RESULTS: The median age was 58 years (range 50-64 years) and the median prostate volume was 49.65 cc (range 21-68 cc). Prostate cancer with a Gleason score of 6 (3 + 3) and 7 (3 + 4) was noted in seven and three patients, respectively. The median number of radiofrequency ablation cycles was 2.5 (range 2-5). All patients were catheter-free and able to void the day of surgery. Within 6 months after ablation, all adverse events were low grade, with the exception of one grade 3 hematuria that required cystoscopy without coagulation. Six months after ablation bowel, urinary and hormonal functions, and overall satisfaction remained stable. Erectile dysfunction occurred in two out of four patients who had normal sexual function before the procedure. Neither urinary incontinence nor urinary infection was noted. CONCLUSIONS: This first report on focal bipolar radiofrequency ablation documents a safe and feasible treatment option for selected patients with localized prostate cancer.

Contemporary management of early stage testicular seminoma.

Therapy for early stage testicular seminoma has changed radically over the past several decades. Given high cure rates and clinical trials supporting less active therapy in most cases, close observation after radical orchiectomy is now considered standard of care for clinical stage (CS) IA/IB seminoma, with either radiation therapy (RT) or chemotherapy salvage options possible. For CS IIA/IIB seminoma characterized by non-bulky retroperitoneal lymph node involvement (≤5 cm in greatest dimension), RT or combination chemotherapy are the standard of care. Given high comparable survival rates, preventing treatment-related toxicity and second malignancy, and limiting quality of life deficits associated with intense treatment has gained much greater importance. Clinical trials are currently testing the feasibility of retroperitoneal lymph node dissection (RPLND) for low volume CS IIA/IIB metastatic testicular seminoma to this end. Likewise, one cycle of chemotherapy is being evaluated as an adjuvant approach to reduce recurrence rates in CS I disease with unfavorable risk factors. Moreover, recent genomic and molecular studies have recently identified novel signatures and a potential biomarker for testicular seminoma. In this review, we first summarize the evolution of early stage seminoma management and discuss the effectiveness and drawbacks of contemporary treatment strategies. We further outline future perspectives and potential challenges in management of early stage testicular seminoma.

Current management and management controversies in early- and intermediate-stage of nonseminoma germ cell tumors.

Early stage nonseminomatous germ cell tumor (NSGCT) remains a treatable disease, with stage I cancer specific survival exceeding 95%. Using a risk-adapted approach; active surveillance (AS), adjuvant chemotherapy, and retroperitoneal lymph node dissection (RPLND) all options for treatment; with surveillance being increasingly used. With persistently elevated markers (stage IS), chemotherapy remains the hallmark of treatment. Management of stage II NSGCT varies based on status of tumor markers. With negative markers, both induction chemotherapy and upfront RPLND remain options. Management of a residual mass <1 cm after chemotherapy remains controversial, with AS and nerve-sparing RPLND considered options. The development of miR-371a-3p microRNA shows promise a novel biomarker for testicular cancer (GCT). Despite controversies in management, cures for NSGCT are achievable in 95-99% of patients.

Therapeutic strategies for uncommon testis cancer histologies: teratoma with malignant transformation and malignant testicular sex cord stromal tumors.

Testicular cancer is the most common solid malignancy in male adolescents and young adults, with germ cell derived seminomas and non-seminomas being by far the most common histologies. Teratoma with somatic-type malignancy is a rare chemo-resistant phenotype of testis cancer associated with poor prognosis in patients with advanced stage disease. Malignant gonadal-stromal tumors comprise 5% of testicular neoplasms and approximately 10% are malignant and considered chemo-radiation resistant. Prognostic factors and treatment strategies for these uncommon histologies are lacking.

Identifying an optimal lymph node yield for penile squamous cell carcinoma: prognostic impact of surgical dissection.

OBJECTIVE: To evaluate the prognostic impact of lymph node yield (LNY) on survival outcomes for penile squamous cell carcinoma (SCC). PATIENTS AND METHODS: In all, 532 patients who underwent inguinal LN dissection (ILND) across tertiary referral centres from Europe, China, Brazil and North America were retrospectively evaluated. From this cohort, 198 patients received pelvic LND (PLND).We identified threshold values for ILND and PLND using receiver operating characteristic curves. We tested prognostic value of LNY for recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) using the Kaplan-Meir method and Cox proportional hazard regression models. RESULTS: The median (interquartile [IQR]) age was 59 (49-68) years and the median (IQR) follow-up after ILND was 28 (12-68.2) months. Overall, 85% of the patients had bilateral dissections. The median (IQR) number of inguinal LNs removed was 15 (10-22). Of those receiving PLND, The median (IQR) number of LNs was 13 (8-19). A LNY of ≥15 was used for dichotomisation of ILND patients, and a LNY of ≥9 was used in the PLND cohort. Patients with a LNY ≥15 had significantly better 5-year OS vs patients with a LNY <15 (70.1% vs 58.7%). On multivariable analyses, a LNY ≥15 was a predictor of OS (hazard ratio [HR] 0.68, P = 0.029). For cN0 patients, a LNY ≥15 was an independent predictor of RFS (HR 0.52, P = 0.043) and OS (HR 0.53, P = 0.021). In the PLND cohort, a LNY ≥9 was a predictor of RFS (HR 0.53, P = 0.032). CONCLUSIONS: Using one of the largest LND datasets to date, we found LNY to be a significant predictor of outcomes after lymphatic staging for penile SCC. Prospective validation is warranted.

Treating advanced penile cancer: where do we stand in 2019?

PURPOSE OF REVIEW: Penile squamous cell carcinoma (PSCC) remains a challenging malignancy to treat and there is an urgent need of significant improvements at all levels of medical care. In the current review, we summarized the significant obstacles encountered during management of PSCC and discussed the clinical relevance of novel findings and their potential to address these obstacles. RECENT FINDINGS: The recent genetic and immunological advances suggest that patients with PSCC can benefit from available targeted therapy and immunotherapy options. Moreover, evidence has accumulated over time suggesting that majority of the patients diagnosed with PSCC suffer from psychosocial problems and impaired rehabilitation. SUMMARY: Effective prevention strategies against PSCC are urgently needed especially in developing countries given the limited therapeutic options. About a quarter of patients with metastatic PSCC appear to benefit from available targeted therapies and about half of the patients can be a suitable candidate for immune checkpoint blockade as half of the PSCC cases exhibit PD-L1 expression. Moreover, increased public awareness, healthcare provider education and social support programs may help patients suffering from PSCC coping with the psychosocial burdens of the disease.

Optimal Management of Upper Tract Urothelial Carcinoma: an Unmet Need.

OPINION STATEMENT: Upper tract urothelial carcinoma (UTUC) is a rare genitourinary entity of the renal pelvis and the ureter characterized by a more aggressive disease phenotype when compared with urothelial carcinoma of the bladder (UCB) with more than half of UTUC cases presenting with invasive disease at diagnosis compared to 20% for bladder tumors. There is growing evidence suggesting that its distinct natural history from that of bladder cancer can be related to several genetic and epigenetic differences. Treatment of low-risk disease consists of kidney-sparing surgeries such as ureteroscopic and percutaneous treatments, segmental ureterectomy, and adjuvant topical and intracavitary chemo-immunotherapies. The standard of care for high-risk non-metastatic disease remains radical nephroureterectomy and bladder cuff excision with increasing utilization rates of minimally invasive approaches leading to reduced morbidity without compromising outcomes while the role of lymphadenectomy is still being investigated. The prognosis of UTUC has been stagnant over the past decade highlighting the need for further studies on the role of multimodal therapy (neoadjuvant/adjuvant chemotherapy, immunotherapy, targeted therapy) to optimize management and improve outcomes.

Important surgical concepts and techniques in inguinal lymph node dissection.

PURPOSE OF REVIEW: Penile cancer is a rare disease with significant physical and psychosocial morbidity. It has a propensity to spread to the inguinal lymph nodes where it can progress to the pelvis and beyond. Here, we present a contemporary review on the surgical management of the lymph nodes. RECENT FINDINGS: Appropriate management of the lymph nodes is critical, and has been shown to impact survival for these patients. Those with lower stage disease can achieve cure with inguinal lymph node dissection (ILND), whereas a multidisciplinary approach is required in those with more extensive disease. Tertiary referral center should be strongly considered. Advances in surgical techniques have allowed for improved outcomes and lower morbidity postoperatively. Modified ILND can be safely performed for those with nonpalpable nodes, whereas diagnostic sentinel node biopsy is a good alternative in centers of experience. Minimally invasive ILND has recently gained popularity with favorable results at short-term follow-up. For those with more advanced disease, the literature remains scarce with no high-level evidence as of yet. SUMMARY: Early upfront surgery appears the best way to approach men with early involvement of the inguinal lymph nodes, whereas systemic therapy is typically reserved for higher volume disease. Clinical trial enrollment continues to be a priority to garner more evidence-based recommendations for this aggressive malignancy.

Current controversies and developments on the role of lymphadenectomy for penile cancer.

Penile squamous cell carcinoma is a rare cancer in men. The main prognosticators of survival for penile cancer patients remain the presence and the extent of lymph node metastasis. While radical inguinal lymphadenectomy has been the cornerstone of regional lymph node management for many years, it is still associated with significant morbidity and psychological distress. Recent developments in penile squamous cell carcinoma management have been met with some controversy in the urologic oncology community. Herein, we review the current controversies and developments on the role of inguinal lymphadenectomy for penile cancer.

Do Illuminated Foot Pedals Improve the Speed and Accuracy of Pedal Activation During Endoscopic Procedures?

PURPOSE: Endourologic procedures such as percutaneous nephrolithotomy (PCNL) employ the use of foot pedals in low-light operating room (OR) settings. These pedals can be especially difficult to locate or distinguish when several pedals are present during a single operation. Improper instrument activation in the OR has led to serious complications ranging from unintentional electrocautery to patient burns and even an intraoperative explosion. This study evaluates the impact of color-coded illumination on speed and efficiency of foot pedal activation. MATERIALS AND METHODS: During a simulated PCNL procedure, the foot pedals for a C-arm, laser, and ultrasonic lithotripter (USL) were placed in random positions. Ten participants performed pedal activation in a randomized sequence. Objective outcomes included time to instrument activation, number of attempted pedal presses, number of incomplete pedal presses, and number of incorrect pedal presses. Subjective preferences for pedal illumination were also determined. Data were analyzed using Mann-Whitney U, Wilcoxon signed-rank, and Chi-square tests with p < 0.05 indicating statistical significance. RESULTS: Illuminated foot pedals were associated with decreases in the average activation time for all instruments collectively (3.95 seconds vs 6.49 seconds; p = 0.017) and individually (C-arm: 3.07 seconds vs 4.21 seconds; p = 0.006; laser: 13.04 seconds vs 15.18 seconds; p < 0.001; USL: 3.28 seconds vs 4.91 seconds; p < 0.001) compared with nonilluminated pedals. Illuminated pedals were associated with fewer attempted pedal presses (33.5 vs 39.5; p = 0.007) and incomplete pedal presses (1.5 vs 8.5; p = 0.002). The number of incorrect pedal presses decreased with illumination, but this did not reach statistical significance (0 vs 0.5; p = 0.08). Participants reported that illumination simplified pedal activation and recommended its use (p < 0.01). CONCLUSION: Color-coded illumination improved the speed and efficiency of foot pedal activation during simulated PCNL. Participants subjectively preferred using illuminated foot pedals for endourologic procedures and felt that they improved safety and efficiency.

Jackets Off: The Impact of Laser Fiber Stripping on Power Output and Stone Degradation.

PURPOSE: To investigate the effect of laser fiber stripping on stone fragmentation and laser fiber power output. MATERIALS AND METHODS: In a benchtop simulation of laser lithotripsy, 20 BegoStone phantoms were positioned within a ureteral model and irradiated for 10 minutes at 8 Hz and 0.8 J. A freshly cleaved 365 µm laser fiber was used for all trials, with half of the fibers also undergoing stripping. Power output was measured at 1-minute intervals, beginning with an initial prelithotripsy recording at 0 minutes. Fiber tips were imaged with scanning electron microscopy. In a single-blinded manner, final masses of residual stone fragments were measured and used to quantify stone breakdown. Independent-sample Mann-Whitney U tests were performed with significance set at p < 0.05, comparing stripped and unstripped fiber tips with respect to power output and fraction of stone fragmentation. RESULTS: Mean power output after 1 minute of lasing was significantly greater in unstripped laser fibers (p = 0.015), while fibers, whether stripped or not, demonstrated no significant output differences prelithotripsy or at any time from 2 to 10 minutes. However, stripped laser fibers achieved significantly increased stone breakdown compared to unstripped fibers (p = 0.004), fragmenting 63 mg (25%) more of the initial stone mass per trial. CONCLUSIONS: Although unstripped laser fibers provided superior power output at 1 minute, output at all other time points was similar between stripped and unstripped fibers. However, despite similar optical output, stripped laser fibers achieved greater stone fragmentation, possibly due to improved contact between stone and fiber tip.

Percutaneous Externally Assembled Laparoscopic vs Laparoendoscopic Single-Site Nephrectomy in a Porcine Model: A Prospective, Randomized, Blinded, Study.

OBJECTIVE: To compare the outcomes between laparoendoscopic single-site (LESS) and a novel percutaneous externally assembled laparoscopic (PEAL) nephrectomy in an in vivo porcine model. MATERIALS AND METHODS: Ten female farm pigs were randomized to LESS nephrectomy (5) or PEAL nephrectomy (5). Operative times, estimated blood loss, and intraoperative and postoperative complications were compared. The surgeons used a Likert scale to grade difficulty of peritoneal access, port placement, tool assembly, hilar dissection, closure, and overall difficulty of surgery. Scar assessment was performed by a blinded plastic surgeon using the Vancouver Scar Scale. Descriptive statistics were reported as median and range. The Mann-Whitney U test was used for continuous and ordinal variables. A p value <0.05 was considered significant. RESULTS: Median operative time was significantly shorter in the PEAL group vs the LESS group (85 minutes vs 127 minutes, p = 0.03). Median Likert scores showed overall hilar dissection and nephrectomy to be significantly easier using PEAL compared with LESS (2 vs 9, p < 0.01 for both). The PEAL instruments left no visible scar at 5 feet in any animal, and only 1 out of 10 scars could be identified on physical examination. CONCLUSIONS: The PEAL surgical paradigm demonstrates nearly scarless outcomes while providing shorter operative times and easier performance than LESS nephrectomy in a porcine model.

The Impact of Operating Room Noise Upon Communication During Percutaneous Nephrostolithotomy.

OBJECTIVE: Equipment and personnel contribute to the overall noise level in the operating room (OR). This study aims to determine intraoperative noise levels during percutaneous nephrostolithotomy (PCNL) and the effects of this noise upon intraoperative communication. METHODS: A PCNL benchtop model was used to measure intraoperative noise and determine its effect upon communication in three progressively increasing sound environments (baseline ambient noise, ambient noise with PCNL equipment, and ambient noise with both PCNL equipment and music). Five trials with 20 different medical words/phrases were spoken by the surgeon and responses were recorded by the first assistant, anesthesiologist, and circulating nurse. In addition, noise levels during PCNL were compared to common environmental noise levels. RESULTS: In the bench top model, noise levels were 53.49 A-weighted decibels (dBA) with ambient noise, 78.79 dBA with equipment in use, and 81.78 dBA with equipment and music. At the ambient noise level, the first assistant, anesthesiologist, and circulator correctly recorded 100%, 100%, and 96% of the words, respectively. The correct response rate by the subjects decreased to 97% (p = 0.208), 81% (p = 0.012), and 56% (p < 0.001) upon addition of PCNL equipment, and 90% (p = 0.022), 48% (p = 0.002), and 13% (p < 0.001) upon addition of music and PCNL equipment in the first assistant, anesthesiologist, and circulator, respectively. In the simulated OR model, PCNL noise level (81.78 dBA) was comparable to a passing freight train at 30 feet (82.2 dBA, p = 0.44). CONCLUSION: Noise pollution decreases effective intraoperative communication during PCNL. It is important for surgeons to understand the effect noise can have on attempted communication to prevent errors due to miscommunication. In addition, methods to decrease intraoperative noise pollution and improve communication in the OR could improve patient safety and outcomes.

The use of non-invasive instruments in characterizing human facial and abdominal skin.

BACKGROUND AND OBJECTIVE: The skin is highly variable. This variation, although helpful for function, causes inconsistencies when assessed using subjective scales. The purpose of this study is to measure differences in skin on the face and abdomen using non-invasive, objective devices as a method to eliminate subjective error and help reduce intra- and inter-observer variability in clinical analysis. STUDY DESIGN/MATERIALS AND METHODS: Eighty-eight subjects between the ages of 18 and 61 were enrolled in this study. These subjects varied in age, ethnicity, and Fitzpatrick score. Facial analysis was performed by clinical evaluation and utilizing non-invasive objective devices which included the DermaScan C 20 MHz HFUS (Cyberderm, Broomall, PA), Tru Vu (Johnson and Johnson), BTC 2000 (SRLI Technologies, Nashville, TN), Derma Unit SSC3 (CK Electronic, Köln, Germany), and the Chromometer. RESULTS: Non-invasive devices were shown to be consistent and accurate through repeated measurement at each of the anatomical points with error rates of less than 5%. Chromometer measurements were able to categorize patients into Fitzpatrick level. DermaScan measurements demonstrated decreasing skin thicknesses associated with increasing age, smoking, and female gender. Derma Unit SSC 3 showed gender and sun exposure related differences in sebum concentration, pH, and moisture content. The Derma Unit SSC 3 sebum concentration also showed correlation with Tru Vu readings for clogged pores and bacterial activity. CONCLUSION: The skin assessment scales that are in use today are often prone to variability and inaccuracy due to their subjectivity. Use of the described objective non-invasive facial analysis method provides an accurate, objective analysis of human skin which can be used to measure changes pre- and post-operatively, or even screen patients prior to procedure to identify non-responders or those prone to adverse events. Utilization of these devices introduces a foundation on which a strong evidence-based approach to aesthetic medicine can be built.

Protein kinase C delta-mediated processes in cholecystokinin-8-stimulated pancreatic acini.

OBJECTIVES: To define the role of protein kinase C delta (PKC delta) in acinar cell responses to the hormone cholecystokinin-8 (CCK) using isoform-specific inhibitors and a previously unreported genetic deletion model. METHODS: Pancreatic acinar cells were isolated from (1) rat, and pretreated with a PKC delta-specific inhibitor or (2) PKC delta-deficient and wild type mice. Isolated cells were stimulated with CCK (0.001-100 nmol/L) and cell responses were measured. RESULTS: The PKC delta inhibitor did not affect stimulated amylase secretion from rat pancreatic acinar cells. Cholecystokinin-8 stimulation induced a typical biphasic dose-response curve for amylase secretion in acinar cells isolated from both PKC delta(-/-) and wild type mice, with maximal stimulation at 10-pmol/L CCK. Cholecystokinin-8 (100 nmol/L) induced zymogen and nuclear factor kappaB activation in both PKC delta(-/-) and wild type mice, although it was up to 50% less in PKC delta(-/-). CONCLUSIONS: In contrast to previous studies, this study has used specific and complementary approaches to examine PKC delta-mediated acinar cell responses. We could not confirm that it mediates amylase release but corroborated its role in the early stages of acute pancreatitis.