Moben Mirza

Gleason 6 prostate cancer: Translating biology into population health

PURPOSE Gleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management. MATERIALS AND METHODS Members of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes. RESULTS The Gleason scoring system was devised in the early 1960s, widely adopted by 1987 and revised in 2005 with a more restrictive definition of Gleason 6 disease. There is near consensus that Gleason 6 meets pathological definitions of cancer, but controversy about whether it meets commonly accepted molecular and genetic criteria of cancer. Multiple clinical series suggest that the metastatic potential of contemporary Gleason 6 disease is negligible but not zero. Population based studies in the U.S. suggest that more than 90% of men newly diagnosed with prostate cancer undergo treatment and are exposed to the risk of morbidity for a cancer unlikely to cause symptoms or decrease life expectancy. Efforts have been proposed to minimize the number of men diagnosed with or treated for Gleason 6 prostate cancer. These include modifications to prostate specific antigen based screening strategies such as targeting high risk populations, decreasing the frequency of screening, recommending screening cessation, incorporating remaining life expectancy estimates, using shared decision making and novel biomarkers, and eliminating prostate specific antigen screening entirely. Large nonrandomized and randomized studies have shown that active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes. CONCLUSIONS The definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening.

Effects of Immunonutrition for Cystectomy on Immune Response and Infection Rates: A Pilot Randomized Controlled Clinical Trial

UNLABELLED After radical cystectomy (RC), patients are at risk for complications including infections. The expansion of myeloid-derived suppressor cells (MDSCs) after surgery may contribute to the lower resistance to infection. Immune response and postoperative complications were compared in men consuming either specialized immunonutrition (SIM; n=14) or an oral nutrition supplement (ONS; n=15) before and after RC. MDSC count (Lin- CD11b+ CD33+) was significantly different between the groups over time (p=0.005) and significantly lower in SIM 2 d after RC (p<0.001). MDSC count expansion from surgery to 2 d after RC showed a weak association with an increase in infection rate 90 d after surgery (p=0.061). Neutrophil:lymphocyte ratio was significantly lower in SIM compared with ONS 3h after the first incision (p=0.039). Participants receiving SIM had a 33% reduction in postoperative complication rate (95% confidence interval [CI], 1-64; p=0.060) and a 39% reduction in infection rate (95% CI, 8-70; p=0.027) during late-phase recovery. The small sample size limits the study findings. PATIENT SUMMARY Results show that the immune response to surgery and late infection rates differ between radical cystectomy patients receiving specialized immunonutrition versus oral nutrition supplement in the perioperative period. TRIAL REGISTRATION ClinicalTrials.gov NCT01868087.

Erectile Dysfunction and Urinary Incontinence After Prostate Cancer Treatment

OBJECTIVES To review the current knowledge and treatment of incontinence and erectile dysfunction after treatment of localized prostate cancer. DATA SOURCES Journal and research articles. CONCLUSION The unique aspects of each treatment lends to different considerations in treatment techniques that mitigate incontinence and impotence. Although the pathophysiology of incontinence and impotence after various treatments can be different, the treatments can be similar in many ways. IMPLICATIONS FOR NURSING PRACTICE Nursing care of men undergoing treatment of prostate cancer begins at the time of diagnosis and continues throughout the management of the two main adverse effects of treatment: erectile dysfunction and urinary incontinence. Nursing care focuses heavily on psychosocial support and education to help patients to live with the aftermath of prostate cancer.

A comparison of radical perineal, radical retropubic, and robot-assisted laparoscopic prostatectomies in a single surgeon series.

Objective. We sought to compare positive surgical margin rates (PSM), estimated blood loss (EBL), and quality of life outcomes (QOL) among perineal (RPP), retropubic (RRP), and robot-assisted laparoscopic (RALP) prostatectomies. Methods. Records from 463 consecutive men undergoing RPP (92), RRP (180), or RALP (191) for clinically localized prostate cancer were retrospectively reviewed. Age, percent tumor volume, Gleason score, stage, EBL, PSM, and QOL using the expanded prostate cancer index composite (EPIC) were compared. Results. PSM were similar when adjusted for stage, grade, and volume. EBL was significantly less in the RALP (189 ml) group compared to both RPP (475 ml) and RRP (999 ml) groups. When corrected for nerve sparing, there were no differences in erectile function and sexual function amongst the three groups. Urinary summary and pad usage scores showed no significant differences. Conclusion. RPP, RRP, and RALP offer similar surgical and QOL outcomes. RALP and RPP demonstrate less EBL compared to RRP.

Leukemoid reaction and autocrine growth of bladder cancer induced by paraneoplastic production of granulocyte colony-stimulating factor – a potential neoplastic marker: a case report and review of the literature

IntroductionGranulocyte colony-stimulating factor produced by nonhematopoietic malignant cells is able to induce a leukemoid reaction by excessive stimulation of leukocyte production. Expression of granulocyte colony-stimulating factor and its functional receptors have been confirmed in bladder cancer cells. In vitro studies have demonstrated that granulocyte colony-stimulating factor/receptor exhibits a high affinity binding and this biological axis increases proliferation of the carcinoma. Urothelial carcinoma of the bladder is rarely associated with a leukemoid reaction and autocrine growth induced by paraneoplastic production of granulocyte colony-stimulating factor. In the world literature, there have been less than 35 cases reported in the last 35 years. The clinicopathological aspects, biology, prognosis and management of granulocyte colony-stimulating factor-secreting bladder cancers are poorly understood.Case presentationA 39-year-old Caucasian woman with an invasive high-grade urothelial carcinoma presented with hematuria and low-grade fevers. Laboratory tests revealed an elevated white blood cell count and absolute neutrophil count and an elevated 24-hour urine protein. Upon further evaluation she was found to have locally advanced high-grade urothelial carcinoma without nodal or distant metastasis. Her serum granulocyte colony-stimulating factor level was 10 times the normal limit. This led to the diagnosis of a paraneoplastic leukemoid reaction. Her white blood cell count immediately normalized after cystectomy but increased in concordance with recurrence of her disease. Unfortunately, she rapidly progressed and expired within 10 months from the time of first diagnosis.ConclusionsThis is one of the few cases reported that illustrates the existence of a distinct and highly aggressive subtype of bladder cancer which secretes granulocyte colony-stimulating factor. Patients presenting with a leukemoid reaction should be tested for granulocyte colony-stimulating factor/receptor biological axis. Moreover, granulocyte colony-stimulating factor could be a potential neoplastic marker as it can follow the clinical course of the underlying tumor and thus be useful for monitoring its evolution. Neoadjuvant chemotherapy should be considered in these patients due to the aggressive nature of these tumors. With a better understanding of the biology, this autocrine growth signal could be a potential target for therapy in future.

Venous thromboembolism after radical cystectomy: Experience with screening ultrasonography

Abstract Objectives: To detect the incidence of immediate postoperative deep vein thrombosis (DVT) using screening lower extremity ultrasonography (US) in patients undergoing radical cystectomy (RC) and to determine the rate of symptomatic pulmonary embolism (PE) after RC and identify risk factors for venous thromboembolic (VTE) events in a RC population. Patients and methods: We performed a retrospective review of prospective data collected on patients who underwent RC between July 2008 and January 2012. These patients underwent screening US at 2/3 days after RC to determine the rate of asymptomatic DVT. A chart review was completed to identify those who had a symptomatic PE. Univariate and multivariable analysis was used to identify risk factors associated with DVT, PE and total VTE events. Results: In all, 221 patients underwent RC and asymptomatic DVT was identified in 21 (9.5%) on screening US. Nine (4.5%) developed symptomatic PE at a median of 9 days, of which no patients had positive lower extremity US postoperatively. Increased length of hospital stay, increased estimated blood loss, and lower body mass index were linked to risk of PE, and only a previous history of DVT was associated with postoperative DVT. Conclusion: Patients who undergo RC are at high-risk for thromboembolic events and multimodal prophylaxis should be administered. Clinicians should be especially vigilant in those who demonstrate factors associated with higher risk for VTE events.

Alvimopan in an Enhanced Recovery Program Following Radical Cystectomy.

Abstract Background: Radical cystectomy (RC) carries a high complication rate, including post-operative ileus. Alvimopan is an FDA approved peripherally acting μ-opioid receptor antagonist that has shown favorable results for improved recovery of gastro-intestinal function resulting in decreased hospital length of stay. Many enhanced recovery pathways (ERP) have been published demonstrating improved outcomes with decreased hospital stay and morbidity. Objective: We evaluated the addition of alvimopan to an ERP in patients undergoing RC. Methods: Patients undergoing RC at our institution during the implementation phase of alvimopan to our established ERP were retrospectively reviewed. Effect of alvimopan as it related to the use of nasogastric tubes, time to initiation of regular diet, and length of hospital stay was assessed using Chi-squared and Student’s T-tests. Linear regression was performed for univariate analysis and binary logistic regression was performed as a multivariate assessment of the effect of alvimopan. Results: Between July 2011 and January 2013, 80 patients were identified who underwent RC under the ERP (34 alvimopan and 46 standard care). Age, sex, neoadjuvant chemotherapy, surgical technique (open vs. robotic), and type of urinary diversion were not different between groups. Alvimopan was associated with a reduction in mean time to regular diet (5.3 vs 4.1 days, p <  0.01) and a reduction in mean length of hospital stay (6.9 vs 5.7 days, p = 0.01). After controlling for other variables, alvimopan usage predicted for shorter time to regular diet and total hospital stay. Conclusions: Alvimopan may help to improve time to regular diet and decrease hospital stay in patients on an enhanced recovery pathway.

Post-prostatectomy erectile dysfunction: contemporary approaches from a US perspective.

Success of cancer surgery often leads to life-changing side effects, and surgical treatment for malignant urologic disease often results in erectile dysfunction (ED). Patients that undergo surgical prostatectomy or cystoprostatectomy will often experience impairment of erections due to disruption of blood and nerve supply. Surgical technique, nerve sparing status, patient age, comorbid conditions, and pretreatment potency status all have an effect on post-surgical ED. Regardless of surgical technique, prostatectomy results in disruption of normal anatomy and nerve supply to the penis, which governs the functional aspects of erection. A variety of different treatment options are available for men who develop ED after prostatectomy, including vacuum erection device, oral phosphodiesterase 5 inhibitors (PDE5I), intracorporal injections, and penile prosthesis. The vacuum erection device creates an artificial erection by forming a vacuum via suction of air to draw blood into the penis. The majority of men using the vacuum erection device daily after prostatectomy, regardless of nerve-sparing status, have erections sufficient for intercourse. Phosphodiesterase 5 inhibitors remain a common treatment option for post-surgical ED and are the mainstay of therapy. They work through cyclic adenosine monophosphate and cyclic guanine monophosphate pathways and are recommended in all forms of ED. Intracorporal injections or intraurethral use of vasoactive substances may be a good second-line therapy in men who do not experience improvement with oral medications. Surgical placement of a penile prosthesis is typically the treatment strategy of choice after other options have failed. Semi-rigid and inflatable devices are available with high satisfaction rates. With careful patient counseling and proper treatment selection, patient satisfaction and improved erectile function can be achieved. We advise that patients use a vacuum erection device daily in the early postoperative period in combination with an oral PDE5I. For patients who do not respond to a vacuum erection device or PDE5I, consideration should be given to intraurethral alprostadil, intracorporal injections, or a penile prosthesis.

Perioperative Immunonutrition Modulates Inflammatory Response after Radical Cystectomy: Results of a Pilot Randomized Controlled Clinical Trial

Purpose: Poor preoperative nutritional status is associated with a higher complication rate after radical cystectomy in patients with bladder cancer. Given the short interval between diagnosis and radical cystectomy, we compared the effect of short‐term specialized immunonutrition to that of a standard oral nutritional supplement on the acute inflammatory response and arginine status in patients treated with radical cystectomy. Materials and Methods: In this prospective, randomized study in 29 men 14 received specialized immunonutrition and 15 received oral nutritional supplement. Each group drank 3 cartons per day for 5 days before and 5 days after radical cystectomy. The Th1‐Th2 balance, plasma interleukin‐6 and plasma amino acids were measured at baseline, intraoperatively and on postoperative days 2, 14 and 30. Body composition was measured by dual energy x‐ray absorptiometry at baseline and on postoperative days 14 and 30. Differences in outcomes were assessed using the generalized linear mixed model. Results: In the specialized immunonutrition group there was a 54.3% average increase in the Th1‐Th2 balance according to the tumor necrosis factor‐&agr;‐to‐interleukin‐13 ratio from baseline to intraoperative day, representing a shift toward a Th1 response. In the oral nutritional supplement group the Th1‐Th2 balance decreased 4.8%. The change in the Th1‐Th2 balance between the specialized immunonutrition and oral nutritional supplement groups significantly differed (p <0.027). Plasma interleukin‐6 was 42.8% lower in the specialized immunonutrition group compared to the oral nutritional supplement group on postoperative day 2 (p = 0.020). In the specialized immunonutrition group plasma arginine was maintained from baseline to postoperative day 2 and yet the oral nutritional supplement group showed a 26.3% reduction from baseline to postoperative day 2 (p = 0.0003). The change in appendicular muscle loss between the groups was not statistically significant. Conclusions: Th1‐to‐Th2 ratios, peak interleukin‐6 levels and plasma arginine suggest that consuming specialized immunonutrition counteracts the disrupted T‐helper balance, lowers the inflammatory response and prevents arginine depletion due to radical cystectomy.

Management of Small Renal Masses in the Older Adult

Small renal masses in older adults are common and usually found incidentally. Although many small renal masses are benign, most are malignant. In older patients, the small renal mass poses a challenge because the treatment paradigm has to strike the balance between competing comorbidities and a lethal cancer. Partial nephrectomy, mainly via robot-assisted technique, has gained favor over radical nephrectomy as the intervention of choice. Cryoablation and radiofrequency ablation are also viable treatment options and have a role to play in patients who desire treatment but either are not suitable surgical candidates or prefer not to have a surgical intervention.