Chlamydia trachomatis Growth and Cytokine mRNA Response in a Prostate Cancer Cell Line In the present paper, we report that C. trachomatis can be efficiently propagated and affect mRNA expression for two major cytokines, relevant to tumor progression, in CWR-R1 cells, a malignant prostate cell line. CWR-R1 and McCoy cells, a classic cell line for chlamydial research, were grown and infected with C. trachomatis under similar conditions. Cell monolayers were harvested for RNA analysis and immunostaining with major outer membrane protein (MOMP) antibody at 24, 48, and 72 hours of the postinfection (hpi) period. It was shown that the infectious cycle of chlamydial pathogen in CWR-R1 cells resembles the progression of C. trachomatis infection in McCoy cells but with a few important differences. First of all, the initial stage of C. trachomatis propagation in CWR-R1 cells (24 hpi) was characterized by larger inclusion bodies and more intense, specific immunofluorescent staining of infected cells as compared with McCoy cells. Moreover, there was a corresponding increase in infective progeny formation in CWR-R1 cells along with mRNA for EUO, a crucial gene controlling the early phase of the chlamydial development cycle (24 hpi). These changes were more minimal and became statistically insignificant at a later time point in the infectious cycle (48 hpi). Altogether, these data suggest that the early phase of C. trachomatis infection in CWR-R1 cells is accompanied by more efficient propagation of the pathogen as compared with the growth of C. trachomatis in McCoy cells. Furthermore, propagation of C. trachomatis in CWR-R1 cells leads to enhanced transcription of interleukin-6 and fibroblast growth factor-2, genes encoding two important proinflammatory cytokines implicated in the molecular mechanisms of chemoresistance of prostate cancer and its ability to metastasize. The possible roles of reactive oxygen species and impaired mitochondrial oxidation in the prostate cancer cell line are discussed as factors promoting the early stages of C. trachomatis growth in CWR-R1 cells.
The Current Role of Osteoclast Inhibitors in Patients with Prostate Cancer Purpose. Prostate cancer (PCa) is one of the most frequently diagnosed malignancies worldwide. Hormonal deprivation therapy is a well-established treatment for locally advanced or metastatic diseases but exposes patients to the risk of osteoporosis and fragility fractures. Furthermore, the tropism of the PCa cells to osseous metastases increases the incidence of skeletal-related events (SREs). Methods. A nonsystematic review of the international literature was performed in respect to the use of osteoclast inhibitors zoledronic acid (ZA) and denosumab (DEN) in PCa patients. Results. DEN and ZA have proved their efficacy in preventing osteoporosis and bone mass loss in patients treated with hormonal therapy with no proven superiority of one agent over the other. However, the effectiveness in reducing fragility fractures has been proved only for DEN so far. In metastatic-free castrate-sensitive high-risk PCa patients, ZA has not shown any efficacy in preventing osseous metastasis, and evidence is lacking in favor or against the use of DEN. The use of osteoclasts inhibitors had no evident positive effect in overall and disease-specific survival in this group of patients. In advanced castrate-refractory malignancy, DEN has shown clinical superiority over ZA in preventing new SRE but not in overall survival. Conclusion. Superiority of DEN over ZA has been proved only in advanced castrate refractory disease in terms of preventing new SRE. In the rest of the cases, the selection of either agent should be based on the clinical condition of each patient and the cost of the treatment.
Comparison of Oxidative Effects of Two Different Administration Form of Oxybutynin in the Potential Target Tissues Oxybutynin is an important anticholinergic agent that prevents uncontrolled contractions in the treatment of overactive bladder (OAB). However, drugs containing oxybutynin have significant side effects such as dry eyes, dry mouth, increased heart rate, constipation, blurred vision, and confusion. In recent years, new delivery methods for this agent are being searched. One of them is vaginal delivery. In this study, we aimed to compare the effects of oxybutynin on oxidative parameters in the potential target tissues of the oral and vaginal delivery. Female New Zealand white rabbits () were divided into two groups: oral delivery and vaginal delivery. The animals were sacrificed 48 h after administration and nitric oxide (NOx), thiobarbituric acid-reactive substances (TBARs), and glutathione (GSH) levels were determined spectrophotometrically in the aorta, salivary gland, and small intestine tissue samples. Vaginal delivery significantly decreased NOx levels in all tissue samples as compared to oral delivery (). Moreover, it reduced TBARs levels in salivary gland and aorta tissue samples (). In the light on these findings, it can be said that vaginal delivery may decrease the oxidant-induced side effects of oxybutynin as compared to oral delivery.
Alexis Wound Retractor for Radical Cystectomy: A Safe and Effective Method for Retraction Surgical site infection rates remain a common postoperative problem that continues to affect patients undergoing urologic surgery. Our study seeks to evaluate the difference in surgical site infection rates in patients undergoing open radical cystectomy when comparing the Bookwalter vs. the Alexis wound retractors. After institutional review board approval, we performed a retrospective chart review from February 2010 through August 2017 of patients undergoing open radical cystectomy with urinary diversion for bladder cancer. We then stratified the groups according to whether or not the surgery was performed with the Alexis or standard Bookwalter retractor. Baseline characteristics and operative outcomes were then compared between the two groups, with the main measure being incidence of surgical site infection as defined by the CDC. We evaluated those presenting with surgical site infections within or greater than 30 postoperatively. Of 237 patients who underwent radical cystectomy with either the Alexis or Bookwalter retractor, 168 patients were eligible to be included in our analysis. There was no statistical difference noted regarding surgical site infections (SSIs) between the two groups; however, the trend was in favor of the Alexis (3%) vs. the Bookwalter (11%) at less than 30 days surgery. The Alexis wound retractor likely poses an advantage in reducing the incidence in surgical site infections in patients undergoing radical cystectomy; however, multicenter studies with larger sample sizes are suggested for further elucidation.
Quality of Health Information on the Internet for Prostate Cancer Introduction. To compare (1) the quality of prostate cancer health information on the Internet, (2) the difference in quality between websites appearing earlier or later in the search, and (3) the sources of sponsorship for each of these websites. Materials and methods. The top 150 listed websites on the Google search engine for each of the 11 search terms related to prostate cancer were analysed. Quality was assessed on whether the website conforms to the principles of the Health On the Net Foundation. Each of these websites was then reviewed to determine the main source of sponsorship. Statistical analysis was performed to determine if the proportion of HON accreditation varied among the different cohorts of listed websites and among the 11 search terms used. Results. In total, 1650 websites were analysed. Among these, 10.5% websites were HON-accredited. The proportion of HON-accredited websites for individual search terms ranged from 3.3% to 19.3%. In comparison with the search term of “Prostate cancer,” four search terms had statistically significant odds ratio of the rate of HON accreditation. Websites 51–150 were statistically less likely to have HON accreditation than websites 1–50. The top three website sponsors were journal/universities (28.8%), commercial (28.1%), and physician/surgeon (26.9%). Conclusions. The lack of validated and unbiased websites for prostate cancer is concerning especially with increasing use of the Internet for health information. Websites sponsored or managed by the government and national departments were most likely to provide impartial health information for prostate cancer. We need to help our patients identify valid and unbiased online health resources.
Outcomes from the Introduction of a Combined Urology Outpatient Clinic Background. A combined urology clinic staffed by four consultants and four non‐consultant hospital doctors (NCHDs) was introduced in our institution in October 2015. This clinic is supported by a pre‐clinic radiology meeting and a synchronous urology clinical nurse specialist (CNS) clinic with protected uroflow/trial of void slots. Herein, we report on the outcomes of this clinic in comparison with the standard format of urology outpatient review. Methods. We carried out a retrospective review of clinic attendances from May to July 2016. We recorded the number of new and return attendances, which team members had reviewed the patient and patient outcomes. We also calculated the waiting times for new patients to be reviewed in the outpatient clinic. Results. The combined urology clinic reviewed an average of 12 new and 46 return patients per clinic. The standard urology clinic reviewed an average of 8 new and 23 return patients per clinic. 54% of patients were seen by a consultant in the combined urology clinic, and 20% of patients were seen by a consultant in the standard urology clinic. The rate of patient discharge for new patients was 14.8% in the combined clinic compared to 5.9% in the standard clinic. Overall patient outcomes are outlined in the table. The waiting time for review of new patients in the combined clinic was reduced by 39% from 144 days to 89 days over a one-year period. Conclusions. The introduction of a combined urology outpatient clinic with the support of pre‐clinic radiology meeting and synchronous urology CNS clinic facilitates patient discharge.
The Benefits of Using a Small Caliber Ureteroscope in Evaluation and Management of Urethral Stricture Introduction and Objective. The proper evaluation of urethral strictures is an essential part of the surgical planning in urethral reconstruction. The proper evaluation of the stricture can be challenging in certain situations, especially when the meatus is involved. We propose that the use of a small caliber ureteroscope (4.5 Fr and 6.5 Fr) can offer additional help and use for the surgical planning in urethroplasty. Methods. We prospectively collected data on 76 patients who underwent urethroplasties in Kulkarni Reconstructive Urology Center, Pune, India and Thunder Bay Regional Health Sciences Center, Thunder Bay, Canada. Patients had retrograde and micturition urethrograms performed preoperatively. The stricture was assessed visually using a 6.5 Fr ureteroscope. If the stricture was smaller than 6.5 Fr, we attempted using the 4.5 Fr ureteroscope. In nonobliterated strictures, we attempted bypassing the stricture making sure not to dilate the stricture. A glide wire would be passed to the bladder under vision. Stricture length, tissue quality, presence of other proximal strictures, false passages, and bladder tumors or stones would be assessed visually. If the penile stricture was near obliterative (smaller than 4.5 Fr caliber), a two-staged procedure is elected to be performed. For proximal bulbar strictures, if the urethral caliber is less than 4.5 Fr and the stricture length is less than 1 cm, we perform a nontransecting anastomotic urethroplasty (NTAU). If the stricture length is >1 cm, we perform a double-face augmented urethroplasty (DFAU). If the urethral caliber is >4.5 Fr and particularly those who are sexually active, ventral inlay with buccal mucosal grafts (BMGs) is performed. In mid to distal bulbar strictures, if the urethral caliber is >4.5 Fr, our procedure of choice is dorsal onlay with BMG. For those with urethral caliber <4.5 Fr and a stricture less than 1 cm, we perform a NTAU. For strictures longer than 1 cm, we perform a DFAU. With the exception of trauma, we very rarely transect the urethra. For panurethral strictures, we almost exclusively perform Kulkarni one-sided dissection. Results. Urethroscopy was performed in 76 patients who presented for urethroplasty from July 2014 to September 2014 (in Pune) and between April 2016 and September 2017 (in Thunder Bay). Bypassing the stricture was achieved in 68 patients (89%) while it was unsuccessful in 8 patients (11%). In all unsuccessful urethroscopies, the stricture was near obliterative <4.5 Fr. Our surgical planning changed in (13) 17% of the cases. Out of 43 bulbar strictures, the decision was changed in (9) 21% where we performed 4 DFAU, 3 AAU (augmented anastomotic urethroplasty), and 2 EAU (end anastomotic urethroplasty). In 13 penile strictures, we opted for staged urethroplasty including 3 Johansons and 1 first-stage Asopa in 30.7%. In 20 panurethral urethroplasties, 1 patient (5%) had a urethral stone found in a proximal portion of the bulbar urethra distal to a stricture ring that was removed using an endoscopic grasper. Conclusion. The use of the small caliber ureteroscope can help in evaluation of the stricture caliber, length, and tissue quality. The scope can also aid in placing a guide wire, evaluating the posterior urethra, and screening for urethral or bladder stones. It can also improve the preoperative patient counselling and avoid unwanted surprises.
Analysis of the Learning Curve of Surgeons without Previous Experience in Laparoscopy to Perform Robot-Assisted Radical Prostatectomy Objective. To assess the learning curve in robot-assisted radical prostatectomy (RARP) performed by surgeons without previous experience in laparoscopic prostatectomy. Materials and Methods. We analyzed 119 patients submitted to RARP performed by two surgeons without previous experience in laparoscopic prostatectomy, with emphasis on the relevant outcomes such as continence, erectile function, and oncologic control with a minimum follow-up of 24 months. We used Fisher’s exact test and the chi-square test to investigate the existence of a relationship between the variables and analysis of variance (ANOVA) to verify possible statistically significant differences between groups, at the 5% level. Results. The patients’ age varied from 41 to 72 years (mean = 61.09), with 68 (57.14%) cases having intermediate or high risk. There was a consistent decline in operative time. Of the 119 patients, 80.67% were continent 6 months after surgery and 89.07% 12 months afterward, while 35.29% were potent 6 months after surgery and 60.50% 12 months following surgery. Twelve months after surgery, the trifecta outcome rate was 51.26% and the pentafecta rate was 31.09%. There was progressive postoperative improvement and maintenance of continence and sexual potency until the last patient was operated in our sample. Conclusions. Robot-assisted radical prostatectomy does not require previous experience in laparoscopic radical prostatectomy, but the learning curve is not short to achieve the plateau.
Undescended Testes and Laparoscopy: Experience from the Developing World Background. Cryptorchidism or undescended testes is the most common disorder of the male endocrine glands in children. With the advancements in laparoscopic techniques and instruments, laparoscopic orchidopexy has become the standard procedure in the management of nonpalpable undescended testes. Aim. To evaluate and determine the therapeutic role, sensitivity, and specificity of laparoscopy in localizing nonpalpable testes and the mean operative time, the conversion rate (and reasons thereof), postoperative wound infection, postoperative stay, and time taken for return to daily activities following laparoscopic orchidopexy or orchidectomy. Materials and Methods. This was a prospective study carried out in the Postgraduate Department of Surgery, Government Medical College, Srinagar, J&K, India, from May 2008 to August 2011. All patients who presented to the outpatient department with complaints of absent testes were examined, and the ones with nonpalpable testes were included in the study. Results. The mean operative time for bilateral and unilateral nonpalpable testis was 102.76 and 53.67 minutes, respectively. Minor postoperative wound infections were noted in 4 of our patients. Mean duration of hospital stay was 14.23 hrs for unilateral cases and 16.27 hrs for bilateral cases. Patients who underwent laparoscopic orchidopexy resumed their normal activities within 4 ± 1 days. Conclusion. Laparoscopy clearly demonstrates the anatomy and provides visual information upon which a definitive decision can be made for further management of the undescended nonpalpable testis.
The Modified Gil-Vernet Antireflux Surgery: A Successful Technique for High-Grade Vesicoureteral Reflux Correction in Children—Long-Term Follow-Up Introduction. Vesicoureteral reflux (VUR) is a common urologic anomaly in children. Many techniques have been offered to manage this condition, in which one of them is modified Gil-Vernet antireflux surgery. The study fullfiled to evaluate the efficacy and safety of modified Gil-Vernet antireflux surgery in correction of high-grade VUR. Materials and Methods. A retrospective study in which we evaluated efficacy, safety, and complications of modified Gil-Vernet antireflux surgery as a choice procedure for high-grade reflux in all patients who underwent it since 2000 to 2016 at 2 hospitals of Kermanshah University of medical sciences that all of them were done by one surgeon. Results. 183 patients with 290 high-grade refluxing units (grade IV or V) were reviewed. 182 refluxing units were grade IV, and 108 units were grade V. There were 76 (41.54%) patients with unilateral and 107 (58.46%) patients with bilateral VUR. Reflux in high-grade group corrected completely in 278 (95.86%) refluxing units and 175 patients (95.62%). Conclusions. Our results are remarkable and compatible with other techniques’ results. This simple and safe technique can correct bilateral VURs simultaneously; thus, it is rational to be considered for high-grade VUR correction. According to our results, we suggest the modified Gil-Vernet antireflux procedure for high-grade VUR correction as a simple, safe, and successful technique. This trial is registered with 67145/86/1233.
Efficacy of Transdermal Oxybutynin in the Treatment of Overactive Bladder Syndrome: Does It Make Sense Using It in 2017? Objectives. Evaluation of changes in symptoms among patients with overactive bladder syndrome treated with transdermal oxybutynin and tolerability after 12 months of follow-up. Methods. This was a multicenter, retrospective, single-cohort, observational study. Changes in symptoms were evaluated primarily with a 3-day voiding diary. Results were compared to baseline. Subgroup analyses were performed in patients previously treated for OAB or not and aged < 65 years versus ≥65 years. Results. Clinical records of 105 patients were examined; 92.4% were women. At 12 months, 58 patients continued to receive transdermal oxybutynin. Changes in symptoms according to the voiding diary were evaluated in 47 patients. Significant improvements from baseline were observed in urinary frequency (−2.6 voids/24 hours (95% CI: −3.5; −1.8), ); daily number of urgent episodes (−4.7 episodes/day (95% CI: −6.1; −3.6), ); and urge incontinence (−1.9 episodes/day (95% CI: −2.9; −1.3), ). No statistically significant differences were found in subgroup analyses. In total, 38.1% of patients had adverse events, primarily in the application site (27.6%). No severe systemic adverse events occurred. Only 6 patients (5.7%) reported dry mouth. Conclusions. Improved symptoms and good tolerability observed after 1 year of treatment with transdermal oxybutynin shows that it currently has a place in the treatment of OAB patients.
A Review of Outcomes and Technique for the Robotic-Assisted Laparoscopic Retroperitoneal Lymph Node Dissection for Testicular Cancer Objectives. The robotic-assisted laparoscopic retroperitoneal lymph node dissection (R-RPLND) represents a new frontier in the surgical management of testicular cancer in the realm of minimally invasive urologic oncology. We aimed to review the early outcomes as compared to the laparoscopic and open approaches as well as describe the operative technique for the R-RPLND. Materials and Methods. We reviewed all the literature related to the R-RPLND based on an electronic PubMed search up until July 2017. Results and Discussion. Encouraged by favorable early oncologic and safety outcomes for treatment of clinical stage (CS) I nonseminomatous germ cell tumor (NSGCT), the R-RPLND affords the same recovery advantages as the laparoscopic retroperitoneal lymph node dissection (L-RPLND) while offering greater dexterity, superior visualization, and a theoretically shorter learning curve for the surgeon. While R-RPLND has a promising future in the management of patients with primary and postchemotherapy NSGCT, larger and more vigorous prospective studies are needed before supplanting the open RPLND as the gold standard approach for primary low-stage NSGCT or becoming an equivalent surgical modality in the postchemotherapy setting.
Pattern of Ureteric Pathology Presenting to a Fistula Centre in Western Kenya Background. Ureteric pathology arises from surgical misadventures, trauma, and congenital anomalies. Early detection and treatment is of the essence. Objectives. To determine the types/etiology and outcome of ureteric pathology presenting to Gynocare Fistula Centre, Eldoret, Kenya. Methods. Descriptive retrospective study that evaluated patients presenting with ureteric pathology at Gynocare between 1st January 2012 and 31st December 2016. We pulled out patient charts and extracted and analyzed relevant data using STATA 13E statistical software. Results. We analyzed 33 charts, and their age ranged from 10 to 58 years. Annual proportion for 2012, 2013, 2014, 2015, and 2016 was 2.5%, 2.8%, 1.2%, 1.4%, and 3.0% respectively among all the fistula patients treated in the hospital. All the patients presented with urinary incontinence, and 7 (21.2%) had flank pain. Iatrogenic injuries contributed 84.8% (28), and 3 (9.1%) were congenital while trauma and infection had 1 each. Of those resulting from surgical misadventures, 17 (60.7%) were from obstetric while 11 (39.2%) were from gynecological surgery. All the injuries were in the distal third of the ureter; 5 were bilateral; and 11 were left sided while 17 were right-sided. Repair and/or reimplantation was successful in 31 (93.93%) of the patients. Conclusion. Highest proportion of ureteric pathologies was accounted for by iatrogenic causes and surgical repair and/or reimplantation has a high success rate.
The Use of Modified Templates in Early and Advanced Stage Nonseminomatous Germ Cell Tumor The surgical management of both early and advanced stage germ cell tumors of the testis remains a complex process of surgical decision making to maximize oncologic control while minimizing morbidity. Over the past 5 decades, the evolution of the surgical template for retroperitoneal lymphadenectomy (RPLND) has resulted in important modifications to achieve these goals. In this review, we will characterize the historical motivating factors that led to the modified template, outline patient and clinical factors in selecting these approaches in both early and advanced stage disease, and briefly discuss future horizons for their implementation.
Adjuvant Therapy for Stage IB Germ Cell Tumors: One versus Two Cycles of BEP Testicular germ cell tumours are the commonest tumours of young men and are broadly managed either as pure seminomas or as ‘nonseminomas’. The management of Stage 1 nonseminomatous germ cell tumours (NSGCTs), beyond surgical removal of the primary tumour at orchidectomy, is somewhat controversial. Cancer-specific survival rates in these patients are in the order of 99% regardless of whether surveillance, retroperitoneal lymph node dissection, or adjuvant chemotherapy is employed. However, the toxicities of these treatment modalities differ. Undertreating those destined to relapse exposes them to the potentially significant toxicities of 3-4 cycles of bleomycin, etoposide, and cisplatin (BEP) chemotherapy. Conversely, giving adjuvant chemotherapy to all patients following orchidectomy results in overtreatment of a significant proportion. Therefore, the challenge lies in delineating the patient population who require adjuvant chemotherapy and in determining how much chemotherapy to give to adequately reduce relapse risk. This chapter reviews the factors to be considered when adopting a risk-adapted strategy for giving adjuvant chemotherapy in Stage 1B NSGCT sand discusses the data regarding the number of BEP cycles to administer.
Experience with Renal Autotransplantation: Typical and Atypical Indications Introduction and Objectives. Renal autotransplantation is a kidney-saving surgical procedure used in selected patients. The purpose of this report is to review nine typical and atypical indications for kidney autotransplantation and evaluate its effectiveness in maintaining kidney function and avoiding cancer recurrence. Materials and Methods. From 1999 till 2014, nine renal autotransplantations were performed in our center. A retrospective case review was done. Four of nine patients had a solitary functioning kidney. Typical indications for autotransplantation included extended ureteric disease in 5 patients, intrasinusal tumor on a solitary kidney in 1 patient, and renal artery aneurysm in 1 patient. Atypical indications consisted in bilateral urothelial tumors in 1 patient and interrupted live kidney transplantation in 1 patient. Mean cold ischemia time was 209 minutes. Demographic factors, indications, renal function before and after surgery, and in the long term, cancer recurrence and disease-free survival were evaluated. Results. Renal function was maintained in 8 patients during the early follow-up. No serious complications occurred in the postoperative period. Median duration of follow-up was 50 months. In 4 patients with a normal contralateral kidney, mean preoperative and at discharge creatinine clearance were 105.45 ml/min and 121.02 ml/min, respectively. Although values showed an improvement in the kidney function, the difference was not significant ( value 0.3). In the other 4 patients with a solitary kidney, mean discharge creatinine clearance was 99.24 ml/min surprisingly higher than the preoperative value 96.92 ml/min. At the last follow-up, kidney function was preserved for the two groups (normal contralateral kidney/solitary kidney) with relatively stable creatinine clearance values: 108.45 ml/min and 85.9 ml/min, respectively. No patients required secondary dialysis. Conclusion. Renal autotransplantation is a rare, safe, and effective surgical procedure for the treatment of complex urologic conditions. In some instances, it may be of great utility for kidney salvage in some carefully selected patients.
Antibiotic Prophylaxis with Trimethoprim-Sulfamethoxazole versus No Treatment after Mid-to-Distal Hypospadias Repair: A Prospective, Randomized Study Purpose. To evaluate the impact of prophylactic antibiotics after distal hypospadias repair on postoperative bacteriuria, symptomatic urinary tract infection, and postoperative complications in a prospective, randomized trial. Materials and Methods. Consecutive patients aged 6 months to 2 years were enrolled at our institution between June 2013 and May 2017. Consenting patients were randomized to antibiotic prophylaxis with trimethoprim-sulfamethoxazole versus no antibiotic. Patients had catheterized urine samples obtained at surgery and 6–10 days postoperatively. The primary outcome was bacteriuria and pyuria at postoperative urine collection. Secondary outcomes included symptomatic urinary tract infection and postoperative complications. Results. 70 patients consented to the study, of which 35 were randomized to receive antibiotics compared to 32 who did not. Demographics, severity of hypospadias, and type of repair were similar between the groups. Patients in the treatment group had significantly less pyuria (18%) and bacteriuria (11%) present at stent removal compared to the nontreatment group (55% and 63%; and , resp.). No patient had a symptomatic urinary tract infection. There were 11 postoperative complications. Conclusions. Routine antibiotic prophylaxis appears to significantly decrease bacteriuria and pyuria in the immediate postoperative period; however, no difference was observed in symptomatic urinary tract infection or postoperative complications. Clinical Trial Registration Number NCT02593903.
Conventional-Dose versus High-Dose Chemotherapy for Relapsed Germ Cell Tumors The majority of metastatic germ cell tumors (GCTs) are cured with cisplatin-based chemotherapy, but 20–30% of patients will relapse after first-line chemotherapy and require additional salvage strategies. The two major salvage approaches in this scenario are high-dose chemotherapy (HDCT) with autologous stem cell transplant (ASCT) or conventional-dose chemotherapy (CDCT). Both CDCT and HDCT have curative potential in the management of relapsed/refractory GCT. However, due to a lack of conclusive randomized trials, it remains unknown whether sequential HDCT or CDCT represents the optimal initial salvage approach, with practice varying between tertiary institutions. This represents the most pressing question remaining for defining GCT treatment standards and optimizing outcomes. The authors review prognostic factors in the initial salvage setting as well as the major studies assessing the efficacy of CDCT, HDCT, or both, describing the strengths and weaknesses that formed the rationale behind the ongoing international phase III “TIGER” trial.
Immune-Related Concepts in Biology and Treatment of Germ-Cell Tumors Germ-cell tumors (GCTs) are highly curable with chemotherapy. Salvage chemotherapy or surgery can cure a proportion of patients, but the ones failing these treatments will die of their disease in the young age. Immune checkpoint pathways are emerging as powerful targetable biomarkers, and a significant preclinical and clinical research is underway to widen our knowledge and expand the treatment possibilities with immune therapy. The concept of immune modulation that was currently adopted in many solid tumors is understudied in GCTs. Herein, we summarize the current knowledge of published literature discussing the immune mechanisms and immune therapy in GCTs.
Urinary Bladder Cancer in Egypt: Are There Gender Differences in Its Histopathological Presentation? We investigated gender differences in the histopathologic presentation of bladder cancer cases in Egypt, where both urothelial cell carcinoma (UC) and squamous cell carcinoma (SCC) types are highly prevalent. We used logistic regression to estimate the unadjusted (OR) and adjusted odds ratio (AOR) and 95% confidence interval (CI) of the associations between gender and different histopathologic and sociodemographic parameters of 2,186 confirmed cases of primary bladder cancer (1,775 males and 411 females; 784 SCC and 1,402 UC). There were no statistically significant gender differences in tumor grade, stage, mucosal ulcer, or inflammatory cystitis, regardless of the cancer type, but men were less likely than women to have undergone cystectomy with pelvic lymphadenectomy. Having Schistosoma haematobium (SH) ova in the bladder tissue was significantly associated with male gender in the fully adjusted model of either SCC (AOR (95% CI) = 2.12 (1.15–3.89)) or UC cases (3.78 (1.89–7.55)). Compared to females, male cases were significantly older at time of diagnosis and smokers. In Egypt, regardless of the type of bladder cancer (SCC or UC), male more than female cases had evidence of SH infection, but not other histopathologic differences, in bladder tissue specimens.
Supine Percutaneous Nephrolithotripsy in Double-S Position Background. At present, the percutaneous nephrolithotripsy (PCNL) is performed both in supine and in prone position. The aim of this paper is to describe an innovative position during PCNL. Methods. We describe a supine position. The patient’s legs are slightly abducted at the hips. The thorax is laterally tilted (inclination 30°–35°) and kept in the right position by one or two gel pads placed between the scapula and the vertebrae. External genitalia can be accessed at any time, so that it is always possible to use flexible instruments in the upper urinary tract. We used this position for a period of 12 months to treat with PCNL 45 patients with renal lithiasis. Results. All the procedures were successfully completed without complications, using the position we are describing. The following are some of its benefits: an easier positioning of the patient; a better exposure of the flank for an easier access to the posterior renal calyces of the kidney; a lower risk of pressure injuries compared to positions foreseeing the use of knee crutches; the possibility of combined procedures (ECIRS) through the use of flexible instruments; and a good fluoroscopic visualization of the kidney not overlapped by the vertebrae. Conclusions. This position is effective, safe, easy, and quick to prepare and allows for combined anterograde/retrograde operations.
Dissecting the Evolving Risk of Relapse over Time in Surveillance for Testicular Cancer Testicular cancer is the most common malignancy in young men, and the incidence is increasing in most countries worldwide. The vast majority of patients present with clinical stage I disease, and surveillance is being increasingly adopted as the preferred management strategy. At the time of diagnosis, patients on surveillance are often counselled about their risk of relapse based on risk factors present at diagnosis, but this risk estimate becomes less informative in patients that have survived a period of time without experiencing relapse. Conditional survival estimates, on the other hand, provide information on a patient’s evolving risk of relapse over time. In this review, we describe the concept of conditional survival and its applications for surveillance of clinical stage I seminoma and nonseminoma germ cell tumours. These estimates can be used to tailor surveillance protocols based on future risk of relapse within risk subgroups of seminoma and nonseminoma, which may reduce the burden of follow-up for some patients, physicians, and the health care system. Furthermore, conditional survival estimates provide patients with a meaningful, evolving risk estimate and may be helpful to reassure patients and reduce potential anxiety of being on surveillance.
Toxicities Associated with Cisplatin-Based Chemotherapy and Radiotherapy in Long-Term Testicular Cancer Survivors Testicular cancer has become the paradigm of adult-onset cancer survivorship, due to the young age at diagnosis and 10-year relative survival of 95%. This clinical review presents the current status of various treatment-related complications experienced by long-term testicular cancer survivors (TCS) free of disease for 5 or more years after primary treatment. Cardiovascular disease and second malignant neoplasms represent the most common potentially life-threatening late effects. Other long-term adverse outcomes include neuro- and ototoxicity, pulmonary complications, nephrotoxicity, hypogonadism, infertility, and avascular necrosis. Future research efforts should focus on delineation of the genetic underpinning of these long-term toxicities to understand their biologic basis and etiopathogenetic pathways, with the goal of developing targeted prevention and intervention strategies to optimize risk-based care and minimize chronic morbidities. In the interim, health care providers should advise TCS to adhere to national guidelines for the management of cardiovascular disease risk factors, as well as to adopt behaviors consistent with a healthy lifestyle, including smoking cessation, a balanced diet, and a moderate to vigorous intensity exercise program. TCS should also follow national guidelines for cancer screening as currently applied to the general population.
Combined Dorsal and Ventral Onlay Buccal Graft Technique for Large and Complex Penile Strictures Purpose. To present a modified technique of managing extensive penile urethral strictures with dorsal and ventral onlay buccal mucosa grafts. Patients and Methods. From October 2014 to January 2016, a total of 12 patients underwent urethroplasty for penile urethral strictures, using dorsal and ventral onlay grafts from buccal mucosa. The mean age was 42.75 (17–71). All patients completed the IPSS and QoL questionnaire, and uroflowmetry was done preoperatively. After surgery, the follow-up included completion of IPSS and QoL questionnaire and measuring of uroflow at 1, 3, 6, and 12 months. Postoperative urethrography was performed in complex cases or in the event of deterioration of voiding symptoms. Results. The mean length of the strictures was 5.45 (2, 2–16) cm. Mean Qmax changed from 3.45 ml/sec preoperatively to 18.33 postoperatively, and mean IPS score significantly decreased from 20.1 preoperatively to 8.98 postoperatively. All values were statistically significant (). No intraoperative or immediate postoperative complications were recorded. Overall, at 12 months, 11 out of 12 patients (91.6%) had a marked improvement in quality of life and uroflowmetry parameters. Conclusions. In the properly selected patient, the combined use of double graft for penile urethral strictures can be successful with minimal morbidity, at short-term follow-up.
Kidney Stone Disease: An Update on Current Concepts Kidney stone disease is a crystal concretion formed usually within the kidneys. It is an increasing urological disorder of human health, affecting about 12% of the world population. It has been associated with an increased risk of end-stage renal failure. The etiology of kidney stone is multifactorial. The most common type of kidney stone is calcium oxalate formed at Randall’s plaque on the renal papillary surfaces. The mechanism of stone formation is a complex process which results from several physicochemical events including supersaturation, nucleation, growth, aggregation, and retention of urinary stone constituents within tubular cells. These steps are modulated by an imbalance between factors that promote or inhibit urinary crystallization. It is also noted that cellular injury promotes retention of particles on renal papillary surfaces. The exposure of renal epithelial cells to oxalate causes a signaling cascade which leads to apoptosis by p38 mitogen-activated protein kinase pathways. Currently, there is no satisfactory drug to cure and/or prevent kidney stone recurrences. Thus, further understanding of the pathophysiology of kidney stone formation is a research area to manage urolithiasis using new drugs. Therefore, this review has intended to provide a compiled up-to-date information on kidney stone etiology, pathogenesis, and prevention approaches.
Pediatric Germ Cell Tumors: A Developmental Perspective Germ cell tumors (GCTs) arising in infants, children, and adolescents present a set of special challenges. GCTs make up about 3% of malignancies in children aged 0–18 and nearly 15% of cancers in adolescents. Epidemiologic and molecular evidence suggests that GCTs in young children likely represent a distinct biologic group as compared to GCTs of older adolescents and adults. Despite this difference, pediatric GCTs are typically treated with cisplatin-based multiagent regimens similar to those used in adults. There is evidence that children are particularly vulnerable to late effects of conventional therapy, including ototoxicity, pulmonary abnormalities, and secondary malignancies, motivating the search for molecular targets for novel therapies. Evidence is accumulating that the genes and mechanisms controlling normal germ cell development are particularly relevant to the understanding of germ cell tumorigenesis. Perturbations in the epigenetic program of germ cell differentiation, with resulting effects on the regulation of pluripotency, may contribute to the marked histologic variability of GCTs. Perturbations in the KIT receptor signaling pathway have been identified via next-generation sequencing studies and in genome-wide association studies of testicular cancer susceptibility. Here, we review these and other biological insights that may fuel further translational and clinical research in childhood GCTs.
Retroperitoneal Lymph Node Dissection as Primary Treatment for Metastatic Seminoma Reducing the long-term morbidity in testicular cancer survivors represents a major area of interest. External beam radiation therapy and systemic chemotherapy are established treatments for seminoma; however, they are associated with late toxicities such as cardiovascular disease, insulin resistance, and secondary malignancy. Retroperitoneal lymph node dissection (RPLND) is a standard treatment for nonseminomatous germ cell tumors (NSGCT) that has minimal long-term morbidity. Given the efficacy of RPLND in management of NSGCT, interest has developed in this surgery as a front-line treatment for seminoma with isolated lymph node metastasis to the retroperitoneum. Four retrospective studies have shown promising results when surgery is performed for seminomas with low-volume retroperitoneal metastases. To better determine if RPLND can be recommended as a primary treatment option, two prospective clinical trials (SEMS and PRIMETEST) are underway. This review will examine the literature, discuss the benefits/limitations of RPLND, and compare the methodologies of the two ongoing clinical trials.
Adolescent and Young Adult Testicular Germ Cell Tumors: Special Considerations While testicular germ cell tumors (T-GCTs) make up only 0.5% of pediatric malignancies and less than 2% of adult malignancies, they comprise 14% of adolescent malignancies, making it the most common solid tumor in this age group. The transition in incidence at this age is also accompanied by a transition in tumor histology with adolescents having mostly pure embryonal carcinoma and mixed nonseminomatous germ cell tumors. Similar to T-GCTs of all ages, surgical excision with orchiectomy is the standard initial step in treatment. Chemotherapy, retroperitoneal lymph node dissection, and targeted treatment of distant metastases make even widely disseminated disease treatable and curable. For this reason, in many ways, the future focus has expanded beyond survival alone to emphasize quality of life issues such as fertility and hypogonadism. However, adolescents remain the age group least studied or understood as they fall in between the ages included in most study designs. Also, they require the most psychosocial support because of the challenges unique to the adolescent period. In this review, we aim to highlight the known outcome data for T-GCTs in this population and also to discuss the unique aspects of treatment and support for this age group.
Impact on the Quality of Erections after Completing a Low-Intensity Extracorporeal Shock Wave Treatment Cycle on a Group of 710 Patients Objective. The aim of this study is to evaluate the response to low-intensity extracorporeal shock wave therapy in a group of patients with organic vascular erectile dysfunction. Materials and Methods. This is an observational retrospective study. The researchers reviewed 710 patients with a clinical diagnosis of organic vascular erectile dysfunction (ED) of more than 3-month duration from male sexual health clinics of the Boston Medical Group from 12 cities in Spain and 4 in Mexico. Patients received 5 outpatient shock wave therapy sessions. They were evaluated with the erection hardness score (EHS) before the first session (n = 710), at the end of the last session (n = 710), and one month after the last session (n = 412). Results. In the first examination, the EHS improved in 43.1% (306/710) of subjects compared to the baseline measurement and ability to penetrate increased from 26.8% to 44% . In the second examination, the ability to penetrate was 37.9%, lower than in the first but higher than the baseline .Conclusions. The results suggest that the shock wave therapy with or without concomitant treatments improved the quality of erections in patients with erectile dysfunction treated in specialised male sexual health clinics. This trial is registered with NCT03237143.
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