Sequence Variants in PSMB8/PSMB9 Immunoproteasome Genes and Risk of Urothelial Bladder Carcinoma.

BACKGROUND: The PSMB8 and PSMB9 immunoproteasome genes are essential in cell processes, such as decisions on cell survival or death, the cell cycle, and cellular differentiation. Because recent evidence has demonstrated an immunological role for proteasomes in various malignancies, including urothelial bladder carcinoma (UBC), we evaluated single nucleotide polymorphisms (SNPs) in PSMB9 and PSMB8. We determined any associations between these SNPs and susceptibility to UBC in the Saudi community. METHODS: Samples of genomic DNA were taken from buccal cells of 111 patients with UBC and 78 healthy controls. TaqMan Real-Time PCR was used to determine genotype distributions and allele frequencies for the PSMB9 rs17587 G>A and PSMB8 rs2071543 G>T SNPs. We used SNPStats (https://www.snpstats.net) to choose each SNP's best interactive inheritance model. RESULTS: The PSMB9 rs17587 SNP was associated with the risk of UBC (odds ratio [OR] = 5.21, P < 0.0001). In contrast, the PSMB8 rs2071543 SNP showed no association with UBC risk (OR = 1.13, P = 0.7871). In terms of genotypic distribution, the rs17587 G>A SNP was more frequent in UBC cases than controls in both the dominant (OR = 7.5; 95% confidence interval, 3.7-15.1; P = 0.0051) and recessive (OR = 17.11, 95% confidence interval 5.1-57.4; P = 0.0026) models. Genotypic distribution of the PSMB8 rs2071543 G>T SNP was not significantly different between cases and controls in any interactive inheritance models (P > 0.05). CONCLUSION: These results suggest a potential role for PSMB9 as a biomarker for increased UBC risk. Discovering more genetic variants within immunoproteasome genes related to antigen presentation could help further our understanding of this risk.

Effective ureteral access sheath insertion during flexible ureteroscopy: Influence of the ureteral orifice configuration.

INTRODUCTION: We sought to determine the possible predictors for effective insertion of the ureteral access sheath (UAS) during flexible ureteroscopy (fURS) in virgin ureters and their impact on postoperative ureteral wall injury and the procedural outcome. METHODS: A retrospective review of prospectively collected data was performed for all consecutive patients scheduled for fURS of virgin ureters at two tertiary care centers between 2018 and 2020. Demographics, stone characteristics, and perioperative data, including the configuration of the ureteral orifice (UO) over introductory guidewire insertion, were collected. Multivariate logistic regression was used to detect possible predictors of successful UAS insertion. RESULTS: In total, 128 patients who underwent primary fURS were included, with a mean age of 43.3±12.3 years and a stone burden of 12.3±6.9 mm. One hundred and ten patients (85.9%) achieved successful ureteral access insertion, including 81 (63.3%) without ureteral dilatation and 35 with dilation, of which 29 (22.7%) had a successful UAS afterward, while six failed. Total patients who underwent ureteral orifice dilatation were 35. 29 had a successful UAS afterward, while 6 failed. Patients who underwent successful UAS placement into virgin ureters were significantly older and had a lower body mass index (BMI). A tent-shaped UO over the guidewire led to successful UAS insertion. In multivariate regression analysis, cases with BMI <30 kg/m2 (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.28-7.03) and those with a tent-shaped UO over the introductory guidewire (OR 6.60, 95% CI 3.8-7.2) maintained their significance to predict successful UAS insertion into virgin ureters. Nine patients (8.2%) had ureteral mucosal injuries, and the overall stone-free rate was 78.2%. CONCLUSIONS: Patients with normal BMIs and tent-shaped UOs over the introductory guidewires are more likely to achieve primary UAS insertion without the need for ureteral dilation.

High-Grade Non-Muscle Invasive Bladder Cancer: When to Move to Early Radical Cystectomy?

Objectives To compare the outcomes of bladder preservation therapy with early or deferred radical cystectomy (RC) in high-grade non-muscle invasive bladder cancer. Methods Prospectively collected data were obtained for patients undergoing transurethral resection of bladder tumor (TURBT) at a tertiary care center between 2007 and 2018. Patients with a high-grade tumor (HGT1) were divided into three groups, depending on the treatment plan: conservative (GI), early RC (GII), or deferred RC (GIII). Kaplan-Meier analysis was performed to assess the cancer-specific survival (CSS). Results Seventy-one patients were included, and the patients had a median (range) age of 49 (32-72) years. The GI, GII, and GIII groups included 34 (47.9%), 14 (19.7%), and 23 (32.4%) patients, respectively. A significantly lower number of GII patients underwent >2 TURBTs (14.3% vs. 100%, p<0.001). Compared to GIII patients, GII patients had a shorter time to RC from the initial diagnosis (5.7 vs. 36.2 months, p=0.03). Ileal conduit and orthotropic bladder diversions were comparable between both groups, with significantly higher postoperative complications in GIII patients. The median (IQR) follow-up times for the groups were 84 (49-102), 82 (52-112), and 73 (36-89) months, respectively. The five-year and 10-year CSS for GII and GIII patients was 79% vs. 75% and 78% vs. 64%, respectively (log rank=0.19). Conclusion Early RC should be considered an alternative treatment option in selected patients with HGT1 BC with expected longer life expectancy, which may significantly decrease postoperative complications and improve the CSS. However, selection bias in the current retrospective study may influence these outcomes.

Robot-Assisted Radical Prostatectomy in Low-Volume Regions: Should It Be Abandoned or Adopted? A Multi-Institutional Outcome Study.

Purpose: To present multinational experience in robot-assisted radical prostatectomy (RARP) by fellowship-trained expertise in low-volume regions in Gulf Cooperation Council (GCC) countries and to compare the current results with global outcomes reported in recent meta-analyses. Methods: A retrospective review of prospectively collected data was performed for patients undergoing RARP for localized prostate cancer (PCa). Three fellowship-trained surgeons at four academic and referral centers in Saudi Arabia and Kuwait performed all procedures between February 2014 and December 2019. Data on demographics, perioperative characteristics, pathology, and adverse events were collected. Results: A total of 207 patients were included with a median (IQR) follow-up duration of 28 (15-38) months. The median prostate volume and prostate-specific antigen were 42 (32-53) g and 9.1 (5.8-14.1) ng/mL, respectively. While 65.2% of patients had a Gleason score ≥7, 20% had grade group 4 disease, and 7.8% had ≥cT3 disease. The mean ± SD operative time was 203 ± 52 minutes, and the mean estimated blood loss was 158 ± 107 mL. Only 4 (1.9%) patients received perioperative blood transfusions. Positive surgical margins were observed in 21.7% of patients, all of whom had ≥pT3 disease. There were 23 complications in 18 (8.7%) patients, including Clavien-Dindo grade III complications in 2.4%. At the 12-month follow-up, 35.8% of patients were potent, 94.6% were continent, and 9.2% had biochemical recurrence. Conclusions: The safety and efficacy of RARP by fellowship-trained expertise in GCC countries were well established. The outcomes seem promising and comparable to international centers and should improve with increasing case volume and fellowship-trained expertise.

Explication of the roles of prostate health index (PHI) and urokinase plasminogen activator (uPA) as diagnostic and predictor tools for prostate cancer in equivocal PSA range of 4-10 ng/mL.

BACKGROUND: Prostate cancer (PCa) is one of the most commonly encountered cancers and the leading cause of death worldwide. Currently used biomarkers accounts difficulties in discriminating benign from malignant cases or predicting outcome, so investigating new biomarkers performance is needed. OBJECTIVES: Assessment of diagnostic and predictor roles of prostate health index (PHI) and urokinase plasminogen activator (uPA) in PCa. METHODS: 194 males with initial tPSA of 4-10 ng/mL were categorized into three groups: PCa, benign prostatic hyperplasia (BPH) and healthy control. Serum levels of tPSA, fPSA, p2PSA, and uPA were performed by ELISA with calculation of PHI as (p2PSA/fPSA) × âˆšPSA. RESULTS: PHI and uPA were significantly higher in PCa patients relevant to BPH and healthy control (p ≤ 0.001). Both markers outperformed all assessed biomarkers and showed the highest area under the curve (AUC) in ROC curve analysis. Both were significantly higher in PCa patients with {Gleason score ≥ 7, late stages (cT2b,c; T3), LN extension and distant metastasis}relative to their counterparts. Additionally, PHI and uPA and were independent predictors of distant metastasis and Gleason score ≥ 7, while PHI was predictor of LN invasion (ß = 0.25, p = 0.004). CONCLUSION: PHI and uPA would be of potential value in discriminating between PCa, BPH and healthy men in addition, both are promising as independent predictors of adverse pathological features.

Assessment of expression levels of leptin and leptin receptor as potential biomarkers for risk of prostate cancer development and aggressiveness.

BACKGROUND: Prostate cancer (PCa) is one of the most frequently diagnosed cancers worldwide. Despite the growing evidence associating obesity and adipokines, particularly leptin and its receptors, with cancer development and progression, it is still a debatable matter in PCa. OBJECTIVES: We aimed to assess the role of leptin and its receptors as potential biomarkers for the risk of PCa development and aggressiveness. METHODS: In this study, 176 men were included and categorized according to an established histopathological diagnosis into three age- and BMI-matched groups. The PCa group included 56 patients while the BPH group and the control group comprised 60 men each. Serum levels of total PSA (tPSA) were assessed by ELISA and mRNA expression levels of leptin and leptin receptors were assessed by RT-PCR. RESULTS: Leptin and leptin receptor mRNA expression levels were significantly higher in PCa patients relative to BPH and to healthy control men. Both were overexpressed in PCa patients with aggressive and distantly metastasizing tumors compared to patients with confined tumors. Leptin receptor mRNA was an independent predictor of high Gleason score ≥ 7, distant metastasis, LN, and seminal vesicles invasion. CONCLUSION: Leptin and its receptors are suggested to be potential biomarkers for PCa; leptin receptor mRNA might predict risk and aggressiveness of PCa.

Serum Levels of Selenium, Zinc, Copper, Manganese, and Iron in Prostate Cancer Patients.

BACKGROUNDS: Variations of trace element contents may be associated with several diseases including metabolic disorders, cellular growth disturbance, mutation and tumorigenesis. Prostate cancer is the second most common male cancer worldwide and stand fifth most common male cancer in Saudi Arabia. OBJECTIVE: In the present study, Serum levels of selenium, zinc, copper, manganese, and iron were measured in patients with BPH and prostate cancer aiming to explore the association between these elements and prostate cancer. PATIENTS AND METHODS: The study included 40 newly diagnosed prostate cancer patients, 22 patients with BPH and 30 healthy male subjects. All participant groups had similar socio-economic levels. Fasting blood samples were collected from all subjects and before any intervention for the patients. Serum PSA concentrations were analyzed by ELIZA and trace elements Se, Zn, Cu, Mn and Fe were measured by ICP-MS. RESULTS: Serum Se, Zn, and Mn levels of prostate cancer patients were significantly decreased compared to control groups. The levels of serum Cu and Fe were significantly higher in prostate cancer patients than in control groups. CONCLUSION: In the present study, an association was noticed between serum trace elements disturbance and prostate cancer. The decreased levels of Se, Zn, and Mn, and increased Cu and Fe levels may play significant roles in the initiation of prostate cancer. However, future prospective studies on the causes of trace elements alteration in prostate cancer patients are needed as well as to illustrate the relation between different prostate cancer stages and trace elements concentrations.

A piece in prostate cancer puzzle: Future perspective of novel molecular signatures.

Prostate cancer (PCa) has a variable biological potential. It constitutes the second most common cancer amongst men worldwide and the fifth most common cancer in Saudi Arabia. Identifying men at higher risk of developing PCa, differentiating indolent from aggressive disease and predicting the likelihood of progression will improve decision-making and selection for active surveillance protocols. Biomarkers have been utilized for PCa screening and predicting cancer behavior and response to treatment. The prostate specific antigen (PSA) screening helps detect PCa in early stages, while implementing a plan for management and outcome. However, PSA screening is still controversial, due to the risks of over diagnosis and treatment, and its inability to detect a good proportion of advanced tumors. Alternatively, a new era of PCa biomarkers has emerged with higher PCa specificity than PSA and its isoforms hopefully improving screening methods, such as Prostate Health Index (PHI) score, Progensa Prostate Cancer Antigen 3 (PCA3), Mi-Prostate Score (MiPS), Prostate Stem Cell Antigen (PSCA), 4Kscore test, and Urokinase Plasminogen Activation (uPA and uPAR). Few novel biomarkers have shown promise in preliminary results. This review will display promising biomarkers including some important FDA approved ones, highlighting their clinical implication and future place in the PCa puzzle, along with addressing their current limitations.

Prevalence and characterization of urolithiasis in the Western region of Saudi Arabia.

OBJECTIVES: The main objective of this study is to determine the prevalence and risk factors of urolithiasis among the Saudi population in Makkah region. METHODS: A cross-sectional survey was conducted on February 2017 in Makkah region (Makkah, Jeddah, and Taif). Data were obtained through direct interviews with participants, using an 18-questions-self-questionnaire, inquiring about demographic data (age, gender, weight, height, location, and occupation), educational level, history of renal stone disease (symptoms, modality of diagnosis, hospital admission, and previous treatment), and risk factors of stone formation such as family history and daily fluid intake. RESULTS: A total of 1506 individuals were interviewed, including 82% from Makkah, 15.7% from Jeddah, and only 2.3% from Taif. The overall percentage of those diagnosed urolithiasis was 6.2%; including 6.6% males and 5.8% females (P = 0.06). Of those with stones, 5% were medically treated, 1.7% were hospitalized, and 1.2% were surgically managed for stones. There was a positive linear correlation between the prevalence of stones and participants' age group (r = 0.87, P = 0.01). More than 80% of participants were highly educated, which did not impact the prevalence of stones formation (P = 0.14). Urolithiasis was reported by 8.9% obese participants, 5.9% overweight, and 5.4% with normal body mass index (r = 0.68, P = 0.03). When stratified by jobs, stone prevalence significantly increased in retired participants (17.2%) than in workers (8.8%), followed by those without work (7.7%) and finally by students (3.3%) (P < 0.001). There was no significant difference between urolithiasis and type of drinking water (P = 0.62). CONCLUSION: The prevalence of urolithiasis in the Western region of Saudi Arabia has not changed much since the previous report, which was 30 years ago. It seems that the middle-aged population in their third decade of life, those who are overweight and obese people are at a high risk of developing urolithiasis.

Urological knowledge among primary health care physicians in Saudi Arabia.

OBJECTIVES: To evaluate the general knowledge among primary health care (PHC) physicians regarding the management of common urological problems in Saudi Arabia. METHODS: This is an observational prospective study, where a self-administered questionnaire was distributed to practicing PHC physicians in the western region of Saudi Arabia on January 2017. The questionnaire consisted of 21-item questions, inquiring about demographics and general urological knowledge and skills. The management of common urological problems was assessed by case scenarios for specific urological condition, including urethral catheterization, definition and evaluation of hematuria, recognition of age-specific increase in prostatic specific antigen (PSA), and management of lower urinary tract symptoms. Results: A total of 148 questionnaires were distributed, with a response rate of 75.7%, where 112 respondents completed the questionnaires,  including 54.3% residents, 39% general practitioners, and 5.4% specialists. Fifty-seven percent of respondents were males and 68% were Saudi practitioners. A higher number of respondents expressed that they were able to catheterize a male than female patient (56.5% versus 34.3%). Only 6.4% of respondents defined microscopic hematuria accurately. Knowledge about hematuria, serum prostate specific antigen and overactive bladder was low in all groups. Apart from hematuria, seeking urological consultations was less than 35% for all other disease entities. CONCLUSION: Urological knowledge among PHC physicians seems to be insufficient. Significant percentages of the participants were unable to catheterize a female patient, did not know the definition of hematuria; and whether to ask for urological consultations in cases of hematuria, increased PSA, and overactive bladder.

Surface functionalized folate targeted oleuropein nano-liposomes for prostate tumor targeting: Invitro and invivo activity.

AIMS: This study aims to develop and evaluate oleuropein loaded surface functionalized folate-targeted - PEG liposomes for the effective management of prostate cancer in an animal model. MATERIALS AND METHODS: Film hydration-cum-extrusion technique was used to produce liposomes. Particle size, entrapment efficiency, drug loading, electron microscopy, and drug release study were performed for the characterization. Cell viability and various in vitro studies (phosphatidylserine internalization, TUNEL assay, measurement of mitochondrial membrane potential and caspase-3 assay) were performed to compare the anticancer and apoptotic effects of developed liposomes against the plain oleuropein. Comparative pharmacokinetic profiling and anticancer efficacy studies including a change in tumor volume, body weight, and survival analysis were performed in mice model. KEY FINDINGS: The developed liposomes (OL-FML) showed the particle size of 184.2 ±â€¯9.16 nm, the zeta potential of 1.41 ±â€¯0.24 mV, entrapment efficiency of 63.52 ±â€¯4.15% and drug loading of 21.31 ±â€¯2.37%. OL-FML showed higher in vitro anti-proliferative effect and apoptosis on 22Rv1 cells. In vivo pharmacokinetic study revealed a nearly 6 fold increase in the bioavailability of OL-FML (AUC0→∞ = 641.78 ±â€¯103.764 µg/mL·hr) as compared to OL solution (AUC0→∞ = 104.11 ±â€¯18.374 µg/mL·hr) in mice. Increased tumor suppression, weight loss resistance, and survival probability were observed in 22Rv1 induced tumor-bearing mice with OL-FML treatment as compared to OL. SIGNIFICANCE: The study provides conclusive evidence for the utilization of combining passive and active targeting strategy to enhance the anticancer effect of OL.

Resveratrol-loaded PLGA nanoparticles mediated programmed cell death in prostate cancer cells.

Resveratrol (RL), a natural polyphenol, is known for its diverse biological effects against various human cancer cell lines. But low aqueous solubility, poor bioavailability, and stability limit its efficacy against prostate cancer. In this study polymeric nanoparticles encapsulating resveratrol (RLPLGA) were designed and their cytotoxic and mode of apoptotic cells death against prostate cancer cell line (LNCaP) was determined. Nanoparticles were prepared by solvent displacement method and characterized for particle size, TEM, entrapment efficiency, DSC and drug release study. RLPLGA exhibited a significant decrease in cell viability with 50% and 90% inhibitory concentration (IC50 and IC90) of 15.6 ±â€¯1.49 and 41.1 ±â€¯2.19 µM respectively against the LNCaP cells. This effect was mediated by apoptosis as confirmed by cell cycle arrest at G1-S transition phase, externalization of phosphatidylserine, DNA nicking, loss of mitochondrial membrane potential and reactive oxygen species generation in LNCaP cells. Furthermore, significantly greater cytotoxicity to LNCaP cells was observed with nanoparticles as compared to that of free RL at all tested concentrations. RLPLGA nanoparticles presented no adverse cytotoxic effects on murine macrophages even at 200 µM. Our findings support the potential use of developed resveratrol loaded nanoparticle for the prostate cancer chemoprevention/ chemotherapy with no adverse effect on normal cells.

Current status of robot-assisted urologic surgery in Saudi Arabia: Trends and opinions from an Internet-based survey.

OBJECTIVES: The objective of this study is to assess the current status of urologic robot-assisted surgery (RAS) in Saudi Arabia and evaluate perceptions of its importance and utility. METHODS: A 59-item questionnaire was E-mailed to urologists and trainees in Saudi Arabia to assess the demographics and individual and institutional surgical practices of minimally invasive surgery (MIS) with a focus on RAS and urologic subtypes. RESULTS: Ninety-five surveys were completed. Nearly 53%, 46%, and 21% of respondents were formally trained in laparoscopic surgery, MIS, and RAS, respectively. Forty percent had used a robot console during training. Nearly 72% of participants felt that RAS training should be included to accomplish their career goals and stated that it would strengthen the department academically and financially. The absence of a robotic system (45%) and administrative disinterest with lack of support (39%) were the most common deterrents. Robot-assisted radical prostatectomy (RARP), robot-assisted radical cystectomy (RARC), and robot-assisted radical nephrectomy (RARN) were regarded as the gold standard for 34%, 23%, and 17% of respondents, respectively. Respondents would recommend RARP (74%), RARC (50%), and RARN (57%) for themselves or their family. The greatest perceived benefits of RAS were its ease of use and improvement in the patient's quality of life. CONCLUSION: Urologists in Saudi Arabia recognize the superiority of RAS over traditional surgical methods but lack exposure, training, and access to RAS. This survey reveals increasing acceptance of RAS and willingness to incorporate the technology into practice.

Cystoscopic enucleation of bladder leiomyoma.

We are presenting a rare case of bladder leiomyoma. A 61-year-old female patient was found to have a bladder mass during a work up of lower urinary tract symptoms. After full investigation, she underwent transurethral excision of the mass. The histopathology revealed typical feature of bladder leiomyoma. No recurrence was seen after a follow-up period of 12 months.

Knowledge about urology in the general population of Jeddah, Saudi Arabia.

INTRODUCTION: The knowledge of the general population about the medical specialties is not well studied in our community. Our aim is to explore the amount of knowledge known about urology by the general population. MATERIALS AND METHODS: A questionnaire was completed by 154 respondents in Jeddah, Saudi Arabia. After measuring the amount of knowledge in our population, we looked forward to compare it with English as well as French speaking population in North America (NA). We translated to Arabic the same questionnaire used in their study. Two extra questions were added to further serve our aim. RESULTS: Of the 154 respondents, 66% (102) said that they know little or nothing about urology, and 43% (66) did not know that urology involves surgery. When asked to mention three diseases within the field of urology, only 37% (57) were able to do so. Fourteen percent (21) were unable to mention even one disease. When asked about naming modalities of treatment in urology, 67% (104) were able to mention one or more. The rest were unable to mention even one modality. Most of the wrong answers were related to mixing urology with anatomically related fields rather than pronunciation similarity. Most of the results were better when compared to the studies done in NA. CONCLUSION: Although significant proportion of our population know little about the field of urology, the overall result is better when compared to North American population. The clarity of Arabic terminology related to the field may explain the difference.

Progression of pressure ulcer to vesico-cutaneous fistula.

A 72-year-old female known to have diabetes, multiple medical problems, and bedridden with indwelling Foley's catheter. She presented with an ulcer which progressed to a Grade 4 pressure ulcer. She was known to have recurrent urinary tract infection. Contrast study through the fistula revealed a communicating fistula between the left buttock ulcer and the bladder. Conservative way of management was followed due to the overall health status of the patient. She was sent to home with daily dressings, mattress, and an occupational therapy plan. Fortunately, her fistula healed spontaneously after six months. To our knowledge, in addition to the unique presentation and outcome, the case we reported is the first with such communication.