Log Odds of Positive Lymph Nodes (LODDS) as an Independent Predictor of Overall Survival Following Radical Cystectomy in Urothelial Bladder Cancer: Time to Rethink Conventional Node Staging.

BACKGROUND: Radical cystectomy (RC) with lymph node dissection is the mainstay of treatment for patients with muscle-invasive bladder cancer (MIBC) and high risk non-MIBC. The American Joint Committee on Cancer's (AJCC) node staging and lymph node ratio (LNR) systems are used in estimating prognosis; however, they do not directly factor in negative dissected nodes. In this study, we evaluated the log odds of positive lymph nodes (LODDS), a novel measure of nodal involvement, as a predictor of survival. PATIENTS AND METHODS: Eighty-three patients who underwent RC were retrospectively included and their demographic and clinical data were collected. Kaplan-Meier curve and Cox regression were used for survival analyses. RESULTS: Median number of dissected lymph nodes was 13 (range 3-45). ROC curve analysis indicated -0.92 as the optimal LODDS cutoff. LODDS > -0.92 was associated with higher T stage, lymphovascular invasion, and significantly worse overall survival (OS) (mean OS 18.6 vs. 45.1 months, P-value < .001). Furthermore, we evaluated AJCC node staging, LNR, and LODDS in three separate multivariable Cox regression models. Among 3 different measures of nodal disease burden, only LODDS was an independent predictor of OS (HR 2.71, 95% CI 1.28-5.73, P = .009). CONCLUSIONS: Our results show that LODDS is an independent predictor of OS and outperforms AJCC node staging and LNR in forecasting prognosis among patients with urothelial bladder cancer who undergo RC.

The effect of Melatonin on Improving the benign Prostatic Hyperplasia Urinary Symptoms, a Randomized Clinical Trial.

PURPOSE: to investigate the effect of melatonin along with tamsulosin in improving BPH urinary symptoms. MATERIALS AND METHODS: A total of 108 men with BPH symptoms, age of ≥ 50 years, and International Prostate Symptom Score (IPSS) ≥ 8 entered into the parallel group randomized, double-blind clinical trial with balanced randomization. The treatment group received of 3mg melatonin plus 0.4mg tamsulosin and the control group received placebo plus 0.4mg tamsulosin. Patients and physicians were concealed by sealed and opaque envelopes. Symptoms were assessed at baseline and 1 month after treatment. Finally all scores at the initial and end of the study were compared and analyzed using SPSS software. RESULTS: This study showed that adding melatonin to the classic treatment of BPH patients with tamsulosin could significantly reduce the likelihood of nocturia by 2.39 times (95% CI: 1.07-5.32, OR = 2.39, p = 0.033) and could also reduce the frequency of urination by 2.59 times (95% CI: 1.15-5.84, OR = 2.59, p = 0.021). There was no statistically significant difference between the two groups in IPSS, intermittency, incomplete emptying, straining, urgency, and weak stream. CONCLUSION: Melatonin plus tamsulosin treatment is associated with a significant improvement of nocturia and frequency in patients with benign proststic hyperplasia. However, it is necessary to do more studies.

Comprehensive analysis of ceRNA networks to determine genes related to prognosis, overall survival, and immune infiltration in clear cell renal carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the common subtypes of kidney cancer. Circular RNAs (circRNAs) act as competing endogenous RNAs (ceRNAs) to affect the expression of microRNAs (miRNAs), and hence the expression of genes involved in the development and progression of ccRCC. However, these interactions have not been sufficiently explored. METHODS: The differential expression of circRNAs (DEC) was extracted from the GEO database, and the expression of circRNAs was analyzed by the Limma R package. The interaction of miRNAs with circRNAs was predicted using (cancer-specific circRNA database) CSCD and circinteractome database. The genes affected by the miRNAs were predicted by miRwalk version 3, and the differential expression was retrieved using TCGA. Functional enrichment was assessed and a PPI network was created using DAVID and Cytoscape, respectively. The genes with significant interactions (hub-genes) were screened, and the total survival rate of ccRCC patients was extracted from the Gene Expression Profiling Interactive Analysis (GEPIA) database. To confirm the expression of OS genes we used the Immunohistochemistry (IHC) data and TCGA database. The correlation between gene expression and immune cell infiltration was investigated using TIMER2.0. Finally, potential drug candidates were predicted by the cMAP database. RESULTS: Four DECs (hsa_circ_0003340, hsa_circ_0007836, hsa_circ_0020303, and hsa_circ_0001873) were identified, along with 11 interacting miRNAs (miR-1224-3p, miR-1294, miR-1205, miR-1231, miR-615-5p, miR-940, miR-1283, and miR-1305). These miRNAs were predicted to affect 1282 target genes, and function enrichment was used to identify the genes involved in cancer biology. 18 hub-genes (CCR1, VCAM1, NCF2, LAPTM5, NCKAP1L, CTSS, BTK, LILRB2, CD53, MPEG1, C3AR1, GPR183, C1QA, C1QC, P2RY8, LY86, CYBB, and IKZF1) were identified from a PPI network. VCAM1, NCF2, CTSS, LILRB2, MPEG1, C3AR1, P2RY8, and CYBB could affect the survival of ccRCC patients. The hub-gene expression was correlated with tumor immune cell infiltration and patient prognosis. Two potantial drug candidates, naphazoline and lithocholic acid could play a role in ccRCC therapy, as well other cancers. CONCLUSION: This bioinformatics analysis brings a new insight into the role of circRNA/miRNA/mRNA interactions in ccRCC pathogenesis, prognosis, and possible drug treatment or immunotherapy.

Association Between Preoperative De Ritis (AST/ALT) Ratio and Oncological Outcomes Following Radical Cystectomy in Patients With Urothelial Bladder Cancer.

BACKGROUND: Radical cystectomy in combination with neoadjuvant chemotherapy is the standard of care for muscle invasive bladder cancer (BC). However, response to treatment varies between patients. Considering the role of hepatic glucose metabolism in urothelial cancer, AST/ALT ratio (De Ritis ratio) has the potential to serve as a prognostic factor for bladder cancer and a predictor for treatment outcome. MATERIALS AND METHODS: We retrospectively analyzed patients who underwent radical cystectomy between March 2016 - March 2019. Patients were classified into 2 groups based on De Ritis ratio (< 1.3 [normal] vs. ≥ 1.3 [high]). Demographics, disease severity, treatment status, and disease outcome (90-day mortality and overall survival [OS]) were compared between 2 groups. RESULTS: A total of 89 patients were included, 62.9% of them having a De Ritis ratio of < 1.3 and 37.1% with a De Ritis ratio of ≥ 1.3. Mean OS was significantly higher in patients with normal De Ritis ratio (40.84 vs. 18.28 months, P < .001), and 90-day mortality rate was lower in these patients (8.9% vs. 36.4%, P = .001). Moreover, De Ritis ratio was the sole independent predictor of OS in multivariable regression analysis. CONCLUSION: De Ritis ratio is an independent prognostic factor in BC patients who underwent radical cystectomy. Furthermore, higher De Ritis ratio is associated with worse OS and a higher 90-day mortality rate after surgery, and therefore, has the potential to serve as a predictor of treatment outcome in BC patients.

The role of nutritional interventions in prostate cancer: A review.

The high prevalence rate in conjunction with the long latency period made prostate cancer (PCa) an attractive and reasonable candidate for preventive measures. So far, several dietary and nutritional interventions have been implemented and studied with the aim of preventing the development or delaying the progression of PCa. Calorie restriction accompanied by weight loss has been shown to be associated with decreased likelihood of aggressive PCa. Supplements have played a major role in nutritional interventions. While genistein and lycopene seemed promising as preventive agents, minerals such as zinc and selenium were shown to be devoid of protective effects. The role of vitamins has been widely studied, with special emphasis on vitamins with antioxidant properties. Data related to Vitamin A and Vitamin C were rather controversial and positive effects were of insignificant magnitude. Vitamin E was associated with a decreased risk of PCa in high-risk groups like smokers. However, when it comes to Vitamin D, the serum levels might affect the risk of PCa. While deficiency of this vitamin was associated with increased risk, high serum levels imposed the risk of aggressive disease. Despite the seemingly promising effects of dietary measures on PCa, no firm recommendation could be made due to the limitations of the studies and evidence. However, the majority of these advices could be followed by the patients with the intent of living a healthy lifestyle.

A possible protective role for Bacillus Calmette-Guérin therapy in urinary bladder cancer in the era of COVID-19: a brief report.

Given the systemic immunogenic effects of Bacillus Calmette-Guérin (BCG) therapy in patients with bladder cancer and its non-specific immunogenic effects in viral respiratory diseases, we aimed to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in bladder cancer patients with a history of BCG therapy. In the present study, all bladder cancer survivors with a history of BCG therapy were identified and included in the study according to the data recovered from the UORC (Uro-Oncology Research Center) registry database. These patients were followed up in terms of acquiring coronavirus disease 2019 (COVID-19). Among the studied patients, 102 eligible bladder cancer patients with a history of BCG therapy entered the study. The males constituted the majority of the patients (86.3%), and more than half of the study population (55.9%) were above 65 years old. Among the understudy patients, 12.7% were confirmed for COVID-19. The study results did not show a statistically significant association between the time and number of BCG therapy courses and SARS-CoV-2 infection. Although no statistically significant association was observed between receiving BCG therapy and developing COVID-19, the infection rate in patients who had recently received BCG therapy was lower than those who had received therapy more than a year ago.

The Potential of T Cell Immunoglobulin and Mucin-Domain Containing-3 (Tim-3) in Designing Novel Immunotherapy for Bladder Cancer.

Targeting inhibitory receptors on T cells in the tumor sites can promote effective anti-tumor immunity in bladder cancer. Unfortunately, the main dilemma is that a large number of patients remain refractory to CTLA-4, PD-1, and PD-L1 blockade therapies. T-cell immunoglobulin and mucin domain 3 (Tim-3) is an inhibitory receptor expressed on T cells and innate immune cells. Both in vivo and in vitro data from patients with advanced cancers support the role of Tim-3 inhibition in satisfactory anti-tumor immunity. In bladder cancer, the expression level of Tim-3 significantly increases with advanced pathological grade and T stage. Therefore, rationality implies that designing novel monoclonal antibodies reactive with Tim-3 alone or in combination with other checkpoint inhibitors may indicate a favorable response in bladder cancer. Here, we aimed to investigate the possibility of targeting Tim-3 as a novel anti-cancer treatment for bladder cancer.

Human microbiome and prostate cancer development: current insights into the prevention and treatment.

The huge communities of microorganisms that symbiotically colonize humans are recognized as significant players in health and disease. The human microbiome may influence prostate cancer development. To date, several studies have focused on the effect of prostate infections as well as the composition of the human microbiome in relation to prostate cancer risk. Current studies suggest that the microbiota of men with prostate cancer significantly differs from that of healthy men, demonstrating that certain bacteria could be associated with cancer development as well as altered responses to treatment. In healthy individuals, the microbiome plays a crucial role in the maintenance of homeostasis of body metabolism. Dysbiosis may contribute to the emergence of health problems, including malignancy through affecting systemic immune responses and creating systemic inflammation, and changing serum hormone levels. In this review, we discuss recent data about how the microbes colonizing different parts of the human body including urinary tract, gastrointestinal tract, oral cavity, and skin might affect the risk of developing prostate cancer. Furthermore, we discuss strategies to target the microbiome for risk assessment, prevention, and treatment of prostate cancer.

Role of Chronic Inflammation as a Predictor of Upstaging/Upgrading in Prostate Cancer: Finding a New Group Eligible for Active Surveillance.

PURPOSE: We aimed to investigate the correlation between presence of inflammation and pathology upgrading/upstaging in patients with prostate cancer. MATERIALS AND METHODS: A retrospective study was accomplished on 315 patients with prostate cancer, eligible for active surveillance except prostate-specific antigen (PSA) level (PSA<30ng/dL), who underwent radical prostatectomy between 2005 and 2015. Patients were divided into two groups based on needle biopsy: A; with evidence of inflammation (chronic prostatitis) and B; without inflammation. The frequency of upstaging and upgrading in both groups was compared in different ranges of PSA level (<10, 10-20 and 20-30ng/dL). Upgrading/Upstaging was defined as increase from one prognostic grade group to another. Statistical analyses were performed to investigate the relation between inflammation and upgrading/upstaging. RESULTS: The mean age of the patients was 68.2 years and the mean PSA level was 10.2 ng/mL. Chronic prostatitis was identified in 82 of 315 cases therefore upgrading/upstaging were seen in only three patients (3.7%) while 39 of 233 (16.7%) patients without inflammation had upgrading/upstaging in final pathology (P = 0.003). Other variables including the patient's PSA before surgery, PSA density, and the presence of hypoechoic areas in ultrasound had a significant relationship with the incidence of postoperative upgrading/upstaging. Among studied variables, presence of inflammation in biopsies was found to be the most important predictor of upstaging/upgrading (OR: 0.205). CONCLUSION: Our data demonstrated that patients with concurrent prostatitis and PCa may have a better prognosis even if the PSA level is higher than 10ng/mL.

Preemptive Analgesia with a Second Dose of Pregabalin, Acetaminophen, Naproxen, and Dextromethorphan: A Comparative Clinical Trial in Major Surgeries.

BACKGROUND: Postoperative pain management can improve patients' quality of life and decrease hospitalization rates. Preemptive analgesia may provide an effective approach for both pain control and opioid consumption decrease. A common approach for pain management after surgery is to relieve the pain that has already occurred. OBJECTIVES: The aim of this clinical trial was to compare the preemptive analgesic effect of single-dose versus two-dose administration of pregabalin, acetaminophen, naproxen, and dextromethorphan (PAND) combination. METHODS: This study involved 60 patients who had undergone one surgery (including nephrectomy, cystectomy, prostatectomy, colectomy, Whipple, and RPLND). They were randomly divided into two groups: The first group received a single dose of PAND, while the other group received a second dose within 6 hours after discharge from recovery. Pain intensity was assessed by the Universal Pain Assessment Tool (UPAT) in both groups 2, 4, 6, 8, 12, 24, and 48 hours postoperatively. The postoperative morphine dose in both groups was also recorded. Data were analyzed using SPSS version 25. RESULTS: Mean pain scores were significantly different between the two groups at 2, 12, 24, and 48 hours after surgery (P < 0.05). There was a statistically significant difference between the two groups in terms of opioid consumption (P < 0.001). The total opioid consumption in the second group (with the second administration of PAND) was lower than the first group. CONCLUSIONS: Preemptive analgesia with a second dose of PAND is an effective method for reducing pain and morphine consumption after surgery.

The Role and Function of Ras-association domain family in Cancer: A Review.

Ras gene mutation has been observed in more than 30% of cancers, and 90% of pancreatic, lung and colon cancers. Ras proteins (K-Ras, H-Ras, N-Ras) act as molecular switches which are activated by binding to GTP. They play a role in the cascade of cell process control (proliferation and cell division). In the inactive state, transforming GTP to GDP leads to the activation of GTpase in Ras gene. However, the mutation in Ras leads to the loss of internal GTPase activity and permanent activation of the protein. The activated Ras can promote the cell death or stop cell growth, which are facilitated by Ras-association domain family. Various studies have been conducted to determine the importance of losing RASSF proteins in Ras-induced tumors. This paper examines the role of Ras and RASSF proteins. In general, RASSF proteins can be used as a suitable means for targeting a large group of Ras-induced tumors.

Primary upper pole liposarcoma of the kidney with invasion to inferior vena cava: A case report.

Genitourinary tract liposarcoma is considered as the second most commonly reported type of sarcomas. Renal liposarcoma with tumor invasion to inferior vena cava (IVC) is distinctly rare. This tumor has a relatively indolent clinical course with risk of local recurrences (20%-85% rate) after surgery. Angiomyolipomas (AML) are the most important differential diagnosis because both are large fat-containing lesions. Herein, a patient with upper pole kidney liposarcoma with tumor invasion to renal vein and IVC is presented. The optimal management is radical nephrectomy and IVC tumor resection. Chemotherapy and radiotherapy have not shown significant survival benefit.

Radical cystectomy for management of inflammatory myofibroblastic tumor of the urinary bladder: A rare case report.

Inflammatory myofibroblastic tumor (IMT) of the bladder also known as pseudosarcomatous myofibroblastic proliferation is a rare lesion in the genitourinary tract was first described in 1980 by Roth. We herein report a case of urinary bladder IMT in a 42-year-old female patient presented with gross hematuria. The hematuria was difficult to control and radical treatment has been done. Monitoring for recurrence is strongly advisable.

Feasibility and Safety of Ultrasonography Guidance and Flank Position during Percutaneous Nephrolithotomy.

PURPOSE: Percutaneous nephrolithotomy is generally performed using fluoroscopy, which is associated with exposure to radiation. Another drawback of fluoroscopic guided percutaneous nephrolithotomy is the prone position, which is not suitable for all patients. In this study we evaluated the feasibility, safety and efficacy of ultrasound guided percutaneous nephrolithotomy with the patient in the flank position. MATERIALS AND METHODS: A total of 603 patients with a mean ± SD age of 50.9 ± 13 years were included in this study from December 2010 to July 2016. Access to the collecting system and tract dilation were performed under ultrasound guidance. Perioperative data on the stone-free rate, operative time, length of stay and complication rates were recorded. RESULTS: Successful access was achieved in all but 1 patient. Mean operative time was 56.6 ± 6.5 minutes. Complete stone clearance was achieved in 529 patients (87.7%) and Clavien-Dindo grade 3 complications were noted in 17 (2.8%). Blood transfusion was necessary in 43 patients (7.1%). However, bleeding was self-limited in all cases and did not require angioembolization. CONCLUSIONS: To our knowledge this is the largest series of ultrasound guided percutaneous nephrolithotomy with the patient in the flank position. Unlike in other studies we used this procedure in all patients irrespective of stone burden, renal anomaly and body habitus. Ultrasound guided percutaneous nephrolithotomy has outcomes comparable to those of conventional percutaneous nephrolithotomy and it is not associated with radiation exposure. Furthermore, anesthesia while in the flank position might be less harmful in some patients, including those with obesity or cardiopulmonary comorbidities.

Prostate-Specific Antigen Density and Gleason Score Predict Adverse Pathologic Features in Patients with Clinically Localized Prostate Cancer.

BACKGROUND: According to recent studies, prostate cancer is the second most common cancer among Iranian men. Radical prostatectomy has been considered the gold standard treatment in patients with clinically localized prostate cancer. Gleason score, PSA density, and PSA velocity are some of the parameters used to predict adverse pathologic features. OBJECTIVES: The aim of this study was to evaluate the prognostic value of PSA density and Gleason score in predicting adverse pathologic features in patients with localized prostate cancer who undergo radical prostatectomy. METHODS: We conducted a cross-sectional study of 105 patients with localized prostate cancer who underwent radical prostatectomy between 2006 and 2013. We recorded Gleason scores and PSA levels, in addition to the results of pathological evaluations after radical prostatectomy, including prostate volume, stage, LNI (lymph node involvement), SVI (seminal vesicle invasion), and extraprostatic extension (EPE). Data were analyzed using SPSS version 21. RESULTS: Mean PSA density was 0.27 (0.17 SD). The frequencies of EPE, SVI, and LNI were 21.9, 16.2, and 2.9, respectively. The Mann-Whitney U-test demonstrated a significant correlation between PSA density and adverse pathologic features (EPE, SVI, and LNI). CONCLUSIONS: PSA, PSA density, and Gleason score should be considered together in order to more accurately predict the adverse pathologic features of prostate cancer.

Relationship Between Perineural Invasion in Prostate Needle Biopsy Specimens and Pathologic Staging After Radical Prostatectomy.

BACKGROUND: Prostate cancer is the second most common malignancy among men worldwide and the sixth cause of cancer-related death. Some authors have reported a relationship between perineural invasion (PNI), Gleason score, and the invasion of peripheral organs during prostatectomy. However, it is not yet clear whether pathological evidence of PNI is necessary for risk stratification in selecting treatment type. OBJECTIVES: The clinical and pathological stages of prostate cancer are compared in patients under radical prostatectomy and in patients without perineural invasion. PATIENTS AND METHODS: This cross-sectional study was conducted using a sample of 109 patients who attended a tertiary health care center from 2008 to 2013. The selection criteria were PNI in prostate biopsy with Gleason scores less than six, seven, and eight to ten. The participants were enrolled in a census manner, and they underwent clinical staging. After radical prostatectomy, the rates of pathological staging were compared. The under-staging and over-staging rates among those with and without perineural invasion in biopsy samples were compared. RESULTS: The concordance between Gleason scores according to biopsy and pathology was 36.7% (40 subjects). The concordance rate was 46.4% and 33.3% among those with and without PNI, respectively. The concordance rates were significantly varied in different subclasses of Gleason scores in patients without PNI (P = 0.003); the highest concordance rate was a Gleason score of 7 (63.6%) and the lowest was a Gleason score of eight to ten (25%). However, there were no significant differences in patients with PNI (P > 0.05). CONCLUSIONS: Although the presence of PNI in prostate biopsy is accompanied by higher surgical stages, PNI is not an appropriate independent factor in risk stratification.