Primary urethral carcinoma in female: An extremely rare case series at a single tertiary referral hospital and literature review.

INTRODUCTION AND IMPORTANCE: Primary urethral carcinoma (PUC) is exceedingly uncommon and accounts for 0.02 % of all female cancers and <1 % of female genitourinary tract malignancy. PUC in female usually presents late with a higher disease stage and, hence, has higher cancer-specific mortality. Due to its rarity, the current recommendation for the management of PUC is still unclear. CASE PRESENTATION: This study reports two rare cases of 59-year-old and 65-year-old women with PUC, presenting with chief complaint of hematuria. Urethrocystoscopy and biopsy were performed. Pathology results revealed mucinous adenocarcinoma (AC) and urothelial carcinoma (UC) of the urethra, respectively. Radiological imaging was conducted for staging. Both were diagnosed with cT4N2M0. The first patient underwent anterior pelvic exenteration with bilateral ureterocutaneoustomy (UCS), while the second patient received cisplatin-based chemotherapy before the surgery. Radiological follow-up was planned 3 months after the surgery. CLINICAL DISCUSSION: Both mucinous AC and UC are considered incredibly unusual subtypes, with no defined treatment guidelines. Anterior exenteration with or without neoadjuvant chemotherapy may be opted for advanced PUC affecting the proximal urethra and adjacent organs. Following the previous studies, in this case series, both patients (locally advanced) underwent anterior exenteration. Additionally, the UC subtype received multimodal treatment with neoadjuvant chemotherapy which was shown to improve overall survival. CONCLUSION: In conclusion, PUC is extremely rare, and the choice of management remained various. Long-term follow-up for these patients is mandatory to improve understanding of this incredibly uncommon disease.

Evaluation of Cutoff Point Prostate Specific Antigen (PSA) and Prostate Specific Antigen Density (PSAD) in Patients with Suspected Prostate Cancer.

Background: Prostate cancer is the second leading cause of cancer death in men worldwide. There is no national standard for PSA cut-off levels even through the transrectal prostate biopsy procedure causes many serious complications such as bleeding, infection, and sepsis. Therefore, determining cut-off levels for PSA and PSAD is essential to avoid unnecessary biopsies. Objective: This study aims to determine the Prostate Specific Antigen (PSA) and Prostate Specific Antigen Density (PSAD) cut-off points in patients with suspected prostate cancer. Methods: A retrospective study was conducted from January 2018 until March 2021 in Saiful Anwar General Hospital Malang Indonesia. Inclusion criterias were patients with suspected prostate cancer; > 50 years old; underwent PSA, PSAD, and prostate biopsy. Exclusion criterias were patients refuse to participate in the study and incomplete patient medical record data. Medical records from 53 patients who underwent transrectal ultrasonography (TRUS)-guided prostate biopsy were reviewed. Statistical analysis was performed using Mann-Whitney U, Chi-Square, Fisher's Exact, and Receiver Operator Characteristic (ROC) curves. Results and Discussion: Medical records conducted 53 patients who met inclusion criteria and underwent transrectal ultrasonography (TRUS)-guided prostate biopsy were reviewed. PSA cut off level for prostate biopsy was 19.71 ng/ml with a sensitivity of 69.23% and a specificity of 72.5%. The positive predictive value is 45% and the negative predictive value is 87.87%. PSAD cut off level for prostate biopsy was 0.4113 with a sensitivity of 61.54% and a specificity of 63.16%. The positive predictive value is 36.36% and the negative predictive value is 82.76%. Conclusion: Results from this study, the cut off levels of PSA and PSAD in prostate disease patients is higher than the recommended cut off; prostate cancer is the largest malignancy in men worldwide and has a higher incidence in the older age and high serum PSA levels group.

Methylenetetrahydrofolate Reductase C677T (rs1801133) Polymorphism Is Associated with Bladder Cancer in Asian Population: Epigenetic Meta-Analysis as Precision Medicine Approach.

The etiology of bladder cancer remains unclear. This study investigates the impact of gene polymorphisms, particularly methylenetetrahydrofolate reductase gene (MTHFR), on bladder cancer susceptibility, focusing on the rs1801133 single-nucleotide polymorphism (SNP). A meta-analysis was conducted after systematically reviewing the MTHFR gene literature, adhering to PRISMA guidelines and registering in PROSPERO (CRD42023423064). Seven studies were included, showing a significant association between the MTHFR C677T (rs1801133) polymorphism and bladder cancer susceptibility. Individuals with the T-allele or TT genotype had a higher likelihood of bladder cancer. In the Asian population, the overall analysis revealed an odds ratio (OR) of 1.15 (95% CI 1.03-1.30; p-value = 0.03) for T-allele versus C-allele and an OR of 1.34 (95% CI 1.04-1.72; p-value = 0.02) for TT genotype versus TC+CC genotype. The CC genotype, however, showed no significant association with bladder cancer. Notably, epigenetic findings displayed low sensitivity but high specificity, indicating reliable identified associations while potentially overlooking some epigenetic factors related to bladder cancer. In conclusion, the MTHFR T-allele and TT genotype were associated with increased bladder cancer risk in the Asian population. These insights into genetic factors influencing bladder cancer susceptibility could inform targeted prevention and treatment strategies. Further research is warranted to validate and expand these findings.

Survival Outcome of Urinary Diversion in Advanced Cervical Cancer Patients with Hydronephrosis.

OBJECTIVE: Urinary diversion is the treatment of choice for cervical cancer patients with urinary tract obstruction. The aim of this study is to determine the survival rate among advanced cervical cancer patients with hydronephrosis who undergo urinary diversion and factors that affect patient survival. METHODS: Clinical data of cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) Stage-IIIB or advanced cervical cancer were not surgical candidates admitted to Saiful Anwar Hospital, Malang from May 2016 to August 2022 were retrospectively analyzed. The parameters including age, cancer stage, comorbidity, cancer treatment at diagnosis, hydronephrosis treatment, grade, site, and survival, were analyzed using the IBM SPSS Statistics version 21. The significance level was set up to 0.05. RESULT: One hundred eighteen patients were included in this study. Most patients were under 60 (84.75%) and presented with stage IIIB (79.66%). Diabetes mellitus type 2 (8.47%), hypertension (7.63%), acute kidney injury (16.10%), and chronic kidney disease (36.78%) were comorbidities discovered in patients. More than half of patients received chemotherapy (54.24%). Ureteral stents were inserted in 85.59% of patients. Patients with moderate hydronephrosis were the most common, accounting for 67.80% of all cases. Patients with bilateral hydronephrosis outnumber those with unilateral by 91.53% to 8.47%. The survival rate did not differ significantly between ureteral stents (median survival was 11.00 months) and percutaneous nephrostomies (median survival was 15.00 months), p=0.749. In univariate analysis, age, cancer stage, and hydronephrosis stage were associated with worse 1-year survival. In multivariate analysis, age, DM type 2, cancer staging and hydronephrosis staging were associated with worse 1-year survival. CONCLUSION: In advanced cervical cancer patients, urinary diversion techniques such as ureteral stents and percutaneous nephrostomy offer similar survival rates. In addition, age, cancer stage, DM type 2, and hydronephrosis site are strong predictors of a worsening survival rate in patients.

Method for determining predictor factor for worse outcomes in kidney transplant recipients infected with coronavirus disease 2019 in a systematic review and meta-analysis research.

The systematic review and meta-analysis were conducted for COVID-19 infections in kidney transplant patients. Recent research on this topic was still scarce and limited meta-analysis research discussion, specific to some risks or treatment in kidney transplantation patients with COVID-19 infection. Therefore, this article demonstrated the fundamental steps to conducting systematic review and meta-analysis studies to derive a pooled estimate of predictor factors of worse outcomes in kidney transplant patients with positive for the SARS-CoV- 2 test•PICOT Framework to determine the research scope•PRISMA strategy for study selection•Forest Plot for meta-analysis study.

Predictor factor for worse outcomes in kidney transplant recipients infected with coronavirus disease 2019: A systematic review and meta-analysis.

INTRODUCTION: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a massive impact on the health sector, especially in patients with pre-existing comorbidities. This study aims to define the predictor factors for worse outcomes in kidney transplant patients infected with SARS-CoV-2 and affected by coronavirus disease 2019 (COVID-19). We have analyzed in these patients their prior medical history, their clinical symptoms, and their laboratory results. METHOD: We assessed outcomes of kidney transplant patients with confirmed COVID-19 until July 2021 from PubMed, Medline, Science Direct, Cochrane databases, EMBASE, Scopus, and EBSCO. We performed meta-analyses of nine published studies to estimate predictor factors. The analysis was analyzed by the Newcastle-Ottawa Scale (NOS) and then using the Review Manager 5.4 software. RESULT: Our analysis demonstrated that the most significant risk factors for the worse COVID-19 outcomes for kidney transplant patients included: age of 60 and older [MD 9.31(95% CI, 6.31-12.30), p < 0.0001, I2 = 76%], diabetic nephropathy [OR 2.13 (95% CI, 1.49-3.04), p < 0.0001, I2 = 76%], dyspnea [OR 4.53, (95% CI, 2.22-9.22), p < 0.0001, I2 = 76%], acute kidney injury (AKI) [OR 4.53 (95% CI, 1.10-5.21), p = 0.03, I2 = 58%], and some laboratory markers. Many patients had two or multiple risk factors in combination. CONCLUSION: Age and several comorbidities were the most significant factors for COVID-19 outcomes for kidney transplant recipients.

Complex Complicated Posterior Urethral Stricture with Contracted Bladder and Prostatorectal Fistula: How Do We Manage It?

Background: Posterior traumatic urethral strictures due to PFUI have a wide variety of complication, such as erectile dysfunction, incontinence, bulbar urethral necrosis, and fistula. Bulbar urethral necrosis caused by inadequate blood supply for bulbar urethra, fistula developed by many surgical attempts done by inexperience surgeon worsen the patient's condition, low vascular capability manifested as erectile dysfunction as well, and long term catheterization causes contracted bladder. This condition deteriorates the function and quality of life. Therefore this is very challenging condition to treat. Case Presentation: Thirty-years-old man presented with the chief complaint of urine leakage from rectum and cutaneous fistula since 9 years ago. Patient also come with complex PFUI, iatrogenic bulbar urethral necrosis, erectile dysfunction with EHS score of 1, contracted bladder, and prostatorectal fistula. Patient underwent eight various surgical procedures including open surgery and internal urethrotomy previously. We performed cystoprostatectomy and fistula repair transabdominally. Continent cutaneous stoma ileal neobladder with Mansoura approach was performed afterwards. Patient was counselled and educated on how to do clean intermittent self-catheterization, patient was fully satisfied with his bladder function which increase quality of life. Conclusion: In this case of BUN with contracted bladder and prostatorectal fistula, continent cutaneous stoma is an option to improve patient's quality of life. PFUI could be treated with high success rate if treated properly from the beginning, more intervention by inexperience surgeon could deteriorate success rate and also quality of life.

Effect of Conjugated Linoleic Acid (CLA) Supplementation on Expression of B-Cell Lymphoma-2 (Bcl-2) in the Bladder Epithelium of Wistar (Rattus norvegicus) Rats Exposed to Cigarette Smoke.

Background: Bladder carcinoma is the 10th most common cancer in the world with an incidence about 3% of all cancers. The risk factor for smoking is found in 81% of all cases of bladder carcinoma. One of the protein groups associated with bladder urothelial carcinoma is B-Cell Lymphoma-2 (Bcl-2). Nicotine-derived nitrosamine ketone (NNK) contained in cigarette smoke would increase the proliferation of cancer cells through increased the expression of Bcl-2. The expression of Bcl-2 could be suppressed in the presence of Conjugated Linoleic Acid (CLA), a polyunsaturated fatty acid that has role in reducing the risk of cancer development which is reported in several studies, and then stimulate cell apoptosis. Objective: To determine the effect of CLA supplementation on Bcl-2 expression in the bladder of rats which is exposed to cigarette smoke. Methods: The study is an experimental study with true experimental posttest only control group design on Wistar rats. Sample was divided into 2 case groups: 0.5% of diet (125 mg) CLA supplementation in group A, 1% of diet (250 mg) CLA in group B; and 2 control groups: group without CLA supplementation (group C) as positive control and without cigarette smoke exposure (group D) as negative control. The study takes 60 days of exposure and then Bcl-2 expression on bladder epithelial was evaluated by immunohistochemistry staining. Results: The results descriptively showed that rats in group C has an average Bcl-2 expression of 25.8±7.33%, while rats in group D has an average Bcl-2 expression 14.1±7.73% which means cigarette smoke exposure has been shown to increase the expression of Bcl-2 by 45.35% (p=0.019) in the bladder mucosa of experimental animals. Group B obtained an average Bcl-2 expression was 14.2±9.6% and has a significant difference when compared to group C, it shows that the addition of 1% CLA would reduce the expression of Bcl-2 by 44.96% (p=0.032). However, for group A, group with 0.5% diet of CLA supplementation did not showed decrease of Bcl-2 expression when compared to the group C (p=0.37). Conclusion: Conjugated Linoleic Acid (CLA) supplementation 1% of diet can reduce Bcl-2 expression in bladder epithelium of wistar rats (Rattus norvegicus) exposed to cigarette smoke.

Comparison Between Intravesical Chemotherapy Epirubicin and Mitomycin-C after TURB vs TURB Alone With Recurrence Rate of Non-Muscle Invasive Bladder Cancer: Meta-Analysis.

Background: Bladder cancer is still a burden on the world of oncology medicine, which every year affects about 3.4 million people globally with 430,000 new cases per year. It is the fourth most common cancer in men and eighth most common women malignancy in the world. This makes bladder cancer a "silent killer" and it needs appropriate treatment planning. Single immediate instillation of chemotherapy after transurethral resection of the bladder (TURB) is recommended by EAU guideline, but its use remains a controversy. Objective: Study aimed to analyze benefit of intravesical chemotherapy following TURB in terms of recurrency of non-muscle invasive bladder cancer (NMIBC). Methods: Systematic review and meta-analysis of randomized controlled trials comparing the efficacy of a single instillation after TURB with TURB alone in NMIBC (pTa-pT1) patients was conducted. Studies searched throughout Medline, PubMed, Embase, and Cochrane in December 2018. Keywords were intravesical chemotherapy, combination, transurethral resection, bladder cancer. Inclusion criteria were RCT studies, subjects in study were treated single immediate chemotherapy instillation after TURB compared to TURB alone in patient with pTa-pT1 urothelial carcinoma of the bladder. Trials with additional treatment prior to first reccurence were not eligible. Studies using recurrence rate as dependent variable. From 361 studies, in total 11 studies were eligible for this meta-analysis. Results: From those 11 studies, it is shown that intravesical chemotherapy using Epirubicin and Mitomycin-C following TURB showed significant decrease of recurrence rate of bladder cancer even to progression of the disease compared to TURB alone (p<0.05) with pooled Risk Ratio were 0.69 and pooled heterogeneity (I2) were 26.6%. Conclusion: This meta-analysis study showed that combination therapy of intravesical chemotherapy after TURB is superior to TURB alone in showing the recurrence rate of NMIBC.

Modulation of T-cell Regulators Associated with Advanced Stage of Prostate Cancer.

BACKGROUND: Benign prostatic hyperplasia (BPH) and prostate cancer are the most common prostate diseases. The possible role of the immune system in the pathogenesis of BPH and prostate cancer in recent years has begun to be widely studied. Although many studies have focused on T lymphocytes on the development of BPH and prostate cancer, the role of regulatory T-cells in the pathogenesis of BPH and prostate cancer is still not well known. OBJECTIVE: To determine the amount of regulatory T-cells in prostate cancer and BPH so that it can contribute to the concept of understanding the pathogenesis of prostate cancer and BPH. METHODS: This study used cross-sectional design study. Total samples were 24 patients, with 13 subjects prostate cancer group, and 11 subjects BPH group. Furthermore, peripheral blood samples are taken and then the amount of regulatory T-cells is calculated. After obtaining data on the amount of CD4+ CD25+ Foxp3+ regulatory T-cells in the blood, data analysis was performed between groups of patients diagnosed with prostate cancer and benign prostatic hyperplasia. RESULTS: The average amount of regulatory T-cells in the CRPC group was 53.44±29.43, prostate cancer group was 57.02±22.49 and the BPH group 89.71±9.31. One Way ANOVA test results showed that the average amount of regulatory T-cells between treatment groups gave a significant difference in regulatory T-cells with a p-value (0,003) <0.05. It can be concluded that there are differences in the average amount of regulatory T-cells, so we continued the testing with Tukey test. We continue to Pearson correlation study and resulted in significantly correlated with p value = 0.011 (P<0.05) and r = 0.414. CONCLUSIONS: It can be concluded there was significant difference between the average number of regulator T-cells in the BPH group compared with prostate cancer and CRPC patient. Further research is needed regarding the number of regulator T-cells CD4 + CD25 + FOXP3 + in prostate cancer patients (grouped according to Gleason score) and benign prostatic hyperplasia before and after therapy with bigger samples.

miRNA-21 as Reliable Serum Diagnostic Biomarker Candidate for Metastatic Progressive Prostate Cancer: Meta-analysis Approach.

BACKGROUND: Prostate cancer is the second leading cause of cancer death in men, moreover when it develops metastasis. However, PSA detection in serum as current gold standard to measure disease progressivity had wide variability leading to confounding outcomes. MicroRNA-21 has diagnostic values for cancer over period of time researched, yet results are still inconclusive. OBJECTIVE: The aim of the study was to conduct recent meta-analysis to assess reliability of miRNA-21 as diagnostic biomarker especially in progressivity of prostate cancer. METHODS: Published papers from PubMed, Science Direct, and Embase" as of 1 July 2021 assessing circulating miRNA-21 in progressivity of prostate cancer patients were analyzed using Comprehensive Meta-Analysis tool. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR) and SROC assessed with 95 % confidence intervals were estimated using fixed-effects or random-effects models. RESULTS: In total, we included 6 papers total of 651 samples reporting miRNA-21 capability of detecting progressive prostate cancer. The pooled sensitivity and specificity showed 0.91 (95% CI 0.88-0.94, I2=0%) and 0.89 (95% CI 0.85-0.92, I2=44.8%), respectively. Positive and negative likelihood ratio showed 7.18 (95% CI 4.31-11.96, I2=56%) and 0.11 (95% CI 0.07-0.16, I2=11.8%). SROC were assessed and got Area Under Curve around 97.4%. CONCLUSION: miRNA-21 could serve as biomarkers of prostate cancer progressivity since remarkable diagnostic value of circulating miRNA-21 in prostate cancer metastasis process.

miRNA-21 Serum Evaluation in BPH, Hormone Sensitive Prostate Cancer, and Castrate Resistant Prostate Cancer: Attempt for Diagnostic Biomarker Evaluation.

BACKGROUND: Some of prostate cancer cases could progress to be Castrate Resistant Prostate Cancer (CRPC). However it is still a challenge to early diagnose it since no reliable examination could be done except PSA, which has high variability. It is now known that miRNAs are involved in nearly all inflammatory responses. Several malignancies in humans that specifically express miRNA have been detected and identified. The expression values of miRNA-21 also correlates with the occurrence of resistant castration of prostate cancer and metastases, therefore miRNA-21 is expected to be a biomarker to estimate the progression of cancer. OBJECTIVE: The purpose of this study was to analyze the expression values and cut-off markers of miRNA-21 as markers of CRPC progression. METHODS: This study used a retrospective cohort design with observational analysis. The forty-eight total sample was obtained from serum, then the RT-PCR was performed to obtain expression values of miRNA-21. Data were analyzed using One Way ANOVA to see the difference in the expression values of miRNA-21. Furthermore, to determine the cut-off analysis was carried out using the ROC curve. RESULTS: In the BPH group, an average expression value of miRNA-21 was 33,785±1.80 ng/dL, in the Prostate cancer group the average miRNA-21 was 34.51±1.32 ng/dL, while in the CRPC group, an average miRNA-21 was obtained, reaching to 34.51±1.32 ng/dL. The cut-off value of miRNA-21 from the BPH category was <33,595, PPV = 50%, NPV = 80% with a value of p = 0.081, the prostate Ca category was 33.595-35.21, PPV = 87.5%, NPV = 66.7% with p value = 0.003, while the value of miRNA-21 in the CRPC category was> 35.21, PPV = 80%, NPV = 58.3 with a value of p = 0.04. CONCLUSION: There is a significant difference in the expression values of miRNA-21 between BPH with CRPC and Prostate cancer and CRPC, therefore, miRNA-21 cut-off point is potential to differentiate the diagnosis.