Cost-effectiveness Analysis of Triptorelin, Goserelin, and Leuprolide in the Treatment of Patients with Metastatic Prostate Cancer: A Societal Perspective.

OBJECTIVES: Metastatic prostate cancer is the most common malignant cancer and the second leading cause of death due to various types of cancer among men after lung cancer. This study aimed to analyze the cost-effectiveness of triptorelin, goserelin, and leuprolide in the treatment of the patients with metastatic prostate cancer from the societal perspective in Iran in 2020. METHODS: This is a cost-effectiveness study in which a 20-year Markov transition modeling was applied. In this study, local cost and quality-of-life data of each health state were gathered from cohort of patients. The TreeAge pro 2020 and Microsoft Excel 2016 software were used to simulate cost-effectiveness of each treatment in the long term. The one-way and probabilistic sensitivity analyses were also performed to measure robustness of the model outputs. RESULTS: The findings indicated that the mean costs and utility gained over a 20-year horizon for goserelin, triptorelin, and leuprolide treatments were $ 13 539.13 and 6.365 quality-adjusted life-years (QALY), $ 18 124.75 and 6.658 QALY, and $ 26 006.92 and 6.856 QALY, respectively. Goserelin was considered as a superior treatment option, given the estimated incremental cost-effectiveness ratio. The one-way and probabilistic sensitivity analyses confirmed the robustness of the study outcomes. CONCLUSIONS: According to the results of the present study, goserelin was the most effective and cost-effective strategy versus 2 other options. It could be recommended to policy makers of the Iran healthcare system to prioritize it in clinical guidelines and reimbursement policies.

Expression analysis of hsa_circ_0020397, hsa_circ_0005986, hsa_circ_0003028, and hsa_circ_0006990 in renal cell carcinoma.

Renal cell carcinoma (RCC) is a prevalent heterogeneous kidney cancer. So far, different genes have been reported for RCC development. However, its particular molecular mechanism remains unclear. Circular RNAs (circRNAs), a class of non-coding RNAs, are involved in numerous biological processes in different malignancies such as RCC. This study aims to assess the expression and underlying mechanism of four circRNAs (hsa_circ_0020397, hsa_circ_0005986, hsa_circ_0003028, hsa_circ_0006990) with possible new roles in RCC. In the experimental step, we investigated the expression of these four circRNAs in our RCC samples using quantitative real-time polymerase chain reaction. In the bioinformatics step, the differential expressed mRNAs (DEmRNAs), and miRNAs (DEmiRNAs) were obtained from the GEO datasets using the GEO2R tool. A protein-protein interaction network was constructed using the STRING database, and hub genes were identified by Cytoscape. Molecular pathways associated with hub genes were detected using KEGG pathway enrichment analysis. Then, we utilized the ToppGene database to detect the relationships between DEmiRNAs and hub genes. Furthermore, interactions between circRNAs and DEmiRNAs were predicted by the StarBase and circinteractome databases. Finally, a circRNA-DEmiRNA-hub gene triple network was constructed. Our results revealed that the expression of hsa_circ_0020397, hsa_circ_0005986, and hsa_circ_0006990 was downregulated in RCC tissues. Moreover, these circRNAs had a significantly lower expression in patients with a history of kidney disease. Furthermore, hsa_circ_0003028 and hsa_circ_0006990 showed higher expression in the tumor of participants with Lymphovascular/perineural invasion and oncocytoma type, respectively. Based on bioinformatic results, 15 circRNA-DEmiRNA-hub gene ceRNA regulatory axes were predicted, which included three hub genes, five miRNAs, and four selected circRNAs. In conclusion, the current work is the first to emphasize the expression of the hsa_circ_0020397, hsa_circ_0005986, hsa_circ_0003028, and hsa_circ_0006990 in RCC patients presents a novel perspective on the molecular processes underlying the pathogenic mechanisms of RCC.

Concordance between Gleason score of prostate biopsies and radical prostatectomy specimens and its predictive factors.

OBJECTIVE: The Gleason score is an essential factor for making decisions about prostate cancer management and its prognosis. Thus, we conducted this research to discover the histologic-grading accuracy of needle biopsy specimens, and to identify preoperative clinical and pathological factors that predict upgrading and downgrading from biopsy to radical prostatectomy specimen. PATIENTS AND METHODS: This study was performed on 570 patients who were referred to the medical centers affiliated with Shiraz University of Medical Sciences and underwent radical prostatectomy from 2013 to 2017. Concordance was evaluated between the Gleason score of needle biopsy and radical prostatectomy specimens. Predictors of upgrades and downgrades were assessed in univariate and multivariate logistic regression analyses. RESULTS: Scores were the same in 50% of cases, downgraded in 26%, and upgraded in 24%. The variables predicting a Gleason score upgrade were higher Prostate specific antigen level, larger tumors, and older age. Lower tumor volume, lower Prostate specific antigen, and low maximum percentage of cancer in cores were predictors of downgrading from Gleason score>6 to ⩽6. Also, Body mass index>30, smaller tumor size, and negative lymph nodes were predictors of downgrading from Gleason score>7 to 7. CONCLUSION: The correlation between biopsy and Radical prostatectomy Gleason scores was only 50%. After dividing them into the new grading groups, this coordination increased by only 5.6%. Physicians need to consider possible limitations of the Gleason score of biopsy and factors that can be predictive of upgrading to high-risk prostate cancer before making treatment decisions.

Synchronized Laparoscopic Bilateral Adrenalectomy for Pheochromocytoma in Multiple Endocrine Neoplasia Syndrome: A Case Report.

Pheochromocytomas are tumors producing catecholamines that arise from chromaffin cells in the adrenal medulla. They are usually benign in multiple endocrine neoplasia type 2 (MEN2) syndrome, but they tend to present bilaterally in 50-80% of the patients. Few researchers have reported success with simultaneous laparoscopic bilateral adrenalectomy. Hence, we report a 48-year-old woman who presented with a panic attack, headache, and abdominal discomfort that had started 10 years ago. The computed tomography (CT) scan showed a large bilateral cystic lesion in both adrenal glands in favor of pheochromocytomas (30 × 22 mm and 18 × 15 mm on the right side and 40 × 33 mm and 35 × 28 mm on the left side). The patient underwent bilateral laparoscopic adrenalectomy without intraoperative or postoperative complications. The total blood loss was 50 cc, and the operative time was 4 h. The histopathology of the specimen revealed pheochromocytomas of adrenal masses. In conclusion, our case demonstrates that synchronized laparoscopic bilateral adrenalectomy can be a safe and feasible treatment option for pheochromocytomas in MEN2 patients.

Comparison of Male and Female Sexual Dysfunction between Hemodialysis and Peritoneal Dialysis in Patients with End-Stage Renal Disease: An Analytical Cross-Sectional Study.

Background: Maintenance dialysis is the most common treatment for end-stage renal disease (ESRD) patients. One of the most ignored but important health issue among dialysis patients is sexual dysfunction, which interferes with quality of life (QoL). Studies showed that the side effects of the two conventional methods of dialysis (hemodialysis (HD) and peritoneal dialysis (PD)) are different on a patient's health. Therefore, we sought to compare the sexual dysfunction score, both male and female, between patients undergoing HD and PD. Methods: One hundred seventy adults (85 HD and 85 PD) subject with end-stage renal disease (ESRD) on dialysis for at least 2 months were included. For male subjects, the erectile function (EF) domain of the International Index of Erectile Function (IIEF) questionnaire was calculated. Moreover, the Female Sexual Function Index (FSFI) questionnaire was calculated for females. Data were analyzed via SPSS software. Two independent sample t-test with two-sided significance level of 5% was used for comparing the sexual dysfunction score between HD and PD patients. Results: Out of 170 patients with mean age of 49.34 ± 11.7 years, 52.9% were female. Better sexual function scores were obtained in the HD group's females for desire, orgasm, and satisfaction domains, as well as the total score (P = 0.03, 0.016, 0.02, and 0.039, respectively). The erectile function was significantly better in the PD group's males (P). Conclusion: We found better sexual life in the HD group's females and PD group's males. Considering dialysis as a life-long treatment of CKD patients, this part of a patient's life must be taken seriously by the healthcare providers to choose the most suitable method for patients based on their personalized conditions.

An Investigation of the Pathology Report of Bladder Cancer Patients with Radical Cystectomy in Southern Iran, 2013-2018: A Cross-Sectional Study.

Background: The oncological outcomes of bladder cancer are directly associated with disease pathology and surgical technique. Therefore, we investigated the pathologic factors of radical cystectomy (RC) specimens. Methods: In this retrospective study, 365 patients who underwent RC between March 2013 to March 2018 in hospitals affiliated to Shiraz University were enrolled. The patients' clinicopathological parameters, such as tumor type, tumor grade, carcinoma in situ, lymph node (LN) involvement, lymphovascular invasion (LVI), perineural invasion (PNI), and age, were recorded from their pathology reports. For comparison of variables, an independent t test was used. P < 0.05 was regarded as significant. The statistical software SPSS version 22 was used to examine the data. Results: The participants' mean age was 64.52 ± 11.54 years, and 320 (87.7%) patients were men and 45 (12.3%) were women. The mean dissected LN was 9.69 ± 8.70 nodes and 1.06 ±3.49 of the dissected LNs were involved by tumor. PNI and perivesical invasion were presented in 148 (40.5%) and 96 (26.3%) patients, respectively. Ureteral, urethral, and prostate involvements were seen in 23 (6.3%), 50 (13.7%), and 66 (18.1%) patients. Most patients had pathologic tumor stage 2 (36.4%). Factors such as LVI, PNI, perivesical invasion, and prostate involvement, were strongly correlated with positive LN (P ≤ 0.05). Conclusion: The examination of the RC specimen is critical for patient care, outcome, and justification of adjuvant therapy. Factors such as LVI, perineural invasion, perivesical invasion, and prostate involvement were strongly correlated with positive LN.

Genital exam, a missed piece of the puzzle in medical diagnosis, can be lifesaving in men: A lesson from a case of a state of shock due to duodenal metastasis of testicular choriocarcinoma.

Here we reported a case of a 17-year-old man with a history of weakness, vertigo, nausea, vomiting and dark stool within the last three months prior to admission. He was taken to the Emergency Room in a state of shock. After resuscitation, vital signs became stable, but due to low hemoglobin (HB = 5 g/dl), to find the source of bleeding, endoscopy was performed and a mass in the duodenum was detected. The pathology report was metastatic germ cell tumor. On genital physical exam (PE) there was a mass in the right testis; thus, the patient underwent radical orchiectomy and choriocarcinoma was diagnosed. The patient then received chemotherapy for six months, and he responded well to the treatment. This case report confirmed that genital PE should be part of a patients visit, even when we cannot find logical relation between clinical presentation and genital PE.

Testicular papillary serous carcinoma of ovarian type, a rare case report, however an important timely diagnostic issue.

A 28 years old man presented with left testicular swelling for recent few months. Ultrasonography and Computed tumor scan was in favor of solid cystic mass. The patient underwent left radical orchiectomy. The pathology diagnosis with aid of Immunohistochemistry staining approved the mullerian duct origin. Papillary serous carcinoma of ovarian type(PSCOT) is diagnosed for him. The patient treated successfully he was symptom free in two years follow up after orchiectomy. Timely diagnosis of PSCOT and orchiectomy are the keys of the patient survival; because prior to tumor spreading, the patient can be discharged after orchiectomy without adjuvant treatment.

Clinical relevance and prognostic significance of PD-1/PD-Ls in non-metastatic bladder cancer: A role for PD-L2.

BACKGROUND: Bladder cancer (BC) can be successfully treated by manipulating immune responses with intravesical Bacillus Calmette-Guerin instillation or targeting the PD-1/PD-L signaling pathway. In the present study we investigated the prognostic significance of the immune checkpoint inhibitor PD-1 and its ligands PD-L1 and PD-L2 on tumor cells and infiltrating lymphocytes, in the tumor microenvironment and draining lymph nodes in patients with non-metastatic BC. PATIENTS AND METHODS: Cells were mechanically isolated from tissues and draining lymph nodes from 58 patients, and surface-stained for CD45, PD-1, PD-L1 and PD-L2. The cells were then analyzed with a flow cytometric method. RESULTS: Approximately 2% of CD45-negative tumor and stromal cells expressed PD-L1. Expression was not associated with the main clinicopathological characteristics of the disease or with survival. However, as tumors progressed the frequency of PD-L1+CD45hi cells and the mean expression of PD-1 on CD45hi cells increased remarkably on immune cells in tumor tissues and draining lymph nodes. In addition, frequency analysis showed that cell percentages as well as mean expression of PD-L2 on total CD45+ lymphocytes and their CD45hi subpopulation in tumor-draining lymph nodes was significantly associated with cancer-related death (P < 0.05). Multiple Cox regression also revealed that while CD45+ (hazard ratio: 0.596, 95 % CI 0.439-0.809, P = 0.001) was associated with improved survival, CD45neg (HR: 0.615, 95 % CI 0.454-0.831, P = 0.002), and PD-L2+CD45+ cells (hazard ratio: 1.472, 95 % CI 1.023-2.120, P = 0.038) in draining lymph nodes were associated with lower survival. CONCLUSION: Our results suggest that in patients with BC, PD-1 and PD-L expression on immune cells, especially in draining lymph nodes, is valuable for predicting prognosis and survival, and possibly responsiveness to immunotherapy. However, expression of the inhibitor molecule or its ligands on tumor cells was not associated with prognosis. The results highlight the significance of PD-L2 as a second important suppressive molecule in tumors.

Scrotal leiomyoma a rare benign intra-scrotal mass could lead to unnecessary orchiectomy.

Leiomyoma is a benign tumor originating from smooth muscle cell, Mostly from uterus. However, in men is a very rare entity. Scrotal leiomyoma is a very rare tumor. Here we presented a case of scrotal leiomyoma in a 71-year-old man. He presented with a slowly growing, painless mass and heaviness in the left testis for 10 years. Due to huge size, testicular attachment and preoperational diagnosis of atypical leiomyoma/leiomyosarcoma, orchiectomy was performed. Pathology report diagnosed leiomyoma. We suggest frozen section diagnosis as a useful tool, to prevent unnecessary procedure.

Primary amelanotic melanoma of the male urethra: A rare entity and diagnostic challenge.

Malignant melanoma (melanoma) is a tumor of melanocytes that usually presents as cutaneous lesions. While melanoma can infrequently appear as a primary tumor elsewhere in the body, it is extremely rare in the urethra and even rarer as amelanotic malignant melanoma. We report the case of a 66-year-old male who presented with painless gross hematuria and lower urinary tract obstructive symptoms in the recent 2 weeks prior to his visit to our clinic. History and physical examination, including external genital examination, abdominopelvic sonography, and urine culture, were not conclusive. Cystourethroscopy revealed a creamy pink fragile mass located in the anterior proximal urethra that extended to the mid portion. Pathological examination of this lesion confirmed the diagnosis of amelanotic malignant melanoma using immunohistochemistry. Radical cystourethrectomy with ileal conduit was subsequently conducted. Although this tumor is extremely rare, urologists and pathologists should consider malignant melanoma as a diagnosis in patients with urethral tumor because of the likelihood of early metastasis and, consequently, poor prognosis. Complete surgical removal of the tumor and use of effective therapies can improve outcomes in these patients.

The prevalence of undiagnosed type 2 diabetes and prediabetes in Eastern Mediterranean region (EMRO): A systematic review and meta-analysis.

BACKGROUND: Previous studies of diabetes in Eastern Mediterranean Region (EMRO) did not assess the prevalence of either unknown diabetes or prediabetes. We conducted a systematic review and meta-analysis to estimate the prevalence of undiagnosed type 2 diabetes and prediabetes as well as variations by region in EMRO, using the relevant publications since 2000. METHODS: We carried out a comprehensive electronic search on electronic databases from January 1, 2000 to March 1, 2018. We selected cross-sectional and cohort studies reporting the prevalence of undiagnosed type 2 diabetes, prediabetes, or both. Two independent reviewers initially screened the eligible articles; then, synthesized the target data from full papers. Random- or fixed-effect models, subgroup analysis on Human Development Index (HDI), and publication year and sensitivity analysis to minimize the plausible effect of outliers were used. RESULTS: Amongst 849 identified citations, 55 articles were entered into meta-analysis, involving 567,025 individuals. The forest plots estimated 5.46% (confidence intervals [CI]: 4.77-6.14) undiagnosed diabetic and 12.19% (CI: 10.13-14.24) prediabetics in EMRO. Low HDI countries and high HDI countries had the highest (7.25%; CI: 4.59-9.92) and the lowest (3.98%; CI: 3.11-4.85) undiagnosed diabetes prevalence, respectively. Very high HDI countries and low HDI countries had the highest (13.50%; CI: 8.43-18.57) and the lowest (7.45%; 1.20-13.71) prediabetes prevalence, respectively. In addition, meta-regression analysis showed a statistically significant association between publication year and prevalence of prediabetes (Reg Coef = 0.059, P = 0.014). But such finding was not observed for undiagnosed diabetes and publication year (Reg Coef = 0.034, P = 0.124), prediabetes and HDI (Reg Coef = 0.128, P = 0.31) and undiagnosed diabetes and HDI (Reg Coef = - 0.04, P = 0.96). CONCLUSION: The prevalence of undiagnosed diabetes and prediabetes was high and increasing. The notion of universal health coverage is a priority; that is the integration of the primary, secondary and tertiary health levels, as well as employing the available action plans. Therefore, future studies, using identical screening tool and diagnostic criteria, are warranted to make an accurate picture of diabetes in EMRO.

Western Dietary Pattern, But not Mediterranean Dietary Pattern, Increases the Risk of Prostate Cancer.

BACKGROUND AND AIM: Prostate cancer is the most common cancer among men. Several studies have investigated the effects of dietary patterns on prostate cancer risk, but this topic is still a matter of debate. This study aimed to examine the association between dietary patterns and prostate cancer risk. METHODS: In a case-control study, 60 newly diagnosed prostate cancer cases and 60 hospital-based controls were selected from two main hospitals of Shiraz, Iran. Data on dietary intakes, anthropometric features, and demographic characteristics were collected. To determine the dietary patterns factor analysis, and to estimate the odds ratios (ORs), multivariable logistic regression was performed. RESULTS: Two major dietary patterns were identified: Western dietary (WD) pattern and Mediterranean dietary (MD) pattern. After adjusting for potential confounders, men who had higher scores for WD pattern (above the median) were more likely to have prostate cancer (OR = 5.15; 95% CI (1.44-18.47); P = 0.01) compared with men who had lower scores. A nonsignificant inverse association was found for MD pattern (OR = 0.62; 95% CI (0.22-1.77); P = 0.37). CONCLUSIONS: Our findings suggest that WD pattern may increase the risk of prostate cancer and the beneficial effects of MD pattern on prostate cancer risk need further research.

Detection of Y Chromosome Microdeletions and Hormonal Profile Analysis of Infertile Men undergoing Assisted Reproductive Technologies.

BACKGROUND: Y chromosome deletions (YCDs) in azoospermia factor (AZF) region are associated with abnormal spermatogenesis and may lead to azoospermia or severe oligozoospermia. Assisted reproductive technologies (ART) by intracytoplasmic sperm injection (ICSI) and testicular sperm extraction (TESE) are commonly required for infertility management of patients carrying YCDs. The aim of this study was to estimate the frequency of YCDs, to find the most frequent variant in infertile men candidate for ART and to compare YCD distribution with a control fertile group. The semen parameters, hormonal profiles and ART outcomes of the infertile group were studied. MATERIALS AND METHODS: This case-control study consisted of 97 oligozoospermic or non-obstructive azoospermic (NOA) infertile men, who had undergone ART, as the case group and 100 fertile men as the control group. DNA samples were extracted from blood samples taken from all 197 participants and YCDs were identified by multiplex polymerase chain reaction (PCR) of eight known sequence-tagged sites. The chi-square test was used to compare the mean values of hormone and sperm parameters between the two groups. P<0.05 was considered statistically significant. RESULTS: No YCD was detected in the control group. However, 20 out of 97 (20.6%) infertile men had a YCD. AZFc, AZFbc and AZFabc deletions were detected in 15 (75%), four (20%) and one (5%) YCD-positive patients. No fertilization or clinical pregnancy was seen following ICSI in this sub-group with YCD. The mean level of FSH was significantly higher in the group with YCD (28.45 ± 22.2 vs. 4.8 ± 3.17 and 10.83 ± 7.23 in YCD-negative patients with and without clinical pregnancy respectively). CONCLUSION: YCD is frequent among NOA men and YCD screening before ART and patient counseling is thus strongly recommended.

CD8+ T Lymphocyte Subsets in Bladder Tumor Draining Lymph Nodes.

BACKGROUND: Cytotoxic CD8+ T cells, as essential parts of the adaptive immune system, play pivotal roles in anti-tumor immune responses. It is well documented that cytokine expression profiles and activation status of these cells during anti-tumor immune responses affect the outcome of host-tumor interaction. OBJECTIVE: To investigate the percentages of CD8+ lymphocytes and their subsets in tumor draining lymph nodes of patients with bladder cancer. METHODS: Forty-five patients with bladder cancer, candidate for radical cystectomy, were recruited. Mononuclear cells were isolated from draining lymph nodes using Ficoll-Hypaque gradient centrifugation, and were activated by PMA/Ionomycin in the presence of Golgi inhibitors. The cells were then permeabilized and stained with appropriate flourochrome conjugated antibodies against CD3, CD8, IFN-γ, IL-17 and IL-4 molecules. Data were collected on a four-color flow cytometer and analyzed by CellQuestPro software. RESULTS: Despite no difference in the frequency of IL-17 producing CD8+ (Tc17) lymphocytes, the mean expression of IL-17 in this subset was significantly elevated in high-grade patients (p=0.011). The percentage of double positive IFN-γ/IL-17 CD8+ lymphocytes was also significantly increased in node positive patients compared to node negative ones (p=0.046). Our results also demonstrated that the percentage of IFN-γ producing CD8+ (Tc1) lymphocytes was significantly increased in the patients with higher histological grade compared to those with lower ones (p=0.038). CONCLUSION: IFN-γ and IL-17 producing CD8+ T cells may increase in advanced stages of bladder cancer, but their correlation with tumor prognosis remains to be investigated.

Prostate-specific antigen doubling time as a predictor of Gleason grade in prostate cancer.

INTRODUCTION: Our aim was to evaluate the value of serum prostate-specific antigen doubling time (PSADT) to identify patients with high-grade prostate cancer who require more aggressive therapy from those with low-grade cancer. MATERIALS AND METHODS: Of 460 patients with extended 12-core transrectal ultrasonography-guided biopsy of the prostate, 59 with confirmed prostate cancer were selected. They had not received any previous treatment for prostate cancer and had at least 2 consecutive serum PSA tests with a rising trend. The PSADT was calculated in patients with 2 serum PSA levels measured with an interval more than 3 months. RESULTS: Of 59 patients with prostate cancer, 35 (59.3%) had low-grade and 24 (40.7%) had high-grade tumors. There was no difference in age between the two groups. The median PSADT in patients with high-grade and low-grade tumors were 12.70 months (range, 0.7 to 44.8 months) and 25.00 months (range, 1.65 to 41.2 months; P = .001). A total of 21 patients with high-grade tumors (87.5%) had a PSADT less than 12 months, while only 9 of those with low-grade tumors (25.7%) had a PSADT less than 12 months. A PSADT cutoff of 12 months provided a sensitivity of 74% and a specificity of 87% for differentiation of high-grade from low-grade cancers. CONCLUSION: We showed that men with a short PSADT (< 12 months) were at a higher risk of harboring a high-grade prostate cancer. Our data suggests PSADT to identify patients with high-grade tumors who require more aggressive therapy.