Comparative proteomics analysis in different stages of urothelial bladder cancer for identification of potential biomarkers: highlighted role for antioxidant activity.

BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) has a high recurrence rate and muscle-invasive bladder cancer (MIBC) has unfavorable outcomes in urothelial bladder cancer (UBC) patients. Complex UBC-related protein biomarkers for outcome prediction may provide a more efficient management approach with an improved clinical outcome. The aim of this study is to recognize tumor-associated proteins, which are differentially expressed in different stages of UBC patients compared non-cancerous tissues. METHODS: The proteome of tissue samples of 42 UBC patients (NMIBC n = 25 and MIBC n = 17) was subjected to two-dimensional electrophoresis (2-DE) combined with Liquid chromatography-mass spectrometry (LC-MS) system to identify differentially expressed proteins. The intensity of protein spots was quantified and compared with Prodigy SameSpots software. Functional, pathway, and interaction analyses of identified proteins were performed using geneontology (GO), PANTHER, Reactome, Gene MANIA, and STRING databases. RESULTS: Twelve proteins identified by LC-MS showed differential expression (over 1.5-fold, p < 0.05) by LC-MS, including 9 up-regulated in NMIBC and 3 up-regulated in MIBC patients. Proteins involved in the detoxification of reactive oxygen species and cellular responses to oxidative stress showed the most significant changes in UBC patients. Additionally, the most potential functions related to these detected proteins were associated with peroxidase, oxidoreductase, and antioxidant activity. CONCLUSION: We identified several alterations in protein expression involved in canonical pathways which were correlated with the clinical outcomes suggested might be useful as promising biomarkers for early detection, monitoring, and prognosis of UBC.

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.

Prognostic significance of immunoscore related markers in bladder cancer.

BACKGROUND: The significance of total and specific subpopulations of tumor-infiltrating lymphocytes (TILs) in cancer is now well-documented. In the present study, we investigated the relevance of CD3+, CD8 +, CD45RO +, and FOXP3 + TILs to the prognosis and survival of patients with bladder cancer and the disease's clinical-pathological parameters. METHODS: Infiltration of each subset was immunohistochemically evaluated in both stromal and intratumoral regions of tumor tissues from 85 patients with urothelial cell carcinoma of the bladder, with known survival. RESULTS: Our results indicated that intratumoral CD45RO+ lymphocytes were significantly higher in high-grade tumors than in low-grade ones (P = 0.028). The frequencies of intratumoral CD3+ (P = 0.002), CD8 + (P = 0.008), intratumoral (P = 0.002), and stromal (P = 0.017) CD45RO+ lymphocytes were also higher in patients with muscular invasion than those without invasion. The frequencies of intratumoral CD3+ (P = 0.043), CD8+ (P = 0.003), CD45RO+ (P = 0.023), and total CD45RO+ (P = 0.015), showed variation in patients with different T-stage, as well; mostly increased in T2 versus Ta and T1. Comparing patients in different stages revealed an increase in the frequencies of total CD3+ (P = 0.011), intratumoral CD3+ (P = 0.006), total CD8+ (P = 0.012), intratumoral CD8+ (P = 0.009) and stromal CD8+ (P = 0.034), as well as total and stromal CD45RO+ lymphocytes (P = 0.01 and P = 0.034, respectively) in stage II comparing to stage I, while the frequencies of stromal CD3+ (P = 0.077) and CD8+ (P = 0.053) cells tended to be decreased in stage III compared to stage II. CONCLUSIONS: We collectively observed that the frequency of immune cells, especially CD45RO+, CD3+, and CD8+ lymphocytes, were significantly higher in early-progressed tumors. This observation could be explained by continuous and prolonged stimulation of immune cells with tumor antigens during tumor progression or an increase in the recruiting factors, especially in the early stages, to eliminate tumor cells. However, with tumor progression to the late stages, the inhibitory microenvironment provided by tumor cells suppresses or changes the functionality of the effector and memory immune cells to help tumor growth. However, more functional studies with larger sample sizes are needed to reveal the real status of the immune system in patients with bladder cancer.

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.

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.

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.

Serum concentration of interleukin-35 and its association with tumor stages and FOXP3 gene polymorphism in patients with prostate cancer.

IL-35 is an immunosuppressive cytokine that is largely synthesized by regulatory T (Treg) cells and may inhibit antitumor immune responses. This investigation aimed to determine the serum IL-35 concentrations and a single nucleotide polymorphism (SNP) in position of rs3761548, within the promoter region of FOXP3 gene, in patients with prostate cancer (PC). The blood specimens were obtained from 150 PC patients prior to using radiation therapy, chemo- or immunotherapy and 150 age-matched healthy men as a control group. The serum IL-35 concentrations and the pattern of genetic variation at position of rs3761548 were assessed using ELISA and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), respectively. The mean serum IL-35 concentrations were significantly higher in PC patients when compared with healthy control group (20.01 ±â€¯7.03 Pg/mL vs. 11.60 ±â€¯2.49 Pg/mL, P < 0.001). The serum IL-35 concentrations raised with progression of PC stages so that there was a significant difference between PC stages concerning the IL-35 concentrations (P < 0.001). The mean serum IL-35 concentrations in patients with Gleason scores of 1-6 and Gleason scores 7-10 were significantly higher as compared with healthy controls (P < 0.001). Moreover, the serum IL-35 concentrations in patients with having Gleason scores of 7-10 were significantly higher as compared with patients with Gleason scores of 1-6 (P < 0.001). Evaluation of the genetic variations in position SNP rs3761548 revealed that the AA genotype and A allele were more prevalent whereas CC genotype and C allele were less prevalent in PC patients when compared with healthy men (P < 0.01, P < 0.001, P < 0.002 and P < 0.001, respectively). The AA genotype and A allele were associated with higher risk of PC incidence [OR: 2.42 (95% CI: 1.179-4.99); P < 0.001 and OR: 1.732 (95% CI: 1.244 - 2.413); P < 0.001, respectively]. The mean serum IL-35 concentrations were significantly higher in total subjects (PC patients + healthy individuals) with AA genotype and A allele than individuals with CC genotype and C allele at SNP rs3761548 (P < 0.05 and P < 0.01, respectively). Higher serum IL-35 concentrations observed in patients with PC that were increased with progressive tumor stages. These findings indicate that the IL-35 is possibly involve in tumor progression. Moreover, SNP rs3761548 may affect the susceptibility to PC and the serum IL-35 concentrations.

Clinical grading and color Doppler ultrasonography-based grading of varicocele: how compatible are the two grading systems?

OBJECTIVE: Inhere, we compared two of the most common grading systems based on color Doppler ultrasonography (CDU) and physical examination in patients suspected of varicocele. METHODS: This is a cross-sectional study. Overall, 66 patients clinically suspected of varicocele were visited by an attending urologist and a radiologist for physical examination and CDU. Varicocele was then graded according to the WHO criteria and Sarteschi criteria. For comparing the results of the two grading systems, each grading systems was then categorized into four scoring groups. Clinical- and CDU-based scoring, and mean maximum variceal vein diameter (MMVD) were evaluated and compared. RESULTS: The two scoring systems were statistically similar (p < 0.001). CDU scoring of right and left testicles had significant agreement with clinical scoring of varicocele (κ = 0.723 and κ = 0.809, respectively; p < 0.001). MMDV was associated with clinical (right sided: r = 0.681; left sided: r = 0.797; p < 0.001) and ultrasonography scoring (right sided: r = 0.648; left sided: r = 0.821; p < 0.001). CONCLUSION: Grades zero, one and two in ultrasonographic grading are most compatible with grade zero (sub-clinical) in clinical evaluation; so these grades most probably remain undetected in routine physical examination. Furthermore, grade three in ultrasonography and grade one in clinical grading, grade four in ultrasonography and grade two in clinical grading, and finally grade five in ultrasonography and grade three in clinical grading are most compatible. So, by deducting two grades from the ultrasonography grading of varicocele measured by the Sarteschi method, one can obtain a compatible estimate of the clinical grading.

KIRs gene content diversity in Iranians with urothelial bladder cancer.

Natural killer cells (NK) are the first arm of the innate immune system in defense against tumor and infection. 16 distinct Killer-cell immunoglobulin-like receptors (KIRs) are involved in orchestrating NK cell function. The KIR family contains 14 genes and 2 pseudogenes. Six of these receptors are activating (aKIR) and the remaining receptors are inhibitory KIRs (iKIR), that interact with MHC-I molecules; producing signals which stop NK cell function. In the current study, we have investigated the genomic diversity of KIRs and determining the A and B haplotypes as well as Bx subsets in 119 patients with bladder cancer and 200 healthy controls to find out if there is an association between KIR system and susceptibility to bladder cancer. Polymerase chain reaction with sequence specific primers (SSP-PCR) typing system was used to determine the KIR gene profile. The results implicated decreased frequency of inhibitory KIR2DL2 and activating KIR2DS2 while increased frequency of CxT4 genotypes in patients compared with healthy controls. Among Bx subsets, the CxT4 gene cluster is more frequent in bladder cancer patients compared to controls. Our results provide a conclusion that KIR2S2 and KIR2L2 may play a protective role against bladder cancer development while the CxT4 gene cluster may underlie susceptibility to bladder cancer in Iranian population.

Natural Killer Cell Subsets in Tumor Draining Lymph Nodes of Patients with Bladder Cancer and Their Clinical Implications.

Background: Natural killer (NK) cells are crucial innate components in anti-tumor immunity. However, the clinical impacts and their phenotypes in bladder cancer (BC) remain unclear. Objective: To assess the clinical significance of NK cell subsets in tumor-draining lymph nodes of patients with BC. Methods: In a cross-sectional study, pelvic lymph nodes were obtained from 49 untreated patients with BC. Mononuclear cells were isolated and immunophenotyped using CD3, CD56, CD16, CD27, and CD11b markers. NK cells were then classified based on their expression patterns of CD56/CD16 (conventional) and CD27/CD11b (new). Results: On average, NK cells constituted 2.99±1.44% of the total lymphocytes in the draining lymph node of patients with BC. The CD56dim and regulatory NK subsets (CD27+CD11b+/-) were the predominant old and new NK, respectively. The NK cells significantly increased in patients with at least one involved node (LN+) compared with those with free nodes (LN-; p=0.022). Conversely, CD56dimCD16- subset significantly decreased in higher stages (p=0.032) and in tumors with muscle invasion (p=0.038). Significant variations were also observed in different T-stages (p<0.05). Regarding new classification, the frequency of CD11b+ regulatory NK cells was significantly lower in node-positive patients (p=0.025). Conclusion: These findings emphasize the dynamic nature of NK cell subsets in bladder cancer and their potential relevance in disease progression and management, suggesting potential implications for therapeutic strategies targeting these specific subsets.

Clinical and prognostic significance of follicular helper and regulatory T cells in bladder cancer draining lymph nodes.

Follicular helper and regulatory T cells (Tfh/TFR) cells are distinct subsets of CD4+ cells that have been recognized for their critical role in regulating cellular reactions within the germinal centers of lymphoid follicles. In the present study, we aimed to determine the presence and the frequency of these cells in draining lymph nodes of patients with bladder cancer (BC). Forty-six patients with BC who had undergone radical cystectomy and pelvic lymph node dissection were enrolled. Following routine pathological examination, a portion of the dissected lymph nodes was minced to obtain a single-cell suspension. Mononuclear cells were then separated using Ficoll-Hypaque gradient centrifugation, and the samples with proper viability (> 95%) were subjected to further analysis. To phenotype the follicular subsets, cells were stained with appropriate fluorochrome-conjugated antibodies specific for CD4, CXCR5, BCL6, and FOXP3. The cells were then acquired on a four-color flow cytometer. The data were analyzed with the FlowJo software version 10.8.1 package. Our analysis indicated that, on average 37.89 ± 16.36% of CD4+ lymphocytes in draining lymph nodes of patients with BC expressed CXCR5. The majority of them were negative for FOXP3, representing helper subsets (28.73 ± 13.66). A small percent simultaneously expressed BCL6 transcription factor (1.65% ± 1.35), designated as Tfh (CD4+BCL6+CXCR5+FOXP3-). While less than 10% of CD4+ lymphocytes expressed CXCR5 and FOXP3, 1.78 ± 2.54 were also positive for BCL6, known as TFR. Statistical analysis revealed that the frequency of both Tfh and TFR cells was higher in draining lymph nodes of patients with tumor-infiltrated nodes (P = 0.035 and P = 0.079, respectively) compared to those with negative ones. The percentage of these cells was also higher in high-grade tumors compared to low-grade ones (P = 0.031 for both). Our data collectively indicated that however approximately one third of CD4+ lymphocytes expressed CXCR5 and accordingly had the capacity to enter the follicles, less than 2% of them represented Tfh and TFR phenotypes. The percentage of these cells increased in progressed tumors and showed an association with negative prognostic factors.

Diversity of Memory CD8+ T Cells in Tumor-Draining Lymph Nodes from Patients with Bladder Cancer.

The role of memory T cells in orchestrating memory responses to previously known tumor antigens is well documented. The aim of this study was to assess the frequency of different memory T cell subsets in tumor-draining lymph nodes of patients with bladder cancer (BC) and their prognostic significance. Mononuclear cells were isolated from 50 tumor-draining lymph nodes of untreated patients with BC and stained with antibodies against the markers CD8, CD95, CD45RO and CCR7. Data were collected using the FACSCalibur flow cytometer and analyzed using FlowJo software. Among the CD8+ cytotoxic lymphocytes, the frequency of different subsets was determined including total memory cells (CD8+CD45RO+CD95+), T central memory (TCM: CD8+CCR7+CD45RO+CD95+), T effector memory (TEM: CD8+CCR7-CD45RO+CD95+), T stem cell memory (TSCM: CD8+CCR7+CD45RO-CD95+) and naïve T cells (CD8+CCR7+CD45RO-CD95-). The analysis revealed that on average 49.32±20.15 (between 1.62% and 87.20%) percent of CD8+ lymphocytes in draining lymph nodes of BC had a memory phenotype. TCM cells showed the highest frequency (34.71±17.04), while TSCM cells (7.51±8.53) demonstrated the lowest. The total frequency of memory cells tended to be higher in patients with tumor invasion to muscle layer (P=0.052) and stage III (P=0.042) than in patients without invasion and stage I. The TCM subset was more frequent in patients with necrotic tumors than in patients without necrosis (P=0.048). TSCM significantly increased in patients with N2 compared to N0 (P=0.042). Conversely, the ratio of TSCM cells to total memory cells was higher in lower tumor stages (P=0.059), tumors without muscle invasion (P=0.026) and low T grouping (P=0.043). Overall the data indicated an increase in the frequency of memory T cells and their TSCM and TCM cells with tumor progression. In contrast, the ratio of TSCM to total memory cells was higher in less advanced tumors. These results suggest that the immune system is frequently exposed to tumor antigens and strives to create a memory T cell reservoir, but this is suppressed by inhibitory factors provided by the tumor. These findings emphasize the importance of understanding the dynamic interplay between memory T cell subsets and BC progression.

Sudden cardiovascular collapse during the TUL procedure: A case series.

Although ureteroscopy is a minimally invasive procedure, there have been reports of some minor and major complications, from self-limited to complicated events such as ureteral avulsion, urosepsis, and even death due to cerebrovascular accidents and deep vein thrombosis. Herein, we aim to report seven patients who presented with cardiovascular collapse during ureteroscopy in a 19-year period from January 2002 to January 2021.

Two metabolic enzymes, LDH and FASN, serum levels in Bladder cancer patients.

Background: Bladder cancer is one of the most common cancers in the world and is associated with high treatment costs and mortality. The role of different enzymes and molecules in this cancer has been the subject of extensive research in recent years. Among these, the role of metabolic enzymes such as FASN and LDH has been studied less than others. Therefore, the present study was designed to investigate the role of FASN and LDH in bladder cancer patients. Methods: One hundred cases diagnosed with bladder cancer and 50 sex-age- matched healthy individuals as control were examined. FASN and LDH serum levels in both patients and controls were determined by human-specific sandwich ELISA kits. Results: Serum levels of FASN and LDH elevated in bladder cancer patients in comparison to healthy individuals (P= 0.03, P= 0.01, respectively). We also found that than higher stages of bladder cancer (III-IV) had higher serum levels of LDH and FASN compared to early stages (I-II) (P= 0.007 and P= 0.006, respectively). Moreover, there was a statistically significant association between smoking history and serum FASN levels in bladder cancer patients (P=0.015). However, there were no remarkable associations between the serum levels of LDH and FASN with other clinicopathological features including sex, age, tumor grade, and tumor size. Conclusion: The data indicate that LDH and FASN may be good and useful biomarkers in the diagnosis and clinical management of bladder cancer. However, further studies are needed.

The impact of killer cell immunoglobulin-like receptor (KIR) genes and human leukocyte antigen (HLA) class I ligands on predisposition or protection against prostate cancer.

Natural killer (NK) cell development largely depends on killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands. In the current study, we investigated the role of KIR genes, HLA ligands, and KIR-HLA combinations in vulnerability or protection against prostate cancer (PC). To analyze the frequency of 16 KIR genes and 5 HLA ligands, polymerase chain reaction with sequence-specific primers (PCR-SSP) was conducted in 150 PC patients and 200 healthy controls (CNs). KIR2DL5 (p = 0.0346, OR = 0.606, CI = 0.3916-0.9336), KIR2DS5 (p = 0.0227, OR = 0.587, CI = 0.3793-0.9139), HLA-B Bw4Thr80 (p = 0.0401, OR = 0.3552, CI = 0.1466-0.9059), HLA Bw4 (p = 0.0190, OR = 0.4744, CI = 0.2656-0.8521), and T4 gene cluster (including KIR2DS5-2DL5-3DS1-2DS1 genes) (p = 0.0194, OR = 0.5575, CI = 0.3449-0.8938) had a lower frequency in the PC patients compared to the control group. Moreover, a lower frequency of the genotypes contacting activating KIR (aKIR) > inhibitory KIR (iKIR) (p = 0.0298, OR = 0.5291, CI = 0.3056-0.9174) and iKIR + HLA < aKIR + HLA (p = 0.0183, OR = 0.2197, CI = 0.0672-0.7001) in PC patients compared to the CNs implies a protective role for aKIR genes. In the case of KIR-HLA interactions, we detected a significant association between KIR3DS1+ + HLA-A Bw4+ (p = 0.0113, OR = 0.5093, CI = 0.3124-0.8416) and KIR3DL1- + HLA-A Bw4+ (p = 0.0306, OR = 0.1153, CI = 0.0106-0.6537) combinations and resistance to prostate cancer. In contrast, the presence of KIR3DL1 in the absence of HLA-A Bw4 (p = 0.0040, OR = 2.00, CI = 1.264-3.111), HLA Bw4 (p = 0.0296, OR = 2.066, CI = 1.094-3.906), and HLA-Bw4Thr80 (p = 0.0071, OR = 2.505, CI = 1.319-4.703) genes probably predisposes to prostate cancer. Carrying the CxT4 genotype in PC patients was positively associated with lower tumor grades (Gleason score ≤ 6) (p = 0.0331, OR = 3.290, and CI = 1.181-8.395). Altogether, our data suggest a protective role for aKIRs, HLA-B Bw4Thr80, and HLA Bw4 ligands as well as a predisposing role for certain KIR-HLA combinations in prostate cancer. The findings of this study offer new insight into the population's risk assessment for prostate cancer in men. Additionally, predicting immunotherapy response based on KIR-HLA combinations aids in implementing the most effective therapeutic approach in the early stages of the disease.

Penile Girth Enhancement Using Amniotic Membrane in a Rabbit Model: A stereological study.

Objectives: This study aimed to evaluate the efficacy of penile girth enhancement (PGE) using amniotic membrane (AM) as a graft in a rabbit model. Additionally, quantitative histological data of the structure of the penis were obtained by stereological studies. Methods: This study was conducted at the Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. In this study, 20 adult male rabbits of similar age and weight were allocated to two groups: sham surgery and surgery+AM. Both groups underwent surgery in which a longitudinal I-shaped midline incision was made in the tunica albuginea on the dorsal surface of the penis. The surgery+AM group underwent PGE using AM as a graft. The penile length and mid circumference were measured using a vernier caliper before and two months after the surgery. Results: The mean total volume and diameter of the penis significantly increased in the surgery+AM group (P <0.03 and P <0.04, respectively). On stereological evaluation, a significant increase in the mean volumes of the tunica albuginea and corpora cavernosa was observed in the surgery+AM group compared to the sham group (P <0.01 and P <0.03, respectively). Additionally, the mean volume densities of the collagen bundles, muscle fibres, cavernous sinuses, and the total number of fibroblasts and smooth muscle cells increased in the surgery+AM group compared to the sham group (P <0.05 each). No infections, bleeding or other complications were observed. Conclusion: The use of AM as a graft is a method that shows promising results for material use in penile enhancement. Thus, it may be considered for PGE in the future.

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.

The effect of retroperitonealization of ureteroileal anastomosis on perioperative complications of radical cystectomy with ileal conduit urinary diversion.

BACKGROUND: Radical cystectomy (RC) has been considered the standard management of muscle-invasive bladder cancer. Despite the improvements in surgical techniques and perioperative care, RC is still associated with high perioperative morbidity and mortality. OBJECTIVE: This study aims to evaluate the effect of retroperitonealization of ureteroileal anastomosis on perioperative complications of RC with ileal conduit urinary diversion. PATIENTS AND METHODS: This is a retrospective cohort study. We reviewed medical charts of 876 patients who underwent RC between 2016 and 2021. Based on the inclusion and exclusion criteria, 748 patients entered the study. According to retroperitonealization of the ureteroileal anastomosis, patients were categorized into two groups (group I without retroperitonealization of the ureteroileal anastomosis and group II with retroperitonealization of the ureteroileal anastomosis). Patients' characteristics and occurrences of any complications and high-grade complications were compared between these groups. RESULTS: In comparing the complication categories between the two groups, fewer patients in group II suffered from gastrointestinal, urinary, and cardiac events (p values were 0.018, 0.021, and 0.013, respectively). Moreover, fewer patients in group II experienced any complications and high-grade complications (p values were < 0.001 and < 0.001, respectively). The length of hospital stay was also significantly shorter in group II (p < 0.001). CONCLUSIONS: RC is associated with comparatively high perioperative morbidity and mortality. In the present study, 61% of the patients experienced at least one complication postoperatively. Retroperitonealization of the ureterointestinal anastomosis may decrease perioperative adverse events of RC with ileal conduit urinary diversion.

Primary Rhabdomyosarcoma of Kidney with Local Recurrence and Liver Metastasis in Adults: A Case Report.

Primary rhabdomyosarcoma (RMS) of the kidney in an adult is rare, with only a few cases published in the literature. It is a mesenchymal tumor associated with an aggressive and rapid clinical progression course. We present a case of primary renal RMS in a 58-year-old female who presented with intermittent abdominal pain in the past year. The computed tomography (CT) scan revealed a 20×25×8 cm heterogeneous solid mass in the middle pole extended to the lower pole of the right kidney. Therefore, the patient underwent a right radical nephroureterectomy. Histopathology examination and immunohistochemistry studies confirmed the diagnosis of RMS with pleomorphic components. Postoperatively, the patient was discharged without any complications and was referred to an oncologist for chemotherapy. However, a follow-up CT scan in 2 months showed widespread liver metastasis and local recurrence. The patient received Gemcitabine and Docetaxel, but her condition worsened, and she passed away 5 months later. Primary renal RMS is rare in adults. In addition, liver metastasis is uncommon and poorly understood. Hence, we describe the clinicopathologic characteristics, including clinical follow-up of our case, focusing on the disease progression, treatment, and outcome.