Diagnosis and management of urinary bladder paragangliomas: A Sino-American-European retrospective observational study.

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

Follicular Fluid-Derived Exosomal MicroRNA-18b-5p Regulates PTEN-Mediated PI3K/Akt/mTOR Signaling Pathway to Inhibit Polycystic Ovary Syndrome Development.

Small RNA sequences in follicular fluid (FF)-derived exosomes (extracellular vesicles contain proteins, DNA, and RNA) vitally function in the development of polycystic ovary syndrome (PCOS). It has been identified that microRNA (miR)-18b-5p is one of miRs that differ between control and PCOS women that passed the false discovery rate, and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is an important modifier of biological functions of ovarian granulosa cells (GCs) in PCOS. However, whether miR-18b-5p could functionally mediate the progression of PCOS via PTEN was not clarified completely, which was the issue we wanted to solve in our research. FF-derived exosomes were isolated using an extraction kit. KGN cells were co-cultured with miR-18b-5p-modified exosomes or transfected with a PTEN-related vector. After treatment, cell proliferation and apoptosis were observed. A rat model of PCOS was established by letrozole and then injected with miR-18b-5p-modified exosomes. Then, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and estradiol (E2) levels in PCOS rats were measured. miR-18b-5p, PTEN, and phosphatidylinositol 3 kinases/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway-related genes were tested. In PCOS patients, miR-18b-5p was downregulated, and PTEN was highly expressed in FF and GCs. PTEN knockdown increased KGN cell proliferation and limited apoptosis. FF-derived exosomes stimulated proliferation and suppressed apoptosis of KGN cells; decreased FSH, LH, and testosterone; and increased E2 in PCOS rats. Upregulating miR-18b-5p further enhanced the inhibitory effects of exosomes on suppressing the progression of PCOS. miR-18b-5p targeted PTEN and could activate PI3K/Akt/mTOR pathway. miR-18b-5p produced by FF-derived exosomes reduces PTEN expression and promotes the activation of the PI3K/Akt/mTOR signaling pathway to improve PCOS. Based on that, circulating miR-18b-5p levels can contribute to the progression of PCOS complications.

The Microultrasound-Guided Prostate Biopsy in Detection of Prostate Cancer: A Systematic Review and Meta-Analysis.

Background: To compare the detection rate of microultrasound with that of multiparametric magnetic resonance imaging targeted biopsy (mpMRI-TB) for prostate cancer (PCa) diagnosis. Methods: The studies on microultrasound prostate biopsy for PCa diagnosis were searched in PubMed, Cochrane library, and EMBASE databases from inception to April 2021. We performed a systematic review and cumulative meta-analysis based on search results using Software Rev-Man 5.3. Results: A total of 11 studies involving 1081 patients were included. The meta-analysis showed that no significant difference was found between microultrasound and mpMRI-TB in the total detection of PCa (odds ratio [OR]: 1.01, 95% confidence interval [CI]: 0.85-1.21, p = 0.89), of grading groups (GGs) = 1 (OR: 0.92, 95% CI: 0.68-1.25, p = 0.59), of GGs ≥2 (OR:1.01, 95% CI: 0.83-1.22, p = 0.92), and of GGs ≥3 (OR: 1.31, 95% CI: 0.95-1.81, p = 0.10). Conclusions: Microultrasound-guided prostate biopsy provides detection rates for PCa diagnosis comparable with those of the mpMRI-TB, which is expected to challenge mpMRI-TB in the diagnosis of PCa.

Application of intra-arterial chemotherapy in high-risk non-muscle invasive bladder cancer: a systematic review and meta-analysis.

BACKGROUND: To summarize the current evidence on the effects of intra-arterial chemotherapy (IAC) on high-risk non-muscle invasive bladder cancer (NMIBC) and compare oncology results with intravesical chemotherapy (IVC). METHODS: We performed a systematic review and cumulative meta-analysis of the primary outcomes of interest by a systematical search of multiple scientific databases in February 2021. The mean difference (MD) and odds ratio (OR) were calculated for continuous and dichotomous variables respectively, with 95% confidence intervals (CIs). The hazard radio (HR) with 95% CIs was used for overall survival (OS), recurrence-free survival (RFS) and progression-free survival (PFS). RESULTS: A total of six studies with 866 patients were included. For IAC combined with IVC versus IVC alone, statistically significant differences were found regarding tumor recurrence rate (OR: 0.51, 95% CI [0.36∼0.72], p = 0.0001), tumor progression rate (OR: 0.47, 95% CI [0.30∼0.72], p = 0.0006), tumor-specific death rate (OR: 0.49, 95% CI [0.25∼0.99], p = 0.05), PFS (HR: 0.47, 95% CI [0.23∼0.96], p = 0.04) and RFS (HR: 0.60, 95% CI [0.41∼0.87], p = 0.007). No significant difference between two groups was found for time to first recurrence (MD: 3.27, 95% CI [-2.37∼8.92], p = 0.26) and OS (HR: 1.20, 95% CI [0.44∼3.32], p = 0.72). For IAC alone versus IVC, There was no statistical difference in the terms of tumor-specific death rate (OR: 0.67, 95% CI [0.29∼1.53], p = 0.34), RFS (HR: 0.90, 95% CI [0.56∼1.46], p = 0.68) and PFS (HR: 0.71, 95% CI [0.32∼1.55], p = 0.39). Adverse events mainly included nausea/vomiting (36.3%), hypoleukemia (19.4%), neutropenia (16.0%), increased creatinine (9.9%), increased alanine aminotransferase (18.7%), and thrombocytopenia (9.9%). CONCLUSION: The IAC combined with IVC is a safe and effective treatment for high risk NMIBC, with lower rates of recurrence, progression, tumor-specific death, PFS and RFS, and with minor and tolerable events. The effectiveness of the IAC alone is parallel to the IVC alone.

Comparison of different laser-based enucleation techniques for benign prostate hyperplasia: A systematic review and meta-analysis.

BACKGROUND: To summarize the current evidence on different laser-based enucleation techniques for benign prostate hyperplasia and compare the efficacy and safety of en-bloc, two-lobe and three-lobe techniques. MATERIALS AND METHODS: Through a systematical search of multiple scientific databases in March 2021, we performed a systematic review and cumulative meta-analysis of the primary outcomes of interest according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines, whose protocol was registered with PROSPERO(CRD42021240684). RESULTS: A total of 9 studies were included. All three laser enucleation techniques had no statistically significant difference in terms of enucleated prostate weight, maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), international prostate symptom score (IPSS), transient UI (TUI), persistent UI (PUI) and early postoperative complications. A shorter enucleation time was associated with the en-bloc technique compared to three technique (MD: -8.26, 95%CI: -12.73--3.79, p = 0.0003), whereas no significant difference was found in en-bloc versus two-lobe technique (MD:0.97,95%CI: -0.30-2.24,p = 0.13) and two-lobe versus three-lobe technique (MD: -3.19, 95%CI: -7.45-1.06, p = 0.14). A higher enucleation rate was associated with the en-bloc and two-lobe technique (MD: 0.05, 95%CI: 0.00-0.10, p = 0.03; MD: 0.09, 95%CI: 0.01-0.17, p = 0.03, respectively). A superior QoL was related to the two-lobe enucleation technique compared to three-lobe technique (MD: 0.22, 95%CI: 0.06-0.39, p = 0.009), whereas no meaningful difference was found in the group of en-bloc versus two-lobe (MD: -0.12, 95%CI: -0.62-0.37, p = 0.62) and group of en-bloc versus three-lobe (MD: -0.14, 95%CI: -0.56-0.29, p = 0.52). CONCLUSIONS: En-bloc and two-lobe laser-based enucleation techniques are feasible and safe alternative to three-lobe technique with comparable surgical outcomes and similar functional outcomes. A superior enucleation efficiency was associated with En-bloc and the two-lobe techniques compared to the three-lobe technique.

Robot-Assisted Radical Cystectomy with Intracorporeal Urinary Diversion: A New Standard of Urinary Diversion.

Background: To summarize the current evidence on robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) and compare perioperative outcomes and postoperative complications of patients undergoing RARC with extracorporeal urinary diversion (ECUD) and ICUD. Patients and Methods: Through a systematical search of multiple scientific databases in March 2020, we performed a systematic review and cumulative meta-analysis of the primary outcomes of interest. Also, we assessed the quality of the relevant evidence according to the framework in the Cochrane Handbook for Systematic Reviews of Interventions. Results: Thirteen studies with 4696 participants were included in this review. No significant differences were found between the ECUD and ICUD in operation time (OT) (mean difference [MD]: -6.45, 95% confidence interval [CI]: -35.20 to 22.30), length of stay (MD: 0.36, 95% CI: -0.81 to 1.54), 30-day overall complications (odds ratio [OR]: 0.92, 95% CI: 0.60-1.41), 30-day minor complications (OR: 1.36, 95% CI: 0.85-2.19), 30-day major complications (OR: 0.70, 95% CI: 0.34-1.43), 90-day overall complications (OR: 1.34, 95% CI: 0.83-2.18), and major complications (OR: 1.03, 95% CI: 0.68-1.57). However, less estimate blood loss (MD: 99.28 mL, 95% CI: 62.59-135.98), lower intraoperative blood transfusion (OR: 1.80, 95% CI: 1.09-2.95), shorter oral intake time (MD: 0.78, 95% CI: 0.43-1.14), and 90-day minor complications (OR: 1.72, 95% CI: 1.08-2.73) were associated with ICUD. The subgroup analysis showed less estimated blood loss (MD: 149.73, 95% CI: 21.33-278.13) and less OT (MD: 32.45, 95% CI: 14.37-50.53) were found in ICUD. Conclusions: The ICUD is a safe and feasible alternative to ECUD, which decreases the need for blood transfusion and reduces 90-day complications. However, further quality studies are needed to evaluate effectiveness of ICUD and its oncologic outcomes, functional outcomes, cost, and the quality of life.

Laparoscopic Versus Open Partial Nephrectomy: A Systemic Review and Meta-Analysis of Surgical, Oncological, and Functional Outcomes.

PURPOSE: To summarize and analyze the current evidence about surgical, oncological, and functional outcomes between laparoscopic partial nephrectomy (LPN) and open partial nephrectomy (OPN). MATERIALS AND METHODS: Through a systematical search of multiple scientific databases in March 2020, we performed a systematic review and cumulative meta-analysis. Meanwhile, we assessed the quality of the relevant evidence according to the framework in the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: A total of 26 studies with 8095 patients were included. There was no statistical difference between the LPN and OPN in the terms of operation time (p=0.13), intraoperative complications (p=0.94), recurrence (p=0.56), cancer-specific survival (p=0.72), disease-free survival (p=0.72), and variations of estimated glomerular filtration rate (p=0.31). The LPN group had significantly less estimated blood loss (P<0.00001), lower blood transfusion (p=0.04), shorter length of hospital stay (p<0.00001), lower total (p=0.03) and postoperative complications (p=0.02), higher positive surgical margin (p=0.005), higher overall survival (p<0.00001), and less increased serum creatinine (p=0.002). The subgroup analysis showed that no clinically meaningful differences were found for T1a tumors in terms of operation time (p=0.11) and positive surgical margin (p=0.23). In addition, the subgroup analysis also suggested that less estimated blood loss (p<0.0001) and shorter length of hospital stay (p<0.00001) were associated with the LPN group for T1a tumors. CONCLUSIONS: This meta-analysis revealed that the LPN is a feasible and safe alternative to the OPN with comparable surgical, oncologic, and functional outcomes. However, the results should be applied prudently in the clinic because of the low quality of evidence. Further quality studies are needed to evaluate the effectiveness LPN and its postoperative quality of life compared with OPN.

The Relationship Between Hormone Replacement Therapy and Risk of Kidney Cancer in Women: A Meta-Analysis.

Results from the epidemiologic studies on the relationship between hormone replacement therapy (HRT) and the risk of kidney cancer in women were not completely consistent. This meta-analysis aimed to evaluate the relationship between HRT and risk of kidney cancer in women. We performed a meta-analysis of observational studies to assess this association. The PubMed and Embase databases were searched from their inception to January 29, 2020, to identify relevant studies that fit the pre-stated inclusion criteria; reference lists from the retrieved articles were also been reviewed. Relative risks (RRs) with corresponding 95% CIs were extracted and combined using random effects models. Furthermore, dose-response, sensitivity analyses, publication bias, and subgroup analysis by study design, regional location, and exposure assessment method were conducted. Thirteen articles involving 6 cohort studies and 8 case-control studies were included in our meta-analysis. Overall, 4194 women were diagnosed with kidney cancer among 648 107 participants. The pooled RR for kidney cancer was 1.08 (95% CI: 0.96-1.22) in those who were administered HRT compared to those who had not. Subgroup analysis indicated the overall result was not influenced by study type, regional location, or adjusted variables. Dose-response analysis showed a nonlinear relationship between HRT and kidney cancer (P = .0021) and the risk of kidney cancer decreased by 15% to 28% with 12 to 18 years of HRT use. No evidence of publication bias was found (P for Egger =.111). Our meta-analysis showed that HRT use is inversely associated with kidney cancer risk in a dose-dependent fashion.

[Study of Kinase Inhibitor WP1066 on the STAT3/JAK2 of Prostate Stromal Cells].

OBJECTIVE: To study the role of JAK2 signaling pathway in prostate stromal cells and the effect of inhibitor WP1066 on its expression. METHODS: The phosphorylation of JAK2 and STAT3 in prostate tissues of patients with benign prostatic hyperplasia (BHP) (n=4) and severe histological prostatitis (HP) plus BPH (n=4) was tested by using Western blot to verify the activation of their mediated signaling pathway. Kinase inhibitor WP1066 was added to prostate stromal cells to detect inhibition of the JAK2 and STAT3 activation launched by IL-6. RESULTS: JAK2 phosphorylation level (pJAK2) was significantly increased in the patients with severe HP plus BPH,and the expression of JAK2 or STAT3 was not decreased in WP1066 treatment cells. However,neither phosphorylation in JAK2 nor STAT3 was able to be detected in the cells treated with WP1066 or WP1066+IL-6,indicating that the signaling pathway of JAK2-STAT3 was inhibited. CONCLUSION: JAK/STAT signaling pathway is activated in patients with severe HP plus BPH , but could be inhibited by WP1066.

Malignant melanoma of the penis and urethra: one case report.

We present a case of a patient with malignant melanoma of the glans penis and urethra, which was found in a 53-year-old man with nonhealing ulcerative penile lesion and bilateral, clinically palpable inguinal lymphadenopathies at diagnosis. A diagnostic biopsy showed the characteristics of a melanoma. We treated the patient with total penectomy and bilateral inguinal lymph node dissection. After surgery, chemotherapy with bleomycin, vincristine and cisplatin and immunotherapy with thymosin injection were started. No recurrence or metastasis occurred during the 3 years after the operation. Melanoma of the penis is very rare, and early diagnosis is important because the patient prognosis is very poor.