Primary pure large cell neuroendocrine carcinoma of the urinary bladder: a case report and literature review.

Background: The large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is a rare malignancy. With its high aggressiveness and poor prognosis, the disease is often accompanied by metastasis or recurrence. The lack of specific clinical manifestations and imaging features causes considerable challenges for clinical diagnosis and treatment. Case presentation: We report a case of LCNEC of the urinary bladder. The patient was a 79-year-old male admitted to our hospital with recurrent episodes of asymptomatic gross hematuria. Based on the computed tomography (CT) scan findings, our patient presented with a bladder mass displaying invasion into the serosal layer, suggestive of muscle involvement and indicative of malignancy. The patient received a radical cystectomy, and the postoperative pathology confirmed primary, pure LCNEC of the urinary bladder. We gave him 16 cycles of toripalimab immunotherapy. As of follow-up, the patient was alive, and periodic CT reexamination showed no evidence of recurrence. Conclusions: We reviewed domestic and foreign literature and found no explicit treatment protocols exist for the disease. Surgical resection combined with chemotherapy were the most common treatments. Herein, we reported the first case of primary, pure LCNEC of the urinary bladder treated by radical cystectomy combined with pure immunotherapy, achieving sustained remission, which provides a new idea for the immunotherapy and integrative treatment of the disease.

MIR210HG is aberrantly expressed in the seminal plasma of varicocele patients and associated with varicocele-related dyszoospermia.

This study aimed to confirm the expression of the seminal plasma long noncoding RNAs (lncRNAs) microRNA210 host gene (MIR210HG) in varicocele (VC) patients, to further explore the association between MIR210HG and VC severity and to evaluate whether MIR210HG can predict VC-related dyszoospermia. Semen samples from 188 VC patients and 92 healthy men were collected. Quantitative reverse transcriptase PCR detected seminal plasma MIR210HG levels. Receiver operating characteristic analysis assessed the ability of MIR210HG to screen patients with VC, or to screen VC patients with abnormal semen quality. Logistic analysis assessed the value of MIR210HG in predicting dyszoospermia in VC patients. The levels of MIR210HG in seminal plasma of VC patients were upregulated, which could screen VC patients. In addition, the levels of seminal plasma MIR210HG were upregulated with VC severity and were downregulated at 6 months after surgery in VC patients. Moreover, elevated MIR210HG levels in VC patients with abnormal semen quality could screen patients with abnormal semen quality and could independently predict the occurrence of dyszoospermia in VC patients. Seminal plasma MIR210HG expression is upregulated in VC patients, is associated with the severity of VC and may function as an independent predictor of VC-related dyszoospermia.

The efficacy and safety of alpha-adrenergic blockers for medical expulsion therapy in patients with ureteral calculi: A meta-analysis of placebo-controlled trials.

PURPOSE: Alpha-adrenergic blockers are commonly used as a medical expulsive therapy (MET) for patients with ureteral calculi. The aim of this meta-analysis was to evaluate the efficacy and safety of alpha-adrenergic blockers compared with a placebo when used as a MET. MATERIALS AND METHODS: We carried out a systematic search of the PubMed, EMBASE, and Web of Science databases, and the Cochrane Library, for relevant articles from inception to November 2020. Our aim was to identify placebo-controlled trails in which patients were randomized to receive either alpha-adrenergic blockers (tamsulosin, alfuzosin, doxazosin, terazosin, naftopidil, or silodosin) or a placebo for the treatment of ureteral calculi. RESULTS: According to strict inclusion criteria, database searches identified 8 placebo-controlled studies that included 2284 patients. Generally, α-blockers had no significant effect on the clearance of stones in the urinary tract (risk ratio [RR] = 1.05; 95% confidence interval [CI] = 1.00-1.11). However, subgroup analysis showed that α-blockers were effective in treating distal urinary tract stones (RR = 1.08; 95% CI = 1.02-1.15). With regards to adverse events, our analysis showed that the combination of MET with α-blockers was likely to cause dizziness (RR = 1.37; 95% CI = 1.06-1.79) and retrograde ejaculation (RR = 3.10; 95% CI = 1.81-5.29). CONCLUSION: Although α-blockers cannot improve the overall ureteral stone clearance rate, these drugs are still effective for the treatment of stones in the distal urinary tract. However, the application of α-blockers is likely to cause dizziness and/or retrograde ejaculation.

Higher impulsivity and lower grey matter volume in the bilateral prefrontal cortex in long-term abstinent individuals with severe methamphetamine use disorder.

BACKGROUND: Previous studies have shown that grey matter volume (GMV) might be lower in individuals with methamphetamine use disorder and that dynamic alterations in selected brain regions might appear in individuals after short-term abstinence. However, the GMV of brains in these individuals after long-term abstinence is poorly understood. Moreover, individuals with severe methamphetamine use disorder have been considered to have high levels of impulsivity, but the biological mechanism is still unclear. METHODS: In this study, the impulsivity of all participants was assessed using the Barratt Impulsiveness Scale (BIS-11). Using voxel-based morphometry (VBM) in conjunction with statistical parametric mapping on structural magnetic resonance images, the GMVs of the whole brain were compared among 32 drug-naïve healthy controls (HC) and 40 individuals with severe methamphetamine use disorder who had been abstinent for at least 20 months (SMUD-A). RESULTS: We observed significantly higher BIS-11 impulsivity scores and lower GMV in the bilateral superior frontal cortex of SMUD-A individuals than in those of control subjects. The impulsivity score was negatively correlated with GMV in the right superior frontal cortex. CONCLUSIONS: These findings offer novel evidence with respect to the impulsivity trait and brain GMV feature in long-term abstinent individuals with severe methamphetamine use disorder. Moreover, our findings suggest that lower GMV in the right superior frontal cortex might reflect a trait marker of higher impulsivity in this population.

Clinical evaluation of the multifunctional suprapubic catheter in patients requiring permanent suprapubic cystostomy: A prospective randomised trial in a single centre.

AIMS AND OBJECTIVES: To assess the clinical effect of the multifunctional suprapubic catheter (MSC) on occurrence of cystospasm, catheter occlusion, the catheter-related urinary tract infection and remission of overactivity bladder, by comparing with the conventional suprapubic catheter (CSC) in patients with permanent suprapubic cystostomy. BACKGROUND: The conventional suprapubic catheter usually presents with high incidence of catheter-associated complications. DESIGN: A prospective randomised clinical trial in a single centre. METHODS: Between January 2014 and January 2015, a total of 91 consecutive patients with permanent suprapubic cystostomy were prospectively randomised into two groups: the MSC group (n = 43) and CSC group (n = 48). RESULTS: Our results showed that the total times of cystospasm in the MSC group were significantly less than that in the CSC group during the follow-up time (p < .001). In addition, the mean spasmodic duration per time in the MSC group was significantly shorter than that in the CSC group (p < .001). Besides, catheter occlusions were observed in 23 (25.27%) patients, including 5 (11.63%) in the MSC group and 18 (37.50%) in the CSC group (p = .005). The lower rate of positive urine culture was also found in the MSC group but with no significant difference (p = .540). Furthermore, the urodynamic measurement data demonstrated that the patients in the MSC group had a greater remission rate of overactivity bladder after catheter change (p < .001). CONCLUSIONS: The present data showed that the multifunctional suprapubic catheter could significantly reduce the incidence of catheter occlusion, ameliorate the symptom of cystospasm and relieve the overactivity bladder, but have no influence on the catheter-related urinary tract infection. RELEVANCE TO CLINICAL PRACTICE: The application of our self-devised multifunctional suprapubic catheter may result in better management of the patients with permanent suprapubic cystostomy.

Craving Responses to Methamphetamine and Sexual Visual Cues in Individuals With Methamphetamine Use Disorder After Long-Term Drug Rehabilitation.

Studies utilizing functional magnetic resonance imaging (fMRI) cue-reactivity paradigms have demonstrated that short-term abstinent or current methamphetamine (MA) users have increased brain activity in the ventral striatum, caudate nucleus and medial frontal cortex, when exposed to MA-related visual cues. However, patterns of brain activity following cue-reactivity in subjects with long-term MA abstinence, especially long-term compulsory drug rehabilitation, have not been well studied. To enrich knowledge in this field, functional brain imaging was conducted during a cue-reactivity paradigm task in 28 individuals with MA use disorder following long-term compulsory drug rehabilitation, and 27 healthy control subjects. The results showed that, when compared with controls, individuals with MA use disorder displayed elevated activity in the bilateral medial prefrontal cortex (mPFC) and right lateral posterior cingulate cortex in response to MA-related images. Additionally, the anterior cingulate region of mPFC activation during the MA-related cue-reactivity paradigm was positively correlated with craving alterations and previous frequency of drug use. No significant differences in brain activity in response to pornographic images were found between the two groups. Compared to MA cues, individuals with MA use disorder had increased activation in the occipital lobe when exposed to pornographic cues. In conclusion, the present study indicates that, even after long-term drug rehabilitation, individuals with MA use disorder have unique brain activity when exposed to MA-related cues. Additionally, our results illustrate that the libido brain response might be restored, and that sexual demand might be more robust than drug demand, in individuals with MA use disorder following long-term drug rehabilitation.

Clinical comparison of the efficacy of three different bowel preparation methods on the infectious complications following transrectal ultrasonography-guided prostate biopsy in nursing practice.

AIMS AND OBJECTIVES: To assess the effects of three different bowel preparation methods on the incidence of infectious complications in patients who underwent transrectal ultrasonography-guided prostate biopsy. BACKGROUND: The standard bowel preparation protocol for prostate biopsy has not been established. DESIGN: A retrospective study in a single centre. METHODS: From January 2013-December 2015, the clinical records of 1,130 patients who underwent prostate biopsy were, respectively, reviewed. All the patients received metronidazole prophylaxis before biopsy. The patients were divided into three groups according to the bowel preparation methods: patients in Group A (n = 402) received only soapy enema; patients in Group B (n = 413) received polyethylene glycol; while patients in Group C (n = 315) received polyethylene glycol plus povidone-iodine enema. Infectious complications were classified as fever (>37.5°C), urinary tract infection and sepsis. The postoperative adverse events were also observed. RESULTS: The overall postbiopsy infectious complications were observed in 48 (4.25%) patients of all the cases, including 23 (5.72%) cases in Group A, 20 (4.84%) cases in Group B and five patients (1.59%) in Group C. There was significant difference among the groups (p = .018). In detail, these infectious complications included 22 (1.95%) cases of fever and 26 (2.30%) cases of urinary tract infection. No sepsis was observed among the total patients. The incidence of adverse events was 14.43% (58/402) occurred in Group A, 25.91% (107/413) in Group B and 26.67% (84/315) in Group C. The difference was statistically significant. CONCLUSIONS: Our study confirmed that combined preparation regimens of polyethylene glycol with povidone-iodine enema could significantly reduce the postbiopsy infection rate. Conventional soapy enema is associated with less adverse events. RELEVANCE TO CLINICAL PRACTICE: Findings of this study provide useful evidence-based information for healthcare professionals. The application of combined preparation regimens of polyethylene glycol with povidone-iodine enema resulted in better improvement in the prevention of postbiopsy infection.

Detection rate of prostate cancer following biopsy among the northern Han Chinese population: a single-center retrospective study of 1022 cases.

BACKGROUND: Prostate cancer is known to have ethnic and regional differences. The study aimed to clinically evaluate the detection rate of prostate cancer on transrectal ultrasonography (TRUS)-guided prostate biopsy and analyze its characteristics among the northern Han Chinese population at a single center. METHODS: Between October 2009 and September 2016, a total of 1027 Chinese men, who had undergone TRUS-guided prostate biopsy at Qingdao Municipal Hospital, were retrospectively analyzed. Prostate biopsies were performed in the case of an abnormally elevated serum PSA level, and/or abnormal digital rectal examination (DRE) findings, and/or suspicious prostatic imaging findings. RESULTS: Of the 1022 men enrolled in the analysis, 438 patients (42.8%) were diagnosed with prostate adenocarcinoma histologically. When serum PSA levels were divided into five subgroups (less than 4.0, 4.0 to 10.0, 10.0 to 20.0, 20.0 to 100.0, and ≥ 100.0 ng/ml), the detection rates of prostate cancer were 12.4, 15.9, 34.1, 66.2, and 93.8%, respectively. With serum PSA levels of 4.0 to 10.0 ng/ml, the cancer detection rates for a normal DRE and a suspect DRE finding were 13.5 and 58.2%, respectively. Accordingly, the cancer detection rates for a normal imaging and a suspect imaging finding were 13.5 and 58.2%, respectively. Besides, a large proportion of the patients were in the clinically advanced stage. CONCLUSIONS: The present study data reported a relatively higher prostate cancer detection rate of 42.8% and that the majority of the patients presented with clinically advanced prostate cancers within a local clinical urologic practice. An early detection and screening program for prostate cancer is of great need to reduce the burden from this disease among the northern Han Chinese population.

Clinical evaluation of embolization of the superior vesical prostatic artery for treatment of benign prostatic hyperplasia: a single-center retrospective study.

INTRODUCTION: Non-surgical minimally invasive treatments are greatly needed for patients with symptomatic benign prostatic hyperplasia (BPH), for whom medical treatment has failed and surgery is contraindicated. This study retrospectively evaluated the efficacy and safety of super-selective prostatic artery embolization (PAE) for BPH, relative to transurethral resection of the prostate (TURP). AIM: To clinically evaluate the efficacy and safety of super-selective PAE for BPH, relative to TURP. MATERIAL AND METHODS: From February 2012 to March 2015, patients with BPH underwent selective PAE (n = 17) or TURP (control group; n = 40). Prostate volume, maximum urinary flow rate (Qmax), International Prostate Symptoms Score (IPSS), and quality of life (QoL) score were evaluated at baseline and postoperative 3, 6, and 12 months. Complications were also recorded. RESULTS: All the procedures were technically successfully. At postoperative 1 year, patients given PAE had significantly greater prostate volume (64.6 ±10.2 ml), IPSS (23.9 ±4.9), and QoL (4.1 ±0.7) compared with the control patients (42.0 ±7.5 ml, 13.1 ±3.5, and 2.1 ±0.7, respectively). The Qmax of the PAE group (9.5 ±3.7 ml/s) was significantly lower than that of the control (21.8 ±4.2 ml/s). The changes in parameters of the TURP patients relative to the preoperative baseline were significantly greater than those of the PAE group. No severe complications occurred. CONCLUSIONS: Prostatic artery embolization was demonstrated as safe and effective and may be considered an alternative treatment for BPH patients, especially for those who are not candidates for or refuse surgery.

Tumor suppressor microRNA-34a inhibits cell proliferation by targeting Notch1 in renal cell carcinoma.

MicroRNA-34a (miR-34a) is a tumor suppressive microRNA, which induces G1 arrest, apoptosis and senescence by repressing the expression of multiple oncogenes. This study aimed to investigate the biological function and molecular mechanisms of miR-34a in human renal cell carcinoma (RCC) cells. Quantitative polymerase chain reaction (qPCR) revealed that miR-34a expression was significantly downregulated in eight of the 10 (80%) RCC tissues compared with adjacent normal tissues. In RCC cell lines, several other target genes of miR-34a were dysregulated at the mRNA level when the expression of miR-34a was elevated. In addition, western blot analysis and qPCR revealed that forced expression of miR-34a downregulated the expression of Notch1 at the protein and mRNA level. The Cell Counting Kit-8 identified that transient forced expression of miR-34a inhibited cell growth and resulted in cell cycle arrest, which was evaluated by flow cytometry. Our data demonstrated that miR-34a inhibits cell proliferation by downregulating Notch1 in RCC cell lines.

Mechanism and function of decreased FOXO1 in renal cell carcinoma.

BACKGROUND AND OBJECTIVES: Forkhead box O-class 1 (FOXO1), a putative tumor suppressor, is dysregulated in many cancers. Our study aims to reveal the underlying functions and regulation mechanisms of FOXO1 in renal cell carcinoma (RCC). METHODS: The clinical significance of FOXO1 expression in surgically resected specimens was assessed by immunohistochemistry. The siRNAs targeted FOXO1 and miR-27a inhibitor were transfected into RCC cells. QRT-PCR, Western blot, and cell proliferation assay were used to assess the expression and function of FOXO1 and miR-27a. RESULTS: The positive immunostaining for FOXO1 was low in 51 RCC samples compared with 15 normal kidney tissues. And the expression of FOXO1 was related with RCC subtypes and the grade and stage in clear cell RCC (cRCC) (P < 0.05). Inhibition of FOXO1 promoted proliferation of 769-P cells. However, upregulation of FOXO1 by miR-27a inhibitor was accompanied by the anti-proliferative effect in cells of 786-O and Caki-1. Furthermore, the expression of FOXO1 mRNA and miR-27a had inverse relation in eight cRCC samples. CONCLUSION: Reduced expression of FOXO1 is common in RCC and a potentially suitable marker of different histological subtypes and prognosis of cRCC. Increasing expression of FOXO1 by the miR-27a inhibitor could prevent cell growth.

Hsa-let-7a functions as a tumor suppressor in renal cell carcinoma cell lines by targeting c-myc.

Widespread functions of the c-myc pathway play a crucial role in renal cell carcinoma (RCC) carcinogenesis. Thus, we evaluated the connection between proto-oncogenic c-myc and anti-neoplastic hsa-let-7a (let-7a) in RCC cell lines. The levels of c-myc and let-7a in 3 RCC cell lines (769P, Caki-1 and 786O) were measured after transfecting the cells with let-7a mimics or a negative control. The change in c-myc protein level was confirmed by Western blot. The anti-neoplastic function of let-7a was evaluated using cell counting kit-8 (CCK-8) for proliferation analysis and cell flow cytometry for cell cycle analysis. The changes of downstream targets of c-myc were measured using reverse transcription quantitative real-time PCR (qRT-PCR). Our results suggest for the first time that let-7a acts as a tumor suppressor in RCC cell lines by down-regulating c-myc and c-myc target genes such as proliferating cell nuclear antigen (PCNA), cyclin D1 (CCND1) and the miR17-92 cluster, which is accompanied by proliferation inhibition and cell cycle arrest.

Comprehensive analysis of clinical significance of stem-cell related factors in renal cell cancer.

BACKGROUND: C-MYC, LIN28, OCT4, KLF4, NANOG and SOX2 are stem cell related factors. We detected whether these factors express in renal cell carcinoma (RCC) tissues to study their correlations with the clinical and pathological characteristics. METHODS: The expressions of c-MYC, LIN28, SOX2, KLF4, OCT4 and NANOG in 30 RCC patients and 5 non-RCC patients were detected with quantitative real-time reverse transcription-PCR (qRT-PCR). The data were analyzed with Wilcoxon signed rank sum test and x2 test. RESULTS: In RCC group, c-MYC expression was significantly higher in RCC tissues compared with normal tissues (P < 0.05). The expression levels of OCT4, KLF4, NANOG and SOX2 were significantly lower in RCC tissues compared with normal tissues (P < 0.05). LIN28 expression level was not significant. No difference was observed when it comes to clinical and pathological characteristics such as gender, age, tumor size, cTNM classification and differentiation status (P > 0.05). Also the expression levels of all above factors were not significantly changed in non-RCC group (P > 0.05). CONCLUSIONS: The present analysis strongly suggests that altered expression of several stem cell related factors may play different roles in RCC. C-MYC may function as an oncogene and OCT4, KLF4, NANOG and SOX2 as tumor suppressors.