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   Table of Contents - Current issue
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January-February 2021
Volume 23 | Issue 1
Page Nos. 1-122

Online since Friday, January 8, 2021

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INVITED RESEARCH HIGHLIGHT  

The emerging role of prostate-specific membrane antigen (PSMA) PET-CT in patients with high-risk prostate cancer: moving the bar in high-risk prostate cancer p. 1
Jeanny B Aragon-Ching
DOI:10.4103/aja.aja_35_20  PMID:32719192
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REVIEW Top

Androgen deprivation therapy and side effects: are GnRH antagonists safer? p. 3
Stephen J Freedland, Per-Anders Abrahamsson
DOI:10.4103/aja.aja_22_20  PMID:32655041
Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists and antagonists is the mainstay of advanced prostate cancer treatment. Both drug classes decrease levels of luteinizing hormone and follicle-stimulating hormones (FSH), thereby lowering testosterone to castrate levels. This is associated with adverse events (AEs), including cardiovascular (CV) disorders, bone fractures, metabolic dysfunction, and impaired cognitive function. This literature review discusses these AEs, with a focus on CV and bone-related events. A hypothesis-generating meta-analysis of six clinical trials showed a potentially increased risk for CV disorders with GnRH agonists versus the GnRH antagonist degarelix. While no study has directly compared GnRH agonists versus antagonists with a primary CV outcome, one hypothesis for this observation is that GnRH agonists lead to initial surges in FSH that may negatively impact CV health, whereas antagonists do not. GnRH agonists are associated with metabolic and cognitive AEs and while data are lacking for GnRH antagonists, no differences in risk are predicted. Other common AEs with ADT include injection site reactions, which are much more common with degarelix than with GnRH agonists, which may reflect differing administration and injection techniques. Future studies are needed to further evaluate and compare the safety profiles of GnRH agonists and antagonists, especially in patients with pre-existing CV disease and other co-morbidities. Physicians should carefully evaluate benefits and risks when prescribing ADT and ensure that side effects are well managed.
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ORIGINAL ARTICLES Top

The hamster egg penetration test may decrease intracytoplasmic sperm injection utilization while maintaining high conventional fertilization rates p. 11
Yetunde Ibrahim, Brett Einerson, Douglas T Carrell, Benjamin R Emery, Erica Johnstone
DOI:10.4103/aja.aja_18_20  PMID:32436865
This was a cohort study of in vitro fertilization (IVF) subjects at the University of Utah, Salt Lake City (UT, USA) utilizing partner sperm. Cycles where both the hamster egg penetration test (HEPT) and semen analysis were performed within 2 years prior to IVF cycles were stratified into four groups based on a normal or an abnormal HEPT and morphology. The mean conventional and intracytoplasmic sperm injection (ICSI) fertilization rates were calculated in each group. We performed a univariate analysis on the primary outcome comparing clinically interesting subjects. We performed a cost-effectiveness analysis of a policy of HEPT versus universal ICSI in couples with an abnormal morphology. Among patients with a normal HEPT, there was no difference in the mean conventional fertilization rates between those with a normal and an abnormal morphology. There was no difference in the mean conventional fertilization rates between subjects with a normal morphology without a hamster test and those with a normal HEPT without a morphology assessment. In 1000 simulated cycles with an abnormal morphology, a policy of HEPT was cost saving compared to universal ICSI, yet produced similar fertilization rates. The HEPT is similar to the World Health Organization edition 5 (WHO-5) morphology in predicting successful conventional fertilization while allowing decreased utilization of ICSI. A policy of HEPT for males with abnormal morphology saves cost in selecting couples for a fertilization method.
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Use of a male antioxidant nutraceutical is associated with superior live birth rates during IVF treatment p. 16
Kelton Tremellen, Richard Woodman, Amy Hill, Helana Shehadeh, Michelle Lane, Deirdre Zander-Fox
DOI:10.4103/aja.aja_41_20  PMID:32769234
Oxidative stress is prevalent among infertile men and is a significant cause of sperm DNA damage. Since sperm DNA damage may reduce embryo quality and increase miscarriage rates, it is possible that untreated sperm oxidative stress may impair in vitro fertilization (IVF) live birth rates. Given that the antioxidant Menevit is reported to reduce sperm DNA damage, it was hypothesized that men's consumption of this supplement may alter IVF outcomes. Therefore, a retrospective cohort study was conducted analyzing outcomes for couples undergoing their first fresh embryo transfer. Men were classified as controls if they were taking no supplements, health conscious controls if taking “general health” supplements, or Menevit users. Men with karyotype abnormalities, or cycles using donated, frozen and surgically extracted sperm were excluded. Among the final study cohort of 657 men, live birth rates were significantly higher in Menevit users than controls (multivariate adjusted odds ratio [OR]: 1.57, 95% confidence interval [CI]: 1.01–2.45, P= 0.046), but not between controls taking no supplements and those using general health supplements, thereby suggesting that potential health conscious behavior in supplement users is unlikely responsible for the superior outcomes in Menevit users. Interestingly, in a post hoc sensitivity analysis, live birth rates among Menevit users were statistically superior to controls for lean men (OR: 2.73, 95% CI: 1.18–6.28; P= 0.019), not their overweight/obese counterparts (OR: 1.29, 95% CI: 0.75–2.22, P = 0.37). The results of this large cohort study therefore support a positive association between men's use of the Menevit antioxidant during IVF treatment and live birth rates, especially in lean individuals.
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Next-generation sequencing: toward an increase in the diagnostic yield in patients with apparently idiopathic spermatogenic failure p. 24
Rossella Cannarella, Rosita A Condorelli, Stefano Paolacci, Federica Barbagallo, Giulia Guerri, Matteo Bertelli, Sandro La Vignera, Aldo E Calogero
DOI:10.4103/aja.aja_25_20  PMID:32655042
A large proportion of patients with idiopathic spermatogenic failure (SPGF; oligozoospermia or nonobstructive azoospermia [NOA]) do not receive a diagnosis despite an extensive diagnostic workup. Recent evidence has shown that the etiology remains undefined in up to 75% of these patients. A number of genes involved in germ-cell proliferation, spermatocyte meiotic divisions, and spermatid development have been called into play in the pathogenesis of idiopathic oligozoospermia or NOA. However, this evidence mainly comes from case reports. Therefore, this study was undertaken to identify the molecular causes of SPGF. To accomplish this, 15 genes (USP9Y, NR5A1, KLHL10, ZMYND15, PLK4, TEX15, TEX11, MEIOB, SOHLH1, HSF2, SYCP3, TAF4B, NANOS1, SYCE1, and RHOXF2) involved in idiopathic SPGF were simultaneously analyzed in a cohort of 25 patients with idiopathic oligozoospermia or NOA, accurately selected after a thorough diagnostic workup. After next-generation sequencing (NGS) analysis, we identified the presence of rare variants in the NR5A1 and TEX11 genes with a pathogenic role in 3/25 (12.0%) patients. Seventeen other different variants were identified, and among them, 13 have never been reported before. Eleven out of 17 variants were likely pathogenic and deserve functional or segregation studies. The genes most frequently mutated were MEIOB, followed by USP9Y, KLHL10, NR5A1, and SOHLH1. No alterations were found in the SYCP3, TAF4B, NANOS1, SYCE1, or RHOXF2 genes. In conclusion, NGS technology, by screening a specific custom-made panel of genes, could help increase the diagnostic rate in patients with idiopathic oligozoospermia or NOA.
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Kinematic analysis of penile reflexes in a rat model of spinal cord injury p. 30
Casey J Steadman, Sai S Vangoor, Charles H Hubscher
DOI:10.4103/aja.aja_1_20  PMID:32341209
The ex-copula penile dorsiflexion reflex (PDFR) is an established measure of sexual dysfunction in male rat models of spinal cord injury. Although the PDFR after complete spinal transection is well described, information regarding the more clinically relevant incomplete spinal contusion injury model is limited. This study examined, using two-dimensional (2D) kinematic analysis, the relationship between the PDFR and degree of white matter sparing (WMS). Male Wistar rats received a T9 contusion with varying degrees of impactor forces. Weekly kinematic recordings of the PDFR were made 3–8 weeks postinjury. Sexual reflex components examined included maximum angle of penile dorsiflexion, total penile event duration, and penile ascent speed. Post hoc comparison between animals grouped based upon injury severity (moderate–severe: 13.33%–17.15% WMS vs moderate: 20.85%–33.50% WMS) indicated PDFR effects. Specifically, the numbers of animals with more moderate contusions having data points above the median in both maximum angle of penile dorsiflexion and penile ascent speed were significantly lower than animals with more severe injuries. Total penile event duration was also affected but only at more chronic time points (6–8 weeks). Thus, 2D kinematic analysis of the PDFR allows for more consistent and quantifiable analysis of the subtle differences that can occur between injury severity groups in the rat contusion model.
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A novel screening strategy for clinically significant prostate cancer in elderly men over 75 years of age p. 36
Hiroaki Iwamoto, Kouji Izumi, Suguru Kadomoto, Tomoyuki Makino, Renato Naito, Hiroshi Yaegashi, Kazuyoshi Shigehara, Yoshifumi Kadono, Atsushi Mizokami
DOI:10.4103/aja.aja_39_20  PMID:32769233
A standard modality for prostate cancer detection in men 75 years and older has not been established. A simple screening method for elderly patients is needed to avoid unnecessary biopsies and to effectively diagnose prostate cancer. A retrospective study was conducted on elderly patients who had prostate biopsy at Kanazawa University Hospital (Kanazawa, Japan) between 2000 and 2017. Of the 2251 patients who underwent prostate biopsy, 254 had clinically significant prostate cancer (CSPC) with a Gleason score (GS) of 7 and 273 had a GS of <7 or no malignancy. In this study, patients aged 75 years or older were classified as elderly patients. GS 7 was characterized by a prostate-specific antigen (PSA) of the maximum area under the curve of 12 ng ml−1 with a sensitivity of 76.2% and a specificity of 73.2%. For PSA levels between 4 ng ml−1 and 12 ng ml−1, based on the maximum area under the curve, patients with three or four of the following factors may present a GS of 7: percent free PSA >24, PSA density 0.24 ng ml−2, positive findings on digital rectal examination, and transrectal with 90.0% sensitivity and 67.4% specificity. In this study, we found that raising the PSA cutoff to 12 ng ml−1 for CSPC in elderly individuals can significantly reduce unnecessary prostate biopsies. Furthermore, CSPC could be efficiently discovered by combining the four supplementary markers in patients with a PSA level of 4–12 ng ml−1. By performing this screening for elderly men over 75 years of age, unnecessary biopsies may be reduced and CSPC may be detected efficiently.
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Development and validation of a nomogram including lymphocyte-to-monocyte ratio for initial prostate biopsy: a double-center retrospective study p. 41
Zhong-Han Zhou, Feng Liu, Wen-Jie Wang, Xue Liu, Li-Jiang Sun, Yao Zhu, Ding-Wei Ye, Gui-Ming Zhang
DOI:10.4103/aja.aja_19_20  PMID:32503957
Here, we developed a prostate cancer (PCa) risk nomogram including lymphocyte-to-monocyte ratio (LMR) for initial prostate biopsy, and internal and external validation were further conducted. A prediction model was developed on a training set. Significant risk factors with P < 0.10 in multivariate logistic regression models were used to generate a nomogram. Discrimination, calibration, and clinical usefulness of the model were assessed using C-index, calibration plot, and decision curve analysis (DCA). The nomogram was re-examined with the internal and external validation set. A nomogram predicting PCa risk in patients with prostate-specific antigen (PSA) 4–10 ng ml−1 was also developed. The model displayed good discrimination with C-index of 0.830 (95% confidence interval [CI]: 0.812–0.852). High C-index of 0.864 (95% CI: 0.840–0.888) and 0.871 (95% CI: 0.861–0.881) was still reached in the internal and external validation sets, respectively. The nomogram exhibited better performance compared to the nomogram with PSA only (C-index: 0.763, 95% CI: 0.746–0.780, P < 0.001) and the nomogram with LMR excluded (C-index: 0.824, 95% CI: 0.804–0.844, P < 0.010). The calibration curve demonstrated good agreement in the internal and external validation sets. DCA showed that the nomogram was useful at the threshold probability of >4% and <99%. The nomogram predicting PCa risk in patients with PSA 4–10 ng ml−1 also displayed good calibration and discrimination performance (C-index: 0.734, 95% CI: 0.708–0.760). This nomogram incorporating age, PSA, digital rectal examination, abnormal imaging signals, PSA density, and LMR could be used to facilitate individual PCa risk prediction in initial prostate biopsy.
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Application and efficacy of reconstructing forked corpus spongiosum in distal/midshaft hypospadias repair p. 47
Bin Zhang, Yun-Li Bi, Shuang-Sui Ruan
DOI:10.4103/aja.aja_42_20  PMID:32859871
We reviewed our experience in reconstructing forked corpus spongiosum (FCS) in distal/midshaft hypospadias repair and analyzed the efficacy of this surgical technique. From August 2013 to December 2018, 137 consecutive cases of distal/midshaft hypospadias operated by the same surgeon in Urology Department, Children's Hospital of Fudan University (Shanghai, China), were retrospectively analyzed. Sixty-four patients who underwent routine tubularized incised plate (TIP) or onlay island flap (ONLAY) surgery were included in the nonreconstructing group, and 73 patients who underwent reconstructing FCS during TIP or ONLAY surgery were included as the reconstructing group. Thirty-eight cases underwent TIP, and 26 underwent ONLAY in the nonreconstructing group, with a median follow-up of 44 (range: 30–70) months. Twenty-seven cases underwent TIP, and 46 underwent ONLAY in the reconstructing group, with a median follow-up of 15 (range: 6–27) months. In the nonreconstructing/reconstructing groups, the mean age at the time of surgery was 37.55 (standard deviation [s.d.]: 29.65)/35.23 (s.d.: 31.27) months, the mean operation duration was 91.95 (s.d.: 12.17)/93.84 (s.d.: 14.91) min, the mean neourethral length was 1.88 (s.d.: 0.53)/1.94 (s.d.: 0.53) cm, and the mean glans width was 11.83 (s.d.: 1.32)/11.56 (s.d.: 1.83) mm. Twelve (18.8%)/5 (6.8%) postoperative complications occurred in the nonreconstructing/reconstructing groups. These included fistula (5/2), glans dehiscence (3/0), diverticulum (1/2), residual chordee (3/0), and meatus stenosis (0/1) in each group. There was a significant difference in the overall rate of complications (P= 0.035). These results indicate that the technique of reconstructing FCS provides excellent outcomes with fewer complications in distal/midshaft hypospadias repair.
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Serum vitamin D content is associated with semen parameters and serum testosterone levels in men Highly accessed article p. 52
Inari M Ciccone, Elaine MF Costa, Juliana R Pariz, Thiago A Teixeira, Joel R Drevet, Parviz Gharagozloo, Robert J Aitken, Jorge Hallak
DOI:10.4103/aja.aja_9_20  PMID:32341213
The present study aimed to evaluate the influence of serum vitamin D levels on semen quality and testosterone levels. This is a cross-sectional study conducted at Androscience, Science and Innovation Center in Andrology and High-Complex Clinical and Andrology Laboratory in Sao Paulo, Brazil, with 508 male patients, aged 18–60 years, from 2007 to 2017. Seminal parameters and serum sexual hormones were correlated with serum vitamin D concentrations in 260 men selected by strict selection criteria. Patients were divided into normozoospermic group (NZG, n = 124) and a group with seminal abnormalities (SAG, n = 136). Evaluation included complete physical examination, past medical history, habits and lifestyle factors, two complete seminal analysis with sperm functional tests, serum levels of 25-hydroxy-vitamin D3(25(OH)VD3), total and free testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), total cholesterol, homeostatic model assessment of insulin resistance (HOMA-IR) index, and karyotype. The mean concentration of 25(OH)VD3was significantly lower in the SAG (P < 0.001) and positively correlated with all baseline seminal parameters and total testosterone levels. In addition, serum vitamin D3concentration was found to be positively correlated with sperm concentration (β= 2.103; P < 0.001), total number of spermatozoa with progressive motility (β = 2.069; P = 0.003), total number of motile spermatozoa (β = 2.571; P = 0.015), and strict morphology (β = 0.056; P = 0.006), regardless of other variables. This is the first comparative study to address the issue of serum vitamin D3content between normozoospermic patients and those with sperm abnormalities. It clearly demonstrates a direct and positive relationship between serum vitamin D level and overall semen quality, male reproductive potential, and testosterone levels.
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Sperm retrieval rates and clinical outcomes for patients with different causes of azoospermia who undergo microdissection testicular sperm extraction-intracytoplasmic sperm injection p. 59
Hong-Liang Zhang, Lian-Ming Zhao, Jia-Ming Mao, De-Feng Liu, Wen-Hao Tang, Hao-Cheng Lin, Li Zhang, Ying Lian, Kai Hong, Hui Jiang
DOI:10.4103/aja.aja_12_20  PMID:32341210
The aim of our study was to compare the sperm retrieval rates (SRRs) and clinical outcomes of patients with different causes of azoospermia who underwent microdissection testicular sperm extraction-intracytoplasmic sperm injection (micro-TESE-ICSI). We conducted a retrospective study at the Reproductive Medicine Center of Peking University Third Hospital in Beijing, China, from January 2014 to December 2017. This study examined 769 patients with nonobstructive azoospermia who underwent 347 cycles of micro-TESE-ICSI. Patients with azoospermia were classified into Group A (Klinefelter syndrome, n = 284, 125 cycles), Group B (azoospermia Y chromosome factor c [AZFc] microdeletion, n = 91, 64 cycles), Group C (cryptorchidism, n = 52, 39 cycles), Group D (previous mumps and bilateral orchitis, n = 23, 23 cycles), and Group E (idiopathic azoospermia, n = 319, 96 cycles). Clinical characteristics, SRR, embryonic development, and pregnancy outcomes of the patients were compared between all groups. Patients in Group D had the highest and most successful SRR. The average SRR for all patients was 46.0%. The rates of clinical pregnancy, implantation, and live birth in Group D were 78.3%, 65.0%, and 74.0%, respectively, which were higher than those in all other groups (P < 0.05). Group B patients had the lowest clinical pregnancy, implantation, and live birth rates of all groups (P < 0.05). No differences were found in the miscarriage rate or birth defects among the groups (P > 0.05). Patients with orchitis had the highest SRR and best clinical outcomes. Although AZFc microdeletion patients had a higher SRR, their clinical outcomes were worse.
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Prostatic anatomical parameters correlate with clinical characteristics suggestive of benign prostatic hyperplasia p. 64
Ye Tian, Hong-Ming Liu, Bing Yang, Xiu-Shu Yang, Zhao-Lin Sun, Fa Sun, Guang-Heng Luo, Shu-Jie Xia
DOI:10.4103/aja.aja_47_20  PMID:32930102
We conducted the present study to assess the correlation of the prostatic anatomical parameters, especially the ratio of peripheral zone thickness and transitional zone thickness, with clinical and uroflowmetry characteristics suggestive of benign prostate hyperplasia (BPH). A total of 468 consecutive patients with a detailed medical history were identified. All patients were evaluated by scoring subjective symptoms with the International Prostate Symptom Score (IPSS) and quality of life (QoL). The prostatic anatomical parameters were measured using transrectal ultrasonography, and postvoid residual urine and maximum flow rate (Qmax) values were also determined. Pearson's correlation analysis revealed that both total prostate volume (TPV; r = 0.160, P < 0.001) and transitional zone volume (TZV; r = 0.104, P = 0.016) increased with patients' age; however, no correlations were observed of TPV, TZV, transitional zone index (TZI), and transitional zone thickness (TZT) with IPSS or QoL (all P >0.05). Peripheral to transitional zone index (PTI) was found negatively correlated with total IPSS (r = −0.113, P = 0.024), storage IPSS (r = −0.103, P = 0.041), and voiding IPSS (r = −0.123, P = 0.014). As regards the uroflowmetry characteristics, PTI (r = 0.157, P = 0.007) was indicated to be positively correlated with Qmaxand negatively correlated with TZI (r = −0.119, P = 0.042) and TZT (r = −0.118, P = 0.045), but not correlated with TPV, TZV, or peripheral zone thickness (PZT) (all P > 0.05). Postvoid residual urine (PVR) had not correlated with all the prostatic anatomical variables (all P > 0.05). This is the first study that formally proposed the concept of PTI, which is an easy-to-measure prostate anatomical parameter which significantly correlates with total IPSS, storage IPSS, voiding IPSS, and Qmax, suggesting that PTI would be useful in evaluating and managing men with lower urinary tract symptoms (LUTS)/BPH. However, well-designed studies are mandatory to verify the clinical utility of PTI.
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Prevalence of gene mutations in a Chinese 46,XY disorders of sex development cohort detected by targeted next-generation sequencing p. 69
Bing-Qing Yu, Zhao-Xiang Liu, Yin-Jie Gao, Xi Wang, Jiang-Feng Mao, Min Nie, Xue-Yan Wu
DOI:10.4103/aja.aja_36_20  PMID:32985417
46,XY disorders of sex development (DSD) is characterized by incomplete masculinization genitalia, with gonadal dysplasia and with/without the presence of Müllerian structures. At least 30 genes related to 46,XY DSD have been found. However, the clinical phenotypes of patients with different gene mutations overlap, and accurate diagnosis relies on gene sequencing technology. Therefore, this study aims to determine the prevalence of pathogenic mutations in a Chinese cohort with 46,XY DSD by the targeted next-generation sequencing (NGS) technology. Eighty-seven 46,XY DSD patients were enrolled from the Peking Union Medical College Hospital (Beijing, China). A total of fifty-four rare variants were identified in 60 patients with 46,XY DSD. The incidence of these rare variants was approximately 69.0% (60/87). Twenty-five novel variants and 29 reported variants were identified. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, thirty-three variants were classified as pathogenic or likely pathogenic variants and 21 variants were assessed as variants of uncertain significance. The overall diagnostic rate was about 42.5% based on the pathogenic and likely pathogenic variants. Androgen receptor (AR), steroid 5-alpha-reductase 2 (SRD5A2) and nuclear receptor subfamily 5 Group A member 1 (NR5A1) gene variants were identified in 21, 13 and 13 patients, respectively. The incidence of these three gene variants was about 78.3% (47/60) in patients with rare variants. It is concluded that targeted NGS is an effective method to detect pathogenic mutations in 46,XY DSD patients and AR, SRD5A2, and NR5A1 genes were the most common pathogenic genes in our cohort.
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Does intraoperative frozen section really predict significant positive surgical margins after robot-assisted laparoscopic prostatectomy? A retrospective study p. 74
Se Young Choi, Byung Hoon Chi, Tae-Hyoung Kim, Bumjin Lim, Wonchul Lee, Dalsan You, Choung-Soo Kim
DOI:10.4103/aja.aja_16_20  PMID:32362599
We investigated the relationship between positive surgical margin (PSM)-related factors and biochemical recurrence (BCR) and the ability of intraoperative frozen sections to predict significant PSM in patients with prostate cancer. The study included 271 patients who underwent robot-assisted laparoscopic prostatectomy with bilateral nerve sparing and maximal urethral preservation. Intraoperative frozen sections of the periurethra, dorsal vein, and bladder neck were analyzed. The ability of PSM-related factors to predict BCR and significant PSM was assessed by logistic regression. Of 271 patients, 108 (39.9%) had PSM and 163 (60.1%) had negative margins. Pathologic Gleason score ≥8 (18.9% vs 7.5%, P = 0.015) and T stage ≥T3a (51.9% vs 24.6%, P < 0.001) were significantly more frequent in the PSM group. Multivariate analysis showed that Gleason pattern ≥4 (vs <4; hazard ratio: 4.386; P = 0.0004) was the only significant predictor of BCR in the PSM cohort. Periurethral frozen sections had a sensitivity of 83.3% and a specificity of 84.2% in detecting PSM with Gleason pattern ≥4. Multivariate analysis showed that membranous urethra length (odds ratio [OR]: 0.79, P = 0.0376) and extracapsular extension of the apex (OR: 4.58, P = 0.0226) on magnetic resonance imaging (MRI) and positive periurethral tissue (OR: 17.85, P < 0.0001) were associated with PSM of the apex. PSM with Gleason pattern ≥4 is significantly predictive of BCR. Intraoperative frozen sections of periurethral tissue can independently predict PSM, whereas sections of the bladder neck and dorsal vein could not. Pathologic examination of these samples may help predict significant PSM in patients undergoing robot-assisted laparoscopic prostatectomy with preservation of functional outcomes.
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Periprostatic fat thickness measured on MRI correlates with lower urinary tract symptoms, erectile function, and benign prostatic hyperplasia progression p. 80
Bo Zhang, Xiang Chen, Yu-Hang Liu, Yu Gan, Pei-Hua Liu, Zhi Chen, Wei-Ping Xia, Guo-Yu Dai, Feng Ru, Ze-Xiang Jiang, Yao He
DOI:10.4103/aja.aja_51_20  PMID:32859870
This study investigated the correlation between periprostatic fat thickness (PPFT) measured on magnetic resonance imaging and lower urinary tract symptoms, erectile function, and benign prostatic hyperplasia (BPH) progression. A total of 286 treatment-naive men diagnosed with BPH in our department between March 2017 and February 2019 were included. Patients were divided into two groups according to the median value of PPFT: high (PPFT >4.35 mm) PPFT group and low (PPFT <4.35 mm) PPFT group. After the initial evaluation, all patients received a combination drug treatment of tamsulosin and finasteride for 12 months. Of the 286 enrolled patients, 244 completed the drug treatment course. Patients with high PPFT had larger prostate volume (PV; P = 0.013), higher International Prostate Symptom Score (IPSS; P = 0.008), and lower five-item version of the International Index of Erectile Function (IIEF-5) score (P = 0.002) than those with low PPFT. Both high and low PPFT groups showed significant improvements in PV, maximum flow rate, IPSS, and quality of life score and a decrease of IIEF-5 score after the combination drug treatment. The decrease of IIEF-5 score was more obvious in the high PPFT group than that in the low PPFT group. In addition, more patients in the high PPFT group underwent prostate surgery than those in the low PPFT group. Moreover, Pearson's correlation coefficient analysis indicated that PPFT was positively correlated with age, PV, and IPSS and negatively correlated with IIEF-5 score; however, body mass index was only negatively correlated with IIEF-5 score.
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Androgen downregulation of miR-760 promotes prostate cancer cell growth by regulating IL6 p. 85
Shuo Wang, Yong Yang, Yu-Dong Cao, Xing-Xing Tang, Peng Du
DOI:10.4103/aja.aja_20_20  PMID:32415054
Prostate cancer (PCa) is one of the most common malignancies in Western countries. Studies have shown that androgen contributes to the progression of PCa, but how androgen promotes PCa remains largely unknown. Here, we demonstrated that androgen suppressed the expression of miR-760 depending on the interaction between androgen and androgen receptor (AR). miR-760 was downregulated in prostate cancer tissues compared with normal tissues. Functional experiments showed that miR-760 downregulation promoted the proliferation and growth of LNCaP and 22rv1 cells. In contrast, miR-760 ectopic expression inhibited the proliferation of LNCaP and 22rv1 cells. DNA synthesis was suppressed by miR-760. Mechanistically, miR-760 bound to the 3'UTR of interleukin 6 (IL6 ). A mutation in the binding site disrupted their interaction. In addition, silencing ofIL 6 suppressed the proliferation of LNCaP and 22rv1 cells. IL6 was upregulated in PCa tissues. Our study reveals that androgen downregulates miR-760 to promote the growth of PCa cells by regulating IL6.
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Improving native human sperm freezing protection by using a modified vitrification method p. 91
Dai Zhou, Xing-Ming Wang, Rui-Xue Li, Yi-Ze Wang, Yuan-Chi Chao, Zhi-Zhong Liu, Zeng-Hui Huang, Hong-Chuan Nie, Wen-Bing Zhu, Yue-Qiu Tan, Li-Qing Fan
DOI:10.4103/aja.aja_29_20  PMID:32567578
Slow freezing is the most commonly used technique for the cryopreservation of spermatozoa in clinical practice. However, it has been shown to have a negative impact on sperm function and structure. Vitrification as a successful alternative method has been proved to have better protective effects on human embryos, but vitrification of spermatozoa is still subject to low recovery rates. In this study, a modified vitrification method for native spermatozoa was developed. A total of 28 semen samples were included; each sample was divided into three equal parts and assigned to fresh, slow freezing, and vitrification groups. Sperm vitality, motility, morphology, DNA integrity, and acrosome reaction were assessed for each of the groups. The results showed that vitrification achieves better results for several sperm protection parameters than slow freezing; vitrification achieves a higher recovery rate (P < 0.05), motility (P <0.05), morphology (P <0.05), and curve line velocity (P <0.05) than slow freezing. Furthermore, DNA fragmentation was decreased (P <0.05) and better acrosome protection (P <0.05) was exhibited in the spermatozoa after vitrification. Principal component analysis of all sperm parameters revealed that the vitrification cluster was closer to the fresh cluster, indicating that spermatozoa are better preserved through vitrification. In conclusion, while both slow freezing and vitrification have negative effects on sperm function and structure, the vitrification protocol described here had a relatively better recovery rate (65.8%) and showed improved preservation of several sperm quality parameters compared with slow freezing.
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Establishment and internal validation of preoperative nomograms for predicting the possibility of testicular salvage in patients with testicular torsion p. 97
Wan-Xiang Zheng, Guang-Dong Hou, Wei Zhang, Di Wei, Xue-Lin Gao, Mei-Hong Chen, Lu-Guang Huang, Fei Yan, Geng Zhang, Lei Yu, Fei Liu, Bo Zhang, Jian-Lin Yuan
DOI:10.4103/aja.aja_31_20  PMID:32687070
This study aimed to establish nomograms to preoperatively predict the possibility of testicular salvage (TS) in patients with testicular torsion. The clinical data of 204 patients with testicular torsion diagnosed at Xijing Hospital and Tangdu Hospital (Xi'an, China) between August 2008 and November 2019 were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to determine the independent predictors of TS. Based on multivariate regression coefficients, nomograms to predict possibility of TS were established. The predictive ability of the nomograms was internally validated by receiver operating characteristic (ROC) curves and calibration plots. The duration of symptoms ranged from 2 h to 1 month, with a median of 3.5 days. Thirty (14.7%) patients underwent surgical reduction and contralateral orchiopexy, while the remaining 174 (85.3%) underwent orchiectomy and contralateral orchiopexy. Finally, long symptom duration was an independent risk predictor for TS, while visible intratesticular blood flow and homogeneous testicular echotexture under color Doppler ultrasound were independent protective predictors. Internal validation showed that the nomograms, which were established by integrating these three predictive factors, had good discrimination ability in predicting the possibility of TS (areas under the ROC curves were 0.851 and 0.828, respectively). The calibration plots showed good agreement between the nomogram-predicted possibility of TS and the actual situation. In conclusion, this brief preoperative prediction tool will help clinicians to quickly determine the urgency of surgical exploration.
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The presence of intraductal carcinoma of the prostate is closely associated with poor prognosis: a systematic review and meta-analysis p. 103
Yu-Cong Zhang, Guo-Liang Sun, De-Lin Ma, Chao Wei, Hao-Jie Shang, Zhuo Liu, Rui Li, Tao Wang, Shao-Gang Wang, Ji-Hong Liu, Xia-Ming Liu
DOI:10.4103/aja.aja_21_20  PMID:32496222
We aimed to confirm the predictive ability of the presence of intraductal carcinoma of the prostate (IDC-P) for prognosis and the associations between IDC-P and clinicopathological parameters. Studies were identified in PubMed, Cochrane Library, EMBASE, Web of Science, and SCOPUS up to December 1, 2019. Hazard ratios (HRs) for survival data and odds ratios for clinicopathological data with 95% confidence intervals (CIs) were extracted. Heterogeneity was evaluated by the I[2] value, and quality was assessed by the Newcastle–Ottawa Scale criteria. A total of 4179 patients from 13 studies were included. The results showed that IDC-P presence was significantly associated with poor progression-free survival (PFS; HR = 2.31; 95% CI: 1.96–2.73), cancer-specific survival (HR = 1.89; 95% CI: 1.28–2.77), and overall survival (HR = 2.14; 95% CI: 1.53–3.01). In the subgroup analysis, IDC-P presence was significantly associated with poor PFS in prostate cancer treated by radical prostatectomy (HR = 2.48; 95% CI: 2.05–3.00) and treated by radiotherapy (HR = 2.83; 95% CI: 1.65–4.85). Regarding clinicopathological characteristics, patients with IDC-P presence had significantly higher tumor clinical stages, Gleason scores, probabilities of lymph node invasion, positive surgical margins, and positive extraprostatic extension. Our meta-analysis indicates that the presence of IDC-P is closely associated with poor prognosis and adverse clinicopathological characteristics. Our data support the value and clinical utility of the routine detection of IDC-P by pathological examination. These conclusions need further validation, and prospective studies are needed to find better treatment modalities other than traditional first-line therapy for patients with IDC-P.
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Clinical significance of EPHX2 deregulation in prostate cancer p. 109
Ming-Sheng Liu, Hui Zhao, Chen-Xiang Xu, Ping-Bo Xie, Wei Wang, Ying-Yu Yang, Wen-Hui Lee, Yang Jin, Hong-Qing Zhou
DOI:10.4103/aja.aja_34_20  PMID:32687069
The arachidonic acid (AA) metabolic pathway participates in various physiological processes as well as in the development of malignancies. We analyzed genomic alterations in AA metabolic enzymes in the Cancer Genome Atlas (TCGA) prostate cancer (PCa) dataset and found that the gene encoding soluble epoxide hydrolase (EPHX2) is frequently deleted in PCa. EPHX2 mRNA and protein expression in PCa was examined in multiple datasets by differential gene expression analysis and in a tissue microarray by immunohistochemistry. The expression data were analyzed in conjunction with clinicopathological variables. Both the mRNA and protein expression levels of EPHX2 were significantly decreased in tumors compared with normal prostate tissues and were inversely correlated with the Gleason grade and disease-free survival time. Furthermore, EPHX2 mRNA expression was significantly decreased in metastatic and recurrent PCa compared with localized and primary PCa, respectively. In addition, EPHX2 protein expression correlated negatively with Ki67 expression. In conclusion, EPHX2 deregulation is significantly correlated with the clinical characteristics of PCa progression and may serve as a prognostic marker for PCa.
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LETTER TO THE EDITOR Top

The pelvic pop: an extremely rare case of internal penile fracture presenting with scrotal hematoma and review of the literature p. 116
Michael E Rezaee, Martin S Gross
DOI:10.4103/aja.aja_14_20  PMID:32367836
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A novel approach: successful management of vasectomy reversal with a three-dimensional digital image microscope system p. 118
Peng Li, Er-Lei Zhi, Chen-Cheng Yao, Shu-Jie Xia, Zheng Li
DOI:10.4103/aja.aja_15_20  PMID:32394900
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Transurethral vesiculoscope-assisted laser incision of the prostatic utricle to treat partial ejaculatory duct obstruction p. 120
Ke-Nan Wang, Wen-Long Xie, Lei Zheng, Tao Jiang
DOI:10.4103/aja.aja_144_19  PMID:32129190
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INVITED COMMENTARY Top

Commentary on a novel technique for distal hypospadias repair using forked corpus spongiosum p. 122
Hannah Kay, E Charles Osterberg
DOI:10.4103/aja.aja_52_20  PMID:33208561
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