The influence of prostate volume on pathological outcomes after radical prostatectomy: A single-center retrospective study.

Currently, the association between prostate volume (PV) or prostate weight with pathological outcomes in patients with prostate cancer (PCa) is not well understood. This study aimed to explore whether PV can predict the adverse pathological outcomes of PCa patients after radical prostatectomy (RP). A total of 1063 men with confirmed localized PCa who underwent RP at the First Affiliated Hospital of Zhejiang University from January 2014 to April 2019 were retrospectively analyzed. Patients were assigned into small, medium and large groups based on the PV. The analysis of variance, χ2 test or Student t test was performed to compare differences among groups. Univariate and multivariate analyses were performed to identify significant predictors of pathological outcomes upgrading. Among the 1063 cases, approximately 35.0% had an upgrade of postoperative pathology. Compared with the small prostate group, more patients in the large prostate group achieved a Gleason score (GS) 6 and International Society of Urological Pathology (ISUP) grade 1 of postoperative pathological findings, clinical cT1c and cT2a stages and pathological pT2a and pT2b stages; the incidence of positive surgical margins and extraprostatic extension was relatively low (all P < .001). In multiple logistic regression, PV served as a significant predictor of any Gleason score upgrading (GSU) (odds ratio [OR] 0.988, 95% confidence interval [CI] 0.978-0.998), major GSU (OR 0.980, 95% CI 0.965-0.995) and any ISUP grade group upgrading (GGU) (OR 0.989, 95% CI 0.979-0.999). This study shows that PV can predict adverse pathological outcomes in PCa patients after radical prostatectomy. Pca patients with smaller prostate volume tend to have the high-grade disease at postoperative pathology as well as pathological outcome upgrading.

Loss of SETD2-mediated downregulation of intracellular and exosomal miRNA-10b determines MAPK pathway activation and multidrug resistance in renal cancer.

SET domain-containing 2 (SETD2) is the most frequently mutated gene among all the histone methyltransferases in clear cell renal cell carcinoma (ccRCC). Microarrays, RNA sequencing analysis and exosomes analysis of cellular supernatant were performed after transfection A498 cells with si-SETD2 or siRNA of negative control. Chromatin immunoprecipitation and Luciferase reporter assay were conducted to evaluate the interaction between SETD2 and miR-10b. Functional and drug experiments in vitro and in vivo were performed to verify the role of SETD2, miR-10b and MAP4K4. The results showed that loss of SETD2 mediated downregulation of intracellular and exosomal microRNA-10b. MAP4K4 were relevant to oncogenesis of ccRCC caused by loss of SETD2 and miR-10b. SETD2 could directly target miR-10b and regulate the expression of multidrug resistance (MDR)-1 (P-gp170) through JNK pathway, which was one of the downstream pathways of MAP4K4. The coordinated expression of SETD2/H3K36me3/miR-10b/MAPKs/JNK/MDR pathway was revealed to the progression of ccRCC.

Corrigendum: Transcription factors BARX1 and DLX4 contribute to progression of clear cell renal cell carcinoma via promoting proliferation and epithelial-mesenchymal transition.

[This corrects the article DOI: 10.3389/fmolb.2021.626328.].

Efficacy evaluation of thickened condom in the treatment of premature ejaculation.

Background: This study aimed to evaluate the efficacy of thickened condoms in the treatment of premature ejaculation. Methods: From August to December 2021, patients with premature ejaculation treated in the Urology and Andrology Center of the First Affiliated Hospital of Medical College of Zhejiang University were selected for a clinical controlled study. A total of 100 patients with premature ejaculation were enrolled as the premature ejaculation group and 30 normal men as the control (normal married men, age <30 years, normal sexual life). Each patient's ejaculation latency, contraceptive safety, comfort, glans sensitivity, dorsal nerve conduction velocity, serum reproductive hormone level, penile hardness, and penile erection were measured in the premature ejaculation and normal control groups. Results: The comfortability associated with thickened condoms in the premature ejaculation group was poor (P<0.05). After using a thickened condom, the time to ejaculate of the premature ejaculation group was significantly prolonged (P<0.05). Meanwhile, the penis vibration threshold increased significantly, indicating that the nerve sensitivity decreased (P<0.05). In the premature ejaculation group, the total erection time and the average hardness of coronary sulcus in the thickened condom group were significantly higher than those in the ordinary condom group (P<0.05), and the serum androgen level could be significantly increased after using the thickened condom (P<0.05). Conclusions: The thickened condom can effectively maintain and prolong the hyperemia state of the penis and enhance the intensity of penile erection. Thickened condoms physically preserve and extend the time of penile erection, resist and overcome premature ejaculation, and improve the ejaculation condition to improve the quality of sexual intercourse.

Transcription Factors BARX1 and DLX4 Contribute to Progression of Clear Cell Renal Cell Carcinoma via Promoting Proliferation and Epithelial-Mesenchymal Transition.

Dysregulation of transcription factors contributes to the carcinogenesis and progression of cancers. However, their roles in clear cell renal cell carcinoma remain largely unknown. This study aimed to evaluate the clinical significance of TFs and investigate their potential molecular mechanisms in ccRCC. Data were accessed from the cancer genome atlas kidney clear cell carcinoma cohort. Bioinformatics algorithm was used in copy number alterations mutations, and differentially expressed TFs' analysis. Univariate and multivariate Cox regression analyses were performed to identify clinically significant TFs and construct a six-TF prognostic panel. TFs' expression was validated in human tissues. Gene set enrichment analysis (GSEA) was utilized to find enriched cancer hallmark pathways. Functional experiments were conducted to verify the cancer-promoting effect of BARX homeobox 1 (BARX1) and distal-less homeobox 4 (DLX4) in ccRCC, and Western blot was performed to explore their downstream pathways. As for results, many CNAs and mutations were identified in transcription factor genes. TFs were differentially expressed in ccRCC. An applicable predictive panel of six-TF genes was constructed to predict the overall survival for ccRCC patients, and its diagnostic efficiency was evaluated by the area under the curve (AUC). BARX1 and DLX4 were associated with poor prognosis, and they could promote the proliferation and migration of ccRCC. In conclusion, the six-TF panel can be used as a prognostic biomarker for ccRCC patients. BARX1 and DLX4 play oncogenic roles in ccRCC via promoting proliferation and epithelial-mesenchymal transition. They have the potential to be novel therapeutic targets for ccRCC.

Clinicopathological characteristics of androgen receptor splicing variant 7 (AR-V7) expression in patients with castration resistant prostate cancer: A systematic review and meta-analysis.

BACKGROUND:  Studies have shown that AR-V7 may be correlated with the poor prognosis of castration resistant prostate cancer (CRPC), however, clinicopathological characteristics of AR-V7 have not been fully elucidated. OBJECTIVE: This study aimed at evaluating the clinicopathological features of AR-V7 in CRPC patients. MATERIALS AND METHODS: To evaluate the clinicopathological features of AR-V7 in CRPC patients. A search of PubMed, Embase, and Web of Science was performed using the keywords prostate cancer, prostate tumor, prostate neoplasm, prostate carcinoma, AR-V7, AR3, androgen receptor splicing variant-7, or androgen receptor-3. Twenty-four trials published by February 2020 were included in this study. RESULTS: The proportion of Gleason score ≥ 8 was found to be significantly higher in AR-V7-positive CRPC (69.5%) than negative (54.9%) (OR 1.68, 95% CI 1.25-2.25, p < 0.001), while the rates of T3/T4 stage (OR 1.16, 95% CI 0.60-2.24, p = 0.65) and N1 stage (OR 0.99, 95% CI 0.65-1.51, p = 0.96) were not statistically correlated with AR-V7 status. The AR-V7-positive patients exhibited a significantly higher proportion of any site metastasis (61.3% versus 35.0%; OR 2.19, 95% CI 1.57-3.05, p < 0.001) and bone metastasis (81.7% versus 69.0%; OR 1.97, 95% CI 1.44-2.69, p < 0.001), and a trend close to significance was expected in visceral metastasis (28.8% versus 22.1%; OR 1.29, 95% CI 0.96-1.74, p = 0.09). Incidences of pain in AR-V7-positive CRPC (54.6%) were significantly higher than in negative CRPC (28.1%; OR 4.23, 95% CI 2.52-7.10, p < 0.001), line with worse ECOG performance status (56.7% versus 35.0%, OR 2.18, 95% CI 1.51-3.16, P < 0.001). Limitations of the study include differences in sample sizes and designs, AR-V7 detection assays, as well as disease characteristics of the included studies. CONCLUSIONS: AR-V7 positivity is associated with a higher Gleason score, bone or any site metastasis, pain and worse ECOG performance scores in CRPC. However, it is not correlated with tumor stage or lymph node metastasis. More studies are needed to confirm these findings.

Androgen Receptor Splice Variant 7 Predicts Shorter Response in Patients with Metastatic Hormone-sensitive Prostate Cancer Receiving Androgen Deprivation Therapy.

BACKGROUND: Whether AR-V7 expression can predict the response in patients with metastatic hormone-sensitive prostate cancer (mHSPC) who receive androgen deprivation therapy (ADT) remains to be explored. OBJECTIVE: To evaluate the predictive value of AR-V7 expression in the prognosis of mHSPC patients receiving ADT. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter prospective cohort study, 310 mHSPC patients commencing ADT were enrolled. Standard immunohistochemical staining was used to assess AR-V7 protein expression in biopsy tissues collected before initiation of ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier survival estimates and Cox regression analyses were used to evaluate associations of AR-V7 status (positive vs negative) with progression-free survival (PFS) and overall survival (OS). RESULTS AND LIMITATIONS: Sixty-four (21%) patients were AR-V7-positive and 246 (79%) patients were AR-V7-negative. The median follow-up for patients not confirmed dead was 25 mo (interquartile range 10-30). Compared to AR-V7-negative patients, AR-V7-positive patients had significantly shorter PFS (hazard ratio [HR] 47.39, 95% confidence interval [CI] 25.83-86.94) and OS (HR 3.57, 95% CI 1.46-8.72). In multivariable analysis, AR-V7 was an independent predictive factor (HR 7.61, 95% CI 5.24-11.06) for shorter PFS. Limitations include the sample size and follow-up period. CONCLUSIONS: AR-V7 expression in primary cancer tissue is correlated with poor prognosis for mHSPC patients receiving ADT. PATIENT SUMMARY: In this study of men with metastatic hormone-sensitive prostate cancer, AR-V7 protein expression in primary cancer tissue was associated with poor outcomes on androgen deprivation therapy.

Mid-term Results of Coil Embolization Alone and Stent-assisted Coil Embolization for Renal Artery Aneurysms.

BACKGROUND: Coil embolization (CE) alone and stent-assisted coil embolization (SCE) are two major endovascular techniques to treat renal artery aneurysms (RAAs). This study aimed at providing safety and efficacy data of CE and SCE for RAAs. METHODS: Between August 2015 and June 2019, 40 RAA patients treated with CE or SCE were included in the retrospective study. Patients' demographics, clinical manifestations, aneurysm characteristics, treatment strategies, and follow-up results were collected and analyzed. RESULTS: There were 26 and 14 patients in the CE and SCE group, respectively. The mean aneurysm diameter was 2.5 ± 1.5 cm and 2.2 ± 0.8 cm (CE versus SCE, P = 0.52). The neck width of the aneurysm was 0.63 ± 0.37 cm and 1.07 ± 0.42 cm (CE versus SCE, P = 0.021). Technical success was achieved in 97.5% patients. No death or aneurysm rupture occurred. During the perioperative period, 12% and 7.1% patients suffered partial renal infarction (CE versus SCE, P = 0.45). The mean duration of follow-up was 8.8 ± 9.4 months and 16.1 ± 16.3 months (CE versus SCE, P = 0.158) by imaging and 20.8 ± 11.3 and 22.7 ± 16.5 months by visit/telephone (CE versus SCE, P = 0.703). During the follow-up, 17.4% patients in the CE group and 30.8% patients in the SCE group suffered partial renal infarction, while their overall renal function remained normal. In addition, there was no aneurysm recurrence, sac enlargement, or death in both groups. CONCLUSIONS: Both CE and SCE were safe and effective to treat RAAs. In addition, SCE may prevent coil migration in the wide neck aneurysm in selected patients.

The Prognostic Value of External vs Internal Pancreatic Duct Stents in CR-POPF after Pancreaticoduodenectomy: A Systematic Review and Meta-analysis.

BACKGROUND: There is no specific evidence regarding the benefits of external and internal pancreatic duct stents after pancreaticoduodenectomy since pancreatic fistula (grade A) have been redefined with no clinical treatment effect. We aimed to reevaluate the prognostic value of external and internal stents in clinically relevant postoperative pancreatic fistula over pancreaticoduodenectomy. METHODS: PubMed, Web of Science, EMBASE and the Cochrane Database were specifically searched for pertinent and original articles published before May 2019. The project has been registered in PROSPERO (Registration number: CRD42019137579). RESULTS: Four randomized controlled trials and six nonrandomized controlled trials with a total of 2101 patients were enrolled in this meta-analysis. The use of an external stent resulted in better performance than the use of an internal stent in terms of pancreatic fistula (grade C) (OR 0.58, P = 0.03) but did not reduce the rate of pancreatic fistula (grade B) (OR 0.99, P = 0.94) in all studies. The meta-analysis of randomized controlled trials found that the use of an external stent approached a level of significance for an increased rate of clinically relevant postoperative pancreatic fistula compared to the use of an internal stent (OR 1.40, P = 0.10) but had no significant effect on pancreatic fistula (grade B) (OR 1.34, P = 0.26) or pancreatic fistula (grade C) (OR 1.68, P = 0.62). CONCLUSION: Compared with internal stents, the use of external stent might be associated with a lower rate of pancreatic fistula (grade C). More randomized clinical trials are warranted to further explore safety and efficacy of pancreatic duct external stents.

The clinicopathological significance and prognostic value of programmed death-ligand 1 in prostate cancer: a meta-analysis of 3133 patients.

BACKGROUND: Programmed death-ligand 1 (PD-L1) is considered an adverse factor predicting poor prognosis in various cancers, but the significance of PD-L1 expression for the prognosis of prostate cancer (PCa) is still unclear. We aimed to investigate the clinicopathological significance and prognostic value of PD-L1 expression in PCa. METHODS: Studies were retrieved from PubMed, Web of Science, Cochrane Library and Embase before March 23, 2020. Odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were obtained to assess the results. Begg's test was applied to evaluate publication bias. RESULTS: Fourteen studies involving 3133 cases were analyzed. The pooled data showed that both PD-L1 protein expression and PD-L1 DNA methylation (mPD-L1) were negatively associated with biochemical recurrence-free survival, with HRs of 1.67 (95% CI = 1.38-2.06, p < 0.001) and 2.23 (95% CI = 1.51-3.29, p < 0.001), respectively. In addition, PD-L1 overexpression was significantly related to advanced tumor stage (OR = 1.40, 95% CI= 1.13-1.75, p = 0.003), positive surgical margin (OR = 1.36, 95% CI = 1.03-1.78, p = 0.028), higher Gleason score (OR = 1.81, 95% CI = 1.35-2.42, p < 0.001) and androgen receptor positivity (OR = 2.20, 95% CI = 1.61-3.01, p < 0.001), while no significant correlation with age (p = 0.122), preoperative PSA (p = 0.796) or nodal status (p = 0.113) was observed. CONCLUSIONS: The study revealed that high expression of PD-L1 was related to unfavorable prognosis and advanced clinicopathological factors in PCa patients.

Early outcomes of implanting larger-sized grafts in deceased donor liver transplantation.

BACKGROUND: The outcomes of large-sized graft mismatch in deceased donor liver transplantation (LT) have been rarely studied. The aim of this study was to determine whether a large-sized graft for recipient influenced the post-transplant outcomes. METHODS: A total of 273 patients undergoing LT were enrolled and divided into a large and a normal-sized graft group by graft weight to recipient weight (GWRW) >2.5% (n = 76) or GWRW ≤2.5% (n = 197). Post-operative complications and outcomes were retrospectively analysed. RESULTS: The two groups were comparable in demographic characteristics. The rate of complications was significantly higher in the large-sized graft group including early allograft dysfunction (36.8% versus 17.8%, P = 0.001), hepatic necrosis (26.3% versus 13.7%, P = 0.01) and massive hydrothorax (25% versus 14.7%, P = 0.04). The large-sized graft group suffered higher early mortality compared with the normal-sized graft group (30 days: 14.5% versus 5.6%, P = 0.02, 90 days: 21.1% versus 9.6%, P = 0.01). The primary causes of early death were multiple organ failure (10.5% versus 2%, P = 0.002) and sepsis (2.6% versus 1.5%, P = 0.54). Four parameters including donor alanine transaminase, GWRW, estimated blood loss and model for end-stage liver disease score were significant on multivariate analysis, and indicated significant risk factors for the early mortality of recipients. CONCLUSION: In deceased donor LT, GWRW >2.5% is associated with increased liver injury, risk of early mortality and other adverse outcomes. Thus, donor livers should be allocated to recipients with GWRW ≤2.5%.

The characteristics of androgen receptor splice variant 7 in the treatment of hormonal sensitive prostate cancer: a systematic review and meta-analysis.

BACKGROUND: Accumulating evidence suggests androgen receptor splice variant 7 (AR-V7) may be associated with the prognosis of castration-resistant prostate cancer (CRPC) received novel hormonal therapy while its characteristic and prognosis value in hormonal sensitive prostate cancer is unclear. METHODS: We aimed to evaluate the prognostic role of AR-V7 by progression free survival (PFS) and overall survival (OS) in hormonal sensitive prostate cancer (HSPC), and the AR-V7-positive-proportion difference in HSPC and CRPC. A search of PubMed, Embase, and the Web of Science was performed using the keywords prostate cancer, prostate tumor, prostate neoplasm, prostate carcinoma; AR-V7, AR3, androgen receptor splicing variant-7, or androgen receptor-3. Seventeen trials published due December 2019 were enrolled. RESULTS: AR-V7-positive proportion in CRPC was significantly larger than newly diagnosed prostate cancer (PCa) (odds ratio [OR] 7.06, 95% confidence interval [CI] 2.52-19.83, P < 0.001). Subgroup analyses indicated significantly higher AR-V7-positive proportion in CRPC derived from RNA in situ hybridization (OR 65.23, 95% CI 1.34-3171.43, P = 0.04), exosome RNA (OR 3.88, 95% CI 0.98-15.39, P = 0.05) and tissue RNA (OR 10.89, 95% CI 4.13-28.73, P < 0.001). AR-V7-positive patients had a significantly shorter PFS than those who were AR-V7-negative treated with first-line hormonal therapy (hazard ratio [HR] 3.63, 95% CI 1.85-7.10, P < 0.001) and prostatectomy (HR 2.49, 95% CI 1.33-4.64, P = 0.004). OS (HR 5.59, 95% CI 2.89-10.80, P < 0.001) were better in AR-V7-negative than AR-V7-positive HSPC patients treated with first-line hormonal therapy. The limitations of our meta-analysis were differences in study sample size and design, AR-V7 detection assay, and disease characteristics. CONCLUSION: AR-V7-positive proportion was significantly higher in CRPC than that in newly diagnosed PCa. AR-V7 positive HSPC patients portend worse prognosis of first-line hormonal therapy and prostatectomy. Additional studies are warranted to confirm these findings.

The Prognostic Value of Androgen Receptor Splice Variant 7 in Castration-Resistant Prostate Cancer Treated With Novel Hormonal Therapy or Chemotherapy: A Systematic Review and Meta-analysis.

PURPOSE: This study aimed to evaluate the prognostic role of AR-V7 in terms of prostate-specific antigen (PSA) response, progression-free survival (PFS), and overall survival (OS) in CRPC patients treated with novel hormonal therapy (NHT) (Abiraterone and Enzalutamide) or taxane-based chemotherapy (Docetaxel and Cabazitaxel). METHODS: A comprehensive literature search was conducted on PubMed, Embase, and the Web of Science from inception to February 2020. Studies focusing on the prognostic values of AR-V7 in CRPC patients treated with NHT or chemotherapy were included in our meta-analysis. The OS and PFS were analyzed based on Hazard ratios (HRs) and 95% confidence intervals (CIs). Furthermore, Odds ratios (ORs) and 95% CIs were summarized for the AR-V7 conversion after treatment and the PSA response. RESULTS: The AR-V7 positive proportion increased significantly after NHT treatment (OR 2.56, 95% CI 1.51-4.32, P<0.001), however, it declined after chemotherapy (OR 0.51, 95% CI 0.28-0.93, P=0.003). AR-V7-positive patients showed a significantly decreased PSA response rate after NHT (OR 0.13, 95% CI 0.09-0.19, P<0.001) but not statistically significant for chemotherapy (OR 0.63, 95% CI 0.40-1.01, P=0.06). Notably, PFS (HR 3.56, 95% CI 2.53-5.01, P<0.001) and OS (HR 4.47, 95% CI 3.03-6.59, P<0.001) were worse in AR-V7-positive ttreated with NHT. Similarly, AR-V7 positivity correlated with poor prognosis after chemotherapy as evidenced by shorter OS (HR 1.98, 95% CI 1.48-2.66, P<0.001) and a significantly shorter PFS (HR 1.35, 95% CI 0.97-1.87, P=0.07). CONCLUSION: NHT treatment increased AR-V7 positive proportion whereas chemotherapy decreased it. Moreover, AR-V7 positivity correlated with lower PSA response, poorer PFS, and OS in CRPC treated with NHT, and shorter OS in patients receiving chemotherapy.

The Immune Checkpoint Regulator PDL1 is an Independent Prognostic Biomarker for Biochemical Recurrence in Prostate Cancer Patients Following Adjuvant Hormonal Therapy.

Background: The programmed death 1 (PD1)/programmed death ligand 1 (PDL1) targeted therapies have gained positive outcomes in several tumors, but the evidence of the expression and prognosis value of PD1/PDL1 in high risk prostate cancer was rare. Methods: Immunohistochemical analysis of PDL1/PD1 expression by a validated antibody was performed in a retrospectively collected high risk prostate cancer cohort who received adjuvant hormonal therapy (AHT) after radical prostatectomy (RP). The association between PDL1/PD1 expression and prognosis was determined. Results: In total, 127 patients were enrolled. 49.6% patients were considered PDL1-high expression while the PD1-positive expression proportion was 24.4%. High PDL1 and negative PD1 expression were significantly associated with lower prostate specific antigen (PSA) density (p=0.010 and p=0.033, respectively). Compared with the PDL1-low expression patients, the PDL1-high expression patients had significantly shorter time to PSA nadir (TTN) (P=0.001) and biochemical recurrence (BCR) (P=0.004). In Kaplan-Meier analysis, the PDL1-high expression group (p<0.0001) and the PDL1-high/PD1-negative expression group (p<0.0001) showed markedly lower BCR-free survival in localized disease. Univariate cause-specific Cox proportional hazard regression model concluded total PSA (p=0.047), PDL1-high-expression (p<0.001), PDL1-high/PD1-negative expression (p<0.001) were significant risk factors of shorter progression time to BCR in localized disease. PDL1-high-expression was the independent predictor of time to BCR in multiple Cox regression of all patients (Hazard ratio [HR]: 3.901; 95% Confidence interval [CI]: 1.287-11.824; p=0.016). Conclusions: PDL1 expression is not only highly prevalent in high-risk prostate cancer, but is also an independent biomarker in the prognosis of high-risk prostate cancer received AHT after RP. PDL1/PD1 targeted therapy might be a potentially adjuvant treatment option for high-risk prostate cancer after RP.

Analysis of the role of mutations in the KMT2D histone lysine methyltransferase in bladder cancer.

Histone lysine methyltransferases (HMT) comprise a subclass of epigenetic regulators; dysregulation of these enzymes affects gene expression, which may lead to tumorigenesis. Here, we performed an integrated analysis of 50 HMTs in bladder cancer and found intrinsic links between copy number alterations, mutations, gene expression levels, and clinical outcomes. Through integrative analysis, we identified six HMT genes (PRDM9,ASH1L,SETD3,SETD5,WHSC1L1, and KMT2D) that may play a key role in the development and progression of bladder cancer. Of these six HMTs, histone lysine N-methyltransferase 2D (KMT2D) exhibited the highest mutation rate in bladder cancer. Our comparison of the mRNA and miRNA expression profiles of mutated and wild-type KMT2D suggested that two signaling pathways (FOX1-miR-1224-5p-DLK1 and HIF/GATA5-miR-133a-3p-DRD5) may mediate the tumor suppressive effect of the KMT2D mutation. In summary, our findings indicate that mutations in HMT genes, especially KMT2D mutation, may play a role in the development of bladder cancer.

Primary Prostatic Extra-Gastrointestinal Stromal Tumor Treated with Imatinib Mesylate as Neoadjuvant and Adjuvant Therapy: A Case Report and Literature Review.

The current study presents a case of primary prostatic extra-gastrointestinal stromal tumor (EGIST) in a 43-year-old man who suffered acute urinary retention. The serum level of prostate-specific antigen was normal. Imaging examinations demonstrated a diffusely enlarged prostate compressing the rectum without evidence of metastasis. After excluding the possibility of secondary involvement by a rectal GIST, the pathologic diagnosis of primary prostatic EGIST was established based on microscopic study, immunohistochemistry, and molecular analysis. This patient is the first case with primary EGISTs of prostate received imatinib mesylate as neoadjuvant and adjuvant therapy reported in the literature to date. We hope this case could provide the experience of diagnosis and treatment of primary prostatic EGISTs.

Pure Small Cell Carcinoma of Prostate: A Report of 8 Cases.

PURPOSE: To describe characteristics of pure small cell carcinoma of prostate (SCCP) and assess the prognostic factors. PATIENTS AND METHODS: We summarized data of pure SCCP from published studies and ours and made Kaplan-Meier analysis and Cox regression to evaluate prognosis factors. RESULTS: A total of 2,213 patients with prostate cancer was identified, of which eight (0.36%) patients were pure SCCP. The mean age at diagnosis was 61 years old. And there were 2 patients diagnosed at 34 and 50 years old respectively. Symptoms of these patients were similar to patients with prostate adenocarcinoma. Serum prostate specific antigen of 7 patients was at normal level. Five patients received chemotherapy, average overall survival (OS) was 9.75 months; 3 only received conservative treatment, average OS was 4 months. By univariate and multivariate Cox analysis, chemotherapy is an independent predictor of survival. Kaplan-Meier analysis demonstrated that chemotherapy was associated with longer OS. CONCLUSION: Clinical characteristics, examination and treatment strategy of pure SCCP are very different from prostate adenocarcinoma. According to the data from published studies and from our studies, the average survival of patients receiving chemotherapy is longer than those who received other treatment modalities.

Prognostic Value of Androgen Receptor Splice Variant 7 in the Treatment of Castration-resistant Prostate Cancer with Next generation Androgen Receptor Signal Inhibition: A Systematic Review and Meta-analysis.

CONTEXT: Androgen receptor splice variant 7 (AR-V7) may be associated with resistance to next-generation androgen receptor signaling (ARS) inhibitors in castration-resistant prostate cancer (CRPC) sensitive to chemotherapy. OBJECTIVE: To evaluate the prognostic value of AR-V7 for prostate specific antigen (PSA) response, progression-free survival (PFS), and overall survival (OS) among CRPC patients treated with ARS inhibitors or chemotherapy. EVIDENCE ACQUISITION: A search of PubMed, Embase, and Web of Science databases was performed using the keywords "prostate cancer", "prostate tumor", "prostate neoplasm", "prostate carcinoma"; "AR-V7", "AR3", "androgen receptor splicing variant-7" and "androgen receptor-3". Fourteen trials published up to August 2016 were selected. EVIDENCE SYNTHESIS: A significantly greater proportion of CRPCs than newly diagnosed prostate cancers were AR-V7-positive (odds ratio [OR] 8.29, 95% confidence interval [CI] 5.06-13.57; p<0.001). AR-V7-positive patients treated with ARS inhibitors had a significantly lower PSA response than those who were AR-V7-negative (OR 0.05, 95% CI 0.02-0.16; p<0.001).The difference was not significant in chemotherapy-treated patients (OR 0.64, 95% CI 0.3-1.33; p=0.23). Both PFS (hazard ratio [HR] 4.05, 95% CI 1.91-8.59; p=0.0003) and OS (HR 4.79, 95% CI 2.14-10.72; p<0.001) were better in AR-V7-negative than AR-V7-positive CRPC patients treated with ARS inhibitors. In chemotherapy patients, AR-V7 status had no significant effect on PFS (HR 1.26, 95% CI 0.80-2.00; p=0.32).However, AR-V7-negative patients had significantly better OS (HR 2.82, 95% CI 1.72-4.62; p<0.001). The limitations of our meta-analysis were differences in study sample size and design, AR-V7 assay, and disease characteristics. CONCLUSIONS: AR-V7 positivity was associated with poorer PSA response and PFS prognosis in CRPC patients treated with ARS inhibitors, but did not affect outcomes except OS for those treated with chemotherapy. Additional studies are warranted to confirm these findings. PATIENT SUMMARY: We concluded from several studies that androgen receptor splice variant 7 (AR-V7) could predict the outcomes of prostate cancer. AR-V7-positive patients have poorer outcomes when treated with abiraterone or enzalutamide, but relatively better outcomes when treated by chemotherapy.

Androgen-receptor splice variant-7-positive prostate cancer: a novel molecular subtype with markedly worse androgen-deprivation therapy outcomes in newly diagnosed patients.

Androgen-deprivation therapy has been the standard treatment for metastatic and locally advanced prostate cancer, but the majority of patients will progress to castration-resistant prostate cancer within 2-3 years. Unlike the case in breast cancer, no clinically validated biomarker has been used to predict the outcomes of androgen-deprivation therapy. To evaluate androgen-receptor splice variant-7 (AR-V7) detection in newly diagnosed advanced prostate cancer and describe the distinctive prognosis of this novel molecular subtype, this study retrospectively enrolled 168 newly diagnosed prostate cancer patients from 2003 to 2015 who received androgen-deprivation therapy. AR-V7 immunohistochemical staining was performed with a monoclonal antibody, and AR-V7 expression was determined using Immune-Reactive Score data. The association between nuclear AR-V7 expression and prognosis was determined. Multiple cause-specific Cox regression and stratified cumulative incidences were used to analyze the prognosis risk. Among the 168 patients, 32 (19%) were AR-V7-positive. Compared with the AR-V7-negative patients, the AR-V7-positive patients had significantly lower prostate-specific antigen response rates (P<0.001) to androgen-deprivation therapy and a much shorter time to castration-resistant prostate cancer (P<0.0001). In Kaplan-Meier analysis, the AR-V7-positive group showed markedly lower castration-resistant prostate cancer progression-free survival (P<0.0001) and much lower cancer-specific (P<0.0001) and overall survival (P<0.0001) both in all enrolled patients and in patients with metastases. AR-V7 positivity was a significant predictor of castration-resistant prostate cancer progression in multiple Cox regression (hazard ratio: 4.826; 95% CI: 2.960-7.869; P<0.001). AR-V7 immunohistochemical detection in newly diagnosed prostate cancer patients who are planning to receive androgen-deprivation therapy, especially those with metastases, is necessary and valuable for prognostic assessment. AR-V7-positive prostate cancer should be considered a novel prostate cancer subtype that should be distinguished upon initial biopsy. The main limitation of this study is its observational nature.