作者： 刊期： 2014年第03期

Men with prostate cancer suffer substantially from bone-related complications. Androgen deprivation therapy itself is a cause of loss of bone mineral density and is associated with an increased incidence of osteoporotic fractures. In advanced disease, bone is by far the most common site of metastasis. Complications of bone metastases prominently include pain and the potential for skeletal events such as spinal cord compression and pathologic fractures. Elevated osteoclast activity is an important aspect of the pathophysiology of both treatment-related osteoporosis and skeletal complications due to metastases. The osteoclast is therefore a therapeutic target. Denosumab is a fully human monoclonal antibody to receptor activator of nuclear factor-k-B ligand that was designed to potently inhibit osteoclast activity and is the central focus of this review. Bisphosphonates, radiopharmaceuticals and systemically-active hormonal agents such as abiraterone acetate and enzalutamide have each been shown to improve skeletal morbidity in speciifc clinical situations. Denosumab is the only agent that has been shown to prevent osteoporotic fractures in men receiving androgen deprivation therapy and at elevated risk for fracture. It has also demonstrated superiority to the potent bisphosphonate zoledronic acid for the prevention of skeletal-related events in men with castration-resistant prostate cancer metastatic to bone. Efifcacy and toxicity data will be discussed.

作者： 刊期： 2014年第03期

The objective of this study was to compare the outcomes of the modiifed Nesbit procedure using different techniques for dissecting the neurovascular bundle (NVB) to correct ventral congenital penile curvatures (CPCs). The bundle was mobilized using the medial and lateral dissection technique in 21 (Group 1) and 13 (Group 2) patients, respectively. In the medial technique, Buck’s fascia is opened at the dorsal side of the penis, the deep dorsal vein is removed at the most prominent site of the curvature and a diamond-shaped tunica albuginea (TA) is excised from the midline of the penis. In the lateral technique, the bundle is mobilized using a longitudinal lateral incision of the Buck’s fascia above the urethra at the 5 and 7 o’clock positions via a bilateral approach. The localization and degree of curvature was evaluated using the combined intracavernous injection stimulation test or from the patients’ photographs. The mean patient age and degree of curvature were similar between groups. The mean operation time was longer for Group 2 (P=0.01). In Group 1, nine patients (42.8%) required one diamond excision, 10 (47.6%) required two diamond excisions and two (9.5%) required more than two excisions; in Group 2, six patients (46.2%) required two diamond excisions and seven patients (53.8%) required more than two diamond excisions (P=0.019). The differences in penile shortening, penile straightening and numbness of the glans penis were not statistically signiifcant. Medial dissection of the bundle for the modiifed Nesbit procedure reduces the number of diamond-shaped removals of TA and thus shortens operation time in comparison with its lateral counterpart.

作者： 刊期： 2014年第03期

Avanaifl, a potent new selective phosphodiesterase type 5 (PDE5) inhibitor, has been developed for the treatment of erectile dysfunction (ED). We carried out a systematic review and meta-analysis to assess the efifcacy and safety of this drug for the treatment of ED. A literature review was performed to identify all published randomized, double-blind, placebo-controlled trials of avanaifl for the treatment of ED. The search included the following databases:MEDLINE, EMBASE and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. Four publications, involving a total of 1381 patients, were used in the analysis, including four randomized controlled trials (RCTs) that compared avanaifl with a placebo. Among the co-primary efifcacy end points indicating that avanaifl 100 mg was more effective than a placebo were successful vaginal penetration (SEP2) (the odds ratio (OR)=5.06, 95%conifdence interval (CI)=3.29-7.78, P<0.00001) and successful intercourse (SEP3) (OR=3.99, 95%CI=2.80-5.67, P<0.00001). Men randomized to receive avanaifl were less likely than those receiving the placebo to drop out due to an adverse event (AE) (OR = 1.48, 95% CI = 0.54-4.08, P= 0.44). Speciifc AEs with avanaifl included headache and lfushing, which were signiifcantly less likely to occur with placebo. This meta-analysis indicates that avanaifl 100 or 200 mg is an effective and well-tolerated treatment for ED. Compared with avanaifl 100 mg, patients who take avanaifl 200 mg are more likely to experience headaches.

作者： 刊期： 2014年第03期

In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional therapies have been approved on the basis of showing a survival beneift in phase III studies. These agents include sipuleucel-T, cabazitaxel, abiraterone, enzalutamide and (most recently) radium-223. Amongst radiopharmaceuticals currently used for advanced prostate cancer (e.g. samarium-153 and strontium-89), radium-223 possesses several unique properties. As an alpha-emitting compound, the agent produces a high-energy output over a short range, facilitating selective destruction of tissue within the bone in the region of osteoblastic lesions while sparing surrounding normal tissue. The current review will outline biological rationale for radium-223 and also provide an overview of preclinical and clinical development of the agent. Rational sequencing of radium-223 and combinations, in the increasingly complex landscape of mCRPC will be discussed, along with factors inlfuencing clinical implementation.

作者： 刊期： 2014年第03期

作者： 刊期： 2014年第03期

Defects within apoptotic pathways have been implicated in prostate cancer (PCa) tumorigenesis, metastatic progression and treatment resistance. A hallmark of cancers is the ability to derail apoptosis by inhibiting the apoptotic signal, reducing the expression of apoptotic proteins and/or amplifying survival signals through increased production of antiapoptotic molecule. This review describes associations between heat shock proteins (HSPs) and the human androgen receptor (AR), the role of HSPs and other stress-induced proteins in PCa development and emerging strategies in targeting these protective proteins to treat PCa.

作者： 刊期： 2014年第03期

The speciifcity of prostate-speciifc antigen (PSA) for early intervention in repeat biopsy is unsatisfactory. Prostate cancer antigen 3 (PCA3) may be more accurate in outcome prediction than other methods for the early detection of prostate cancer (PCa). However, the results were inconsistent in repeated biopsies. Therefore, we performed a systematic review and meta-analysis to evaluate the role of PCA3 in outcome prediction. A systematic bibliographic search was conducted for articles published before April 2013, using PubMed, Medline, Web of Science, Embase and other databases from health technology assessment agencies. The quality of the studies was assessed on the basis of QUADAS criteria. Eleven studies of diagnostic tests with moderate to high quality were selected. A meta-analysis was carried out to synthesize the results. The results of the meta-analyses were heterogeneous among studies. We performed a subgroup analysis (with or without inclusion of high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP)). Using a PCA3 cutoff of 20 or 35, in the two sub-groups, the global sensitivity values were 0.93 or 0.80 and 0.79 or 0.75, speciifcities were 0.65 or 0.44 and 0.78 or 0.70, positive likelihood ratios were 1.86 or 1.58 and 2.49 or 1.78, negative likelihood ratios were 0.81 or 0.43 and 0.91 or 0.82 and diagnostic odd ratios (ORs) were 5.73 or 3.45 and 7.13 or 4.11, respectively. The areas under the curve (AUCs) of the summary receiver operating characteristic curve were 0.85 or 0.72 and 0.81 or 0.69, respectively. PCA3 can be used for repeat biopsy of the prostate to improve accuracy of PCa detection. Unnecessary biopsies can be avoided by using a PCa cutoff score of 20.

作者： 刊期： 2014年第03期

Several studies have reported that C-reactive protein (CRP), an inlfammation biomarker, may be associated with the prognosis of prostate cancer (PCa). The objective of this systematic review is to summarize the predictive role of CRP for survival in PCa as reported in previous studies. Related studies were identiifed, and evaluated for quality through multiple search strategies. Data was collected from studies comparing overall and cancer-speciifc survival (CSS) in patients with elevated CRP levels and those having lower levels. However, for progression-free survival (PFS), data were collected according to the log of CRP. The hazard ratio (HR) and its 95% conifdence interval (CI) were used to assess the strength of associations. A total of nine studies (n= 1,497) were evaluated in this meta-analysis (ifve for overall survival (OS), four for CSS and two for PFS). For OS and PFS, the pooled HR of CRP was statistically signiifcant at 1.51 (95%CI, 1.28-1.79) and 1.50 (95%CI, 1.25-1.81), respectively. For CSS, the pooled HR was 1.91 (95%CI, 1.36-2.69) with higher CRP expression in PCa, which strongly indicates poorer survival in PCa. This study demonstrates that CRP may have a critical prognostic value in patients with prostatic cancer.

作者： 刊期： 2014年第03期

To evaluate the effect of statins for erectile dysfunction (ED), a systematic review of the literature was conducted in the Cochrane Library, Embase and PubMed from the inception of each database to June 2013. Only randomized controlled trials (RCTs) comparing treatment for ED with statins were identiifed. Placebo RCTs with the International Index of Erectile Function (IIEF) as the outcome measure were eligible for meta-analysis. A total of seven RCTs including two statins with a total of 586 patients strictly met our criteria for systematic review and ifve of them qualiifed for the meta-analysis. A meta-analysis using a random effects model showed that statins were associated with a signiifcant increase in IIEF-5 scores (mean difference (MD):3.27;95%conifdential interval (CI):1.51 to 5.02;P<0.01) and an overall improvement of lipid proifles including total cholesterol (MD:-1.08;95%CI:-1.68 to-0.48;P<0.01), low-density lipoprotein (LDL) cholesterol (MD:-1.43;95%CI:-2.07 to-0.79;P<0.01), high-density lipoprotein (HDL) cholesterol (MD:0.24;95%CI:0.13 to 0.35;P<0.01) and triglycerides (TGs) (MD:-0.55;95%CI:-0.61 to -0.48;P< 0.01). In summary, our study revealed positive consequences of these lipid-lowering drugs on erectile function, especially for nonresponders to phosphodiesterase type 5 inhibitors (PDE5Is). However, it has been reported that statin therapy may reduce levels of testosterone and aggravate symptoms of ED. Therefore, larger, well-designed RCTs are needed to investigate the double-edged role of statins in the treatment of ED.

作者： 刊期： 2014年第03期

作者： 刊期： 2014年第03期

In our experience patients undergoing circumcision are mostly concerned about pain and penile appearances. We conducted a prospective randomized trial to assess the beneifts of a new disposable circumcision suture device (DCSD). A total of 942 patients were equally divided into three groups (conventional circumcision, Shang ring and disposable suture device group). Patients in the DCSD group were anesthetized with compound 5%lidocaine cream, the others with a 2%lidocaine penile block. Operation time, intra-operative blood loss, incision healing time, intra-operative and post-operative pain, the penile appearance and overall satisfaction degree were measured. Operation time and intra-operative blood loss were signiifcantly lower in the Shang ring and suture device groups compared to the conventional group (P<0.001). Intra-operative pain was less in the suture device group compared with the other two groups (P<0.001);whereas post-operative pain was higher in the conventional group compared to the other two groups (P<0.001). Patients in the suture device (80.57%) and Shang ring (73.57%) groups were more satisifed with penile appearances compared with the conventional circumcision group (20.06%, P<0.05). Patients in suture device group also healed markedly faster than the conventional group (P<0.01). The overall satisfaction rate was better in the suture device group (78.66%) compared with the conventional (47.13%) and Shang ring (50.00%) groups (P<0.05). The combination of DCSD and lidocaine cream resulted in shorter operation and incision healing times, reduced intra-operative and post-operative pain and improved patient satisfaction with the cosmetic appearances.

作者： 刊期： 2014年第03期

In recent years, immunotherapy has emerged as a viable and attractive strategy for the treatment of prostate cancer. While there are multiple ways to target the immune system, therapeutic cancer vaccines and immune checkpoint inhibitors have been most successful in late-stage clinical trials. The landmark Food and Drug Administration approval of sipuleucel-T for asymptomatic or minimally symptomatic metastatic prostate cancer set the stage for ongoing phase III trials with the cancer vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab. A common feature of these immune-based therapies is the appearance of improved overall survival without short-term changes in disease progression. This class effect appears to be due to modulation of tumor growth rate kinetics, in which the activated immune system exerts constant immunologic pressure that slows net tumor growth. Emerging data suggest that the ideal population for clinical trials of cancer vaccines is patients with lower tumor volume and less aggressive disease. Combination strategies that combine immunotherapy with standard therapies have been shown to augment both immune response and clinical beneift.

作者： 刊期： 2014年第03期

作者： 刊期： 2014年第03期

Recent phase I studies have reported single-agent activities of poly (ADP-ribose) polymerase (PARP) inhibitor in sporadic and in BRCA-mutant prostate cancers. Two of the most common genetic alterations in prostate cancer, ETS gene rearrangement and loss of PTEN, have been linked to increased sensitivity to PARP inhibitor in preclinical models. Emerging evidence also suggests that PARP1 plays an important role in mediating the transcriptional activities of androgen receptor (AR) and ETS gene rearrangement. In this article, the preclinical work and early-phase clinical trials in developing PARP inhibitor-based therapy as a new treatment paradigm for metastatic prostate cancer are reviewed.

作者： 刊期： 2014年第03期

Numerous studies have shown associations between the FOXO3Agene, encoding the forkhead box O3 transcription factor, and human or speciifcally male longevity. However, the associations of speciifc FOXO3A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. A comprehensive search was conducted to identify studies of FOXO3A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95%conifdence intervals (CIs) were calculated by comparing the minor and major alleles. A total of seven articles reporting associations of FOXO3A polymorphisms with longevity were identiifed and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rs13217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR=1.36, 95%CI=1.10-1.69, P=0.005;OR=1.20, 95%CI=1.04-1.37, P=0.01;OR=1.27, 95%CI=1.10-1.46, P=0.001;OR=1.14, 95%CI=1.01-1.27 and OR=1.24, 95%CI=1.07-1.43, P=0.003, respectively). Analysis stratiifed by gender indicated signiifcant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR=1.54, 95%CI=1.33-1.79, P<0.001;OR=1.38, 95%CI=1.15-1.66, P=0.001;and OR=1.39, 95%CI=1.15-1.67, P=0.001), but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. In conclusion, this meta-analysis indicates a signiifcant association of ifve FOXO3Agene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-speciifc. Further investigations are required to conifrm these ifndings.

作者： 刊期： 2014年第03期

作者： 刊期： 2014年第03期

This study sought to assess the prognostic signiifcance of the degree of extranodal extension (ENE) and several other risk factors in pathological ENE penile carcinoma. We analyzed prospectively collected data on a consecutive series of 31 chemotherapy-naive patients with proven ENE who underwent therapeutic regional lymphadenectomy. Postoperative external radiotherapy was then performed. We studied the extent of ENE utilizing a novel grading system and correlated patient grades with their outcome measures. ENE was graded as 1-if the capsule of the lymph node (LN) was ruptured less than one-third of its circumference or 2 - if the capsule was disrupted more than one-third of its circumference or the entire LN was disrupted. We estimated overall survival (OS) using the Kaplan-Meier method. Multivariate analysis was performed according to the Cox proportional hazards model using factors that were identiifed as statistically signiifcant in univariate analysis. The incidence rate of ENE was 51.8%in patients with pathological node-positive carcinoma of the penis. The median OS and 5-year survival were 18 months (95%conifdence interval (CI), 14.4-21.6) and 23%, respectively. Prognostic variables on univariate analysis were ENE grade 2,≥3 LNs with ENE, maximal LN≥35 mm,≥5 positive LNs and pelvic LN involvement. On multivariate analysis, only ENE grade 2 remained associated with decreased OS (hazard ratio (HR):6.50). In conclusion, patients with ENE have a poor outcome, and ENE grade 2 is an independent predictive factor of poor OS in patients with pathological ENE penile carcinoma.

作者： 刊期： 2014年第03期

Because of unavoidable complications of vasectomy, this study was undertaken to assess the efifcacy and safety of male sterilization with a nonobstructive intravas device (IVD) implanted into the vas lumen by a mini-surgical method compared with no-scalpel vasectomy (NSV). IVDs were categorized into two types:IVD-B has a tail used for ifxing to the vas deferens (ifxed wing) whereas IVD-A does not. A multicenter prospective randomized controlled clinical trial was conducted in China. The study was comprised of 1459 male volunteers seeking vasectomy who were randomly assigned to the IVD-A (n= 487), IVD-B (n= 485) or NSV (n=487) groups and underwent operation. Follow-up included visits at the 3rd-6th and 12th postoperative months. The assessments of the subjects involved regular physical examinations (including general and andrological examinations) and semen analysis. The subjects’ partners also underwent monitoring for pregnancy by monthly interviews regarding menstruation and if necessary, urine tests. There were no signiifcant differences in pregnancy rates (0.65% for IVD-A, 0 for IVD-B and 0.21% for NSV) among the three groups (P>0.05). The cumulative rates of complications at the 12th postoperative month were zero, 0.9%and 1.7%in the three groups, respectively. In conclusion, IVD male sterilization exhibits a low risk of long-term adverse events and was found to be effective as a male sterilization method, similar to the NSV technique. IVD male sterilization is expected to be a novel contraceptive method.

作者： 刊期： 2014年第03期

prostate cancer has been recognized as being responsive to androgen deprivation since the 1940s when Charles Huggins ifrst described the role of surgical castration in managing these patients. However, androgen deprivation only results in transient disease control for the vast majority of men, with those progressing in spite of castrate testosterone levels labeled as having castrate-resistant prostate cancer (CRPC). Until 2004, the therapeutic arena for these patients had remained stagnant, with no agent having shown a survival gain in the CRPC setting. Two landmark publications changed the prostate cancer treatment landscape by providing‘level-1 evidence’ that docetaxel-based chemotherapy led to prolongation in overall survival (OS). This was followed by the approval of cabazitaxel in 2010 on the basis of Phase III data demonstrating its efifcacy in patients pretreated with docetaxel. More recently, a number of next-generation androgen-directed agents (e.g. abiraterone and enzalutamide) have also been shown to lead to a survival beneift in men with CRPC. With so many new treatment options available, a number of questions remain. These include:how to best sequence chemotherapy with these newer hormonal agents, the clinical implication of cross-resistance between taxanes and androgen-directed agents and which subsets of patients may beneift most from early use of chemotherapy. This review will provide an overview of the evolving role of chemotherapy in the management of advanced prostate cancer in the current era.

作者： 刊期： 2014年第03期