Search

Background Indoleamine 2,3‐dioxygenase 1 (IDO1) and tryptophan (Trp) catabolism have been demonstrated to play an important role in tumor immunosuppression. This study examined the expression and catalytic activity of IDO1 in penile squamous cell carcinoma (PSCC) and explored their clinical significance. Methods IDO1 expression level, serum concentrations of Trp and kynurenine (Kyn) were examined in 114 PSCC patients by immunohistonchemistry and solid‐phase extraction‐liquid chromatography‐tandem mass spectrometry. The survival was analyzed using Kaplan‐Meier method and the log‐rank test. Hazard ratio of death was analyzed via univariate and multivariate Cox regression. Immune cell types were defined by principal component analysis. The correlativity was assessed by Pearson's correlation analysis. Results The expression level of IDO1 in PSCC cells was positively correlated with serum Kyn concentration and Kyn/Trp radio (KTR; both P

Simple Summary Penile squamous cell carcinoma (PSCC) has been regarded as an HPV-related cancer for a long time. However, the integration pattern and carcinogenic pathways of HPV in PSCC remain unclear. The results of this study provide insights into the HPV-related carcinogenic mechanism in PSCC, which may be less prone to involvement in the traditional E6/E7 carcinogenic process, and are characterized by effects on the host genome, which result in the inactivation of tumor suppressors (CADM2, etc.) and the activation of oncogenes (KLF5, etc.), thus activating oncogenic signaling pathways (MAPK, JAK/STAT, etc.). This study could enhance our understanding of HPV integration and pave the way for subsequent HPV studies in PSCC. Abstract Human papillomavirus (HPV) is a significant etiologic driver of penile squamous cell carcinoma (PSCC). The integration pattern of HPV and its carcinogenic mechanism in PSCC remain largely unclear. We retrospectively reviewed 108 PSCC cases who received surgery between 2008 and 2017. Using high-throughput viral integration detection, we identified 35 HPV-integrated PSCCs. Unlike cervical cancer, the HPV E2 oncogene was not prone to involvement in integration. Eleven of the 35 (31.4%) HPV-integrated PSCCs harbored intact HPV E2; these tumors had lower HPV E6 and E7 expression and higher expression of p53 and pRb proteins than those with disrupted E2 did (p < 0.001 and p = 0.024). Integration breakpoints are preferentially distributed in or near host genes, including previously reported hotspots (KLF5, etc.) and newly identified hotspots (CADM2, etc.), which are mainly involved in oncogenic signaling pathways (MAPK, JAK/STAT, etc.). Regarding the phosphorylation levels of JNK, p38 was higher in HPV-positive tumors with MAPK-associated integration than those in HPV-positive tumors with other integration and those in HPV-negative tumors. In vitro, KLF5 knockdown inhibited proliferation and invasion of PSCC cells, while silencing CADM2 promoted migration and invasion. In conclusion, this study enhances our understanding of HPV-induced carcinogenesis in PSCC, which may not only rely on the E6/E7 oncogenes, but mat also affect the expression of critical genes and thus activate oncogenic pathways.

Purpose To investigate the puncture accuracy and feasibility of contrast-enhanced ultrasound (CEUS) guided percutaneous nephrolithotomy (PCNL) in flank position for patients with no apparent hydronephrosis. Methods Between May 2018 and June 2020, 72 kidney stone patients with no or mild hydronephrosis were randomized into two groups: a CEUS-guided PCNL group and a conventional ultrasound (US)-guided group. Patients’ demographics and perioperative outcomes were compared, including the success rate of puncture via calyceal fornix, the success rate of a single-needle puncture, puncture time, operative time, postoperative hemoglobin loss, stone-free rate, incidence of complications and postoperative stay. Results The success rate of puncture via calyceal fornix for CEUS-guided group was significantly higher than that for conventional US-guided group (86.1 vs. 47.2%, p = 0.002). Patients performed with CEUS-guided PCNL required shorter renal puncture time than those guided with conventional US (36.5 s vs. 61.0 s, p p Conclusion CEUS guidance facilitates identification of the renal calyx fornix, and benefits more precise renal puncture and less hemoglobin loss in PCNL. CEUS-guided PCNL in flank position is a feasible approach to the treatment of kidney stone patients with no apparent hydronephrosis. Trial registration number: ChiCTR1800015417.

Purpose There are limited therapeutic options for patients with advanced penile squamous cell carcinoma (PSCC) after chemotherapy failure. Thus, we evaluated the feasibility of salvage treatment using the epidermal growth factor receptor (EGFR) mono-antibody nimotuzumab in chemotherapy-failed PSCC patients and explored potential response or resistance biomarkers. Materials and methods Six chemotherapy-failed PSCC patients with locally advanced disease or distant metastasis were enrolled consecutively to nimotuzumab treatment. Clinical responses and side effects were evaluated, and genetic characteristics of cancer specimens were analyzed through the next-generation sequencing of hotspot regions in cancer-related genes. Results Two of 6 patients showed partial responses, one was identified as having stable disease, while the other 3 had disease progression after nimotuzumab therapy. Side effects were all welltolerated. Genetic analysis revealed that TP53, CDKN2A, RB1, SMAD4, FLT3, and PIK3CA were the most frequently mutated genes in PSCC specimens, while altered KRAS, HRAS, EGFR, ERBB2, and FLT3 may be correlated with nimotuzumab resistance. Furthermore, 3 patients that were human papillomavirus-positive each showed clinical response or stable disease. Conclusions EGFR mono-antibody may be a potential modality for locally advanced PSCC patients after chemotherapy failure. Further large-scale clinical studies are needed to elucidate the role of human papillomavirus status and critical gene mutations in the clinical response to EGFR-targeted therapy.

Backgroud：At present, there is still no consensus on the early inguinal lymph node dissection (eILND) of T1G2 or T1aG2. In this study, we investigated the peculiarities of penile cancer T1G2 and T1aG2 to assess the necessity of eILND for this subgroup.Methods: A total of 144 patients had been treated for penile squamous cell carcinoma with primary tumor excision and early bilateral inguinal lymphadenectomy in my institution from January 2002 to March 2017, thus, 53 patients definitely diagnosed as T1G1 or T1G2 were included in this study. According to the recent guideline, T1aG1 and T1aG2 were even researched. The chi-square test and the Fisher exact test were used to compare categorical variables. Survival were retrospectively analyzed by the Kaplan-Meier method and assessed by log-rank tests. RESULTS: Among 53 patients, the proportion of positive lymph node of T1G2 was 68.8%, which was significantly higher than T1G1 (18.9%, P=0.001). Then we analyzed the patients of clinically node-negative patients (cN0), micro metastatic disease occurred in T1G2 was 50% but in T1G1 was 14.8%, which also reached statistical significance (p=0.043). According to the recent guideline, T1aG1 and T1aG2 had been further analyzed. As the risk for lymphatic spread, T1aG2 was 44.4% while only 4.5% of T1aG1 was found Inguinal lymph node metastasis, significant differences of which were also reached (P=0.017). In an addition, Survival Curve had been demonstrated but no statistical differences found between T1G1 and T1G2, as the same result also existed in the cohort of T1aG1 and T1aG2, all of which revealed a strong proof of therapeutic benefits of eILND.CONCLUSIONS: The option of a surveillance strategy is not applicable to patients of T1G2 or T1aG2, eILND should be highly recommended for this subgroup to achieve the most therapeutic benefits.

To evaluate the modifications and feasibility of radical videoscopic inguinal lymphadenectomy (VIL).From January 2010 to December 2017, more than 200 patients who have underwent bilateral radical inguinal lymphadenectomy for penile cancer in Sun Yat-Sen University Cancer Center. And there were 33 patients who received radical VIL and 174 patients who received open inguinal lymphadenectomy (OIL). According to similar factors of age, body mass index, T stage, and N stage, two matched groups were created with a rate of 1:2, one group received VIL, and another group received OIL. The numbers of harvested lymph nodes, operating times, and complications were compared between the two groups. Descriptive statistical analyses, t tests, chi-square tests, and rank sum tests were performed.In total, 93 patients were selected, including 31 patients who underwent bilateral VIL and 62 who underwent OIL. The numbers of harvested lymph nodes did not differ significantly (p = 0.983), the operating time was longer for the VIL than the open lymphadenectomy (p 0.01), and the morbidity was lower among the VIL than the open lymphadenectomy.Modified radical VIL is feasible, practical, and results in reduced morbidity. The dissecting field and the defined plane were critical to these modifications.

// Zai-Shang Li 1, 2, 3, * , Chuang-Zhong Deng 1, 2, 3, * , Yun-Lin Ye 1, 2, 3, * , Kai Yao 1, 2, 3 , Sheng-Jie Guo 1, 2, 3 , Jie-Ping Chen 1, 2, 3 , Yong-Hong Li 1, 2, 3 , Zi-Ke Qin 1, 2, 3 , Zhuo-Wei Liu 1, 2, 3 , Bin Wang 4 , Qi Zhao 1, 2, 5 , Peng Chen 6 , Qi-Wu Mi 7 , Xiao-Feng Chen 8 , Hui Han 1, 2, 3 and Fang-Jian Zhou 1, 2, 3 1 Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China 2 State Key Laboratory of Oncology in Southern China, Guangzhou, P. R. China 3 Collaborative Innovation Center of Cancer Medicine, Guangzhou, P. R. China 4 Department of Urology, Cancer Center of Guangzhou Medical University, Guangzhou, P. R. China 5 School of Life Science, Sun Yat-sen University, Guangzhou, P. R. China 6 Department of Urology, Affiliated Tumor Hospital of Xinjiang Medical University, Urumchi, P. R. China 7 Department of Urology, Dong Guan People’s Hospital, Guang Dong, P. R. China 8 Department of Urology, The First People's Hospital of Chenzhou, Chenzhou, P. R. China * First authors, they contributed equally to this research Correspondence to: Hui Han, email: hanhui@sysucc.org.cn Fang-Jian Zhou, email: zhoufj@sysucc.org.cn Keywords: casein kinase 2α, penile neoplasm, squamous cell carcinoma Received: September 13, 2016 Accepted: February 21, 2017 Published: May 16, 2017 ABSTRACT Purpose: In this study, we assess the CK2α expression in human penile squamous cell carcinoma (SCC) and its clinical significance. Methods: A total of 157 human penile SCC tissue samples were immunohistochemically analyzed. In addition, 12 human penile SCC and adjacent normal tissues were examined for CK2α protein and mRNA expression by Western blotting and real-time quantitative PCR, respectively. Survival was analyzed using the Kaplan-Meier test and the log-rank test. Multivariate Cox proportional hazard regression analysis was performed to determine the impacts of CK2α expression and the clinicopathological features on patient disease-specific survival (DSS). Likelihood ratios (LRs), Akaike information criterion (AIC) values, and concordance indexes (C-indexes) were investigated to evaluate the accuracies of the factors. Bootstrap-corrected C-indexes were used for internal validation (with sampling 1000 times). Results: A significant difference in the distribution of CK2α was observed between the normal and penile carcinoma tissues ( P

Because there is a lack of evidence, it is not generally recommended to use adjuvant radiotherapy plus chemotherapy to treat lymph node disease in penile cancer. The aim of this study was to determine the benefit of using adjuvant radiotherapy after inguinal surgery for penile cancer.Multi-institutional data were obtained from a total of nine centers from April 2003 to April 2015 and retrospectively analyzed. pN3 patients with an extracapsular nodal extension who received adjuvant therapy after inguinal surgery were included. Cancer-specific survival (CSS) was estimated using the Kaplan-Meier method. The multivariate analysis was performed using a Cox proportional hazards model.A total of 93 pN3 patients met the inclusion criteria. During the study period, 32 (34.4%) and 61 (65.6%) of these patients received adjuvant radiotherapy plus chemotherapy (AR + AC) or adjuvant chemotherapy alone (AC). The median CSS in all patients was 12.0 months (interquartile range [IQR] 7.5-16.5). The Kaplan-Meier estimated 3-year CSS rate was significantly longer in the AR + AC group (28.5%) than the AC group (16.2%) (p = 0.036). AC + AR was associated with an improvement in CSS by 7.7 months (17.7 [IQR 3.8-31.6] vs. 10.0 [IQR 6.6-13.4] months). In the Cox regression analysis, AR + AC was an independent predictor of CSS [model a: HR 0.486 (95% CI 0.258-0.916), model b: HR 0.527 (95% CI 0.286-0.972)].In conclusions, AR + AC was associated with improved CCS in patients with penile cancer who displayed an extracapsular nodal extension after inguinal surgery. This hypothesis requires further confirmation.

Current guidelines recommend pelvic lymphadenectomy (PLND) for patients with pelvic lymph node metastasis and special state. However, these data and recommendations do not distinguish the role of PLND in different patient groups and confirm the final benefits. The aim of this study was to confirm the efficacy of pelvic lymphadenectomy (PLND) for the different groups of patients. Data obtained from 7 centers were retrospectively analyzed. Of the patients, 190 pN2-3 penile carcinoma patients confirmed by bilateral inguinal lymph node excision were included in this study. Sixty-nine and 121 of these patients did and did not undergo bilateral PLND, respectively. The baseline differences from the patients were matched by propensity score analysis. In this study, the Kaplan–Meier estimated disease-specific survival (DSS) was not significantly different between the PLND and no-PLND groups (P = 0.796). According to the propensity score matching for T stage, N stage, grade, adjuvant therapies, and lymph node stage (number of inguinal lymph node metastasis and extranodal extension), 48 patients were selected for each group. Among the pN2 patients, the PLND group showed higher DSS rates than the no-surgery group (P = 0.030). However, even after matching, survival did not differ between the PLND and no-PLND patients among all patients (P = 0.609) and pN3 patients (P = 0.417) with comparable DSS. Bilateral PLND may improve survival in pN2 patients. Men with pN3 may not benefit from bilateral PLND.

Object: In this study, we evaluated the role of lymph node density (LND) and validated whether LND increases the accuracy of survival prediction when combined with the American Joint Committee on Cancer (AJCC) pathological node (N) staging system for penile cancer (7th edition). Methods: A total of 270 Chinese penile cancer patients treated between March 1999 and October 2014 were retrospectively analyzed. LND was analyzed as a trichotomous variable for the prediction of DSS in this cohort. We developed a new prediction model, which we refer to as the ND staging system, that is based on LND and pathological N staging. The predictive accuracy of this model was further assessed using the concordance index. Results: LND was correlated with the laterality of lymph node metastasis, extranodal extension, pelvic lymph node metastases, and pathologic tumor (T) and N stages (P

Background The 8th American Joint Committee on Cancer tumor–node–metastasis (AJCC-TNM) staging system is based on a few retrospective single-center studies. We aimed to test the prognostic validity of the staging system and to determine whether a modified clinicopathological tumor staging system that includes lymphovascular embolization could increase the accuracy of prognostic prediction for patients with stage T2–3 penile cancer. Methods A training cohort of 411 patients who were treated at 2 centers in China and Brazil between 2000 and 2015 were staged according to the 8th AJCC-TNM staging system. The internal validation was analyzed by bootstrap-corrected C-indexes (resampled 1000 times). Data from 436 patients who were treated at 15 centers over four continents were used for external validation. Results A survivorship overlap was observed between T2 and T3 patients (P = 0.587) classified according to the 8th AJCC-TNM staging system. Lymphovascular embolization was a significant prognostic factor for metastasis and survival (all P

Cell line models are essential tools to study the molecular mechanisms underlying tumor initiation and progression. There are limited treatment options for penile squamous cell carcinoma (PSCC), accounting for 1–2% of male tumors in developing countries, and limited progress in preclinical research in PSCC due to lacking available models with identified genomic characteristics. Here, biological and molecular characteristics and whole-genomic alterations were analyzed in a panel of PSCC cell lines newly established in our laboratory. These cell lines were all human papillomavirus (HPV)-negative, epithelial-like, immortalized, and tumorigenic in nude mice, whereas they displayed different proliferation, migration and invasion capacities in vitro, and tumorigenic ability in nude mice. They were all cisplatin sensitive, anti-EGFR therapy resistant, and androgen irresponsive. Whole-genomic sequecing analysis revealed that transition mutations (C:G>T:A and T:A>C:G) were the most common substitution types in these cell lines, whereas ERCC5, TP53, PTH1, CLTCL1, NOTCH2, MAP2K3, CDK11A/B, USP6, ADCH5, BCLAF1, CDKN2A, FANCD2, HRAS, and NOTCH1 were the most frequently altered genes. Amplifications of MYC, PLAG1, NCOA2, RUNX1T1, COX6C, and EGFR and losses of FBXW7, TET2, XPC, and FANCE were frequently observed in cell lines. The exomic variations between cell lines and their corresponding cancer tissues were highly consistent. Genetic variations were mainly involved in the MAPK, Jak-STAT, TGF-beta, Notch, and apoptosis signaling pathways. Conclusively, these panel of PSCC cell lines established in our laboratory harbor some common or specific biological characteristics and genomic variations, and they may serve as optimal models to investigate the molecular mechanisms underlying the progression, metastasis, relapses, and treatment resistance of PSCC and to develop effective treatment strategy.

OBJECTIVE To evaluate the relevance of C-reactive protein (CRP) and squamous cell carcinoma antigen (SCC-Ag) levels in relation to clinicopathological factors and prognosis in penile cancer. PATIENTS AND METHODS A total of 124 Chinese patients with penile squamous cell carcinoma (SCC), treated between November 2007 and October 2014, were analysed retrospectively. Receiver-operating characteristic curves were used to identify the combination of markers with the best sensitivity and specificity for prognosis prediction. Statistical data analysis was performed using a non-parametric method, and survival analysis was performed using the log-rank test and Cox proportional hazard model. RESULTS Levels of CRP ≥4.5 mg/L and SCC-Ag ≥1.4 ng/mL were both significantly associated with lymph node metastasis (LNM) laterality (chi-squared trend test, P = 0.041), extranodal extension (chi-squared trend test, P < 0.001), pelvic LNM (chi-squared trend test, P = 0.024), pathological tumour status (chi-squared trend test, P = 0.002), pathological nodal status (chi-squared trend test, P < 0.001), and disease-specific survival (DSS; log-rank test, P < 0.001). Moreover, the influence of CRP and SCC-Ag levels on DSS (P = 0.033, hazard ratio 3.390, 95% confidence interval 1.104-10.411) remained after adjusting for smoking history, phimosis, tumour status, tumour cell differentiation and nodal status. CONCLUSIONS The present study shows that the combined measurement of preoperative CRP and SCC-Ag levels may serve as an independent biomarker for LNM, advanced tumour stage and DSS in patients with penile SCC.

Objective To investigate the value of removed lymph node (LN) count and LN density (LND) for predicting disease-specific survival (DSS) rate following radical lymphadenectomy in patients with penile cancer. Methods We retrieved data from 146 patients who were surgically treated between 2002 and 2012. receiver-operating characteristic curve analysis was used to calculate the optimal cutoff value of LN count and LND for predicting DSS rate. LND was analyzed as a categorical variable by grouping patients with pN+tumors into 2 categories. Multivariate Cox regression analysis was used to test the effect of various variables on DSS rate based on collinearity in various models. Results Median follow-up was 42 months. Overall, 75 patients (51.4%) had pN0 disease, and 71 patients (48.6%) had pN+disease. The optimal cutoff value of LN count and LND were 16% and 16%, respectively. Among patients with pN0 tumors, the number of LNs removed (≥16 LNs) was an independent significant predictor of DSS rate in univariate and multivariate analyses (all P P Conclusions The removal of at least 16 LNs was associated with a significantly longer DSS rate in patients with pN0 penile cancer. Additionally, an LND above 16% is an independent predictor of DSS rate in patients with pN+tumors. Further independent validation is required to determine the clinical usefulness of LN count and LND in this patient population.

Objective To investigate local groin recurrence and morbidity associated with fascia lata preservation during inguinal lymphadenectomy (LAD) for penile carcinoma. Methods Between January 2002 and December 2011, 201 inguinal dissections with preservation of the fascia lata were performed in 104 patients with clinical disease staged at ≤N2. The dissection boundaries were the same as those for radical inguinal LAD. All superficial inguinal nodes were removed en bloc. The cribriform fascia near the femoral canal was divided, and the deep inguinal lymph nodes were dissected. The fascia lata was completely preserved and sutured to the subcutaneous tissue. Sartorius muscle transposition was eliminated. Survival and morbidity data were retrospectively analyzed, and survival probabilities were calculated. Results The median operative time for unilateral inguinal LAD was 45 minutes (range, 40-60 minutes). Median follow-up was 36 months (range, 10-130 months). A mean number of 12.5 nodes were removed per groin. One patient (1%) had a recurrence outside the borders of the fascia lata after 7 months of follow-up. The 3-year disease-free survival rate was 92.1% (100% for pN0, 91.3% for pN1, 80% for pN2, and 33.3% for pN3 disease). A total of 59 complications (29.3%) occurred, including wound infection (2.5%), skin necrosis (5.5%), lymphedema (11.8%), seroma formation (1.5%), lymphocele (5%), paresthesia (3.5%), and deep venous thrombosis (0.5%). Conclusion Inguinal dissections with preservation of the fascia lata for penile carcinoma patients without extranodal extension is as effective as the classic dissection technique but decreases complications related to groin dissection.

// Zai-Shang Li 1,2,3,* , Peng Chen 4,* , Kai Yao 1,2,3,* , Bin Wang 5,* , Jing Li 5 , Qi-Wu Mi 6 , Xiao-Feng Chen 7 , Qi Zhao 8 , Yong-Hong Li 1,2,3 , Jie-Ping Chen 1,2,3 , Chuang-Zhong Deng 1,2,3 , Yun-Lin Ye 1,2,3 , Ming-Zhu Zhong 9 , Zhuo-Wei Liu 1,2,3 , Zi-Ke Qin 1,2,3 , Xiang-Tian Lin 10 , Wei-Cong Liang 10 , Hui Han 1,2,3 and Fang-Jian Zhou 1,2,3 1 Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China 2 State Key Laboratory of Oncology in Southern China, Guangzhou, P. R. China 3 Collaborative Innovation Center of Cancer Medicine, Guangzhou, P. R. China 4 Department of Urology, Affiliated Tumor Hospital of Xinjiang Medical University, Urumchi, P. R. China 5 Department of Urology, Cancer Center of Guangzhou Medical University, Guangzhou, P. R. China 6 Department of Urology, Dong Guan People’s Hospital, Guang Dong, P. R. China 7 Department of Urology,The First People’s Hospital of Chenzhou, Chenzhou, P. R. China 8 School of Life Science, Sun Yat-sen University, School of Life Science, Guang Dong, P. R. China 9 Department of Urology, The People’s Hospital of Jiangmen, Jiangmen, P. R. China 10 Zhongshan School of Medicine, Sun Yat-sen University, Guang Dong, P. R. China * These authors have contributed equally to this work Correspondence to: Hui Han, email: // Fang-Jian Zhou, email: // Keywords : penile neoplasms, neoplasm staging, prognosis, body mass index, C-reactive protein Received : October 25, 2015 Accepted : January 24, 2016 Published : March 11, 2016 Abstract Purpose: To determine the predictive value and feasibility of the new outcome prediction model for Chinese patients with penile squamous cell carcinoma. Results: The 3-year disease-specific survival (DSS) was 92.3% in patients with < 8.70 mg/L CRP and 54.9% in those with elevated CRP ( P < 0.001). The 3-year DSS was 86.5% in patients with a BMI < 22.6 Kg/m2 and 69.9% in those with a higher BMI ( P = 0.025). In a multivariate analysis, pathological T stage ( P < 0.001), pathological N stage ( P = 0.002), BMI ( P = 0.002), and CRP ( P = 0.004) were independent predictors of DSS. A new scoring model was developed, consisting of BMI, CRP, and tumor T and N classification. In our study, we found that the addition of the above-mentioned parameters significantly increased the predictive accuracy of the system of the American Joint Committee on Cancer (AJCC) anatomic stage group. The accuracy of the new prediction category was verified. Methods: A total of 172 Chinese patients with penile squamous cell cancer were analyzed retrospectively between November 2005 and November 2014. Statistical data analysis was conducted using the nonparametric method. Survival analysis was performed with the log-rank test and the Cox proportional hazard model. Based on regression estimates of significant parameters in multivariate analysis, a new BMI-, CRP- and pathologic factors-based scoring model was developed to predict disease-specific outcomes. The predictive accuracy of the model was evaluated using the internal and external validation. Conclusion: The present study demonstrated that the TNCB score group system maybe a precise and easy to use tool for predicting outcomes in Chinese penile squamous cell carcinoma patients.

To explore the roles of different casein kinase 2 (CK2) catalytic subunits in androgen receptor (AR) signaling in prostate cancer cell lines.Prostate cancer cell lines were maintained.Immunofluorescent staining was performed to determine AR nuclear translocation in PC-3/AR cells with R1881 pretreatment and luciferase gene reporter assay used to determine AR transactivation in LNCaP cells. And reverse transcription-polymerase chain reaction (RT-PCR) was employed to evaluate the mRNA level of prostate-specific antigen (PSA).R1881-induced AR nuclear localization was reduced significantly (P0.01).R1881-stimulated ARE-LUC reporter activity in LNCaP cells decreased with reduced level of PSA mRNA, an AR endogenous target (P0.05). To confirm the target specificity, the gene-specific siRNAs were used for both CK2α and CK2α' subunits. The results of ARE-LUC assay (38.5 vs 31.4) suggested that both CK2 catalytic subunits were involved in androgen-stimulated AR nuclear translocation and AR-mediated gene expression in prostate cancer cells.Both CK2 catalytic subunits are involved in androgen receptor signaling of prostate cancer cells.

To investigate the value of removed lymph node (LN) count and LN density (LND) for predicting disease-specific survival (DSS) rate following radical lymphadenectomy in patients with penile cancer.We retrieved data from 146 patients who were surgically treated between 2002 and 2012. receiver-operating characteristic curve analysis was used to calculate the optimal cutoff value of LN count and LND for predicting DSS rate. LND was analyzed as a categorical variable by grouping patients with pN+tumors into 2 categories. Multivariate Cox regression analysis was used to test the effect of various variables on DSS rate based on collinearity in various models.Median follow-up was 42 months. Overall, 75 patients (51.4%) had pN0 disease, and 71 patients (48.6%) had pN+disease. The optimal cutoff value of LN count and LND were 16% and 16%, respectively. Among patients with pN0 tumors, the number of LNs removed (≥16 LNs) was an independent significant predictor of DSS rate in univariate and multivariate analyses (all P0.05). Stratifying pN+ patients as above versus below the LND threshold demonstrated significant differences in 5-year DSS: 81.2% versus 24.4% (P0.001). In multivariate models including known prognostic factors, LND was a statistically significant independent predictor of DSS rate (hazard ratio = 4.31 and 3.96 for above vs. below the LND threshold, respectively).The removal of at least 16 LNs was associated with a significantly longer DSS rate in patients with pN0 penile cancer. Additionally, an LND above 16% is an independent predictor of DSS rate in patients with pN+tumors. Further independent validation is required to determine the clinical usefulness of LN count and LND in this patient population.

To introduce the technique of anatomical retroperitoneoscopic retroperitoneal lymph node dissection (ARRPLND) was performed in 12 consecutive patients with a clinical stage I nonseminomatous germ-cell tumor (NSGCT) between February 2008 and October 2010. All procedures were performed using a modified template nerve-sparing approach. The retroperitoneal space was adequately expanded using double gasbags. After the retroperitoneal fat was cleared, two relatively bloodless planes were entered consecutively to expose the lymph node and permit dissection. Dissection proceeded first in the plane between the anterior renal fascia and posterior peritoneum, and secondly in the avascular plane between the posterior renal fascia and transversalis fascia. The proximal spermatic vein was clipped at the initial stage. En bloc resection of the lymph tissue and fat between the anterior renal fascia and posterior renal fascia were performed. Three patients (25%) had pathologic stage IIA disease and received adjuvant chemotherapy. No recurrence was observed during follow-up ranging from 26 to 58 months. The median operative time was 205 min (range: 165-430 min) and median estimated blood loss was 320 ml (range: 100-1200 ml). There were two intraoperative complications (Clavien grade II) and one open conversion due to perforation of the peritoneum. Postoperative complications (Clavien I) developed in three patients. Normal antegrade ejaculation recovered by 1 month following the operation. Our preliminary results indicate that ARRPLND is technically feasible and associated with satisfactory clinical outcomes for clinical stage I NSGCT. Further studies are necessary to evaluate this technique.