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The objective of this study is to describe the technique and evaluate the clinical value of normal saline (NS) injection for expanding the anterior perirectal space during prostate cryoablation for prostate cancer (PCa) patients.PCa patients who received cryoablation between August 2014 and December 2019 were enrolled, and the technique of NS injection was adopted. The complications were evaluated. The prostate-specific antigen (PSA) nadir and biochemical progression-free survival (bPFS) were measured in localized PCa patients who received cryoablation as the primary treatment.A total of 159 PCa patients were included. Among 147 patients with the data of anterior perirectal space, the median (interquartile range [IQR]) distance of estimated iceball edge beyond the prostatic capsule was 8.3 (7.0-10.0) mm. No cases of urethrorectal fistula were reported; 29 patients developed urinary retention and 25 patients presented scrotal edema. All complications below Clavien-Dindo grade IIIb disappeared within 7 weeks after surgery. Urinary incontinence was reported in 6 patients. Among localized PCa patients, the median (IQR) follow-up time was 56.5 (36.0-73.5) months. The estimated 5-year bPFS was 82.3% overall, 82.8% for low-to intermediate-risk PCa patients, and 82.1% for high-risk PCa patients. For 52 patients received cryoablation alone, the median (IQR) PSA nadir was 0.147 (0.027-0.381) ng/mL.The technique of NS injection for expanding the anterior perirectal space during cryoablation surgery could avoid urethrorectal fistula and might benefit localized PCa patients with lower PSA nadir and longer bPFS.

Suppression of PTPN3 increased the cell colony numbers. Representative micrographs and quantification of crystal violet stained cells from 3 independent experiments. Columns, average of three independent experiments; bars, SD. *P < 0.05, **P < 0.01, Student t test.

Shortening of the 3′ untranslated regions (3′UTR) of mRNA is an important mechanism for oncogene activation. However, 3′UTR alteration events, their pathologic functions, and underlying mechanisms in human urothelial carcinoma of the bladder (UCB) are not clear. Here, we combine RNA sequencing, bioinformatics, and clinical studies in two independent cohorts of patients with UCB to identify a novel RAC1 shorter 3′UTR isoform that is frequently expressed in UCB and is critical in the tumorigenesis and acquisition of a poor prognostic phenotype in patients. Short 3′UTR isoform of RAC1 substantially upregulated RAC1 expression by escaping from miRNA-targeted repression and played an essential oncogenic role in UCB pathogenesis. An important cleavage/polyadenylation factor, cleavage stimulation factor 2 (CSTF2), induced 3′UTR shortening of RAC1 in UCB by mediating slow transcriptional elongation at RAC1. Cotranscriptional recruitment of CSTF2 on the GUAAU motif at proximal polyadenylation site of RAC1 attenuated the recruitment of two transcription factors AFF1 and AFF4, causing the defects in elongation. CSTF2 regulated the tumorigenic functions of the shorter RAC1 isoform in UCB cells, enhancing cell proliferation, migration, and invasion. The combination of high expression of CSTF2 and high usage of RAC1 short-3′UTR isoform may be used as a powerful biomarker to predict poor prognosis in UCB. Our findings also suggest a CSTF2-regulated RAC1-3′UTR shortening program as an exploitable therapeutic strategy for patients with UCB.Significance: These findings demonstrate that the short isoform of RAC1 is critical in UCB tumorigenesis and may have implications for developing new therapeutic strategies to treat this disease. Cancer Res; 78(20); 5848–62. ©2018 AACR.

Supplementary Figure S1. CircPRMT5 is upregulated in UCB cells. Supplementary Figure S2. CircPRMT5 promotes migration and invasion of UCB cells. Supplementary Figure S3. CircPRMT5 contains multiple target sites of miRNAs. Supplementary Figure S4. CircPRMT5 promotes migration and invasion of UCB cells by reducing the inhibitory effect of miR-30c via sponge activity. Supplementary Figure S5. SNAIL1 is a target of miR-30c. Supplementary Figure S6. Representative images of SNAIL1 and E-cadherin expressions examined by IHC in UCB tissues with high (left) and low (right) expression of circPRMT5. Supplementary Figure S7. The correlation between expressions of SNAIL1 and miR-200 family in UCB tissues derived from TCGA database. Supplementary Figure S8. CircPRMT5 was secreted into exosomes derived from serum and urine of UCB patients. Supplementary Table S1. Correlation between expression of circPRMT5 and patients' clinicopathological variables in UCB patients Supplementary Table S2. The up-regulated and down-regulated circRNAs in UBCs Supplementary Table S3. Correlation of miR-30c expression with patients' clinicopathological variables in TCGA UCB cohorts Supplementary Table S4. Correlation of circPRMT5 expression in serum exosomes with patients' clinicopathological variables in 71 cases of UCB

Supplementary Figure S1. Identification of 3'UTR shortening of RALA and RAC1 from UCB, colorectal carcinoma, hepatocellular carcinoma and non-small cell lung cancer samples. Supplementary Figure S2. RAC1 with short 3'UTR promotes tumorigenesis and produces more protein due to evasion of miRNA-mediated repression. Supplementary Figure S3. Screening of APA factors that contribute to the PAS selection of RAC1 in UCB. Supplementary Figure S4. CSTF2 regulates colony formation and invasiveness abilities of shorter RAC1 isoform in UCB. Supplementary Table S1. PDUI value calculated from DaPars analysis of 15 pairs of UCB and adjacent normal bladder tissues. Supplementary Table S2. KEGG pathway analyses of APA genes identified from RNA-Seq. Supplementary Table S3. RAC1 genomic mutations identified from TCGA UCB database. Supplementary Table S4. Correlation between the expression of CSTF2 and clinicopathologic characteristics of UCB patients

Purpose: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in cancer cells epithelial–mesenchymal transition (EMT) remains unclear. In this study, we aimed to identify novel circRNAs that regulate urothelial carcinoma of the bladder (UCB) cells’ EMT and explored their regulatory mechanisms and clinical significance in UCBs.Experimental Design: We first screened circRNA expression profiles using a circRNA microarray in paired UCB and normal tissues, and then studied the clinical significance of an upregulated circRNA, circPRMT5, in a large cohort of patients with UCB. We further investigated the functions and underlying mechanisms of circPRMT5 in UCB cells’ EMT. Moreover, we evaluated the regulation effect of circPRMT5 on miR-30c, and its target genes, SNAIL1 and E-cadherin, in two independent cohorts from our institute and The Cancer Genome Atlas (TCGA).Results: We demonstrated that upregulated expression of circPRMT5 was positively associated with advanced clinical stage and worse survival in patients with UCB. We further revealed that circPRMT5 promoted UCB cell's EMT via sponging miR-30c. Clinical analysis from two independent UCB cohorts showed that the circPRMT5/miR-30c/SNAIL1/E-cadherin pathway was essential in supporting UCB progression. Importantly, we identified that circPRMT5 was upregulated in serum and urine exosomes from patients with UCB, and significantly correlated with tumor metastasis.Conclusions: CircPRMT5 exerts critical roles in promoting UCB cells’ EMT and/or aggressiveness and is a prognostic biomarker of the disease, suggesting that circPRMT5 may serve as an exploitable therapeutic target for patients with UCB.

Skip lymph node metastasis (SLNM) refers to lateral lymph node metastasis (LLNM) without involving central lymph node (CLN). Some microscopic nodal positivity may be difficult to detect before surgery due to atypical imaging characteristics. These patients are misdiagnosed as having clinically node-negative (cN0) papillary thyroid cancer (PTC) even after central lymph node dissection, leading to a high risk of developing LNM after surgery. Current prediction models have limited clinical utility, as they are only applicable to predict SLNM from clinically node-positive (cN+) PTC, not cN0 PTC, and this has little impact on treatment strategies.This study aimed to establish a nomogram for preoperatively assessing the likelihood of SLNM in cN0 PTC patients with increased risk of LNM, thus optimizing their therapeutic options.The records of 780 PTC patients undergoing thyroidectomy along with bilateral central lymph node dissection were retrospectively reviewed. The cN0 patients with postoperative LLNM (occult SLNM) and cN+ patients without central lymph node metastasis (CLNM) (typical SLNM) were included in the SLNM group (n = 82). The CLNM-negative cN0 patients without postoperative LLNM were assigned to the non-SLNM group (n = 698). The independent correlates of SLNM constituted the nomogram for determining the likelihood of SLNM in high-risk cN0 PTC patients.The independent correlates of SLNM were age (hazard ratio (HR) = 1.016), tumor location (HR = 1.801), tumor size (HR = 1.528), and capsular invasion (HR = 2.941). They served as components in the development of the nomogram. This model was verified to present acceptable discrimination. It showed good calibration and a decent net benefit when the predicted probability was60%.We developed a nomogram incorporating preoperative clinical data to predict the probability of SLNM development in high-risk cN0 PTC patients, which contributed to their optimized treatment options.

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

Recurrent renal cell carcinoma(reRCC) is associated with poor prognosis and the underlying mechanism is not yet clear. A comprehensive understanding of tumor microenvironment (TME) of reRCC may aid in designing effective anticancer therapies, including immunotherapies. Single-cell transcriptomics holds great promise for investigating the TME, however, this technique has not been used in reRCC. Here, we aimed to explore the difference in the TME and gene expression pattern between primary RCC (pRCC) and reRCC at single-cell level.We performed single-cell RNA sequencing analyses of 32,073 cells from 2 pRCC, 2 reRCC, and 3 adjacent normal kidney samples. 41 pairs of pRCC and reRCC samples were collected as a validation cohort to assess differences observed in single-cell sequencing. The prognostic significance of related cells and markers were studied in 47 RCC patients underwent immunotherapy. The function of related cells and markers were validated via in vitro and in vivo experiments.reRCC had reduced CD8We delineated the heterogeneity of reRCC and highlighted an innovative mechanism that CAFs acted as a suppressor of CD8

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.

Increasing evidence suggests that cancer progression is strongly influenced by the host immune response, which is represented by immune cell infiltrates. The T-lymphocyte-based Immunoscore is reported to be a reliable prognostic factor in colon cancer, but its significance in urothelial carcinoma of the bladder (UCB) is at an early stage of exploration. This study aimed to determine whether the tumor immune infiltrate, as evaluated by the Immunoscore, could act as a useful prognostic marker for UCB patients who have undergone radical cystectomy (RC). In this study, immunohistochemistry was used to examine the Immunoscore of 221 UCB patients who underwent RC. The Immunoscore of the patients was determined by the densities of CD3+ and CD8+ T cells at the tumor center and the invasive margin. A highly significant association between a low Immunoscore and a shortened patient survival (P

Although 5-methylcytosine (m5C) is a widespread modification in RNAs, its regulation and biological role in pathological conditions (such as cancer) remain unknown. Here, we provide the single-nucleotide resolution landscape of messenger RNA m5C modifications in human urothelial carcinoma of the bladder (UCB). We identify numerous oncogene RNAs with hypermethylated m5C sites causally linked to their upregulation in UCBs and further demonstrate YBX1 as an m5C 'reader' recognizing m5C-modified mRNAs through the indole ring of W65 in its cold-shock domain. YBX1 maintains the stability of its target mRNA by recruiting ELAVL1. Moreover, NSUN2 and YBX1 are demonstrated to drive UCB pathogenesis by targeting the m5C methylation site in the HDGF 3' untranslated region. Clinically, a high coexpression of NUSN2, YBX1 and HDGF predicts the poorest survival. Our findings reveal an unprecedented mechanism of RNA m5C-regulated oncogene activation, providing a potential therapeutic strategy for UCB.

Summary Background Identification of high-risk localised renal cell carcinoma is key for the selection of patients for adjuvant treatment who are at truly higher risk of reccurrence. We developed a classifier based on single-nucleotide polymorphisms (SNPs) to improve the predictive accuracy for renal cell carcinoma recurrence and investigated whether intratumour heterogeneity affected the precision of the classifier. Methods In this retrospective analysis and multicentre validation study, we used paraffin-embedded specimens from the training set of 227 patients from Sun Yat-sen University (Guangzhou, Guangdong, China) with localised clear cell renal cell carcinoma to examine 44 potential recurrence-associated SNPs, which were identified by exploratory bioinformatics analyses of a genome-wide association study from The Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) dataset (n=114, 906 600 SNPs). We developed a six-SNP-based classifier by use of LASSO Cox regression, based on the association between SNP status and patients' recurrence-free survival. Intratumour heterogeneity was investigated from two other regions within the same tumours in the training set. The six-SNP-based classifier was validated in the internal testing set (n=226), the independent validation set (Chinese multicentre study; 428 patients treated between Jan 1, 2004 and Dec 31, 2012, at three hospitals in China), and TCGA set (441 retrospectively identified patients who underwent resection between 1998 and 2010 for localised clear cell renal cell carcinoma in the USA). The main outcome was recurrence-free survival; the secondary outcome was overall survival. Findings Although intratumour heterogeneity was found in 48 (23%) of 206 cases in the internal testing set with complete SNP information, the predictive accuracy of the six-SNP-based classifier was similar in the three different regions of the training set (areas under the curve [AUC] at 5 years: 0·749 [95% CI 0·660–0·826] in region 1, 0·734 [0·651–0·814] in region 2, and 0·736 [0·649–0·824] in region 3). The six-SNP-based classifier precisely predicted recurrence-free survival of patients in three validation sets (hazard ratio [HR] 5·32 [95% CI 2·81–10·07] in the internal testing set, 5·39 [3·38–8·59] in the independent validation set, and 4·62 [2·48–8·61] in the TCGA set; all p Interpretation Our six-SNP-based classifier could be a practical and reliable predictor that can complement the existing staging system for prediction of localised renal cell carcinoma recurrence after surgery, which might enable physicians to make more informed treatment decisions about adjuvant therapy. Intratumour heterogeneity does not seem to hamper the accuracy of the six-SNP-based classifier as a reliable predictor of recurrence. The classifier has the potential to guide treatment decisions for patients at differing risks of recurrence. Funding National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Provincial Science and Technology Foundation of China, and Guangzhou Science and Technology Foundation of China.

Chromobox homolog 8 (CBX8), also known as human polycomb 8, is a repressor that maintains the transcriptionally repressive state in various cellular genes, and has been reported to promote tumorigenesis. In the present study, we examined CBX8 expression in eight pairs of muscle invasive bladder cancer tissues and adjacent non-tumor tissues, and found that CBX8 was frequently upregulated in muscle invasive bladder cancer tissues when compared to adjacent non-tumor tissues. Analysis showed that high expression of CBX8 in 152 muscle invasive bladder cancer specimens was associated with progression of the T, N, and M stages (P = 0.004, 0.005

// 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

Background Testis-sparing surgery is not popular in South China. This study aimed to investigate this procedure for pediatric testicular tumors. Methods Children with testicular benign tumors were retrospectively analyzed from January 2001 to June 2015 in the Sun Yat-sen University Cancer Center (SYSUCC) and the First Affiliated Hospital (SYSU-1st). Follow-up was performed until June 2016, and the proportions of TSS in the two hospitals during the different periods were compared. Results Forty-seven children with testicular benign tumors were enrolled, and 16 cases underwent testis-sparing surgery. All patients were cured and discharged, which included mature teratoma (n = 37), testicular adrenal rest tumors (n = 4), epidermal cysts (n = 3), granulomatous inflammation (n = 2) and adenomatoid tumors (n = 1). Inguinal testis-sparing surgery was performed in 16 children, and no recurrence was detected during follow-up. It was performed more frequently in SYSUCC than in SYSU-1st (P = 0.031), and the tumor size of these patients was smaller than those of patients who underwent radical orchiectomy (P = 0.044). Moreover, testis-sparing surgery has become more common in the past 5 years, although differences over time have not reached significance (P = 0.051). Conclusions Testis-sparing surgery is reliable, and tumor size and special hospitals affect its success. Additionally, its use has become more popular in recent years. However, advocacy is still needed for the use of this technique in pediatric testicular benign tumors that are small sized. Electronic supplementary material The online version of this article (doi:10.1186/s12893-017-0230-1) contains supplementary material, which is available to authorized users.

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.

Regulatory T cells (Tregs) represent an important contributor to cancer immune escape, but the molecular mechanism responsible for Treg expansion in tumors is heterogeneous and unclear. Here, we investigated the role of S1P1, a receptor of the bioactive lipid sphingosine 1-phosphate (S1P), in regulating the crosstalk between tumor cells and tumor-associated Tregs in bladder cancer (BC). We found that the frequency of CD4+Foxp3+ Tregs was increased in circulating and tumor-infiltrating lymphocytes from BC patients. S1P1 expression was upregulated in BC tissues compared with tumor-adjacent tissues and was positively correlated with the density of tumor-infiltrated Foxp3+ Tregs. Both S1P1 and Treg predicted poor overall survival in BC patients. The in vitro data paralleled the in vivo data and suggested that the activation or overexpression of S1P1 in BC cells promoted the generation of BC-induced (i)Tregs from CD4+CD25−cells, and the generation of these cells was reversed by treatment with anti-IL-10 or anti-TGF-β. Moreover, S1P1 promoted Treg migration mediated by BC cells. Mechanistically, S1P1 activated the TGF-β signaling pathway, leading to the secretion of TGF-β and IL-10 from BC cells. In total, our findings suggest that S1P1 induces tumor-derived Treg expansion in a cell-specific manner and serves as a potent prognostic biomarker and therapeutic target in BC.

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.

Clear cell renal cell carcinoma (ccRCC) is a common pathological subtype of renal cancer. Although the recent application of molecular-targeted agents has modestly improved the prognosis of ccRCC patients, their outcome is still poor. It is therefore important to characterize the molecular and biological mechanisms responsible for the development of ccRCC. Approximately 25% ccRCC patients involves the loss of RNA-binding protein QKI at 6q26, but the role of QKI in ccRCC is unknown. Here, we found that QKI-5 was frequently downregulated in ccRCC patients and its down-regulation was significantly associated with clinical features including T status, M status, and differentiation grade, and poorer patient prognosis. Moreover, QKI-5 inhibited the proliferation of kidney cancer cells both in vitro and in vivo. The subsequent functional studies showed that QKI-5 stabilized RASA1 mRNA via directly binding to the QKI response element region of RASA1, which in turn prevented the activation of the Ras-MAPK signaling pathway, suppressed cellular proliferation and induced cell cycle arrest. Overall, our data demonstrate a suppressive role of QKI in ccRCC tumourigenesis that involves the QKI-mediated post-transcriptional regulation of the Ras-MAPK signaling pathway.

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

To evaluate the two newly established nomograms for predicting lymph node metastasis in penile cancer based on the clinical data on a large cohort of patients.We retrospectively studied the clinical data on 93 patients with penile cancer treated in the Center for Tumor Prevention and Treatment. Using the two recently established nomograms (Bhagat nomogram and Zhu nomogram), we predicted lymph node metastasis in the patients, analyzed the differences between prediction and the results of postoperative pathology, and compared the accuracy of prediction between the two nomograms with the receiver operating characteristic (ROC) curve and the area under the curve (AUC).The median age of the patients was 55 (27－82) years. Positive lymph nodes were found in 31 cases (33.3%) postoperatively and in 9 (21.9%) of the 41 clinically negative cases. The AUC of the Bhagat nomogram was 0.739 and that of Zhu nomogram was 0.808, both of which were similar to the prediction accuracy of internal verification and manifested a medium predictive ability.The newly established Bhagat and Zhu nomograms can be used for predicting lymph node metastasis in penile cancer, but with a low precision, and therefore cannot be relied exclusively for the option of inguinal lymphadenectomy.目的： 通过阴茎癌患者资料来独立地外部验证新近建立的2个诺模图，并阐述其中的联系与不足。方法： 回顾并分析93例阴茎癌患者资料，应用新近建立的2个诺模图（Bhagat诺模图，Zhu诺模图）对阴茎癌患者淋巴结转移进行预测，比较预测结果与实际术后病理结果之间的差异。为比较各自模型的预测准确性，选择了临床中常用的受试者工作特征曲线 （ROC）下面积（AUC）来分析。结果： 93例患者年龄为55（27~82）岁，术后发现阳性淋巴结比例为33.3%，其中41例患者为临床阴性淋巴结，术后发现阳性淋巴结的比例为21.9%。Bhagat诺模图的AUC为0.739，Zhu诺模图的AUC为0.808，均与其内部验证的预测准确性相近，表现出中等的预测能力。结论： 预测阴茎癌淋巴结转移的Bhagat和Zhu诺模图均表现出一定的预测能力，但离高准确性仍有一定的差距，临床上单纯依赖诺模图而决定该患者是否需行腹股沟淋巴结清扫术仍需谨慎。

Cytokine-induced killer (CIK) cells that are stimulated using mature dendritic cells (DCs), referred to as (DC-CIK cells) exhibit superior anti-tumor potency. Anti-programmed death-1 (PD-1) antibodies reinvigorate T cell-mediated antitumor immunity. This phase I study aimed to assess the safety and clinical activity of immunotherapy with PD-1 blockade (pembrolizumab)-activated autologous DC-CIK cells in patients with advanced solid tumors. Patients with selected types of advanced solid tumors received a single intravenous infusion of activated autologous DC-CIK cells weekly for the first month and every 2 weeks thereafter. The primary end points were safety and adverse event (AE) profiles. Antitumor responses, overall survival (OS), progression-free survival (PFS) and cytolytic activity were secondary end points. Treatment-related AEs occurred in 20/31 patients. Grade 3 or 4 toxicities, including fever and chills, were observed in two patients. All treatment-related AEs were reversible or controllable. The cytotoxicity of DC-CIK cells induced up-regulation of PD-L1 expression on autologous tumor cells. When activated using pembrolizumab ex vivo, DC-CIK cells exerted superior antitumor properties and elevated IFN-γ secretion. Objective responses (complete or partial responses) were observed in 7 of the 31patients.These responses were durable, with 6 of 7 responses lasting more than 5 months. The overall disease control rate in the patients was 64.5%. At the time of this report, the median OS and PFS were 270 and 162 days, respectively. In conclusions, treatment with pembrolizumab-activated autologous DC-CIK cells was safe and exerted encouraging antitumor activity in advanced solid tumors. A larger phase II trial is warranted.

Shortening of the 3' untranslated regions (3'UTR) of mRNA is an important mechanism for oncogene activation. However, 3'UTR alteration events, their pathologic functions, and underlying mechanisms in human urothelial carcinoma of the bladder (UCB) are not clear. Here, we combine RNA sequencing, bioinformatics, and clinical studies in two independent cohorts of patients with UCB to identify a novel

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 Tumor necrosis has been indicated as a factor for the poor clinical outcome in human cancers. We aim to disclose the association between tumor necrosis and overall survival and recurrence-free survival in node-negative upper urinary tract urothelial carcinoma patients treated with radical nephroureterectomy. METHODS A retrospective cohort of 100 patients with upper urinary tract urothelial carcinoma from January 1990 to June 2011 was enrolled in this study. Univariate analysis with Log-rank test and multivariate analysis with Cox proportional hazards regression models were conducted to determine the correlations of tumor necrosis with overall survival and recurrence-free survival. RESULTS Tumor necrosis was presented in 48 patients with upper urinary tract urothelial carcinoma and was significantly associated with the advanced pathological stage (P < 0.001), high tumor grade (P < 0.001), subsequent bladder tumor (P = 0.018), vascular invasion (P < 0.001) and lymph node metastasis (P = 0.026). Multivariate analysis revealed tumor necrosis as an independent unfavorable predictor of overall survival in node-negative upper urinary tract urothelial carcinoma patients by multivariate analysis (hazard ratio = 9.23, 95% confidence interval = 1.05-80.89, P = 0.045). CONCLUSIONS Tumor necrosis was an independent factor of adverse clinical outcomes in node-negative upper urinary tract urothelial carcinoma patients who received radical nephroureterectomy. Evaluation of tumor necrosis might be of clinical significance to determine whether patients with node-negative upper urinary tract urothelial carcinoma should be given further therapy after radical nephroureterectomy.

Background Many studies have reported the oncological outcomes between open radical nephroureterectomy (ONU) and laparoscopic radical nephroureterectomy (LNU) of upper tract urothelial carcinoma (UTUC). However, few data have focused on the oncological outcomes of LNU in the subgroup of localized and/or locally advanced UTUC (T1–4/N0-X). The purpose of this study was to compare the oncological outcomes of LNU vs. ONU for the treatment in patients with T1–4/N0-X UTUC. Methods We collected and analyzed the data and clinical outcomes retrospectively for 265 patients who underwent radical nephroureterectomy for T1–4/N0-X UTUC between April 2000 and April 2013 at two Chinese tertiary hospitals. Survival was estimated using the Kaplan-Meier method. Cox’s proportional hazards model was used for univariate and multivariate analysis. Results The mean patient age was 62.0 years and the median follow-up was 60.0 months. Of the 265 patients, 213 (80.4%) underwent conventional ONU, and 52 (19.6%) patients underwent LNU. The groups differed significantly in their presence of previous hydronephrosis, presence of previous bladder urothelial carcinoma, and management of distal ureter (P

Clinical characters of children with testicular benign tumors. (PDF 24 kb)

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.

The prognosis of locally advanced or recurrent squamous cell carcinoma (SCC) of the penis after conventional treatment is dismal. This study aimed to evaluate the therapeutic effects of intraarterial chemotherapy with gemcitabine and cisplatin on locally advanced or recurrent SCC of the penis. Between April 1999 and May 2011, we treated 5 patients with locally advanced penile SCC and 7 patients with recurrent disease with intraarterial chemotherapy. The response rate and toxicity data were analyzed, and survival rates were calculated. After 2 to 6 cycles of intraarterial chemotherapy with gemcitabine and cisplatin, 1 patients with locoregionally advanced disease achieved a complete response, and 4 achieved partial response. Of the 7 patients with recurrent disease, 2 achieved complete response, 3 achieved partial response, 3 had stable disease, and 1 developed progressive disease. An objective tumor response was therefore achieved in 10 of the 12 patients. The median overall survival for the patients was 24 months (range, 10-50 months). Three out of 10 patients who responded were long-term survivors after intraarterial chemotherapy. Intraarterial chemotherapy with gemcitabine and cisplatin may be effective and potentially curative in locoregionally advanced or recurrent penile SCC. The contribution of this therapy in the primary management of advanced or recurrent penile SCC should be prospectively investigated.

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.

Objective To investigate the association between body mass index and oncological outcomes in Chinese patients who had undergone radical nephroureterectomy for upper urinary tract urothelial carcinoma. Methods Between August 1998 and October 2009, 236 consecutive Chinese patients underwent radical nephroureterectomy for upper urinary tract urothelial carcinoma at Sun Yat-sen University Cancer Center (Guangzhou, China). Body mass index data were available for 230 (97.5%) of these patients. All 230 patients were classified into three groups according to the body mass index criteria for Asians, issued by the Asia Cohort Consortium: underweight, body mass index

The reporting of complications following transperitoneal and retroperitoneal open radical nephrectomy (RN) is nonstandardized. This study aimed to compare early complications between the two approaches using a standardized reporting methodology in a large contemporary cohort. Between 1996 and 2009, 558 patients underwent open RN for renal cell carcinoma (RCC) in our two centers (424 from Sun Yat-sen University Cancer Center and 134 from the First Affiliated Hospital of Sun Yat-sen University). Records were reviewed for clinicopathologic features and complications. Complications were graded using the Clavien system based on the severity of impact. One hundred and five patients (18.8%) had one or more early complications (168 complications overall). The overall rates of grades I to V complications were 5.6%, 10.8%, 2.2%, 0.4%, and 0.2%, respectively. Patients who underwent transperitoneal RN did not experience more overall or procedure-related complications than those who underwent retroperitoneal RN (P = 0.911 and P = 0.851, respectively). On subgroup analysis, neither grade I/II nor grades III-V complications were significantly different between the transperitonal RN and retroperitoneal RN groups. Multivariate analysis showed that for any grade of complication, age (P = 0.016) and estimated blood loss (P = 0.001) were significant predictors. We concluded that open RN is a safe procedure associated with low rates of serious morbidity and mortality. Compared with retroperitoneal RN, transperitoneal RN was not associated with more complications. Older patient and more blood loss at surgery were independent predictors for higher early postoperative complication rates.