A chromosome-level genome assembly of Hong Kong catfish (Clarias fuscus) uncovers a sex-determining region.

BACKGROUND: Hong Kong catfish (Clarias fuscus) is an ecologically and economically important species that is widely distributed in freshwater regions of southern China. Hong Kong catfish has significant sexual growth dimorphism. The genome assembly of the Hong Kong catfish would facilitate study of the sex determination and evolution mechanism of the species. RESULTS: The first high-quality chromosome-level genome of the Hong Kong catfish was constructed. The total genome was 933.4 Mb, with 416 contigs and a contig N50 length of 8.52 Mb. Using high-throughput chromosome conformation capture (Hi-C) data, the genome assembly was divided into 28 chromosomes with a scaffold N50 length of 36.68 Mb. A total of 23,345 protein-coding genes were predicted in the genome, and 94.28% of the genes were functionally annotated in public databases. Phylogenetic analysis indicated that C. fuscus and Clarias magur diverged approximately 63.7 million years ago. The comparative genome results showed that a total of 60 unique, 353 expanded and 851 contracted gene families were identified in Hong Kong catfish. A sex-linked quantitative trait locus identified in a previous study was located in a sex-determining region of 30.26 Mb (0.02 to 30.28 Mb) on chromosome 13 (Chr13), the predicted Y chromosome. This QTL region contained 785 genes, of which 18 were identified as sex-related genes. CONCLUSIONS: This study is the first to report the chromosome-level genome assembly of Hong Kong catfish. The study provides an excellent genetic resource that will facilitate future studies of sex determination mechanisms and evolution in fish.

[Changes in the penis size of prostate cancer patients after radical prostatectomy and its influencing factors].

OBJECTIVE: To investigate the changes in the size of the penis after radical prostatectomy (RP) and the possible influencing factors. METHODS: This study included 45 cases of RP for PCa performed by the same surgeon from January to June 2019. Before and at 2 weeks after surgery, we measured the stretched penile length (SPL), flaccid penile length (FPL) and penile circumference of the patients. We conducted an IIEF-5 questionnaire investigation on the preoperative characteristics of the patients and their attitudes towards postoperative penile rehabilitation. We also analyzed the factors associated with the postoperative changes in the size of the penis. RESULTS: Compared with the baseline, the postoperative SPL (ï¼»9.72 ± 1.87ï¼½ vs ï¼»7.80 ± 1.57ï¼½ cm, P = 0), FPL (ï¼»6.26 ± 1.14ï¼½ vs ï¼»5.13 ± 1.10ï¼½ cm, P = 0) and penile circumference (ï¼»7.69 ± 0.83ï¼½ vs ï¼»7.26 ± 0.78ï¼½ cm, P = 0.012) were decreased significantly, by (1.92 ± 0.12) cm, (1.13 ± 0.09) cm and (0.43 ± 0.08) cm, respectively. The age of the patients was significantly correlated with the change of the FPL (P = 0.042), but not the other factors with the change of the penile size. Twenty-six (57.7%) cases of severe and moderate ED were observed in the patients postoperatively. Those with better preoperative sexual function took a more positive attitude towards penile rehabilitation and treatment postoperatively (n = 3, 75.0%). CONCLUSIONS: The penile size of the PCa patient is decreased markedly after radical prostatectomy, with a significant correlation between the patient's age and the postoperative change of the flaccid penile length. The patients with better preoperative sexual function are more likely to seek penile rehabilitation and treatment postoperatively.

Extended versus non-extended lymphadenectomy during radical cystectomy for patients with bladder cancer: a meta-analysis of the effect on long-term and short-term outcomes.

BACKGROUND: Pelvic lymphadenectomy (PLND) is an integral part of curative surgery for high-risk non-muscle invasive and muscle-invasive bladder cancer. The therapeutic value of extended PLND is controversial. METHODS: We conducted a comprehensive online search in PubMed, EMBASE, and the Cochrane Library databases for relevant literature directly comparing extended PLND (e-PLND) with non-extended PLND (ne-PLND) from database inception to June 2019. We performed the meta-analysis to evaluate the impact of PLND templates on recurrence-free survival (RFS), disease-specific survival (DSS), overall survival (OS), rates of postoperative major complications, and mortality within 90 days of surgery. RESULTS: A total of 10 studies involving 3979 patients undergoing either e-PLND or ne-PLND were included. The results showed that e-PLND was significantly associated with better RFS (HR 0.74, 95% CI 0.62-0.90, p = 0.002) and DSS (HR 0.66, 95% CI 0.55-0.79, p < 0.001). However, no correlation was found between e-PLND template and a better OS (HR 0.93, 95% CI 0.55-1.58, p = 0.79). Postoperative major complications were similar between e-PLND group and ne-PLND group, as was mortality within 90 days of surgery. CONCLUSION: e-PLND template is correlated with favorable RFS and DSS outcomes for patients with bladder cancer. e-PLND did not have more postoperative major complications than did ne-PLND.

[Attitudes of prostate cancer patients towards postoperative penile rehabilitation and their influencing factors].

OBJECTIVE: To investigate the attitudes of prostate cancer (PCa) patients towards postoperative penile rehabilitation and their influencing factors. METHODS: Seventy-nine PCa patients underwent radical prostatectomy from January through June 2017 and all received a questionnaire investigation before surgery on IIEF-5 and their attitudes towards postoperative penile rehabilitation. We analyzed the reasons for the patients' rejection of postoperative penile rehabilitation. RESULTS: Totally 56 (71%) of the patients accepted and the other 23 (29%) refused postoperative penile rehabilitation. The factors influencing their attitudes towards penile rehabilitation mainly included age (P = 0.023), income (P = 0.040), tumor stage (P = 0.044), and preoperative sexual activity (P = 0.004). The patients who accepted penile rehabilitation had significantly higher IIEF-5 scores than those who refused it (14.75 ± 0.88 vs 8.48 ± 1.16, P = 0.000 2). During the follow-up period, only 29 (36.7%) of the patients bought the vacuum erection device but not the other 50 (63.3%). The tumor stage (P = 0.004), income (P < 0.01) and preoperative androgen-deprivation therapy (P = 0.039) significantly influenced the patients' decision on the purchase of the device. Relevant admission education achieved a 45% decrease in the number of the patients unwilling to accept penile rehabilitation for worrying about its negative effect on cancer treatment, a 25% decrease in those rejecting penile rehabilitation because of age, and a 20% decrease in those refusing it due to the tumor stage. The cost of treatment was an important reason for the patients' rejection of postoperative penile rehabilitation. CONCLUSIONS: The tumor stage and income are the main factors influencing PCa patients' decision on postoperative penile rehabilitation. Relevant admission education and reduced cost of rehabilitation are important for popularization of postoperative penile rehabilitation in PCa patients.

The use of MMSE and MoCA in patients with acute ischemic stroke in clinical.

BACKGROUND: The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are brief cognitive screening tools that have been developed for the screening of patients with Mild Cognitive Impairment. METHODS: A total of 105 patients were included in this study, aged 53-89 years, with acute ischemic stroke admitted to hospital and fell into two groups: stroke patients with cognitive impairment (SCI) and controls with no cognitive impairment (n-SCI). The patient's characteristics are collected and regression analyses were performed to predict cognitive impairments. We use MMSE and MoCA assessment as prognostic indices for cognitive impairments of patient's with stroke. OBJECTIVES: Our aim was to examine the effectiveness of the MMSE and MoCA in screening cognitive impairments. MAIN RESULTS: There were significant difference among the two groups in the prevalence of diabetes mellitus (p < 0.05) and intracranial atherosclerosis (p < 0.05). A linear regression determined that the age, diabetes, intracranial atherosclerosis predicted the cognitive impairments. The ROC results for MoCA with an AUC of 0.882 and the corresponding results for MMSE show a similar AUC of 0.839. CONCLUSION: Neuropsychological performance of stroke patients was influenced by biological and demographic variables: age, diabetes and intracranial atherosclerosis. The MoCA and MMSE are both reliable assessments for the diagnosis of cognitive impairment after stroke.

Estrogen enhances activity of Wnt signaling during osteogenesis by inducing Fhl1 expression.

Estrogen is a crucial hormone for osteoclast inhibition and for preventing osteoporosis. However, the hormone's role in osteoblast growth and differentiation remains unclear. The complexity of estrogen's role in guiding osteoblast behavior arises partly from crosstalk with other signaling pathways, including Wnt signaling. In this study, we show that the Wnt agonist, LiCl, induced Fhl1 gene expression, which substantially enhanced osteoblast differentiation. Staining with alizarin red revealed that MC3T3-E1 mineralization was enhanced by overexpression of Fhl1. In addition, Fhl1 promoted the expression of the osteogenic markers, Runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and osteopontin (OPN), whereas MC3T3-E1 cells with gene knockdown of Fhl1 exhibited limited mineralization and expression of Runx2, OCN, and OPN. We further demonstrate evidences from quantitative reverse transcription real-time polymerase chain reaction and reporter assay that Fhl1 expression was synergistically stimulated by estrogen (E2) and LiCl, but reduced by the estrogen-receptor inhibitor fulvestrant (ICI 182,780). However, estrogen could not enhance osteogenesis while Fhl1 expression was knocked down. Because estrogen and Wnt signaling frequently interact in developmental processes, we propose that Fhl1 can be an acting molecule mediating both signaling pathways during osteogenesis.

[Penile rehabilitation after radical pelvic surgery].

Prostate cancer, bladder cancer, and rectal cancer are common malignancies in the male pelvis. The incidence rate of erectile dysfunction (ED) following radical prostatectomy, cystectomy or rectal cancer surgery is about 25% - 100%. The main cause of post-surgery ED is mainly attributed to injury of neurovascular bundles, which may lead to reduced oxygenation in and fibrosis of the penile tissue. Early penile rehabilitation after surgery can improve or restore the erectile function of the patients. This article focuses on penile rehabilitation after radical pelvic surgery.

Downregulation of DAB2IP results in cell proliferation and invasion and contributes to unfavorable outcomes in bladder cancer.

The DOC-2/DAB2 interactive protein (DAB2IP) is a member of the Ras GTPase-activating protein family. It has been shown to be often downregulated and a poor prognostic factor in several human malignancies. In this study, we analyzed the clinicopathological features and outcomes of DAB2IP expression in 135 patients with urothelial carcinoma of the bladder (UCB) treated by radical cystectomy plus bilateral lymph node dissection, and evaluated the effect of DAB2IP knockdown in vitro using the MTT method, colony formation assay, cell cycle assay, and cell migration and invasive assay. We found low expression of DAB2IP was significantly associated with high pathological stage (P = 0.002), high pathological grade (P = 0.02), tumor size more than 3 cm (P = 0.04), and presence of histological variants (P = 0.01). DAB2IP was an independent prognostic factor of disease recurrence (hazard ratio, 2.67; P = 0.034) and cancer-specific survival (hazard ratio, 2.79; P = 0.038). Knockdown of DAB2IP could promote cell proliferation, migration, and invasion. Downregulation of DAB2IP could activate the ERK and Akt pathways and was correlated with the expression of epithelial-mesenchymal transition markers, such as E-cadherin and vimentin. In conclusion, downregulation of DAB2IP is associated with features of biologically aggressive UCB and results in cell proliferation, migration, and invasion of bladder cancer. DAB2IP may serve as a promising biomarker in patients with UCB treated by radical cystectomy and bilateral lymph node dissection.

Down-regulation of Dicer and Ago2 is associated with cell proliferation and apoptosis in prostate cancer.

Dicer and Argonaute2 (Ago2) are critical components responsible not only for RNA interference but also for microRNA synthesis. The present study investigated the roles of Dicer and Ago2 in prostate cancer (Pca). First, the expression levels of Dicer and Ago2 in Pca tissues were determined by immunohistochemistry (IHC) and compared with pathological features. Next, RNA interference was used to down-regulate the expression levels of Dicer and Ago2 in the Pca cell lines LNCaP, PC-3, and DU145, and effects on proliferation, apoptosis, and cell cycle were detected using the CCK-8 assay and flow cytometry, respectively. We found that Dicer and Ago2 expression levels in Pca tissues were higher than those in adjacent benign tissues and correlated with lower Gleason patterns, with the exception of Dicer expression in localized Pca. In vitro, silencing Dicer or Ago2 inhibited cell proliferation and induced apoptosis in LNCaP, PC-3, and DU145, as well as arrested the cell cycle at the G2/M phase in androgen-dependent LNCaP, or at S phase in the androgen-independent PC-3 and DU145. Altogether these findings suggest that Dicer and Ago2 play important roles in proliferation, apoptosis, and the cell cycle in Pca and might serve as both promising biomarkers for Pca progression and potential therapeutic targets.

Visceral fat accumulation is associated with different pathological subtypes of renal cell carcinoma (RCC): a multicentre study in China.

OBJECTIVE: To investigate whether visceral obesity is associated with certain histological subtypes of renal cell carcinoma (RCC) ina multicentre Chinese cohort. PATIENTS AND METHODS: A kidney tumour database was created using three tertiary centres in China; 487 patients were enrolled presenting with localised RCC and complete computer tomography(CT)/magnetic resonance imaging (MRI) information. A single-slice CT image was used to measure the area of visceral and subcutaneous adipose tissues in each patient. Statistical methods were used to analyse clear-cell RCC (ccRCC) and non-clear-cell RCC (non-ccRCC) as they relate to visceral fat area (VFA) and other risk factors, such as age, gender, tumour size, diabetes, hypertension, total fat area (TFA) and body mass index (BMI). RESULTS: In all, 418 patients had a ccRCC subtype and 69 had a non-ccRCC subtype. For all the patients with RCC, the mean VFA was 102 cm2, while mean BMI was 24 kg/m2. The mean VFA was greater in ccRCC than non-ccRCC patients by 25 cm2. There were significant differences in the mean VFA and TFA between patients with ccRCC and those with non-ccRCC.Multivariate analysis showed that the presence ofVFA was more important than the effects of BMI and Type 2 diabetes on pathology prediction. In patients with a normal BMI, those with a higher quartile of VFA were more likely to develop ccRCC than those with a low VFA. CONCLUSIONS: Increased visceral fat was found to be associated with ccRCC and the significance of VFA outweighed the effects of BMI and Type 2 diabetes for the prediction of RCC pathology in multivariate analyses. As a result, VFA could constitute a primary explanation for the link between obesity and ccRCC.

A Phase II trial of dosage escalation of sorafenib in Asian patients with metastatic renal cell carcinoma.

AIM: To investigate the role of sorafenib dosage escalation in Asian patients with metastatic renal cell carcinoma that had progressed after routine dosages. PATIENTS & METHODS: Sorafenib dosage escalation to 600 or 800 mg twice a day was offered to 41 patients with metastatic renal cell carcinoma who had progressed on normal dosages. Clinical outcome, toxicity and favorable clinical covariables for progression-free survival (PFS) were evaluated. RESULTS: The median PFS with dosage-escalated therapy was 7 months. Drug-related adverse events were tolerable. The pre-escalation Karnofsky performance status, serum calcium concentration, neutrophil/lymphocyte ratio, PFS and the highest toxicity grade at the routine dosage were associated with a longer PFS in the dosage-escalation period. CONCLUSION: Sorafenib dosage escalation was efficacious and tolerable in Asian patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry (no. ChiCTR-ONRC-12002088).

External validation of nomograms for predicting cancer-specific mortality in penile cancer patients treated with definitive surgery.

Using a population-based cancer registry, Thuret et al. developed 3 nomograms for estimating cancer-specific mortality in men with penile squamous cell carcinoma. In the initial cohort, only 23.0% of the patients were treated with inguinal lymphadenectomy and had pN stage. To generalize the prediction models in clinical practice, we evaluated the performance of the 3 nomograms in a series of penile cancer patients who were treated with definitive surgery. Clinicopathologic information was obtained from 160 M0 penile cancer patients who underwent primary tumor excision and regional lymphadenectomy between 1990 and 2008. The predicted probabilities of cancer-specific mortality were calculated from 3 nomograms that were based on different disease stage definitions and tumor grade. Discrimination, calibration, and clinical usefulness were assessed to compare model performance. The discrimination ability was similar in nomograms using the TNM classification or American Joint Committee on Cancer staging (Harrell's concordance index = 0.817 and 0.832, respectively), whereas it was inferior for the Surveillance, Epidemiology and End Results staging (Harrell's concordance index = 0.728). Better agreement with the observed cancer-specific mortality was shown for the model consisting of TNM classification and tumor grade, which also achieved favorable clinical net benefit, with a threshold probability in the range of 0 to 42%. The nomogram consisting of TNM classification and tumor grading was shown to have better performance for predicting cancer-specific mortality in penile cancer patients who underwent definitive surgery. Our data support the integration of this model in decision-making and trial design.

Visceral obesity and risk of high grade disease in clinical t1a renal cell carcinoma.

PURPOSE: Accurate assessment of disease characteristics is a prerequisite for treatment decision making regarding small renal masses. In this study we evaluate the association between visceral obesity and Fuhrman grade in patients with cT1a renal cell carcinoma. MATERIALS AND METHODS: We retrospectively collected data on 186 patients with surgically treated cT1a renal cell carcinoma. Single slice computerized tomography was used to measure the area of visceral and subcutaneous adipose tissue. Visceral obesity was calculated as the proportion of visceral adipose tissue to overall adipose tissue. Other analyzed factors included clinical characteristics (age, gender, body mass index and tumor size) and anatomical features of the tumor defined by the R.E.N.A.L. nephrometry score. The association between predictors and high grade disease (Fuhrman grade III or IV) were assessed using logistic regression analyses. RESULTS: A total of 47 (25.3%) tumors were classified as high grade. The percentage of visceral adipose tissue was higher in male participants but did not correlate with body mass index, age or tumor size. In univariate analyses the percentage of visceral adipose tissue and tumor size were significantly associated with higher Fuhrman grade. Multivariate analysis showed that the percentage of visceral adipose tissue (OR 1.06, p = 0.0018) and tumor size (OR 1.91, p = 0.047) were independent predictors of high grade cancer. Addition of the percentage of visceral adipose tissue to a model including clinical characteristics and anatomical features of the tumor remarkably improved its discriminatory ability (p = 0.0010). CONCLUSIONS: Increased visceral obesity was found to be strongly associated with higher Fuhrman grade in patients with cT1a renal cell carcinoma. Further studies are needed to confirm these findings and discover the underlying biological mechanism.

[Hematologic adverse effects in patients with renal cell carcinoma treated with sunitinib].

OBJECTIVE: To explore the hematologic adverse effects in patients with renal cell carcinoma treated with sunitinib. METHODS: A total of 136 patients with advanced renal cell carcinoma were treated with sunitinib at our hospital from 2008 to 2011. There were 91 males and 45 females with an average age of 55.5 years. They received sunitinib in repeated 6-week cycles consisting of 4 weeks of sunitinib 50 mg per day followed by 2 weeks of treatment (schedule 4/2). The hematologic toxicities, collected at baseline and 14, 28, 42 (after a 2-week rest period) days, were graded according to the National Cancer Institute common terminology criteria for adverse events version 3.0. The paired Wilcoxon test was used to evaluate the kinetics of hematologic adverse effects at days 14, 28, and 42 post-treatment. RESULTS: The hematologic toxicities included leukopenia (n = 91, 66.9%), neutropenia (n = 95, 69.8%), lymphopenia (n = 58, 46.2%), thrombopenia (n = 89, 65.4%) and hypohemoglobinemia (n = 48, 35.3%). Among them, 31 cases (22.8%) had the high-grade (including grades 3 and 4) toxicity of thrombopenia. There were depressions in hematopoietic cell populations including leukocytes, neutrophils, and platelets at days 14, 28 and 42 versus the baseline level (all P < 0.05). The median hemoglobin level transiently increased at days 14 and 28 (both P < 0.01) and returned to the level of baseline at days 42 (P = 0.754). CONCLUSIONS: The incidence of hematologic adverse effects of sunitinib slightly varies with what have been observed in previous studies. And the incidence of high-grade toxicity of thrombocytopenia is higher than that reported in studies conducted in the US and Europe.

[Exploratory analysis of the effect of toxicity of sunitinib on the clinical outcome of patients with advanced renal cell carcinoma].

OBJECTIVE: To explore the effect of toxicity of sunitinib on the clinical outcome of patients with advanced renal cell carcinoma (RCC) . METHODS: A total of 136 patients with advanced RCC were treated with sunitinib from 2008 to 2011. There were 91 males and 45 females with an average age of 56 years. Their 6-week therapy cycle was 4 weeks of sunitinib 50 mg daily followed by 2-week off-treatment (schedule 4/2). The median follow-up time was 15 months. Correlation between toxicities and overall survival (OS) was evaluated in a Cox model using log-transformed levels after adjusting for MSKCC model.Log-rank test and Cox proportional hazard model were used to assess the value of drug toxicity as the prognostic factors. RESULTS: The increased hemoglobin on cycle 1 day 14 (HR:0.950, 95%CI:0.923-0.978) and the increased lymphocytes on cycle 1 days 28 and 42 (HR:0.405, 95%CI:0.203-0.809, HR:0.394, 95%CI:0.179-0.867) were significantly associated with OS (P adj = 0.001, 0.014 and 0.022 respectively). Hypertension class III/IV (HR:0.066, 95%CI:0.008-0.582), and the number of neutrophils screening and lymphocyte count ratio (HR:2.537, 95%CI:1.182-5.404) were the survival prognosis independent predictors. CONCLUSION: Early hematopoietic toxicities may potentially predict the outcomes of advanced RCC after a therapy of sunitinib.

[Vacuum therapy for erectile dysfunction that fails to respond to PDE-5i: report of 70 cases].

OBJECTIVE: To assess the efficacy and safety of the Osbon ErecAid Vacuum Therapy System in the treatment of erectile dysfunction (ED) that fails to respond to PDE-5i. METHODS: This study included 70 cases of ED not responding to the medication of PDE-5i. The patients were aged 25 -66 (38.9 +/- 9.1) years. Under our direction, the patients used the Osbon ErecAid Vacuum Therapy System for a month to increase blood oxygenation to the corpora cavernosa, and then employed the vacuum constriction device (VCD) to maintain penile erection for sexual intercourse. We compared their IIEF-5 scores and their and their partners' sexual satisfaction before and 3 months after treatment, and evaluated the safety and effect of the vacuum therapy. RESULTS: The mean IIEF-5 scores of the patients were significantly increased from 10.2 +/- 4.0 before treatment to 13.3 +/- 4.7 at 3 months after the vacuum therapy (P < 0.05). The rate of therapeutic effectiveness was 77.1% (54/70), and the rates of sexual satisfaction of the patients and their partners were 64.3% (45/70) and 65.7% (46/70), CONCLUSION: Vacuum therapy for ED that does not respond to PDE-5i can significantly improve the patients' erectile function as well as their and their partners'sexual satisfaction, and therefore deserves clinical application.

A nomogram to predict the duration of drainage in patients with penile cancer treated with inguinal lymph node dissection.

PURPOSE: We developed a nomogram to predict the duration of drainage in patients with penile cancer treated with inguinal lymph node dissection. MATERIALS AND METHODS: A total of 111 groin basins in 56 patients who underwent radical inguinal lymph node dissection for penile cancer were retrospectively assessed. We retrieved the clinicopathological factors from the medical records including age, body mass index, albumin, smoking history, hypertension, diabetes, preoperative radiotherapy/chemotherapy, palpable lymph nodes, previous lymph node biopsy, total number of resected lymph nodes and ratio of positive lymph nodes. The criterion of drain removal was total drain output of 50 ml or less per day for 2 days starting from postoperative day 3. A multivariate Cox proportional hazards model was used to explore the risk factors of drainage duration and variable selection was performed according to Akaike's information criteria. A nomogram was built based on regression coefficients and internally validated with 200 bootstrap resamples. RESULTS: Median postoperative drainage duration was 7 days. The prediction model using pretreatment factors showed a concordance index of 0.55. With the addition of lymph node related variables a second model was constructed which produced a better concordance index (0.65) and good calibration. On multivariate analysis young age, high body mass index, total number of resected lymph nodes and ratio of positive lymph nodes were independent predictors of prolonged lymphatic drainage. CONCLUSIONS: On the basis of readily obtained clinicopathological variables we developed a nomogram to predict the duration of lymphatic drainage which, if externally validated, could be helpful for patient consultation, treatment decision making and clinical trial design.

External validation of a nomogram using RENAL nephrometry score to predict high grade renal cell carcinoma.

PURPOSE: A novel nomogram using the RENAL ([R]adius maximal diameter in cm, [E]xophytic/endophytic properties, [N]earness of the tumor to the collecting system or sinus in mm, [A]nterior/Posterior, [L]ocation relative to the polar lines and [H]ilar) nephrometry score was developed to predict high grade renal cell carcinoma. It showed good performance in internal evaluation. We externally validated the prediction model. MATERIALS AND METHODS: We identified a cohort of 391 Chinese patients in whom renal cell carcinoma was surgically resected at our institution from 2008 to 2011. Fuhrman grade was reviewed by an experienced genitourinary pathologist and radiological images were independently assessed by 2 senior urologists. Using a 2-tiered system high grade disease was defined as Fuhrman grade III/IV. The statistical performance of the prediction model was evaluated by discrimination, calibration and clinical usefulness. RESULTS: Of the 391 patients 45.5% were considered to have high grade tumors. External validation of the nomogram revealed an AUC of 0.73. The calibration plot showed that the predicted probability of high grade disease had concordance comparable to the observed frequency. On decision curve analysis the prediction model provided a superior net benefit and reduction at a greater than 20% probability threshold. CONCLUSIONS: We confirm the predictive value of the nomogram using the RENAL nephrometry score to identify high grade renal cell carcinoma in an independent cohort. Further research is required to evaluate its performance using a head-to-head comparison with renal biopsy results.

Penile metastasis from primary bladder cancer: a study of 8 cases and review of the literature.

BACKGROUND: Penile metastases from primary bladder cancer are extremely rare. CASE REPORT: The medical records of 8 patients who presented with metastatic penile carcinoma originating from bladder between 2002 and 2010 were analyzed. The main complaint was a painless nodule (6 cases), priapism (1 case), and penile pain (1 case). All of the penile metastases were metachronous. The interval between primary cancer and penile metastases ranged from 1 to 100 months (mean 26.4 months). Total penectomy combined with systemic chemotherapy was the treatment of choice in 4 cases. 1 patient only accepted external beam radiotherapy, and 3 patients only accepted chemotherapy due to disseminated disease. The time interval between penile metastases and death ranged from 4 to 23 months (mean 11.4 months). CONCLUSION: Penile metastases secondary to primary bladder cancer are rare and represent a challenging problem. The common mode of spread to the penis is by retrograde venous route. The overall outcome is very poor, and most patients will die within 1 year despite systemic chemotherapy and supportive care. Radical ablative surgery is justified only for symptomatic relief.

High level interleukin-6 in the medium of human pancreatic cancer cell culture suppresses production of neurotransmitters by PC12 cell line.

It has been suggested that pancreatic cancer is associated with a greater prevalence of depression than many other cancers, but the mechanism accounting for this potential association has not yet been illustrated. In the present study, conditioned media (CM) from three pancreatic cancer cell lines and primary pancreatic cancer cells from two patients were added to culture system of differentiated pheochromocytoma cell line PC12. The release of dopamine (DA) and norepinephrine (NE) by PC12 was significantly inhibited after CM treatment (P < 0.05), similar to what happened after recombinant interleukin 6(IL-6) treatment. Furthermore, pretreatment with anti-IL-6 antibody significantly blocked the inhibitory effects of pancreatic cancer CM on DA and NE production (P < 0.05). We also demonstrated that tyrosine hydroxylase (TH), the rate-limiting enzyme for synthesis of catecholamine, was reduced after exposure to IL-6, which was accompanied by JAK-STAT3 pathway activation. Our results demonstrated that IL-6 in CM from pancreatic cancer down-regulated the production of DA and NE by PC12 cell. The possible underlying mechanisms might be decreasing TH production via activation of JAK-STAT3 signal transduction pathway. The present study might help to better understand the close relationship between pancreatic cancer and depression.