Comparison of two different methods of establishment of canine urethroplasty model: an experimental trial.

BACKGROUND: Graft substitute urethroplasty is recommended for patients with long segment anterior urethral stricture. The therapeutic effects of the grafts need to be validated on the animal models. Therefore the aim of this study was to compared the operative time, blood loss, intra- and post- operative complications of two different methods of establishment of canine urethroplasty model. METHODS: Twelve Beagle dogs were randomly separated into control and experimental group using a random number table. Six animals in the control group received the conventional urethroplasty, while the other 6 in the experimental group received the modified procedures. Tube cystostomy and urethroplasty were performed in the control group. The cystostomy not the tube cystostomy were performed in the experimental group, and the testes were simultaneously removed with the scrotum. Per- and postoperative outcomes, complications were evaluated. RESULTS: The urethroplasty were successfully performed for all dogs and all of these procedures were done by the same surgeon. The median operative time in the control and experimental groups was 186.8 min and 188.7 min respectively. The blood loss in the control and experimental groups was 40.8 ml and 45.8 ml respectively. No intraoperative complications occurred. 3 animals in the control group developed acute urinary retention after the accidental removal of suprapubic bladder tube and the cystostomy was done again. There was no occurrence of urinary retention in the experimental group. 4 animals in the control group developed the perineal hematoma, in which one animal had the urine leakage and incision infection. Perineal hematoma occurred in only one animal in the experimental group. CONCLUSION: The occurrence of urinary retention and perineal hematoma decreased in the modified group, in which the cystostomy not the tube cystostomy were performed and the testes with the scrotum were simultaneously removed.

PCNL in COPD patient in the sit position under local infiltration anesthesia case report.

BACKGROUND: Percutaneous nephrolithotomy is traditionally performed in the prone or supine position. We report the first case of percutaneous nephrolithotomy in sit position under local infiltration anesthesia. A 69-year-old male presented with left flank pain. Kidney B ultrasound and computed tomography scan showed multiple left renal calculi and hydronephrosis. He had a long history of chronic obstructive pulmonary disease, with severe ventilatory and cardiac dysfunction, and cannot tolerate the prone or supine position. The patient received the surgery in sit position under local infiltration anesthesia. The operative time was 1 h. The visual analogue scale score during the surgery was 3. The patient had no intraoperative and postoperative complications. The postoperative plain radiography showed no residual stone fragments. CONCLUSIONS: We believe that in high-risk patients who need to undergo PCNL, a combination of sit position and local infiltration anesthesia is an alternative method.

[Management of female urethral obliteration with the rotary excision appliance].

OBJECTIVE: To describe a new technique using the rotary excision appliance for the treatment of female urethral obliteration and to evaluate the effect of the management. METHODS: Between October 2000 and July 2013, 5 cases of female urethral obstruction (age from 23 to 65 years, time to treatment from 3 to 60 months, obliteraion length from 0.5 to 1.8 cm) were managed using the rotary excision appliance and the patients had been followed up. RESULTS: After a mean of 32.4 months (range: 5 to 75 months) of follow-up, normal micturation had been achieved in all the patients. The maximal urinary flow rate (MFR) ranged from 15 to 28 mL/s (mean 20.6 mL/s). Three patients were continent and 2 patients had slight incontinence. CONCLUSION: The rotary excision appliance is a useful instrument for the management of female urethral obliteration. Our Long-term follow-up provides further support for use of this technique by demonstrating that urethral continuity can be established without increased incidence of stricture formation or incontinence.

[Surgical treatment of bone metastases from renal cell carcinoma].

OBJECTIVE: To retrospectively analyze the survival of renal cell carcinoma patients with bone metastases, evaluate the effect of treatment and identify the prognostic factors in these patients. METHODS: A total of 66 renal cell carcinoma patients with bone metastases treated at our hospital between October 1990 and October 2010 were divided into 3 groups: solitary bone metastasis referred for radical surgery (n = 19); palliative surgery for solitary/multiple bone metastasis (n = 31); extraosseous metastasis without orthopedic surgery (n = 16). The effects of different variables on survival were determined according to the Kaplan-Meier method and Log-Rank test. And Cox proportional hazard regression model was used to estimate the prognostic factors. RESULTS: Their mean follow-up period was 25 (6-68) months. The survival significantly improved if bone metastases were solitary (45 vs 29 and 13 months, both P < 0.01), there was no vertebral bone involvement (31 vs 10 months, P < 0.01) and radical surgery was performed (50 vs 28 and 13 months, both P < 0.01). Age, gender, tumor size, alkaline phosphatase and lactate dehydrogenase had no effect on survival (all P > 0.05). Based on Cox regression analysis, survival was influenced by the number of metastasis foci (RR = 0.259, 95%CI:0.075-0.897) , type of procedure (RR = 17.845, 95%CI:4.246-74.992) and vertebral bone involvement (RR = 4.526, 95%CI:1.896-10.803) (all P < 0.05). CONCLUSIONS: Surgery is a better option for achieving local tumor control, providing good function and increasing the survival of patients with bone metastases. And radical resection is indicated for the patients with a solitary metastasis.

[Association between HPV DNA and disease specific survival in patients with penile cancer].

OBJECTIVE: To examine the prevalence of human papilloma virus (HPV) in penile squamous-cell carcinomas (SCCs), explore the relationship between HPV and clinicopathological variables and determine its value for predicting disease-specific survival. METHODS: We retrospectively collected clinicopathological data of 28 patients with penile squamous cell carcinomas from 2000 to 2009 at Beijing Cancer Hospital, Beijing Hospital and Peking University People's Hospital. Polymerase chain reaction (PCR) was used to detect the presence of HPV DNA in tumor specimens. Regular follow-ups were conducted. Disease-specific survival plots were drawn with the Kaplan-Meier method and compared with the Log-Rank test. Cox proportional hazard analysis was applied to assess the independent effects of several prognostic factors on survival. RESULTS: HPV DNA was detected in 7/28 samples. After sequencing, all 7 samples were confirmed to be HPV-16 type. The median follow-up period was 60 (6-150) months. By the time of analysis, 8/28 patients died. HPV DNA was not significantly associated with age, pathological grading, pathologic T stage or lymph node metastasis (P = 0.191, 0.165, 1.000, 0.639 respectively). Cox multivariate regression analysis indicated that lymph node status (HR = 5.5, P = 0.023) was an independent predictive factor of disease specific survival, followed by pathological T classification (HR = 11.0, P = 0.035) . The 5-year disease-specific survival in patients with HPV DNA positive was higher than that in those with HPV DNA negative (67% vs 58%) . But survival had no significant differences (P = 0.431). CONCLUSIONS: Higher pathologic T stage and lymph node metastasis are independent prognostic factors for worse survival. And mortality does not increase markedly in penile cancer patients with HPV DNA positive.

[Penile cancer and human papillomavirus infection].

Human papillomavirus (HPV) infection is one of the major risk factors for penile cancer. This article presents an overview on the biological characteristics of HPVs, HPV infection in penile cancer, possible carcinogenic mechanisms of HPV, prognostic value of HPV in penile cancer, and HPV vaccine.

Development and validation of a predictive model for post-percutaneous nephrolithotomy urinary sepsis: a multicenter retrospective study.

BACKGROUND: The objective of this retrospective, multicenter study was to analyze the factors associated with the development of urogenital sepsis after percutaneous nephrolithotomy (PCNL) and to establish a nomogram prediction model of urogenital sepsis after PCNL. METHODS: A total of 2066 postoperative PCNL patients were included from three medical institutions: Zunyi Medical University Hospital, Beijing Jishuitan Hospital Guizhou Hospital, and Fenggang County People's Hospital. Clinical data of 1623 patients from the Department of Urology of Zunyi Medical University Hospital were randomized into a training cohort (Zunyi training cohort, N.=1139) and an internal validation cohort (Zunyi internal validation cohort, N.=484) using computer generated random numbers in a 7:3 ratio. Univariate and multivariate logistic regression analyses were performed on the compliance training cohort to identify risk factors for urogenital sepsis after PCNL and to develop a column line graph prediction model based on these risk factors. Finally, Zunyi internal validation cohort and two external validation cohorts (Guiyang external cohort, N.=306; Fenggang external cohort, N.=137) were used to validate the prognostic accuracy of the nomogram prediction model. R4.2.2 statistical software was used for all statistical data analyses. RESULTS: Multifactorial logistic regression analysis of the Zuiyi training cohort (N.=1139) identified five independent risk factors associated with urogenital sepsis after PCNL, including urine culture positivity (odds ratio [OR]=5.29, P<0.001), urine nitrite positivity (OR=5.97, P<0.001), operation time ≥60 min (OR=4.4, P=0.0037), residual stone (OR=5.18, P<0.001), and size ≥30 mm (OR=3.22, P=0.0086). Nomogram were constructed based on these independent risk factors. The area under the curve (AUC) of the nomogram model was 0.907 in the in-progress sample and 0.948 after internal validation. The AUC of the model was 0.855 and 0.804 after external validation of the Guiyang external validation cohort and the Fenggang validation cohort, respectively, indicating good discrimination ability. The calibration curves of the nomogram showed good agreement, and the decision curve analysis demonstrated high clinical utility. CONCLUSIONS: Based on the clinical independent risk factors such as positive urine culture, positive urine nitrite, operation time ≥60min, stone residue, stone size ≥30mm, nomogram prediction model of urogenital sepsis after PCNL was established, which can provide reference for urologists to develop preoperative evaluation and treatment strategies for patients with percutaneous nephrolithotomy.

FOXP2 confers oncogenic effects in prostate cancer.

Identification oncogenes is fundamental to revealing the molecular basis of cancer. Here, we found that FOXP2 is overexpressed in human prostate cancer cells and prostate tumors, but its expression is absent in normal prostate epithelial cells and low in benign prostatic hyperplasia. FOXP2 is a FOX transcription factor family member and tightly associated with vocal development. To date, little is known regarding the link of FOXP2 to prostate cancer. We observed that high FOXP2 expression and frequent amplification are significantly associated with high Gleason score. Ectopic expression of FOXP2 induces malignant transformation of mouse NIH3T3 fibroblasts and human prostate epithelial cell RWPE-1. Conversely, FOXP2 knockdown suppresses the proliferation of prostate cancer cells. Transgenic overexpression of FOXP2 in the mouse prostate causes prostatic intraepithelial neoplasia. Overexpression of FOXP2 aberrantly activates oncogenic MET signaling and inhibition of MET signaling effectively reverts the FOXP2-induced oncogenic phenotype. CUT&Tag assay identified FOXP2-binding sites located in MET and its associated gene HGF. Additionally, the novel recurrent FOXP2-CPED1 fusion identified in prostate tumors results in high expression of truncated FOXP2, which exhibit a similar capacity for malignant transformation. Together, our data indicate that FOXP2 is involved in tumorigenicity of prostate.

GPNMB overexpression is associated with extensive bone metastasis and poor prognosis in renal cell carcinoma.

Glycoprotein non-metastatic protein B (GPNMB) promotes bone metastasis (BM) in various types of cancer. However, GPNMB expression and its function in patients with renal cell carcinoma (RCC) and BM is still unknown. Therefore, the clinical significance of GPNMB and its biological function in RCC with BM was investigated in the present study. A total of 31 patients with RCC and BM were retrospectively collected. The association between GPNMB protein expression level on the primary tumor and the clinicopathological characteristics of the patients was analyzed. Kaplan-Meier analysis was used to investigate the association between GPNMB expression and the prognosis of the patients. The effects of GPNMB inhibition on cell proliferation, migration and invasion in RCC cells were investigated using short hairpin (sh)RNA. High GPNMB expression level was significantly associated with the number (P=0.001) and the extent of BM (P=0.001), Fuhrman grade (P=0.037), and ERK expression level (P=0.003) of the primary tumor. In addition, GPNMB overexpression was significantly associated with poor prognosis with respect to overall survival time (P=0.001). Furthermore, a specific shRNA sequence targeting the GPNMB gene was constructed and transduced into the ACHN cell line, using a lentivirus vector to obtain a stable cell line with low mRNA expression level of GPNMB. Low GPNMB expression level inhibited RCC cell proliferation, which was measured using a Cell Counting Kit-8 assay. Cell migration and invasion ability was significantly decreased in GPNMB knockdown RCC cells compared with that in cells transduced with the negative control shRNA. In addition, the protein expression levels of phosphorylated ERK were lower in the GPNMB shRNA-transduced ACHN cells compared with those in the control cells. Therefore, these results suggested that GPNMB plays an important role in tumor progression in RCC with BM. Furthermore, it might serve as a predictive marker for BM and as a poor prognostic factor in RCC with BM. GPNMB downregulation suppressed the proliferation, migration and invasion of the RCC cells, which may be mediated through the inhibition of the ERK signaling pathway.

[Correlation of CD82 and hTERT expressions and HPV infection with penile cancer].

OBJECTIVE: To study the correlation of the expressions of CD82 and hTERT and HPV infection with the clinical pathological features of penile cancer and identify their prognostic significance in the lymphatic metastasis of the disease. METHODS: A total of 44 patients underwent partial or radical penectomy and lymph node dissection. The expressions of CD82 and hTERT were determined by immunohistochemistry, and HPV infection was detected by PCR. RESULTS: The positive rates of CD82, hTERT, and HPV DNA in penile carcinoma were 47.7%, 38.6% and 25.9%, respectively. The amplified HPV DNA was HPV-16. The pathological stage and hTERT expression were positively correlated with inguinal lymph node metastasis of penile cancer (P = 0.032, P = 0.041), and so was the pathological stage with the expression of CD82 (P = 0.045), but neither the pathological stage, nor the expression of CD82 or the positive rate of HPV DNA showed any correlation with lymph node metastasis (P = 0.627, P = 0.094, P = 0.633). CONCLUSION: The pathological grade and hTERT expression are independent prognostic factors for lymph node metastasis in penile carcinoma. These features help the prognosis and identification of the patient at the risk of nodal metastasis.

Clinical Characteristics and Prognosis of Renal Cell Carcinoma With Spinal Bone Metastases.

BACKGROUND: The prognosis of renal cell carcinoma (RCC) with spinal bone metastasis (sBM) varies greatly. In this study, we aimed to define the clinical characteristics and prognostic factors of RCC with spinal bone metastasis (sBM) in our center. METHODS: The clinical and medical records of RCC patients with sBMs were collected. The gender, age, time of BM, the extent of BM, the number of BMs, the presence or absence of visceral metastasis, and the pathological type of BM were investigated. All patients were followed up regularly. Overall survival (OS) was calculated from the date of BMs diagnosis to death or last follow-up using Kaplan-Meier method and modelled with Cox regression analysis. RESULTS: Forty-three RCC patients with sBM were collected. sBM was found synchronously in 30 patients (70%) and metachronously in 13 patients (30%). The median survival time was 30 months in 13 patients (30%) with solitary sBM and 19 months in 30 patients (70%) with multiple sBMs (P = 0.002). Visceral metastasis occurred in 12 patients (28%) with the median survival time of 17 months, while the other 31 patients (72%) had no visceral metastasis with the median survival time of 29 months (P<0.001). En-block resection was done in 10 patients with median survival time of 40.1 months. Non-en-block resection were done in 33 patients with median survival time of 19.7 months (P<0.001). Multivariate COX regression analysis showed that MSKCC score, number of BM, visceral metastasis, and en-block resection are the independent prognosis factors of RCC patients with sBM. CONCLUSIONS: MSKCC risk stratification, number of sBM, visceral metastasis and en-block resection are significant prognostic factors for OS in RCC patients with spinal BM. Therefore, for selected patients who has solitary spinal BM with no visceral metastasis, en-block resection of spinal BM can potentially prolong survival and is the treatment of choice.

Cell-Seeded Acellular Artery for Reconstruction of Long Urethral Defects in a Canine Model.

The management of urethral stricture remains a major therapeutic challenge in clinics. Herein, we explored the feasibility of reconstructing a relatively long segment of the urethra by the cell-seeded acellular artery in a canine model. The acellular arterial matrix was obtained from the excised carotid artery of donor dogs. Autologous adipose-derived stem cells (ADSCs) from 6 male dogs were grown and seeded onto the premade acellular arterial matrix. A 3 cm long segment of the urethra was resected in 12 male dogs. Urethroplasty was performed with the acellular arterial matrix seeded with ADSCs in 6 animals and without cells in 6. Serial urethrography was performed at 1 and 3 months postoperatively. Wide urethral calibers without any signs of strictures were confirmed in all 6 animals in the experimental group. In contrast, urethral stricture was demonstrated in 3 animals in the control group. The graft was highly epithelialized and smooth in the experimental group, while graft contracture and scar formation were showed in the control group. Histologic analysis of the cell-seeded arterial matrix at 1 month confirmed the presence of multilayered urothelium and muscle. The levels of tissue formation developed over time with a progressive increase in muscle content. In contrast, extensive fibrosis and sparse smooth muscle were seen in animals treated with matrix without ADSCs. This study provides preclinical evidence that the ADSC-seeded arterial matrix can be used as a tubularized scaffold in the reconstruction of 3 cm long urethral defect in a male canine model. The ADSC-seeded arterial matrix remodels and regenerates normal-appearing urethral tissue layers over time.