Surgical treatment of advanced penile cancer.

PURPOSE: To evaluate the therapeutic effect of surgery in patients with advanced penile cancer, who have a dismal prognosis. PATIENTS AND METHODS: Between September 2007 and July 2015, we treated 12 patients with surgical therapy. RESULTS: The median follow-up period for all the patients was 16 months (range 4-60 months). The outcome and concomitant symptoms were analyzed, and the survival rates were calculated. Three of the patients are currently alive. The median overall survival of the patients was 9 months (range 4-13 months). CONCLUSION: The present results suggest that surgery is a valuable treatment option for patients with advanced penile cancer. The prognosis of advanced penile cancer is closely related to lymph node and distant metastases. Flap repair can solve the problem of large area skin defect. Advanced penile cancer is difficult to treat regardless of chemotherapy or radiotherapy, and surgery cannot prolong the lives of patients. However, the dissection of lesions and repair of large area skin defects can dramatically improve the quality of life of patients, especially those with locally advanced disease without distant metastasis.

[Surgical treatment of advanced penile cancer without distant metastasis].

OBJECTIVE: To investigate the effect of surgery on advanced penile cancer without distant metastasis and the factors influencing the prognosis. METHODS: Between September 2007 and July 2015, we treated 8 cases of advanced penile cancer without distant metastasis by penectomy and lymph node dissection. The patients were aged 37－67 (mean 51.1) years. We followed up the patients for 4－60 (mean 19.25) months postoperatively and analyzed the surgical effects and the factors affecting the prognosis. RESULTS: Three of the patients remained alive while the other 5 (62.5%) died at 4－13 (mean 9) months after surgery. No significant complications were observed and myocutaneous flap repair showed good prognosis in 4 of the patients with largearea skin defect. CONCLUSIONS: Surgery is comparatively a valuable option for the treatment of advanced penile cancer without distant metastasis, though with a poor prognosis, and the important factor affecting its prognosis is lymph node metastasis. Flap repair can solve the problem of largearea skin defect after surgery. However, evidence is not yet sufficient to prove the effectiveness of multimodality therapy of this malignancy.

[Effects of different medications with tadalafil on erectile dysfunction in males with primary sexual failure].

OBJECTIVE: To evaluate the effects of three different medications with tadalafil on erectile dysfunction (ED) in young men with primary sexual failure. METHODS: This study included 76 male ED patients aged 21－35 years who had primary sexual failure but normal nocturnal penile tumescence and rigidity and failed to respond to psychotherapy. We randomly assigned them to receive oral tadalafil once daily, on demand, or once-daily + on-demand. After 2－3 months of treatment, we evaluated the effects based on the scores of the patients in the five domains of the International Index of Erectile Function (IIEF-5). RESULTS: After medication, all the patients showed significantly increased scores in the four domains of IIEF-5, namely, erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction. The on-demand group achieved even higher scores in erectile and orgasmic functions but a lower score in sexual desire than the once-daily group. However, the patients in the once-daily + on-demand group exhibited more significant improvement than those in the other two in all the five domains. CONCLUSIONS: Once-daily + on-demand medication with tadalafil can significantly enhance the therapeutic effect on psychogenic ED in young men with primary sexual failure.

The effects of RNA interference mediated VEGF gene silencing on biological behavior of renal cell carcinoma and transplanted renal tumor in nude mice.

OBJECTIVE: This study was to explore the effects of RNA interference mediated vascular endothelial growth factor (VEGF) gene silencing on biological behavior of renal cell carcinoma (RCC), transplanted renal tumor and angiogenesis in nude mice. METHODS: The specific siRNA sequence targeting VEGF were designed and synthesized to construct hVEGF-siRNA plasmid which was transfected into RCC 786-O cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used for the detection of VEGF gene expression and western blot was adopted for the examination of VEGF protein expression. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell growth as well as cell migration and invasion. The transplanted renal tumor models in nude mice were established, and the growth condition of nude mice, and VEGF protein expression in transplanted tumor slices and the microvessel density (MVD) were detected. RESULTS: The expression level of VEGF mRNA in VEGF-siRNA group was significant lower than that in the control group and negative group, suggesting that establishment of plasmid specifically inhibited the expression of VEGF gene The expression level of VEGF protein in VEGF-siRNA group was significant lower than that in the control group and negative group. VEGF gene silencing has the significant inhibition effects on proliferation, migration and invasion of RCC 786-O cells. The tumor weight, VEGF protein positive rate and MVD in VEGF-siRNA group were significant lower than those in negative group and blank group. CONCLUSION: The VEGF gene silencing could inhibit the cell proliferation, migration and invasion of RCC 786-O cells; inhibition of VEGF protein expression could prevent transplanted RCC growth and tumor angiogenesis.

RNAi-mediated knockdown of vascular endothelial growth factor inhibits vascularization and tumor growth in renal cell carcinoma.

In the present study, we aimed to examine the effects of the knockdown of vascular endothelial growth factor (VEGF) by RNA interference (RNAi) on vascularization and tumor growth in renal cell carcinoma (RCC). For this purpose, a lentiviral vector expressing VEGF-shRNA was constructed and transfected into 293T cells. The efficiency of RNAi was determined by infecting human 786-O RCC cells with viral particles and measuring the VEGF mRNA levels by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effect of transfection with VEGF­shRNA on the secreted VEGF levels was also examined and the inhibitory effects on vascularization were also examined using a chick chorioallantoic membrane (CAM) assay. An RCC xenograft model was established in nude mice by implanting 786-O cells to form subcutaneous tumors. VEGF expression was observed by immunohistochemical (IHC) staining of the xenograft tumors. The tumor volume and tumor inhibition rate were also recorded. The apoptosis of the cancer cells was measured by TUNEL assay and the efficiency of tumor inhibition was estimated. The interference rate of VEGF­shRNA was 72.2% in the 786-O cells. Our results revealed that VEGF mRNA expression, the secreted VEGF level in the 786-O cells and the total vessel length were markedly reduced in the VEGF­shRNA-transfected cells compared with the controls (all P<0.05). Compared with the controls, injections of lentivirus expressing VEGF-shRNA significantly inhibited tumor growth, and reduced tumor mass and VEGF expression in the tumor tissue (all P<0.05). The apoptotic index in the treatment group was significantly higher than that in the controls (both P<0.05). Thus, our data indicate that the inhibition of VEGF expression by RNAi reduces VEGF mRNA levels, and inhibits angiogenesis and tumor growth in RCC, providing a future treatment option for RCC.

Metastatic tumors of the penis: a report of 8 cases and review of the literature.

The purpose of this study was to report the clinical characteristics, treatments, and outcomes of secondary penile cancers and review the literature of this rare condition.The records of 8 patients with metastatic penile cancer treated at our hospital from 2006 to 2013 were analyzed. A search of medical databases was conducted.Patient symptoms included penile mass (n = 7, 5 had concomitant pain) and acute urine retention (n = 1). The primary cancers included bladder, lung, gastric, liver, and prostate malignancies and 1 case of pulmonary epithelioid hemangioendothelioma. The longest time from diagnosis of the primary cancer to metastatic penile cancer was 16 years and the shortest was 7 months. Six patients were treated with phallectomy, 1 with resection of the mass, and 1 with only a biopsy because of advanced metastatic disease. Five patients are deceased at the time of this report, and the longest and shortest survival times (from the diagnosis of primary cancer to the death) were 16 years and 9 months, respectively. The literature review identified 17 cases reported since 2011, bringing the total number of reported cases to 480. Genitourinary cancer, primarily bladder and prostate, account for approximately 70 of the primary cancer sites and gastrointestinal cancers account for approximately 21%. Approximately half of the patients had died of their disease within 1 year of the diagnosis of penile metastasis.The prognosis of metastatic penile cancer is poor. Most primary cancers are in the urologic or gastrointestinal systems. Surgery and adjunctive therapy may improve symptoms, but fail to prolong survival.

Two-stage urethroplasty is a better choice for proximal hypospadias with severe chordee after urethral plate transection: a single-center experience.

It is still debatable whether single- or two-stage urethroplasty is a more suitable technique for treating hypospadias with severe chordee after urethral plate transection. This retrospective study evaluated these two techniques. A total of 66 patients of proximal hypospadias with severe chordee were divided into two groups according to the techniques they underwent: 32 and 34 patients underwent single-stage (Duckett) or two-stage urethroplasty, respectively. Median ages at presentation were 7.5 years and 11.0 years in single-stage and two-stage repair groups, respectively. Median follow-ups were 28.5 months (20-60 months) and 35 months (18-60 months) in the single-stage and two-stage groups, respectively. The meatus of the neourethra was located at the top of the glans in all patients. No recurrence of chordee was found during follow-up, and all patients or parents were satisfied with the penile length and appearance. Complications were encountered in eight patients in both groups, with no statistically significant differences between the two techniques. The late complication rate of stricture was higher after the single-stage procedure (18.75% vs 0%). The complication rate after single-stage repairs was significantly lower in the prepubescent subgroup (10.52%) than in the postpubescent cohort (46.15%). These results indicate that the urethral plate transection effectively corrects severe chordee associated with proximal hypospadias during the intermediate follow-up period. Considering the higher rate of stricture after single-stage urethroplasty, two-stage urethroplasty is recommended for proximal hypospadias with severe chordee after urethral plate transection.

The differentiation of human adipose-derived stem cells towards a urothelium-like phenotype in vitro and the dynamic temporal changes of related cytokines by both paracrine and autocrine signal regulation.

PURPOSE: To investigate the differentiation ability of human adipose-derived stem cells (ASCs) towards urothelium-like cells in vitro and the dynamic changes of related cytokines and cytokine receptors in the culture medium. MATERIALS AND METHODS: The ASCs were induced using both conditioned media (CM) and the transwell co-culture system with an immortalized urothelium cell line (SV-HUC-1,HUC) for 21 days. Protein and mRNA expression of the mature urothelium specific markers uroplakin-IA (UP-1A) and uroplakin-II (UP-II) were detected by immunofluorescence and quantitative real-time PCR, respectively. Array detection was used to screen 41 cytokines and receptors in the upper medium of urothelium, non-induced ASCs and urothelium-induced ASCs at three time points, early (12 hours), intermediate (7 days) and late (21 days). RESULTS: After induction for 7 days, the ASCs grown in both CM and transwell co-culture system expressed uroplakin-IA (13.54±2.00%; 17.28±1.84%) and uroplakin-II (19.49±1.73%; 13.98±1.47%). After induction for 21 days, ASCs grown in co-culture had significantly increased expression of uroplakin-IA (48.03±1.25%; 49.57±2.85%) and uroplakin-II (45.38±2.50%; 46.58±1.95%). In the upper medium of urothelium, 28 cytokines and 8 cytokine receptors had significantly higher expression than the counterpart of non-induced ASCs. After 7 days induction, the expression of 22 cytokines and 8 cytokine receptors was significantly elevated in the upper medium of induced ASCs compared to non-induced ASCs. At the early and intermediate time points, ASCs secreted high levels of relative cytokines and soluble receptors, but their expressions decreased significantly at the late time point. CONCLUSION: The adipose-derived stem cells have the potential to be differentiated into urothelium-like cells in vitro by both CM and transwell co-culture system with mature urothelium. Numerous cytokines and receptors were involved in the differentiation process with dynamic temporal changes by both paracrine and autocrine signal regulation. Further studies should be carried out to determine the detailed mechanism of cytokines and receptors and to enhance the urothelium differentiation efficiency of ASCs.

Unsatisfactory outcomes of prolonged ischemic priapism without early surgical shunts: our clinical experience and a review of the literature.

Ischemic priapism is a rare occurrence which can cause severe erectile dysfunction (ED) without timely treatment. This retrospective study reports our experience in treating prolonged ischemic priapism and proposes our further considerations. In this paper, a total of nine patients with prolonged ischemic priapism underwent one to three types of surgical shunts, including nine Winter shunts, two Al-Ghorab shunts and one Grayhack shunt. During the follow-up visit (after a mean of 21.11 months), all patients' postoperative characters were recorded, except one patient lost for death. Six postoperative patients accepted a 25-mg oral administration of sildenafil citrate. The erectile function of the patients was evaluated by their postoperative 5-item version of International Index of Erectile Function Questionnaire (IIEF-5), which were later compared with their premorbid scores. All patients had complete resolutions, and none relapsed. The resolution rate was 100%. Seven patients were resolved with Winter shunts, one with an Al-Ghorab shunt and one with a Grayhack shunt. The mean hospital stay was 8.22 days. There was only one urethral fistula, and the incidence of postoperative ED was 66.67%. Four patients with more than a 72-h duration of priapism had no response to the long-term phosphodiesterase type 5 (PDE-5) inhibitor treatment. These results suggest that surgical shunts are an efficient approach to make the penis flaccid after prolonged priapism. However, the severe ED caused by prolonged duration is irreversible, and long-term PDE-5 inhibitor treatments are ineffective. Thus, we recommend early penile prosthesis surgeries for these patients.

A comparative study of the use of a transverse preputial island flap (the Duckett technique) to treat primary and secondary hypospadias in older Chinese patients with severe chordee.

OBJECTIVE: To investigate the outcome between the primary and secondary hypospadias with severe chordee in older patients by the transverse preputial island flap (TPIF). MATERIALS AND METHODS: We retrospectively analyzed 53 hypospadias patients who were performed with TPIF for urethroplasty, including 25 primary hypospadias (Group 1) and 28 secondary hypospadias (Group 2). The mean age in Group 1 was 12.12 ± 10.709 and 18.64 ± 8.727 in Group 2 (P = 0.0181). The mean follow-up time was 38.7 months (22-60 months). RESULTS: All of the foreskin flaps survived after the operation without necrosis. The overall complication rate was 24 % in Group 1 and 53.57 % in Group 2 (P = 0.0280). All the patients were also divided into two cohorts according to their ages in surgery. In the 0-10-yr cohort, there was a significant difference in the overall complication rate between the primary and secondary groups (P = 0.0173). But in the cases who were over 11 year old, there was no significant difference in the overall complications between two groups (P = 0.1603). Also no significant difference was found in the mean length of the urethral defect between two groups (P = 0.8312). CONCLUSION: The Duckett technique is an optional choice for some older Chinese patients undergoing primary operations, but it has a higher complication rate in those who have undergone previous failed urethroplasties. The unsatisfactory results found in the reoperative group were supposed to be linked to the older age, the lack of subcutaneous flap coverage and local scar tissue, but not to the length of the urethral defect.

[Repair and functional reconstruction of the penis (a report of 62 cases)].

OBJECTIVE: To investigate the effects of surgery treatment on serious penile lesions and malformation. METHODS: Sixty-two patients, aged from 19 to 63 years old (mean 35 ys), were included in the study. Among them, 4 patients suffered from penis partial defection were respectively treated with restoring defective penis, penis lengthening and urethroplasty; three patients with penis completely missing were treated with penis reconstruction surgery; 22 cases with serious penile curvature were treated with the 16-dot plication technique (Lue's procedure); 15 cases with penile fracture were treated with conservative treatment for 1 case and with patch penis, corpus spongiosum, and deep penile dorsal vein ligation for 14 cases; 5 cases with post-operative complications of 3-pieces of penile prosthesis, including the prosthesis perforating to the urethra, water pump failure, broken connection tube, erection angle < 60 degrees and failure to expansion the corpus cavernosum, were treated by taking out prostheses, urethral repair cracks, replacement of the prostheses, excision of fibrosis scar and re-implantation prostheses respectively. Four cases with penis complete amputation were treated with the penis replantation; three cases of avulsion injury were treated with the replantation and free flap skin; 6 with Paget's disease of penises were treated with the lesion free skin buried in the scrotum and penis. RESULTS: All these patients were followed up for 3 months to 4 years, with the average of 9 months. Among the 4 cases of penis partial defection, 2 patients were satisfied with the penile appearance and sexual function; 1 got some satisfactory and 1 was unsatisfied. Three cases with the loss of the penis completely were satisfied with both the postoperative appearance and urination, and 1 was not satisfied. Twenty-two cases of penile curvature deformities were corrected, and one case was recurrence. Fourteen of the 15 patients with penile fracture were followed, and all got the restoration of sexual function. Among them, 5 cases with post-operative complications, including mild bending, algopareunia, subcutaneous induration, poor hardness and poor sexual pleasure, were not further treated, and another case lost; Five cases with post-operative complications of three-pieces penile prosthesis were treated successfully, and 4 of their spouses were satisfied with their sexual function after operation, only 1 of their spouse not satisfied. Among four cases with complete amputation of penis, two cases of penis were replanted successfully while two necrosis. Three cases with avulsion were treated with skin grafting successfully. All 6 cases with penile Paget's disease were followed for 2 -4 years, and free skin grafts were all survival. One patient died of brain metastases 18 months after operation and five cases were disease-free survival. CONCLUSION: The patients should be treated based on the procedure of andrological and urological surgery, together with microsurgical, flap or skin graft technique. The urologist should design personalized surgical procedure. Most of the patient's penis shape and erectile dysfunction can be reconstructed by our procedures, but some patients can not achieve the desired appearance or function of penis. New approaches of the treatment ought to be developed to restore both of the shape and function for those severe injury of the penis.

[Severe hypospadias repair: reconstructing penis, scrotum and urethra].

OBJECTIVE: To investigate the surgical technic of re-shape penis and scrotum, as well as construct urethra in severe hypospadias patients. METHODS: Twenty-two cases of perineal hypospadias with abnormal penis and scrotum were involved in operative repair. All the patients underwent two-stage of repair technic. The penis sponge were completely stretched out and uprighted in the first-stage. Foreskin and partial penis back skin was transferred into the ventral of penis and scrotum crack. At second-stage, urethroplasty was performed using bladder mucosa folded into half tube that sutured with urothra plate to reconstruct the urothra. The scrotum were re-shaped using foreskin and skinflap. RESULTS: The operation's successful rate was 68% (15/22). There were 7 cases (32%) suffered from urethrocutaneous fistula and recovered after repair. Five cases (23%) occurred stricture of urethra and were treated by urethra dilatation. The appearance of penis and scrotum in 22 cases were satisfied. CONCLUSIONS: The operative methods should be made according to the type of hypospadias and of scrotum. The technic were effective on severe hypospadias with abnormal scrotum, even for the patients who need more than 10 cm urethra construct. The appearance of penis and scrotum were satisfied after following up.

[Correlation of age and sex hormones to the transition zone volume of the prostate].

OBJECTIVE: To investigate the correlation of age and sex hormones to the total volume (TV) and transition zone volume METHODS: Eighty-two men were divided into two groups with the age of 60 as the dividing line. Prostatic TV (TZV and TZV were measured with transrectal ultrasound (TRUS) and the concentrations of total testosterone (T), free testosterone (fT) and estradiol (E2) were measured with radioimmunoassay. Exponential curve regression and one-factor analysis of variance (ANOVA) were used for statistical analysis. RESULTS: Age was significantly correlated with TV, TZV and the TZV/TV ratio, P < 0.01. There was a significant positive correlation between the concentrations of fT and TZV, a negative correlation between those of E2 and TZV (P < 0.01), but no correlation between those of T and TZV (P > 0.05). CONCLUSION: The significant acceleration of the TZV of the prostate after the age of 60 is related to sex hormones.

[Pre- and post-prostatectomy variation and supplement of sexual hormones in patients with benign prostatic hyperplasia].

OBJECTIVE: To explore the variation of sexual hormones (T and fT) before and after prostatectomy and their post-operative supplement in patients with benign prostatic hyperplasia (BPH). METHODS: Sixty-four cases of BPH were randomly divided into a treatment group (Group I, n = 25) and a control group (Group II, n = 39). Plasma LH, FSH, T and fT were measured by radioimmunoassay a week before and two weeks after prostatectomy. After operation, Group I received supplement of testosterone undecanoate, while Group II received none. RESULTS: The variations of plasma LH, FSH, T and fT were not statistically significant in the two groups before prostatectomy (P > 0.05), but obviously less in Group I than in Group II after operation (P < 0.01). CONCLUSION: Testosterone supplement is a useful therapy for post-prostatectomy patients with androgen deficiency.