Zhikang Cai

Penile and Scrotal Paget’s disease: 130 Chinese patients with long‐term follow‐up

To report a retrospective series of 130 Chinese patients with penoscrotal extramammary Paget’s diseases (EMPD), with a long‐term follow‐up, and thus improve the diagnosis and therapy of this disease.

A prospective, randomized clinical trial comparing plasmakinetic resection of the prostate with holmium laser enucleation of the prostate based on a 2-year followup.

PURPOSE We compared plasmakinetic resection with holmium laser enucleation of the prostate for the treatment of benign prostatic hyperplasia by analyzing 2-year followup data from a prospective randomized clinical trial. MATERIALS AND METHODS A total of 280 patients were randomly treated with plasmakinetic resection or holmium laser enucleation of the prostate. Perioperative and postoperative outcome data were obtained during a 2-year followup. RESULTS No significant differences between the 2 surgical groups were observed in the preoperative data. Both groups displayed significant improvements after surgery. However, we identified no significant differences between the 2 groups in the 2-year followup data for I-PSS (International Prostate Symptom Score), quality of life scores or maximum flow rate values. Patients in the holmium laser enucleation group displayed a lower risk of hemorrhage, shorter bladder irrigation and catheter times, and shorter hospital stays. A larger amount of prostate tissue was retrieved in the holmium laser enucleation group, but the operation time was longer for this group than for the plasmakinetic resection group. CONCLUSIONS Plasmakinetic resection and holmium laser enucleation of the prostate are effective and safe treatments for benign prostatic hyperplasia. Holmium laser enucleation of the prostate can be applied to prostates of all sizes, and involves less risk of hemorrhage, decreased bladder irrigation and catheter times, as well as reduced hospital stay. Thus, we believe holmium laser enucleation of the prostate should be proposed as a potential new gold standard surgical therapy instead of transurethral resection of the prostate for patients with benign prostatic hyperplasia.

Poly r(C) Binding Protein-1 is Central to Maintenance of Cancer Stem Cells in Prostate Cancer Cells

Aims: To investigate global proteomic changes induced in CD44+CD24- stem cells isolated from the prostate cancer cell lines, LNCaP and DU145, post prolonged TGF-β treatment in order to understand underlying mechanisms that promote stemness in prostate cancer cells. Methods: CD44+CD133+α2β1Integrin+CD24- population was isolated from mock or TGF-β treated (7 days) prostate cancer cell line, LNCaP, through fluorescent activated cell sorting. Cell lysates were obtained from the ±TGF-β cell population and proteomics profiling (MS/MS) was performed by mass spectrometry. Relative enrichment or depletion in the CD44+CD24-population post-TGF-β treatment was determined relative to mock-treated CD44+CD24- cells post normalization to GAPDH expression levels. Results obtained from MS/MS were validated using immunoblotting. Functional validation of one putative regulator was performed using gain-of-function strategy to investigate its role in rendering stemness in LNCaP and DU145 cells in vitro and in promoting tumorigenicity in vivo. Results: TGF-β treatment caused significant enrichment of CD44+CD24- population in LNCaP cells (22.35 ± 0.94% in mock treated vs 95.23 ± 2.34% in TGF-β treated cells; P < 0.01), which were also positive for CD133 and α2β1Integrin. Mass spectrometry analysis of the enriched cell population revealed that sixty-three proteins were either up- or down-regulated greater than five folds, out of which the poly r(C) binding protein (PCBP)-1 was the most down-regulated (9.31 ± 0.05 folds). Ectopic overexpression of PCBP1 in LNCaP and DU145 cells not only attenuated enrichment of CD44+CD133+CD24- population in these cells following TGF-β treatment, but also significantly decreased tumorigenicity of the stem cell subset, as assessed by in vitro soft agar colony formation and in vivo xenograft assays. Conclusion: Our proteomic profiling and subsequent validation indicate that PCBP1 is central to CSCs enrichment and functionality in prostate cancer.

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

AbstractThe 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.

SPOCK1 promotes tumor growth and metastasis in human prostate cancer

Prostate cancer is the most diagnosed noncutaneous cancer and ranks as the second leading cause of cancer-related deaths in American males. Metastasis is the primary cause of prostate cancer mortality. Survival rate is only 28% for metastatic patients, but is nearly 100% for patients with localized prostate cancers. Molecular mechanisms that underlie this malignancy remain obscure, and this study investigated the role of SPARC/osteonectin, cwcv, and kazal-like domain proteoglycan 1 (SPOCK1) in prostate cancer progression. Initially, we found that SPOCK1 expression was significantly higher in prostate cancer tissues relative to noncancerous tissues. In particular, SPOCK1 expression was also markedly high in metastatic tissues compared with nonmetastatic cancerous tissues. SPOCK1 expression knockdown by specific short hairpin RNA in PC3 cells was significantly inhibited, whereas SPOCK1 overexpression in RWPE-1 cells promoted cell viability, colony formation in vitro, and tumor growth in vivo. Moreover, the SPOCK1 knockdown in PC3 cells was associated with cell cycle arrest in G0/G1 phase, while the SPOCK1 overexpression in RWPE-1 cells induced cell cycle arrest in S phase. The SPOCK1 knockdown in PC3 cells even increased cell apoptosis. SPOCK1 modulation was also observed to affect cancerous cell proliferation and apoptotic processes in the mouse model of prostate cancer. Additionally, the SPOCK1 knockdown decreased, whereas the SPOCK1 overexpression increased cell migration and invasion abilities in vitro. Injection of SPOCK1-depleted PC3 cells significantly decreased metastatic nodules in mouse lungs. These findings suggest that SPOCK1 is a critical mediator of tumor growth and metastasis in prostate cancer.

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.

An Improved Morcellation Procedure for Holmium Laser Enucleation of the Prostate

PURPOSE We modified the conventional morcellation procedure for holmium laser enucleation of the prostate (HoLEP), and its outcomes are presented in this article. MATERIALS AND METHODS As 395 patients were included, the conventional morcellation procedure was performed in the first 100 cases (group 1, cases 1-100), and an improved procedure was used in the last 100 cases (group 2, cases 296-395). The improved morcellation process has three steps to execute. The morcellation time, collected tissue weight, morcellation rate, and associated complications were recorded. RESULTS The tissue-resected weight was similar between group 1 (60.7±33.9 g) and group 2 (62.4±36.8 g). The mean morcellation time in group 1 was greater than that in group 2 (11.3±7.1 and 8.3±4.1 minutes, respectively), and the mean morcellation rate was better in group 2 than in group 1 (5.75±1.7 g/minutes in group 1 v 7.3±1.1 g/minutes in group 2). Complications, such as bladder injury, were similar in both groups. CONCLUSION The improved morcellation procedure described in this article can be used in various situations of suction and can be performed in a more fluent manner and with better efficiency.

Human Stromal Cells in the Peripheral Zone of the Prostate Promote Tumorigenesis of Prostatic Cancer Stem Cells through Up-regulation of C-Kit Expression

Objective: Most prostate cancers originate from the prostatic peripheral zone (PZ). We tested the hypothesis that the stromal cells from PZ and transitional zone (TZ) have differential effects on the ability of tumorigenesis. Methods: Stromal cells isolated from the PZ and TZ of normal human prostates mixed with DU145 cells subcutaneously injected into athymic nude mice. The volume and weight of tumors was measured and analyzing the ability of purified DU145 cells isolated from the tumors to migrate and proliferate. The expression patterns of stem cell-specific genes of these DU145 cells were examined. The C-Kit inhibitor, imatinib mesylate, was administrated to confirm the effect of stromal cells on the tumorigenesis. Results: The volume and weight of tumors were significantly higher in mice transplanted with DU145 and stromal cells from PZ. In contrast, the data was significantly lower with DU145 and stromal cells from TZ than DU145 alone. The purified DU145 cells isolated from the tumors with DU145 and stromal cells in PZ had increased ability to migrate and proliferate, and had increased expression of C-Kit. These effects of the stromal cells in the PZ on DU145 cells could be blocked using imatinib mesylate. Conclusions: Human stromal cells in the PZ promote the in vivo tumorigenesis of DU145 through up-regulating C-Kit; in contrast, the stromal cells in the TZ inhibit it through down-regulating the expression of C-Kit. The model will be useful for understanding the mechanisms by which the prostatic stem cell niche controls the tumorigeneis of prostatic cancer stem cells.

Losartan Preserves Erectile Function by Suppression of Apoptosis and Fibrosis of Corpus Cavernosum and Corporal Veno-Occlusive Dysfunction in Diabetic Rats

Background/Aims: Transforming growth factor-β1 (TGF-β1) plays important roles in penile corporal fibrosis and veno-occlusive dysfunction (CVOD). Angiotensin II (Ang II) is critically involved in erectile dysfunction, and blocking of Ang II is more important than inhibition of TGF-β in non-penile tissue fibrosis. However, the role of Ang II in corporal fbrosis and CVOD in a diabetic condition has not been investigated. Methods: Diabetic rats were treated with sildenafil or losartan (an Ang II antagonist) alone or in combination. Intracavernosal pressure, dynamic infusion cavernosometry, and histological and molecular alterations of the corpus cavernosum were examined. Results: Diabetic rats exhibited decreases in erectile response, severe CVOD, apoptosis, fibrosis, and activation of the TGF-β1 pathway. Treatment with sildenafil had a modest effect on erectile response and an insignificant suppressive effect on CVOD, apoptosis, fibrosis, and the TGF-β1 pathway. Although losartan greatly improved the histological and molecular changes and CVOD as compared with sildenafil, its effect on erectile response was low. The combination of sildenafil and losartan had superior effects on these parameters than did either compound alone. Conclusion: Ang II activation may be involved in apoptosis and fibrosis of the corpus cavernosum through Smad and non-Smad pathways, resulting in CVOD and ED. The low efficacy of sildenafil in a diabetic ED rat model was at least partly due to its inadequate effects on apoptosis, fibrosis, and CVOD.

Sulforaphane Ameliorates Bladder Dysfunction through Activation of the Nrf2-ARE Pathway in a Rat Model of Partial Bladder Outlet Obstruction.

Purpose. We evaluated the effect of sulforaphane (SFN) treatment on the function and changes of expression of Nrf2-ARE pathway in the bladder of rats with bladder outlet obstruction (BOO). Materials and Methods. A total of 18 male Sprague-Dawley rats at age of 8 weeks were divided into 3 groups (6 of each): the sham operated group, the BOO group, and the BOO+SFN group. We examined histological alterations and the changes of oxidative stress markers and the protein expression of the Nrf2-ARE pathway. Results. We found that SFN treatment could prolong micturition interval and increase bladder capacity and bladder compliance. However, the peak voiding pressure was lower than BOO group. SFN treatment can ameliorate the increase of collagen fibers induced by obstruction. SFN treatment also increased the activity of SOD, GSH-Px, and CAT compared to the other groups. The level of bladder cell apoptosis was decreased in BOO rats with SFN treatment. Moreover, SFN could reduce the ratio of Bax/Bcl-2 expression. Furthermore, SFN could activate the Nrf2 expression with elevation of its target antioxidant proteins. Conclusions. The sulforaphane-mediated decrease of oxidative stress and activation of the Nrf2-ARE pathway may ameliorate bladder dysfunction caused by bladder outlet obstruction.