Seung Hwan Jeon

Comparison of Laparoscopic Radical Nephrectomy and Open Radical Nephrectomy for Pathologic Stage T1 and T2 Renal Cell Carcinoma With Clear Cell Histologic Features: A Multi-institutional Study

OBJECTIVES To assess the oncologic efficacy of laparoscopic radical nephrectomy (LRN) compared with open radical nephrectomy (ORN) in patients with clear cell renal cell carcinoma (RCC). METHODS We analyzed the data from 2561 patients who had undergone radical nephrectomy for RCC at 26 institutions in Korea from June 1998 to December 2007. The clinical data of 631 patients with clear cell RCC in the LRN group were compared with the clinical data of 924 patients in the ORN group. The patients with Stage pT3 or greater and those with lymph node or distant metastases were excluded to avoid a selection bias. To evaluate the technical adequacy and oncologic outcome, we compared the perioperative parameters and 5-year overall and disease-free survival rates. RESULTS The operative time was significantly longer in the LRN group than in the ORN group (219 ± 77 vs 182 ± 62 minutes, P < .001), but the estimated blood loss and complication rate were significantly lower in the LRN group than in the ORN group (P < .001 and P < .001, respectively). On univariate analysis, the LRN group had 5-year overall (93.5% vs 89.8%, P = .120) and recurrence-free (94.0% vs 92.8%, P = .082) survival rates equivalent to those of the ORN group. Even after adjusting for age, sex, T stage, tumor grade, and body mass index in a Cox proportional hazards model, statistically significant differences between the 2 groups were not found for the 5-year overall (hazard ratio 1.523, P = .157) and recurrence-free (hazard ratio 0.917, P = .773) survival rates. CONCLUSIONS Our large multi-institutional data have shown that LRN provides survival outcomes equivalent to those of ORN in patients with Stage pT1-T2 clear cell RCC.

Combination Therapy Using Human Adipose-derived Stem Cells on the Cavernous Nerve and Low-energy Shockwaves on the Corpus Cavernosum in a Rat Model of Post-prostatectomy Erectile Dysfunction.

OBJECTIVE To investigate combined therapeutic efficacy of human adipose-derived stem cells (h-ADSCs) application on injured cavernous nerve and low-energy shockwave therapy (SWT) on the corpus cavernosum in a rat model of post-prostatectomy erectile dysfunction. MATERIALS AND METHODS Rats were randomly divided into 5 groups: control, bilateral cavernous nerve injury (BCNI), adipose-derived stem cell (ADSC) (BCNI group with h-ADSCs on the cavernous nerve), SWT (BCNI group with low-energy SWT on the corpus cavernosum), and ADSC/SWT (BCNI group with a combination of h-ADSCs and low-energy SWT). After 4 weeks, erectile function was assessed using intracavernosal pressure. The cavernous nerves and penile tissue were evaluated through immunostaining, Western blotting, and a cyclic guanosine monophosphate assay. RESULTS ADSC/SWT significantly improved intracavernosal pressure compared to the other experimental group. ADSC had significantly increased β-III tubulin expression of the cavernous nerve, and SWT had a markedly enhanced vascular endothelial growth factor expression in corpus cavernosum. The ADSC/SWT group had a significantly increased in alpha smooth muscle actin content (P < .05), neural nitric oxide synthase (nNOS) of the dorsal penile nerve (P < .05), endothelial nitric oxide synthase (eNOS) protein expression (P < .05), and cyclic guanosine monophosphate level (P < .05) compared to the ADSC or SWT alone group. In addition, ADSC/SWT reduces the apoptotic index in the corpus cavernosum. CONCLUSION In this study, h-ADSCs showed an effect on the recovery of injured cavernous nerve and low-energy SWT improved angiogenesis in the corpus cavernosum. The h-ADSCs combined with low-energy SWT showed beneficial effect on the recovery of erectile function in a rat model of postprostatectomy erectile dysfunction.

Comparison Between Subcutaneous Injection of Basic Fibroblast Growth Factor-Hydrogel and Intracavernous Injection of Adipose-derived Stem Cells in a Rat Model of Cavernous Nerve Injury

OBJECTIVE To compare the effects of subcutaneous penile injection of basic fibroblast growth factor (bFGF)-hydrogel and intracavernous injection of human adipose-derived stem cells (h-ADSCs) on improving erectile function in a rat model of cavernous nerve injury. MATERIALS AND METHODS Adult male Sprague-Dawley rats were randomly divided into 5 groups (n = 10 per group): age-matched control (normal group), bilateral cavernous nerve injury (BCNI group), penile subcutaneous injection of hydrogel after BCNI (hydrogel group), penile subcutaneous injection of bFGF-hydrogel after BCNI (bFGF-hydrogel group) and intracavernous injection of h-ADSCs after BCNI (ADSC group). Four weeks after the treatment, all rats underwent an erectile function test. Then, penile tissue was harvested for immunohistological analysis of bFGF, phalloidin, and cluster of differentiation (CD) 31. The cyclic guanosine monophosphate (cGMP) level of the corpus cavernosum was quantified by cGMP assay. RESULTS From the functional test and immunohistological result, we observed that bFGF-hydrogel and h-ADSCs injection significantly elevated intracavernous pressure. The evaluation of filamentous actin content, CD31 expression, and cGMP concentration in the corpus cavernosum were meaningfully increased in the bFGF-hydrogel and ADSC groups compared with BCNI group. The bFGF released from bFGF-hydrogel prevented smooth muscle atrophy. Moreover, bFGF expression was significantly increased in bFGF-hydrogel group. CONCLUSION The subcutaneous injection of bFGF-hydrogel prevented smooth muscle atrophy, increased the intracavernous pressure, and improved erectile function like an intracavernous injection of h-ADSCs.

The Effect of PnTx2-6 Protein From Phoneutria nigriventer Spider Toxin on Improvement of Erectile Dysfunction in a Rat Model of Cavernous Nerve Injury

OBJECTIVE To explore the therapeutic potential of PnTx2-6 injected 3 times a week for 4 weeks into the intracavernosal tissue in a rat model of bilateral cavernous nerve crush injury (BCNI). METHODS Eight-week-old male Sprague-Dawley rats were randomly divided into the following 6 groups (n = 5 per group): age-matched control (normal group), BCNI (injury group), post-BCNI phosphate-buffered saline injection (PBS group), post-BCNI Sf9 cell-lysate injection (N/C group), post-BCNI injection of cell lysate from S9 cells infected with wild-type recombinant baculovirus (W/T group), and post-BCNI injection of cell lysate from S9 cells infected with recombinant baculovirus containing PnTx2-6 (PnTx2-6 group). Injections were delivered 3 times a week for 4 weeks. After 4 weeks, intracavernosal pressure-to-mean arterial pressure ratio, smooth muscle and collagen content via the Masson trichrome staining, levels of neural nitric oxide synthase, phosphoendothelial nitric oxide synthase, and cyclic guanosine monophosphate were all measured. RESULTS The PnTx2-6 group showed significantly higher intracavernosal pressure-to-mean arterial pressure ratio (P <.05), smooth muscle-to-collagen ratio (P <.01), expression levels of neural nitric oxide synthase, phosphoendothelial nitric oxide synthase (P <.05), and cyclic guanosine monophosphate (P <.05) than all other experimental groups. CONCLUSION We conclude that PnTx2-6 improved erectile function and prevented muscle atrophy in a rat model of BCNI via increased synthesis of nitric oxide and cyclic guanosine monophosphate.

Bladder reconstruction using stem cells seeded on multilayered scaffolds in a mucosa preserving partial cystectomy model

Recently, studies have focused more towards using biocompatible scaffolds and stem cells to augment or replace the abnormal bladder. But, due to the lack of biomaterials with appropriate thickness as a suitable scaffold for smooth muscle regeneration, several structural, mechanical, and biocompatibility problems are encountered. Therefore, we aimed to demonstrate whether human muscle-derived stem cells (h-MDSCs) seeded on multilayered polycaprolactone (PCL) nanofiber is an appropriate scaffold for bladder smooth muscle regeneration. h-MDSCs were seeded on a multilayered PCL/collagen nanofiber sheet and implanted in the bladder of a mucosa preserving partial cystectomy rat. From our findings, h-MDSCs seeded on multilayered PCL showed efficient cell seeding and proliferation. In addition, the histological and immunohistochemical analysis showed cell survival in between the multilayered nanofiber sheet, which led to smooth muscle cell regeneration with improved pro-angiogenesis in the regenerated region of the bladder. Therefore, h-MDSCs seeded nanofibers could be a promising tool in treating neurogenic bladder and related diseases.

Visualization of prostatic nerves by polarization-sensitive optical coherence tomography

We demonstrate that polarization-sensitive optical coherence tomography (PS-OCT) can identify the cavernous nerve in the human and rat prostate ex vivo based on its birefringence. PS-OCT may be useful for nerve preservation during radical prostatectomy.

Effects of Next-Generation Low-Energy Extracorporeal Shockwave Therapy on Erectile Dysfunction in an Animal Model of Diabetes

Purpose Gene therapy, stem cell therapy, and low-energy extracorporeal shockwave therapy (ESWT) have been investigated as treatments for refractory erectile dysfunction (ED), but inconclusive evidence has been obtained. We investigated the effect of a next-generation electromagnetic cylinder ESWT device on an animal model of ED. Materials and Methods Diabetes mellitus (DM)-induced rats were divided into 3 groups: group 1, control; group 2, DM; and group 3, DM+ESWT. Rats were treated with ESWT 3 times a week for 2 weeks. After the treatment course, intracavernous pressure was measured and the corpus cavernosum and cavernous nerve were evaluated. Results In the DM group, all parameters predicted to be significantly lower in the ED model had statistically significantly decreased (p<0.01). As a measurement of erectile function, intracavernous pressure was evaluated. The DM+ESWT group exhibited significantly restored erectile function compared to the DM group (p<0.05). Moreover, ESWT treatment restored smooth muscle content, as assessed by Massons trichrome staining (p<0.05). Finally, corporal tissue and the dorsal nerve were evaluated by immunohistochemistry, Western blotting, and ELISA. After ESWT treatment, vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), platelet endothelial cell adhesion molecule-1, cyclic guanosine monophosphate, and neuronal nitric oxide synthase (nNOS) expression levels were restored to levels in the DM group (p<0.05). Conclusions Electromagnetic cylinder ESWT device resulted in increased VEGF, nNOS, and eNOS expression; reduced smooth muscle atrophy; and increased endothelial cell regeneration in a DM-associated ED model. Our data suggest that safe and effective application could be possible in future clinical studies.

Visualization of prostatic nerves using polarization-sensitive optical coherence tomography

We demonstrate that polarization-sensitive optical coherence tomography (PS-OCT) can identify the cavernous nerve in the human and rat prostate ex vivo based on its birefringence. PS-OCT may be useful for nerve preservation during radical prostatectomy.

Lycium chinense Mill improves hypogonadism via anti-oxidative stress and anti-apoptotic effect in old aged rat model

Abstract Purpose: To evaluate the pharmacological effects of goji berry (Lycium chinense P. Mill) in an animal model of late-onset hypogonadism (LOH). Materials and methods: Thirty 18-month-old male Sprague–Dawley (SD) rats were used as the LOH aged rat model. Rats were divided into five groups: a control group (n = 6), low concentration goji berry extract group (150 mg/kg/day) (n = 6), high concentration goji berry extract group (300 mg/kg/day) (n = 6), low concentration goji berry complex extract group (150 mg/kg/day) (n = 6), and high goji berry complex concentration extract group (300 mg/kg/day) (n = 6). After six weeks of treatment, sperm counts and motility, serum testosterone level, androgen receptor (AR) expression, oxidative stress marker, and apoptotic factors were examined. Results: Goji berry extracts increased testosterone level to 2.07 ± 0.06 pmol/L in the goji berry 150 mg/kg group, 2.39 ± 0.08 pmol/L in the goji berry 300 mg/kg group, 2.97 ± 0.03 pmol/L in the goji berry complex 150 mg/kg group, and 3.34 ± 0.04 pmol/L in the goji berry complex 300 mg/kg group compared to 1.86 ± 0.03 pmol/L in the control group, respectively (p < .05). AR expressions were increased in testis tissue significantly but were not significant in prostate tissue. Conclusions: Goji berry might improve LOH by reversing testicular dysfunction via an anti-oxidative stress mechanism without inducing prostate disease.

Efficient Promotion of Autophagy and Angiogenesis Using Mesenchymal Stem Cell Therapy Enhanced by the Low-Energy Shock Waves in the Treatment of Erectile Dysfunction

Background Mesenchymal stem cell therapy (MSCT) and defocused low-energy shock wave therapy (ESWT) has been shown to ameliorate erectile dysfunction (ED). However, the interactions and effects of action between MSCT and ESWT remain poorly understood. In this study, we investigated the mechanisms of combination therapy with MSCT and ESWT in a rat model of diabetic ED. Materials and Methods Eight-week-old male Sprague-Dawley rats were randomly divided into 2 parts. Diabetic rats induced by streptozotocin (65 mg/kg) were randomly divided into 4 groups: (1) DM control group, (2) DM + ESWT group, (3) DM + MSCT group, and (4) DM + ESWT + MSCT group. The sham group was a normal control group (without streptozotocin). MSCT and (or) ESWT were, respectively, administered to each group according to the proposal for 8 weeks. Immediately after recording of intracavernous pressure (ICP), the penis was then harvested for histologic analysis, ELISA, and Western blotting. Results The ratio of ICP/MAP was significantly higher in the DM + ESWT + MSCT group than in ESWT or MSCT treated group (P < 0.05). Also, the treatment stimulated angiogenesis and vasodilatation in the corpus cavernosum (P < 0.05). ESWT increased the quantity of MSCs in the corpus cavernosum and also induced MSCs to express more VEGF in vitro and vivo (P < 0.05) which activated the PI3K/AKT/mTOR and NO/cGMP signaling pathways in the corpus cavernosum. The combination approach stimulated autophagy and decreased apoptosis in the corpus cavernosum. NGF and BDNF expressions were higher in the DM + ESWT + MSCT group than in the DM control group (P < 0.01). Furthermore, the treatment promoted the MSC recruitment by inducing penile tissues to express more PECAM and SDF-1. Conclusions Combination of LI-ESWT and MSCT can get a better result than a single treatment by expressing more VEGF which can take part in autophagy by triggering the PI3K/AKT/mTOR signaling pathway. This cooperative therapy would provide a new research direction in ED treatment for the future.