Jinwook Kim

Human glans penis augmentation using injectable hyaluronic acid gel

Although augmentation phalloplasty is not an established procedure, some patients still need enlargement of their penis. Current penile augmentation is girth enhancement of penile body by dermofat graft. We performed this study to identify the efficacy and the patient’s satisfaction of human glans penis augmentation with injectable hyaluronic acid gel. In 100 patients of subjective small penis (Group I) and 87 patients of small glans after dermofat graft (Group II), 2u2009cm3 of hyaluronic acid gel was injected into the glans penis, subcutaneously. At 1u2009y after injection, changes of glandular diameter were measured by tapeline. Patient’s visual estimation of glandular size (Gr 0–4) and patient’s satisfaction (Grade (Gr) 0–4) were evaluated, respectively. Any adverse reactions were also evaluated. The mean age of patients was 42.2 (30–70)u2009y in Group I and 42.13 (28–61)u2009y in Group II. The maximal glandular circumference was significantly increased compared to basal circumference of 9.13±0.64u2009cm in Group I (P<0.01) and 9.49±1.05u2009cm in Group II (P<0.01) at 1u2009y after injection. Net increase of maximal glandular circumference after glans augmentation was 14.93±0.80u2009mm in Group I and 14.78±0.89u2009mm in Group II. In patient’s visual estimation, more than 50% of injected volume was maintained in 95% of Group 1 and 100% of Group II. The percentage of postoperative satisfaction (Gr 4, 5) was 77% in Group 1 and 69% in Group II. There was no abnormal reaction in area feeling, texture, and color. In most cases, initial discoloration by glandular swelling recovered to normal within 2 weeks. There were no signs of inflammation and no serious adverse reactions in all cases. These results suggest that injectable hyaluronic acid gel is a safe and effective material for augmentation of glans penis.

Effects of glans penis augmentation using hyaluronic acid gel for premature ejaculation.

The main limitation of medical treatment for premature ejaculation is recurrence after withdrawal of medication. We evaluated the effect of glans penis augmentation using injectable hyaluronic acid (HA) gel for the treatment of premature ejaculation via blocking accessibility of tactile stimuli to nerve receptors. In 139 patients of premature ejaculation, dorsal neurectomy (Group I, n=25), dorsal neurectomy with glandular augmentation (Group II, n=49) and glandular augmentation (Group III, n=65) were carried out, respectively. Two branches of dorsal nerve preserving that of midline were cut at 2u2009cm proximal to coronal sulcus. For glandular augmentation, 2u2009cc of HA was injected into the glans penis, subcutaneously. At 6 months after each procedure, changes of glandular circumference were measured by tapeline in Groups II and III. In each groups, ejaculation time, patients satisfaction and partners satisfaction were also assessed. There was no significant difference in preoperative ejaculation time among three groups. Preoperative ejaculation times were 89.2±40.29, 101.54±59.42 and 96.5±52.32u2009s in Groups I, II and III, respectively. Postoperative ejaculation times were significantly increased to 235.6±58.6, 324.24±107.58 and 281.9±93.2u2009s in Groups I, II and III, respectively (P<0.01). The percentage of postoperative satisfaction in both patient and his partner was 68% (17/25) and 44% (7/16) in Group I, 80% (39/49) and 66% (25/38) in Group II and 75% (49/65) and 62% (32/52) in Group III, respectively. Maximal glandular girth was significantly increased from 9.16±0.59 to 10.95±0.4u2009cm in Group II and 8.95±0.54 to 11.67±0.71u2009cm in Group III, respectively. These results suggest that glandular augmentation with injectable HA gel is a safe and effective modality to reduce sensory of glans penis. Long-term follow-up for residual volume and efficacy should be requested to establish its precise therapeutic potentials in premature ejaculation.

Bisphenol A inhibits penile erection via alteration of histology in the rabbit

Despite extensive research into the toxicity of bisphenol A (BPA), no report of its effect on erectile function exists. We performed this study to investigate the effect of BPA on erectile function. New Zealand white rabbits were treated intraperitoneally with 150u2005mg/kg of BPA every other day for 12 days (cumulative dose of 900u2005mg/kg). Four and 8 weeks after administration of BPA, the contractions and relaxation of cavernosal tissue strips were significantly suppressed in the BPA-treated animals compared to the control animals. Histologically, thickening of tunica albuginea, subtunical deposition of fat and decreased sinusoidal space with consequent increase of trabecular smooth muscle content were observed in the BPA-treated animals. These results suggest that xenoestrogen BPA may affect the erectile function through evident histological changes of the penis.

Long-term effects of glans penis augmentation using injectable hyaluronic acid gel for premature ejaculation

The authors created the glans penis augmentation by injectable hyaluronic acid gel and reported the 6-month result for premature ejaculation. In a total of 38 patients, long-term effects of 5 years were compared to those of 6 months in terms of residual volume of implants and efficacy on premature ejaculation. Maximal glandular circumference measured by tapeline significantly decreased by 15% (P<0.05) but mean patients visual estimation (Gr 0–Gr 4) did not decrease (3.60 vs 3.56, P>0.05). Compared to 6-month follow-up, intravaginal ejaculatory latency time and vibratory threshold decreased at 5 years (P<0.05), but still well increased considering those of preaugmentation. Hence, 76% of patients and 63% of partners were still satisfied. There was no serious adverse reaction. In the 5-year long-term follow-up of glans penis augmentation by filler, the implants were well maintained and effective for glans penis hypersensitivity in premature ejaculation patients.

Altered contractile response of penis under hypoxia with metabolic acidosis

Previous studies concerning ischemic priapism revealed that hypoxia alters the erectile and contractile responses of penis. But the effects of accompanying acidosis on those responses have not been fully evaluated or understood yet. We performed this study to elucidate the role of acidosis on the trabecular smooth muscle contractility like in ischemic priapism.Under the general anesthesia, 55 mature male cats were conditioned to systemic metabolic acidosis by hypoventilation by animal ventilator. The changes of intracavernous pressure (ICP) to erectogenic agents (acetylcholine, L-arginine, prostaglandin E1: PGE1), erectolytic agents (epinephrine, thromboxane A2; TXA2), K channel-related drugs (pinacidil, 4-aminopyridine, tetraethylammonium; TEA, glibenclamide) and calcium ionophore were monitored at Set 1 (PO2>60u2005mmHg,u2005pH>7.25), Set 2 (PO2<30u2005mmHg,u20057.25>pH>7.0), Set 3 (PO2<30u2005mmHg, pH<7.0), and Set 4 (PO2>60u2005mmHg,u2005pH<7.0) in vivo.At Set 1 and Set 2, epinephrine, TXA2, and ionomycin decreased the ICP by acetylcholine or PGE1 (n=9, P<0.01). The decrease of ICP was in order of epinephrine, TXA2 and ionomycin. Acidosis reduced the increase of ICP to acetylcholine or PGE1 (n=8, P<0.01), TXA2 or ionomycin did not affect ICP under severe acidosis but epinephrine decreased ICP even under severe acidosis (n=7, P<0.05). Pretreatment of potassium channel blockers did not suppress the increase of ICP by erectogenic agents under acidosis (n=6, P<0.05). Pinacidil did not affect ICP under acidosis (n=6, P<0.01).These results suggest that acidosis impairs the contractile response of cavernous smooth muscle to erectolytic agents. It may be the results of the interference by [H+] with the intra and extracellular mechanisms that regulate the homeostasis of [Ca2]. Conclusively, besides hypoxia, acidosis is another limiting factor of trabecular smooth muscle contractility like in ischemic priapism

Effect of TCDD on corpus cavernosum histology and smooth muscle physiology.

A polyhalogenated aromatic hydrocarbon, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is one of the most potent toxic environmental pollutants. Decreases in spermatogenesis and the ability to conceive and carry a pregnancy to term are the most sensitive signs of reproductive toxicity by TCDD in the mammal, but no report of its effect on the erectile function exists. We performed this study to investigate the effect of TCDD on the erectile function. New Zealand white rabbits were treated intraperitoneally with 1u2009μg/kg of TCDD. At 4 (Gr I) and 8 (Gr II) weeks after the administration of TCDD, cavernosal tissues were harvested for strip study in the organ bath and testes were prepared for histologic examination. Compared to the maximal amplitude of 17.1±4.12u2009mN in normal control (Gr III), the contractions to cumulative concentrations of NE (10−8–10−4u2009M) were significantly decreased to 6.57±1.34 and 5.45±1.01u2009mN in Groups I and II, respectively. Compared to 51.12±7.38% in Gr III, relaxation to cumulative concentration (10−8–10−4u2009M) of acetylcholine was significantly decreased to 17.25±2.17% (Gr I) and 9.73±2.17% (Gr II) at a concentration of 10−4u2009M, respectively. Compared to 75.12±13.18% in Gr III, relaxation to cumulative concentration (10−8–10−4u2009M) of SNP was significantly decreased to 31.49±7.89% (Gr I) and 18.54±6.12% (Gr II) at a concentration of 10−4u2009M, respectively. Histologically, intracavernosal fibrosis, abnormal subtunical deposition of fat and decreased sinusoidal space with consequent increase of trabecular smooth muscle contents were identified in TCDD-treated groups. In TCDD-treated animals, seminiferous tubules showed a decrease of germ cells with vacuolar degeneration and apoptotic cells. Spermatids were hardly seen. These results suggest that TCDD inhibits spermatogenesis and has a potential harmful effect on erectile function via changes of corpus cavernosum histology and smooth muscle physiology.

In vivo characterization of a prostate-specific antigen promoter-based suicide gene therapy for the treatment of benign prostatic hyperplasia.

To develop a novel gene therapeutic modality for the effective treatment of benign prostatic hyperplasia (BPH), we investigated the properties of toxic gene therapy utilizing prostate-specific antigen (PSA) promoter driving herpes simplex virus thymidine kinase (HSV-TK) suicide gene to induce highly selective molecular ablation of epithelial cells with minimal systemic toxicity in canine prostate. Replication-defective recombinant adenoviral vectors containing HSV-TK gene under transcriptional control of long PSA promoter (Ad-PSA-HSV-TK) were developed and delivered in an situ manner. Briefly, laparotomies were performed and Ad-PSA-HSV-TK (1 × 109u2009PFUs) was injected into the left lateral lobe of prostate only on days 1 and 7 with appropriate prodrug acyclovir in adult Beagle dogs. The therapeutic efficacy was evaluated on the 56th experimental day. The striking apoptosis of epithelial cells was identified in the treated left half of canine prostate on TUNEL assay. On immunohistochemical studies, there was markedly decreased number of PSA-secreting epithelial cells compared to control. Also significant atrophy of prostate glands, associated with dense infiltration of lymphocytes and plasma cells, was identified in the treated side. The PSA promoter-based suicide gene therapy induced highly selective and definite ablation of epithelial cells in benign canine prostate. Our novel approach could open opportunity of gene therapeutic modality for the treatment of clinical BPH.

The role of nitric oxide in vivo feline erection under hypoxia.

Previous in vitro studies have demonstrated that the cavernous relaxation under hypoxia does not involve the endothelium dependent mechanism. However, the mechanism of nitric oxide pathway under hypoxia are not fully evaluated or understood yet in vivo.The changes of intracavernous pressure to various vasoactive substances were monitored in 45 mature male cats in vivo under normoxia and hypoxia (pHu2005:u20057.03, PO2:u200525.52u2005mmHg, PCO2:u200584.66u2005mmHg). L-arginine and SNAP (s-nitroso-n-acetyl-penicillamine) produced cavernous relaxation under normoxia, but not under hypoxia (n=19, P<0.01). The L-arginine-induced relaxations were inhibited by L-NAME (Nω-nitro-1-arginine-methyl-ester) or methylene blue under normoxia (n=19, P<0.01). The cavernous relaxation was 58% suppressed under hypoxia compared to normoxia with 10−3u2005M/0.2u2005ml of acetylcholine (n=22, P<0.01). Moreover, L-NAME attenuated the acetylcholine-induced relaxation under normoxia, but not under hypoxia (n=22, P<0.05). Epinephrine suppressed the acetylcholine-induced relaxation in both conditions (n=10, P<0.01), while indomethacin significantly potentiated the acetylcholine-induced relaxation under normoxia compared to hypoxia (n=6, P<0.05). However, none of these substances responded in severe hypoxia (PO2<15u2005mmHg, n=3).These results suggest that erectile and contractile responses are attenuated under hypoxia. The endothelium derived relaxation via nitric oxide does not play a role in cavernous relaxation under definitive hypoxia with acidosis like in ischemic priapism (PO2<30u2005mmHg, pH<7.25).

Combination therapy of testosterone enanthate and tadalafil on PDE5 inhibitor non-reponders with severe and intermediate testosterone deficiency

Several studies have suggested combination therapy with testosterone supplementation in patients not responding to PDE5 inhibitors. Considering the pathophysiological basis for testosterone supplementation, the present study aims to identify whether combination therapy allows persistence of treatment effect after testosterone discontinuation. Furthermore, we evaluated whether the degree of testosterone depletion affects treatment outcome from combination therapy. Hypogonadal patients (<350u2009ngu2009dl−1) with erectile dysfunction who previously did not respond to PDE5 inhibitors were treated with testosterone enanthate injections and daily tadalafil. Patients were stratified into two groups depending on the level of testosterone deficiency, with 250u2009ngu2009dl−1 as a reference point. Following testosterone supplementation (12 weeks) and combination therapy (12 weeks), patients with severe testosterone deficiency showed higher IIEF (International Index of Erectile Function) erectile function (EF) domain score (16.47±4.019 vs 12.36±4.051, P=0.001) and more patients responding satisfactorily to treatment by general assessment (57.9 vs 16.0%, P=0.009), despite reaching similar levels of serum total testosterone (602±169u2009ngu2009dl−1 vs 698±165u2009ngu2009dl−1, P=0.057). Testosterone supplementation was then discontinued and patients were maintained only on daily tadalafil (12 weeks). The severe depletion group maintained higher EF domain scores than baseline (13.06±3.38 vs 7.20±2.24, P=0.0004), despite testosterone levels returning to baseline. The results suggest that combination therapy was more beneficial to patients with severe testosterone depletion, possibly by improving underlying pathophysiology.

Augmentation of glans penis using injectable hyaluronic acid gel

Recently, injectable hyaluronic acid gel has been widely used in soft-tissue augmentation. We performed this study to identify the feasibility of hyaluronic acid gel for the augmentation of the glans penis. In experiment I, 0.2u2009cm3 of hyaluronic acid gel (HA) was injected into the dermis of the glans penis of 25 New Zealand white rabbits via a 30u2009G needle. At 3, 7, 14, 30, and 90 days after injection, histological changes of glans were studied, respectively. In experiment II, 0.5u2009cm3 of HA was injected into the dermis of the glans penis of 14 Beagle dogs via a 27u2009G needle. At 6 months after injection, histological changes of the glans penis were also evaluated. At the time of autopsy, the lung, liver, and spleen were studied for systemic adverse reaction in each separate experiment.In experiment I, various sized cavities filled with amorphous basophilic materials were noted in the lamina propria and corpus spongiosum of the glans penis. All implants were positively stained on alcian blue. The intensity decreased in a time-dependent manner. Until 14 days, minimal inflammatory reactions were noted, but no signs of inflammation were identified at 90 days. With the gradual decrease of inflammation, fibrosis and deposition of collagen were noted. In experiment II, implants were well maintained at 6 months after injection in the lamina propria. Grade 1 of the inflammatory reaction was noted in one case. In both the experiments, all the specimens were free from any foreign body reaction and systemic adverse reactions.In conclusion, these results suggest that hyaluronic acid gel can be easily injected into the lamina propria of the glans penis and reside until 6 months. Injectable hyaluronic acid gel has a potential as a new bioimplant for the augmentation of the glans penis.