The Synergism of Penile Venous Surgery and Oral Sildenafil in Treating Patients with Erectile Dysfunction
Hsien-Sheng Wen,* Cheng-Hsing Hsieh,* Geng-Long Hsu+, Yu-Chi Kao,* Pei-Ying Ling,* Hsiu-Mei Huang,* Chii-Jye Wang,* and E. Ferdinand Einhorn*
*Microsurgical Potency Reconstruction and Research Center, Taiwan Adventist Hospital, Taipei Medical University, Taipei, Taiwan, and +Foundation for Microsurgical Potency Research, Texas, USA.
A possible synergistic effect between penile venous surgery and oral sildenafil was inadvertently found in treating patients with erectile dysfunction in our clinic. We therefore sought to elucidate the possible synergic effect between venous surgery and sildenafil through studying patients who were non-responders preoperatively. From July 1998 to July 2003, 128 patients were diagnosed with veno-occlusive dysfunction. Subsequently, 65 of them underwent penile venous surgery and were assigned to the surgical treatment group. The remaining 63 men were assigned to the control group, and were subject to a simple re-exposure of oral sildenafil. All patients were evaluated with the international index of erectile function (IIEF-5) scoring. Sildenafil (12.5–100 mg) was prescribed postoperatively to all surgical patients as venous surgery alone was unsatisfactory and similarly, 100mg preparation was prescribed for patients in the control group. The IIEF-5 scoring in the control group changed from a preoperative mean IIEF-5 score of 9.4 ± 3.9 to 10.7 ± 3.5 postoperatively. In surgical patients, however, the mean preoperative IIEF-5 score of 9.2 ± 5.0, which increased to 15.1 ± 5.0 (p < 0.001) postoperatively, further increased to 20.1 ± 5.4 (p < 0.0001) after the addition of sildenafil. Although there was no significant difference between the two groups characteristics, there was a statistically significant difference between treatment results (p < 0.001). Overall, 61 men (93.8%) reported a positive response to sildenafil after venous stripping surgery. In contrast, only eight patients (12.7%) felt a beneficial response in the control group (p < 0.001). Forty-one of 65 patients had scores of ≧22, and 19 of these had a score of 25. No response was found in three (4.6%), and a decrease of 7 was seen in one (1.5%). In summary, patients in whom sildenafil was not effective preoperatively can become excellent responders after careful penile venous surgery. It appears that together, oral sildenafil and penile venous surgery may provide an encouraging solution to impotent patients with veno-occlusive dysfunction who are non-responders to sildenafil.
男性學論文獎基礎組
Human Reproduction Vol.21, No.1 pp. 138–144, 2006
Decreased mRNA Transcripts of M-phase Promoting Factor and Its Regulators in the Testes of Infertile Men
Yung Ming Lin1, Yen Ni Teng2, Chia Ling Chung3, Wan Ching Tsai1, Ying Hung Lin4,Johnny Shinn Nan Lin1 and Pao Lin Kuo3 Departments of 1Urology, 3Obstetrics & Gynecology, and 4Institute of Basic Medical Science, National Cheng Kung University, College of Medicine, Tainan, and 2Department of Early Childhood Education and Nursery, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
Background: M-phase promoting factor (MPF), which is comprised of Cyclin B and a catalytic subunit, Cdc2, is a key enzyme required for cells to enter M phase in both mitosis and meiosis. MPF activity is controlled by the stimulatory dephosphorylation of the Cdc25 family and the inhibitory phosphorylation of Wee1. We determined the levels of mRNA transcripts of MPF and its regulators in the testes of infertile men, and evaluated the relationship between the transcript levels and patients’ testicular phenotypes and sperm retrieval results.
Methods and Results: The mRNA transcript levels of CDC2, CCNB1, CCNB2, CDC25A, CDC25B, CDC25C and WEE1 in the testes of 37 azoospermic patients were examined by quantitative real-time polymerase chain reaction. Significant decreases in CDC2, CCNB1, CCNB2, CDC25A, CDC25C and WEE1 mRNA transcript levels were detected in patients with spermatogenic failure. CDC2 mRNA transcript levels correlated significantly with those of CCNB1 and CCNB2 mRNA. Significantly higher CDC2, CCNB1, CCNB2, CDC25C and WEE1 mRNA transcript levels were detected in 18 patients with successful sperm retrieval than in 11 patients with failed sperm retrieval.
Conclusions: We suggest that the decreased mRNA transcripts of MPF and its regulators play important roles in human spermatogenesis.
輝瑞論文獎臨床組
Journal of Andrology 2006; 27:700-706
Insufficient Response to Venous Stripping Surgery: Is the Penile Vein Recurrent or Residual?
Geng-Long Hsu,* Heng-Shuen Chen, + Cheng-Hsing Hsieh,* Pei-Ling Ling,* Hsien-Sheng Wen,* Li-Jen Liu,* Cheng-Wen Chen,* AND Ming-Wei Liu* From the *Microsurgical Potency Reconstruction and Research Center, Taiwan Adventist Hospital; and the +Department of Medical Informatics and Family Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.
There is currently controversy on whether the insufficient response to penile venous surgery done in an attempt to restore erectile function is due to recurrent or residual veins. In order to elucidate this issue, we report a study on those patients who failed to respond to the first venous surgery and subsequently underwent or declined a second operation. From July 1996 to July 2003, a total of 83 patients, aged 25 to 83, who were dissatisfied with their first venous surgery and were later diagnosed with a persistent veno-occlusive dysfunction via our dual cavernosography, were recruited into our study. Subsequently, 45 men underwent penile venous stripping surgery for a second time and were assigned to the surgery group, whereas the remaining 38 men were subject to followup and routine management and were assigned to the control group. All were evaluated with the abridged 5-item version of the international index of erectile function (IIEF-5) every 6 months for 1 to 5 years and cavernosogram, if necessary. In the surgery group their preoperative IIEF-5 score was 10.1 ± 3.7, which increased to 17.1 ± 3.2 (P<.001) after the first surgery and further increased to 20.7 ± 3.1 (P<.001) after a second venous stripping of the cavernosal vein that was consistently demonstrated on the cavernosogram. Overall, 41 men (91.1%) reported a positive response to further venous surgery, with more satisfactory coitus, after the residual veins were stripped thoroughly, although eventually 4, 3, and 3 men required additional oral sildenafil, penile implant, and intracavernosal injection, respectively. The follow-up period ranged from 12 months to 72 months, with an average of 37.0 ± 11.5 months. In the control group, however, their corresponding IIEF-5 score changed from 17.4 ± 2.9 to 16.9 ± 3.2 (P>.05). Finally, 11, 7, and 8 men required additional oral sildenafil, penile implant, and intracavernosal injection, respectively. Although there was no statistical significance between the 2 groups in the first postoperative IIEF-5 scores, there was a significant difference in their IIEF-5 after further venous surgery. In this study, we propose that the clinical relapse of erectile dysfunction is a result of ‘‘residual’’ veins rather than ‘‘recurrent’’ ones.
輝瑞論文獎基礎組
Human Reproduction Vol.21, No.9 pp. 2346–2352, 2006
Association of Spermatogenic Failure with Decreased CDC25A Expression in Infertile Men
Yu Sheng Cheng1,2, Pao Lin Kuo3, Yen Ni Teng4, Ting Yi Kuo1, Chia Ling Chung3, Ying Hung Lin5, Rui Wen Liao3, Johnny Shinn Nan Lin1 and Yung Ming Lin1 1Department of Urology, 2Institute of Clinical Medicine, 3Department of Obstetrics & Gynecology, National Cheng Kung University, College of Medicine, 4Department of Early Childhood Education and Nursery, Chia Nan University of Pharmacy and Science and 5Institute of Basic Medical Science, National Cheng Kung University, College of Medicine, Tainan, Taiwan.
Background: DAZ gene family is crucial for human spermatogenesis that requires the precise co-ordination of cell cycle events. CDC25A is recognized as the downstream substrate of DAZ gene family and is thought to function on the M-phase regulation of cell cycles. We investigated the expression profiles of CDC25A in the testes of infertile men and evaluated the relationship between CDC25A levels and testicular phenotype, clinical hormonal parameters and sperm retrieval results.
Methods: The protein and mRNA transcript levels of CDC25A in the testes of 40 azoospermic men were determined by immunohistochemistry and quantitative real-time-PCR. CDC25A in human spermatozoa was investigated by western blotting and immunofluorescence staining.
Results: The CDC25A protein was expressed mainly in spermatocyte, spermatid and spermatozoa. CDC25A transcript levels were significantly decreased (P = 0.0009) in patients with spermatogenic failure, especially in men with meiotic arrest and Sertoli cell-only syndrome. Significantly higher CDC25A transcript levels were detected in patients with successful sperm retrieval than in patients with failed sperm retrieval (P = 0.005).
Conclusions: Decreased CDC25A is associated with spermatogenic failure and failed sperm retrieval in infertile men. Further studies are necessary to explore the functional roles of CDC25A in human spermatozoa.