【作者】 李兴华；

【导师】 郑少斌；

【作者基本信息】 南方医科大学 ， 泌尿外科， 2011， 博士

【摘要】 背景与目的普遍认为早泄(premature ejaculation, PE)是一种比勃起功能障碍更常见的疾病,一些研究表明接近50%的成年男性患有早泄,还有一些学者的研究结果是早泄的发病率最高可达70%。早泄的机理并没有完全被弄清,同样针对早泄的合适的治疗方法也不多。早泄的众多的病因中,只有一小部分人的早泄病因是清楚的,是因为某些器质性病变例如多发性硬化而导致的。一些学者运用了阴茎生物震感阈测量仪和阴茎体部感觉测量的手段,对阴茎的超敏感性以及神经反射的兴奋性过强展开了研究。他们认为阴茎的超敏感性以及神经反射的兴奋性过强是导致早泄的原因。尽管早泄有很多的定义,但是还没有一种能被广泛地接受。通常来说,早泄是以男性射精潜伏期时间和女性性高潮的频率来衡量的。一个成年男性如果不能很好的延缓射精,在他的性活动中,他的性伴侣的满意率如果达不到50%,就可以理解为早泄。阴道内射精潜伏期小于2分钟常常被定义为早泄。美国泌尿外科协会推荐的早泄的定义是男性阴茎还没有插入女性阴道或者阴茎插入阴道但是比预期提前射精,从而导致性伴侣或者配偶苦恼。以前对早泄的研究停留在患者的主观评价,这样计算出的发病率会大大降低。不同的调查研究应用不同的诊断标准,得出的患病率的结果也不一样。阴道内射精潜伏期时间的定义是：从阴茎插入阴道到射精的时间。2008年国际性医学学会(International Society for SexualMed icine, ISSM)将阴道内射精潜伏期的时间1分钟设定为早泄与否的分界点。90%的原发性早泄的患者抱怨,阴茎插入阴道后不到1分钟就射精了。相比较正常没有早泄的人来说,从阴茎插入阴道到射精的时间平均为5.4分钟。临床实践中,常采用患者自己秒表测量或者自己估计阴道内射精潜伏期时间的办法来诊断是否患有早泄。阴茎背神经是阴部神经的感觉分支,传导由感觉神经感受器感受到的神经冲动。阴茎背神经游离的神经末梢位于阴茎头、阴茎以及阴囊的皮肤等处。射精所需要的神经冲动主要是靠阴茎背神经来传入完成的。射精主要是由交感神经控制。阴部神经分布于周围的的横纹肌,在射精时起到重要的作用。早泄患者近年来就诊者日益增多,现约有1/3的已婚男性存在着不同程度的早泄。尽管毫无疑问,药物治疗(例如氯丙咪嗪、5—羟色胺再吸收抑制剂)早泄的有效率很高,但是会伴随着令人讨厌的并发症,例如出现困倦、打哈欠、口干、恶心、头晕、头痛等。患者常常因为这些情况而停药。所以药物治疗常常因为它的并发症而受到限制。行为治疗长期来看,可能很有效,但是很难长期坚持。早泄分为原发性早泄和继发性早泄。原发性早泄(primary premature ejaculation):是指自从首次性生活开始即出现阴道内射精潜伏期时间过短。原发性早泄的手术治疗(改良式阴茎背神经切除术)在国内已经开展了很多年,但是很多的泌尿外科以及男科医生担心术后并发症,尤其是勃起功能障碍,所以致使该手术开展的并不广泛。研究目的：1.明确正常人群阴茎背神经数量和原发性早泄患者的阴茎背神经数量,并做对比。如果原发性早泄的患者阴茎背神经数量明显高于正常人群,说明阴茎背神经数量过多,可能是导致原发性早泄的病因。2.确定阴茎背神经与阴茎海绵体勃起的关系。3.确定阴茎背神经缺失不会对阴茎海绵体细胞产生影响,从而不会导致勃起功能障碍。4.消除临床上泌尿外科和男科医生对阴茎背神经切除过多可能会导致阴茎勃起功能障碍的恐惧,有利于阴茎背神经切除术更广泛的开展。研究内容共分为四部分：第一部分人体阴茎背神经解剖学研究；第二部分白兔阴茎背神经缺如模型建立及术后阴茎勃起功能观察；第三部分雄兔双侧阴茎背神经和/或海绵体神经离断后海绵体组织细胞凋亡的研究；第四部分原发性早泄手术方法及相关并发症。第一部分人体阴茎背神经解剖学研究1.目的研究正常人的阴茎背神经数目、走行和分布。该研究在阴茎背神经选择性切断术治疗原发性早泄手术中具有重要的应用价值。为原发性早泄的手术提供解剖学理论依据。2.材料和方法1)对47具成年男性尸体的阴茎解剖。为了显示清晰,将阴茎皮肤、背浅筋膜及阴茎背深筋膜游离后切除,.暴露出阴茎深筋膜与白膜之间的阴茎背神经及血管。仔细游离出阴茎背神经以及阴茎背深静脉和阴茎背动脉。对其进行观察和计数,仔细观察阴茎背神经的走形,分布及数量。2)利用手术显微镜,HE染色和神经性一氧化氮合成酶(nNOS)免疫组织化学染色,观察3具完整成年男性尸阴茎海绵体神经的走向和分布,目的是了解3具完整男尸阴茎海绵体神经与阴茎背神经的解剖学关系。3.结果1)47具尸体阴茎背神经数量总结如下：7支1例；6支2例；5支7例；4支9例；3支18例；2支10例。其中各支大多平行分布,仅少量尸体中各分支间有小神经分支相连。一些神经发出弓状小分支分布于阴茎侧面。少数尸体标本的阴茎腹侧面发现阴茎背神经的细小分支。有的细小分支穿入阴茎海绵体及尿道海绵体。同时可见到有的细小分支通过冠状沟穿入龟头。大多数尸体有一支阴茎背神经与阴茎背深静脉伴行。2)阴茎海绵体神经穿过尿生殖膈下筋膜后,走行于阴茎背神经、海绵体动静脉的下方,发出1支分支融合入背神经,其余2-3支海绵体神经分支分布于阴茎海绵体脚部。阴茎海绵体神经组织nNOS免疫组织化学染色存在棕黄色nNOS颗粒。阴茎背神经远端同样存在棕黄色nNOS颗粒。4.结论1) 47具尸体阴茎背神经数量平均值为3.49±1.23支。2)阴茎海绵体神经有1个分支加入阴茎背神经与之相融合。第二部分白兔阴茎背神经缺如模型建立及术后阴茎勃起功能观察1.目的明确阴茎背神经切除过多甚至全部切除后,是否会出现阴茎勃起功能障碍。从动物实验的角度论证改良式阴茎背神经切断术治疗原发性早泄的可行性。2.材料和方法1)切断20只雄性白兔的全部阴茎背神经。2)观察术后1个月是否还能阴茎勃起并进行交配。3)切除的组织嗜银染色以确认是神经组织。3.结果20只雄兔阴茎背神经全部切除术后1周内2雄兔只死亡,其余18只均可以阴茎勃起,并能进行交配。4.结论雄兔阴茎背神经切除过多,不会导致勃起功能障碍。第三部分雄兔双侧阴茎背神经和/或海绵体神经离断后海绵体组织细胞凋亡的研究1.目的观察双侧阴茎背神经、海绵体神经损伤,以及联合神经损伤后阴茎海绵体组织细胞凋亡表达。确定阴茎背神经即使全部切断也不会引起阴茎海绵体组织细胞的变化。间接说明阴茎背神经全部切除不会导致勃起功能障碍。2.材料和方法将25只雄兔随机分为阴茎背神经离断组(A组)、海绵体神经离断组(B组)、阴茎背神经和海绵体神经联合离断组(A+B组)、手术对照组(C组)和非手术对照组(D组)。术后第2天通过TUNEL法进行凋亡细胞检测。3.结果阴茎背神经离断组(A组)分别与双侧海绵体神经离断组(B组)(P<0.001)及联合离断组(A+B)之间的凋亡率(P<0.001)均有显著差异,与手术对照组(C组)(P=0.054)和非手术对照组(D组)(P=0.233)之间的差异无显著性。A+B组与C组和D组均有显著性差异(P<0.001),B组与C组和D组均有显著性差异(P<0.001)。4.结论海绵体神经损伤可引起白兔阴茎海绵体平滑肌的凋亡；阴茎背神经损伤对阴茎组织细胞凋亡无明显影响；联合损伤对海绵体平滑肌细胞凋亡的影响同单纯海绵体神经损伤。第四部分原发性早泄手术方法及相关并发症1.目的详细介绍该改良式阴茎背神经切除术的手术适应症、具体手术方法以及手术的注意事项。以及把改良式阴茎背神经切断术的经验与大家分享。2.材料和方法1)回顾广州、乐清、哈尔滨三家三级医院在2007年9月到2011年2月期间对338例原发性早泄的患者实行的改良式阴茎背神经切断手术。对术后的疗效,并发症给予客观的评价。2)疗效判定标准于手术前和术后3月后分别记录手术前后阴道内IELT0术后IELT记录是取最近4次从插入至性交结束时间的平均值,2 min<IELT术后≤5min为好转,IELT术后≥5min为显效,IELT术后≤2min为无效。同时记录治疗前后患者性生活满意度评分(国际勃起功能指数评分IIEF6、7、8项0-15分),配偶性生活满意度评分(国际勃起功能指数评分IIEF10、13、14项0-15分)。比较上述指标的变化,同时观察性生活不射精与勃起功能障碍(ED)等并发症的发生率。3.结果1)随访2年以上的123例患者,手术中发现患者阴茎背神经的数目为4支5例,5支9例,6支16例,7支26例,8支26例,9支25例,10支9例,11支4例,12支3例。平均7.69±1.77支。2)338例原发性早泄患者,随访2年以上的有123例患者。这123例患者,阴道内射精潜伏期时间(IELT)大部分有不同程度的延长,其中显效57例,好转48例,无效18例,显效率46.30%,总有效率85.4%。术后射精潜伏期没有明显变化18例,阴茎麻木感2例,勃起功能障碍1例,阴茎血肿1例,切口感染2例。3)统计学分析术前与术后阴道内射精潜伏期时间对比有显著意义(t=19.630,P<0.001),患者性生活满意度评分术前术后对比有显著意义(t=39.527,P<0.001),配偶性生活满意度评分术前术后对比有显著意义(t=38.738,P<0.001)。4.结论改良式阴茎背神经切断术治疗原发性早泄安全、有效。全文结论1)人体阴茎背神经在阴茎深筋膜和白膜之间走形,尸体阴茎解剖证实阴茎背神经数量为3.49±1.23支,而不是传统上人为的2支。阴茎背神经与海绵体神经存在小分支融合。阴茎背神经的解剖学研究是改良式阴茎背神经切断术的理论基础。2)雄性白兔阴茎背神经全部切除术后不会出现阴茎勃起功能障碍,能够正常交配以及射精。间接说明人体阴茎背神经即使全部切除也可能不会导致阴茎勃起功能障碍。消除了临床泌尿外科和男科医生对改良式阴茎背神经切断术可能会出现阴茎勃起功能障碍的并发症的担忧。3)雄性白兔阴茎背神经全部切除术后阴茎海绵体细胞组织无明显凋亡,而海绵体神经切除以及海绵体神经联合阴茎背神经切除的雄兔会出现阴茎海绵体细胞组织的凋亡。说明阴茎背神经与海绵体细胞无明显的关系,间接说明阴茎背神经切除不会导致阴茎勃起功能障碍。4)动物实验研究说明阴茎背神经切断术是安全的,不会导致勃起功能障碍,也不会导致不射精等情况。基于这个理论,我们为338例原发性早泄的患者实性改良式阴茎背神经切断术并总结了手术的适应症、并发症、手术方法以及注意事项。临床对原发性早泄的患者实行的改良式阴茎背神经切断术是有效、安全的。更多还原

【Abstract】 Background and objectives:It is generally accepted that premature ejaculation (PE) is a more common problem than erectile dysfunction. Several surveys demonstrated that approximately 50% adults have suffered from PE. Other researches also revealed very high prevalence of PE with the highest being 70%. It is similarly poorly understood and inadequately treated. The cause for PE is largely unknown. In only a small percentage of patients with PE can an organic cause be found (such as multiple sclerosis). Penile hypersensitivity and reflex hyper-excitability have been investigated in different studies by the penile Bio-Thesiometer or genital somato- sensory. They demonstrated that penile hypersensitivity and reflex hyper-excitability cause the PE happened. Although there are several definitions, there has not been one that has been universally accepted. Conventionally, PE is assessed in terms of latency of ejaculation in male and frequency of orgasm in female. If a man is unable to delay ejaculation until his partner sexually satisfied in at least 50% of their sexual encounters is considered PE too. It is usually defined as intravaginal latency of less than 2 minutes. The American Urology Association (AUA) recommended that PE should be identified as ejaculation before expectation, before or after intercourse, as well as the resulting partner or couple distress. Previous studies of PE mainly depended on subjective self-assessment, which may lead to underestimate of prevalence. The differences of PE’s prevalence maybe due to different diagnosticcriteria used in different investigations.Intravaginal ejaculatory latency time (IELT) is defined as the time between vaginal intromission and ejaculation. In 2008, International Society for Sexual Medicine (ISSM) for the Definition of Premature Ejaculation determined that 1 min was an appropriate cutoff point to diagnose premature ejaculation, as 90% of men complaining of primary premature ejaculation ejaculated within 1 min after penetration as compared with a median of 5.4 min in men not suffering from premature ejaculation. Stopwatch measure or estimated IELT correlate reasonably well, providing support for the use of self-estimation of IELT for the diagnosis of premature ejaculation in clinical practice.The dorsal nerve of the penis, a sensory branch of the pudendal nerve, carries impulses from sensory receptors and free nerve endings located in the glans, the penile skin and the scrotum to the upper sacral and lower lumbar segment of the spinal cord. This nerve has been reported to be the major contributor to the sensory input necessary for ejaculation, as its bilateral transsection prevents ejaculation. Ejaculation is mostly under sympathetic control, mainly throughα1-receptor activation. The pudendal nerve innervates all the striated muscles that play a role in the expulsive phase of ejaculation.The patients with PE are increasing in recent years, and about 1/3 of married men have different degrees of premature ejaculation now. Although there is no doubt that daily drug therapies (Such SSRIs, clomipramine) are highly effective in the treatment of PE, the accompanying nuisance side effects (such as sleepiness, yawning, dry mouth, nausea, headaches and dizziness). These annoying problems may lead to treatment discontinuations. So drug therapies is limited by its side effects. Behavioural techniques is likely to be more effective in the long-term treatment. But it very difficult to perseverance.Premature ejaculation is divided into primary premature ejaculation and secondary premature ejaculation. Primary premature ejaculation:intravaginal ejaculation latency time is short since the the first time. Surgical treatment of primary premature ejaculation(modified dorsal penile neurectomy) have been carried out in our country for many years, but many Urology and Andrology doctors worry about postoperative complications, especially erectile dysfunction, so the surgery was not carried out widely.Objective:1. Identify the quantity of dorsal nerve of penis of health adult and primary premature ejaculation, and compare them. If the quantity of dorsal nerve of penis of primary premature ejaculation is more than health adult obviously, the quantity of dorsal nerve of penis is maybe important etiological factor to premature ejaculation.2. Identify the relationship between dorsal penile nerve and penis erection.3. Identify dorsal penile nerve loss will not affect the cell of cavernous body of penis and will not lead to erectile dysfunction.4. Eliminate the worry of Urology and Andrology doctors of the dorsal penile nerve cut too much maybe led to erectile dysfunction, and profit dorsal penile neurectomy carry out extensively.The research was divided into four parts. Part one:topographic anatomy study of dorsal nerve of penis. Part two:establishment of animal model with absence of rabbit penile dorsal nerve and observation of penis erectile function after surgery. Part three:apoptosis in rabbits corpus cavernous penis after neruotomy of bilateral dorsal nerve of penis and/or cavernous nerve. Part four:surgical method and complications of primary premature ejaculation.Part one topographic anatomy study of dorsal nerve of penis1. ObjectiveTo investigate the number, course and distribution of normal dorsal penile nerves. The research have important clinical value for selective neurectomy of the dorsal penile nerve to the treatment of primary premature ejaculation (PPE). It is guide to dorsal penile neurectomy for primary premature ejaculation (PPE) patients. 2. Material and methods1) The study comprised 47 adult male autopsy specimens. In order to displayed clearly, we educe and cut superficial fascia, deep fascia of back, expose dorsal nerve of penis and blood vessel between deep fascia and albuginea. Educe dorsal nerve of penis, deep dorsal vein of penis and dorsal artery of penis carefully. We observe and count them, with specific attention on the course, distribution and quantity of the dorsal nerve of penis.2) Following the cavernous nerve of the neurovascular bundle, we give penile cavernous nerve detailed anatomical observation and measurement.The penile cavernous nerve were performed on 3 adult formalin preserved cadavers with operative microscope SXP1B. The genital tissue and penile cavernous nerves were explored with HE staining and nitric oxide synthase immunohistochemistry staining. The sections were then observed under microscope. The purpose is to know the relationship between them cavernous nerve and dorsal nerve of penis.2. Results1) Summary of dorsal nerve of penis quantity are as follows:7 branches 1 corpse; 6 branches 2 corpse; 5 branches 7 corpse; 4 branches 9 corpse; 3 branches 18 corpse; 2 branches 10 corpse. Most of them are parallel each other. Only a small quantity of autopsy specimens have communicating branches to connect adjacent branches. The lateral portions of the penile shaft were innervated by branches arcading from the dorsal midline radiating toward the ventral surface. In a few specimens, some branches continue their pathway over the ventral portions of penis. During its pathway, fine nerve fibers course into the corpus spongiosum and corpus cavernosum. We also observed that fine nerve fibers course into coronary sulcus to glans. Most specimens have one dorsal nerve of penis go along with deep dorsal vein of penis.2) 2 The penile cavernous nerve of the neurovascular bundle pierced the inferior genitourinary diaphragm at the postero lateral border of the urethral external sphincter. The cavernous nerve traveled under the penile dorsal nerve and blood vessels after piercing the genitourinary diaphragm. One branch of the cavernous nerve joined the dorsal nerve, and the other 2～3 branches of the cavernous nerve entered into the crural body of the penile corporal body. The positive staining for nitricoxide synthase nerve fibers had been noted in the distal part of the dorsal nerve. The positive staining for nitric oxide synthase nerve fibers was noted in the distal part of the dorsal nerve and penile cavernous nerve.3. Conclusions1) Average quantity of dorsal nerve of penis is 3.49±1.23 in 47 autopsy specimens.2) There is one branch of the cavernous nerve joined the dorsal nerve.Part two:establishment of animal model with absence of rabbit penile dorsal nerve and observation of penis erectile function after surgery1. ObjectiveTo clear whether the total penile dorsal nerves removal will lead to erectile dysfunction or not.2. Material and methods1) removal of all 20 male rabbits penile dorsal nerves.2) observed if these rabbits still be able to penile erection and mate after 1 month.3) Confirming the tissue of excised is nerves by staining immunohistochemistry.3. Results2 rabbits died 1 week after operation, and the remainings all have penile erection, and can carry out mating.4. ConclusionsIt will not lead to erectile dysfunction if dorsal penile nerves cut too much.Part three:apoptosis in rabbits corpus cavernous penis after neruotomy of bilateral dorsal nerve of penis and/or cavernous nerve1. Objective To observe the apoptosis in penile corpus cavernous after neurotomy.For sure even all the dorsal penile nerves transection will not induces apoptosis in smooth muscle cells of the rabbits penis. It indicated even even all the dorsal penile nerves transection will not lead to erectile dysfunction indirectly. The purpose of this reseach is to discuss the feasibility of modified dorsal penile neurectomy to primary premature ejaculation (PPE) by animal experiment.2. Material and methods25 male rabbits were randomly assigned to experimental and normal control groups, and every group have 5 rabbits. The quantity of cavernous apoptosis cells was measured by TUNEL2 days after neurotomy.3. ResultsAfter transaction, the apoptosis in experimental in A showed a statistically significant difference(P<0.001) to B group and A+B group; however there was no statistically significant difference after bilateral dorsal nerve transaction (A) to control C (P=0.054)and D (P=0.233). A+B showed a statistically significant difference to C group and D group(P<0.001); B showed a statistically significant difference to C group and D group(P<0.001).4. ConclusionsCavernous nerve transection induces apoptosis in smooth muscle cells of the rabbits penis, but nor does dorsal nerve transaction alone. There is no statistically significant difference in apoptosis between cavernous nerve injury alone and combination injuries of cavernous nerve and dorsal nerve.Part four:Surgical method and complications of primary premature ejaculation1. ObjectiveTo intrduce the Operation indication,extensional surgical methods and surgical attention of primary premature ejaculation (PPE) detailedly. And share the operation experience with others.2. Material and methods1) Total of 338 PPE patients who come from Guangzhou, Yueqing, Harbin three tertiary hospitals in September 2007 to February 2011, were analyzed retrospectively. The efficacy and postoperative complications were given objective assessment.123 patiens is above 2 years follow up time. IELT, patiens sexual life satisfaction score and spouse sexual life satisfaction score of these patiens is given statistics analysis.2) curative effect standardImprovement:2min< IELTpostop≤5min; obvious effect:IELTpostop> 5min; inefficacy:IELTpostop≤2min. Patiens sexual life satisfaction score (IIEF no. 6,7,80～15score) and spouse sexual life satisfaction score (IIEF no.10,13,14 0-15score) were recorded and compared. At the same time the complications incidence rate (such as anejaculation and erectile dysfunction) were observed.3. Results1) Dorsal nerve of penis quantity of 123 above 2 years follow up patiens:4 branches 5 cases; 5 branches 9 cases; 6 branches 16 cases; 7 branches 26 cases; 8 branches 26 cases; 9branches 25 cases; 10 branches 9 cases; 11 branches 4 cases; 12 branches 3 cases. Average 7.69±1.77.2) The follow up time of 123 cases is over 2 years of all 338 cases. Most of these 123 cases IELT have different degree extension.Among them:obvious effect 57cases; improvement 48cases; inefficacy 18 cases, obvious effective rate is 46.30%; total effective rate is 85.4%. Ejaculation latency did not change after surgery 18cases, penile numbness 2 cases, erectile dysfunction 1 case, penile hematoma 1 case, wound infection 2 cases.3) Statistics analysis The IELT of preoperative and postoperative showed statistically significant difference (t=19.630, P<0.001); Sexual life satisfaction score of preoperative and postoperative showed statistically significant difference (t=39.527, P<0.001); spouse sexual life satisfaction score of preoperative and postoperative showed statistically significant difference (t=38.738, P<0.001).4. ConclusionsModified dorsal penile neurectomy is safe and effective to PPE patients. Conclusions of full text1) Dorsal nerve of penis lies between penis deep fascia of back and albuginea. the number of dorsal penile nerves in patients with primary premature ejaculation (PPE) is not consistent with the average number (2 branches), but 3.49±1.23. All the three specimens which we anatomized have a fine nerve fibers connect with dorsal nerve of penis. Topographic anatomy study of dorsal nerve of penis is the theory foundation of modified dorsal penile neurectomy.2) It will not lead to erectile dysfunction or ejaculatory dysfunction if dorsal penile nerve cut too much to rabbits, and the rabbits can copulation and ejaculation normally. It indirect indicateing that It will not lead to man erectile dysfunction if all dorsal penile nerve resected. Eliminate the worry of urinary surgery and andriatry doctors that dorsal penile nerve cut too much may lead to erectile dysfunction.3) Cavernous nerve transection induces apoptosis in smooth muscle cells of the rabbits penis, but nor does dorsal nerve transaction alone. It means dorsal nerve have no relationship with cavernous cells. It indirect indicateing that It will not lead to man erectile dysfunction if dorsal penile nerve resected.4) Animal experiment indicate dorsal nerve ectomy is safe and will not lead to erectile dysfunction, and the at same time it will not lead to anejaculation.By this theory,338 PPE patients were given modified dorsal penile neurectomy. We summarize operation indication, complication,surgical methods and surgical attention of primary premature ejaculation detailedly. Modified dorsal penile neurectomy is effective and safe to primary premature ejaculation.更多还原