保留盆腔自主神经在根治性子宫切除术中的循证医学研究与基础、临床研究

【作者】 龙颖；

【导师】 姚德生；

【作者基本信息】 广西医科大学 ， 妇科肿瘤学， 2010， 硕士

【摘要】 根治性子宫切除术(radical hysterectomy,RH)是治疗早期宫颈癌的标准术式,一百多年前由Wertheim提出,19世纪50年代Meigs将其改良并得到普及,术后5年生存率达80%~90%。但是,传统的根治性子宫切除术不可避免会导致一些脏器功能的障碍:如膀胱功能障碍、结直肠蠕动紊乱、性功能障碍。其中,膀胱功能障碍是最常见的。这些并发症的发生与术中盆腔神经丛的损伤密切相关。因此,如何在术中既不减少切除范围,又尽可能保留盆腔神经丛,从而尽可能地减少盆腔脏器功能的损伤,成为妇科专家研究的热点。这就产生了一种新的术式—保留盆腔自主神经的根治性子宫切除术(Never sparing radical hysterectomy,NSRH)。§1 NSRH与传统RH治疗宫颈癌临床疗效比较的系统评价目的:本研究比较NSRH和传统RH治疗宫颈癌的临床疗效和手术的安全性。方法:计算机检索Cochrane图书馆、MEDLINE、EMbase、CBM、维普中文科技期刊数据库、清华同方数据库,手工检索治疗宫颈癌相关的文献,收集符合标准的随机对照试验和临床对照试验。文献质量评价采用Cochrane的评价标准。数据提取和文献质量评价由两名评价员独立进行。采用Cochrane协作网专用软件Revman4.2.2对数据进行统计分析。结果:未获得随机对照试验,纳入9个临床对照试验,总样本量为749例。结果显示: NSRH组术后膀胱功能的恢复优于传统的RH组,其差异有统计学意义;手术时间NSRH组长于RH组,差异有统计学意义;术中出血量、术后生存率和复发率、手术切除范围及术后病理的相关情况,两组无明显统计学差异;⑥单个研究显示NSRH组的直肠功能紊乱和性功能紊乱的发生率要比RH组低,差异有统计学意义。结论:NSRH与传统RH相比,具有术后膀胱、直肠功能和性功能恢复快的优点。NSRH除手术时间长于RH外,而术中出血量、术后复发率和生存率、手术切除范围两者无明显差别,因本系统评价纳入的病例数较少,纳入的均为非随机对照试验。一些结局指标仅单个研究报道。因此,目前还无法得到以上结论的确切疗效,有必要开展和设计大样本前瞻性随机对照研究来进一步验证。§2 NSRH相关的盆腔神经临床解剖学研究目的:通过尸体解剖,熟悉盆腔神经的大体组成、位置、行程,为探讨和开展NSRH术式奠定基础。方法:选用经10%福尔马林固定的成年女性盆腔标本4具,均无盆腔手术史。应用大体解剖法进行解剖,以文字、照片等形式记录相关结果。结果:上腹下从(又称骶前神经)行至第3骶椎高度,与S2~S4发出的盆腔内脏神经、骶交感节后神经纤维共同组成网状分布的下腹下从(即盆丛),并发出支配膀胱、直肠、子宫的神经支。结论:盆腔神经的临床解剖学是临床手术开展的基础,应该得到临床医师的重视。§3 NSRH治疗宫颈癌临床效果的初步研究目的:探讨NSRH治疗宫颈癌的临床疗效及技术上的可行性。方法:2008年4月至2009年10月间,选择我院FIGO分期为Ⅰb~Ⅱb的子宫颈癌患者69例,研究组(n=33)采用NSRH,对照组为传统的Ⅲ型宫颈癌根治术RH(n=36),比较两组术后膀胱、直肠功能的恢复,手术时间、术中出血量、手术切除范围。结果:研究组和对照组相比,术后残余尿<100ml的平均时间分别为12.64±4.49d与17.89±4.19d(P<0.001),术后残余尿<50ml的平均时间分别为14.30±5.87d与19.69±4.48d(P<0.001);术后肛门排气时间分别为62.99±11.99h与79.32±13.22h(P<0.001),术后排便时间分别为95.42±12.54h与120.04±21.00h(P<0.001)。两者比较差异均有统计学意义。部分患者术后尿流动力学的测定结果显示:无论是在膀胱灌注阶段还是排尿阶段,两组结果均有统计学差异。术中总出血量中位数分别750ml(350~1800ml)与700ml ( 300~1800ml )( P>0.05 ),子宫切除的出血量中位数610ml(180~1200ml)与550ml(150~1200ml)(P>0.05);总手术时间中位数分别为252min(180~330min)与205min(150~270min)(P<0.05),子宫切除时间中位数89min(65~105min)与70min(55~90min)(P<0.05),两者比较差异有统计学意义。主、骶韧带切除的长度两组没有显著性差异。结论:保留盆腔自主神经的根治性子宫切除术具有可行性和安全性,有利于术后膀胱、直肠功能的恢复。§4 NSRH相关的盆腔神经组织病理学研究目的:比较NSRH与传统RH中宫骶韧带、主韧带、膀胱宫颈韧带手术切缘神经的分布密度情况。方法:分别取保留组、对照组手术中宫骶韧带、主韧带、膀胱宫颈韧带的切缘组织,10%福尔马林固定保存。进行常规HE、免疫组织化学(S100)、特殊染色(银染)。使用图像分析法,对免疫组织化学(S100)的结果图像进行分析,计算神经组织所占的面积比。结果:三种染色方法均能显示神经组织。显微镜下观察研究组的神经组织少于对照组,神经组织的面积比计算结果两组有统计学差异(P<0.05)。结论:NSRH能有效的避免对盆腔神经组织的损伤。§5 NSRH治疗宫颈癌患者的生活质量及性功能的调查分析目的:比较NSRH和传统RH治疗宫颈癌患者的生活质量、性功能变化,以及探讨影响总体宫颈癌患者术后性功能的因素。方法:2008年4月至2009年10月间,选择我院FIGO分期为Ⅰb~Ⅱb的子宫颈癌患者65例,研究组(n=31)实行NSRH,对照组为传统的Piver-RutledgeIII型根治性子宫切除术RH(n=34)。采用欧洲癌症研究与治疗组织(EORTC)所提出的生活质量评分表EORTC QLQ C-30以及女性性功能指标量表(FSFI)对两组患者的生活质量、性生活质量进行评分,并对总体宫颈癌患者进行了性生活质量相关因素的多元回归分析。结果:术后宫颈癌患者的生活质量和性生活质量均会有所下降。研究组与对照组相比,术后性生活评分除性欲望P=0.065外,余五项指标和总分均显示研究组的性功能要优于对照组(P<0.05)。术后生活质量评估中身体功能、疲倦、便秘、腹泻两组评分差异有统计学意义(P<0.05)。年龄、手术治疗结束时间、卵巢切除、临床分期、职业、文化水平对于宫颈癌患者术后性生活质量有一定影响。结论:NSRH相比传统的RH,能提高术后宫颈癌患者生活质量和性生活质量。除手术方式外,术后宫颈癌患者的性生活质量受多因素影响,对宫颈癌患者进行心理咨询、生活指导及辅助治疗,可进一步改善治疗后性生活质量。更多还原

【Abstract】 The classical surgical management of early-stage cervical carcinoma, known as radical hysterectomy(RH), was first described by Wertheim more than one hundred years ago and was then modified and repopularized by Meigs in 1950s. This operation yields 5-year survival rates of 80%~90%. But radical hysterectomy for early cervical cancer is associated with typical postoperative morbidity: bladder disfunction, sexual disfunction and colorectal motility disorders. Accidental damage the pelvic autonomic nerves during the surgery is thought to play a crucial role in the aetiology of the morbidity after radical hysterectomy. Therefore, some gynecologists have focused on preserving the pelvic nerves without reducing the radicality of surgery. The new technique is called nerve sparing radical hysterectomy(NSRH).§1 Nerve sparing radical hysterectomy versus radical hysterectomy for cervical cancer: a Systematic ReviewObjective: To evaluate the clinical efficiency and safety of nerve sparing radical hysterectomy(NSRH) for cervical cancer compare with radical hysterectomy (RH). Methods: We searched the Cochrane Library, MEDLINE, EMbase, CBM, CQVIPand CNKI, we also handsearched some Chinese journals. Using a defined search strategy, randomized controlled trails and controlled clinical trials of comparing NSRH with RH for cervical cancer were identified. Data were extracted and evaluated by two reviewers independently. The quality of the included trails was evaluated by Cochrane’s evaluation criterion. Meta–analysis was done using the Cochrane collaboration’s Revman4.2.2. Results: Nine controlled clinical trials(749 patients)were included, The meta-analysis showed that: NSRH is beneficial for recover of postoperative bladder function versus RH with a significant difference; The operative time of NSRH is longer than RH with a significant difference; there are no significant difference between the two groups in terms of the blood loss, extension of resection, survival and recrudescent rate and pathologic outcome. One trail showed that NSRH is beneficial for recovery of postoperative anorectal and sexual functions function with a significant difference versus RH. Conclusions: NSRH can improve the recovery of postoperative bladder, anorectal and sexual functions compare with RH, but have no more operative blood loss, less extension of resection, lower survival rates and higher recrudescent rates except longer operation time. NSRH can improve quality of life in patients after operation and is not associated with reducing safety of surgery. However, the trails available for this systematic review are limited, as well as non-randomized controlled trails. Some outcomes were only included by one trail. So there is no confirmed conclusion about these. A prospective randomized controlled trial is warranted to fully investigate.§2 Clinical pelvic anatomical study for NSRHObjective: We studied the composing, place, route of pelvic autonomic nerve through anatomizing cadavers to lay a base for NSRH. Methods: Macroscopical dissection was performented on four female cadavers without pelvic surgery were fixed by 10% formaldehyde. Record ways include character, photo and so on. Results: Inferior hypogastric plexus is composed of hypogastric nerve, pelvic splanchnic nerve and sacral sympathetic nerve, and delivers nerves that dominate bladder, rectum and uterus. Conclusion: Gynecologist should pay attention to pelvic anatomical study because it can lay a base for surgery.§3 Preliminary study on clinical effect of NSRH for cervical cancerObjective: To evaluate the clinical effect of NSRH and the feasibility of this technique. Methods: Between April 2008 and October 2009, sixty-nine patients with FIGO stageⅠb~Ⅱb cervical cancer were selected to receive NSRH(study group, 33 cases)or TypeⅢradical hysterectomy(RH)(control group, 36 cases). The urethra /bladder and anal/ rectum function after the operation, duration of surgery, blood loss and the excision extent were compared between the two groups. Results: The time to achieve a postvoid residual urine volume (PVR) less than 100 ml of study group and control group were 12.64±4.49d and 17.89±4.19d(P<0.001), the time to achieve PVR less than 50ml were 14.30±5.87d and 19.69±4.48d(P<0.001); the first exhaust time were 62.99±11.99h and 79.32±13.22h(P<0.001), the first stool time were 95.42±12.54h and 120.04±21.00h(P<0.001), all with a significant difference. Urodynamic study on postoperative bladder function in partial patients show that there were a significant difference between two groups in storage phase and voiding phase.The median blood loss during whole operation were 750ml (350~1800ml)and 700ml(300~1800ml)(P >0.05), The median blood loss during uterus removal were 610ml(180~1200ml) and 550ml(150~1200ml) (P>0.05), with no significant difference; The median whole operation time were 252min (180~330min) and 205min(150~270min) (P<0.05), The median operation time of uterus removal were 89min(65~105min) and 70min(55~90min)(P<0.05), with a significant difference; There is no difference between two groups in the excision extent of cardinal ligament and uterosacral ligament. Conclusion: Nerve sparing radical hysterectomy(NSRH) for the patients with FIGO stageⅠb~Ⅱb cervical cancer is safe and feasible,and improve the recovery of postoperative bladder and rectum function.§4 Histopathological sdudy on pelvic nerves for NSRHObjective:Compare nerves density of surgical margins of uterosacral ligament, cardial ligament and vesicouterine ligament in NSRH with in RH. Methods: Specimens of surgical margins in NSRH and RH were fixed by 10% formaldehyde. HE staining, silver staining and immunochemistry staining(S100) were performed. Immunohistochemical outcome is analyzed by image analytical method to calculate nerves proportion. Results: Nerves can be show in three staining ways. Nerves were less in sdudy group than in control group under microscopical view. There is a significance difference between two groups according to nerves proportion(P<0.05). Conclusion: NSRH can avoid damaging pelvic nerves during surgery effectively.§5 Investigation of quality of life and sexual function in cervical cancer patients treated by surgeryObjective:To compare quality of life and sexual function in patients with cervical cancer treated with NSRH or RH and the factors influence sexual function after surgery . Methods:Between April 2008 and October 2009, sixty-five patients with FIG0 stageⅠb~Ⅱb cervical cancer were selected to receive NSRH(study group, 31cases) or Piver-RutledgeIII radical hysterectomy (RH)(control group, 34 cases). EORTC QLQ C-30 and FSFI were used to score the quality of life and sexual function, and multivariate linear regression regression was used to analyse the factors influence sexual function. Results:Quality of life and sexual function were impaired in all patients after surgery. Except sexual desire, the remaining five index and overall sores indicate that sexual function is better in study group than in control group(P<0.05). There was a significant difference between two groups in physical function, fatigue, constipation, diarrhea in quality of life(P<0.05). Age, the time of end of treatment, ovariotomy, clinical staging, occupation and education were related to the sexual function of patients with cervical cancer. Conclusion:NSRH compares with RH, can improve postoperative quality of life and sexual function in patients with cervical cancer. Postoperative sexual function is affected not only by surgery technique, but also many factors. Psychological counseling, life guidance and adjuvant therapy should be used to improve the sexual function of patients with cervical cancer after treatment.更多还原