超声引导经皮内置冷循环射频消融治疗子宫平滑肌瘤的临床研究
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摘要
第一部分超声引导下经皮冷循环射频消融子宫平滑肌瘤的有效性及安全性研究
     目的:通过观察射频消融(RFA)治疗后子宫肌瘤组织的光镜及电镜下的病理变化及术中术后不良反应的症状和体征异常变化,探讨RFA治疗对子宫肌瘤组织结构凝固的范围、坏死程度和副作用及并发症,评价经皮冷循环射频消融治疗子宫肌瘤的疗效及安全性。
     方法:2007年3月至2008年1月共有子宫肌瘤患者104例共123个肌瘤,在我院行RFA治疗。随机选择其中30例患者,30个肌瘤分别于治疗前、治疗后即刻行超声引导下穿刺活检。根据取材位置的不同分为:消融灶中央组(A)、消融灶边缘组(B)、消融灶边缘1cm组(C);每组10名患者。标本常规固定,分别行光镜和电镜检查。观察RFA治疗中104例患者的生命体征、氧饱和度、心电监护;治疗后患者生命体征、皮肤毒性反应、治疗后阴道流血,下肢感觉和功能指标,疼痛等情况;观察月经周期,经期,月经量改变相关症状。通过上述观察指标探讨RFA治疗子宫肌瘤的安全性。
     结果:RFA治疗后标本光镜显示:A组可见大量均匀红染无结构物质,细胞结构消失;B组可见消融灶边缘平滑肌细胞固缩,细胞间隙扩大;C组可见消融灶边缘可见一明显分界,其内部为典型凝固性坏死。电镜显示:A组见大量髓鞘样结构,细胞轮廓不清,细胞核浓缩,染色质呈团块状;B组可见小血管内红细胞聚集血栓形成,内皮细胞变性;C组肌瘤边缘可见正常的平滑肌细胞及明显的肌丝。RFA治疗过程均顺利按计划完成,治疗过程中监测患者生命体征、心电图、氧饱和度均未出现异常情况。RFA治疗子宫肌瘤不良反应主要为阴道渗出分泌物、少许血液及术后低热(体温38.2±0.4℃,持续1-3天后消失)。极少数病例有小腹疼痛,腹部疼痛程度不重,术后24小时疼痛视觉模拟(Visual analogue scale, VAS)得分3.7±1.1,对患者影响轻微。超声全程监控可避开膀胱及肠管,未出现烧伤及穿孔并发症,早期(3个月内)未发生与治疗相关的副作用及感染、神经损伤等不良事件。
     结论:RFA治疗后可以使靶区组织出现凝固性坏死,对周围平滑肌细胞无损伤,证明RFA是一种安全有效的微创治疗子宫平滑肌瘤方法。
     第二部分超声引导下经皮冷循环射频消融子宫平滑肌瘤疗效评估的研究
     目的:利用超声造影坏死区灌注显影变化评估RFA治疗后的早期疗效,通过对瘤体大小以及临床症状改善的随访,探讨RFA治疗子宫肌瘤的早期疗效评价方法。
     方法: 2007年3月至2008年1月共有子宫肌瘤患者104例共123个肌瘤,在我科采用冷却探头(Cool-tipTM)射频消融治疗系统行RFA治疗。治疗后RFA一周内再次行超声造影检查,观察已治疗的肌瘤是否均为无灌注区,有无残留病灶,评价其早期疗效。以后1,3,6,12月行超声随访,计算瘤体均径和体积,并与治疗前进行比较;每半年对患者临床症状进行随访调查,填写子宫肌瘤症状与健康相关生活质量表(UFS-QOL)调查表记录得分,并与治疗前比较。
     结果:本研究共104例,随访时间12-26月,平均随访时间19.6±2.4月。治疗后114(92.7%)个肌瘤整体无超声造影剂灌注区,提示没有血流灌注,有9(7.3%)个肌瘤术后造影剂显示仍有部分增强需补充治疗。超声随访结果显示,RFA治疗后治疗后1个月随访瘤体均径即有缩小,与治疗前比较,差异有显著性意义(P<0.05)。RFA治疗后1,3,6,以及12月的肌瘤体积平均缩小率分别为32.4%, 48.3%, 64.1%和76.7%。患者临床症状随访显示RFA治疗对减轻子宫肌瘤引发的临床症状效果明显。RFA治疗后12个月随访显示:104例患者中,69例患者(66.3%)月经过多、痛经、贫血、盆腔疼痛等临床症状完全缓解,42例患者(40.4%)临床症状明显改善,7例患者(6.7%)临床症状无改善,3例患者(2.9%)症状加重。48例患者的子宫肌瘤症状与健康相关生活质量表(UFS-QOL)调查表得分显示术后6月,肌瘤症状得分低于术前,生活质量得分高于术前,差异有显著性意义(P<0.05)。RFA治疗后随访期内,有7例(6.7%)因肌瘤复发进行再次治疗,2例因月经量过多而行子宫切除术,5例再次对复发病灶行RFA。RFA治疗后患者满意度调查结果,93(89.4%)例患者对治疗非常满意,95(91.3%)例患者愿意把这项治疗推荐给朋友亲人。
     结论: RFA治疗子宫肌瘤是一种有效的临床治疗方法。
     第三部分超声引导下内置冷循环射频消融和微波凝固治疗子宫平滑肌瘤的对比研究
     目的:比较超声引导下内置冷循环射频消融和微波凝固治疗子宫肌瘤的临床疗效及副作用。
     方法:回顾性研究2006年8月至2008年1月于我中心行RFA和MCT治疗的子宫肌瘤患者的临床资料,其中RFA组104例123个肌瘤,平均直径4.8±1.4cm (3.0-9.93cm),MCT组48例60个肌瘤,平均直径4.7±1.2cm (3.0-7.17cm)。比较两种方法对肌瘤的完全消融率,对临床症状改善的有效率,原位复发率及并发症的发生率。
     结果:肌瘤完全消融率RFA组为92.7% (114/ 123),MCT组为86.7% ( 52/ 60 ),两者比χ2 = 1.73,P>0.05,差异无显著性意义。症状改善的有效率为RFA组为90.3 %(94/ 104),MCT组为87.5% ( 42/ 48 ),两者比较χ2 = 0. 29,P>0.05,差异无显著性意义。RFA后7个结节(5. 7 %)局部复发、MCT后9个结节(15 %),P<0.05,两组差异有显著性意义(χ2 = 4.37)。并发症的发生率,两组在阴道排液方面无显著性差异(χ2 = 2.61, P>0.05),术后发热,MCT组要高于RFA组,两组差异有显著性意义(χ2 = 4.04, P<0.05),此外MCT组有1例患者在拔针过程中出现“断针”,另有4例术后出现腹腔积液。
     结论:射频消融和微波消融均是微创治疗子宫平滑肌瘤的有效方法,RFA在肌瘤完全消融率和对症状的改善方面与MCT无差异,但是RFA在肌瘤的原位复发率及并发症的发生率上要低于微波凝固治疗。
Part one Effectiveness and safty study on percutaneous ultrasound guided radiofrequency ablation with internally cooled electrod for uterine leiomyoma
     Objective: To evaluate the therapeutic efficacy and the safty of uterine fibroid treated with radiofrequency ablation (RFA) by using pathological examination and clinical data.
     Methods: From Mar 2007 to Jan 2008, 104 patients with 123 uterine fibroids were treated with RFA in Xijing hospital. From these patients, ultrasound guided needle puncture biopsy was performed in 30 patients one week before and after treatment to analyze RFA therapeutic response pathologically using light microscope and transmission electron microscope. 30 fibroids were divided 3 groups according to location of the puncture: group A (center of lesion), group B (marginal), group C (1-cm away from the margin). Control groups were obtained from puncture biopsy before RFA treatment in the same leiomyoma. We observed patient's vital signs, oxygen saturation of hemoglobin during the procedure, skin toxicity, bleeding, pains paresthesia and disfunction in lower limb following treatment; menstrual cycle, menstruation, menorrhea and hypoestrogen related symptoms after the treatment were evaluated.
     Results: Microscopic examination after RFA showed the cellular membranes were ruptured, and the cytoplasm was overflowed in group A, the smooth-muscle cells contracted and the interstitial spaces dilated in group B and an inter-texture or reticulate appearance characteristic of coagulative necrotic in group C. Electron microscopy showed overall debris and implosion cysts in group A, the chromatin in nucleolus of smooth muscle cell formed rounded aggregates, myofilament structure was damaged and endothelial cell death and red blood cell in together in group B, normal nuclei of smooth muscle cells and normal myofilament in group C. All procedures were performed according to the plan and patients were recruited. During the procedures, vital signs, ergocardiogram, and oxygen saturation of hemoglobin were normal. The major adverse Effects of treatment of uterine fibroids by RFA were virginal discharge and light febris (Fever 38.2±0.4℃in 1-3 days post-procedure mostly). The pains of abdomen was light and the score of Visual analogue scale (VAS) were 3.7±1.1 in 24 hours post–procedure. Penetration/burn injuries of the bowel or bladder, sepsis and peritonitis were not reported.
     Conclusions: RFA can extracorporeally induce necrosis in target uterine fibroid tissue and surrounding tissue without damage. The evidence directly validates RFA as an effective and safty treatment of uterine fibroid.
     Part two Evaluation of therapeutic efficacy on percutaneous ultrasound guided radiofrequency ablation with internally cooled electrod for uterine leiomyoma
     Objective: To study the clinical value of real time contrast enhanced ultrasonography (CEUS) in evaluating the therapeutic efficacy and clinical long term results of percutaneous ultrasound guided radiofrequency ablation (RFA) in the treatment of uterine fibroids by following up the volume change and symptom relief after RFA treatment.
     Methods: From From Mar 2007 to Jan 2008, 104 consecutive patients with 123 uterine fibroids were treated with RFA. Immediate therapeutic effects were assessed at follow-up with CEUS and CDFI. All patients were followed up to observe long-term therapeutic effects. Leiomyoma mean diameters, volumes and reduction rates 1, 3, 6 and 12 months after RFA treatment were calculated and compared by using one-way ANOVA and Student-Newman-Keuls tests.
     Improvement in myoma-related symptoms and impacton quality of life were assessed using a validated questionnaire (UFS-QOL).
     Results: All patients were followed up for 12-26 months (mean, 19.6±2.4 months). After the RFA, on the CEUS, complete tumor ablation was observed in 92.7% of the 114 uterine leiomyomas and residual unablated fibroids were found in 9 leiomyomas (7.3%). Follow-up images showed absence or reduction of blood supply in the lesions after RFA. Results showed that the mean diameter began to decrease one month after RFA, Median reductions in tumor size as a percentage of initial fibroid volume at 1, 3, 6, and 12 months after RFA treatment were 32.4%, 48.3%, 64.1% and 76.7% respectively. 40.4% of women in our study declared significant relief from previous symptoms 12 months after RFA treatment and 66.3% reported completely asymptomatic after RFA treatment. One year after the procedure, 7 women (6.7%) were recurrence of fibroid-related symptoms. Quality-of-life measures showed significant and durable improvement compared with baseline.
     Conclusions: RFA ablation appears to be an effective treatment of uterine leiomyomain reducing the volume and treating the symptoms.
     Part three Ultrasound guided ablation treatments for uterine leiomyoma: a comparison between radiofrequency ablation and microwave coagulation treatment
     Objective: Comparing the value in clinical practice of ultrasound guided ablation therapies for uterine leiomyoma between using radiofrequency ablation and microwave coagulation treatment.
     Methods: From Aug 2006 to Jan 2008, percutaneous radiofrequency (RFA) was used to treat 104 cases with 123 fibroids, with a diameter of 4.8±1.4cm (3.0-9.93cm), percutaneous microwave coagulation therapy (MCT) was employed to treat 48 cases with 60 fibroids, with a diameter of 4.7±1.2cm (3.0-7.17cm). To compare RFA and MCT in local ablation effect, effective rate of improve symptoms, recurernce rate in local and the incidence of complications.
     Results: The fibroid completely ablation rate was 92.7% (114/123) in RFA and 86.7% (52/60) in MCT, which showed no significant difference in statistics(χ2 = 0. 17, P>0.05). The effective rate of improve symptoms was 90.3 %(94/104) in RFA, 87.5% ( 42/48 ) in MCT, which showed no significant difference in statistics(χ2 = 0. 29,P>0.05). The recurernce rate was 5.7% (7/123) in RFA, 15% (9/60) in MCT, which showed significant difference in statistics(χ2= 4.37,P<0.05). There was also no difference in vaginal between the two ablations (x2= 2.61, P>0.05), the light fever was 7.7% (8/104) in RFA and 18.8% (9/48) in MCT, which showed significant difference (χ2 = 4.04, P<0.05). In addition, one microwave antenna was broken in the pull needle.
     Conclusions: RFA is contemporary ideal therapeutic approaches of interventional ultrasound for uterine leiomyoma. The rate of recurrence and complication were lower in RFA compare with MCT.
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