子宫纤维瘤的微创治疗 P.M. Yuen 阮邦武 Director of Minimally Invasive Gynaecology, Hong Kong Sanatorium & Hospital Honorary Clinical Associate Professor, CUHK Honorary Professor, Capital University of Medical Sciences, Beijing Past President, Asia Pacific Association for Gynecologic Endoscopy & Minimally Invasive Therapy (APAGE)

Surgical Treatment for Fibroids 纤维瘤的外科治疗 Surgery is the principal treatment for fibroids The main indications are: Symptomatic fibroids Enlarging fibroids, especially after menopause Subfertility and recurrent miscarriage Failed alternative treatment Large asymptomatic fibroids 外科是纤维瘤的原则治疗 主要的适应症是 症状性纤维瘤 增大性纤维瘤，特别是闭经后 低生育力和复发性流产 失败的交替治疗 大的无症状性的纤维瘤

MIS is the standard… MIS是……标准 Surgical management of fibroids has changed from laparotomy to minimally invasive surgery Most fibroids can be managed endoscopically either by laparoscopy or hysteroscopy Surgeon’s expertise, especially laparoscopic suturing, is crucial 纤维瘤的外科管理已经从剖腹术转变到了微创外科 大多数的纤维瘤能借助于内窥镜管理，腹腔镜或宫腔镜 外科的专业特长，特别是腹腔镜的缝合是很关键的

子宫切除术或肌瘤切除术 Hysterectomy or Myomectomy The decision to perform hysterectomy or myomectomy depends on: The age of the woman The desire to retain reproductive potential The desire to retain the uterus The position, number and size of the fibroids The woman’s preference should be respected 执行子宫切除术和肌瘤切除术的决定依赖于 妇女的年龄 对保留生育潜力的渴望 对保留子宫的渴望 纤维瘤的位置、数量和大小 妇女的优先权应该被尊重

Hysterectomy 子宫切除术 A definite treatment which eliminates both symptoms and risk of recurrent problems from fibroid Remove menstruation and future fertility Improve quality of life High satisfaction rate (>95%), both short term and long term, even in those with experiencing complications Complication rate 10-15%, major complication 4.5-5.6% No adverse effects on sexual, bowel or urinary functions Pinion et al 1994 O’Connor et al 1997 排除纤维瘤的症状和复发问题风险性的确定治疗 消除月经和将来的生育能力 提高生活质量 高满意度（>95%) 短期和长期，甚至在经历并发症的人群中 并发率10-15%，主要并发症4.5-5.6% 在性功能，肠功能或泌尿功能中没有副作用

Total vs Subtotal hysterectomy 全子宫切除术与次子宫切除术比较 3 RCTS involving 733 patients followed by 1-2 years All hysterectomy were by laparotomy No evidence to support that leaving the cervix was associated with improved sexual function or lower rates of incontinence or constipation Blood loss was reduced with supracervical hysterectomy but the transfusion rates were the same Length of stay was decreased in the supracervical group Lethaby et al Cochrane Database Syst Rev 2006 3RCTS 包含733个病人跟踪大于1-2年 所有的子宫切除术是通过剖腹产 无证据支持存留的子宫颈与改善性功能有关，或降低失禁率或便秘 阴道上子宫切除术，失血减少了，但是输血率是相同的 在阴道上子宫切除术群里，住院时间减少了

Laparoscopic approach is the choice 腹腔镜方法是可选择的 Longer operating time Faster postoperative recovery Shorter duration of hospital stay Lower intra-operative blood loss Smaller drop in haemoglobin level Fewer post-operative febrile morbidity Fewer wound or abdominal wall infections Faster return to normal activity Cochrane Database Syst Rev 2006 腹腔镜与剖腹术比较 更长的手术时间 更快的术后恢复 更短的住院时间 减少手术期间的失血 血红蛋白水平更少降低 更少的术后纤维瘤发病率 更少的伤口或腹腔感染 更快恢复正常活动

Additional Advantages of LH LH的额外的优点 Evaluation of the pelvic and abdominal cavity before hysterectomy Ligation of infundibulo-pelvic ligament to facilitate difficult ovary removal Management of uterine fibroids that complicate the performance of vaginal hysterectomy Lysis of adhesions Treatment of endometriosis Better control of haemostasis 子宫切除术前盆腔和腹腔的评估 漏斗形骨盆韧带的结扎有利于疑难卵巢的切除 使阴道子宫切除术的操作复杂化的子宫纤维瘤的管理 粘连的松解术 子宫内膜异位的治疗 止血的更好控制

TLH is the choice… TLH是…的选择 All under direct and clear vision Avoid difficult vaginal surgery Avoid injury to bladder and ureter by distending the vaginal fornix for incision Less shortening of the vagina Less damage to the ligamentous support of the vagina Better haemostasis on the vaginal cuff 所有的都在直接和清楚的视线下 避免困难的阴道手术 切割时避免损伤被阴道穹窿膨胀的膀胱和输尿管 阴道更少的缩短 更少损伤阴道韧带的支持 阴道断端的更好止血

What is the limit for TLH? 对TLH的限制是什么 The choice of route for hysterectomy “depends on the patient’s anatomy and the surgeon’s experience” – ACOG 子宫切除术的途径选择 根据病人的解剖和外科医生的经验

Myomectomy 肌瘤切除术 去除纤维瘤，保留子宫为目的 减轻症状 保留生育功能 提高生育力 症状的消除发生在80-100% Aims to remove fibroids and conserve the uterus  To relieve symptoms  To preserve reproductive function  To improve fertility Symptoms resolution occurs in 80-100% Hysterectomy risk is 2% Complication rate 8-11% An option even in peri-menopausal women 去除纤维瘤，保留子宫为目的 减轻症状 保留生育功能 提高生育力 症状的消除发生在80-100% 子宫切除术的危险性在2% 病发率在8-11% 甚至在绝经前妇女中选择

Fibroids and Fertility 纤维瘤和生育能力  Fibroids distorting cavity  less likely to become pregnant (RR 0.36, 95% CI 0.18–0.74)  more likely to have a spontaneous abortion (RR 1.7, 95% CI 1.4–2.1) (Pritts et al 2009 )  Myomectomy for cavity-distorting fibroids Increase conception rate (RR 2.03, 95% CI 1.08–3.83) Decrease miscarriage rate (38.5 versus 50 percent;  RR 0.77, 95% CI 0.36–1.66) (Casinir et al 2006) 纤维瘤畸变腔 更少可能怀孕 （RR 0.36,95%, CI 0.18-0.74) 更多可能自然流产 (RR1.7，95%,CI 1.4-2.1) 对畸形腔纤维瘤的肌瘤切除术 增加怀孕率(RR2.03，95%,CI 1.08-3.83) 降低流产率 (38.5 VS 50%;RR 0.77，95%,CI 0.36-1.66)

Post-operative adhesions 术后粘连  Adhesions rate higher in laparotomy than laparoscopy  without adhesion barrier - 28.1% vs 22.6%  with adhesions barrier - 22% vs 15.9% Tinelli et al 2010 Postoperative wound adhesion higher in protruding wound than flat wound (odds ratio, 2.53; p=0.02). The number of enucleated subserosal myomas (odds ratio, 3.29; p<0.001) and the diameter of the largest fibroid (odds ratio, 1.05; p<0.001) were significantly associated with wound protrusion Kumakiri et al 2012 剖腹术的粘连率高于腹腔镜 无粘连障碍-28.1%vs22.6% 有粘连障碍-22%vs15.9% 术后伤口粘连突出的伤口高于平伤口 （比值比，2.53；P=0.02） 摘出的浆膜下肌瘤数（比值比，3.29；P<0.001) 和最大的子宫肌瘤直径（比值比，1.05；P<0.00） 与伤口突出有相当大的关系。

Outcome compared with AM  Less adhesions formation  Uterine adhesion - 45% Vs 90%  Adnexal adhesion - 25% Vs 70% Similar post-operative fertility  Pregnancy rate - 48% vs 54% Live birth rate – 75% vs 78% No difference in the scar rupture rate  during pregnancy  After AM – 0.002-0.5% (Garnet 1964; Falcone & Badaiwy 2002)  After LM <1% (Mecke et al 1995; Dubuisson et al 2000) No difference in fibroid recurrence  AM – Singleton 11%, multiple 26%  LM - Singleton 16.3%, multiple 36.6% (Malone 1969, Rossetti et al 2001) 更少的粘连形成 子宫粘连-45%vs90% 附件粘连-25%-70% 相似的术后生育能力 怀孕率-48%vs54% 活产率-75%vs78% 怀孕期间疤痕破裂率没有不同 AM后- 0.002-0.5% LM后- <1% 纤维瘤的复发率没有不同 AM-单个11%，多个26% LM-单个16.3%，多个36.6%

Laparoscopic suturing 腹腔镜缝合 Multilayered closure and meticulous haemostasis are mandatory Laparoscopic suturing is difficult and time consuming 多层的闭合和精确的止血是必行的 腹腔镜的缝合是困难的,消耗时间的

V-Loc Wound Closure Device  The unidirectional barbs precisely grasp the tissue at numerous points, providing distribution of tension across the wound. The efficient barb and welded loopp design speeds closure by eliminating the need to tie any knots. The use of V-Loc suture significantly reduces  Suturing time (10 ± 4 vs 16 ± 5 min)  Operative time (51 ± 18 vs 58 ± 18 min) Intraopertive bleeding and haemoglobin drop Angioli et al 2012 单向的倒钩在许多点上准确地抓起组织，跨越伤口提供张力的分配 有效的倒钩和焊接环设计通过消除打结的需要加速了关闭速度 V-Loc缝合的用途： 显著减少了—— 缝合时间（10±4 vs 16±5min) 手术时间 (51±18 vs 58±18min) 手术期间出血和血红蛋白的下降

Is there a limit? 有限制吗？ 禁忌症 4个或超过3CM的多个纤维瘤 Contraindications  4 or more fibroids over 3 cm  Fibroid  8 cm after GnRH analogues  Fibroid near uterine artery or cornu (Dubuisson & Chapron 1996)  > 7 fibroids (Rossetti et al 2001) Individual choice based on pathological findings and surgical skill (Hasson et al 1992; Cittadini 1998) 禁忌症 4个或超过3CM的多个纤维瘤 使用(GnRH)促性腺激素释放激素类似物后纤维瘤≥8CM 接近子宫动脉或子宫角的纤维瘤 >7 纤维瘤 个体选择基于病理结果和外科技能

Lap Uterine Artery Occlusion 腹腔镜子宫动脉闭合  Laparoscopic bipolar coagulation of uterine arteries and anastomotic sites of uterine arteries with ovarian arteries Uterine artery is occluded at the level of the internal iliac artery  The collateral arteries between ovaries and uterus (in the utero-ovarian ligament) are coagulated using bipolar forceps (Lichtinger et al 2002; Lee et al 2005)  Result of LUAO  Mean reduction of dominant fibroid 57.8%  Symptoms improvement 93.2%  Low complication rate 7.3%  Fibroid recurrence rate 9.0% at 2 yrs (Holub et al 2004, Holub et al 2006) 子宫动脉和子宫动脉与卵巢动脉的吻合点的腹腔镜双极凝血 子宫动脉在内髂骨动脉的水平是闭合的 在卵巢与子宫之间的副动脉（在子宫卵巢韧带内）用双极镊子是可凝固的 LUAO的结果 显性纤维瘤平均降低58.8% 症状改善93.2% 低并发率7.3% 纤维瘤复发率2年9.0%

Role of concurrent LUAO in LM 在LM中LUAO的角色  LUAO with LM (non RCT)  Reduced operative blood loss  Improved symptoms resolution (98.1% vs 83.1%)  Decreased fibroid recurrence (6.2% vs 20.7%)  No difference in pregnancy rate (Alborzi et al 2009)  Similar operative blood loss  Longer operating time (100 ± 34 vs 90 ± 37 min)  Decreased fibroid recurrence (2% vs 13%) (Bae et al 2011) LUAO和LM（非RCT） 减少了手术失血 改善了症状的消散（98.1%VS83.1%) 降低了纤维瘤复发（6.2%VS20.7%） 怀孕率没有不同 LUAO与LM（非RCT) 相似的手术失血 更长的手术时间（100±34 VS 90±37min) 降低了纤维瘤复发（2%VS13%)

UAE vs LUAO UAE LUAO P价值 年龄 33.1 34.9 NS 显性纤维瘤 68 48 NS LAUO P-value Age (years) 33.1 34.9 NS Dominant fibroid (mm) 68 48 Fibroid volume shrinkage at 6 months 53% 39% 0.063 Complete myoma infarction at 6 months 82% 23% 0.001 Complication rate Intrauterine necrosis Pregnancy rate Delivery rate Abortion rate Birth weight (gms) IUGR rate 31% 69% 50% 34% 3270 13% 11% 3% 67% 46% 33% 2768 38% 0.006 0.001 NS 0.013 0.046 Non RCT with 100 women in each group (Mara et al 2012) UAE LUAO P价值 年龄 33.1 34.9 NS 显性纤维瘤 68 48 NS 纤维瘤容积萎缩在6个月 53% 39% 0.063 完全肌瘤梗死在6个月 82% 23% 0.001 并发率 31% 11% 0.006 子宫内坏死 31% 3% 0.001 怀孕率 69% 67% NS 分娩率 50% 46% NS 流产率 34% 33% NS 出生体重（gms) 3270 2768 0.013 IUGR率 13% 38% 0.046

Uterine Artery Embolization 子宫动脉栓塞  An option for appropriately selected women who wish to retain their uteri and are not interested in optimizing future fertility  Technical success 98-100% Menorrhagia improved in 81- 94% Pressure symptoms improved in 64-96%  Mainly for symptom control Efficacy decreases with uterine size and multiple fibroids  Uterine volume reduction 35- 52% Fibroid volume reduction 37- 69% 适当选择妇女的方法，希望保留子宫的和对最优化未来生育能力没有兴趣的妇女 主要对症状的控制 有效减少子宫大小和多发性纤维瘤 技术成功 98%-100% 月经过多改善81%-94% 压力性症状改善64%-96% 子宫容积减少35%-52% 纤维瘤容量减少37%-69%

Post-procedural complications 操作后并发症 Significant pelvic pain Post-embolization syndrome – 20-35% (Goodwin et al 1999; Hemingway et al 1988) Expulsion of fibroids – up to 4-10% (Bradley et al 1998, Berkowitz et al 1999 Walker et al 2004, Oligiari et al 2005) Loss of ovarian function – 5-8% Uterine infection – < 1% (Ravina et al 1998; Chrisman et al 2000) (Tropeano et al 2008 ) Pulmomary embolism - 0.25% (Czeyda-Pommersheim,et al 2006) 明显的骨盆疼痛 栓塞后综合症 20%-35% 子宫肌瘤的排出 多达4-10% 卵巢功能的散失 5-8% 子宫感染 <1% 肺栓塞-0.25%

Long term result 长期结果 Symptoms control decreased to 72-73% of patients after 5-7 years (Popovic et al 2009) Fibroid recurrence  10% within 2.5 years and 53.3% after ≥ 4 years  Mostly are new growths with re-growth occurred in 12.5- 37.5% (Marret et al 2003; Kim et al 2010) Hysterectomy risk  2.9-6.9% at 12-18 months  13.7-32% at 5 years (Spies et al 2005; Huang et al 2006: Gabriel-Cox et al. 2007; van der Kooij et al 2010; Moss et al 2011) 5-7年后症状控制降低到72%-73%的病人数 纤维瘤复发率 2.5年内10%，4年后53.3% 大多数是新生长和再生长一起发生在12.5-37.5% 子宫切除术的风险 12-18个月为2.9-6.9% 5年13.7-32%

UAE vs Surgery UAE与手术比较 Compared with hysterectomy and myomectomy, UAE resulted in shorter hospital stay, quicker return to activities, and a higher minor complication rate after discharge as well as the unscheduled visits and readmission rates. There was no difference in the major complication rates. (Cochrane Syst Rev 2006) UAE is associated with a higher re-operation rate than myomectomy (29-33% vs 3-6%) (Broder et al 2002, Spies et al 2005 与子宫切除术和肌瘤切除术比较，UAE使住院时间更短，更快恢复活动，出院后更高的次要并发症，还有无计划的就诊和再住院率 主要并发率没有不同 UAE与子宫肌瘤切除术相比，UAE与更高的再手术率有关（29-33% vs3-6%）

Major complications 主要并发症 UAE Surgery REST trial (N = 157) Edwards et al 2007 HOPEFUL trial (N = Dutton et al 2007 EMMY trial (N = 177) Hehenkamp et al 2005 12% 20% 4.5% 14.8% 1.3% 14.5% UAE 手术 REST试验（N=157） 12% 20% HOPEFUL试验（N= 4.5% 14.8% EMMY试验（N=177） 1.3% 14.5%

UAE increases pregnancy complications An RCT showed that the likelihood of conceiving is higher after myomectomy than UAE (77.5% vs 50%) (Mara et al 2008) UAE increases risk of spontaneous miscarriage (35% vs 16% in fibroid containing pregnancies) (Homer & Saridogan 2010) UAE increases risk of Caesarean section and post- partum haemorrhage Homer & Saridogan 2010 一个RCT显示肌瘤切除术后怀孕的可能性要比UAE高（77.5%vs50%） UAE增加了自发性流产的风险 （在纤维瘤中，包括怀孕，35%vs16%） UAE增加了剖腹产和产后出血的风险

Temporary uterine artery occlusion 临时的子宫动脉闭合 Doppler guided paracervical clamp to occlude the uterine arteries - The Flowstat system The clamp is placed along the lateral vaginal fornices at the 9 and 3 o’clock positions to identify the uterine artery by the Doppler auditory signal The clamp is closed on both sides to squeeze the uterine artery against the lateral border of the uterus The clamps remain in situ for 6 hours 多普勒指引宫颈旁的钳子关闭子宫动脉 钳子沿着侧阴道穹窿放置在9和3点的位置，通过多普勒听觉信号来区分子宫动脉 钳子在两侧被关闭以便挤压子宫动脉对抗子宫的侧边缘 钳子保留在此位置6个小时

Initial experience 最初的经验 迄今为止，共75个妇女被报告 没有明显的术后疼痛 6个月子宫和纤维瘤容量减少近40-50% A total of 75 women reported so far No significant post-operative pain Uterine and fibroid volume reduced by 40-50% at 6 months Symptoms improved by 80-90% at 6 months 2 cases of hydronephrosis requiring temporary stenting Series too small and long term results unknown (Dickner et al 2004; Istre et al 2004; Garaza-Leal et al 2005; Lichtinger et al 2005; Vilos et al 2006) Angiography and pyelography in 8 patients after clamping Bilateral uterine occlusion confirmed in 4, unilateral in 2 Ureter was occluded in 2 (Hald et al 2008) 迄今为止，共75个妇女被报告 没有明显的术后疼痛 6个月子宫和纤维瘤容量减少近40-50% 6个月症状改善近80-90% 2例肾盂积水要求临时支架 系列太小的和长期结果未知 在8例夹钳后的病人中行血管造影术和肾盂造影术 两侧子宫闭合确认在4，单侧在2， 输尿管被关闭在2

Prospective pilot study 预测试验性研究 Group 1 : Bilateral uterine artery occlusion for 5.8±1.4 hours Group 2 : Bilateral uterine artery occlusion for 6 to 9 hours (7.05±1.0) Group 1 Group 2 N = 17 N = 13 Menorrhagia scores change at 1 month 3 months 6 months Volume reduction at 6 months Dominant fibroid Whole uterus -16% -22% -39% 24% 16% +3% -24% -42% 29% 16% ( Vilos et al 2010) 群组1：两侧子宫动脉闭合为5.8±1.4小时 群组2：两侧子宫动脉闭合为6-9小时（7.05±1.0） Group1 Group2 N=17 N=13 月经过多量的改变在 1个月 -16% +3% 3个月 -22% -24% 6个月 -39% -42% 6个月容积减少 显性的纤维瘤 24% 29% 全子宫 16% 16%