乐巢优品是真是假:子宫内膜异位症 诊断及治疗的进展
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子宫内膜异位症 诊断及治疗的进展
(2007-05-24 18:50:51)转载子宫内膜异位症 诊断及治疗的进展
北大医院
周应芳
大体病理
郎景和教授将内异症分为四个类型:
腹膜型
卵巢型
阴道直肠型
特殊部位型或盆腔外型
大体病理
日本产科妇人科学会所分的类型:
1.无色素异位病灶
2.含色素异位病灶
3.继发性病变
无色素异位病灶
1. 小水泡
2. 浆液性囊泡
3. 表面隆起
含色素异位病灶
1 .紫蓝色结节
2. 血性囊泡
3. 散在烧灼样灶
4. 含铁血黄素着色
5. 点状出血斑
6. 浆膜下出血
7. 子宫内膜异位囊肿
子宫内膜异位症继发性病变
1. 粘连及腹膜袋形成
2. 挛缩状瘢痕
异位症的治疗
郎景和教授总结近年来国内外多数学者达成的共识子宫内膜异位症的治疗有5个“最好方法”:
腹腔镜手术是最好的治疗
卵巢抑制是最好的治疗
手术?药物治疗?再次腹腔镜手术的3阶段治疗(three phase therapy)是最好的治疗
妊娠是最好的治疗
助孕技术是最好的治疗
腹腔镜手术
Feasibility of robotic laparoscopic surgery: 146 cases(Belgium)
Gynecological surgeries:
tubal reanastomoses
hysterectomies
endometriosis cure
neosalpingostomy
World J Surg
保守性手术 (手段)
二氧化碳激光
治疗内异症经循征医学证实疗效肯定,安全性高,但因设备昂贵、手术速度慢和止血效果差等近年来临床报道明显减少
单极和双极电凝
微波
超声刀
手术方法
1.分离粘连
2.清除子宫内膜异位结节
3.去除卵巢子宫内膜异位病灶
卵巢子宫内膜异位囊肿分型
Nezhat等对216个出血性囊肿(子宫内膜异位囊肿)进行了仔细的病理研究后,将卵巢子宫内膜异位囊肿分为两型。
Ⅰ型子宫内膜异位囊肿(原发性)
Ⅱ型子宫内膜异位囊肿(继发性)
ⅡA
ⅡB
ⅡC
囊肿部分切除术 不可取!
手术要点
充分分离粘连----防止损伤
彻底剥除囊肿----减少复发
认真止血----防止血肿及粘连
多保留正常卵巢----利于日后妊娠
硬化疗法
腹腔镜下或超声监测下囊肿穿刺抽液注入无水乙醇或重组白介素-2(最近),认为创伤小、恢复快,囊肿复发率减少。
Noma 和Yoshida(J Gynaecol Obstet 2001)83例:
随访半年以上者有74例,复发11例(14.9% );
同期30例腹腔镜下剥除术的复发率3.8%(P>0.05);
乙醇留置时间小于10min及多发囊肿的复发率明显高 。
Epithelial abnormalities in cystic ovarian endometriosis (Italy)
339 cases:
metaplasia
hyperplasia
atypia
endometrioid carcinoma arising in endometriosis
子宫神经去除术或 骶前神经切除术
缓解盆腔中央疼痛
我们近年来开展了子宫神经去除术 (laparoscopy uterine nerve
循证医学证据
国外循证医学证据:
对下腹中央疼痛者行骶前神经切除术(PSN)疗效明显
近年来许多医生提倡用腹腔镜子宫神经去除术(laparoscopy uterine nerve
但也有学者研究发现LUNA缓解疼痛的效果并不明显,此外,LUNA的远期疗效也不如PSN
国内循证医学研究:尚缺乏资料
药物治疗
EBM data
腹腔镜保守性手术后用药疗程以6个月为宜,3个月的疗程不能降低疼痛复发率
重度内异症有生育要求者,术后是否有必要行药物治疗仍有争议,虽然药物治疗推迟了患者的妊娠时机,但也有报道认为积极助孕治疗后妊娠机会还会增加
Danazol
国外已少用
RCT( Morgante 等,Hum Reprod 1999):腹腔镜手术+ GnRH-a治疗6个月后每天100mg小剂量达那唑再用药6个月:
能减少中重度子宫内膜异位症患者的盆腔疼痛复发,并且几乎没有副作用
国内许多医生更倾向于使用孕三烯酮或内美通
Danazol-loaded IUD
A danazol-loaded IUD
Containing 300-400 mg of danazol
Inserted for 6 months (n = 18) (median age 36.6 years) referred for recurrent pelvic pain.
Dysmenorrhea, dyspareunia, and pelvic pain significantly decreased after the first month, with a persistent effect during the 6 months of IUD insertion.
GnRH-a治疗
是发达国家最常使用的药物缓解疼痛效果明显(90%以上)
保守性手术后使用可以推迟疼痛复发(Br J Obstet Gynaecol 1999)
价格昂贵
低雌激素效应
对不孕患者能提高受孕力?(Curr Opin Obstet Gynecol 2000)
GnRHa 对 骨密度(BMD)的影响
反向添加疗法 ( add-back therapy)
定义:使用GnRH-a类的同时补充小剂量雌激素和
作用:即可防止骨质丢失,又减少了低雌激素的
添加方案:
GnRH-a减量治疗 (draw-back therapy)
目前使用的剂量偏大?
buserelin减量治疗的报道(J Obstet Gynaecol Res 1999);
减量治疗:先用全量nafarelin,4周后将药量减半维持,疗效同全量,低雌激素症状减轻,骨质丢失减少(Fertil Steril 2000 );
triptorelin作用时间较长,可每6周注射1次(Hong Kong Med J 2000);
避孕药
假孕疗法(pseudopregnancy therapy)
已少用
短效避孕药
1~2片/d,以闭经为准,连服6~9个月
疗效和假孕疗法相似
副作用轻
Mifepristone
国外有学者用米非司酮治疗子宫内膜异位症,国内近年来报道明显增多
结果认为闭经率高,副反应轻,控制疼痛效果满意
米非司酮价格便宜,使用前景好
国内正在做临床验证
Others
芳香化酶抑制剂(aromatase inhibitor) 瑞宁得(anastrozole,阿那曲唑)
环氧合酶抑制剂
LNG-IUS (Mirena)
SERM: raloxifene (USA)
含药物阴道环?
GnRH拮抗剂
芳香化酶抑制剂(Ais)
In premenopausal women, the ovary can overcome the estrogen blockade by reflex increments of LH and FSH, so AIs must be combined with a gonadotropin releasing hormone (GnRH) agonist to prevent the reflex LH and FSH increments.
AIs have been used in infertility and can increase ovulation rate.
A pilot trials showed that aromatase inhibitors could decrease pelvic pain associated with endometriosis.
芳香化酶抑制剂-临床研究
Treatment of endometriosis and chronic pelvic pain with letrozole and norethindrone acetate: a pilot study.
letrozole (2.5 mg, po) and norethindrone acetate (2.5 mg) for 6 months
Second-look laparoscopy
环氧合酶抑制剂 COX-2 specific inhibitor
Animal researchs
Regression of endometrial explants in rats treated with the cyclooxygenase-2 inhibitor rofecoxib.
Dogan E, Fertility & Sterility. 82 Suppl 3, 2004
Cyclooxygenase-2 selective inhibitor prevents implantation of eutopic endometrium to ectopic sites in rats.
Matsuzaki S. Fertility & Sterility. 2004 France
环氧合酶抑制剂-临床应用
STUDY DESIGN
pelvic pain after conservative surgery for symptomatic endometriosis (Stage I and II) (n = 28) .
a COX-2 specific inhibitors (rofecoxib, 25mg per day) (n = 16) or placebo (n = 12) was given for 6 months.
RESULTS
A significant improvement of both pelvic pain and dyspareunia was observed after a 6 months persisting since the end of the treatment (P < 0.0001).
The efficacy of rofecoxib was higher than placebo and no recurrence occurred, while in the placebo-treatment a 16% (2/12) occurred.
No significant side effects have been found with the use of rofecoxib.
CONCLUSIONS
rofecoxib was effective, safe and low cost therapy in the management of pelvic pain associated to endometriosis and might be also proposed in early stage of endometriosis.
Cobellis L,European Journal of Obstetrics, Gynecology, & Reproductive Biology. 116(1):100-2, 2004 Italy
Successful treatment of severe endometriosis in two premenopausal women with an aromatase inhibitor
Methods
anastrozole with the addition of 200-mg oral progesterone (P) capsules once daily, hs, and calcitriol 0.5 microg oral capsules twice daily. All three medications were given daily for 21 days followed by 7 days off, for a 28-day treatment cycle. rofecoxib 12.5 mg was administered once a day continuously for the 28-day cycle.
RESULT(S):
Treatment resulted in a rapid, progressive reduction in symptms over 3 months with the maintenance of remission of symptoms for over 24 months after treatment in both cases. There was confirmation of absence of disease in one case by follow-up laparoscopy 15 months after treatment. Pregnancy was achieved in both cases after 24 months.
Shippen ER, Fertility & Sterility, 2004 USA.
含药物宫内节育器 (LNG-IUS)
Vercellini 等(Fertil Steril 1999 )治疗20例行保守性手术后痛经复发患者,12个月后随访效果:
很满意
满意
一般
不满意
Fedele等(Fertil Steril 2001)治疗11例直肠阴道膈子宫内膜异位症,患者痛经、性交痛和盆腔痛症状明显改善,异位结节缩小
新近报道:对中重度内异症行腹腔镜保守性手术后即刻放置LNG-IUS可明显降低疼痛的复发率
GnRH拮抗剂-临床报道(Germany)
GnRH antagonist cetrorelix (Cetrotide) subcutaneous injection in a 3 mg dosage once weekly over 8 weeks
All the 15 patients
Serum oestradiol oscillated around a mean concentration of 50 pg/ml during therapy.
Second look Lap: regression occurred in 60% of cases (9/15), a mean stage III of disease. declined to stage II.
新的治疗探索
内异症的基础研究将会继续地推动临床治疗,甚至会改变人们治疗内异症的传统思路
抗黏附
抗侵袭
抗血管生成药物可能会逐步用于临床
细胞因子调控
受体干预
基因治疗
动物实验
抗肿瘤坏死因子
Efficacy of anti-tumor necrosis factor therapy in the treatment of spontaneous endometriosis in baboons(狒狒).
A statistically significant decrease in red lesion surface area in the treatment group
Barrier,-B-F,et al. Fertil-Steril. 2004 Mar; 81 Suppl 1: 775-9
动物实验
Antiangiogenesis therapy for endometriosis
antihuman vascular endothelial growth factor
TNP-470
Endostatin
The angiostatic compounds significantly decreased microvessel densities and the number of established endometriosis lesions
Nap,-A-W,et al.J-Clin-Endocrinol-Metab. 2004 Mar; 89(3): 1089-95
人体研究
血管生成抑制剂(肿瘤治疗方面)
进入临床研究的有20种
抗体有3中
抗VEGF抗体(endostatin,内皮抑素)
Ⅲ期临床
抗VEGF-R2抗体
Ⅰ期临床
抗av?3抗体
Ⅱ期临床
新的治疗探索
郎景和教授创立的内异症发病的“在位内膜决定论” :
加强对在位子宫内膜进行调控、干预和治疗的研究,以改变其生物学特质和行为
这种 “源头治疗”即可治疗异位病灶又有利于防治出现新的异位病灶,可望收到“标本兼治”的理想效果
给内异症的治疗开辟了一个崭新的天地
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