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1、,子宫内膜癌治疗相关问题 北京大学人民医院妇产科 王建六,子宫内膜癌新分期 子宫内膜癌淋巴结切除必要性 子宫内膜癌子宫切除的范围,子宫内膜癌09分期修订1,和II期有关的新证据（修订2）,累及宫颈内膜腺体的预后和期无差异,09分期把累及宫颈内膜腺体归入期,和III期有关的新证据,腹水或腹腔冲洗液细胞学阳性88分期为A期 多项大样本病例对照研究结果，腹水细胞学阳性和腹腔或淋巴结的转移不相关，不影响预后 没有足够的证据说明腹水细胞学阳性与复发风险和治疗效果有何关系 针对腹水细胞学阳性的治疗尚有争议：不处理？化疗？放疗？激素治疗？,子宫内膜癌09分期修订3,09分期删去细胞学检查结果,子宫内膜癌09
2、分期修订4,资料表明主动脉旁淋巴结转移预后比盆腔淋巴结转移差。,妇科常见肿瘤诊治指南 中华医学会妇科肿瘤分会 p49 I期子宫内膜癌应行手术分期 术式为筋膜外子宫切除术及双附件切除术 盆腔及腹主动脉旁淋巴结切除和（或）取样术 术中如无明显淋巴结肿大，应系统切除淋巴结 术中有可疑淋巴结肿大，取样明确有无转移即可 腹主动脉旁淋巴结切除/取样指征： 可疑淋巴结转移 特殊组织类型 CA125显著升高 宫颈受累 深肌层受累 低分化,子宫内膜癌淋巴结切除的必要性？,全国高等院校教材 妇产科学 乐杰主编 林仲秋编写 p275 I期子宫内膜癌应行筋膜外子宫切除术及双附件切除术 盆腔及腹主动脉旁淋巴结切除和（或
3、）取样术 下列情况之一，应行盆腔及腹主动脉旁淋巴结切除 和（或）取样术 可疑淋巴结增大 宫颈受累 CA125显著升高 特殊组织类型 癌灶累及宫腔面积超过50% 低分化 深肌层受累,Cochrane Database Syst Rev. 2010 Jan 20;(1):CD007585. Lymphadenectomy for the management of endometrial cancer. May K, Bryant A, Dickinson HO, Kehoe S, Morrison J University of Oxford, Womens Centre,No evidence
4、 that lymphadenectomy decreases the risk of death or disease recurrence compared with no lymphadenectomy in women with presumed stage I disease. The evidence on serious adverse events suggests that women who receive lymphadenectomy are more likely to experience surgically related systemic morbidity
5、or lymphoedema/lymphocyst formation.,J Natl Cancer Inst. 2008 Dec 3;100(23):1707-16. Epub 2008 Nov 25 Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial. Rome, Italy,CONCLUSION: Although systematic pelvic lymphadenectomy statistic
6、ally significantly improved surgical staging, it did not improve disease-free or overall survival.,Lancet. 2009 Jan 10;373(9658):125-36. Epub 2008 Dec 16. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study.,Collaborators (180) Amos C, Blake P, B
7、ranson A, Buckley CH, Redman CW, Shepherd J, Dunn G, Heintz P, Yarnold J, Johnson P, Mason M, Rudd R, Badman P, Begum S, Chadwick N, Collins S, Goodall K, Jenkins J, Law K, Mook P, Sandercock J, Goldstein C, Uscinska B, Cruickshank M, Parkin DE, Crawford RA, Latimer J, Michel M, Clarke J, Dobbs S, M
8、cClelland RJ, Price JH, Chan KK, Mann C, Rand R, Fish A, Lamb M, Goodfellow C, Tahir S, Smith JR, Gornall R, Kerr-Wilson R, Swingler GR, Lavery BA, Chan KK, Kehoe S, Flavin A, Eddy J, Davies-Humphries J, Hocking M, Sant-Cassia LJ, Pearson S, Chapman RL, Hodgkins J, Scott I, Guthrie D, Persic M, Dani
9、el FN, Yiannakis D, Alloub MI, Gilbert L, Heslip MR, Nordin A, Smart G, Cowie V, Katesmark M, Murray P, Eddy J, Gornall R, Swingler GR, Finn CB, Moloney M, Farthing A, Hanoch J, Mason PW, McIndoe A, Soutter WP, Tebbutt H, Morgan JS, Vasey D, Cruickshank DJ, Nevin J, Kehoe S, McKenzie IZ, Gie C, Davi
10、es Q, Ireland D, Kirwan P, Davies Q, Lamb M, Kingston R, Kirwan J, Herod J, Fiander A, Lim K, Head AC, Lynch CB, Browning AJ, Cox C, Murphy D, Duncan ID, Mckenzie C, Crocker S, Nieto J, Paterson ME, Tidy J, Duncan A, Chan S, Williamson KM, Weekes A, Adeyemi OA, Henry R, Laurence V, Dean S, Poole D,
11、Lind MJ, Dealey R, Godfrey K, Hatem MM, Lopes A, Monaghan JM, Naik R, Evans J, Gillespie A, Paterson ME, Tidy J, Ind T, Lane J, Oates S, Redford D, Ford M, Fish A, Larsen-Disney P, Johnson N, Bolger A, Keating P, Martin-Hirsch P, Richardson L, Murdoch JB, Jeyarajah A, Lamb M, McWhinney N, Farthing A
12、, Mason PW, Kitchener H, Beynon JL, Hogston P, Low EM, Woolas R, Anderson R, Murdoch JB, Niven PA, Kerr-Wilson R, Chin K, Flynn P, Freites O, Newman GH, McNally O, Cullimore J, Olaitan A, Mould T, Menon V, Redman CW, George M, Hatem MH, Evans A, Fiander A, Howells R, Lim K, Cawdell G, Warwick AP, Eu
13、stace D, Giles J, Leeson S, Nevin J, van Wijk AL, Karolewski K, Klimek M, Blecharz P, McConnell D.,Hysterectomy and bilateral salpingo-oophorectomy (BSO) is the standard surgery for stage I endometrial cancer. Systematic pelvic lymphadenectomy has been used to establish whether there is extra-uterin
14、e disease and as a therapeutic procedure,median follow-up of 37 months (IQR 24-58) 191 women had died: 88/704 standard surgery group 103/704 lymphadenectomy group 251Recurrent disease 107/704 standard surgery group 144/704 lymphadenectomy group),INTERPRETATION no evidence of benefit in terms of over
15、all or recurrence-free survival for pelvic lymphadenectomy in women with early endometrial cancer. Pelvic lymphadenectomy cannot be recommended as routine procedure for therapeutic purposes outside of clinical trials.,子宫内膜癌淋巴结切除利与弊 争论“由来已久”！,早期：淋巴结转移率较低,国内 中山肿瘤：临床7.9%,8.6%, 38.4% 浙江肿瘤：临床4.4%,14%，34.
16、8% 国外 Stageb（a）G1-2 或 IaG3：转移率 0-2% Stageb（a）G3或 Ic（b）G1：转移率16%-20%,早期：LND并未降低复发 改善生存,1996年10月到2006年3月 意大利多个中心的514例术前FIGO分期为期子宫内膜癌患者 随机分配接受盆腔淋巴结切除术（n=264）或者不进行此手术（n=250）,“冲锋在前”的意大利研究,生存上没有差异,5年DFS 5年OS 未接受淋巴结切除术 81.7% 90.0% 接受淋巴结切除术 81% 85.9%,复发时间和复发率相似,复发时间 复发率 （mth） （49mth） 未进行淋巴结切除 13mth 33例（13.2
17、%） 淋巴结切除术者为 14mth 34例（12.9%）,复发部位相似,LND手术并发症明显增加,在手术时间和住院时间上，两组有显著的统计学差异 接受盆腔淋巴结切除术的患者有较高的早期和晚期术后并发症率，两组出现并发症的患者分别为81例和34例。,改变观念 无容置疑,子宫内膜癌治疗正朝个性化治疗发展 已有充足证据证明期子宫内膜癌患者，淋巴结切除术不能带来任何生存获益。,特殊患者手术难度增加，风险增加 肥胖 高龄 心血管疾病 糖尿病,淋巴结真的可以不切除吗？,Lesion sites and region Depth of myometrial invasion Cervical invasio
18、n Extrauterine invasion or not, single or multiple Pathological grade and classification Lymph vascular invasion(LVI),淋巴转移相关因素,病灶大小与淋巴结转移,Tumor Size LN mets: 2cm 4% 2cm 15% entire uterine cavity 35% 5-y survival: 2cm - 98% 2cm - 84% entire uterine cavity - 64%,建议有指征的行腹膜后淋巴结切除术,腹膜后淋巴结切除指征,术前B超、MRI等估计
19、深肌层受侵 术前病理分级为G3 术前临床分期II期以上 术中探查腹膜后淋巴结可疑转移 术中发现侵肌1/2 术中发现宫腔50%以上有病灶累及 子宫内膜浆乳癌、透明细胞癌等,一定要切除腹主动脉旁淋巴结吗？,Eur J Gynaecol Oncol. 2007;28(2):98-102. Prince of Wales Hospital, Shatin, Hong Kong Is aortic lymphadenectomy necessary in the management of endometrial carcinoma? 75 (46.0%) pelvic lymphadenectomy
20、alone 88 (54.0%) had both pelvic and aortic lymphadenectomy 35 (21.5%) nodal metastases positive pelvic 26 (16.0%) positive aortic 24 (27.3%) Isolated aortic metastases 17 cases (19.3%),35 patients with nodal metastases recurrence developed in 15 (42.9%) and all except one died within five to 50 mon
21、ths The recurrence rate was higher (63.6%) among patients with upper aortic lymph node metastases all those who recurred died of disease within seven to 28 months.,CONCLUSIONS,aortic lymphadenectomy provides both diagnostic and therapeutic value in the management of endometrial carcinoma with high m
22、etastatic risk.,Todo Y et al.Survival effect of para-aortic lymphadenectomy in endometrial cancer (SEPAL study): a retrospective cohort analysis. Lancet. 2010 Apr 3;375(9721):1165-72,671 patients with endometrial carcinoma systematic pelvic lymphadenectomy (n=325) pelvic and para-aortic lymphadenect
23、omy (n=346) INTERPRETATION: Combined pelvic and para-aortic lymphadenectomy is recommended as treatment for patients with endometrial carcinoma of intermediate or high risk of recurrence.,期子宫内膜癌子宫切除范围,33,I期子宫内膜癌 子宫切除范围： 全子宫切除术？筋膜外子宫切除术？二者异同？ 次广泛子宫切除术？,FIGO 2009 子宫内膜癌分期改变 影响子宫内膜癌子宫切除范围的选择吗？,局限于子宫的内膜癌
24、手术选择 争议：局限于子宫，宫颈累及？广泛子宫切除术？,子宫切除范围值得探讨,内膜癌病变局限于子宫-手术方式,Disease limited to uterus,Medically inoperable,operable,Tumor directed RT,Total hysterectomy and bilateral salpingo-oophorectomy Lympho nodes dissection pelvic+para aortic,The current NCCN Clinical Practice Guideline recommends practicing radica
25、l hysterectomy only when cervical infiltration is suspected on MRI or when confirmed by cervical biopsy.,2009NCCN,FIGO: 筋膜外子宫切除术 GOG2010:Women with endometrial cancers should undergo total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO), pelvic/paraaortic dissection 妇科常见恶性肿瘤治疗指南
26、：筋膜外子宫切除术 林巧稚妇科肿瘤学：全子宫切除术 中国妇产科学（曹泽毅主编）：筋膜外子宫切除术,I 期子宫内膜癌-手术方式,I 期子宫内膜癌-手术方式,Gan To Kagaku Ryoho. 1995 Aug;22(9):1163-8. Total hysterectomy is done for cases of stage 0, modified radical hysterectomy for stage I, radical hysterectomy for stage II, and radical hysterectomy combined with resection of
27、the metastatic lesions for stage III and IV Zhonghua Fu Chan Ke Za Zhi. 2002 Feb;37(2):90-3. Surgical method is not the main factor influenced the survive of stage I endometrial carcinoma.,为什么不行广泛或次广泛子宫切除术,Mauro Signorelli, et al. Gynecologic Oncology 2009 Modified Radical Hysterectomy Versus Extraf
28、ascial Hysterectomy in the Treatment of Stage I Endometrial Cancer,筋膜外子宫切除术,目的 to ensure that the cervix is entirely removed 适应症：子宫内膜癌，早期宫颈癌 与全子宫切除术异同？ 定义？ 手术中要点？,筋膜外子宫切除术,方法： The position of the ureters is determined by palpation without freeing the ureters from their beds. The parametrium is trans
29、ected medial to the ureter, but lateral to the cervix, keeping the paracervical ring intact. The uterosacral and vesicouterine ligaments are transected close to the uterus. There is no removal of paracolpos and a minimal part of vagina is resected at fornix level.,病变累及宫颈手术范围的选择,II期子宫内膜癌子宫切除范围首选广泛子宫切
30、除术（IIIII型子宫根治术） 累及宫颈粘膜，现在归为I期，子宫切除范围？ 累及粘膜和间质如果应该选择不同的手术范围，如何术前鉴别诊断之？ 宫颈是否累及？是否间质浸润？术前诊断困难,40,分期改变带来的新问题,累及宫颈粘膜（I期）？,OLD：IC差于IIA NEW：II差于所有I期 IIA期宫旁累及？ 宫颈癌早期手术范围 如何识别粘膜累及还是间质浸润,累及宫颈粘膜（ 一期）？,诊断和鉴别宫颈粘膜累及还是间质浸润,宫颈累及时子宫切除范围选择,指 南：广泛子宫切除术 局限于子宫归为一类 II期子宫内膜癌: 筋膜外或广泛子宫切除术 KOREA， JAPAN： Choose the surgical
31、extent of hysterectomy through their own disposition and do not strictly adhere the results of pre operative evaluation. JAPANESE group more than 70% of institutes never perform RH without regarding the preoperative status of cervical involvement (Watanabe) NORTH AMERICAN：20-30% center,II期子宫内膜癌RH 手术
32、的必要性,II期子宫内膜癌手术方式的选择,II期子宫内膜癌RH 手术的必要性,Depth of myometrial invasion and pelvic or paraaortic lymph node positivity were significantly correlated with paramatrial involvement. Of the 19 patients with pelvic lymph node metastasis, 8 patients (42.1%) had concomitant PMI. Conversely, of the 10 patients with PMI, 8(80.0%) had lymph node metastasis.,