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预防性卵巢切除术

时间:2023-05-01 理论教育 版权反馈
【摘要】:后逐步改为≥45岁者,腹部手术时可预防性切除卵巢。预防性子宫切除和双附件切除术是预防Lynch综合征的有效手段。所以,提出预防卵巢癌的措施中提出遗传性卵巢癌家族史和BRCA基因突变者不愿做预防性卵巢切除者,可做输卵管切除,既保留卵巢又防止卵巢癌发生的设想。

卵巢是女性生殖器官恶性肿瘤中最常见的肿瘤之一,以宫颈癌、子宫内膜癌和卵巢癌最常见,号称“妇科三癌”。卵巢癌是妇科致死最高的恶性肿瘤,至今仍无早期筛查的好方法,一经发现70%已属晚期,70%手术等治疗后会复发,女性一生中1/70左右可能发生卵巢囊肿,其中1/70可能为恶性,约70%的患者在5年内死亡,所以妇女对卵巢患有肿瘤是十分恐慌的事。卵巢癌目前尚未发现可检测到癌前病变状态(浸润前癌变可能不存在),大多卵巢癌进展非常迅速,局限在局部的诊断窗口期非常短暂,且也难以发现和捕捉到。也有称卵巢癌在普通妇女中发病率仍为40/10万,每年只有很少妇女能有机会筛查,筛查结果假(+)会导致严重心理问题,加重经济负担,而真正确诊卵巢癌的唯一途径是手术和病理检查。

一、早年做预防性卵巢切除术

由于卵巢癌至今病因不明,早期症状不典型,现有筛查方法(妇科检查、B超、CA125检测)均实际意义不大,但一旦确诊卵巢癌常是预后不良。所以早有提出预防性卵巢切除问题。20世纪六七十年代均有因其他妇科疾病而行开腹手术时,同时切除患者双侧卵巢。也实有“校枉过正”,不考虑双侧正常健康的卵巢对女性的生理、心理、内分泌及性生活质量的重要性,为了预防一侧卵巢癌而需牺牲无数妇女的正常卵巢,在这种“宁可错杀一千,而不能漏一个”的指导下,以往基层医院妇产科医师力量薄弱,尚由外科医师协助手术,外科医师等对卵巢的作用不清楚,稍见卵巢增大即切除,也“理直气壮”的称预防日后卵巢癌发生,现今看来均是知识面问题而造成的“过度治疗”之一。也以早年提出对35—40岁妇女已生育过者,在开腹手术中,为预防日后卵巢癌者,均予切除双卵巢,实为对卵巢认识的无知,是对预防性卵巢切除术误解。后逐步改为≥45岁者,腹部手术时可预防性切除卵巢。随着对卵巢功能的认识,现在一般建议≥50岁的患者在开腹时可作预防性卵巢切除术,目前术中是否切除卵巢在术前均与患者及家属沟通,也有至绝经年龄手术时也不愿切除卵巢者。因绝经当年也并非卵巢功能一点也不存在。在绝经早年卵巢功能虽还低落,但还有微功能。所以,术前与患者说明切除与否的利弊,最后患方定夺。好在现今的诊疗技术与水平,对卵巢功能的认知程度较20世纪六七十年代有较大进步,所以在双方沟通后再按医疗原则办事为妥。

子宫切除同时切除正常卵巢(预防性卵巢切除),可去除卵巢日后恶变可能,但保留卵巢有可能与阴道穹窿或盆侧壁发生粘连,造成性交痛,或慢性盆腔疼痛,也有发生残余卵巢综合征或残留卵巢综合征可能(详见本书卵巢综合征章节),保留的卵巢也可能因发生良性肿瘤而需再次手术可能。

二、现今对预防性卵巢切除术的见解

1.遗传性卵巢癌 占卵巢癌的5%~10%,早在20世纪50年代已有描述。卵巢上皮性卵巢癌发生与3个遗传性癌综合征有关。①遗传性乳癌-卵巢癌(hereditary breast and ovarian cancer,HBOC);②遗传性位点特异性卵巢癌(hereditary site specific ovarian cancer,HSSOC);③遗传性非息肉性结肠直肠综合征(hereditary non-polyposis colorectal cancer syndrome,HNPCC),其中尤以遗传性乳癌—卵巢癌(HBOC)最常见,通常家族中有3个或更多的卵巢癌认为是遗传性卵巢癌,若家族中在一二级亲属中有5个或更多人患乳癌或卵巢癌则可成为遗传性乳癌卵巢癌综合征。对这类高危人群欧美国家就要进行BRCA基因突变筛查。具有这类遗传性卵巢癌家族史的妇女,她一生中患卵巢癌的风险可高达50%。随着年龄增大,由于遗传基因突变则患乳癌、卵巢癌风险增加。若到70岁可增加到94%,所以造成对生育后或35—40岁具有高危家属史的妇女双侧预防性卵巢切除。至于切除术的途径根据个人具体情况采取开腹、腹腔镜或经阴道切除。

遗传性非息肉性结肠直肠癌综合征又称Lynch综合征,是常染色体显性遗传性疾病,由DNA错死修复基因突变引在。分为Ⅰ型(无肠外肿瘤)和Ⅱ型(有肠外肿瘤),Ⅱ型除结肠直肠癌外,常有多样肠外肿瘤,常见为子宫内膜癌和卵巢癌,家属中还可有输尿管和肾盂的移行细胞癌、胃癌、小肠癌、甲状腺癌、皮肤癌等,在卵巢癌中BRCA1和BRCA2基因突变引起遗传性乳腺癌,卵巢癌综合征和LynchⅡ型占大多数。Lynch综合征相关基因突变者患卵巢癌总体风险为12%。临床平均年龄42岁,54%为浆液性乳头状癌,12%为内膜样癌,诊断时大多为Ⅰ期及Ⅱ期,此与一般卵巢上皮癌70%诊断时已散发为晚期有明显区别,因期别早、早发现,所以5年生存率近70%。预防性子宫切除和双附件切除术是预防Lynch综合征的有效手段。

2.有关卵巢癌的二元论模式与卵巢外起源学说 人们对卵巢癌发病机制不明,卵巢表面生发上皮起源假说已基本否定,高级别卵巢浆液性癌大多起源输卵管的观点已被国际上多数学者接受。2004年美国霍普金斯大学病理学家提出两级分级标准:高级别卵巢浆液性癌大多起源于输卵管,低级别卵巢浆液性癌主要间接来源输卵管。所以,提出预防卵巢癌的措施中提出遗传性卵巢癌家族史和BRCA基因突变者不愿做预防性卵巢切除者,可做输卵管切除,既保留卵巢又防止卵巢癌发生的设想。是否真正有效可行?还需进一步研讨和观察。

三、预防性卵巢切除术可否完全预防卵巢癌

尽管预防性卵巢切除术在防止高危者的卵巢癌发生有一定作用,但仍需谨慎行事,因仍有难以与卵巢癌区别的腹腔内癌的发生,有报道16个高危家庭中28名成员预防性卵巢切除后有3名发生弥漫性腹腔内癌。也有报道具高风险者,已切除卵巢者腹膜癌是一般人群的8.4倍。作者认为,遗传性的易感性不仅局限于卵巢,而且可延伸和扩张到相关组织,而仅仅是局限于卵巢组织;同样上述遗传性卵巢癌家族史和BRCA基因突变者作输卵管切除以企图预防卵巢癌,也仅是设想,还须深入进一步研讨。

(石一复)

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中英文名词对照

肿瘤细胞减灭术(primary debulking surgery,PDS)

国家综合癌症网(National Comprehensive Cancer Network,NCCA)

满意的肿瘤细胞减灭术(optimal debulking surgery,ODS)

间歇性肿瘤细胞减灭术(intervel debulking surgery,IDS)

新辅助化疗(neoadjuvant chemotherapy,NACT)

细胞周期特异性药物(cell cycle specific agents,CCSA)

化疗相关停经(chemotherapy-related amenorrhea,CRA)

化疗药物总剂量(cumulative dose,CD)

剂量强度(dose intensity,DI)

剂量密度(dose dengsity)

先期化疗(primary chemotherapy)

称新辅助化疗(neoadjuvant Chemotherapy,NACT)

诱导化疗(induction chemotherapy)

疾病复发间隔(treatment-free interval,TFI)

铂类药再治的间隔(platimum-free interval,PFI)

单纯疱疹病毒胸苷激酶(herpes simplex virus thymidine kinase,HSV-tk)

更昔洛韦(ganciclovir,GCV)

旁观者效应(bystander effect)

多药耐药(multidrug resistance,MDR)

多药耐药基因1(multidrug resistance-1,MDR-1)

基因芯片(DNA microarray)

谷胱甘肽过氧化物酶3(glutathione peroxidase 3,GPX3)

切除修复交叉互补基因(excision repair cross complementation group 1,ERCC1)

条件复制型腺病毒(conditionally replicative adenovirus,CRAds)

腺相关病毒载体(adeno-asssociated virus,AAV)

柯萨奇-腺病毒受体(Coxsackie and adenovirus receptor,CAR)

条件性复制型腺病毒载体(conditionally replicating adenovirus vectors,CRAds)

树突状细胞(dendritic cell,DC)

肿瘤相关抗原(tumor associated antigen,TAA)

肠内营养(enteral nutrition,EN)

肠外营养(parenteral nutrition,PN)

经皮内镜下胃造口(percutaneous endoscopic gastrostomy,PEG)

经皮内镜下空肠造口术(percutaneous endoscopic jejunostomy,PEJ)

早期肠内营养(early enteral nutrition,EEN)

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