中国Peutz-Jeghers综合征女性患者妇科疾病诊治现状调查

石月; 陈奕清; 丁景新; 宁燕; 汪清; 马凤华; 谭灏文; 康玉

doi:10.19401/j.cnki.1007-3639.2022.11.003

您当前的位置：

首页 >

文章列表页 >

中国Peutz-Jeghers综合征女性患者妇科疾病诊治现状调查

专题论著 | 更新时间：2025-12-31

- 中国Peutz-Jeghers综合征女性患者妇科疾病诊治现状调查
- Questionnaire survey on current status of clinical screening and treatment of gynecological disease in females with Peutz-Jeghers syndrome
- 中国癌症杂志 2022年32卷第11期页码：1049-1064
- 作者机构：
  
  1. 复旦大学附属妇产科医院妇科肿瘤科，上海 200090
  2. 复旦大学上海医学院临床医学院，上海 200032
  3. 江西合因教育科技有限公司，江西赣州 342604
- 作者简介：
  
  [ "石月（ORCID: 0000-0003-3213-3863），博士，主治医师;" ]
  [ "陈奕清（ORCID: 0000-0003-0374-4059），博士。" ]
  [ "康玉，医学博士，主任医师，博士研究生导师，复旦大学附属妇产科医院临床研究中心办公室主任，复旦大学附属妇产科医院Ⅰ期临床试验病房负责人，遗传性妇科肿瘤诊疗和预防团队首席专家。获教育部科技发明二等奖、教育部科技进步二等奖、中华医学奖三等奖，以及上海医学科技奖三等奖3次。获“上海市科技启明星”称号，上海市卫生系统第十四届“银蛇奖”，第十七届“明治生命科学奖”，上海卫生系统优秀学科带头人，Gynecologic Oncology杂志编委。" ]
- 基金信息：
  
  上海申康医院发展中心临床科技创新项目(SHDC12020108);上海市老龄化和妇儿健康研究专项(2020YJZX0202)
- DOI：10.19401/j.cnki.1007-3639.2022.11.003
  中图分类号： R737.33
- 收稿：2022-10-12，
  
  修回：2022-11-16，
  
  纸质出版：2022-11-30
- 稿件说明：
移动端阅览
石月, 陈奕清, 丁景新, 等. 中国Peutz-Jeghers综合征女性患者妇科疾病诊治现状调查[J]. 中国癌症杂志, 2022,32(11):1049-1064.

Yue SHI, Yiqing CHEN, Jingxin DING, et al. Questionnaire survey on current status of clinical screening and treatment of gynecological disease in females with Peutz-Jeghers syndrome[J]. China Oncology, 2022, 32(11): 1049-1064.
石月, 陈奕清, 丁景新, 等. 中国Peutz-Jeghers综合征女性患者妇科疾病诊治现状调查[J]. 中国癌症杂志, 2022,32(11):1049-1064. DOI： 10.19401/j.cnki.1007-3639.2022.11.003.

Yue SHI, Yiqing CHEN, Jingxin DING, et al. Questionnaire survey on current status of clinical screening and treatment of gynecological disease in females with Peutz-Jeghers syndrome[J]. China Oncology, 2022, 32(11): 1049-1064. DOI： 10.19401/j.cnki.1007-3639.2022.11.003.

摘要

背景与目的：

Peutz-Jeghers综合征（Peutz-Jeghers syndrome，PJS）相关的妇科疾病包括小叶状子宫颈内膜腺体增生（lobular endocervical glandular hyperplasia，LEGH）、子宫颈胃型腺癌（gastric type adenocarcinoma of the uterine cervix，GAS）和卵巢环状小管性索肿瘤（sex cord tumor with annular tubules，SCTAT）等。特别是LEGH发病早，疾病进展为GAS快，早诊困难，预后不佳，为患者诊治带来了巨大挑战。目前相关研究数据，尤其是在中国进行的临床研究有限。本研究旨在调查中国PJS患者妇科相关疾病的临床表现、患病情况、健康筛查及诊治现状，以期帮助指导早筛早诊，为PJS女性妇科疾病，特别是为恶性肿瘤的诊治和预后预测提供可靠的临床依据。

方法：

基于目前妇科临床PJS患者诊疗现状、患者反馈，结合文献阅读设计针对性调查问卷，并于2022年3月26日—2022年7月29日发放，以有效填写的患者为调查对象，统计患者的一般情况、既往史、家族史、妇科临床表现和诊疗情况。对各项目进行分层分析以找出相关高危因素保护因素及诊疗欠缺之处。

结果：

本调查共回收有效问卷154份，根据入组和排除标准剔除5份，149例患者中114例（76.51%）具有妇科临床症状，主诉多为异常子宫出血（55.70%），近一半（41.61%）患者诉阴道排液。不到一半（47.65%）的患者接受过子宫颈筛查，人乳头状瘤病毒（human papilloma virus，HPV）阳性率低（7.04%）。约1/3（36.91%）的患者接受过基因检测，52例（94.5%）的患者存在

STK

11突变，其中64.52%系蛋白截断突变，但在癌症和癌前病变发病率及发病年龄上差异无统计学意义。胚系突变遍布整个基因，但未发现位于非编码的9号外显子（E9）上的突变，突变发生率最高为E7（25.81%）。本研究中，无亲缘关系的患者携带相同突变，其发病年龄和疾病谱完全不同。因妇科肿瘤接受手术的患者中，1/3出现了女性生殖道多部位同步胃型黏液性病变（synchronous mucinous metaplasia and neoplasia of the female genital tract，SMMN-FGT）。GAS患者中不到一半的患者得到了及时干预和规范化手术治疗，73.33%的患者接受了术后辅助治疗。40%的患者术前完成生育，0例接受植入前遗传学检测（preimplantation genetic testing，PGT）。

结论：

本研究聚焦中国PJS女性妇科临床表现及相关诊治现状，发现子宫异常出血、阴道排液作为主要临床症状存在于一半的PJS女性中，发生年龄显著左移。蛋白截断突变作为队列中主要突变类型，与临床表型无相关性，并不影响其癌症风险及发病年龄。携带相同突变的无亲缘关系女性疾病发生情况完全不同，证明环境因素极大地影响PJS患者的疾病外显率。中国PJS女性群体未建立起遗传咨询和妇科健康筛查意识，基因检测普及度低，不到一半罹患妇科肿瘤的患者接受标准手术和辅助治疗。罹患妇科肿瘤的PJS患者普遍生育率低，极少接受PGT。这主要由于临床对于PJS的认知度局限，遗传咨询普及度低，干预不及时，使得PJS患者，尤其罹患妇科肿瘤的PJS女性患者失去了优生优育的机会。

Abstract

Background and purpose:

Peutz-Jeghers syndrome (PJS)-related diseases in female reproductive system include lobular endocervical glandular hyperplasia (LEGH)

gastric type adenocarcinoma of the uterine cervix (GAS) and sex cord tumor with annular tubules (SCTAT)

etc. In particularly

PJS-related LEGH has an early age-onset

and the disease could progress rapidly to GAS. Early diagnosis is difficult

and the prognosis has been proved poor

which brings great challenges to the diagnosis and treatment of patients. Research data are limited

especially in China. The purpose of this study was to investigate the clinical manifestations

disease pattern

related risk factors

and the status of disease screening

management of gynecological diseases in Chinese PJS patients

providing more clinical evidence and helping with the early screening and early diagnosis of gynecological diseases

especially malignant diseases in female PJS patients.

Methods:

Based on the status of management of gynecological diseases in female patients with PJS and patients’ feedback

our questionnaire was designed and launched from March 26

2022 to July 29

2022. The general condition

past family history

past medical history

gynecological clinical manifestations and management of the patients were investigated. A stratified analysis of each item was conducted to find out the high-risk factors and protective factors associated.

Results:

A total of 154 valid questionnaires were recruited in our study

and 5 patients were excluded according to the inclusion/exclusion criteria. 114/149 patients (76.51%) had gynecological symptoms

and the main complaint was abnormal uterine bleeding (83 patients

55.70%)

nearly half of them had vaginal watery discharge (62 patients

41.61%)

47.65% (71/149) had received cervical screening tests

and the human papilloma virus (HPV) positive rate was only 7.04%. Only one-third of the patients (55/149

36.91%) had received genetic testing

and 52 patients had

STK

11 mutations (94.5%). 64.52% were truncating mutations

but with no significant differences in the incidence and oneset age of gynecological disease compared with non-truncating mutations in our cohort.

STK

11 germline mutations were found all over the whole gene

while no mutation found in

non-coding exon 9. Exon7 was found with the highest mutation rate (25.81%). Unrelated patients with the same

STK

11 mutation had completely different disease spectrum and onset age of gynecological diseases. Among the patients with gynecological cancer treated with surgery

1/3 were found with synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT) on pathology. Less than half received standardized intervention and prompt surgery

and only 73.33% of them received adjuvant therapy. Only 40% of the patients completed fertility before surgery

and none received PGT.

Conclusion:

This study first put the focus on the gynecological symptoms

diagnosis and management of Chinese women with PJS. We found that abnormal uterine bleeding and vaginal watery discharge were the main symptoms in half of the women with PJS

and the age of onset was significantly shifted to the younger population. Truncating mutations

as the main mutation type in Chinese women with PJS

has no significant association with clinical phenotype

for which the mutation type does not affect their risk of cancer or age onset. Environmental factors may play an important role in disease development and progression of PJS patients as the age onset and disease spectrum of unrelated females carrying the same

STK

11 mutation were completely different. At the same time

the awareness of genetic counseling and gynecological disease screening system have not been established in the PJS female population

as the genetic test coverage is low (1/3)

and only less than half of the patients with gynecological cancer received standard surgery and adjuvant therapy. PJS patients with gynecological cancer generally have low fertility rate

and only one case received PGT in our cohort

which is mainly due to the low cognition and understanding of PJS in our society. The low coverage of genetic counseling

and the delay of intervention made PJS patients

especially females with gynecological diseases

lose their fertility opportunity.

关键词

Keywords

references

GIARDIELLO F , TRIMBATH J . Peutz-Jeghers syndrome and management recommendations [J ] . Clin Gastroenterol Hepatol , 2006 , 4 ( 4 ): 408 - 415 . DOI: 10.1016/j.cgh.2005.11.005 http://doi.org/10.1016/j.cgh.2005.11.005 https://linkinghub.elsevier.com/retrieve/pii/S1542356505010931 https://linkinghub.elsevier.com/retrieve/pii/S1542356505010931

李白容 , 孙涛 , 蒋宇亮 , 等 . Peutz-Jeghers综合征发病机制及临床诊治研究进展 [J ] . 世界华人消化杂志 , 2019 , 27 ( 9 ): 576 - 582 .

LI B R , SUN T , JIANG Y L , et al. Pathogenesis, diagnosis, and treatment of Peutz-Jeghers syndrome [J ] . World Chin J Dig , 2019 , 27 ( 9 ): 576 - 582 .

KHANNA K , KHANNA V , BHATNAGAR V . Peutz-Jeghers syndrome: need for early screening [J ] . BMJ Case Rep , 2018 , 11 ( 1 ): e225076 . DOI: 10.1136/bcr-2018-225076 http://doi.org/10.1136/bcr-2018-225076 https://casereports.bmj.com/lookup/doi/10.1136/bcr-2018-225076 https://casereports.bmj.com/lookup/doi/10.1136/bcr-2018-225076

VAN LIER M G , WAGNER A , MATHUS-VLIEGEN E M , et al. High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations [J ] . Am J Gastroenterol , 2010 , 105 ( 6 ): 1258 - 1264 ; DOI: 10.1038/ajg.2009.725 http://doi.org/10.1038/ajg.2009.725

WAGNER A , ARETZ S , AURANEN A , et al. The management of Peutz-Jeghers syndrome: European hereditary tumour group (EHTG) guideline [J ] . J Clin Med , 2021 , 10 ( 3 ): 473 . DOI: 10.3390/jcm10030473 http://doi.org/10.3390/jcm10030473 https://www.mdpi.com/2077-0383/10/3/473 https://www.mdpi.com/2077-0383/10/3/473

LATCHFORD A , COHEN S , AUTH M , et al. Management of Peutz-Jeghers syndrome in children and adolescents: a position paper from the ESPGHAN polyposis working group [J ] . J Pediatr Gastroenterol Nutr , 2019 , 68 ( 3 ): 442 - 452 . DOI: 10.1097/MPG.0000000000002248 http://doi.org/10.1097/MPG.0000000000002248 https://journals.lww.com/00005176-201903000-00031 https://journals.lww.com/00005176-201903000-00031

薛誉 , 石月 , 徐言 , 等 . 妇科肿瘤诊疗中遗传咨询开展现状的问卷调查 [J ] . 第二军医大学学报 , 2021 , 42 ( 6 ): 641 - 650 .

XUE Y , SHI Y , XU Y , et al. Questionnaire survey on status quo of genetic counseling on gynecologic tumors [J ] . Acad J Second Mil Med Univ , 2021 , 42 ( 6 ): 641 - 650 .

FREY M K , LEE S S , GERBER D , et al. Facilitated referral pathway for genetic testing at the time of ovarian cancer diagnosis: uptake of genetic counseling and testing and impact on patient-reported stress, anxiety and depression [J ] . Gynecol Oncol , 2020 , 157 ( 1 ): 280 - 286 . DOI: S0090-8258(20)30007-X http://doi.org/S0090-8258(20)30007-X

FARHAN M . Green tea catechins: nature’s way of preventing and treating cancer [J ] . Int J Mol Sci , 2022 , 23 ( 18 ): 10713 . DOI: 10.3390/ijms231810713 http://doi.org/10.3390/ijms231810713 https://www.mdpi.com/1422-0067/23/18/10713 https://www.mdpi.com/1422-0067/23/18/10713

BEGGS A D , LATCHFORD A R , VASEN H F , et al. Peutz-Jeghers syndrome: a systematic review and recommendations for management [J ] . Gut , 2010 , 59 ( 7 ): 975 - 986 . DOI: 10.1136/gut.2009.198499 http://doi.org/10.1136/gut.2009.198499

ISHIDA H , TAJIMA Y , GONDA T , et al. Update on our investigation of malignant tumors associated with Peutz-Jeghers syndrome in Japan [J ] . Surg Today , 2016 , 46 ( 11 ): 1231 - 1242 . DOI: 10.1007/s00595-015-1296-y http://doi.org/10.1007/s00595-015-1296-y

FADARE O . Mucinous proliferations of the uterine corpus: comprehensive appraisal of an evolving spectrum of neoplasms [J ] . Adv Anat Pathol , 2022 , 29 ( 5 ): 275 - 296 . DOI: 10.1097/PAP.0000000000000348 http://doi.org/10.1097/PAP.0000000000000348

MIKAMI Y . Gastric-type mucinous carcinoma of the cervix and its precursors-historical overview [J ] . Histopathology , 2020 , 76 ( 1 ): 102 - 111 . DOI: 10.1111/his.13993 http://doi.org/10.1111/his.13993 https://onlinelibrary.wiley.com/doi/10.1111/his.13993 https://onlinelibrary.wiley.com/doi/10.1111/his.13993

顾伟勇 , 陶祥 , 张丽虹 , 等 . 女性生殖道同期发生的黏液上皮化生和肿瘤 [J ] . 中华病理学杂志 , 2018 , 47 ( 11 ): 845 - 850 .

GU W Y , TAO X , ZHANG L H , et al. Synchronous mucinous metaplasia and neoplasia of the female genital tract [J ] . Chin J Pathol , 2018 , 47 ( 11 ): 845 - 850 .

陈默 , 李佳佳 , 陶祥 , 等 . 女性生殖道同期发生的黏液性上皮化生和肿瘤14例分析 [J ] . 复旦学报(医学版) , 2022 , 49 ( 3 ): 402 - 410 .

CHEN M , LI J J , TAO X , et al. Clinical analysis of 14 cases of synchronous mucinous metaplasia and neoplasia of the female genital tract [J ] . Fudan Univ J Med Sci , 2022 , 49 ( 3 ): 402 - 410 .

ABU-RUSTUM N R , YASHAR C M , BEAN S , et al. Cervical cancer, version 1. 2021 NCCN clinical practice guidelines in oncology [EB/OL ] . ( 2020-10-02 )[ 2022-05-10 ] . https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf. https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf.

周晖 , 刘昀昀 , 罗铭 , 等 . 《2021 NCCN子宫颈癌临床实践指南(第1版)》解读 [J ] . 中国实用妇科与产科杂志 , 2020 , 36 ( 11 ): 1098 - 1104 . DOI: 10.19538/j.fk2020110115 http://doi.org/10.19538/j.fk2020110115

ZHOU H , LIU Y Y , LUO M , et al. Interpretation of the NCCN clinical practice guidelines for cervical cancer(2021.v1) [J ] . Chin J Pract Gynecol Obstet , 2020, 36 ( 11 ): 1098 - 1104 .

TUNG N , LIN N U , KIDD J , et al. Frequency of germline mutations in 25 cancer susceptibility genes in a sequential series of patients with breast cancer [J ] . J Clin Oncol , 2016 , 34 ( 13 ): 1460 - 1468 . DOI: 10.1200/JCO.2015.65.0747 http://doi.org/10.1200/JCO.2015.65.0747

LIM W , OLSCHWANG S , KELLER J J , et al. Relative frequency and morphology of cancers in STK 11 mutation carriers [J ] . Gastroenterology , 2004 , 126 ( 7 ): 1788 - 1794 . DOI: 10.1053/j.gastro.2004.03.014 http://doi.org/10.1053/j.gastro.2004.03.014 https://linkinghub.elsevier.com/retrieve/pii/S0016508504003804 https://linkinghub.elsevier.com/retrieve/pii/S0016508504003804

MEHENNI H , RESTA N , PARK J G , et al. Cancer risks in LKB 1 germline mutation carriers [J ] . Gut , 2006 , 55 ( 7 ): 984 - 990 . DOI: 10.1136/gut.2005.082990 http://doi.org/10.1136/gut.2005.082990 https://gut.bmj.com/lookup/doi/10.1136/gut.2005.082990 https://gut.bmj.com/lookup/doi/10.1136/gut.2005.082990

WANG Z Q , WANG Z , WANG Y , et al. High risk and early onset of cancer in Chinese patients with Peutz-Jeghers syndrome [J ] . Front Oncol , 2022 , 12 : 900516 . DOI: 10.3389/fonc.2022.900516 http://doi.org/10.3389/fonc.2022.900516 https://www.frontiersin.org/articles/10.3389/fonc.2022.900516/full https://www.frontiersin.org/articles/10.3389/fonc.2022.900516/full

HEARLE N , SCHUMACHER V , MENKO F H , et al. STK 11 status and intussusception risk in Peutz-Jeghers syndrome [J ] . J Med Genet , 2006 , 43 ( 8 ): e41 . DOI: 10.1136/jmg.2005.040535 http://doi.org/10.1136/jmg.2005.040535

RESTA N , PIERANNUNZIO D , LENATO G M , et al. Cancer risk associated with STK 11/ LKB 1 germline mutations in Peutz-Jeghers syndrome patients: results of an Italian multicenter study [J ] . Dig Liver Dis , 2013 , 45 ( 7 ): 606 - 611 . DOI: 10.1016/j.dld.2012.12.018 http://doi.org/10.1016/j.dld.2012.12.018 https://linkinghub.elsevier.com/retrieve/pii/S1590865812004963 https://linkinghub.elsevier.com/retrieve/pii/S1590865812004963

浏览量

2658

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

卵巢癌患者血清唾液酸含量检测的价值