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마더세이프라운드 - 임신중부인암(이인호 교수)


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마더세이프라운드 - 임신중부인암(이인호 교수)

  1. 1. Gynecologic Cancer in Pregnancy In Ho Lee M.D., Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University, College of Medicine, Seoul, Korea
  2. 2. Issues in Pregnancy • Is termination of the pregnancy necessary or advantageous? • Will the malignant neoplasm or the therapy for it affect the fetus? questions is difficult! Finding answers to these • Should therapy be deferred and initiated at the termination of the pregnant stage? • Should patients be advised against future pregnancies?
  3. 3. Cancer and Young women Site Occurrence in women aged 15-44 years (%) Cervix 35 Ovary 15 All genital 18 Lymphomas 23 Thyroid 50 Bones and joints 27 Melanoma 27 Breast 15 Leukemia 10 Soft tissues 20
  4. 4. Incidence of Cancer in Pregnancy Site Estimated incidence Per 1000 pregnancies Cervix uteri Noninvasive 1.3 Invasive 1.0 Breast 0.33 Melanoma 0.14 Ovary 0.10 Thyroid Unknown Leukemia 0.01 Lymphoma 0.01 Colorectal 0.02
  5. 5. Cervical Cancer in Pregnancy
  6. 6. Diversity of Opinion • Cervical cancer prevents pregnanacy ↔ Pregnancy prevents cervical cancer • Pregnancy accelerates cervical cancer ↔ Pregnancy slows the growth of cervical cancer • Young age is a good prognostic indicator ↔ Youth is a detriment • High estrogen levels predispose to cervical cancer ↔ High estrogen content controls cervical cancer • Radiotherapy is the treatment of choice ↔ Primary radical surgery is the best treatment
  7. 7. Five-year survival rates Pregnant Non-pregnant Author survival (%) survival (%) Creasman (1970) Stage I 85 80 Stage II 60 70 Sablinska (1977) Stage I 72 76 Pregnancy has Stage II not been shown convincingly to 54 56 Lee (1981) adverse effect on cancer of the cervix! have an Stage Ib - surgery 93 91 Stage Ib - radiation 80 88 Nisker and Shubat (1983) Stage Ib 70 87 Sivanesaratnam (1993) Surgery 78 92
  8. 8. Incidence • The incidence of CIN varies but it is generally between 1% to 8% of abnormal cytology. • Invasive cancer is the most common solid tumor during pregnancy • Fortunately its incidence is 0.2% to 0.9% of all pregnancies • 1.4% of all cases of cervical cancer
  9. 9. Symptom • Usually asymptomatic, detected during routine Pap smear • Vaginal bleeding and discharge may be mistaken for pregnancy complications • Pelvic pain : less frequent
  10. 10. Cervical cancer screening • Cervical cancer peaks between age 30 to 49 years • The mean age of pregnant women with invasive cervical cancer 31.8y. • Significant numbers diagnosed in 2nd or 3rd trimester • Efficacy and safety of screening is well- documented
  11. 11. Diagnosis • Colposcopy is safe and well tolerated and should be used to evaluate abnormal Pap smear • Any suspicious lesion should be biopsed • Overall risk of biopsy-related complications is approximately 0.6% : usually mild bleeding .
  12. 12. Diagnosis • Cervical conization during pregnancy is crucial in diagnosis and staging of MIC • Complications – Hemorrhage 2-13% – Fetal loss : 17%-50%, <10% in 2nd and 3rd – PMRM, preterm labor, infection, laceration and stenosis – Fetal Salvage rate : 89-95%
  13. 13. Workup • Physical examination • Cervical biopsy • Conization • Chest x-ray with abdominal shield • Since about 83% of cases are stage I, cys toscopy and proctoscopy are eliminated : also I.V.U and Enema.
  14. 14. Treatment of CIN • No indications for immediate treatment of cases with CIN during pregnancy • Pap smear or Colposcopy every trimester • Vaginal Delivery with higher rate of regression at 6-week examination compared to Caesarean delivery • Definitive treatment : 6 weeks postpartum
  15. 15. Treatment of invasive cancer • For a microinvasive cancer of cervix, excision can be performed – The outcome is usually good, the pregancy can proceed and a vaginal delivery can be anticipated • Invasive cancer during pregnancy is curable • Treatment is clear in the 1st and 3rd trimester but less clear in the 2nd trimester • Two modalities used are surgery or RT as in non-p regnant
  16. 16. First trimester(1-12weeks) • Fetal salvage is not feasible in women rece iving treatment for invasive cancer • The maternal risk from delaying therapy unt il fetal maturity is excessive • Surgery with the fetus in situ
  17. 17. Second trimester (13-25weeks) • The period of greater uncertainty • Fetal salvage is exceedingly rare with high neonatal mortality rate • Delaying therapy for several weeks may subject the mother to the theoretical risk of disease progression
  18. 18. Second trimester (13-25weeks) • If patient elects to interrupt pregnancy : The same as in 1st trimester • If not ..define a target gestational age for fetal delivery • Monitor by U/S and MRI for tumor extension • Documented lung maturity
  19. 19. Summary of t.t Delays Author N. Stage Delays outcome Monk et al 3 IB Mean DOD (1992) 24wk Duggan et 8 IA-IB Mean NED al (1993) 20.6w Sorosky 8 I Mean NED et al (1996 15.6w
  20. 20. 3rd trimester Treatment • Wait for few weeks till fetal maturity then apply definitive therapy • Surgery in 89% may be coordinated with fetal delivery and completed as a 1-stage operation. • If R.T..external beam immediately after delivery followed by intracavitary radiation
  21. 21. Effect of Mode of Delivery Author C.S %survival vaginal %survival Creasman 9 89% 15 87% et al(1970) Lee et al 12 90% 11 89% (1981) Nisker et al 14 64% 17 65% (1983) Van Der 28 78% 16 67% Vang et al (1995)
  22. 22. Treatment before 20 weeks • The ‘standard’ management for stage-1b1 cervical cancer up to 20 weeks’ gestation would be a radical hysterectomy with the fetus in situ, and should be offered as a management option. • For more advanced disease chemoradiation will be preferred. • In early pregnancy spontaneous miscarriage will usually occur after the woman has received 34–40 Gy, although after 20 weeks’ gestation miscarriage can be protracted (mean 33–44 days), or may not occur spontaneously in 60%, so that the uterus will need to be emptied.
  23. 23. Treatment after 20 weeks • A planned delay to allow fetal viability or even maturity is also an option, and may not actually significantly affect her survival. • A delay of up to 6 weeks for stage-1b2 and 12 weeks for stage-1b1 disease is reasonable, with careful clinical and/or MRI monitoring of the woman every 2–4 weeks. • Steroids can be given with no apparent adverse effects on the cancer to expedite fetal lung maturity.
  24. 24. Treatment after 20 weeks • Caesarean section with radical hysterectomy after fetal viability or maturity is reached with stage-1b disease. • Radical hysterectomy 48–72 h after vaginal delivery, assuming labour is not obstructed – the advantages of reduced blood loss and a better vaginal cuff with the resected specimen. • Delaying intervention even further may be an option with reassurance gained by negative histology following laparoscopic lymphadenectomy • Chemotherapy, particulary after the first trimester, is well tolerated without deterimental effects on the fetus and appears to be an option for the selected patient
  25. 25. Ovary Cancer in Pregnancy
  26. 26. Adnexal Masses in Pregnancy • 0.05-3.2% of live birth • Mature teratomas and paraovarian or corpus luteum cysts • Malignancy rate : 3.6-6.8% in persistent masses • Germ cell, stromal, or epithelial tumors of low malignant potential • TVS or TAS • MRI if additional imaging is needed
  27. 27. Adnexal Masses in Pregnancy • CA125 – Peak in the first trimester (7-251 U/ml) and decrease consistently thereafter – Low level elevations are not associated with malignancy • Surgical removal of persistent masses in the second trimester • 51-70% resolve during pregnancy • Acute complication : less than 2%
  28. 28. Adnexal Masses in Pregnancy • Indication of Surgical Intervention – A strong suspicion of malignancy and/or large size (>8-10 cm) – Symptomatic patients – An increased risk of torsion/rupture/obstruction of labor Leiserowitz GS, Obset Gynecol Surv 2006;61(7):463-70 • Ovarian malignancy has no effect on pregnancy and pregnancy has no effect on prognosis of ovarian cancer • Benign cyst may undergo torsion causing acute abdomen commonly in puerperium
  29. 29. Management • Benign tumor – First trimester : observe and follow-up with ultrasound till second trimester (to reduce risk of abortion) and then removal – Second trimester : laparotomy – Third trimester : Caesarean section and removal of tumor • Malignant tumors : treated as non-pregnant i.e. surgical staging and cytoreductive surgery
  30. 30. Management of an ovarian mass in pregnancy Size<10cm Size>5cm Simple, Unilateral Complex, papilations No evidence of Ascites and/or Bilateral Follow to 18 weeks Follow with ultrasound Persists or growth Persistent at 18 weeks or any 30%-50% increase in size of mass at any point in gestation Surgical exploration Surgical exploration
  31. 31. Aspiration of Cyst Fluid • Poor sensitivity to detect malignancy (25- 82%) • 25% of cysts recur within 1 yr • Spillage and seeding of cancer cell into the peritoneal cavity -> Changing the stage and prognosis • Exception – Clinical and radiolographic evidence of advanced ovarian cancer and unfit to ungergo surgery – Permit initiation of neoadjuvant chemotherapy
  32. 32. Adnexal Masses in Pregnancy (Cheil General Hospital)
  33. 33. Materals • 1996년 1월 – 2001년 12월 • 255명 / 50,126 분만 (0.5%) • 평균연령 : 28.7세 • 평균크기 : 9.5cm • 수술시기 – 분만전 (160명, 62.7%) : 15.2 주 – 분만시 (95명, 37.3%) • 응급수술 (42명,17.6%) – 난소염전 (30명) – 난소파열 (5명) – 동통 (7명)
  34. 34. Histologic Diagnosis of Adnexal Mass 5.5% (14/255)
  35. 35. Fetal Outcomes *Spontaneuos abortion (3), Artificial abortion (2) ** Intrauterine fetal death (1)
  36. 36. Ovary Cancer and Chemotherapy
  37. 37. Three stages of Embryonic development • The first stage – The first 2 weeks of life – Blastocyst is resistant to teratogens – A surviving blastocyst will not manifest any organ’s specific abnormalities as a result of that teratogen – Early embryonic cells have not differentiated sufficiently, so if one cell dies, another can take over
  38. 38. Three stages of Embryonic development • The second stage – Organogenesis or the process of organ differentiation – The most critical period extends from the 3rd to 8th weeks of development (5th through 10th weeks of gestational age) when susceptibility to teratogenic agents is maximal – In the human fetus, this period usually ends by the 13th week of gestation
  39. 39. Three stages of Embryonic development • The third stage – characterized by increase in fetal and organ size – Brain and gonadal tissue are exceptions because they continue to differentiate beyond the second period – Affect general fetal growth but will not produce organ-specific morphologic malformations.
  40. 40. Characteristics of patients
  41. 41. Histologic characteristics
  42. 42. Surgical management
  43. 43. Histology of tumor in Literature
  44. 44. Adjuvant Chemotherapy (n=8) • 3 patients received chemotherapy with fetus in utero • 5 patients received chemotherapy just after delivery • One patient with EOC complicating ectopic pregnancy received postoperative chemotherapy.
  45. 45. Adjuvant Chemotherapy (n=8) • Of five patients with germ cell tumor, 3 patients received it with the fetus in utero (range, 22.8-30.6 weeks of GA) and two patients at 2 weeks after cesarean delivery with 4 courses of bleomycin, etoposide and cisplatin (BEP). • Three patients with EOC received 6 courses of paclitaxel plus carboplatin at 2 weeks after cesarean delivery. • All 26 patients with ovarian cancer complicating pregnancy were successful in having a full term delivery
  46. 46. Chemotherapy during first trimester of pregnancy All cancer chemotherapeutic agents should be considered teratogenic and should be avoided in the first trimester of pregnancy if it is at all possible!
  47. 47. Chemotherapy during preg in Literature • Zemlickis D, Lishner M, Degendorfer P, Panzarella T, Sutcliffe SB, Koren G. Fetal outcome after in utero exposure to cancer chemotherapy. Arch Intern Med 1992; 152: 573-6. • Doll DC, Ringenberg QS, Yarbro JW. Antineoplastic agents and pregnancy. Semin Oncol 1989; 16: 337-46. • Arango HA, Kalter CS, Decesare SL, Fiorica JV, Lyman GH, Spellacy WN. Management of chemotherapy in a pregnancy complicated by a large neuroblastoma. Obstet Gynecol 1994; 84: 665-8. • Horbelt D, Delmore J, Meisel R, Cho S, Roberts D, Logan D. Mixed germ cell malignancy of the ovary concurrent with pregnancy. Obstet Gynecol 1994; 84: 662-4.
  48. 48. Chemotherapy during pregnancy in Literature • Huang HP, Fang CN, Kan YY. Chemotherapy for ovarian mucinous cystadenocarcinoma during pregnancy: a case report. Eur J Gynaecol Oncol 2004; 25: 635-6. • Bayhan G, Aban M, Yayla M, Gul T, Yaldiz M, Erden AC. Cisplatinum combination chemotherapy during pregnancy for mucinous cystadenocarcinoma of the ovary. Case report. Eur J Gynaecol Oncol 1999; 20: 231-2. • Mendez LE, Mueller A, Salom E, Gonzalez-Quintero VH. Paclitaxel and carboplatin chemotherapy administered during pregnancy for advanced epithelial ovarian cancer. Obstet Gynecol 2003; 102: 1200-2. • Sood AK, Shahin MS, Sorosky JI. Paclitaxel and platinum hemotherapy for ovarian carcinoma during pregnancy. Gynecol Oncol 2001; 83: 599- 600
  49. 49. Chemotherapy in Pregnancy • The administration of chemotherapy during the first trimester can be associated with morphologic abnormalities and fetal loss • Chemotherapy administrated in second and third trimesters appears not to be associated with a significant risk of structural anomalies, but some reports suggest an associated with preterm delivery, fetal death in utero, and intrauterine growth retardation • When cytotoxic drugs are used in late pregnancy, the nadir should be timed to avoid the interval when delivery is expected
  50. 50. Endometrial Cancer in Pregnancy
  51. 51. Incidence • Endometrial cancer in association with pregnancy is extremely rare – It is a disease mainly of postmenopausal women – high levels of progesterone in pregnancy would be expected to antagonize the effect of oestrogen on the endometrium • Only 28 cases are reported in the literature • Diagnosis is usually made following curettage for persistent bleeding after a miscarriage or postpartum
  52. 52. Management • The outcome is usually good, and the treatment is the same as for the nonpregnant woman. • It may be reasonable to treat conservatively very early stage, well differentiated endometrial cancer in young women wishing to retain their fertility. • High-dose progestin treatment over 6–10 months with regular sampling allowed five of 10 women to have babies • However, at long-term follow-up of nine of them, eight developed recurrent cancer, although all survived.
  53. 53. 경청해 주셔서 감사합니다.