Why is needed?

1014 cell duplication

The Magdelen with Smoking Flame, 1640
77000 kcal/322.6 MJ

Cancer
in  Pregnant  women

•  Notes in adult
To provide increased blood flow

In adult angiogenesis is a rare

event except in defined
physiological stimuli (e.g. ovary,
endometrium, pregnancy, wound
healing, tumor) or pathological
condition
Placenta, 2008
 successful vascularization =
normal pregnancy
Physician Reaction
• Ob/Gyn: Oh No! She has cancer!
• Med Onc: Oh No! She’s pregnant!
• Surgeon/Primary Care: Oh No! She’s
pregnant and has cancer!
• Get a Gyn/Onc involved!

Incidence
• 1/1000 – 1/1500 term pregnancies
• Incidence increasing: delayed childbearing
Frequency by Cell Type Frequency in Reproductive Age
Group

Breast Cancer 30%

Lymphoma 10%
Leukemia 23%
Melanoma 30%
Cervix 35%
Ovary 15%
Bone/soft tissue tumors 25%
Thyroid 50%
8

General Considerations
• Pregnancy does not have a proven
negative effect on any cancer
• Maintaining pregnancy after diagnosis
– Delay of treatment (assume delivery at 34th week)
• First trimester diagnosis: up to 28 week delay
• Second trimester diagnosis: up to 22 week delay
• Third trimester diagnosis: up to 10 week delay
What’s Different About Pregnancy?
• Hormones
• Metabolic Changes
• Hemodynamics
• Immunology
• Increased vascularity
• Age
• Few cases – anecdotal experience
• Inherent bias – breast, ovarian cancer
General Considerations
• Surgery
– Wait until 16-18 weeks for abdominal surgery:
Spontaneous Abortion: 40% à 3%
– Don’t remove corpus luteum if possible until
14th week (progesterone supp. 50mg BID)
– Deliver at maturity (at around 34 weeks)
– No proven teratogenic effects of anesthesia
 General Considerations General Considerations
• Chemotherapy – Chemotherapy and Breastfeeding
– First trimester (organogenesis ends at 12th week)
• Increase incidence of anomalies and abortion; drug
• Generally not recommended
dependent i.e. antimetabolites (MTX) – Long-term effects of chemotherapy on children
• IUGR and preterm labor are common exposed in utero
– Second and Third trimester
• Aviles, et.al. 43 cases with f/u for 3-19 yrs.
• Delay chemotherapy if possible until 16th week
– end of the rapid growth phase
• No increase in incidence of abortion Normal: Physically
Neurologically
• IUGR and preterm labor are common Intelligence
• Delay chemotherapy if possible until 16th week Psychologically
Sexual Development
– end of the rapid growth phase Hemotologically
Bone Marrow Cytogenics

General Considerations General Considerations

• Radiation Exposure • Obstetrical Considerations
– Diagnostic Radiation Dose to Fetus
– First trimester SONO: if dates?
• Avoid “unnecessary” diagnostic KUB 200 millicentigray

pelvic x-rays B.E. 450-900

– Level 2 SONO at 20 weeks
• Use MRI when possible CXR 1 – Chromosome analysis
• CXR/Mammogram – little risk CT Scan 900 • Amnio: 15 weeks
with shielding
– Therapeutic Radiation
IVP 600
• CVS: Transcervical (except cervix ca)
• High incidence of abortion and
L/S Scan 275-725
or transabdominal at 10-12 weeks
Lung Scan 370
anomalies Pelvic X-ray 210
– Deliver when mature
-Dose and trimester dependent
UGI Series 170-330 • L/S ratio at 34 weeks
• Betamethasone
Epidemiology of Genital HPV/SIL/Cancer in Pregnancy
Screening for Cervical Cancer/SIL

• Up to 40% of reproductive age women have HPV
• 2.0-6.5% cases of CIN/SIL occur in pregnant women
• 13,500 cases of cervical cancer & 4,000 deaths/ year in
U.S.
• 25% of women with cervical cancer are < 36 years old
• 1-13 cases of cervical cancer for every 10,000
pregnancy
• 1.9% of microinvasive cervical ca. occurs in pregnancy
• Stage for stage – prognosis is not effected by
pregnancy
• Symptoms of cancer similar to physiologic changes
of pregnancy
• Often a delay in diagnosis (fear of biopsies)
• Pap smear at registration and 8 weeks postpartum
– Ectocervical scrape
– Endocervical swab / brush – risky
– Reflex HPV typing
• Pap less accurate in pregnancy:
– increased false negative rate
• Blood, inflammation
• Failure to sample SCJ
• Concern about bleeding
• Difficult to see cervix: put CONDOM over speculum
• Absence of endocervical cells

Absence of Endocervical Cells Diagnosis of SIL and Cervical Cancer

• Careful palpation of cervix: no induration or enlargement

Conventional PAP Liquid PAP
• Biopsy all suspicious lesions: even if Pap/HPV are neg.
Non-pregnant 20% 10%
• Abnormal Pap:
– ASCUS/LSIL and HPV negative – repeat post partum
– ASCUS/LSIL and HPV positive: colposcopy
Pregnant 40% 20%
– ASCH: Colposcopy
- HSIL: Colposcopy
Post partum 30% 15%
• Don’t defer biopsy because of fear of bleeding or preterm
labor. First trimester easiest.
Post menopause 70% 35%
• Control bleeding with:
– Pressure
– Monsel’s solution (Ferric subsulfate)
– Silver nitrate
 Management of Cervical SIL On
Biopsy Management of Cervical SIL
• Satisfactory Colposcopy • Cone biopsy in pregnancy
– Indications
– LSIL / HPV+/- : Re-evaluate 6-8 weeks • Unsatisfactory colposcopy/ Pap: SCC, HSIL
• Adenocarcinoma in situ
postpartum • Microinvasive SCC
– HSIL / HPV+/- : F/U depends on trimester – Perform at 16-18 weeks
– Risks
– Low grade SIL (50%) regress postpartum • Abortion: 5%
• Hermorrhage: immediate: 9%, delayed: 4%
(Delivery route seems to matter) – Technique
– High grade SIL(30%) regress postpartum • Local wedge resection
• Shallow cone
– Vaginal delivery • LEEP
• Circumferential figure 8 sutures at cervical-vaginal junction
• Vasopressin/ local anesthetic with epinephrine

Vulvar/ Vaginal Condylomata or SIL in

Management of Cervical SIL Pregnancy
• Warts and SIL often enlarge rapidly in pregnancy
HSIL/ HPV positive: No Lesion Visible on • No treatment unless symptomatic
Colposcopy • Often regresses dramatically postpartum
• Treat if symptomatic or interferes with vaginal delivery -
– Reinspect: Vulva, Vagina, Anus and Cervix disease on perineal body or posterior fourchette
– Lugol’s: Vagina and Cervix • Treatment options:
– Trichloroacetic Acid
– Review Cytology – Podophyllin
– Aldara
– Consider Random Biopsies: 6 and 12:00 – 5-FU cream
– Laser
– Careful Follow-up: Pap and Colpo – Excision: scalpel; LEEP
– Cryotherapy
 Cervical Cancer in Pregnancy:
Cervical Cancer in Pregnancy Treatment by Stage
• Work-up • Stage IA1 - <3mm invasion; < 7mm wide
– MRI of pelvis/abdomen – 1.2% positive nodes
– Chest X-ray – Cone biopsy
– Carcinoembryonic Antigen (CEA)
– No further treatment necessary; simple
– CBC, BUN, Creatine, LFT’s hysterectomy
• Advanced disease – Vaginal delivery at term
– Urine cytology/ cystoscopy
– Stool for occult blood/ sigmoidoscopy

Cervical Cancer in Pregnancy: Cervical Cancer in Pregnancy:

Treatment by Stage Treatment by Stage
• Stage IA2 (3-5mm invasion, no vascular inv.): • Stage IA2, IB, IIA
– 6.3% positive nodes
– Second trimester: delay of up to 22 weeks
• Stage IB – Disease confined to cervix • Depends on desire for pregnancy
• Stage IIA – vaginal extension – Can probably safely wait until maturity
– Vaginal delivery: increased risk of hemorrhage and – Third trimester: delay of up to 10 weeks
cervical laceration
– Depends on desire for pregnancy • C-section, Radical hysterectomy and pelvic
• First trimester: delay of up to 28 weeks – degree of risk Lymph node dissection at maturity
unknown
• Radical hyst. and pelvic LND at diagnosis
• “Radical” cone biopsy/ trachelectomy/ cerclage and
extraperitoneal pelvic and aortic LND at 16-18 weeks
• C-Section and Radical hyst. and pelvic LND when mature
 Cervical Cancer in Pregnancy: Treatment
by Stage
• Stage IB (bulky) or Stages IIb-IV
– First trimester – delay of up to 28 weeks
• Depends on desire for pregnancy
– Unwanted
» Whole pelvic radiation therapy/ chemotherapy
» If SAB occurs before XRT is finished – proceed with cesium
insertions (about 35 days)
» Occasionally will need hysterotomy and pelvic LND if no SAB
and then cesium insertions; or a “small” radical hyst. & pelvic
LND if small residual cervical disease
– Wanted
» Consider chemotherapy until maturity at 34 weeks
Cervical Cancer in Pregnancy:
Treatment by Stage
• Stage IB (bulky) or Stages IIb-IV
– Second trimester – delay of up to 22 weeks
• Unwanted: pregnancy – Radiation therapy as above
– Spontaneous abortion at 35 days
• Wanted: pregnancy – consider chemotherapy until maturity
– Third trimester – delay of up to 10 weeks
• C-Section at maturity/ staging lap; transpose ovaries
• Start radiation therapy 2 weeks postpartum
• Consider chemotherapy until maturity

Juvenile Laryngeal HPV Ovarian Masses in Pregancy

• 3.5 million deliveries in U.S./year • Overall incidence
– 1:500 pregnancies
• Prevalence of HPV: 10-40%
– Increased incidence secondary to sonography
• Infected pregnant women: 350k - 1.5 • Incidence of true neoplasms
million – 1:1,000 pregancies
• 120 cases annually • Incidence of ovarian cancer
• Risk to infant (1:2,900 – 1:12,500) – 1:10,000 – 1:25,000 pregancies

• VAGINAL DELIVERY • Unexpected adnexal mass at C-Section

– 1:700 pregnancies
 Ovarian Masses in Pregnancy Management of Ovarian Masses in
Frequency by Type Pregnancy
• Generalizations
• Non-neoplastic – 33% – Symptoms
– Ultrasound/ MRI appearance
– Corpus luteum cyst
– Size
– Follicular cyst
– Gestational age
• Neoplastic – Benign – 63% – Tumor markers
– Dermoid (36%) • B-HCG, AFP, CA-125 all increased in pregnancy
– Serous cystadenoma (17%) • CA-125 should be normal after 1st trimester
– Mucinous cystadenoma (8%) – Fear of missing cancer or development of complications
– Others (2%) • Corpus luteum resolves by 14th week
• Neoplastic – Malignant – 5% • Ovarian cysts “benign” by Ultrasound or MRI, < 6 cm,
that do not change over time, do not require surgery
– Low malignant potential (3%)
• Cysts greater than 6-8 cm or inc. in size: “usually” operated on
– Adenocarcinoma (1%) • Cysts which persist after 18th week are “usually” operated on
– Germ cell / Stromal tumor (1%) – Usually operate at 18 weeks to minimize fetal loss

Complications of Ovarian Masses in Complications of Ovarian Masses in

Pregnancy Pregnancy
• Severe pain: 25% • Rupture/ tumor dissemination (10%)
• Obstruction of labor: 15% – C-Section • Anemia
• Torsion: 10% of cases • Malpresentations
– Sudden pain, Nausea & Vomiting etc. • Necrosis
– Most common at: • Infection
• 8-16 week – rapid uterine growth (60%)
• Postpartum – involution (40%)
• Ascites
• Hemorrhage: 10% of cases • Masculinization of female fetus
– Ruptured corpus luteum – Hilar cell tumor
– Germ cell tumor – Luteoma of pregnancy
– Sertoli-Leydig cell tumor
 Work-up of Ovarian Cancer Management of Ovarian Cancer
• Pelvic ultrasound • Prognosis not affected by pregnancy
• MRI pelvis/ abdomen • Tumors of Low Malignant Potential – all stages (20%)
• Adenocarcinoma Stage I, grade 1 or 2 (10%)
• Chest X-ray
• Germ cell tumors (5%) – may require chemotherapy
• CA-125: elevated in normal pregnancy, should • Gonadal stromal tumors (15%)
normalize after 12 weeks • Surgery at 16-18 weeks if possible
• AFP, B-HCG, LDH – predominantly solid mass • Frozen section: beware of inaccuracies
• Liver FunctionTests, BUN, Creatinine • Conservative ovarian surgery
– Adnexectomy/ Oophorectomy/ Cystectomy
• GI studies only if clinically indicated • Hysterectomy not indicated
• Thorough staging:
– Pelvic/ aortic node disection/ Omentectomy/ peritoneal biopsies

Management of Ovarian Cancer Malignant Germ Cell Tumors

• Epithelial Ovarian Cancer Stage IC – IV • Dysgerminoma
– Try to delay chemotherapy until 12-16 weeks of – 30% of Ovarian malignant neoplasms in pregnancy
pregnancy – Most stage IA
– Try to delay removal of corpus luteum until 14 weeks – Average 25cm; solid
– Therapy
– First trimester • Surgery: USO, wedge biopsy of opposite ovary, surgically stage
• TAB followed by appropriate surgery and chemotherapy – 25% are bilateral
• Chemotherapy after FNA: • Stage IA & IB: No further treatment
– C-Section and appropriate management at maturity • Advance stages
– Hysterectomy not required
– Second and Third Trimester – Chemotherapy
• Chemotherapy first
– C-Section and appropriate surgical management at maturity

Malignant Germ Cell Tumors
• Endodermal sinus tumor
• Grade 2-3 malignant teratoma
• Choriocarcinoma (non-gestational)
• USO and staging for early disease
• All require chemotherapy regardless of
stage
Tumor like Ovarian Lesions
Associated with Pregnancy
• All resolve spontaneously after delivery
• Conservative surgical approach: frozen section +/-
oophorectomy
– Luteoma of pregnancy - usually an incident. finding at C-Section
• Microscopic. -20cm – multiple nodules
• Bilateral: 1/3 of cases
• 25% have increased. testosterone
• Maternal masculinization. – later ½ of pregnancy
• Fetal virilization – 70% of female infants
–
–
Hyperreactio Luteinalis - Bilateral multicystic theca lutein cysts
Large solitary luteinized follicular cyst of pregnancy
– Hilar Cell Hyperplasia – masculinized fetus
– Intrafollicular Granulosa cell proliferations
– Ectopic Decidua

Breast Cancer in Pregnancy 


(2nd most common cancer in pregnancy)
Treatment of Breast Cancer
• 20% of cases are in women <40 years old • Treatment same as non-pregnant
• Lumpectomy
• 1-2% of cases are pregnant at time of diagnosis • Sentinal node biopsy
– 2.5mCi technetium 99 – 4.3 mGy at worst. Usually contraindicated.
• One case/1500-3000 pregnancies – +/- radiation
– Chemotherapy
• Often difficult to diagnose • Modified radical mastectomy and nodes
• Low dose mammogram with appropriate shielding of • Adjuvant chemotherapy after 16 weeks
– CAF better than CMF in 1st trimester
fetus is “safe” • Axillary or localized chest wall RXT is probably safe after the first trimester
but can be difficult to shield fetus.
• MRI – probably best • Prognosis:
• Diagnosis often delayed
5 Yr Disease Free
• Increase incidence of positive nodes (80%) Survival

• Termination of pregnancy & proph. castration is not Stage I 85%

beneficial Stage II 60%

Stage II 40%
• No adverse effects on prognosis from subsequent Stage IV 5%
pregnancies
 Hodgkins Disease/Lymphoma in
Leukemia in Pregnancy Pregnancy
• Most abort spontaneously • Gestational Age/ Stage
• Average age is 28 – <20 weeks: TAB
• Usually recommend termination of – >20 weeks: XRT
pregnancy because of aggressive
chemotherapy • Chest mantle first
• Chemotherapy depending on stage
• Prognosis – dependant on cell type
• Abdominal XRT after delivery
5 Yr Disease Free
Survival
• 80% curable – depending on cell type
AML 10%
ALL 40-60%
CML 50%
CLL Excellent

Melanoma in Pregnancy Ovarian Function and Chemotherapy

• Incidence rising • Dose and age related

• 50% occur in women of child bearing age
• 9% of cases occur in pregnancy
• Extremities most common site
• Pregnancy does not affect prognosis
– Younger than 25: permanent amenorrhea uncommon
– Older than 40: 50% permanent ovarian failure
• Birth control pills may prevent ovarian failure
• Risk of birth defects in offspring not increased (4%)
• Wait 2-3 years after therapy to become pregnant
– Allow for possible recurrent disease
 Ovarian Function and Fertility and
Radiation Therapy
Metastases to Fetus/Placenta
• Age and dose related (<20 years old – better) • Only 50 cases in literature
– Ovaries outside radiation field (avg. dose 54 cGy):
• No failure • Melanoma (50% of reported cases)
– Ovaries at edge of radiation field (avg. dose 290 cGy):
• 25% failure
• Leukemia: 1/100 affected pregnancies
• Start to lose function at 150 cGy • Lymphoma
– Ovaries in radiation field:
• At 500 cGy most women are amenorrheic • Breast
• Oophoropexy to the iliac fossa
– Use clips to identify ovaries

Turning..

Thank  you
ありがとうございました

If it doesn't kill the cat, curiosity is a luxury

Nicolaides et al, 2010 自信は努力から

 Acknowledgements

Kanazawa  Med.  Univ.  :  Haruo  Takabayashi,  Miki  Kita  

Showa  Univ.  :  Akihiko  Sekizawa,  Keiko  Koide,  Masamitsu  Nakamura,  

Asami  Fukuda,  Hiroshi  Chiba,  Hanako  Shimizu,  Ryu  Matsuoka,  
Kiyotake  Ichizuka,  Junichi  Hasegawa,Takashi  Okai  

King’s  College:  Kypros  Nicolaides,  Tylki  Eliza  

Univ.  Indonesia  :  Noroyono  Wibowo,  Handaya,  Azen  Salim,  Damar  

Prasmusinto,  Bambang  Karsono,  Ali  Sungkar,  Yudianto  BS,  Aria  
Wibawa,  Rima  Irwinda,  Edwina  FrisdianRny  

Bologna  Univ:  Antonio  Farina,  Nicola  Rizzo  

NCCHD,  Tokyo:  Michihiro  Kitagawa,  Satoshi  Hayashi,  Hirohiko  Sagou 54