OBGYN - Gyn Cancers

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Revision as of 13:25, 16 December 2011 by 134.68.138.157 (Talk)

Contents

Gyn Cancers

Cancers

  • Ovarina / fallopian tube
    • Primary peritoneal cancer, looks the same, treated the same
  • cervical
  • Endometria
  • rare:
    • vulva
    • vagina
    • trophoblastic


Cancer Incidence Kills (Rank) Lifetime Risk Risk Factors
Cervical 12.2k / year (#3) #3 (#1 worldwide, 4.2k / year) 1/135 High Grade Dysplasia, smoking, a lifestyle cancer (early parity, early coitus, multiple partners)
Endometrial (Uterine) 41k / year (#1) #2 (7.1k / year) 1/38 Obesity, HTN, Diabetes, Atypical Hyperplasia
Ovarian 23k / year (#1 at 23% of gyn ca) #1 (47% of gyn ca) ~1/70 BRCA1, BRCA2, HNPCC, (not smoking)

Epidemiology

  • Who gets it and how many?

Presentation - Differential Dx

  • Common presentations of gyn cancers include:
    • Adnexal Mass
    • Abnormal Pap
    • Post Menopausal Bleeding

Prevention

  • Prevention
    • Screening: BRCA
    • Vaccines
    • Role of HRT

Detection / Diagnosis

  • Pathology
  • Staging
  • (Treatment)

Adnexal mass and ovarian cancer

  • 23k new cases / year
    • breast cancer is 200k
    • teal is the color of ribbon for ovarian
  • 16k deaths / year
  • 23% of gyn cancers are ovarian.
  • 47% of deaths are caused by ovarian
  • 1 / 70 lifetime risk in US

Embryology / Oncology

  • Epithelial adenocarcinoma:
    • originate from the peritoneal mesothelium
    • make up 65% of Ovarian cancers
  • Germ Cell:
    • originiate from the yolk sac (dysgerminoma, teratoma)
    • make up 25% of ovarian cancers
  • Stromal:
    • Originate from the gonadal ridge –mesenchyme near protonephros (granulosa and theca cells)
    • Make up 8% of ovarian cancers
  • Metastatic:
    • Make up only 2% of ovarian cancers
    • Called Krukenburg tumors

Epithelial Ovarian Cancer: Histologic Types

  • Histology (and the structure it recapitulates)
    • Serous (Tube)
    • Endometrioid (Endometrium)
    • Mucinous (Cervix)
    • Clear cell (Kidney)
    • Brenner (Transitional)

Ovarian Cancer: Pt History

  • Epidemiology - Clinical
  • History: there is NO classic profile:
    • Age / Parity
    • Menstrual history
    • Surgical Hx: hysterectomy or BTL
    • BCP / hormonal therapy history
    • Personal and family cancer history
    • Ethnicity

Ovarian Cancer: Risk Factors

Factors that Decrease Risk

  • Factor: Relative Risk
  • Nulliparous: 1.0
  • 1 Full term pregnancy: 0.6
  • > 5 Full term pregnancies: 0.29
  • Use of Oral Contraceptions:
    • Never: 1.0
    • Ever 0.75
    • 3 mo - 4 yrs: 0.6-0.7
    • > 10 years: 0.2
  • Bilateral Tubal Ligation: 0.5
  • Hysterectomy: 0.5
  • Breast feeding (linear with duration): 0.7


  • Tying the tubes decreases one's risk, probably because there is decreased environmental exposure.
  • Anything that makes the ovary quiescent will decrease the risk of ovarian cancer.

Factors that Increase Risk

  • Factor: Relative Risk
  • Hx of Breast Cancer:
    • None: 1.0
    • 1st Degree Relative: 2.1
    • Personal History: 10
  • Hx of Ovarian Cancer:
    • None: 1.0
    • One 1st Degree Relative: 3.1
    • >2 1st Degree Relatives: 4-15
    • Hereditary Cancer Syndrome: 12-30
  • Saturated Fat Diet: ?


  • Family history of breast cancer increases the risk for ovarian cancer by 2 fold.
    • A personal history makes the risk 10 fold higher!
  • Diet is questionable.

Adnexal Mass Ddx

  • The differential diagnosis for an adnexal mass should include all of the following:
    • Physiologic
    • Gestational
    • Inflammatory
      • PID can form a pretty big, complex mass on the ovary with fallopian tube involvement.
    • Congenital
    • Traumatic
    • Neoplastic


  • How do we tell between good and bad?
  • Good indicators:
    • Asymptomatic
    • Cystic
      • fluid filled (not solid)
    • Age between 15 and 45
    • Resolves
  • Bad indicators:
    • Pain or other vague symptoms
    • Symptomatic: Ascites
    • Complex, Solid: Omental cake
    • Persists: Adenopathy

Detective work: Diagnosis

  • ROS:
    • 65% of ovarian cancer patients DO have sypmtoms; often vague and non-gynecologic
      • Not really the "silent killer"
    • Pain, GI symptoms, Fatigue, Weight change


  • Physical Exam:
    • Lungs: dullness (Pleural effusion), ronchi, or wheezes?
    • Abdomen-mass or fluid wave?
    • Rectovaginal exam; mass, nodularity
    • General appearance


  • Pelvic Exam
  • Labs
  • Imaging
    • Ultrasound
    • CT Scan
    • U/S > CT


  • Operation

Surgical: FIGO Staging

  • I = Limited to ovary (ies)
  • II = Extension to uterus, tubes, other pelvic tissues
  • III = Peritoneal surface implants, nodes
    • Surface of the liver is stage 3 but parenchymal liver mets is stage 4.
  • IV = Distant metastasis
    • Ovarian often goes to the lung.

Ovarian Cancer: Outcomes

  • 5 year survival:
    • Stage I: 75%
    • Stage II: 60%
    • Stage III: 30%
    • Stage IV: 15%

Ovarianc cancer

  • usually requires histology to know it is cancer.

Ovarian Cancer: Treatment

  • Goals of Operation:
    • Is this cancer?
    • Is this ovarian cancer?
    • What stage?
  • If apparently confined to ovary, do a “staging” operation.
  • If bulky disease, do a “debulking” operation


  • Operation
    • USO / BSO
    • Omentectomy
    • Lymphadenectomy
    • Peritoneal biopsies
    • Hysterectomy


  • Young patients, early stage: possibility of fertility-sparing surgery

Epithelial Cancers: Treatment

  • Recall that epithelial is one origin of ovarian cancer.
  • Epitheilal ovarian cancer treatment is specifically treated with chemotherapy.
  • Platinum and taxane-based combination chemotherapy
    • Platinum: Cisplatin, carboplatin
    • Taxane: Paclitaxel, docetaxel

Ovarian Cancer: Familial Inheritance

  • Ovarian Cancer Inheritance risks:
    • Lifetime risk in U.S.: 1.4%
    • One 1st-degree relative: 5%
    • > two 1st-degree relatives: 7%
    • HBOC: 6-50%
  • OF THESE, 3% WILL HAVE A HEREDITARY CANCER SYNDROME


  • Hereditary cancer syndromes are characterized by:
    • 1/800 US BRCA and 1/600 HNPCC
    • Autosomal dominant inheritance
    • Early age of onset
    • Younger affected members in subsequent generations
    • Multiple cancers in individuals
    • Bilaterality of certain cancers
    • Male breast cancer (BRCA 2)

Cancer: Family History

  • Obtaining a Family History of Cancer
  • 3 + generation family history.
  • Update regularly
  • Maternal and paternal data
  • Race, ethnic background, all cancers, current age, age at diagnosis, age at death
  • Medical records review
  • Genetic counseling BEFORE TESTING!

Familial Ovarian cancer

  • HBOC = hereditary breast ovarian cancer syndrome.
    • BRCA is an example.
  • If one person has breast and ovarian cancer, there is s90% chance that they carry brca mutations.
  • Male breast cancer is so rare that if seen, suspect brca(2) mutation.

==Clinical Use of Serum CA 125

  • CA 125 can be used to following response to chemotherapy
  • CA 125 can be used for surveillance for patients with known genetic mutation or strong family history indicative of a hereditary inheritance pattern
    • + rectovaginal exam, +/- transvaginal pelvic ultrasound


  • CA 125 does not detect ovarian cancer at an earlier stage.


  • When NOT to Obtain a Serum CA 125 Level:
    • When a low-risk patient asks you for it!
      • Requires extensive counseling
      • Poor sensitivity and specificity
  • When operation is already indicated


  • Non-malignant conditions that may elevate the CA 125:
    • PID
    • Adenomyosis
    • Benign neoplasm
    • Endometriosis
    • Functional cyst
    • Menstruation
    • Infertility
    • Leiomyomata
    • Hepatitis
    • Pancreatitis
    • Cirrhosis
    • Colitis
    • CHF
    • Diverticulitis
    • Postoperative period
    • Renal disease
    • SLE
    • Pneumonia
    • Diabetes

Chemoprevention with Oral Contraceptives

  • OC use for > 5 years reduces risk of ovarian cancer by 60% in the general population
  • Protective effect increases with increasing duration of use
  • Protection continues for 10 years following discontinuation

Prophylactic Surgery

  • Oophorectomy:
    • Reduced ovarian cancer risk by 95-100%
    • Reduced breast cancer risk by 53-68%
    • Reduced risk of fallopian tube cancer and primary peritoneal cancer
    • Evidence suggests that many BRCA-related ovarian cancers are actually fallopian tube primaries


  • Bilateral Mastectomy:
    • BRCA patients ~ 85-100% reduction in risk for breast cancer


  • These prophylactic surgeries (breast and ovary) are not completely protective because we just can't find every cell.
  • After prophy, a 5% risk over 20 years for developing cancer (as a brca pt).
    • But that's much better.

Abnormal Pap Smear and Cervical Cancer

Cervical Cancer Epidemiology

  • 12,200 new cases in the US per year
  • 4,210 deaths in the US per year
  • 180 new cases in Indiana
  • < 100 deaths in Indiana
  • Life time risk 1 / 135
  • 2nd to breast cancer for cancer death in women ages 20-39
  • 500,000 women die each year world wide
  • Number one cancer killer of women worldwide


  • In the US 60% are Stage I at diagnosis
  • More common in minorities, disadvantaged
  • Early coitus, early parity, multiple partners
  • Associated with / caused by HPV 16,18,31,33
  • Not all infected patients develop cancer
  • Smoking increases risk

Cervical Cancer: Prevention

  • Randomized Double-Blind Clinical Trial:
    • 2392 Young women vaccinated with 3 doses of placebo or HPV-16 virus-like particle vaccine
    • At a median of 17.4 months, 3.8 / 100 women of the placebo women and 0 / 100 of the treated women had persistent HPV infection
  • Nine CIN events were all the placebo group

Cervical Cancer: Screening

  • Begin screening at age 21 regardless of age of onset of sexual intercourse
    • Moved up to 21 b/c we were over treating.
  • Repeat every 2 years if normal and lowrisk from age 21-29
  • After age 30, and 3 consecutive negatives, and low-risk, screen every 3 years
  • May stop after age 70
  • No need for Pap after total hysterectomy


  • Low risk: No history of high grade dysplasia, HIV, or other immunosuppression
  • Remember the pap is a screening test
    • If abnormal, or if the cervix appears or feels abnormal, proceed with diagnostic test
  • Colposcopy
  • Directed Biopsy


  • ASCUS = atypica squamous cells of undetermined significance

Interpreting Results

  • The Bethesda system: 
**LGSIL
**HGSIL
**AGUS/ASCUS


  • Histologic diagnoses:
    • CIN 1
    • CIN 2
    • CIN 3/CIS
    • Invasive cancer

Classification Terminology for Cervical Cytology

  • The 2001 Bethesda System


  • Two types of atypical squamous cells (ASC)
    • Atypical squamous cells of undetermined significance (ASCUS)
    • Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions (ASC-H)


  • Squamous intraepithelial lesions (SIL)
    • Low-grade SIL (LSIL): Mild dysplasia, cervical intraepithelial neoplasia 1 (CIN 1)
    • High-grade SIL (HSIL): Moderate and severe dysplasia, CIN 2/3, carcinoma in situ (CIS)


  • Cervical intraepithelial neoplasia (CIN)
    • CIN 1: Mild dysplasia; includes condyloma (anogenital warts)
    • CIN 2: Moderate dysplasia
    • CIN 3: Severe dysplasia; includes CIS
  • CIN caused by HPV can clear without treatment.

Cervical Cancer: Diagnosis

  • Inadequate Colposcopy:
    • T-Zone not fully visualized
    • Can’t see the entire lesion
    • Lesion extends into canal
    • Discordance
    • Positive endocervical curettage (ECC)
    • Suspect invasion

What is a colposcopy?

  • Use of a magnifying instrument
  • Application of a vinegar-like solution onto the cervix
    • Use acetic acid to highlight abnormal spots; biopsy them.
  • See abnormalities that can’t be seen with the naked eye
  • Feels like getting a Pap test, but lasts longer
  • Must do a cone biopsy if you have an inadequate simple (cervical) biopsy.

Cervical Biopsy

  • Removal of a small piece of tissue from the cervix
  • Endocervical curettage is often performed to evaluate lesions within the cervical canal

Biopsy Results and Management

  • CIN I
    • Observation
  • CIN II and III
    • Laser
    • Cryotherapy
    • Cone Biopsy: LEEP, laser cone, or cold-knife cone
    • Hysterectomy may be recommended


  • Cancer: Gynecologic Oncology Consultation


  • If the colposcopy is inadequate, or invasion is suspected, proceed with definitive diagnostic test:
    • LEEP Excision
    • Cold Knife Cone


  • If lesion is visible, biopsy can be diagnostic without cone

What is a cervical conization?

  • Removes a coneshaped piece of tissue
  • Often allows for diagnosis and treatment
  • Performed with local anesthesia in the office or under general anesthesia in the operating room

Abnormal Pap: Epidemiology

  • 12,210 cancers
    • Treat
  • 300,000 HSIL
    • Treat
  • 1.25 million LSIL
    • Wait and see
  • 2-3 million ASC
    • Wait and see
  • 50-60 million women screened

Clinical Staging of Cervical Cancer

  • Stage I: Disease confined to the cervix
  • Stage II: Vagina or parametrial extension
  • Stage III: Distal vagina, lateral pelvic wall, or hydronephrosis
  • Stage IV: Mucosa of bowel / bladder, or distant disease


  • Estimates of 5 year survival:
    • Stage I: 82-85%
    • Stage II: 61-66%
    • Stage III: 37-39%
    • Stage IV: 11-12%

Cervix Cancer: Treatment

  • Goal is to get a negative margin.
  • Will irradiate the entire tumor.
    • Try not to do sx if they will need radiation b/c radiation has more adverse effects if post-op.
  • Even radical hysterectomy leaves the ovaries.
    • Cervical cancer very rarely involves the ovaries.

Chemotherapy

  • Stage IA1 (microinvasive): Cone vs. Simple Hysterectomy
  • Stage IA2-IB1: Radical Hysterectomy vs. Radiation
  • >Stage IB2: Concurrent platinum-based chemotherapy and radiation

Surgical Treatment

  • Only indicated if “negative margin” can be achieved
  • Advantages:
    • Permits More Accurate Assessment
    • Preserves Ovarian Function
    • Preserves Vaginal Function
    • Less Long-Term Morbidity

Radiation Therapy

  • Appropriate for all stages and patients with high surgical risk
  • Indicated when negative surgical margin cannot be achieved
    • Advanced disease >IB2
    • Obesity (BMI>30)

Post-Menopausal Bleeding and Endometrial Carcinoma

  • Incidence in US women:
    • 41,000 cases / year
  • Most common gynecologic cancer
  • 1 / 38 lifetime risk
  • 7,100 deaths / year
  • 2nd most common cause of death due to gynecologic cancer

Endometrial Pt Profile

  • Age: 75% post-menopausal
  • Etiology: Prolonged unopposed estrogen stimulation
  • Clinical Presentation:
    • Abnormal bleeding, post-menopausal
    • Associated factors: obesity, hypertension, diabetes
  • HNPCC (Lynch)

Endometrial Cancer: Risk Factors

Endometrial Cancer: Two Types

  • Type I
    • Estrogen Related
    • Younger and heavier patients
    • Low grade
    • Perimenopausal
    • Exogenous estrogen
    • Insulin resistance
  • Type II
    • Aggressive
    • Unrelated to estrogen stimulation
    • Occurs in older & thinner women
    • Potential genetic basis
      • Lynch syndrome
      • Familial trend


Endometrial Carcinoma

  • Pathology
    • > 70% adenocarcinomas
    • Histologic grade important
    • Poor prognosis cell types: papillary serous and clear cell carcinomas, mixed tumors


  • FIGO Stage - Surgical Findings:
    • Stage 1: Confined to uterus
    • Stage 2: Extension to cervix
    • Stage 3: Regional spread (serosa, adnexa, vagina, parametria, pelvic / aortic nodes)
    • Stage 4: Metastases (Bladder / rectum, inguinal nodes, distant metastases)


  • Stage: Frequency; Survival
    • Stage 1: 75%; 90%
    • Stage 2: 13%; 60%
    • Stage 3: 9%; 40%
    • Stage 4: 3%; <10%

Endometrial (uterine) Cancer: Diagnosis

  • Pts with uterine cancer often present with AUB / PMB:
    • Abnormal Uterine Bleeding
    • Postmenopausal bleeding


  • Office biopsy (Pipelle)
  • Dilation and curettage (D&C)
  • Hysteroscopy

Endometrial (uterine) Cancer: Treatment

  • Mainstay is surgical
    • Total hysterectomy
    • BSO
    • Pelvic & PA Nodes

Endometrial (uterine) Cancer: Surgical Staging

  • Conceptual rationale:
    • Defines extent of disease
    • Minimizes over / under treatment
    • Minimally increases perioperative morbidity / mortality
    • Decreases overall Rx risks and costs
    • Allows comparison of therapeutic results

Endometrial (uterine) Cancer: Adjuvant Therapy

  • Options:
    • Brachytherapy
    • External beam radiotherapy
    • Hormonal therapy
    • Cytotoxic chemotherapy
    • Combination therapy


  • Determining Factors:
    • Stage
    • Histologic subtype
    • Staging completeness
    • Tumor biology
    • Medical conditions
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