Editing OBGYN - Gyn Cancers

=Gyn Cancers=

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


{|border=1
!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 (#2 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%

==Uterine Cancer==

===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

===Uterine Cancer: Treatment===
*Mainstay is surgical 
**Total hysterectomy 
**BSO 
**Pelvic & PA Nodes 

===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

===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