Gynecologic Malignancies – Flashcards

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3 most common gynecologic malignancies
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1. adenomocarcinoma of the endometrium 2. Epithelial ovarian cancer 3. Squamous cell carcinoma of the cervix
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Type I endometrial cancer
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-*Estrogen related* -younger perimenopausal patients -*heavier patients* -low grade
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Type II endometrial cancer
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-*Unrelated to estrogen* -*older patients* -thinner patients -*aggressive* -Potential genetic basis: Lynch Syndrome (but can be associated with either type, more commonly II)
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Most common sites for cancers of the female reproductive tract
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-Uterine corpus not including the cervix -ovaries -uterine cervix
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Less common sites for cancers of the female reproductive tract
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-Fallopian tubes -vagina -Vulva/perineum -placenta
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Most common type of cancer in the female reproductive tract
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Carcinomas
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Most common site for sarcomas in the female reproductive tract
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Uterine corpus
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Other types of cancers that occur in the female reproductive tract
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Melanomas and lymphomas
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Ovarian cancer risk
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1 in 70
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Uterine cancer risk
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1 in 40
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Cervical cancer risk
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One in 140
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Breast cancer risk
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One in 8
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Risk factors for type I endometrial cancer
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-Obesity ? >50 lbs overweight = 10X relative risk -extended reproductive life -nulliparous -late menopause -hypertension -diabetes type I and type II -Exogenous estrogen (unopposed) *think more years of ? estrogen, and HTN and DM*
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Percent of endometrial carcinomas that are type I
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80%
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Atypical hyperplasia
Atypical hyperplasia
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in-situ Phase that precedes type I endometrial carcinoma -characterized by increased* gland to stroma ratio* -histologically there are enlarged in round nuclei, loss of cell polarity, and prominent nucleoli
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atypical hyperplasia rate of progression to carcinoma
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8 to 25% or higher
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Endometrial endometriod carcinoma
Endometrial endometriod carcinoma
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Characterized by confluent glands or solid sheets of tumors *type I*
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Percent of type I endometrial carcinomas that have mutations in the *PTEN tumor suppressor gene*
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80%
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Percent of endometrial hyperplasia is that have a *PTEN mutation*
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20%, which supports the theory that It is a precursor lesion
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Risk factors for type II endometrial adenocarcinoma
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-lean women -African-American
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Percent of endometrial carcinoma is better type II
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15%
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Type II endometrial carcinoma histology
Type II endometrial carcinoma histology
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*serous* -Cells with very high nuclear to cytoplasmic ratios -numerous, atypical mitoses
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Percent of patients with type II serous endometrial carcinomas that have mutations in the p53 tumor suppressor gene
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>90%
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Presentation of endometrial cancer
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-Most common presenting complaint is postmenopausal or abnormal perimenopausal bleeding
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true or false: bleeding after menopause is NEVER normal
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True
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Only life-threatening cause of postmenopausal bleeding
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Cancer
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Percent of postmenopausal bleeding that is accounted for by cancer
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20%
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Who Needs an Endometrial Biopsy?
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1. Abnormal bleeding -*Postmenopausal bleeding* - Perimenopausal intermenstrual bleeding - Bleeding with history of anovulation 2. Postmenopausal women with endometrial cells on Pap test 3. Thickened endometrial stripe via sonography - Especially an *endometrial thickness of >5 mm in a postmenopausal woman*
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Staging Endometrial/Uterine and Ovarian Cancer
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-Staging is* surgical/pathologic* -performing a predefined operation and assigning stage based on pathological evaluation of tissues removed
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Goals of endometrial cancer staging
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- define the extent of the disease - minimize both over and under use of adjuvant treatment - decrease both patient risks and costs associated with treatment - allow for optimal comparison of outcomes
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Components of endometrial cancer staging
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-Abdominal exploration -peritoneal cytology -total abdominal hysterectomy -bilateral salpingo-oopherectomy -bilateral pelvic and aortic lymph node dissection
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Stage I
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Confined to uterus: A) endometrium only or 1/2 myometrium
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Stage II
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Cervix involvement A: glands only B: stromal invasion
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Stage III
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Uterine serosal adnexal disease positive cytology vaginal mets pelvic or aortic node involvement
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Stage IV
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Bladder or bowel invasion inguinal nodes involved other distant metastases *not curable*
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Survival rates of surgical stage one disease
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-In the absence of pathologic porpoise factors, surgery can be therapeutic with survival rates = 90-98%
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Pathologic risk factors for recurrence of disease
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-High histologic *grade* (2 or 3) -depth of *myometrial invasion* -tumor* size* (>2 cm) -presence of* lymph-vascular* space invasion -*aggressive histologic cell type* (serous or clear cell cancer) the presence of 2 or more of these risk factors increases the recurrence rate to as high as 30% and justifies the use of postoperative adjuvant therapy
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Stages II-IV
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Requires adjuvant therapy -generally pelvic radiation therapy with vaginal cuff boost -chemo therapy for cases with adnexal, nodal, or distant metastases
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Percent of all endometrial cancers that are stage I
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70%
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Percent of all endometrial cancers that are staged II
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18%
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Percent of all endometrial cancers that are stage III
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8%
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Percent of all endometrial cancers that are staged IV
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4%
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Overall survival rate of stage I endometrial cancer
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76%
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Overall survival rate of stage II endometrial cancer
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60%
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Overall survival rate of stage III endometrial cancer
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30%
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Overall survival rate of stage for endometrial cancer
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10%
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Recurrent disease
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-Generally considered incurable -exception is isolated vaginal cuff recurrence and a woman who has not received adjuvant radiation
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management of recurrent disease
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platinum-based chemotherapy participation in clinical trials is encouraged
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Endometrial Cancer: Adjuvant Postoperative Therapy
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Whole Pelvic Radiation and Vaginal Cuff Boost Most common indications - cervical spread (stage II) - nodal involvement (stage IIIC) Can reduce recurrence rate by up to 50% Estimated cost 5,040 cGy PRT: $20,000 Treatment duration: 25 to 30 days Chemotherapy
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Ovarian Cancer
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- Second most common gynecologic malignancy in the US - Responsible for 25,000 cases annually - 14,500 deaths annually - *Most lethal gynecologic malignancy * - 70% of patients present with advanced disease - no effective screening
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Most common source of malignant ovarian tumors
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Surface epithelium
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Risk factors for ovarian cancer
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-Age/postmenopausal -family history/genetics -infertility/low parity or other factor resulting in uninterrupted ovulation -personal cancer history (most commonly breast cancer) *has to do with ovulation, increased # of ovulations, means more repair to the ovaries = ? risk*
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Factors that reduce the risk for ovarian cancer
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-Oral contraceptive use -pregnancy -tubal ligation -breast-feeding
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Most common presenting templates for ovarian cancer
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-Abdominal bloating -early satiety -small or large bowel obstruction -many women do seek medical attention earlier in the disease process but symptoms are overlooked as minor gastrointestinal or genitourinary conditions such as *irritable bowel or UTI*
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Definitive diagnostic modality for ovarian cancer
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Surgical exploration/pathology
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Most common histologic subtype of epithelial ovarian cancer
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Serous carcinoma
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2 categories of serous carcinoma of the ovary
2 categories of serous carcinoma of the ovary
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-Low grade -high-grade
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Mutations commonly seen with low-grade serous cancers of the ovary
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- KRAS - BRAF - PTEN - B-catenin
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Type of serous ovarian cancer with better purposes
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Low grade
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Mutations associated with high-grade serious cancers of the ovary
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p53
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The vast majority of epithelial covariant cancers are of which grade?
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High grade serous
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Reason why the serum tumor marker CA125 and pelvic ultrasound are not reliable screening tests for ovarian cancer?
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-Lack the sensitivity (too many false negatives) -lack the specificity (too many false positives)
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Management of ovarian cancer
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-Involves both surgery and systemic adjuvant, platinum and taxane paste chemotherapy
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2 major surgical concepts of important in ovarian cancer
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-Complete surgical staging of disease that clinically appears to be confined to the ovaries -cytoreductive surgery or debulking
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Complete staging of ovarian cancer
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-Peritoneal cytology -TAH/BSO -omentectomy -peritoneal biopsies from pelvis, mid abdomen, and diaphragmatic surfaces -pelvic and aortic node dissections
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Ovarian Cancer: CA125 Testing
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- Elevated in > 80% of advanced EOCs and functions well as a tumor marker in majority of these cases - Elevated in 25-50% of Stage I cancers ? POOR SENSITIVITY - Elevated by many non-malignant conditions especially in premenopausal women ? POOR SPECIFICITY - NOT a screening test for the general population
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Stage I ovarian cancer
Stage I ovarian cancer
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*Confined to the ovaries* A ? one ovary B ? both ovaries C ? one or both with surface disease or positive cytology
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Stage II ovarian cancer
Stage II ovarian cancer
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*Confined to the Pelvic Organs*
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Stage III ovarian cancer
Stage III ovarian cancer
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*Spread to the Upper Abdomen* (lymph nodes) A ? microscopic disease only B ? Largest lesion 2cm ( most common overall stage)
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Stage IV ovarian cancer
Stage IV ovarian cancer
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*Malignant pleural effusion or liver mets*
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Percent of ovarian cancers that appear confined to the ovary (stage I) in which there is microscopic spread upstaging to stage IIIC
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30%
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Key to a good outcome of ovarian cancers that have spread beyond the ovaries
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Tumor mass reduction and debulking -the more tumor removed, the better chance for survival
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Optimal surgical debulking
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*leaving no tumor nodule >0.5 cm *
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Post operative edge event chemotherapy for ovarian cancer
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Required in all cases other than stage IA grade 1 lesions
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most common drug combinations used in Ovarian cancer chemotherapy
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-IV carboplatin and Taxol -intraperitoneal cisplatin and Taxol
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Percent of women that will have good response to chemotherapy and will be in remission after 6 to 8 cycles of therapy
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70-80%
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Percent of women who reach remission that will have a recurrence within the 1st 3 years after completing treatment
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>50%
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Therapy for ovarian cancer recurrence
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-Reoperation for debulking -pretreatment with chemotherapy
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Cure rate of recurrent ovarian cancer
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0%; considered incurable
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percent of ovarian cancers that are diagnosed as stage I
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24%
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Percent of ovarian cancers that are diagnosed in stage II
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6%
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Percent of ovarian cancers that are diagnosed in stage III
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55%
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Percent of ovarian cancers that are diagnosed as stage IV
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15%
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Percent survival of stage I ovarian cancer
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95%
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Percent survival of stage II ovarian cancer
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65%
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Percent survival of stage III ovarian cancer
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15-30%
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Percent survival of stage IV ovarian cancer
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0-20%
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Overall survival rates of ovarian cancer
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50%
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Surgical Rx for Early Stage ovarian cancer Disease
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*TAH BSO + staging * Infracolic omentectomy Peritoneal samples pelvis, gutters, diaphragm Pelvic and aortic lymph node dissection -In younger women, reproductive conservation may be appropriate -Approximately 30% will have histologic evidence of metastatic disease when clinically disease appears confined to the ovary
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Surgical Treatment for Advanced ovarian cancer Disease
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Significant survival advantage for women optimally cytoreduced Procedures may include: En bloc resection of uterus, ovaries and pelvic tumor Omentectomy Bowel resection Removal of diaphragmatic and peritoneal implants Splenectomy, appendectomy
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Ovarian Cancer Chemotherapy
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- All patients should receive a taxane and a platinum - 73% response rate, however more than half of these women will experience recurrence of the disease - Median survival: 38 months for Stage III/IV - Many new agents being tested - Encourage clinical trial participation
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Ovarian Cancer Follow-up
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-Recto-Vaginal pelvic exam and CA125 q 3-4 mo x 2 years, q 6 mo for years 3-5 - CT scan for symptoms - General health maintenance (mammography, Pap smear, bone density, colon-rectal screening, cholesterol, etc.) - Discuss HRT, diet, exercise
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Cervical Cancer Incidence
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American Cancer Society Estimates 12-13,000 cases of invasive cervical cancer/year 4600 of these women die International estimates Approximately 500,000 deaths/year! Number 1 or 2 cancer killer of women worldwide
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Cervical Cancer Risk Factors
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-Early age of intercourse -Number of sexual partners -Smoking -Lower socioeconomic status -High-risk male partner -Other sexually transmitted diseases -Up to 50% of the U.S. population is infected with HPV
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Percent of cervical cancers worldwide contain Human Papilloma Virus DNA
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*99.7%*
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Cervical cancer screening
Cervical cancer screening
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Pap test
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Percent of cervical cancers accounted for by type 16 HPV
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60%
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Percent of cervical cancers accounted for by type 18 HPV
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10%
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HPV infections locations
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-Basal cells of the squamous epithelium, usually at the squamocolumnar junction of the cervix
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koilocytosis
koilocytosis
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Squamous cell with a dark, irregular nucleus and a sharply defined perinuclear halo which is characteristic of HPV infection
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Low-grade or mild dysplasia
Low-grade or mild dysplasia
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Cervical Intraepithelial Neoplasia grade 1
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high grade or severe dysplasia
high grade or severe dysplasia
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Cervical Intraepithelial Neoplasia grade 3"
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Why does the Pap test work?
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- cervix can be sampled relatively non-invasively - natural history of cervical cancer is slowly progressive - dysplastic (pre-invasive) changes can be recognized microscopically - dysplastic (pre-invasive) changes can be treated and prevented from progressing to invasive cancer - test is relatively inexpensive - HPV testing is integrated into screening in patients over 29 years of age (extends interval)
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Cervical Cancer Prevention
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*HPV vaccination* available in US since 2006 recommended to males and females age 9-26 years 3 dose schedule
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Where HPV viral particles are found in epithelial cells
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-Halo area
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Treatment of cervical squamous cell dysplasia
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conization Cryotherapy
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Oncogenesis from HPV
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Occurs when the virus becomes integrated into the host DNA and viral E6 and E7 proteins bind to retinoblastoma tumor suppressor genes and to the p53 tumor suppressor gene
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mild cervical squamous cell dysplasia definition
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Abnormal cells confined to the lower 1/3 of the epithelium
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Moderate cervical squamous cell dysplasia definition
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Abnormal cells extend into the middle 1/3
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Severe dysplasia definition
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Abnormal cells are present in the superficial 1/3 of the epithelium
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Signs and Symptoms of Invasive Cervical cancer
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May be silent until advanced disease develops *Post-coital bleeding* *Foul vaginal discharge* *Abnormal bleeding* Pelvic pain Unilateral leg swelling or pain Pelvic mass Gross cervical lesion
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Most common presenting complaints for women with invasive squamous cell carcinoma
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Painless postcoital bleeding
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Clinical staging of cervical squamous cell carcinoma
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-General physical exam -rectovaginal bimanual pelvic exam -plain film chest x-ray -cytoscopy and/or proctoscopy -intravenous pyelogeram
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Type of staging used for cervical cancer
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-Unlike the other 2, it is *staged by clinical criteria* rather than surgical/pathologic staging
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Type of staging used for ovarian cancer
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Surgical/pathologic staging
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Type of staging used for uterine cancer
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Surgical/pathologic staging
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Rationale for clinical staging of cervical cancer
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-The majority of squamous cell carcinoma affects women in the underdeveloped world where access to diagnostic modalities are limited or unavailable -continued clinical staging allows for comparison across every different geographic and socioeconomic population
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Stage I cervical cancer
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*Confined to cervix* - A < 5mm invasion or 7mm lateral spread - B any lesion larger than IA microscopic or any visible lesion
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Stage II cervical cancer
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*Vaginal and/or Parametria involved* A ? Upper 2/3 vagina B ? Parametria but not to the pelvic sidewall
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Stage III cervical cancer
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*Extensive Vaginal or Parametria* A ? Lower 1/3 vagina B ? Parametria to the sidewall or any lesion causing hydronephrosis
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Stage IV cervical cancer
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Distant Disease A ? Bladder or Rectal mucosa invasion B ? Distant mets
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Treating Early Cervical Cancer
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1. Conization or simple hysterectomy - microinvasive cancer 2. Radical hysterectomy - removal of the uterus with its associated connective tissues, the upper vagina, and pelvic lymph nodes. Ovarian preservation is possible. 3. Chemoradiation therapy
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Cervical Cancer Treating Advanced Cervical Cancer
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*Chemoradiation is the mainstay of treatment* - 4-5 weeks of external radiation - Two or more implants (brachytherapy) - Concurrent Cisplatin-based chemotherapy significantly improves the chances of survival - Radiation treats the primary tumor and adjacent tissues and lymph nodes - Chemotherapy acts as a radiation sensitizer and may also control distant disease
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Cervical Cancer recurrence management
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Palliative chemotherapy Pelvic exenteration (if central recurrence) 50% cure rate
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Five-year survival of stage I cervical cancer after treatment with radical hysterectomy
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85-98%
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Five-year survival of stage I cervical cancer after treatment with chemo and radiation therapy
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85-95%
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Five-year survival of stage II cervical cancer after treatment with chemo and radiation therapy
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70-80%
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Five-year survival of stage III cervical cancer after treatment with chemo and radiation therapy
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50-65%
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Five-year survival of stage IV cervical cancer after treatment with chemo and radiation therapy
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20-30% (IVA) <10% (IVB)
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endometriod
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Type I endometrial carcinoma
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serous
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Type II endometrial carcinoma
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BRCA 1 or BRCA2 germline mutation
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35-65% lifetime risk of ovarian cancer
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types of ovarian cancer
types of ovarian cancer
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>90% are surface epithelial cancers (serous)
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postcoital bleeding
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rule out cervical cancer
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postmenopausal bleeding
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rule out uterine (endometrial) cancer
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