Obgyn Week 4b

1. Obgyn Week 4b Cervical Dz, Gynecologic Cancers

2. Cancer • Most common cancers in U.S. women

3. Cancer • Most common cancers in U.S. men

4. Cancer • General Cancer terms: • Stage: determined by clinician; is the degree of invasion of the tumor; usually on a scale of 1-4 • TNM staging where n=nodes, m=mets • Grade: determined by pathologist; is the degree of resemblance of the tumor to its surrounding tissue • The higher the grade the less differentiated

5. Cancer • More general cancer terms: • Carcinoma: tumor derived from epithelial cells • Sarcoma: derived from connective tissue • Adeno-: prefix to denote glandular involvement • Lymphoma: derived from hematopoietic cells (blood cancer)

6. Cancer • TCM description of process (from Dr. Fritz) • Deficiency state (improper diet/lifestyle/emotion) • External pathogen invasion creates disharmony • Blood stastis/phlegm accumulation --> tumor formation • Perpetuation of internal cold-heat cycle • Body unable to disperse, tumor grows

7. PAP • Part of the yearly well-woman exam • PAP smear (named after Dr. Papanicolau) • Is a screening tool only • Looks for abnormalities in cervical cells • Is susceptible to false + and false - results • False negative rate about 5-20% • False positive due to Trichomonas or HSV infections or if history of chemotherapy

8. PAP • Screening guidelines: • Beginning at age 18 or upon sexual activity • ACOG (American College of Gynecology) recommends annual screening indefinitely • American Cancer Society recommends screening at least every 3 years (if no abnormal results); more frequent if patient is at increased risk • Both recommend pelvic exam annually for all women over 40 years old

9. PAP

10. Cervical Dysplasia • Precursor to cervical cancer • Aka Cervical intraepithelial neoplasia • Dysplasia = abnormal tissue development; refers to pre-cancerous changes in cervical cells *Cervical cancer of squamous cells is a preventable disease

11. Cervical Dysplasia • Risk factors: • Early age 1st intercourse; 2x risk if age 14 or 15 • More than 3 sexual partners • Giving birth before age 22 • Cigarette smoking (2x risk) • Low socioeconomic status • OCP use esp. if for 5-10 years (barrier methods protective) • Alterations in immune status (HIV, Lupus) • Current or past chlamydia infection • Vitamin A, C, and folate deficiency

12. Cervical Dysplasia • Pathology: • Cervix covered with mucus membrane • During adolescence, columnar epithelium changes to squamous epithelium • Squamo-columnar junction is most susceptible to dysplastic changes • Junction surrounds cervical os; recedes into os around menopause

13. Cervical Dysplasia

14. Cervical Dysplasia Mild dysplasia: basal layer thickens to about the bottom 1/3rd of membrane Moderate: basal cells thicken to middle 3rd Severe: basal cells thicken to more than 2/3rd of membrane Carcinoma in situ: basal cells through entire thickness of membrane

15. Cervical Dysplasia

16. Cervical Dysplasia

17. Cervical Dysplasia • Classification systems (PAP smear) • Bethesda Classification: • Low-grade SIL squamous intraepithelial lesion • Evidence of HPV • Mild dysplasia • High-grade SIL squamous intrapeithelial lesion • Moderate to severe dysplasia • Carcinoma in-situ

18. Cervical Dysplasia • Traditional Classification • CIN I: mild dysplasia • CIN II: moderate dysplasia • CIN III: severe dysplasia • Normal • Metaplasia • Inflammation • Atypia - cells are not dysplastic but not ideal - show evidence of repair (from infection, inflammation, etc) ASCUS: atypical squamous cells of undetermined significance AGCUS: atypical glandular cells of undetermined significance

19. Cervical Dysplasia • Etiology • HPV: Human Papilloma virus • Most evidence of causal relationship • Subtypes 16 and 18 most aggressive: 18 months until cancer development • HSV II: Herpes simplex virus • Virus detected in cervical cancer tissue • Antibodies found in blood of women with cervical dysplasia and cancer • No clear cause-effect determined (yet)

20. Cervical Dysplasia Approximately 70% women have HPV infection at some point in their lives Most infections and subsequent dysplasia regress on their own ~10% cervical cancer cases appear to rise in absence of detectable HPV DNA

21. Cervical Dysplasia • Evaluation: • Colposcopy: magnification of cervical transformation zone (squamo-columnar junction) • Biopsies of tissue w abnormal appearance • Large abnormal transformation zone correlates with high-grade lesions • Small abnormal transformation zone correlates with low-grade lesions • If entire transformation zone not visualized, need LEEP or conization procedures to sample endocervical canal

22. Cervical Dysplasia • Various levels of dysplasia will have different treatment plans Low-grade - often can recheck in 3-6 months High-grade- colposcopy to determine extent • Cone biopsy if indicated • Re-PAP more frequently if indicated

23. Cervical Dysplasia • Conventional Management: Cryotherapy: frozen carbon dioxide or nitrous oxide applied to abnormal tissue via a probe • Purpose is to eradicate abnormal epithelium a few millimeters thick • No anesthesia required • May result in cervical stenosis • Cure rate 91% CIN I-II; 78% CIN III • Follow up in 4 months to visualize tissue Laser therapy: • Vaporizes target tissue • Equipment more expensive and requires specialized training

24. Cervical Dysplasia • Naturopathic Management • Nutrition and supplementation • Focus on colorful veggies and fruits, cruciferous veggies • Folate 10 mg/day • Vitamin E 400-800 IU/day • Green tea capsules • DIM or I3C - both • Vaginal suppositories • Vitamin A nightly for 6 nights • Green tea nightly for 6 nights • (alternate weeks for 4-12 weeks) • Escharotic treatments also available - weekly, in office • Current research suggests cervical dysplasia may be evidence of FOLATE deficiency

25. Cervical Dysplasia • HPV vaccine: Gardasil • Approved by FDA June 2006 • Protects against 4 HPV strains (out of possibly hundreds): HPV 6, 11, 16, 18 • Vaccine studied for 4 years before release • Already on vaccine schedule for children • Marketed to girls as young as 11 years old • Research underway to study vaccine on boys

26. Cervical Dysplasia • Reported Gardasil adverse effects: • Collapsing after vaccine • Dizzy spells • Fainting • Seizures • Death • Vaccine recipients may still contract HPV and develop cervical dysplasia • Lifestyle choices, screening, and prevention are key against cervical ca.

27. Cervical Cancer Third most common gynecologic malignancy Eighth most common malignancy in US women 4,600 deaths annually Mean age 50 but may occur as young as age 20 HPV types 16, 18, 31, 33, 35, 39 increase risk Cancer occurs when cervical dysplasia or carcinoma in situ penetrates the basement membrane and invades surrounding tissue

28. Cervical Cancer

29. Cervical Cancer • Most (80-85%) cervical cancer is squamous cell carcinoma • The rest is mainly adenocarcinoma • No clear relationship to HPV etiology • Rare: • sarcoma, small cell neuroendocrine tumors, clear cell adenocarcinoma

30. Cervical Cancer • Spread: • Via direct extension to surrounding tissues • Via lymph to pelvic and para-aortic lymph nodes • Via lymph to extra-abdominal lymph nodes : left scalene and left supraclavicular nodes • Via blood to distant tissues - possible but rare in cervical cancer (Lung, liver, bone)

31. Cervical Cancer • Main symptoms: • CIN: usually asymptomatic and discovered with PAP smear • 50% women with cancer have never had a PAP or haven’t had one in over 10 years • Early stage: irregular vaginal bleeding (postcoital, intermenstrual, menometrhorrhagia) • Advanced: foul-smelling discharge, abnormal bleeding, pelvic pain • Late-stage: obstructive uropathy, back pain, leg swelling

32. Cervical Cancer Staging is most important determinant of prognosis • Stage 0 - full-thickness involvement of the epithelium without invasion into the stroma (carcinoma in situ) • Stage I - limited to the cervix • Stage II - invades beyond cervix • Stage III - extends to pelvic wall or lower third of the vagina • Stage IV - metastasis

33. Cervical Cancer

34. Cervical Cancer • 5-year survival rates by stage: • I: 80-90% (invasive squamous cell carcinoma remains localized for a long time) • II: 50-65% • III: 25-35% • IV: 0-15% • ~80% recurrences manifest within 2 years • Recurrences may happen as long as 15 years after primary therapy

35. Cervical Cancer • Diagnosis: • Pelvic exam/ biopsy • CT scan: best method to determine lymph node involvement • Fine-needle aspiration of suspicious nodes • IV pyelogram: determine urinary system involement • Chest x-ray • Barium enema/ sigmoidoscopy

36. Cervical Cancer • Treatment • Stage IA1/ limited tumor spread: hysterectomy • Stage IA2, IB where cancer has spread over 3 mm past basement membrane: • Radical hysterectomy (uterus, cervix, ovaries, oviducts) • Bilateral lymph node dissection • Removal of adjacent ligaments (round, broad)

37. Cervical Cancer • Treatment • Stage IIB, III, IV: Radiation primary treatment • Sometimes with chemo as a radiation sensitizer • If metastases beyond regional lymph nodes or if recurrent nonresectable disease: systemic chemotherapy • Not curative • Tumor regression occurs in only 25-30% women and is short-lived

38. Endometrial Cancer Most common gynecologic malignancy Fourth most common cancer in women Affects mainly postmenopausal women Peak incidence 50-60 year old women Less than 5% are under 40 years old Accounts for approximately 6500 deaths yearly in US; 36,100 new cases in US/ year

39. Endometrial Cancer • Higher incidence in women with: • Increased dietary fat intake • Obesity ( 3x if 21-50#; 10x if >50# overweight) • Pelvic radiation therapy • Family/ personal history of breast, ovarian ca. • Diabetes (2.8x); Hypertension, PCOS • Increased exposure to estrogen: unopposed estrogen therapy, nulliparity. • Late menopause (>52yo), annovulation, estrogen-secreting tumors

40. Endometrial Cancer • Spreads: • Via surface of uterine cavity to cervical canal • Through myometrium to serosa to peritoneal cavity • Via Fallopian tube to ovary • Via blood to distant sites • Via lymph to lymph nodes

41. Endometrial Cancer Precursor is endometrial hyperplasia (occurs during periods of unopposed estrogen) The higher the grade, the greater the chance of deeper invasion of myometrium or extra-uterine spread Over 80% of endometrial cancer is adenocarcinoma Sarcomas approx 5%

42. Endometrial Cancer • Symptoms • Vaginal discharge • Abnormal bleeding patterns • 1/3 of post-menopausal bleeding is due to endometrial carcinoma

43. Endometrial Cancer - staging Stage IA: tumor limited to the endometrium Stage IB: invasion of less than half the myometrium Stage IC: invasion of more than half the myometrium Stage IIA: endocervical glandular involvement only Stage IIB: cervical stromal invasion

44. Endometrial Cancer - staging Stage IIIA: tumor invades serosa or adnexa, or malignant peritoneal cytology Stage IIIB: vaginal metastasis Stage IIIC: metastasis to pelvic or para-aortic lymph nodes Stage IVA: invasion of the bladder or bowel Stage IVB: distant metastasis, including intraabdominal or inguinal lymph nodes

45. Endometrial Cancer

46. Endometrial Cancer

47. Endometrial Cancer • Diagnosis • Endometrial biopsy or Fractional D&C • Transvaginal ultrasound • CT if metastases suspected • Stool guaiac test if bowel metastases suspected

48. Endometrial Cancer • Treatment • Stage I: surgery • Hysterectomy • Bilateral salpingo-oopeherectomy • Peritoneal cytologic examination • 50-70% cases no need for post-op radiation • If patient unable to tolerate surgery, radiation alone used

49. Endometrial Cancer • Treatment • Stages II, III • Additional surgery: para-aortic lymphadenectomy • If extra-pelvic cancer: add radiation, chemotherapy, and/ or hormone therapy • Hormone therapy includes progestin therapy to induce regression of tumors, occurs in 35-40% of patients • Stage IV: systemic chemotherapy

50. Endometrial Cancer Most recurrences of adenocarcinoma of endometrium occur within 3 years of dx 90% occur within 5 years ERT controversial after treatment for endometrial cancer; do benefits outweigh risk?