Endometrial and ovarian cancer

1. Endometrial and ovarian cancer

2. Uterine anatomy and tumor origins Uterine cancer: • Endometrium: endometrial carcinoma (type I and II) • Myometrium: uterine sarcoma Cervical cancer: • Cervix: squamous cell carcinoma and rarely adenocarcinoma of the cervix

3. Epidemiology of uterine cancer

4. Epidemiology of uterine cancer

5. Epidemiology of endometrial cancer • The most common uterine cancer • Approximately 75% of patients are menopausal

6. 2 main categories of endometrial cancer • Endometrial cancer is divided into type I and type II, characterized by distinct biologic and clinical behavior, with different causes • Type I carcinomas account for approximately 85% of all EC and are associated with a hyperestrogenic state and generally are low-grade; histology: endometrioid carcinoma. Patients are usually younger (65). • Type II tumors are estrogen-independent and arise in the setting of uterine atrophy and generally consist of poorly differentiated tumors; histology: papillary serous carcinoma, clear cell carcinoma and malignant mixed müllerian tumor. They represent approximately 15% of all ECs. Type II patients are more often multiparous, older (70), and less likely to be obese. More frequent in blacks than whites. • Molecular genetic studies over the past decade have shown that the two tumor types evolve via distinct pathogenetic pathways

7. Risk factors • For endometrioid uterine cancer the most important risk factor is unbalanced or high estrogen levels • Obesity is an important contributing factor, since fatty tissue produces estrone (E1). (These patients usually have metabolic syndrome.) • Estrone is unbalanced by progesterone, since the ovaries don’t produce enough progesterone in menopausal or premenopausal women=> the endometrial mucosa is always in the proliferative stage=>hyperplasia->atypical hyperplasia -> cancer

8. Risk factors • Late menopause (>52 yrs) • Hormone replacement therapy with estrogen only • Similarly, Tamoxifen, used in the treatment of breast cancer can cause endometrioid uterine cancer, since it is an agonist on the uterine mucosa (and antagonist on breast tissue)

9. Genetic risk factors • hereditary nonpolyposis colorectal cancer syndrome (HNPCC) or Lynch syndrome II

10. Reminder: Metabolic Syndrome The metabolic syndrome is characterized by a group of metabolic risk factors in one person. They include: • Abdominal obesity (excessive fat tissue in and around the abdomen) • Atherogenic dyslipidemia (high triglycerides, low HDL cholesterol and high LDL cholesterol — that foster plaque buildups in artery walls) • HBP • Insulin resistance or glucose intolerance • Prothrombotic state (e.g., high fibrinogen or plasminogen activator inhibitor–1 in the blood) • Proinflammatory state (e.g., elevated C-reactive protein in the blood)

11. Routes of extension-Local spread • myometrium, cervix, vagina, parametria, bladder, rectum, ovaries

12. Lymphatic spread • Lymphatic spread (regional lymph nodes): -tumors in the uterine fundus->directly to paraaortic lymph nodes -tumors from the middle and lower part of the uterus->internal and external iliac lymph nodes->paraaortic lymph nodes or to inguinal lymph nodes

13. Routes of extension • Peritoneal • Distant Metastases: -lung, liver, bone

14. Symptoms of endometrial cancer • Uterine bleeding or discharge Metrorrhagia in menopause is probably endometrial cancer, unless proven otherwise. (can be cervical cancer to) -this symptom is early=> the majority of cases (70%) will be diagnosed with stage I disease confined to the corpus, and these patients have excellent survival • Other symptoms due to compression to adjacent organs or invasion (invasion of the parametria: ureteral obstruction)

15. Diagnosis of endometrial cancer • Gynecologic examination: -bimanual examination: uterus has increased volume -rectal examination: extension to the parametria -speculum examination: the cervix is usually normal; it can detect cervical or vaginal invasion

16. Reminder-Pelvic exam • Step One–External Genital Exam • Purpose: Check for irritation, unusual discharge, cysts or genital warts and to make sure the glands around the opening of vagina or urethra are not swollen or inflamed. • How it's Done: The area is both visually and manually examined. • Step Two–Internal Bimanual Exam • Purpose: Evaluate the size, shape and position of pelvic organs (uterus, ovaries and fallopian tubes) and help detect abnormalities such as adhesions, tears, enlargements, cysts, tumors or tenderness. • How it's Done: One or two gloved, lubricated fingers are placed in the vagina while pressing on the lower abdomen with the other hand. • Step Three–Internal Rectovaginal Exam • Purpose: Evaluate the tissue in between the uterus and vagina and the ligaments that hold the uterus in place. Check for rectal bleeding. • How it's Done: A gloved, lubricated finger is placed in the vagina and another in the rectum while pressing on the lower abdomen. • Step Four–Internal Speculum Exam • Purpose: Examine vaginal walls and cervix for damage, sores, growths, inflammation or unusual discharge. A Pap smear might be taken during this phase of the exam. • How it's Done: A speculum is gently inserted and opened to hold the walls of the vagina apart.

17. Diagnosis of endometrial cancer • Endometrial biopsy (outpatient); • If biopsy not diagnostic => Dilation and curettage=D&C (inpatient)

18. The establishment of the extension and general work-up • For all patients: chest radiography, CBC, platelets, renal function • Tumor limited to the uterus=> additional tests needed for surgery -then the patient is operated and the disease surgically staged 2. Suspected or proven extrauterine disease => CT/MRI of the pelvis + abdomen, +/-cystoscopy, +/- rectoscopy if suspicion of mucosal invasion

19. Treatment of endometrial cancer • Tumor limited to the uterus and no cervical involvement • Medically operable=> total hysterectomy and bilateral salpingo-oophorectomy (TH+BSHO) plus pelvic and para-aortic lymphadenectomy • Medically inoperable=> radiotherapy

20. Treatment of endometrial cancer • Extrauterine disease • Preoperative radiotherapy followed by surgery • Radiotherapy alone

21. Treatment of endometrial cancer • In the presence of risk factors adjuvant radiotherapy might be used after surgery

22. Non-malignant tumors: fibroids

23. Questions • What are the symptoms of endometrial cancer and at which age group is the most common? • How is the diagnosis of endometrial cancer made?

24. Ovarian cancer • The most lethal cancer from the tumors of the female genitalia, because diagnosis is usually late and spread occurs easily to the peritoneum

25. Risk factors • Genetic: -BRCA1/2 -Lynch 2 syndrome etc. II. Reproductive -early menarche -late menopause -nulliparity Protective: oral contraceptives III. Environmental -obesity -”industrialized” living

26. Histology • Epithelial tumors (90%) -most frequent subtype: serous adenocarcinoma 2. Stromal tumors 3. Germinal tumors

27. Routes of spread • Peritoneal • Greater omentum

28. Routes of spread • Invasion of adjacent structures (uterine corpus, salpinx) • Lymphatic: iliac and para-aortic lymph nodes • Hematogenous: liver

29. Symptoms • Abdominal: abdominal pain, dyspepsia, bloating, increase in the perimeter of the abdomen • Pelvic: metrorrhagia, pollakiuria • Thoracic: dyspnea (due to ascites or pleurisy) • General: fatigue, weight loss

30. Diagnosis • Pelvic exam • US or CT of the pelvis and abdomen • CA-125 tumor marker • Chest radiography • additional tests needed for surgery

31. Treatment • SURGERY +/- CHEMOTHERAPY • In some stage I patient: unilateral salpingo-oophorectomy for fertility preservation • All other patients: “optimal debulking”=“optimal cytoreduction” =resection of all tumor tissue, if possible, or leaving behind tumor tissue with a diameter of less than 1 cm

32. Surgery has to include: • total hysterectomy and bilateral salpingo-oophorectomy (TH+BSHO) plus pelvic and para-aortic lymphadenectomy • Omentectomy • Resection of the peritoneal metastases, if present • Resection of involved organs

33. Adjuvant chemotherapy • Intraperitoneal + IV • IV only

34. Questions? • What is the special kind of surgery done in locally advanced ovarian cancer?