Clinico-pathological conference: Gynae Oncology Friday Dec 7 th 2007

1. Clinico-pathological conference:Gynae OncologyFriday Dec 7th 2007 Alex Laios, Orla Sheils, John O’Leary

2. HISTORY • 43 yr old, Irish lady, married, P0+0 • Consulted GP with a 3/12 Hx of: • Abdominal distention (increasing abdominal girth) • Intermittent abdominal pain, progressively worsening (like tightness across the abdomen) • Loss of appetite • Weight loss associated with lower abdominal discomfort of ~3/52 duration • 1 recent episode of SOB and dry cough • No change in urinary or bowel habits

3. Questions • What are the possible causes of increasing abdominal girth? • What is the possible cause of weight loss in this woman? • Why does this woman have shortness of breath and dry cough?

4. Questions • What is the next step in managing this patient? • What investigations would be ordered in this case?

5. Ultrasound examination of the abdomen-pelvis [ordered by GP] • Massive ascites • 9 cm large complex cystic mass probably arising from the pelvis, with multiple septations • Left ovary could not be visualized • Left hydronephrosis

6. Pelvis US scan

7. Referral to gynae oncology service Physical examination • Thin lady, previously healthy • No lymphadenopathy • Breast examination was normal • Lung fields clear on auscultation • Abdominal distention to 28 weeks size by a mass of poor mobility arising from pelvis and upper abdominal fullness, suggesting omental disease • Clinical ascites • Distended pouch of Douglas with thickening on recto-vaginal examination

8. Medical and Gynaecologic History Medical Hx: • HTN, Ulcerative colitis (previously on long term steroids but no evidence of DEXA osteopenia) • Medications: Centyl, Lipitor • Allergies: Penicillin Surgical Hx: Arthroscopy, cholecystectomy Family Hx: Bowel Ca (father), breast Ca (mother) Gynae Hx: • Menarche at age 12y • Regular cycles, no dysmennorhea, LMP 2/52 ago • Last Cx smear 3 years ago • Never on OCP

9. Laboratory investigations On admission • FBC profile: Hb:13, WCC:9.8, PLTS:560 • Renal profile: urea:10.3, sodium:140, potassium:3.6, creatinine:93 (marginally elevated) • Liver profile: Albumin: 25 , LDH:385 • CA125: 534 • CA19.9: 3.9

10. Questions • What is your provisional diagnosis? • Can you identify any risk factors from her medical history? • What is your interpretation of her blood results? • Albumin • urea, creatinine • Hb, plts

11. Radiology investigations • CXR: • Lung fields appear clear • No cardiomegaly • No pleural effusion • CT TAP (chest abdomen pelvis) • 11 X 12.5cm complex pelvic mass arising from the left ovary • Massive ascites • Omental cake • No evidence of retroperitoneal lymphadenopathy • Left hydronephrosis • Splenic hilar and peritoneal nodes • 3-D colour Doppler • FDG-PET

12. CT- pelvis and abdomen

13. Omental cake

14. MRI scan -pelvis

15. 3-D colour Doppler FDG-PET

16. Laparotomy:Optimal debulking Findings on laparotomy TAH, BSO,Omentectomy, Appendicectomy • Gross disease above pelvic brim • 4 litres of ascites was removed • Left ovary replaced by solid-cystic tumour at least 13 cm, densely adherent to the left pelvic sidewall/peritoneum/POD • Tumour deposits on splenic hilum, small deposits in subdiaphragmatic and liver capsule (less than 0.5cm) • Omental deposits

17. Describe the gross pathology findings

18. Peritoneal fluid What does this show?

19. Histology What does this show?

20. Immunocytochemistry: p53

21. Pathological diagnosis • Papillary serous cystadenocarcinoma of the left ovary • TNM stage pT3, N1, Mx • FIGO stage IIIC

22. HISTORY • Uneventful recovery • Histology available at day 9 • Referred to medical oncologists for adjuvant chemotherapy • Discharged on day 13 • Returned 6 weeks after surgery for initiation of chemotherapy

23. HISTORY • Received 6 cycles of Carboplatin and Taxol • Question: what do these agents exactly do?

24. Actions of drugs Mechanism of action of taxol Mechanism of action of carboplatin

25. HISTORY • Chemotherapy completed 3 months later • Remained well and returned for combined follow-up with Gynae-Oncologists and Medical Oncologists • Question: what is entailed in the medical follow-up?

26. Follow-up • History • Clinical examination • CA-125

27. HISTORY • Routine follow-up [3 months] for the first 2 years, then every 6 months for the next 2 years, then annually. • 14 months after the original surgery she complains of: • Tiredness • Intermittent low abdominal pain • Vaginal bleeding

28. Questions • Why does this patient have a vaginal bleeding? • What is the cause of the intermittent abdominal pain?

29. HISTORY • On clinical examination, two nodules are identified close to the vaginal vault • Raising CA125 • CT of thorax, abdomen and pelvis performed • Two small soft tissue masses suspicious for disease recurrence seen at the vaginal vault • Biopsy performed of vaginal lesions

30. Vaginal vault biopsy What does this show?

31. Relapse • Will the patient benefit from the same chemotherapy? • Will she benefit from excision of the nodules?

32. RECURRENCE “The true Killer” Recurrence in ovarian cancer • 70% of ovarian cancer patients present with advanced ovarian cancer [stage III/IV] • 50%-70% of patients relapse • Less than 20% long-term survivors • Gene pathways for ovarian cancer recurrence have just been defined

33. An integrative model for recurrence in ovarian cancer

34. Management algorithm for patients with ovarian cancer

35. CHEMO- PREVENTION PROPHYLACTIC OOPHORECTOMY TREATMENT Ovulation PRE- CLINICAL DISEASE NORMAL OVARY PRE- MALIGNANT CHANGE CLINICAL DISEASE Environment Family history SCREENING Our opportunity for intervention

36. Life sciences Image trait selection Gene expression data Pre- processing Disease traits Image traits Pathological data Proteomic data 3-D colour doppler CT FDG-PET MRI Expression data Information sciences Clustering Classification program learning Gene partition Module network procedure Functional modules Life and Information sciences Annotation analysis Genes Graphic presentation Independent Validation Post- processing