Clinico-pathological conference: Gynae Oncology Friday Dec 7 th 2007 Alex Laios, Orla Sheils, John O’Leary

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

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?

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

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

Pelvis US scan

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

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

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

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

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

CT- pelvis and abdomen

Omental cake

MRI scan -pelvis

3-D colour DopplerFDG-PET

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

Describe the gross pathology findings

Peritoneal fluid What does this show?

Histology What does this show?

Immunocytochemistry: p53

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

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

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

Actions of drugs Mechanism of action of taxol Mechanism of action of carboplatin

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?

Follow-up History Clinical examination CA-125

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

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

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

Vaginal vault biopsy What does this show?

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

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 “The true Killer” RECURRENCE

An integrative model for recurrence in ovarian cancer

Management algorithm for patients with ovarian cancer

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

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