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Clinico-pathological conference: Gynae Oncology Friday Dec 7th 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 rectovaginal 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 Doppler FDG-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 RECURRENCE “The true Killer” An integrative model for recurrence in ovarian cancer Management algorithm for patients with ovarian cancer Our opportunity for intervention CHEMOPREVENTION PROPHYLACTIC OOPHORECTOMY Ovulation Environment Family history NORMAL OVARY PREMALIGNANT CHANGE TREATMENT PRECLINICAL DISEASE SCREENING CLINICAL DISEASE Life sciences Image trait selection Gene expression data Pre- processing Disease traits Image traits Pathological data MRI 3-D colour doppler Proteomic data CT FDG-PET Expression data Information sciences Clustering Classification program learning Module network procedure Life and Information sciences Gene partition Functional modules Annotation analysis Post- processing Independent Validation Genes Graphic presentation