Case 17 cancer: ovarian Flashcards
Ovarian tumours: metastatic
- 5% of ovarian tumours
- Krukenberg tumour- malignant, metastases from a gastrointestinal tumour resulting in a mucin secreting signet ring cell adenocarcinoma
Ovarian tumour: symptoms
- Often asymptomatic
- Bloating or indigestion
- Gradually increasing abdominal distension
- Difficulty eating and feeling full, fatigue, anorexia
- Chronic abdominal, pelvic or back pain, urinary frequency/urgency, constipation/altered bowel habit/bowel obstruction, leg swelling and DVT/PE
- Abnormal vaginal bleeding
- Symptoms of metastatic disease i.e. pleural effusion, ascites, weight loss and fatigue
Complications of ovarian cancer: not metastatic
- Sudden torsion or rupture can present with acute abdominal or pelvic pain
- VTE due to prothrombotic tendency
Other organ involvement in ovarian cancer and symptoms
- Bowel: abdominal bloating or distension, loss of appetite, nausea, vomiting, altered bowel habit, esp. constipation, abdominal pain, bowel obstruction
- Kidney: hydronephrosis secondary to ureteric obstruction, haematuria, recurrent UTI, loin pain, renal failure
- Pleural effusion: breathlessness, respiratory distress (rare) as a result of a large pleural effusion, which is more common on the right
- Umbilical peritoneal deposits in stage 4 disease and Saint Mary Joseph nodules
Symptoms of ovarian cancer due to local mass effect and lymph node involvement
- bladder: urgency, frequency
- para-aortic lymph nodes can be affected causing back ache
- Inguinal or femoral nodes are not normally affected - suggestive of other gynae disease
Differential diagnosis for ovarian cancer
- Gastric cancer: abdo symptoms, early satiety and sometimes ascites
- Bowel cancer: unlikely <50 unless strong family history
- Colon cancer: can present with ascites
- Hepatocellular carcinoma: normally due to alcohol or hepatitis B/C
Clinical signs of ovarian cancer
- general examination – cachexia, lymphadenopathy, signs of pleural effusion
- abdominal examination – distension, ascites, palpable pelvic mass, “omental cake” metastasis
- Cusco speculum examination – usually normal
- bimanual palpation – palpable adnexal/pelvic mass which may be fixed and immobile
Ovarian cancer epidemiology
- Ovarian cancer kills more people than other gynaecological cancer
- 50-75 Caucasian, higher rates in developed countries
- 5-10% have genetic cause
Ovarian cancer bloods and investigations
Bloods Ovarian cancer: FBC, serum biochemistry, LFT, Bone profile, CA-125, CEA. In younger women hCG, AFP, LDH
Investigations
- Pregnancy test
- AFP, beta-hCG: elevated in ovarian germ cell tumours
- Other tumour markers: CA19-9, beta-hcg, ALP (suggests liver mets), AFP, Inhibin and LDH, CA125
- Transabdominal +/- transvaginal ultrasound: first line
- Exploratory laparotomy with biopsy: to confirm diagnosis, for staging
CA-125
- Is present in most cases of advanced ovarian cancer.
- Raised suggests worse prognosis.
- If doubles after remission suggests relapse
- > 30 is suggestive of ovarian cancer
Ovarian cancer: imaging
- Imaging- CXR to check for pleural effusion or lung metastases
- CT +/- MRI abdomen and pelvis to assess mass, pelvic nodes and any metastases in advanced disease
- PET scan may in advanced disease
- Invasive tests – pleural or ascitic tap with cytology
- Laparoscopy and biopsy: to confirm diagnosis, staging
- Preoperative endometrial sampling: women with abnormal vaginal bleeding
- Preoperative cytological or histological evaluation of effusion or tumour mass
- Genetic test: for BRCA
How is transvaginal US scored for ovarian cancer
- 1 point for each of:
- multilocular lump
- bilateral disease
- solid areas, ascites or mets
Risk factors for ovarian cancer
- Age (peaks age 60): postmenopausal
- BRCA1 and BRCA2 genes (family history)- most associated with serous
- Other conditions: Peuz-Jeghers syndrome, Lynch type II
- Obesity, Smoking
- Diet: fat, lactose, coffee
- Recurrent use of clomifene
- Increased number of ovulations: early onset periods, late menopause, no pregnancies, infertility, ovulation inducing drugs
- Other factors: Talc, radiation, viruses (mumps, rubella, influenza)
- Protective: pregnancy, prolonged breast feeding, COCP
RMI: risk of malignancy index
Estimates the risk of an ovarian mass being malignant, taking account of three things:
- Menopausal status: 1 if premenopausal, 3 if postmenopausal
- Ultrasound findings: up to max score of 3. Get 1 point for following: Multilocular, Solid areas, Bilateral, Ascites, Metastases
- CA125 level
- RMI: U x M x serum CA-125
- RMI >200 warrants referral to gynae
Ovarian cancer: further investigations in secondary care
- CT scan to establish the diagnosis and stage the cancer
- Histology (tissue sample) using a CT guided biopsy, laparoscopy or laparotomy
- Paracentesis (ascitic tap) can be used to test the ascitic fluid for cancer cells
Women under 40 years with a complex ovarian mass require tumour markers for a possible germ cell tumour:
- Alpha-fetoprotein (α-FP)
- Human chorionic gonadotropin (HCG)
Staging ovarian cancer
- Stage 1: Confined to the ovary
- Stage 2: Spread past the ovary but inside the pelvis
- Stage 3: Spread past the pelvis but inside the abdomen (microscopic peritoneal mets, superficial liver, regional nodes)
- Stage 4: Spread outside the abdomen (distant metastasis), parenchymal liver metastasis
BRCA mutations ovarian cancer
Most commonly associated with serous cancers of the ovary and occasionally endometrial cancer of the ovary. Autosomal dominant
Other mutations in ovarian cancer
PARP1 mutations in ovarian cancer: PARP inhibitors (Olaparib, Rucaparib, Niraparib) are used following chemo in BRCA mutation carriers
Somatic gene mutation: present in the cancer cells only
Ovarian cancer: management
- Surgery: to remove tumour. Involves laparotomy, total hysterectomy, bilateral salpingo-oopherectomy with omenectomy and lymph node resection
- Adjuvant chemotherapy: with carboplatin and paclitaxel, add bevaclizumab in high risk disease.
- Neoadjuvant chemo in extensive disease or if surgery not initially possible i.e. due to fitness
- Non epithelial ovarian cancer: surgery followed by chemo
- Relapse: offer second line chemo
- Serum CA125 can predict relapse
- Aromatase inhibitors and Tamoxifen
- PARP inhibitor: if BRCA mutation, take for 2 years start within 8 weeks of chemo
Ovarian cancer complications
- Local invasion: Lymphoedema, vaginal discharge, bowel obstruction, ascites, pleural effusion, hydronephrosis (due to ureteric obstruction)
- Distant metastasis: liver, lung, bone, brain
- Non metastatic: PE, dermatomyositis
- Stage 1 have 90% survival rate, whereas stage 4 it is <25%
Management of ascites in cancer
- US, MRI or CT can help guide drainage
- Treatment with paracentesis including indwelling (Pleurx catheters)
- Diuretics and salt restriction aren’t helpful
Summary of ovarian cancer treatment
- surgery with intra-operative histology for staging and to decide extent of procedure
- Minimum surgery: bilateral hystero-salpingo-oophorectomy and appendectomy
- usually also systematic retroperitoneal lymphadenectomy unless stage 1
- adjuvant chemo for 6 months unless low risk stage 1
Investigations for metastatic disease of unknown primary
- FBC, U&E, LFT, calcium, urinalysis, LDH
- Chest X-ray
- CT of chest, abdomen and pelvis
- AFP and hCG
Specific investigations for metastatic disease of unknown primary
- Myeloma screen (if lytic bone lesions)
- Endoscopy (directed towards symptoms)
- PSA (men)
- CA 125 (women with peritoneal malignancy or ascites)
- Testicular US (in men with germ cell tumours)
- Mammography (in women with clinical or pathological features compatible with breast cancer)
Cachexia
reduction in weight, primary cause is cancer. Involves anorexia, weight loss, muscle wasting, anaemia and lack of energy.
Jaundice in malignancy
obstructive jaundice, uraemia, Hodgkin’s disease, allergy, dermatitis, neuropathy or drug reaction (often with opiates). an be caused by widespread parenchymal liver metastases, solitary parenchymal liver metastasis near the porta hepatis, a lymph node mass at the porta hepatis, a drug reaction or viral infection
Hypercalcaemia in malignancy
- The most common metabolic complication of malignancy indicates poor prognosis
- Common in multiple myeloma, breast, lung, kidney, head and neck cancer, lymphoma
- Non specific presentation, can just cause deterioration
- In any patient with confusion consider: Hypercalcaemia, Brain metastasis, Metabolic disturbance
Calcium homeostasis
- If Ca+2 is too high the thyroid releases Calcitonin to increase excretion and decrease uptake
- If Ca+2 is too low, PTH is released increasing uptake
- Tests on ascitic fluid: albumin,amylase, cytology, glucose, lactate dehydrogenase
Causes of hypercalcaemia in malignancy
- Common issue, mainly due to bone metastasis. True paraneoplastic hypercalcaemia is due to tumour production of parathyroid hormone related protein
- Cancer types: NSLC, Head and neck, Renal, SCC of oesophagus
- Clinical presentation: rapid onset nausea, poluria, polydipsia, dehydration, cardiac arrhythmias
- Diagnosis: Serum Ca2+ > 2.7 mmol/l, serum chloride low, hypercalcuria, high urinary phosphate, low or undetectable plasma parathyroid hormone
- Treatment: saline hydration, IV bisphosphonates
Malignancy: bowel obstruction
- When sub-acute: give medications IV, insert an NG tube and steroids (reduce inflammation)
- Avoid Metoclopramide and give Haloperidol instead
Carcinoma of unknown primary
- Malignant tumour arising from the epithelial system of the body
- Where the primary site is able to metastasis before the primary site is large enough to be identified
- Difference to primary tumours: early dissemination, clinical absence of primary tumour, unpredictable metastatic pattern, more aggressive, absence of symptoms due to primary tumour
- Common causes: multiple site involvement, liver, bone, lung, lymph node
Poor prognostic factors for unknown primary cancers
- Median survival 6-9 months
- Poor prognosis: poorly differentiated carcinoma, neuroendocrine carcinoma, lymph node envolvement, number of metastatic sites, male, poor fitness, increased weight loss
- Serum markers: alk phos, LDH, CEA
Approach to carcinoma of unknown primary
Step 1: Search for a primary site
Step 2: Rule out potentially treatable or curable tumours
Step 3: Characterise the specific clinicopathological entity. Treat the patient if favourable sub sets with curative intent if unfavourable with palliative intent
How would a primary peritoneal or ovarian cancer present
Predominantly nodal metastasis of poorly differentiated carcinomas and females with peritoneal carcinomatosis of a high grade serous histological type adenocarcinoma
Common causes of transudate vs exudate
- Transudate: heart failure, liver failure, kidney failure, thyroid failure, respiratory failure, Meig’s syndrome
- Exudate: cancer, pneumonia, PE
Causes of raised CA-125
Cervical adenocarcinoma, Endometrial carcinoma, Fallopian tube cancer, Heart failure, Hypothyroidim, Liver cirrhosis with severe necrosis, Non-Hodgkins lymphoma, Pleural effusion
Investigations for cancer of unknown primary
- Bloods: CEA, CA-125, TTF-1
- CT TAP, CXR, Laproscopy with biopsies
End of life care
- Recognition of approach of death: by clinicians, patient and family
- Assess psychological state: ability to communicate capacity, screen for depression with HAD (hospital anxiety and depression) score
- Manage physical symptoms: pain, N+V, respiratory secretions, agitation
- Spiritual support: for patient and family
- Rationalising prescribing: routes of administration (subcut morphine), discontinue non essential drugs
- Communicating with other professionals
- MDT involvement in decision making
- In final hours may withdraw nutrients and hydration
