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APPENDIX: Self-Assessment Multiple Choice Questions and Answers
Best Practice & Research Clinical Obstetrics & Gynaecology Vol. 15, No. 3, pp. A1±A18, 2001
doi:10.1053/beog.2001.0191, available online at http://www.idealibrary.com on
APPENDIX Endometrial Cancer: Self-Assessment Multiple Choice Questions
For each part of each question, answer true or false by ticking in the appropriate box. The answers will be published in the next issue. Chapter 1 1. Mortality rates for cancer of the corpus uteri in the United States are higher for blacks than they are for whites. This is likely to be due to the fact that:
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(a) Endometrial cancer is more common in US blacks than in US whites (b) The disease is detected later in the US blacks and therefore their prognosis is not as good as for US whites (c) US blacks have poorer access to good quality medical care than US whites (d) US blacks tend to smoke more than US whites (e) Baseline hysterectomy rates are lower than for white women so more Black women are at risk
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2. A number of authors in the 1980s were of the opinion that the association observed between endometrial cancer and oestrogen therapy was not real, and was primarily due to `detection bias'. This was based on the following observations:
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(a) Women on hormone therapy are more likely to have endometrial cancer detected (b) The increase in incidence seen in the 1970s was not mirrored by an increase in mortality (c) There was a worse survival of endometrial cancer patients who had been on oestrogen therapy (d) A large number of undetected endometrial tumours were found at autopsy (e) The increase in risk associated with oestrogen therapy persists for several years after cessation of use
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1521±6934/01/03000A118 $35.00/00
c 2001 Harcourt Publishers Ltd. *
A2 Appendix
3. Smoking is thought to possibly modify the eects of obesity and oestrogen therapy on endometrial cancer. Direct evidence to support this is that:
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(a) Smoking reduces the risk of endometrial cancer (b) The protective eect of smoking is greater among oestrogen users and obese women (c) The risk associated with being overweight is not as large in smokers as it is in non-smokers (d) Smoking increases the risk of hip fractures in post-menopausal women (e) Women who smoke tend to be leaner than women who do not smoke
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4. When ®rst counselling a woman at 50% risk of HNPCC with a family history ful®lling Amsterdam Criteria, but no known family mutation:
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(a) The lifetime risk of bowel cancer is 60% (b) The lifetime risk of endometrial cancer is up to 30% (c) Screening of endometrium by transvaginal ultrasound and hysteroscopy is recommended (d) Blood should be drawn for genetic testing (e) Colorectal tumours in patients with HNPCC arise in pre-existing adenomatous polyps, which are generally present in large numbers (i.e. excess of 100)
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Chapter 2
5. The following statements about HNPCC are true: (a) Prognosis of cancer is better in age- and staged- matched controls than in HNPCC (b) Caecal tumours are more common than in the general population (c) Lung cancer is a common feature of HNPCC (d) Transitional cell carcinoma of the ureter is a diagnostic criteria tumours (e) HNPCC is an autosomal recessive condition 6. Which of the following statements are correct? (a) HNPCC results from a germline mutation in DNA mismatch repair genes (b) Microsatelite instability is a result of failure of DNA mismatch repair genes to detect and correct errors in the genetic code during DNA replication (c) Current recommendations are that known carriers of DNA mismatch genes should undergo colonoscopy every 6±12 months (d) Subtotal colectomy performed prophylactically obviates the need for further gastrointestinal surveillance
Appendix A3
(e) Dietary manipulation using NSAIDs and resistant starch may in the future have a role in the prevention of the formation of adenomas within the colon
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7. A postmenopausal breast cancer patient, 3 years on tamoxifen, presents with vaginal bleeding. Which of the following approaches is evidence based?
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(a) A Pipelle endometrial biopsy (b) A dilatation and curettage in any such patient with a thickened (45 mm) endometrial layer in transvaginal ultrasonography (c) A saline infusion sonography with selective endometrial biopsy in case of asymmetrical endometrial thickening (d) A hysteroscopy with guided endometrial biopsy (e) A course of 14 days of medroxyprogesterone acetate
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8. A 53-year-old healthy asymptomatic postmenopausal woman has lost her sister and mother of breast cancer and is given tamoxifen for 5 years. The gynaecological check up should ideally include:
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(a) A pre-treatment assessment of the uterine cavity with transvaginal ultrasonography and saline infusion sonography or hysteroscopy in case of a thick endometrial layer (45 mm) (b) A yearly vaginal examination with a cervical PAP smear (c) In case of a normal pre-treatment uterine cavity, a yearly transvaginal ultrasonography with hysteroscopy or saline infusion sonography in case of endometrial thickening (45 mm). (d) A ®rst uterine assessment after 3 years of being on tamoxifen in case the patient has a normal pre-treatment uterine cavity. (e) No gynaecological examination at all unless the patient reports vaginal bleeding
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9. The following statements on tamoxifen and newer SERMs can be interpreted as follows:
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(a) Tamoxifen induces the endometrial progesterone receptor (b) Tamoxifen induces aggressive and high-grade endometrial cancers (c) Tamoxifen is contra-indicated following hysterectomy for earlystage endometrial cancer (d) After 3 years of being on raloxifene, a patient is more likely to develop endometrial polyps and endometrial cancer compared with the patient on placebo (e) Raloxifen should now replace tamoxifen as an adjuvant therapy following treatment of an oestrogen receptor positive breast cancer because it has no endometrial side-eects
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Chapter 3
A4 Appendix
Chapter 4 10. The following statements about endometrial carcinoma are true: (a) The median age of patients at diagnosis is 63 years (b) Women with complex endometrial hyperplasia without atypical cytological features are at low risk of uterine cancer (c) It is more likely to occur in women who undergo early menopause (d) Is more likely to be the cause of postmenopausal bleeding in an 80year-old than in a woman aged 60 years (e) Para-aortic lymph node involvement indicates stage IIIB disease 11. Outpatient hysteroscopy: (a) (b) (c) (d)
Can be performed successfully in more than 90% of women Usually requires the use of a paracervical block Reliably distinguishes carcinoma from hyperplasia Has a lower sensitivity for endometrial pathology than dilation and curettage (e) Is associated with less patient discomfort when carbon dioxide rather than saline is used to distend the uterus 12. Endometrial thickness measured by transvaginal ultrasound scan: (a) (b) (c) (d) (e)
Is measured from the midline echo of the endometrial cavity to the nearest point of the myometrium Has a lower sensitivity for the detection of endometrial cancer in women taking hormone replacement therapy When less than 5 mm, the probability of endometrial cancer being present is less than 1% Normally decreases with age Is increased in women taking tamoxifen
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Chapter 5 13. The likelihood of response of endometrial hyperplasia to progestins is aected by: (a) (b) (c) (d) (e)
The progesterone receptor status of the tumour The oestrogen receptor status of the tumour The type of progestin used The presence of nuclear atypia The age of the patient
14. Which of the following statements are true? (a) There is no risk of progression of simple endometrial hyperplasia to invasive carcinoma. (b) The risk of progression of complex hyperplasia to invasive carcinoma is 3%
Appendix A5
(c) Simple atypical hyperplasia has a lower malignant potential than complex hyperplasia (d) The risk of progression of complex atypical hyperplasia to endometrial carcinoma is 29% (e) Complex atypical hyperplasia implies both cytological and architectural atypia
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16. Which of the following statements about endometrial cancer are true?
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(a) In Europe, endometrial cancer is the most common gynaecological cancer (b) Endometrial cancer could be largely prevented by screening (c) Endometrial cancer often presents at an advanced stage (d) Endometrial cancer overall has an average 5-year survival compared with other cancers (e) Endometrial cancer usually metastases initially to the pelvic lymph nodes
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17. Which of the following are regarded as high-risk endometrial tumours?
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(a) Endometrial carcinoma stage 1B G2 (b) Endometrial carcinoma stage 1B G3 and lymphovascular space involvement (c) Papillary serous adenocarcinoma (d) Clear cell adenocarcinoma (e) Squamous carcinoma
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15. Which of the following statements are correct? (a) At least one-third of women with complex atypical hyperplasia may have adenocarcinoma present in the uterus if hysterectomy is performed soon after (b) Failure of endometrial hyperplasia to respond to hormonal therapy signi®cantly increases the risk of endometrial carcinoma (c) Endometrial hyperplasia can be adequately treated over a 3-month period with progestins (d) The presence of cellular atypia and reduced stromal volume in endometrial hyperplasia are suggestive of a greater malignant potential (e) High dose progestins may cause headaches and weight gain as a side eect
Chapter 6
18. In the normal treatment of endometrial cancer: (a) Gynaecological oncologists generally prefer radical hysterectomy (b) Bilateral oopherectomy is mandatory (c) Full surgical staging by lymphadenectomy may avoid the need for adjuvant radiotherapy
A6 Appendix
(d) Lymphadenectomy de®nitely improves survival (e) Naked eye assessment of myometrial invasion is useful
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Chapter 9 19. Which of the following statements are correct? (a) The incidence of nodal metastases with grade 1 or 2 tumours of the endometrium with limited or no myometrial involvement is less than 5% (b) With a poorly dierentiated grade 3 tumour invading the outer third of the myometrium, the risk of pelvic nodal metastasis is 12% (c) Stage 1A grade 3 endometrial carcinoma is considered low risk for nodal metastases (d) In terms of achieving long-term tumour control with radical salvage therapy, vaginal recurrences are more amenable to treatment than extravaginal pelvic involvement (e) All patients with endometrial tumour other than Stage 1A grade 1 should have pelvic brachytherapy as a minimum 20. Which of the following statements are correct? (a) The presence of extrapelvic intra-abdominal disease is an ominous prognostic sign (b) Five-year disease-free survival following radiotherapy in-patients with disease con®ned to pelvic lymph nodes and/or adnexae is 50% (c) In the presence of positive para-aortic nodes, extended ®eld radiotherapy results in long-term disease-free survival in 10% of patients (d) The risk of chronic severe toxicity associated with radiation following hysterectomy approaches 5% (e) The use of high-energy photons and multiple ®elds per day allows normal tissue sparing and reduction in radiation associated complications 21. Which of the following statements are correct (a) When using a combination of external beam and brachytherapy, the total radiation dose to the vaginal cu is 70±75 Gy (b) External beam radiotherapy is prescribed in weekly fractions of 1.8±2.0 Gy (c) The incidence of lymph node metastases depends on the grade of tumour and depth of invasion (d) Primary radiotherapy is associated with 10±20% lower survival rates than similar clinical stage patients who undergo surgery (e) Cervical stromal involvement by tumour may in¯uence the decision to treat with adjuvant external beam radiotherapy
Appendix A7
Chapter 8 22. Which of the following statements are correct?
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(a) Patients with endometriod tumours with squamous dierentiation have a poorer prognosis (b) Papillary serous and clear cell carcinomas make 1% of endometrial cancers (c) 50% of relapses occur in the papillary serous and clear cell subgroups (d) Clear cell and papillary subtypes tend to occur predominantly in younger obese or diabetic women (e) Clear cell carcinomas have an aggressive clinical behaviour
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23. Which of the following statements regarding clear cell endometrial tumours are correct?
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(a) In the majority of patients who relapse, the disease is in the pelvis (b) The most common extrapelvic sites for relapse are the brain and bones (c) With deep myometrial involvement, 5-year survival in patients with clear cell carcinoma is around 15% (d) Systemic therapy with progestagens improves survival in patients with clear cell carcinoma of the endometrium (e) Pathological stage and age are the two most important independent prognostic factors with clear cell carcinoma
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24. Which of the following statements are correct? (a) Psammoma bodies are associated with clear cell carcinoma of the endometrium (b) Depth of invasion is not a prognostic factor in papillary serous carcinoma (UPSC) of the endometrium (c) The overall 5-year survival for all stages of papillary endometrial carcinoma is approximately 60% (d) Uterine papillary serous carcinoma has comparable response rates to cisplatin based chemotherapy as ovarian serous papillary carcinoma that it resembles histopathologically (e) Clear cell carcinomas have a better prognosis than papillary serous tumours Chapter 9 25. Drugs with known single-agent activity against endometrial cancer include: (a) (b) (c) (d) (e)
Doxorubicin Docetaxel Carboplatin Etoposide Paclitaxel
A8 Appendix
26. In regard to the combination of paclitaxel (175 mg/m2 over 3 hours) and cisplatin in the treatment of endometrial carcinoma, which of the following are true?
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(a) Response rates of up to 67% have been reported (b) The rate of severe (grade 3 or 4) neurotoxicity is less than 1% when the paclitaxel is delivered over 3 hours (c) Has a proven survival bene®t in-patients with advanced or recurrent disease (d) The substitution of carboplatin for cisplatin results in more haematological toxicity and more nephrotoxicity (e) Giving cisplatin 24 hours after paclitaxel delivery is a strategy used to reduce neurological complications
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27. The addition of cisplatin to doxorubicin in patients with advanced disease:
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28. Which of the following are true statements regarding oestrogen receptor (ER) function:
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(a) The binding of ER and estrogens occurs initially in the cytoplasm (b) The oestrogen receptor is a member of the superfamily of nuclear receptors (c) Binds to DNA at the hormone responsive element by means of the zinc moieties in the C domain (d) Binding of oestrogen to ER causes downregulation of the progesterone receptor (e) ER levels can be evaluated by the dextran-coated charcoal assay in tissue homogenates or by immunohistochemistry using monoclonal antibodies in tissue sections
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(a) (b) (c) (d)
Increases the overall response rate from 27% to 45% Prolongs overall survival Increases the risk of cardiotoxicity of doxorubicin Combination of doxorubicin with paclitaxel oers a signi®cant survival advantage over the doxorubicin and cisplatin combination (e) There is clear evidence that cytotoxic chemotherapy oers survival advantage over hormonal agents such as megestrol acetate and tamoxifen Chapter 10
29. Which of the following are true regarding tamoxifen: (a) Has estrogen agonist activity in the endometrium (b) Can cause upregulation of the progesterone receptor (c) Causes an increased risk of endometrial hyperplasia and endometrial cancer (d) Produces its eect by binding to the estrogen receptor (e) Postmenopausal patients given tamoxifen have increased levels of HDL-Cholesterol
Appendix A9
30. Which of the following statements are correct? (a) A patient with a papillary serous adenocarcinoma has an omental recurrence after initial hysterectomy and bilateral salpingooophorectomy. The most reasonable treatment would be Tamoxifen 20 mg daily every other week and daily medroxyprogesterone acetate (b) The action of GnRH analogues in advanced endometrial cancer is thought to be only through suppression of pituitary gonadotrophins and the resulting fall in sex steroids (c) Tamoxifen and its derivatives have serum half-lives of 7±14 days (d) Young women with grade 1 endometrial carcinoma are unsuitable for treatment with progestins (e) The risk of disease progression during or after progestin therapy for grade 1 endometrial carcinoma in young women wishing to preserve fertility is around 12±15%
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A10 Appendix
Palliative Care in Obstetrics and Gynaecology: (Vol. 15, No. 2) Self-Assessment Multiple Choice Answers
Chapter 1 1. (a) False; (b) True; (c) True; (d) True; (e) True The context of dying for women involves social and economic issues that may interfere with the care of women at the end of life, thus a woman may decline more eective but also more expensive treatment so as not to place a ®nancial burden on her families. The poverty and low socio-economic status of women worldwide can also place them at a disadvantage by simply not having the money to gain access to palliative care at the end of life. 2. (a) True; (b) False; (c) False; (d) False; (e) False 90% of all cancer patients and 75% of terminally ill cancer patients ®nd relief with simple non-invasive methods. Women, the elderly and minorities are the groups most likely to be undertreated. The most common side-eect of chronic opioid therapy is constipation. In gynaecological cancer patients, somatic, visceral and nociceptive types of pain are encountered. Chapter 2 3. (a) True; (b) False; (c) False; (d) True; (e) True Somatic pain is well localised. It is visceral pain that is poorly localised and is associated with autonomic symptoms. COX 2 inhibitors interfere less with gastric bicarbonate secretion and mucus production and hence are safer with respect to gastrointestinal injury. The rectal route of analgesia administration is contraindicated in neutropenic patients due to the risk of bacteraemia. One stereoisomer of Tramadol blocks reuptake of serotonin while the other stereoisomer blocks reuptake of norepinephrine. 4. (a) True; (b) False; (c) True; (d) False; (e) False When a patient develops intolerable side-eects from one opioid, it may be useful to switch to an alternative opioid as cross tolerance among opioids is not always complete. Controlled-release forms of morphine and oxycodone should not be crushed as
Appendix A11
they become immediately bioavailable. Sedation is a frequent problem at the initiation of treatment or following a steep dose increase but usually resolves in a few days. One strategy to reduce sedation is to increase the frequency of dosing while reducing the actual dosage. Addiction is not a problem in the cancer patient although tolerance (the need for higher doses to achieve the same eect) may rarely be an issue, often heralding disease progression. Physical dependence refers to the development of withdrawal syndrome upon discontinuation or following marked dose reduction after a patient has been on repeated doses for a length of time. Tolerance and physical dependence do not however represent addiction, which is an aberrant behaviour, characterized by compulsive drug use or continued drug use despite harm to the individual. Opiod mode of action is not only via speci®c opioid receptors in the brain. 5. (a) False; (b) True; (c) False; (d) False; (e) True Adjuvant analgesics represent a diverse group of drugs originally indicated for uses other than for pain relief or to enhance the action of the primary analgesic. They may be used at any step of the WHO analgesia ladder. Anticonvulsants are used in the management of neuropathic pain particularly for those with paroxysmal or lancinating pain. The analgesic eect of TCAs is independent of their mood-elevating eects and pain relief occurs 1±2 weeks after initiation of treatment. Octreotide is successfully used in the management of nausea and vomiting secondary to bowel obstruction, radiation and chemotherapy induced diarrhoea amongst other indications. Calcitonin and bisphosphonates through inhibiting osteoclast induced bone resorption are useful in the management of metastatic bone pain. Chapter 3 6. (a) True; (b) False; (c) True; (d) False; (e) True Because of its bioavailability, low cost, multiple formulations and ecacy, morphine is most frequently utilized for control of cancer pain. Drugs such as meperidine which have active metabolites should be avoided to decrease side-eects. Mixed agonist/ antagonist opioids have a ceiling eect and should not be used for women with cancer pain. Long-acting oral opioids are preferable for patient convenience. 7. (a) True; (b) True; (c) False; (d) True; (e) True Common side-eects of opioid therapy include constipation, nausea and sedation. Constipation occurs in essentially all patients who are receiving opioids and should be anticipated and prevented. Most patients become tolerant to opioid-related nausea and sedation over a period of several days to weeks. A major advantage of the newer COX 2 inhibitor NSAIDS is the rarity of gastrointestinal side-eects. Patients who are taking large doses of opioids may have respiratory depression following procedures, which rapidly control their pain. In such cases, Naloxone may be utilized but it should be kept in mind that the half-life is 30±45 minutes, much shorter than an opioid, and hence repeated doses may be required.
A12 Appendix
Chapter 4 8. (a) False; (b) True; (c) False; (d) False; (e) True Bulk-forming laxatives can produce or exacerbate the problem of constipation and should be generally avoided. Rectal examination is mandatory and helps to avoid the fruitless use of suppositories when the rectum is empty. 5HT receptor antagonists actually cause constipation both when used in chemotherapy and palliative care. Oral opioids are one of the most useful drugs in care of women with cancer pain; the solution is to use them in appropriate dosage but with pre-emptive use of laxatives. Many patients with advanced gynaecological cancer have a form of dysmotility which appears to be due to subtle eects of retroperitoneal disease rather than tumour compressing the bowel.
9. (a) True; (b) False; (c) True; (d) False; (e) False A gastrogran enema is prudent to exclude concommitant large bowel obstruction in patients with small bowel obstruction prior to surgery. Gastrogran is preferred to barium as it is less likely to cause problems if bowel resection is required. Steroids are not contraindicated and a short trial of steroids is usually indicated unless there is a condition that requires immediate surgical intervention. Care should be taken in patients with diabetes, active peptic ulceration, TB and major psychological disturbance. Hyoscine butyl bromide is a very useful drug in conservative management of bowel obstruction in women with advanced cancer acting directly on the bowel and hence avoiding the central sedation eects. Some studies have shown an advantage with octreotide but the high cost often outweighs any gain. Metoclopramide and other gastrokinetic antinauseants are contraindicated in women with high intestinal obstruction as they increase nausea and vomiting.
10. (a) True; (b) True; (c) True; (d) False; (e) False Xerostomia or dry mouth may be the result from reduced production of saliva, excessive evaporation from the oral cavity or treatments such as radiotherapy. Drugs such as tricyclic antidepressants, antiparkinsonian drugs, antispasmodics and neuroleptics may also be responsible. Treatments should involve rationalizing medication, frequent small drinks with added orange or lemon juice to stimulate salivation, use of arti®cial saliva or glycerine mouthwashes or pilocarpine drops. Altered taste is a poorly understood problem in advanced cancer patients and various approaches have been tried such as avoidance of food with high urea content by eating white meats, eggs, dairy products, and use of stronger seasonings with food. Dental caries should be excluded as a correctable cause. Simple starvation involves mobilization of fat but sparing of skeletal muscle whereas cachexia involves equal mobilisation of both. Progestational agents and corticosteroids both have been shown to improve appetite.
Appendix A13
11. (a) True; (b) False; (c) True; (d) True; (e) False Drugs such as NSAIDs, mucolytics and antibiotics are emetogenic. The vomiting centre is situated in the medulla oblongata and is the ®nal mediator of nausea and vomiting though various re¯ex pathways may lead to these symptoms. Chemotherapeutic agents, ketosis, uraemia and hypercalcaemia act via the chemoreceptor trigger zone. Ondansetron and other 5HT receptor blockers may precipitate constipation and faecal impacion. In women with advanced cancer presenting with diarrhoea, it is imperative to exclude faecal impaction with over¯ow. 12. (a) True; (b) True; (c) False; (d) False; (e) True Somatostatin reduces enteral secretions and thus may be of symptomatic relief in cases of enterocutaneous ®stulae where surgical diversion (the preferred option) is not feasible. Clear cell and small cell ovarian carcinomas are commonly associated with hypercalcaemia. Subcutaneous calcitonin may be of bene®t in resistant cases of hypercalcaemia. The distressing foul smell from anaerobic organisms may be partially alleviated by metronidazole orally or topically. Chapter 5 13. (a) True; (b) False; (c) True; (d) True; (e) False The initiation of palliative care for a patient implies incurable disease and a limited life expectancy and in its most speci®c sense refers to lessening or alleviation of suering. The basic radiobiology principles underlying radiotherapy are that normal tissues in general have a better capacity to repair sublethal injury than tumours. The therapeutic ratio can be ampli®ed by delivering the radiation over a protracted, fractionated course with sparing of late reacting normal tissues, but this may be at the expense of potential tumour repopulation and patient logistical diculties. Typically external beam radiation is delivered using 1.8±2.0 Gy daily fractions over several weeks with total dosage used in gynaecological malignancies being around 30±40 Gy. Brachytherapy oers the advantage of a high local dose to the tumour with a reduction to surrounding normal structures. 14. (a) False; (b) True; (c) False; (d) True; (e) True High dose of radiation per fraction increases the risk of late complications but is an ecient and convenient way of treatment for the patient and is particularly suitable for palliative treatment, with very high doses being appropriate in cases of advanced pelvic malignancy for symptom control (pain, bleeding), especially where life expectancy is under 12 months. 2±8 % of patients with cervical and endometrial carcinoma and 4% of patients with ovarian carcinoma develop bone metastases and the vertebral column and, in particular, the lumbar spine being the most common site. Radiotherapy achieves relief from pain of bony metastases in 80±90% of cases, with complete resolution in 50% and persistent relief during the following year in 55±65% of patients.
A14 Appendix
15. (a) False; (b) False; (c) True; (d) True; (e) False Lytic lesions in weight-bearing bones with 450% cortical destruction or a lesion 42.5cm in size are typically at high risk of a pathological fracture and should undergo orthopaedic evaluation for prophylactic ®xation, and after ®xation should have radiotherapy. Spinal MRI is the imaging modality of choice in the investigation of spinal cord compression. High dose IV steroids are part of the ®rst-line management of spinal cord compression, along with neurosurgical and radiation oncology reviews. Pamidronate is eective both in providing relief in patients with osteolytic metastases and treating hypercalcaemia. Systemic radionuclide treatment should certainly be considered after radiotherapy where there are multiple sites of painful bone metastases. 16. (a) True; (b) False; (c) True; (d) False; (e) True Brain metastases from gynaecological malignancies are rare with the exception of choriocarcinoma. The imaging modality of choice is MRI with gadolinium. The general management of a patient with brain metastases includes corticosteroids, which provide symptomatic improvement through reduction of peritumour oedema. Palliative radiotherapy provides response rates of 69±90%. Without treatment patients with brain metastases have a median survival of 1 month, increasing to 2 months with steroids alone and 3-6 months with palliative radiotherapy, with 1- and 2-year survival rates of 15% and 5±10% respectively. Chapter 6 17. (a) True; (b) False; (c) False; (d) False; (e) True One of the areas where interventional radiology can contribute greatly to the gynaecological oncology patient is the placement of central venous access devices and also radiologically guided percutaneous procedures. Patients with a contraindication to anticoagulation, patients with a complication of anticoagulation or debilitated patients with a large clot burden are best served with an IVC ®lter. Prior to placement of IVC ®lters it is essential to identify the con¯uence of the iliac veins, the in¯ow of the renal veins and any accessory renal veins, the diameter of the IVC and the presence if any of clot in the IVC. The IVC ®lters are placed infra-renaly, with a success of placement in 98% of cases and reported clot-trapping ability of 98%. 18. (a) False; (b) True; (c) True; (d) False; (e) False Percutaneous nephrostomies are not appropriate in all cancer patients. Speci®c criteria by Fallon et al. may help the clinician to which patients will bene®t from nephrostomy catheter placement. These criteria include patients with undiagnosed malignant disease, prostatic and cervical primary tumours, patients in whom there is a treatment modality and a reasonable chance of response, patients with localized disease and patients who request prolongation of life for legal or ®nancial reasons. In cases of
Appendix A15
vesicovaginal ®stulae where nephrostomies fail to completely divert the urine (required for healing), and where prognosis is not favourable, a dry perineum can be achieved by ureteric coil embolization. Polyvinyl alcohol particles are used for uterine artery embolization for ®broids. Although after diagnostic arteriograms, patients are discharged the same day, an overnight hospital stay is required for therapeutic procedures. Transcatheter embolization has been used to control haemorrhage such as post partum, cases where pelvic malignancies have eroded into adjacent vascular structures. It is also used to control perfusion to visceral structures or tumour masses that arise from them.
Chapter 7 19. (a) False; (b) False; (c) True; (d) False; (e) False Ovarian carcinomas are associated with pulmonary metastases in 4±7% of cases while uterine and cervical carcinomas are associated with pulmonary metastases in 1% of cases. Although as little as 175 ml of ¯uid may produce blunting of the costophrenic angle, as much as 500 ml of ¯uid may be present without blunting of the costophrenic angle. Pleural ¯uid cytology may be positive in 40±87% of malignant pleural eusions. The risk of pneumothorax at thoracocentesis varies between 4 and 30% of cases but the need for a chest drain depends on the size of the pneumothorax, and the cardiovascular health of the patient, so initial management involves supplementary oxygen, observation and serial radiographs. Meig's syndrome is a benign pleural eusion, which in addition to ovarian ®bromas may also be associated with Brenner's tumour, granulosa-theca cell tumours, cystadenoma, germ cell tumour, ovarian adenocarcinoma, fallopian tube carcinoma etc.
20. (a) False; (b) True; (c) False; (d) True; (e) False Chemical pleurodesis is reserved for patients not suitable for or who have failed chemotherapy and are symptomatic of dyspnoea- the principal symptom for which pleurodesis is eective. Talc is the agent of choice with overall success rate of 91%. The complications of pleurodesis include empyema, fever, arrhythmias, pneumonitis and respiratory failure. Pleurodesis is unlikely to be successful if there is mediastinal shift towards the eusion indicating an endobronchial obstructive lesion or trapped lung.
21. (a) False; (b) True; (c) False; (d) True; (e) True Pulmonary metastases are the result of haematogenous spread via the pulmonary arteries or less commonly via the bronchial arteries. Pulmonary nodules tend to be localized to the basal portions of the lungs. High-resolution CT scanning can frequently miss nodules 3 mm in diameter. Transthoracic needle biopsy is the preferred method of diagnosis of the solitary pulmonary nodule with a reported sensitivity in the diagnosis of malignant disease of 70±100%.
A16 Appendix
22. (a) False; (b) False; (c) True; (d) True; (e) False Dyspnoea is a subjective sensation of breathlessness that may originate not only from central chemoreceptors but also from diaphragmatic or intercostal receptors, intrapulmonary receptors, commands from the respiratory control centre or higher cortical centres. Opiates are the treatment of choice for dyspnoea with central and peripheral actions and no respiratory depression occurring at therapeutic doses. Lymphangitic spread of tumour commonly causes disproportionate dyspnoea, with activation of intrapulmonary receptors. Pulmonary metastases are common (25±50%) in choriocarcinoma and are often extensive with more than 10 lesions on a chest radiograph noted in over 40% of patients and a pleural eusion in 48%. Venous thromboembolism occurs in approximately 11% of cancer patients and is even more common in patients with gynaecological cancer. Chapter 8 23. (a) True; (b) False; (c) False; (d) True; (e) True Factors associated with the development of painful decubitus ulcers include emaciation and muscle wasting of chronic and terminal diseases, the decreased skin circulation from both depressed cardiac function and directly diminished skin perfusion with hypovolaemia and often the distention and oedema of the skin itself along with hypoprotinaemia, all contributes to decubitus ulceration. Prevention of pressure sores is the ®rst defence with changing positions every 2±4 hours. Lambskin boots and foam rings protect the heels and elbows. Special air mattresses help to reduce the pain and suering from skin pressure and sores. The early use of antifungal mouth `swish and swallow' may prevent cracking and pain. Occasionally hydrogen peroxide/saline combinations can be helpful in maintaining oral hygiene. Chapter 9 24. (a) False; (b) False; (c) True; (d) False; (e) False Euthanasia is illegal worldwide although it is practiced in around a dozen countries. The de®nition of euthanasia is the intentional termination of life of a patient at his/her request by a physician so question (b) does not ful®l the criteria for euthanasia. A noti®cation procedure in force in the Netherlands since the end of 1990 obliges the physician responsible for euthanasia to notify the coroner as a case of unnatural death. Of the 9700 requests for euthanasia in 1995, 6000 were not granted. The most important reasons stated by patients requesting euthanasia were loss of dignity (57%), pain (46%), dependence on others (33%) and tiredness of life (23%). 25. (a) False; (b) False; (c) False; (d) True; (e) False Although the patient's relatives are always involved in the discussion about a request for euthanasia, if the family members are not in agreement with the request, the autonomy of the patient will be considered the most important. The combination of
Appendix A17
barbiturate and muscle relaxants are the preferred options while opiates are not the preferred option due to tolerance to these agents. Intravenous euthanaticum will take no more than 30 minutes while taken orally it may take a few hours. Where health care is not adequately covered by national or private insurance, introducing euthanasia may not be appropriate as ®nancial reasons may result in family pressure on the patient decision to request euthanasia.
Chapter 10 26. (a) False; (b) True; (c) True; (d) True; (e) False Death is de®ned as irreversible cessation of the function of the entire brain including the brainstem. In brain death the electroencephalogram is always isoelectric. Permanent vegetative state (PVS) on the other hand involves cessation of the function of cerebral hemispheres but retention of some brainstem function and therefore unlike brain death, survival may be possible without or with limited somatic support. In a brain dead pregnant woman, the fetus has ethical and medical standing but is not legally granted the rights of a person.
27. (a) True; (b) True; (c) False; (d) True; (e) False Respiratory support needs to take into consideration the hyperventilation of pregnancy destined to maintain a mild hypocarbia to aid fetal clearance of carbon dioxide. Hypotension develops in brain dead patients, which along with the loss of central circulatory autoregulation and the need for volumic adjustment due to diabetes insipidus further complicates blood pressure management. High doses of dopamine to support renal function and blood pressure through their peripheral vasoconstrictive action lead to dramatic reduction in placental perfusion. Panhypopituitarism occurs leading to multiendocrine failure with the need for ¯uid replacement, vasopressin, corticosteroids and thyroxine. Maternal thermoregulation is also lost with risks of both hyperthermia and hypothermia and given the primordial role of maintaining a temperature of 378 for fetal wellbeing, poses a further challenge.
28. (a) False; (b) True; (c) False; (d) True; (e) False Enteric nutrition through nasogastric feeding or percutaneous gastrostomy is often thwarted by poor motility of the gastrointestinal tract re¯ected by re¯ux regurgitation. Total parental nutrition through a subclavian line is required to maintain fetal caloric supply and normal growth but has the risks of maternal sepsis, thrombosis and sustained hyperglycaemia requiring prophylactic anticoagulation and insulin infusion. There is no lower limit of gestation speci®ed at which to oer life support given that with advancing medical progress longer periods of life support in a brain dead person can be maintained with a case of up to 15 weeks reported in the literature. Cancer in pregnancy occurs at a rate of 1 in 1000 and palliative care cannot be denied to the patient on the grounds of pregnancy despite the increased risks this carries for the fetus.
A18 Appendix
29. (a) True; (b) True; (c) False; (d) True; (e) True If life is being supported in a brain dead patient, betamimetics, corticosteroids, Anti D and vasopressin all have a role in improving the outcome of the pregnancy either by maintaining maternal homeostasis (e), promoting fetal maturity (b) and preventing preterm delivery (a) Anti D may be required to prevent isoimmunization (d) if there are sensitizing events that might aect that pregnancy. Dopamine at the stated dose however is likely to very markedly impair placental perfusion and have a deleterious eect on the pregnancy. 30. (a) False; (b) True; (c) True; (d) True; (e) True The cause of brain death is not directly relevant to the question of continuation of the pregnancy while factors b, c, d, e are all highly relevant. Chapter 11 31. (a) False; (b) True; (c) False; (d) True; (e) False The temptation to try further anticancer treatment if symptom relief is achieved in complex situations, with apparent improvement in the patient's condition, may on occasions lead to a little prolongation in life but at the expense of even more dicult symptoms to control which would invariably lead to a poorer quality of life, hence great wisdom is needed to balance symptom control with active management. When death is very close, there may be a convergence of organ failure as well as psychological signs such as withdrawal into ones self, and hence the diagnosis of the dying phase is crucial and needs to be recognized by all concerned in care including the patient and her family. There should be no need for intravenous ¯uids or food although mouth care is essential. The only drugs that should be continued are those for symptomatic relief and these may well include drugs such as diuretics to keep heart failure symptoms at bay. In the situation of an end of life crisis such as a massive bleed or massive pulmonary embolism rendering the patient unaware by the use of drugs such midazolam, diazepam or phenobarbital does not equate with euthanasia.
doi:10.1053/beog.2001.0191, available online at http://www.idealibrary.com on
APPENDIX Endometrial Cancer: Self-Assessment Multiple Choice Questions
For each part of each question, answer true or false by ticking in the appropriate box. The answers will be published in the next issue. Chapter 1 1. Mortality rates for cancer of the corpus uteri in the United States are higher for blacks than they are for whites. This is likely to be due to the fact that:
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(a) Endometrial cancer is more common in US blacks than in US whites (b) The disease is detected later in the US blacks and therefore their prognosis is not as good as for US whites (c) US blacks have poorer access to good quality medical care than US whites (d) US blacks tend to smoke more than US whites (e) Baseline hysterectomy rates are lower than for white women so more Black women are at risk
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2. A number of authors in the 1980s were of the opinion that the association observed between endometrial cancer and oestrogen therapy was not real, and was primarily due to `detection bias'. This was based on the following observations:
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(a) Women on hormone therapy are more likely to have endometrial cancer detected (b) The increase in incidence seen in the 1970s was not mirrored by an increase in mortality (c) There was a worse survival of endometrial cancer patients who had been on oestrogen therapy (d) A large number of undetected endometrial tumours were found at autopsy (e) The increase in risk associated with oestrogen therapy persists for several years after cessation of use
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1521±6934/01/03000A118 $35.00/00
c 2001 Harcourt Publishers Ltd. *
A2 Appendix
3. Smoking is thought to possibly modify the eects of obesity and oestrogen therapy on endometrial cancer. Direct evidence to support this is that:
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(a) Smoking reduces the risk of endometrial cancer (b) The protective eect of smoking is greater among oestrogen users and obese women (c) The risk associated with being overweight is not as large in smokers as it is in non-smokers (d) Smoking increases the risk of hip fractures in post-menopausal women (e) Women who smoke tend to be leaner than women who do not smoke
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4. When ®rst counselling a woman at 50% risk of HNPCC with a family history ful®lling Amsterdam Criteria, but no known family mutation:
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(a) The lifetime risk of bowel cancer is 60% (b) The lifetime risk of endometrial cancer is up to 30% (c) Screening of endometrium by transvaginal ultrasound and hysteroscopy is recommended (d) Blood should be drawn for genetic testing (e) Colorectal tumours in patients with HNPCC arise in pre-existing adenomatous polyps, which are generally present in large numbers (i.e. excess of 100)
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5. The following statements about HNPCC are true: (a) Prognosis of cancer is better in age- and staged- matched controls than in HNPCC (b) Caecal tumours are more common than in the general population (c) Lung cancer is a common feature of HNPCC (d) Transitional cell carcinoma of the ureter is a diagnostic criteria tumours (e) HNPCC is an autosomal recessive condition 6. Which of the following statements are correct? (a) HNPCC results from a germline mutation in DNA mismatch repair genes (b) Microsatelite instability is a result of failure of DNA mismatch repair genes to detect and correct errors in the genetic code during DNA replication (c) Current recommendations are that known carriers of DNA mismatch genes should undergo colonoscopy every 6±12 months (d) Subtotal colectomy performed prophylactically obviates the need for further gastrointestinal surveillance
Appendix A3
(e) Dietary manipulation using NSAIDs and resistant starch may in the future have a role in the prevention of the formation of adenomas within the colon
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7. A postmenopausal breast cancer patient, 3 years on tamoxifen, presents with vaginal bleeding. Which of the following approaches is evidence based?
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(a) A Pipelle endometrial biopsy (b) A dilatation and curettage in any such patient with a thickened (45 mm) endometrial layer in transvaginal ultrasonography (c) A saline infusion sonography with selective endometrial biopsy in case of asymmetrical endometrial thickening (d) A hysteroscopy with guided endometrial biopsy (e) A course of 14 days of medroxyprogesterone acetate
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8. A 53-year-old healthy asymptomatic postmenopausal woman has lost her sister and mother of breast cancer and is given tamoxifen for 5 years. The gynaecological check up should ideally include:
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(a) A pre-treatment assessment of the uterine cavity with transvaginal ultrasonography and saline infusion sonography or hysteroscopy in case of a thick endometrial layer (45 mm) (b) A yearly vaginal examination with a cervical PAP smear (c) In case of a normal pre-treatment uterine cavity, a yearly transvaginal ultrasonography with hysteroscopy or saline infusion sonography in case of endometrial thickening (45 mm). (d) A ®rst uterine assessment after 3 years of being on tamoxifen in case the patient has a normal pre-treatment uterine cavity. (e) No gynaecological examination at all unless the patient reports vaginal bleeding
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(a) Tamoxifen induces the endometrial progesterone receptor (b) Tamoxifen induces aggressive and high-grade endometrial cancers (c) Tamoxifen is contra-indicated following hysterectomy for earlystage endometrial cancer (d) After 3 years of being on raloxifene, a patient is more likely to develop endometrial polyps and endometrial cancer compared with the patient on placebo (e) Raloxifen should now replace tamoxifen as an adjuvant therapy following treatment of an oestrogen receptor positive breast cancer because it has no endometrial side-eects
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Chapter 3
A4 Appendix
Chapter 4 10. The following statements about endometrial carcinoma are true: (a) The median age of patients at diagnosis is 63 years (b) Women with complex endometrial hyperplasia without atypical cytological features are at low risk of uterine cancer (c) It is more likely to occur in women who undergo early menopause (d) Is more likely to be the cause of postmenopausal bleeding in an 80year-old than in a woman aged 60 years (e) Para-aortic lymph node involvement indicates stage IIIB disease 11. Outpatient hysteroscopy: (a) (b) (c) (d)
Can be performed successfully in more than 90% of women Usually requires the use of a paracervical block Reliably distinguishes carcinoma from hyperplasia Has a lower sensitivity for endometrial pathology than dilation and curettage (e) Is associated with less patient discomfort when carbon dioxide rather than saline is used to distend the uterus 12. Endometrial thickness measured by transvaginal ultrasound scan: (a) (b) (c) (d) (e)
Is measured from the midline echo of the endometrial cavity to the nearest point of the myometrium Has a lower sensitivity for the detection of endometrial cancer in women taking hormone replacement therapy When less than 5 mm, the probability of endometrial cancer being present is less than 1% Normally decreases with age Is increased in women taking tamoxifen
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Chapter 5 13. The likelihood of response of endometrial hyperplasia to progestins is aected by: (a) (b) (c) (d) (e)
The progesterone receptor status of the tumour The oestrogen receptor status of the tumour The type of progestin used The presence of nuclear atypia The age of the patient
14. Which of the following statements are true? (a) There is no risk of progression of simple endometrial hyperplasia to invasive carcinoma. (b) The risk of progression of complex hyperplasia to invasive carcinoma is 3%
Appendix A5
(c) Simple atypical hyperplasia has a lower malignant potential than complex hyperplasia (d) The risk of progression of complex atypical hyperplasia to endometrial carcinoma is 29% (e) Complex atypical hyperplasia implies both cytological and architectural atypia
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(a) In Europe, endometrial cancer is the most common gynaecological cancer (b) Endometrial cancer could be largely prevented by screening (c) Endometrial cancer often presents at an advanced stage (d) Endometrial cancer overall has an average 5-year survival compared with other cancers (e) Endometrial cancer usually metastases initially to the pelvic lymph nodes
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17. Which of the following are regarded as high-risk endometrial tumours?
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(a) Endometrial carcinoma stage 1B G2 (b) Endometrial carcinoma stage 1B G3 and lymphovascular space involvement (c) Papillary serous adenocarcinoma (d) Clear cell adenocarcinoma (e) Squamous carcinoma
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15. Which of the following statements are correct? (a) At least one-third of women with complex atypical hyperplasia may have adenocarcinoma present in the uterus if hysterectomy is performed soon after (b) Failure of endometrial hyperplasia to respond to hormonal therapy signi®cantly increases the risk of endometrial carcinoma (c) Endometrial hyperplasia can be adequately treated over a 3-month period with progestins (d) The presence of cellular atypia and reduced stromal volume in endometrial hyperplasia are suggestive of a greater malignant potential (e) High dose progestins may cause headaches and weight gain as a side eect
Chapter 6
18. In the normal treatment of endometrial cancer: (a) Gynaecological oncologists generally prefer radical hysterectomy (b) Bilateral oopherectomy is mandatory (c) Full surgical staging by lymphadenectomy may avoid the need for adjuvant radiotherapy
A6 Appendix
(d) Lymphadenectomy de®nitely improves survival (e) Naked eye assessment of myometrial invasion is useful
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Chapter 9 19. Which of the following statements are correct? (a) The incidence of nodal metastases with grade 1 or 2 tumours of the endometrium with limited or no myometrial involvement is less than 5% (b) With a poorly dierentiated grade 3 tumour invading the outer third of the myometrium, the risk of pelvic nodal metastasis is 12% (c) Stage 1A grade 3 endometrial carcinoma is considered low risk for nodal metastases (d) In terms of achieving long-term tumour control with radical salvage therapy, vaginal recurrences are more amenable to treatment than extravaginal pelvic involvement (e) All patients with endometrial tumour other than Stage 1A grade 1 should have pelvic brachytherapy as a minimum 20. Which of the following statements are correct? (a) The presence of extrapelvic intra-abdominal disease is an ominous prognostic sign (b) Five-year disease-free survival following radiotherapy in-patients with disease con®ned to pelvic lymph nodes and/or adnexae is 50% (c) In the presence of positive para-aortic nodes, extended ®eld radiotherapy results in long-term disease-free survival in 10% of patients (d) The risk of chronic severe toxicity associated with radiation following hysterectomy approaches 5% (e) The use of high-energy photons and multiple ®elds per day allows normal tissue sparing and reduction in radiation associated complications 21. Which of the following statements are correct (a) When using a combination of external beam and brachytherapy, the total radiation dose to the vaginal cu is 70±75 Gy (b) External beam radiotherapy is prescribed in weekly fractions of 1.8±2.0 Gy (c) The incidence of lymph node metastases depends on the grade of tumour and depth of invasion (d) Primary radiotherapy is associated with 10±20% lower survival rates than similar clinical stage patients who undergo surgery (e) Cervical stromal involvement by tumour may in¯uence the decision to treat with adjuvant external beam radiotherapy
Appendix A7
Chapter 8 22. Which of the following statements are correct?
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(a) Patients with endometriod tumours with squamous dierentiation have a poorer prognosis (b) Papillary serous and clear cell carcinomas make 1% of endometrial cancers (c) 50% of relapses occur in the papillary serous and clear cell subgroups (d) Clear cell and papillary subtypes tend to occur predominantly in younger obese or diabetic women (e) Clear cell carcinomas have an aggressive clinical behaviour
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23. Which of the following statements regarding clear cell endometrial tumours are correct?
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(a) In the majority of patients who relapse, the disease is in the pelvis (b) The most common extrapelvic sites for relapse are the brain and bones (c) With deep myometrial involvement, 5-year survival in patients with clear cell carcinoma is around 15% (d) Systemic therapy with progestagens improves survival in patients with clear cell carcinoma of the endometrium (e) Pathological stage and age are the two most important independent prognostic factors with clear cell carcinoma
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24. Which of the following statements are correct? (a) Psammoma bodies are associated with clear cell carcinoma of the endometrium (b) Depth of invasion is not a prognostic factor in papillary serous carcinoma (UPSC) of the endometrium (c) The overall 5-year survival for all stages of papillary endometrial carcinoma is approximately 60% (d) Uterine papillary serous carcinoma has comparable response rates to cisplatin based chemotherapy as ovarian serous papillary carcinoma that it resembles histopathologically (e) Clear cell carcinomas have a better prognosis than papillary serous tumours Chapter 9 25. Drugs with known single-agent activity against endometrial cancer include: (a) (b) (c) (d) (e)
Doxorubicin Docetaxel Carboplatin Etoposide Paclitaxel
A8 Appendix
26. In regard to the combination of paclitaxel (175 mg/m2 over 3 hours) and cisplatin in the treatment of endometrial carcinoma, which of the following are true?
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(a) Response rates of up to 67% have been reported (b) The rate of severe (grade 3 or 4) neurotoxicity is less than 1% when the paclitaxel is delivered over 3 hours (c) Has a proven survival bene®t in-patients with advanced or recurrent disease (d) The substitution of carboplatin for cisplatin results in more haematological toxicity and more nephrotoxicity (e) Giving cisplatin 24 hours after paclitaxel delivery is a strategy used to reduce neurological complications
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27. The addition of cisplatin to doxorubicin in patients with advanced disease:
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(a) The binding of ER and estrogens occurs initially in the cytoplasm (b) The oestrogen receptor is a member of the superfamily of nuclear receptors (c) Binds to DNA at the hormone responsive element by means of the zinc moieties in the C domain (d) Binding of oestrogen to ER causes downregulation of the progesterone receptor (e) ER levels can be evaluated by the dextran-coated charcoal assay in tissue homogenates or by immunohistochemistry using monoclonal antibodies in tissue sections
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(a) (b) (c) (d)
Increases the overall response rate from 27% to 45% Prolongs overall survival Increases the risk of cardiotoxicity of doxorubicin Combination of doxorubicin with paclitaxel oers a signi®cant survival advantage over the doxorubicin and cisplatin combination (e) There is clear evidence that cytotoxic chemotherapy oers survival advantage over hormonal agents such as megestrol acetate and tamoxifen Chapter 10
29. Which of the following are true regarding tamoxifen: (a) Has estrogen agonist activity in the endometrium (b) Can cause upregulation of the progesterone receptor (c) Causes an increased risk of endometrial hyperplasia and endometrial cancer (d) Produces its eect by binding to the estrogen receptor (e) Postmenopausal patients given tamoxifen have increased levels of HDL-Cholesterol
Appendix A9
30. Which of the following statements are correct? (a) A patient with a papillary serous adenocarcinoma has an omental recurrence after initial hysterectomy and bilateral salpingooophorectomy. The most reasonable treatment would be Tamoxifen 20 mg daily every other week and daily medroxyprogesterone acetate (b) The action of GnRH analogues in advanced endometrial cancer is thought to be only through suppression of pituitary gonadotrophins and the resulting fall in sex steroids (c) Tamoxifen and its derivatives have serum half-lives of 7±14 days (d) Young women with grade 1 endometrial carcinoma are unsuitable for treatment with progestins (e) The risk of disease progression during or after progestin therapy for grade 1 endometrial carcinoma in young women wishing to preserve fertility is around 12±15%
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A10 Appendix
Palliative Care in Obstetrics and Gynaecology: (Vol. 15, No. 2) Self-Assessment Multiple Choice Answers
Chapter 1 1. (a) False; (b) True; (c) True; (d) True; (e) True The context of dying for women involves social and economic issues that may interfere with the care of women at the end of life, thus a woman may decline more eective but also more expensive treatment so as not to place a ®nancial burden on her families. The poverty and low socio-economic status of women worldwide can also place them at a disadvantage by simply not having the money to gain access to palliative care at the end of life. 2. (a) True; (b) False; (c) False; (d) False; (e) False 90% of all cancer patients and 75% of terminally ill cancer patients ®nd relief with simple non-invasive methods. Women, the elderly and minorities are the groups most likely to be undertreated. The most common side-eect of chronic opioid therapy is constipation. In gynaecological cancer patients, somatic, visceral and nociceptive types of pain are encountered. Chapter 2 3. (a) True; (b) False; (c) False; (d) True; (e) True Somatic pain is well localised. It is visceral pain that is poorly localised and is associated with autonomic symptoms. COX 2 inhibitors interfere less with gastric bicarbonate secretion and mucus production and hence are safer with respect to gastrointestinal injury. The rectal route of analgesia administration is contraindicated in neutropenic patients due to the risk of bacteraemia. One stereoisomer of Tramadol blocks reuptake of serotonin while the other stereoisomer blocks reuptake of norepinephrine. 4. (a) True; (b) False; (c) True; (d) False; (e) False When a patient develops intolerable side-eects from one opioid, it may be useful to switch to an alternative opioid as cross tolerance among opioids is not always complete. Controlled-release forms of morphine and oxycodone should not be crushed as
Appendix A11
they become immediately bioavailable. Sedation is a frequent problem at the initiation of treatment or following a steep dose increase but usually resolves in a few days. One strategy to reduce sedation is to increase the frequency of dosing while reducing the actual dosage. Addiction is not a problem in the cancer patient although tolerance (the need for higher doses to achieve the same eect) may rarely be an issue, often heralding disease progression. Physical dependence refers to the development of withdrawal syndrome upon discontinuation or following marked dose reduction after a patient has been on repeated doses for a length of time. Tolerance and physical dependence do not however represent addiction, which is an aberrant behaviour, characterized by compulsive drug use or continued drug use despite harm to the individual. Opiod mode of action is not only via speci®c opioid receptors in the brain. 5. (a) False; (b) True; (c) False; (d) False; (e) True Adjuvant analgesics represent a diverse group of drugs originally indicated for uses other than for pain relief or to enhance the action of the primary analgesic. They may be used at any step of the WHO analgesia ladder. Anticonvulsants are used in the management of neuropathic pain particularly for those with paroxysmal or lancinating pain. The analgesic eect of TCAs is independent of their mood-elevating eects and pain relief occurs 1±2 weeks after initiation of treatment. Octreotide is successfully used in the management of nausea and vomiting secondary to bowel obstruction, radiation and chemotherapy induced diarrhoea amongst other indications. Calcitonin and bisphosphonates through inhibiting osteoclast induced bone resorption are useful in the management of metastatic bone pain. Chapter 3 6. (a) True; (b) False; (c) True; (d) False; (e) True Because of its bioavailability, low cost, multiple formulations and ecacy, morphine is most frequently utilized for control of cancer pain. Drugs such as meperidine which have active metabolites should be avoided to decrease side-eects. Mixed agonist/ antagonist opioids have a ceiling eect and should not be used for women with cancer pain. Long-acting oral opioids are preferable for patient convenience. 7. (a) True; (b) True; (c) False; (d) True; (e) True Common side-eects of opioid therapy include constipation, nausea and sedation. Constipation occurs in essentially all patients who are receiving opioids and should be anticipated and prevented. Most patients become tolerant to opioid-related nausea and sedation over a period of several days to weeks. A major advantage of the newer COX 2 inhibitor NSAIDS is the rarity of gastrointestinal side-eects. Patients who are taking large doses of opioids may have respiratory depression following procedures, which rapidly control their pain. In such cases, Naloxone may be utilized but it should be kept in mind that the half-life is 30±45 minutes, much shorter than an opioid, and hence repeated doses may be required.
A12 Appendix
Chapter 4 8. (a) False; (b) True; (c) False; (d) False; (e) True Bulk-forming laxatives can produce or exacerbate the problem of constipation and should be generally avoided. Rectal examination is mandatory and helps to avoid the fruitless use of suppositories when the rectum is empty. 5HT receptor antagonists actually cause constipation both when used in chemotherapy and palliative care. Oral opioids are one of the most useful drugs in care of women with cancer pain; the solution is to use them in appropriate dosage but with pre-emptive use of laxatives. Many patients with advanced gynaecological cancer have a form of dysmotility which appears to be due to subtle eects of retroperitoneal disease rather than tumour compressing the bowel.
9. (a) True; (b) False; (c) True; (d) False; (e) False A gastrogran enema is prudent to exclude concommitant large bowel obstruction in patients with small bowel obstruction prior to surgery. Gastrogran is preferred to barium as it is less likely to cause problems if bowel resection is required. Steroids are not contraindicated and a short trial of steroids is usually indicated unless there is a condition that requires immediate surgical intervention. Care should be taken in patients with diabetes, active peptic ulceration, TB and major psychological disturbance. Hyoscine butyl bromide is a very useful drug in conservative management of bowel obstruction in women with advanced cancer acting directly on the bowel and hence avoiding the central sedation eects. Some studies have shown an advantage with octreotide but the high cost often outweighs any gain. Metoclopramide and other gastrokinetic antinauseants are contraindicated in women with high intestinal obstruction as they increase nausea and vomiting.
10. (a) True; (b) True; (c) True; (d) False; (e) False Xerostomia or dry mouth may be the result from reduced production of saliva, excessive evaporation from the oral cavity or treatments such as radiotherapy. Drugs such as tricyclic antidepressants, antiparkinsonian drugs, antispasmodics and neuroleptics may also be responsible. Treatments should involve rationalizing medication, frequent small drinks with added orange or lemon juice to stimulate salivation, use of arti®cial saliva or glycerine mouthwashes or pilocarpine drops. Altered taste is a poorly understood problem in advanced cancer patients and various approaches have been tried such as avoidance of food with high urea content by eating white meats, eggs, dairy products, and use of stronger seasonings with food. Dental caries should be excluded as a correctable cause. Simple starvation involves mobilization of fat but sparing of skeletal muscle whereas cachexia involves equal mobilisation of both. Progestational agents and corticosteroids both have been shown to improve appetite.
Appendix A13
11. (a) True; (b) False; (c) True; (d) True; (e) False Drugs such as NSAIDs, mucolytics and antibiotics are emetogenic. The vomiting centre is situated in the medulla oblongata and is the ®nal mediator of nausea and vomiting though various re¯ex pathways may lead to these symptoms. Chemotherapeutic agents, ketosis, uraemia and hypercalcaemia act via the chemoreceptor trigger zone. Ondansetron and other 5HT receptor blockers may precipitate constipation and faecal impacion. In women with advanced cancer presenting with diarrhoea, it is imperative to exclude faecal impaction with over¯ow. 12. (a) True; (b) True; (c) False; (d) False; (e) True Somatostatin reduces enteral secretions and thus may be of symptomatic relief in cases of enterocutaneous ®stulae where surgical diversion (the preferred option) is not feasible. Clear cell and small cell ovarian carcinomas are commonly associated with hypercalcaemia. Subcutaneous calcitonin may be of bene®t in resistant cases of hypercalcaemia. The distressing foul smell from anaerobic organisms may be partially alleviated by metronidazole orally or topically. Chapter 5 13. (a) True; (b) False; (c) True; (d) True; (e) False The initiation of palliative care for a patient implies incurable disease and a limited life expectancy and in its most speci®c sense refers to lessening or alleviation of suering. The basic radiobiology principles underlying radiotherapy are that normal tissues in general have a better capacity to repair sublethal injury than tumours. The therapeutic ratio can be ampli®ed by delivering the radiation over a protracted, fractionated course with sparing of late reacting normal tissues, but this may be at the expense of potential tumour repopulation and patient logistical diculties. Typically external beam radiation is delivered using 1.8±2.0 Gy daily fractions over several weeks with total dosage used in gynaecological malignancies being around 30±40 Gy. Brachytherapy oers the advantage of a high local dose to the tumour with a reduction to surrounding normal structures. 14. (a) False; (b) True; (c) False; (d) True; (e) True High dose of radiation per fraction increases the risk of late complications but is an ecient and convenient way of treatment for the patient and is particularly suitable for palliative treatment, with very high doses being appropriate in cases of advanced pelvic malignancy for symptom control (pain, bleeding), especially where life expectancy is under 12 months. 2±8 % of patients with cervical and endometrial carcinoma and 4% of patients with ovarian carcinoma develop bone metastases and the vertebral column and, in particular, the lumbar spine being the most common site. Radiotherapy achieves relief from pain of bony metastases in 80±90% of cases, with complete resolution in 50% and persistent relief during the following year in 55±65% of patients.
A14 Appendix
15. (a) False; (b) False; (c) True; (d) True; (e) False Lytic lesions in weight-bearing bones with 450% cortical destruction or a lesion 42.5cm in size are typically at high risk of a pathological fracture and should undergo orthopaedic evaluation for prophylactic ®xation, and after ®xation should have radiotherapy. Spinal MRI is the imaging modality of choice in the investigation of spinal cord compression. High dose IV steroids are part of the ®rst-line management of spinal cord compression, along with neurosurgical and radiation oncology reviews. Pamidronate is eective both in providing relief in patients with osteolytic metastases and treating hypercalcaemia. Systemic radionuclide treatment should certainly be considered after radiotherapy where there are multiple sites of painful bone metastases. 16. (a) True; (b) False; (c) True; (d) False; (e) True Brain metastases from gynaecological malignancies are rare with the exception of choriocarcinoma. The imaging modality of choice is MRI with gadolinium. The general management of a patient with brain metastases includes corticosteroids, which provide symptomatic improvement through reduction of peritumour oedema. Palliative radiotherapy provides response rates of 69±90%. Without treatment patients with brain metastases have a median survival of 1 month, increasing to 2 months with steroids alone and 3-6 months with palliative radiotherapy, with 1- and 2-year survival rates of 15% and 5±10% respectively. Chapter 6 17. (a) True; (b) False; (c) False; (d) False; (e) True One of the areas where interventional radiology can contribute greatly to the gynaecological oncology patient is the placement of central venous access devices and also radiologically guided percutaneous procedures. Patients with a contraindication to anticoagulation, patients with a complication of anticoagulation or debilitated patients with a large clot burden are best served with an IVC ®lter. Prior to placement of IVC ®lters it is essential to identify the con¯uence of the iliac veins, the in¯ow of the renal veins and any accessory renal veins, the diameter of the IVC and the presence if any of clot in the IVC. The IVC ®lters are placed infra-renaly, with a success of placement in 98% of cases and reported clot-trapping ability of 98%. 18. (a) False; (b) True; (c) True; (d) False; (e) False Percutaneous nephrostomies are not appropriate in all cancer patients. Speci®c criteria by Fallon et al. may help the clinician to which patients will bene®t from nephrostomy catheter placement. These criteria include patients with undiagnosed malignant disease, prostatic and cervical primary tumours, patients in whom there is a treatment modality and a reasonable chance of response, patients with localized disease and patients who request prolongation of life for legal or ®nancial reasons. In cases of
Appendix A15
vesicovaginal ®stulae where nephrostomies fail to completely divert the urine (required for healing), and where prognosis is not favourable, a dry perineum can be achieved by ureteric coil embolization. Polyvinyl alcohol particles are used for uterine artery embolization for ®broids. Although after diagnostic arteriograms, patients are discharged the same day, an overnight hospital stay is required for therapeutic procedures. Transcatheter embolization has been used to control haemorrhage such as post partum, cases where pelvic malignancies have eroded into adjacent vascular structures. It is also used to control perfusion to visceral structures or tumour masses that arise from them.
Chapter 7 19. (a) False; (b) False; (c) True; (d) False; (e) False Ovarian carcinomas are associated with pulmonary metastases in 4±7% of cases while uterine and cervical carcinomas are associated with pulmonary metastases in 1% of cases. Although as little as 175 ml of ¯uid may produce blunting of the costophrenic angle, as much as 500 ml of ¯uid may be present without blunting of the costophrenic angle. Pleural ¯uid cytology may be positive in 40±87% of malignant pleural eusions. The risk of pneumothorax at thoracocentesis varies between 4 and 30% of cases but the need for a chest drain depends on the size of the pneumothorax, and the cardiovascular health of the patient, so initial management involves supplementary oxygen, observation and serial radiographs. Meig's syndrome is a benign pleural eusion, which in addition to ovarian ®bromas may also be associated with Brenner's tumour, granulosa-theca cell tumours, cystadenoma, germ cell tumour, ovarian adenocarcinoma, fallopian tube carcinoma etc.
20. (a) False; (b) True; (c) False; (d) True; (e) False Chemical pleurodesis is reserved for patients not suitable for or who have failed chemotherapy and are symptomatic of dyspnoea- the principal symptom for which pleurodesis is eective. Talc is the agent of choice with overall success rate of 91%. The complications of pleurodesis include empyema, fever, arrhythmias, pneumonitis and respiratory failure. Pleurodesis is unlikely to be successful if there is mediastinal shift towards the eusion indicating an endobronchial obstructive lesion or trapped lung.
21. (a) False; (b) True; (c) False; (d) True; (e) True Pulmonary metastases are the result of haematogenous spread via the pulmonary arteries or less commonly via the bronchial arteries. Pulmonary nodules tend to be localized to the basal portions of the lungs. High-resolution CT scanning can frequently miss nodules 3 mm in diameter. Transthoracic needle biopsy is the preferred method of diagnosis of the solitary pulmonary nodule with a reported sensitivity in the diagnosis of malignant disease of 70±100%.
A16 Appendix
22. (a) False; (b) False; (c) True; (d) True; (e) False Dyspnoea is a subjective sensation of breathlessness that may originate not only from central chemoreceptors but also from diaphragmatic or intercostal receptors, intrapulmonary receptors, commands from the respiratory control centre or higher cortical centres. Opiates are the treatment of choice for dyspnoea with central and peripheral actions and no respiratory depression occurring at therapeutic doses. Lymphangitic spread of tumour commonly causes disproportionate dyspnoea, with activation of intrapulmonary receptors. Pulmonary metastases are common (25±50%) in choriocarcinoma and are often extensive with more than 10 lesions on a chest radiograph noted in over 40% of patients and a pleural eusion in 48%. Venous thromboembolism occurs in approximately 11% of cancer patients and is even more common in patients with gynaecological cancer. Chapter 8 23. (a) True; (b) False; (c) False; (d) True; (e) True Factors associated with the development of painful decubitus ulcers include emaciation and muscle wasting of chronic and terminal diseases, the decreased skin circulation from both depressed cardiac function and directly diminished skin perfusion with hypovolaemia and often the distention and oedema of the skin itself along with hypoprotinaemia, all contributes to decubitus ulceration. Prevention of pressure sores is the ®rst defence with changing positions every 2±4 hours. Lambskin boots and foam rings protect the heels and elbows. Special air mattresses help to reduce the pain and suering from skin pressure and sores. The early use of antifungal mouth `swish and swallow' may prevent cracking and pain. Occasionally hydrogen peroxide/saline combinations can be helpful in maintaining oral hygiene. Chapter 9 24. (a) False; (b) False; (c) True; (d) False; (e) False Euthanasia is illegal worldwide although it is practiced in around a dozen countries. The de®nition of euthanasia is the intentional termination of life of a patient at his/her request by a physician so question (b) does not ful®l the criteria for euthanasia. A noti®cation procedure in force in the Netherlands since the end of 1990 obliges the physician responsible for euthanasia to notify the coroner as a case of unnatural death. Of the 9700 requests for euthanasia in 1995, 6000 were not granted. The most important reasons stated by patients requesting euthanasia were loss of dignity (57%), pain (46%), dependence on others (33%) and tiredness of life (23%). 25. (a) False; (b) False; (c) False; (d) True; (e) False Although the patient's relatives are always involved in the discussion about a request for euthanasia, if the family members are not in agreement with the request, the autonomy of the patient will be considered the most important. The combination of
Appendix A17
barbiturate and muscle relaxants are the preferred options while opiates are not the preferred option due to tolerance to these agents. Intravenous euthanaticum will take no more than 30 minutes while taken orally it may take a few hours. Where health care is not adequately covered by national or private insurance, introducing euthanasia may not be appropriate as ®nancial reasons may result in family pressure on the patient decision to request euthanasia.
Chapter 10 26. (a) False; (b) True; (c) True; (d) True; (e) False Death is de®ned as irreversible cessation of the function of the entire brain including the brainstem. In brain death the electroencephalogram is always isoelectric. Permanent vegetative state (PVS) on the other hand involves cessation of the function of cerebral hemispheres but retention of some brainstem function and therefore unlike brain death, survival may be possible without or with limited somatic support. In a brain dead pregnant woman, the fetus has ethical and medical standing but is not legally granted the rights of a person.
27. (a) True; (b) True; (c) False; (d) True; (e) False Respiratory support needs to take into consideration the hyperventilation of pregnancy destined to maintain a mild hypocarbia to aid fetal clearance of carbon dioxide. Hypotension develops in brain dead patients, which along with the loss of central circulatory autoregulation and the need for volumic adjustment due to diabetes insipidus further complicates blood pressure management. High doses of dopamine to support renal function and blood pressure through their peripheral vasoconstrictive action lead to dramatic reduction in placental perfusion. Panhypopituitarism occurs leading to multiendocrine failure with the need for ¯uid replacement, vasopressin, corticosteroids and thyroxine. Maternal thermoregulation is also lost with risks of both hyperthermia and hypothermia and given the primordial role of maintaining a temperature of 378 for fetal wellbeing, poses a further challenge.
28. (a) False; (b) True; (c) False; (d) True; (e) False Enteric nutrition through nasogastric feeding or percutaneous gastrostomy is often thwarted by poor motility of the gastrointestinal tract re¯ected by re¯ux regurgitation. Total parental nutrition through a subclavian line is required to maintain fetal caloric supply and normal growth but has the risks of maternal sepsis, thrombosis and sustained hyperglycaemia requiring prophylactic anticoagulation and insulin infusion. There is no lower limit of gestation speci®ed at which to oer life support given that with advancing medical progress longer periods of life support in a brain dead person can be maintained with a case of up to 15 weeks reported in the literature. Cancer in pregnancy occurs at a rate of 1 in 1000 and palliative care cannot be denied to the patient on the grounds of pregnancy despite the increased risks this carries for the fetus.
A18 Appendix
29. (a) True; (b) True; (c) False; (d) True; (e) True If life is being supported in a brain dead patient, betamimetics, corticosteroids, Anti D and vasopressin all have a role in improving the outcome of the pregnancy either by maintaining maternal homeostasis (e), promoting fetal maturity (b) and preventing preterm delivery (a) Anti D may be required to prevent isoimmunization (d) if there are sensitizing events that might aect that pregnancy. Dopamine at the stated dose however is likely to very markedly impair placental perfusion and have a deleterious eect on the pregnancy. 30. (a) False; (b) True; (c) True; (d) True; (e) True The cause of brain death is not directly relevant to the question of continuation of the pregnancy while factors b, c, d, e are all highly relevant. Chapter 11 31. (a) False; (b) True; (c) False; (d) True; (e) False The temptation to try further anticancer treatment if symptom relief is achieved in complex situations, with apparent improvement in the patient's condition, may on occasions lead to a little prolongation in life but at the expense of even more dicult symptoms to control which would invariably lead to a poorer quality of life, hence great wisdom is needed to balance symptom control with active management. When death is very close, there may be a convergence of organ failure as well as psychological signs such as withdrawal into ones self, and hence the diagnosis of the dying phase is crucial and needs to be recognized by all concerned in care including the patient and her family. There should be no need for intravenous ¯uids or food although mouth care is essential. The only drugs that should be continued are those for symptomatic relief and these may well include drugs such as diuretics to keep heart failure symptoms at bay. In the situation of an end of life crisis such as a massive bleed or massive pulmonary embolism rendering the patient unaware by the use of drugs such midazolam, diazepam or phenobarbital does not equate with euthanasia.