Chapter 096. Paraneoplastic Syndromes: Endocrinologic/Hematologic (Part 9)

Clinical Manifestations Patients with cancer who develop deep venous thrombosis usually develop swelling or pain in the leg, and physical examination reveals tenderness, warmth, and redness. Patients who present with pulmonary embolism develop dyspnea, chest pain, and syncope, and physical examination shows tachycardia, cyanosis, and hypotension. Some 5% of patients with no history of cancer who have a diagnosis of deep venous thrombosis or pulmonary embolism will have a diagnosis of cancer within 1 year. The most common cancers associated with thromboembolic episodes include lung, pancreatic, gastrointestinal, breast, ovarian, and genitourinary cancers, lymphomas, and brain tumors. Patients with cancer...
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Chapter 096. Paraneoplastic Syndromes: Endocrinologic/Hematologic (Part 9) Chapter 096. Paraneoplastic Syndromes: Endocrinologic/Hematologic (Part 9) Clinical Manifestations Patients with cancer who develop deep venous thrombosis usually developswelling or pain in the leg, and physical examination reveals tenderness, warmth,and redness. Patients who present with pulmonary embolism develop dyspnea,chest pain, and syncope, and physical examination shows tachycardia, cyanosis,and hypotension. Some 5% of patients with no history of cancer who have adiagnosis of deep venous thrombosis or pulmonary embolism will have adiagnosis of cancer within 1 year. The most common cancers associated withthromboembolic episodes include lung, pancreatic, gastrointestinal, breast,ovarian, and genitourinary cancers, lymphomas, and brain tumors. Patients withcancer who undergo surgical procedures requiring general anesthesia have a 20–30% risk of deep venous thrombosis. Diagnosis The diagnosis of deep venous thrombosis in patients with cancer is made byimpedance plethysmography or bilateral compression ultrasonography of the legveins. Patients with a noncompressible venous segment have deep venousthrombosis. If compression ultrasonography is normal and a high clinicalsuspicion exists for deep venous thrombosis, venography should be done to lookfor a luminal filling defect. Elevation of D-dimer is not as predictive of deepvenous thrombosis in patients with cancer as it is in patients without cancer. Patients with symptoms and signs suggesting a pulmonary embolismshould be evaluated with a chest radiograph, electrocardiogram, arterial blood gasanalysis, and ventilation–perfusion scan. Patients with mismatched segmentalperfusion defects have a pulmonary embolus. Patients with equivocal ventilation–perfusion findings should be evaluated as described above for deep venousthrombosis in their legs. If deep venous thrombosis is detected, they should beanticoagulated. If deep venous thrombosis is not detected, they should beconsidered for a pulmonary angiogram. Patients without a diagnosis of cancer who present with an initial episode ofthrombophlebitis or pulmonary embolus need no additional tests for cancer otherthan a careful history and physical examination. In light of the many possibleprimary sites, diagnostic testing in asymptomatic patients is wasteful. However, ifthe clot is refractory to standard treatment or is in an unusual site, or if thethrombophlebitis is migratory or recurrent, efforts to find an underlying cancer areindicated. Thrombophlebitis: Treatment Patients with cancer and a diagnosis of deep venous thrombosis orpulmonary embolism should be treated initially with IV unfractionated heparin orlow-molecular-weight heparin for at least 5 days and warfarin started within 1 or 2days. The warfarin dose should be adjusted so the international normalized ratio(INR) is 2–3. Patients with proximal deep venous thrombosis and a relativecontraindication to heparin anticoagulation (hemorrhagic brain metastases orpericardial effusion) should be considered for placement of a filter in the inferiorvena cava (Greenfield filter) to prevent pulmonary embolism. Warfarin should beadministered for 3–6 months. An alternative approach is to use low-molecular-weight heparin for 6 months. Patients with cancer who undergo a major surgicalprocedure should be considered for heparin prophylaxis or pneumatic boots.Breast cancer patients undergoing chemotherapy and patients with implantedcatheters should be considered for prophylaxis (1 mg/d warfarin). Further Readings Cutaneous paraneoplastic syndromes are discussed in Chap. 54. Neurologicparaneoplastic syndromes are discussed in Chap. 97. Al-Tourah AJ et al: Paraneoplastic erythropoietin-induced polycythemiaassociated with small lymphocytic lymphoma. J Clin Oncol 24:2388, 2006[PMID: 16710039] DeLellis RA, Xia L: Paraneoplastic endocrine syndromes: A review.Endocr Pathol 14:303, 2003 [PMID: 14739488] Emel EA et al: Sensitivity of fibroblast growth factor 23 measurements intumor-induced osteomalacia. J Clin Endocrinol Metab 91:2055, 2006 Gabrilovich M et al: Paraneoplastic polymyositis associated with squamouscell carcinoma of the lung. Chest 129(6):1721, 2006 [PMID: 16778295] Jan de Beur SM: Tumor-induced osteomalacia. JAMA 294:1260, 2005 Jones PA, Baylin SB: The fundamental role of epigenetic events in cancer.Nat Rev Genet 3:415, 2002 [PMID: 12042769] Stewart AF: Clinical practice. Hypercalcemia associated with cancer. NEngl J Med 352:373, 2005 [PMID: 15673803]