Obstruction of the superior vena cava reduces venous return from the head, neck, and upper extremities (Fig. 27-1). About 85% of cases are due to lung cancer; lymphoma and thrombosis of central venous catheters are other causes. Pts often present with facial swelling, dyspnea, and cough. In severe cases, the mediastinal mass lesion may cause tracheal obstruction. Dilated neck veins and increased collateral veins on anterior chest wall are noted on physical examination. Chest x-ray (CXR) documents widening of the superior mediastinum; 25% of pts have a right-sided pleural effusion.

Accumulation of fluid in the pericardium impairs filling of the heart and decreases cardiac output. Most commonly seen in pts with lung or breast cancers, leukemias, or lymphomas, pericardial tamponade may also develop as a late complication of mediastinal radiation therapy (constrictive pericarditis). Common symptoms are dyspnea, cough, chest pain, orthopnea, and weakness. Pleural effusion, sinus tachycardia, jugular venous distention, hepatomegaly, and cyanosis are frequent physical findings. Paradoxical pulse, decreased heart sounds, pulsus alternans, and friction rub are less common with malignant than nonmalignant pericardial disease. Echocardiography is diagnostic; pericardiocentesis may show serous or bloody exudate, and cytology usually shows malignant cells.

Primary spinal cord tumors occur rarely, and cord compression is most commonly due to epidural metastases from vertebral bodies involved with tumor, especially from prostate, lung, breast, lymphoma, and myeloma primaries. Pts present with back pain, worse when recumbent, with local tenderness. Loss of bowel and bladder control may occur. On physical examination, pts have a loss of sensation below a horizontal line on the trunk, called a sensory level, which usually corresponds to one or two vertebrae below the site of compression. Weakness and spasticity of the legs and hyperactive reflexes with upgoing toes on Babinski testing are often noted. Spine radiographs may reveal erosion of the pedicles (winking owl sign), lytic or sclerotic vertebral body lesions, and vertebral collapse. Collapse alone is not a reliable indicator of tumor; it is a common manifestation of a more common disease, osteoporosis. MRI can visualize the cord throughout its length and define the extent of tumor involvement.

Most paraneoplastic syndromes have an insidious onset (Chap. 78: Paraneoplastic Endocrine Syndromes). Hypercalcemia, syndrome of inappropriate antidiuretic hormone secretion (SIADH), and adrenal insufficiency may present as emergencies.

The most common paraneoplastic syndrome, hypercalcemia occurs in about 10% of cancer pts, particularly those with lung, breast, head and neck, and kidney cancer and myeloma. Bone resorption mediated by parathyroid hormone–related protein is the most common mechanism; interleukin 1 (IL-1), IL-6, tumor necrosis factor, and transforming growth factor β may act locally in tumor-involved bone. Pts usually present with nonspecific symptoms: fatigue, anorexia, constipation, weakness. Hypoalbuminemia associated with malignancy may make symptoms worse for any given serum calcium level because more calcium will be free rather than protein bound.

Induced by the action of arginine vasopressin produced by certain tumors (especially small cell cancer of the lung), SIADH is characterized by hyponatremia, inappropriately concentrated urine, and high urine sodium excretion in the absence of volume depletion. Most pts with SIADH are asymptomatic. When serum sodium falls to <115 meq/L, pts may experience anorexia, depression, lethargy, irritability, confusion, weakness, and personality changes.

The infiltration of the adrenals by tumor and their destruction by hemorrhage are the two most common causes. In addition, the immunologic checkpoint inhibiting antibodies, ipilimumab, nivolumab, and pembrolizumab can produce an autoimmune hypophysitis that leads to adrenal insufficiency. Symptoms such as nausea, vomiting, anorexia, and orthostatic hypotension may be attributed to progressive cancer or to treatment side effects. Certain treatments (e.g., ketoconazole, aminoglutethimide) may directly interfere with steroid synthesis in the adrenal.

Many cancer pts are treated with myelotoxic agents. When peripheral blood granulocyte counts are <1000/µL, the risk of infection is substantially increased (48 infections/100 pts). A neutropenic pt who develops a fever (>38°C [100.4°F]) should undergo physical examination with special attention to skin lesions, mucous membranes, IV catheter sites, and perirectal area. Two sets of blood cultures from different sites should be drawn and a CXR performed, and any additional tests should be guided by findings from the history and physical examination. Any fluid collections should be tapped, and urine and/or fluids should be examined under the microscope for evidence of infection.

When rapidly growing tumors are treated with effective chemotherapy regimens, the dying tumor cells can release large amounts of nucleic acid breakdown products (chiefly uric acid), potassium, phosphate, and lactic acid. The phosphate elevations can lead to hypocalcemia. The increased uric acid, especially in the setting of acidosis, can precipitate in the renal tubules and lead to renal failure. The renal failure can exacerbate the hyperkalemia.