Complications of Cancer: Oncologic Emergencies and Paraneoplastic Syndromes

Jeffrey W. Clark

There are a variety of complications that can arise from cancers. These vary in how urgently intervention is needed. They range from commonly experienced gastrointestinal issues and pain (see Chapters 90.1 and 91) to true emergencies, stubborn malignant effusions, and the uncommon, but important, paraneoplastic phenomena. Most oncologic emergencies and malignant effusions are consequences of anatomic spread. Paraneoplastic syndromes result from release or induction of hormonal and immunologic factors. The primary care physician’s important role in monitoring the cancer patient requires familiarity with early signs of these complications, many of which occur in the setting of advanced disease but are amenable to intervention, which can prolong survival when timely instituted. Frequently, hospital admission for inpatient treatment will be necessary, so the emphasis is on early detection.

ONCOLOGIC EMERGENCIES AND URGENCIES (1, 2, 3, 4 and 5)

The anatomic spread of tumor is capable of causing emergent complications, including spinal cord compression, cardiac tamponade, compression of the superior vena cava, and hypercoagulability with acute bleeding or clotting. Urgent adversities associated with malignancy ensue from a combination of tumor invasion and metabolic/immunologic effects (e.g., hypercalcemia, fever, infection).

Spinal Cord Compression

Extradural or epidural cord compression occurs in approximately 5% of patients with cancer and represents a true emergency, with early diagnosis and treatment essential to preventing serious, permanent neurologic damage. The majority of cases of epidural compression result from bony metastases in the vertebral bodies extending into the epidural space. Less frequently, metastatic tumor reaches the epidural space hematogenously or by direct extension through the intervertebral foramina.

Malignancies with a propensity to spread to bone (e.g., myeloma, lymphoma, melanoma, renal cell carcinoma, and tumors of lung, breast, and prostate) are associated with the greatest risk for cord compression. Lymphoma may metastasize directly to the epidural space and not produce any bony changes. In more than 90% of cases, the initial symptom is back pain, often radicular in nature. The course is progressive; weakness and sensory deficits below the level of compression (especially in the extremities) follow. Sphincter incontinence is a late development, unless the cauda equina is the initial site of compression.

Diagnosis

When symptoms suggestive of potential involvement of the spinal cord are present, a high index of suspicion for malignancy is always warranted. Although plain films of the spine can be helpful in cancer patients with back pain, unless the index of suspicion is low, magnetic resonance imaging (MRI) with gadolinium enhancement of the spine should be obtained since plain x-rays are not sufficiently sensitive for diagnosing the presence of malignant lesions. MRI allows identification of all affected areas without the need for injection of contrast into the spinal canal. If the radiographic findings are abnormal or if any neurologic deficits are noted, then immediate hospital admission and prompt neurologic and oncologic consultations are needed.

Treatment

Initial therapy depends on the exact presentation. For most settings, high-dose corticosteroids (e.g., 4 mg of dexamethasone every 6 hours) and radiation therapy are the mainstays of treatment, with surgical decompression indicated when neurologic function deteriorates rapidly. However, certain patients require surgical decompression as soon as possible. Therefore, it is critical that all patients be seen by a neurosurgeon as well as radiation oncologist. A medical oncologist should be involved in the discussion as well.

Patients with myeloma, lymphoma, or small cell cancers respond well to both chemotherapy and irradiation, and chemotherapy alone is worth considering when the findings do not suggest immediate need for decompression. It may also be considered for those with multifocal obstructing lesions, not all of which are amenable to radiation therapy.

Prognosis depends on the extent of neurologic damage at the time of presentation as well as the responsiveness of the tumor to therapeutic approach. Patients who are ambulatory have a 60% to 80% chance of leaving the hospital able to walk; those with paraplegia have less than a 20% chance of regaining their ability to walk. This underlines the absolute urgency required in evaluating and treating these patients.

Meningeal Carcinomatosis

Diffuse seeding of the meninges with malignant cells is a serious complication of a number of solid tumors (lymphoma, melanoma, cancers of the breast, lung, and stomach) and leukemias. Even if true cord compression is not present, the entire neuraxis may become involved, with the development of meningeal, cranial nerve, and root symptoms. The diagnosis is confirmed by lumbar puncture, which typically reveals malignant cells in the cerebrospinal fluid. Corticosteroids, irradiation, and intrathecal administration of cytotoxic agents are the treatment modalities of choice. High-dose systemic methotrexate might be an option in certain patients with lymphomas.

Cardiac Tamponade

Life-threatening tamponade may arise as a complication of malignancy, either indolently or rapidly, depending on the progression of the underlying tumor. Compression may be caused by tumorous encasement, malignant effusion, or scarring from radiation-induced pericarditis. Although any cancer can potentially cause tamponade, the most common cancers associated with tamponade include tumors of the breast and lung, lymphoma, leukemia, and melanoma. In some instances, symptoms and signs of pericarditis (see Chapter 20) precede those of tamponade. The presence of pulsus paradoxus strongly suggests significant tamponade. Unexplained elevation of neck veins, narrowed pulse pressure, inspiratory distention of neck veins, and
a pericardial friction rub should raise suspicion. Unfortunately, a pericardial friction rub is often absent in cases of tamponade caused by a malignant pericardial effusion. The usual accompanying symptoms (dyspnea, weakness, chest discomfort, cough) are nonspecific. More definitive diagnosis is best made by cardiac ultrasonography, the most sensitive and specific noninvasive test for documenting the problem and its physiologic significance.

A strong clinical suspicion of tamponade necessitates urgent hospitalization for prompt sonography and cardiac consultation. Sometimes a right-sided heart catheterization is performed when the degree of tamponade is unclear or the diagnosis is still questionable. Pericardiocentesis is the treatment of choice for urgent tamponade and may also yield positive cytology to establish the diagnosis.

Hypercoagulability

A number of the natural inhibitors of clotting, many of which are endothelial in origin (protein C, protein S, tissue plasminogen factor, antithrombin III), are disrupted directly by tumor invasion or indirectly by substances elaborated by cancers. Patients with adenocarcinomas appear particularly susceptible to recurrent or migratory thrombophlebitis or even thrombotic arterial occlusions.

Disseminated intravascular coagulation (DIC) is a more disseminated consumption coagulopathy that presents acutely as a generalized bleeding diathesis. Acute DIC is a true medical emergency, and a hematologist should be consulted promptly to assist in its management. Suggestive laboratory findings include prolongations in the prothrombin time, partial thromboplastin time, and thrombin time, a low platelet count, and elevated concentrations of fibrin split products. The peripheral smear can show a microangiopathic picture (schistocytes).

Chronic DIC is more subtle in presentation, with thrombotic end-organ damage and thrombosis being the principal manifestations. Acute DIC requires immediate hospitalization to stop the bleeding. Once the consumptive process has been slowed, platelet and plasma transfusions are given to replace those blood elements that have been consumed. More definitive therapy requires treatment of the underlying malignancy.

Superior Vena Cava Syndrome

Obstruction of the superior vena cava is usually caused by extrinsic compression. The majority of cases are associated with lung carcinoma (especially small cell carcinoma), lymphoma, and metastatic disease. The earliest manifestation is asymptomatic, unexplained distention of the neck veins. Late signs include swelling of the face, neck, and upper extremities, plethora, shortness of breath, and persistent headache. Although the condition is rarely fatal, increased intracranial pressure and thrombosis leading to neurologic deficits may ensue. The clinical diagnosis is reinforced by the finding of a mass on chest radiography in the right superior mediastinum or hilar area. Chest CT with careful evaluation of the vasculature should be performed.

At one time, it was considered essential to treat the mass immediately with emergency radiotherapy. Now, the view is one of urgency rather than emergency. The first task is to consider whether a tissue diagnosis should be obtained before radiotherapy is instituted (see Chapter 44), as a host of tumors with different degrees of sensitivity to radiation therapy or chemotherapy may be responsible for the condition. Although many malignancies respond within 1 week to radiation, some may respond better to chemotherapy, and rarely, a nonmalignant process that would not benefit from radiation is the cause (e.g., tuberculous adenopathy, substernal goiter). When a tissue diagnosis will alter therapy, invasive study to obtain tissue should proceed. If a small cell carcinoma or lymphoma is found, chemotherapy might be placed ahead of radiation as the treatment of choice (see Chapters 53 and 84).

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