Imaging acute complications in cancer patients: what should be evaluated in the emergency setting?
© Guimaraes et al.; licensee BioMed Central Ltd. 2014
Received: 6 February 2014
Accepted: 13 February 2014
Published: 29 April 2014
Increased incidence world-wide of cancer and increased survival has also resulted in physicians seeing more complications in patients with cancer. In many cases, complications are the first manifestations of the disease. They may be insidious and develop over a period of months, or acute and manifest within minutes to days. Imaging examinations play an essential role in evaluating cancer and its complications. Plain radiography and ultrasonography (US) are generally performed initially in an urgent situation due to their wide availability, low cost, and minimal or no radiation exposure. However, depending on a patient’s symptoms, evaluation with cross-sectional imaging methods such as computed tomography (CT) and magnetic resonance imaging (MRI) is often necessary. In this review article, we discuss some of the most important acute noninfectious oncological complications for which imaging methods play an essential role in diagnosis.
Cancer has become one of the leading causes of natural deaths worldwide. The high incidence of neoplasms increased the medical care related to complications of this disease in recent years. These complications may present as an acute life-threatening or insidiously, taking weeks or months to be recognized and treated. Moreover, it is not uncommon such complications being the first manifestation of of the disease .
Major noninfectious acute complications of cancer patients per system
Cord compression syndrome
Superior vena cava syndrome
Pericardial effusion/cardiac tamponade
Inflammatory intestinal changes
Urinary tract obstruction
Imaging examinations play an essential role in evaluating cancer and its complications. Plain radiography and ultrasonography (US) are generally performed initially in an urgent situation due to their wide availability, low cost, and minimal or no radiation exposure. However, depending on a patient’s symptoms, evaluation with cross-sectional imaging methods such as computed tomography (CT) and magnetic resonance imaging (MRI) is often necessary .
In this review article, we discuss some of the most important acute noninfectious oncological complications for which imaging methods play an essential role in diagnosis.
Spinal cord compression syndrome
Spinal cord compression occurs in 2.5–6% of patients with cancer . Early diagnosis of this oncological emergency is extremely important to prevent neurological sequelae such as paralysis and loss of bowel/bladder control, which may be permanent if diagnosis is delayed by even a few hours. The prognosis is poorer in the presence of paralysis or absence of a clinical response to treatment [1, 2, 5].
Most (80%) cases of spinal cord compression syndrome occur in patients with previous cancer diagnoses . The most common and earliest symptom is back pain, present in 90% of patients, which can precede neurological symptoms by weeks . Other symptoms include radicular pain, motor weakness, sensory deficiencies, gait disturbance, and urinary bladder or intestinal dysfunction. The main prognostic factor is the neurological state at the time of diagnosis; because long term neurological deficits may not respond to treatment, this diagnosis should always be suspected in patients with cancer who develop pain in the dorsal area [6–9].
The thoracic vertebral column is most commonly affected (70% of cases) . The majority of cord compressions are of extradural origin, secondary to metastatic vertebral lesions that cause cortical erosion and impress upon into the spinal canal. Cancers of the breast, lung, and prostate are most frequently associated with this condition, accounting for nearly two-thirds of all cases . Less frequently, tumors involving the paravertebral area, such as lymphomas, sarcomas, and lung cancer, can invade through intervertebral foramina and impress upon the spinal cord. More common non-neoplastic causes of cord compression that may be seen in the setting of cancer include spinal fractures and abscesses [6–8].
MRI is the gold standard for the diagnosis of cord compression [5, 6]. This imaging modality enables definition of the extent of the compressed area and aids treatment planning, such as radiation therapy. The use of paramagnetic intravenous contrast improves the method’s sensitivity, including in identifying leptomeningeal or intramedullary metastases.
When MRI is not available or is contraindicated, CT with myelography is the method of choice . When this is not available, CT preferably with intravenous contrast may be performed. Bone scintigraphy and plain films can show bone alterations, but do not visualize the cord.
Increased intracranial pressure is a common and potentially serious neurological complication in patients with cancer [4, 10–12]. It is caused mainly by intraparenchymal metastatic disease. Among malignant tumors, lung cancer, breast cancer, and melanoma most commonly spread to the brain . Other causes of increased intracranial pressure include intratumor hemorrhage and hydrocephalus. Patients with cerebral metastases of melanoma, choriocarcinoma, and renal cell carcinoma are at higher risk for bleeding. Hydrocephalus is most commonly obstructive or non-communicating, caused by lesions at the level of the foramen of Monro, the aqueduct of Sylvius, or the fourth ventricle, but can also be non-obstructive or communicating in patients with diffuse leptomeningeal carcinomatosis, which obstructs the arachnoid granulations, impeding cerebrospinal fluid reabsorption [10–12].
Elevated intracranial pressure can result in general symptoms, such as headache, nausea, vomiting, and reduced level of consciousness . Headache is present in about half of all patients with (primary or secondary) cerebral tumors, especially those showing rapid or infratentorial growth. Projectile vomiting without nausea is frequently observed in patients with tumors of the posterior fossa, which evolve into obstructive hydrocephalus . Other symptoms related to intracranial hypertension secondary to neoplastic disease are focal neurological dysfunction, cognitive deficits, and convulsions. Elevated intracranial pressure and the effect of the mass can cause ischemic encephalic vascular trauma and brain herniation [10–12].
Superior vena cava syndrome
Superior vena cava syndrome results from partial or complete obstruction of the blood flow in the superior vena cava, causing reduction in venous return to the head, neck, and upper limbs [1, 2, 13]. Although it is considered a classic oncological emergency, it is rarely immediately life threatening .
Symptoms include cough, dyspnea, dysphagia, edema, and congestion in the neck, face, and upper limbs. Collateral venous circulation can cause distension of the surface veins of the thoracic cavity wall [14–17].
More than 50% of patients with superior vena cava syndrome become symptomatic after receiving a diagnosis of cancer due to severe clinical worsening of these patients [1, 17, 18]. The prognosis for this syndrome depends on that for the underlying disease. Malignant tumors such as lung cancer, lymphomas, and metastatic mediastinal tumors are responsible for more than 90% of cases [15–17]. Venous thrombosis combined with the presence of a catheter within the superior vena cava is an uncommon cause of this condition in patients with cancer.
CT should be performed with intravenous contrast and images acquired in the later phases to guarantee optimal contrast of the brachiocephalic veins and to avoid streak artifacts from arterial contrast [14, 17]. If iodinated contrast cannot be used MRI may also be performed. Sequences with and without contrast as well multiplanar reconstruction aide MRI evaluation of tumor extent and the compromise of the superior vena cava and adjacent anatomical structures. Cross-sectional imaging is beneficial for therapeutic planning, especially in patients with conditions requiring a surgical approach [14–18].
Pericardial effusion with cardiac tamponade
Malignant pericardial effusions are present in 10–15% of patients with cancer and are caused by the obstruction of lymphatic drainage, direct extension or hematogenous metastasis [18, 19]. Pericardial effusion is generally a late finding in patients with metastatic cancer. The most common causes are lung and breast cancers, followed by melanoma, leukemia, and lymphoma [1, 2, 19]. Benign inflammatory pericardial thickening and effusion may arise as side effects of radiation therapy and certain chemotherapies or from infectious causes in immunocompromised patients. Two-thirds of patients with this condition are asymptomatic. The most common symptoms are dyspnea, orthopnea, fatigue, palpitations, and dizziness .
Cardiac tamponade occurs when a quantity of liquid that has accumulated in the pericardial sac causes restriction in diastolic expansion and hemodynamic instability . This is more common with rapid fluid accumulations rather than slow accumulation. The main signs on physical examination are paradoxical pulse, tachycardia, hypotension, distension of the cervical veins, weak peripheral pulse, and muffled heart sounds .
Echocardiography is the main modality used to confirm a diagnosis of pericardial effusion, to evaluate its hemodynamic impact, and to guide pericardiocentesis . Cytological examination of the pericardial fluid should be performed to confirm or exclude the presence of neoplastic cells.
Benign and malignant pleural effusions are common in patients with cancer. These can lead to compression of the adjacent pulmonary parenchyma and when large, difficulty breathing. Patients are commonly asymptomatic, but may present with dyspnea, cough, thoracic pain, weight loss, anorexia, and/or fatigue .
Benign pleural effusions may be secondary to compromised lymph drainage, to infectious/inflammatory processes, or to reduced oncotic pressure. Malignant pleural effusions are typically caused by pleural compromise from the underlying disease. Malignancies that most frequently affect the pleura are lung, breast, and ovarian cancers and lymphoma. Primary pleural tumors, such as mesothelioma are quite rare and generally cause effusion associated with the pleural mass [23, 24].
Deep vein thrombosis and pulmonary thromboembolism (PTE) are common complications in patients with cancer because of their hypercoagulable state, local tumor effects, or treatment side effects . Malignant tumors most frequently associated with the development of PTE are lung, colon, and prostate cancers . The incidence of venous thromboembolism is higher in patients receiving chemotherapy, reaching 10% in patients with ovarian cancer or lymphoma and 28% in patients with malignant gliomas . Patients with cancer and PTE also have a poorer prognosis, with mortality rate four to eight times that of the general population with PTE [27–30].
It is found incidentally on imaging examinations performed for other reasons in about 4% of patients with cancer  and mainly affects small pulmonary arteries. This finding should be reported urgently and treatment initiated because it is associated with the presence of deep vein thrombosis and the development of new thromboembolic events.
PTE is commonly asymptomatic or associated with non-specific symptoms. Acute onset dyspnea is the most suggestive symptom of PTE, followed by pleuritic pain. Massive PTE can cause pulmonary hypertension and signs of direct cardiac insufficiency. Chemotherapy, history of recent surgery, prolonged immobilization, or signs of deep vein thrombosis are associated with developing PTE [27–29].
The differential diagnosis of PTE includes pulmonary tumor thrombotic microangiopathy (PTTM), an extremely rare and serious complication in patients with cancer caused by the presence of microemboli; it is associated with adenocarcinomas, mainly of gastric origin . A patient with PTTM develops rapidly progressing signs and symptoms of pulmonary hypertension and cardiac failure, evolving to death in a few days [33, 34]. Diagnosing this condition is extremely difficult, and in many cases is performed post-mortem.
CT angiography is the method of choice to diagnose and evaluate the extent of PTE. CT should be performed using a specific angiographic protocol to achieve adequate contrast of the pulmonary arteries, with suitable venous access. Multiplanar reconstructions can be useful in identifying the thrombus [32–35].
In patients who cannot undergo CT angiography, the method of choice is ventilation/perfusion pulmonary scintigraphy. However, this modality may be unavailable in urgent situations in many institutions. Another option is MRI of the thorax, which enables the identification of large thrombi with a balanced steady state free precession sequence, without the use of paramagnetic contrast (Figure 6) . Thoracic x-rays may be normal or yield nonspecific findings, such as focal opacities and a small pleural effusion. Nonspecific and uncommon x-ray signs have been described in patients with PTE, including Hampton’s hump (peripheral triangular opacity with a pleural base), the Fleischner sign (enlargement of the pulmonary artery on the side of the PTE), and the Westermark sign (pulmonary oligemia distal to the PTE) .
PTTM shows nonspecific signs of pulmonary hypertension on thoracic CT images. Because of changes to the small vessels, typical findings of infectious bronchiolitis, such as diffuse centrilobular opacities and a tree-in-bud pattern, have also been described [32–35].
Intestinal obstructions are relatively common in patients with cancer and can be caused by benign etiologies or directly associated with the tumor [37, 38]. Benign causes include postoperative adhesions, actinic sequelae, and inflammatory and infectious changes. Malignant causes include obstruction by the primary tumor, recurrence, and metastasis . The clinical manifestations of benign and malignant obstructions are very similar, and imaging findings may be inconclusive. However, differential diagnosis has important implications for prognosis and treatment [39, 40].
Malignant causes of small intestinal obstruction are less frequent than adhesions and inflammatory changes. Malignant obstruction of the small intestine is caused more frequently by metastatic tumors than by primary tumors of the small intestine, which are responsible for <2% of all gastrointestinal neoplasias . Malignant obstruction of the colon is generally caused by primary colorectal carcinoma [41, 42].
Focal intestinal lesions can also cause intussusception [43, 44]. This condition is generally rare in adults, responsible for only 5% of intestinal obstructions [44, 45]. In addition to foreign bodies, primary neoplasias of the small intestine and colon and metastatic lesions (e.g., melanoma) can cause intussusception. When a neoplasia is suspected, care should be taken to differentiate a real tumor mass from a pseudomass caused by intussusception [43–46].
Radiography can show signs of intestinal obstruction, with gaseous distension of the small bowel or bowel loops forming air-fluid levels on upright images . Small bowel follow-through is not done very commonly presently. CT is generally performed to evaluate the site and possible cause of obstruction and treatment planning. CT findings that suggest malignant intestinal obstruction are the presence of irregular parietal thickening or a mass with soft-tissue density at the point of transition [42–44]. More commonly, no mass is found and the obstruction is due to adhesions.
Inflammatory intestinal changes
Acute intestinal inflammatory changes are common in patients with cancer, and various etiologies may be involved in these processes [46–48]. Neutropenic colitis or typhlitis is a cancer emergency that demonstrates transmural inflammation of the cecum, proximal colon, and terminal ileum . It can develop in immunocompromised children and adults, for example those undergoing treatment for leukemia, receiving chemotherapy, or that have undergone bone marrow transplant. Early identification of this condition is fundamental because it can evolve into intestinal necrosis and has high morbidity and mortality rates. Patients normally present with fever, neutropenia, and abdominal pain .
Pseudomembranous colitis is caused by Clostridium difficile infection, commonly after antibiotic treatment, it should be considered especially in immunocompromised cancer patients with abdominal complaints [51, 52]. It is the most common cause of diarrhea in hospitalized patients. Immunosuppressed patients undergoing chemotherapy who use broad-spectrum antibiotics are at risk of developing this complication. Diarrhea, abdominal pain, and fever typically manifest 1 week after the initiation of antibiotic therapy. In some cases, this condition can evolve into diffuse colitis and toxic megacolon .
Malignant tumors can also be associated with mesenteric ischemia and ischemic colitis . Ischemia can be secondary to vascular occlusion caused by tumor compression/invasion or bacterial proliferation associated with intestinal distension and chronic stasis .
The small intestine and colon are sensitive to radiation therapy. Thus, actinic enteritis and colitis should be considered in the differential diagnosis when signs of an inflammatory process are present in previously irradiated areas .
Ultrasound is useful in some cases, but CT is generally the best method for the evaluation of intestinal complaints [37, 40, 46]. CT is also useful for excluding other causes of abdominal pain, including obstructions and inflammatory changes not associated with cancer, such as appendicitis, diverticulitis, and inflammatory bowel diseases [39, 40, 50].
Biliary obstruction can be secondary to biliary stasis in patients with diffuse metastatic infiltration of the liver, causing obstruction of the small intrahepatic bile ducts, or it can occur due to compression of the main bile ducts in patients due to more commonly metastatic disease or lymphoma or disease within the ducts, for example, from cholangiocarcinoma .
Malignant tumors of the head of the pancreas and the ampulla of Vater are common causes of obstruction of the main bile ducts. Benign differential considerations include pseudocyst from pancreatitits .
Bile duct obstruction manifests mainly as jaundice, dark urine and pale-colored stools. In a patient with abdominal pain and/or fever, the possibility of cholangitis associated with biliary obstruction should also be considered [55, 56].
Imaging methods should be able to define the presence or absence, level, and cause of bile duct obstruction. Ultrasound is generally the first method used and has good diagnostic accuracy in detecting dilation of the intra- and extrahepatic bile ducts . A literature review showed that ultrasound has a sensitivity of 71% in delineating the level of obstruction and 51% in defining the etiology. Fat and gastrointestinal gas may limit evaluation .
Other methods for evaluating the bile ducts include endoscopic retrograde cholangiopancreatography (ERCP), which also allows biopsy. However, this is invasive, more complex and commonly less readily available than CT or MRI. Commonly, the second line test due to ease of availability is CT. MR also visualizes visceral structures, and one can employ heavily T2-weighted MR sequences for visualizing the ducts (MRCP) .
In cases of diffuse metastatic infiltration of the liver, CT or MRI shows multiple hepatic lesions that are more commonly infiltrative or confluent depending on the primary tumor, together with focal dilatation of the small intrahepatic bile ducts adjacent to vessels of the hepatic triad .
Urinary tract obstruction
Urinary tract obstruction can occur in patients with retroperitoneal or pelvic tumors; these are more commonly gynecological or urological cancers of the cervix, ovaries, bladder, and prostate [1, 57]. Metastatic disease, for example, from gastric cancer can also be seen. Sarcoma or lymphoma as a cause is relatively rare. Unilateral urinary obstruction does not normally cause acute renal dysfunction because of compensation by the contralateral kidney. Urinary obstruction can be seen post surgery due to fibrosis involving the ureters. Obstruction of the urinary tract should be suspected in patients with complaints of pain in the flank and sudden anuria who have increased serum creatinine levels [57, 59].
Cancer patients can develop bleeding complications secondary to thrombocytopenia, tumor rupture, or hemorrhage from a vascular neoplasm.
Massive hemoptysis is generally used to describe the expectoration of a large amount of blood and/or a rapid rate of bleeding, and when it occurs secondary to malignant disease, the mortality rate may be as high as 60%. Bronchogenic carcinoma is the most common cause of massive hemoptysis in patients older than 40 years. Endobronchial metastases from carcinoid tumors, breast, colon or kidney cancer, melanoma and sarcomas may also cause hempoptysis. Hemoptysis in cancer patients may also be caused by nonmalignant conditions, such as fungal infections, or may be related to thrombocytopenia or other coagulation disorders [1, 61].
Severe abdominal bleeding in cancer patients is a rare, but potentially fatal complication that requires prompt diagnosis and treatment. Malignant hemorrhage can occur in an organ parenchyma or subcapsular space due to direct tumor rupture or in the peritoneal cavity from carcinomatosis or extension of visceral tumor rupture. Hypervascular tumors, such as hepatocellular carcinoma, renal cell carcinoma, and melanoma, are the most commonly associated to spontaneous hemoperitoneum. Large size of the mass, a peripheral or subcapsular location and increased vascularity are the most important risk factors for intratumoral hemorrhage and subsequent spontaneous rupture. In addition, patients with hematologic malignancies can develop spontaneous hepatic or splenic rupture [40, 61].
At unenhanced CT, hemoperitoneum manifests as high attenuation ascites (typically 30–45 HU). Subcapsular hematomas are elliptical high-attenuation collections bound by the organ capsule in which they originate. Thus, on CT images, the highest-attenuation hematoma, or sentinel clot, is that closest to the site of bleeding. Foci of active extravasation of intravenous contrast material extending into or around the hematoma indicate ongoing bleeding. Angiography of the visceral arteries not only helps identify the source of bleeding but also assists in treatment [40, 61, 63].
Nowadays, the number of oncological visits is increasing in clinical practice, especially those related to acute and insidious noninfectious oncologic complications. Imaging methods play an essential role in diagnosis and as soon as the support team recognizes these conditions, the most appropriate therapeutic approach may be provided improving the quality of life and survival of these patients.
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