Review
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 07/29/15 For personal use only.
2015 update on the diagnosis and management of neoplastic pericardial disease Expert Rev. Cardiovasc. Ther. 13(4), 377–389 (2015)
Chiara Lestuzzi*1, Massimiliano Berretta2 and Witold Tomkowski3 1 Cardiology Unit, Oncology Department, CRO, National Cancer Institute, Via Gallini 2. 33081 Aviano (PN), Italy 2 Oncology Department, CRO, National Cancer Institute, Via Gallini 2. 33081 Aviano (PN), Italy 3 Cardio-Pulmonary Intensive Care; National Tb and Lung Diseases Research Institute, Warsaw, Poland *Author for correspondence: Tel.: +39 0434 659297 Fax: +39 0434 659572 [email protected]
The best approach in diagnosis and treatment of neoplastic pericardial disease has not been defined yet. The authors report the most recent literature about the new diagnostic techniques that are useful to improve the diagnosis. The literature about the therapeutic options is critically reviewed, in order to give suggestions of use to the clinical practice. Pericardial effusion may require urgent drainage; the solid component, however, becomes predominant in some cases. Neoplastic pericardial disease should be assessed following oncologic criteria evaluation of the neoplastic burden; outcome classified as complete or partial response, stable or progressive disease and – in cases with progression – event-free survival. Systemic chemotherapy may be effective in lymphomas and possibly in breast carcinomas. Intrapericardial chemotherapy with systemic chemotherapy is the treatment of choice in lung cancer. Pericardial window with systemic chemotherapy is also effective in preventing the accumulation of large amount of fluid. KEYWORDS: malignant pericardial effusion . neoplastic pericardial disease . neoplastic pericarditis . pericardial metastases
Several tumors may metastasize to the heart causing neoplastic pericarditis. The tumors more frequently involved are lung cancer, lymphomas (mostly with supradiaphragmatic lymph nodes involvement), mesothelioma and breast cancer. Neoplastic pericardial effusion is one of the most frequent causes of cardiac tamponade, and may be the first clinical sign of neoplasm; however, about 30% of the cases of pericardial effusion in cancer patients are due to other causes: lymphatic engorgement (mostly in tumors involving the mediastinal lymph nodes), radiation therapy or even viral pericarditis [1,2]. In order to plan the most appropriate treatment a correct diagnosis is of paramount relevance. A particular form of neoplastic pericarditis is observed in patients with primary effusion lymphoma, which is related to the human herpes virus 8 and usually affects human immunodeficiency virus-infected patients, and causes pleural, pericardial and/or peritoneal effusion without solid masses or lymph node involvement. This particular type of lymphoma generally has a poorer prognosis compared with other non-Hodgkin’s lymphomas [3]. The pericardium may also be infiltrated directly by a mediastinal mass causing both
informahealthcare.com
10.1586/14779072.2015.1025754
external adhesion and pericardial space invasion by the tumor (FIGURE 1). Clinical aspects
Neoplastic pericardial disease may be suspected because of the appearance of symptoms (dyspnea, tachycardia or even cardiac tamponade), or may be an incidental finding during routine chest x-ray or CT scan. The most frequent symptoms are dyspnea and tachycardia. These symptoms, however, are non-specific; in cancer patients, they may be caused by anemia, pleural effusion or pulmonary lymphangitis, for instance. Compared with other forms of pericarditis, a large pericardial effusion and the appearance of signs of cardiac tamponade are more frequent in neoplastic pericardial disease as compared with other causes of pericarditis. This observation is explained by the fact that most pericardial metastases follow a lymphatic retrograde way: the engorged vessels cannot drain the effusion and a large amount of pericardial fluid may accumulate in few days, leading to cardiac tamponade [2,3]. Cardiac tamponade is a clinical syndrome, linked to the intrapericardial/intracardiac pressure: a slowly
2015 Informa UK Ltd
ISSN 1477-9072
377
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 07/29/15 For personal use only.
Review
Lestuzzi, Berretta & Tomkowski
information about the presence, entity and distribution of pericardial effusion and of intrapericardial neoplastic masses. Moreover, it is vey useful in assessing the hemodynamic impairment (cardiac tamponade or impending cardiac tamponade). Pericardial effusion is usually assessed in a semi-quantitative way, measuring the separation between the pericardial layers from several approaches. Both a rapid increase of pericardial effusion and the observation of spontaneous contrast within the pericardial fluid raises the suspicion of Figure 1. Mediastinal mass (lymphoma) infiltrating the pericardium. Left, diastole; a neoplastic component. Also the pericarright, systole. The anterior wall and the apex are fixed to the mass. dial neoplastic masses may be recognized accumulating effusion may become very large before causing by echocardiography. However, epicardial fat and fibrin strands tamponade, a rapid increase of intrapericardial fluid may lead to should not be misdiagnosed as neoplastic masses. Fat has usually cardiac tamponade with even small effusion, overcoming the abil- a low echogenicity and is more evident over the right ventricle ity of parietal pericardium to stretch [4]. Cardiac tamponade is and at the atrioventricular groove. Isolated masses with discrete characterized by engorged jugular veins, pulsus paradoxus dimensions and solid aspect (mostly if they infiltrate the underly(a decrease of >10 mmHg of systolic blood pressure during quiet ing myocardium) and/or with enhanced echogenicity after infuinspiration), tachycardia, low voltages and electric alternans at sion of ultrasonic contrast medium are very likely to be ECG and – in the more severe cases – hypotension, oliguria, syn- neoplastic (FIGURES 2 & 3) [8]. Echocardiographic signs of hemodycope or shock. Even the clinical signs typical of cardiac tamponade namic impairment are: right chambers collapse, changes in mitral may be confusing: the jugular veins may be engorged in patients flow velocities, dilation of the inferior vena cava, but these signs with obstruction of superior vena cava (either due to external com- are not always sensitive and specific. pression or thrombosis); pulsus paradoxus is frequent also in patients with obstructive lung disease or mediastinal masses. On Other imaging techniques the other hand, hypovolemia may masquerade a typical sign as Both CT and MRI are useful in assessing the entity of pericardial jugular vein distension [5,6]. Neoplastic pericardial disease, how- effusion and the presence of intrapericardial masses. These techever, may be represented mostly by solid neoplastic masses with niques are more reliable in the differential diagnosis between fat minimal or no effusion. The extreme condition is the so-called and tumor masses. PET has a high specificity: in fact, the pericartumor encasement of the heart: the epicardium is surrounded by a dium usually does not show any uptake; in case of inflammation, thick epicardial tumor mass that causes a constrictive pericarditis, a diffuse, low epicardial uptake may be observed; a single mass but may mimic clinically a cardiac tamponade [7]. It can be associ- with intense uptake is with very high probability neoplastic [9]. ated with a certain amount of pericardial effusion, but pericardio- On the other hand, it can also exclude a neoplastic pericardial centesis is usually not effective in relieving the hemodynamic involvement, if no uptake is detected (FIGURE 4). impairment. In some cases, the parietal pericardial layer is thickened, and even a small fluid accumulation may lead to constrictive Cytology & pathology hemodynamic (this is the so-called effusive-constrictive pericarditis). To confirm the neoplastic nature of the pericardial effusion, cytology and pathology are the gold standard. False negatives Diagnosis with the cytologic analysis of the pericardial fluid are possible. Chest x-ray One of the causes may be a low concentration of neoplastic Chest x-ray shows an enlarged cardiac shadow, with round cells; raising the probability of detecting the pathologic cells, all appearance. This finding may be missed in presence of large left the drained fluid (not only a small specimen) should be sent to pleural effusion, or of a large mediastinal mass. Other circum- the cytopathology laboratory and centrifuged. Also adding to stances which can limit the diagnosis are the displacement of cytologic fluid the analysis of epicardial or pericardial biopsies mediastinal structures after pneumonectomy, or an abnormal dia- obtained during pericardioscopy reduces the false-negative diagphragm elevation (as in the presence of large abdominal masses noses [10]. Another problem are the cytomorphologic changes and/or ascites). Thus, chest x-ray has a low sensitivity and low of mesothelial cells when stored, which can mimic carcinoma specificity in the diagnosis of neoplastic pericardial disease. or some kind of mesothelioma [11,12]. In the case of mesothelioma, the cytologic diagnosis is even more difficult: the sensitivEchocardiography ity has been reported to be as low as 38–50%; even the Echocardiography is the most used technique to define the differential diagnosis between mesothelioma, carcinomas and presence of neoplastic pericardial disease. It can give useful sarcomas may be challenging in some cases [13–15]. To improve 378
Expert Rev. Cardiovasc. Ther. 13(4), (2015)
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 07/29/15 For personal use only.
2015 update on the diagnosis & management of neoplastic pericardial disease
the reliability of cytologic examination, the fluid should be sent to the pathology laboratory immediately after drainage in the fresh state or refrigerated and stored at 2–8 C [16]. Cell block preparations, in addition to smears, and immunohistochemical markers are useful to make the diagnosis more accurate, and are most useful in rare tumors and in lymphoproliferative disorders [17–20]. Among the immunohistochemical markers, calretinin has been used for the differential diagnosis between mesothelioma and lung carcinoma; Claudin 4 has been reported as highly sensitive and specific in recognizing neoplastic effusions due to carcinomas; it is not tumor-specific, but is useful in differentiating between mesothelioma and carcinoma [21–23]. Also miRNA analysis of tissue samples is a promising tool in diagnosis of mesothelioma, with both sensitivity and specificity >90% [24]. The epithelial membrane antigen is the most widely accepted marker for distinction of benign and malignant proliferations in fluid, but it can give both falsepositive and false-negative results [25]. It should be noted that cytology requires some days to be completed; immediate wet preparations can be used for triage [26]. Pericardioscopy seems to be an effective method by which fragments of pericardial tissue can be obtained increasing the accuracy of diagnostic procedure of malignant pericardial involvement [27]. However, it requires a surgical approach with general anesthesia and special instruments, not available in every hospital; it should be applied in selected cases (if the diagnostic work-up failed to clarify the diagnosis) and requires a specific expertise. It is limited to the largest A referral centers.
Review
Figure 2. Neoplastic pericardial disease in a case of breast cancer, with moderate pericardial effusion and epicardial neoplastic masses (arrows).
a sensitivity of 97.6% and a specificity of 91.4%; a high value of CYFRA 21-1 with low CEA in pleural fluid can identify patients with mesothelioma [29]. Many other tumor markers have been tested, and some have shown promising results (alone or in combination): CA-19-9, CA-72-4, squamous cell
B
Biomarkers in the pericardial fluid
The dosage of tumor markers in the pericardial fluid is easier than cytology, and gives results even with a small amount of fluid and in a few hours. Several markers already used for screening and follow-up of cancer using serum samples have been tested, with variable results according with the marker tested. One of the markers best known and used for most years is carcinoembryonic antigen (CEA); its dosage is possible in most laboratories, and can be used for triage in patients with suspected neoplastic pericardial effusion. The diagnostic cutoff for serous effusion is 5 ng/ml, but usually much higher values are found; the higher the level, the higher the specificity. The other two most used neoplastic markers are serum cytokeratin 19 fragments (CYFRA 21-1) and neuron-specific enolase [28]. CEA is still the most accurate single diagnostic marker, followed by CYFRA 21-1, and the combination of a CEA >6 ng/ml and CYFRA 21-1 >60 ng/ml resulted in informahealthcare.com
C
D
Figure 3. Pericardial, epicardial and myocardial infiltration by lymphoma (same case of Figure 1). (A) Short axis view; (B) at M-Mode the thickening of the pericardial layers is evident, there are no signs of constriction (green line = breath); (C) the apical mass infiltrates the underlying myocardium in this image (arrow); (D) a solid mass is evident at the right ventricular apex.
379
Review A
Lestuzzi, Berretta & Tomkowski
B
echo-guided pericardiocentesis, the use of agitated saline through the needle before inserting the catheter is useful in confirming that the needle did not enter any cardiac chamber or to stop the procedure before inserting the catheter. Moreover, the position of the catheter in the pericardial space may be confirmed.
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 07/29/15 For personal use only.
Prevention of recurrence
Without any additional treatment, the rate of recurrence of neoplastic pericardiFigure 4. Pericardial effusion and epicardial thickening in a patient with relapstis after drainage is high (up to 40%) [38]. ing pleural mesothelioma. At PET (right) both the epicardial thickening (large arrow) To prevent recurrence of symptomatic 18 and the effusion (thin arrow) are evident. There is no FDG uptake, and a neoplastic effusion in patients with a medium-term involvement can be excluded. poor prognosis, three approaches have been used for many years: the use of carcinoma, osteoprotegerin (OPG), TNF-related apoptosis- extended drainage, or of sclerosing therapy or the creation of a inducing ligand, but the studies are still limited so far [30–32]. pericardial window. In patients without other metastatic sites, There is a great interest in the potential use of circulating or in cancer with otherwise good prognosis as regards complete miRNA as diagnostic tools in serous effusions [33,34]. On the recovery or long-term survival, an attempt to cure the metaother hand, pericardial cytokines seem not to be useful in dif- static site possibly prolonging survival is worthy. This can be ferentiating neoplastic from autoreactive and viral pericardi- achieved using local and/or systemic antineoplastic treatments. tis [35]. In patients with lung adenocarcinoma, EGFR mutation To prevent the reaccumulation of fluid, an extended drainage occurred more frequently in those with malignant pericardial may be attempted; the catheter is left in place, permanently or effusion; these patients should be managed with targeted anti- intermittently opened, until the daily drained fluid is reduced EGFR therapies. Thus, the presence of EGFR mutation should to
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 07/29/15 For personal use only.
2015 update on the diagnosis and management of neoplastic pericardial disease Expert Rev. Cardiovasc. Ther. 13(4), 377–389 (2015)
Chiara Lestuzzi*1, Massimiliano Berretta2 and Witold Tomkowski3 1 Cardiology Unit, Oncology Department, CRO, National Cancer Institute, Via Gallini 2. 33081 Aviano (PN), Italy 2 Oncology Department, CRO, National Cancer Institute, Via Gallini 2. 33081 Aviano (PN), Italy 3 Cardio-Pulmonary Intensive Care; National Tb and Lung Diseases Research Institute, Warsaw, Poland *Author for correspondence: Tel.: +39 0434 659297 Fax: +39 0434 659572 [email protected]
The best approach in diagnosis and treatment of neoplastic pericardial disease has not been defined yet. The authors report the most recent literature about the new diagnostic techniques that are useful to improve the diagnosis. The literature about the therapeutic options is critically reviewed, in order to give suggestions of use to the clinical practice. Pericardial effusion may require urgent drainage; the solid component, however, becomes predominant in some cases. Neoplastic pericardial disease should be assessed following oncologic criteria evaluation of the neoplastic burden; outcome classified as complete or partial response, stable or progressive disease and – in cases with progression – event-free survival. Systemic chemotherapy may be effective in lymphomas and possibly in breast carcinomas. Intrapericardial chemotherapy with systemic chemotherapy is the treatment of choice in lung cancer. Pericardial window with systemic chemotherapy is also effective in preventing the accumulation of large amount of fluid. KEYWORDS: malignant pericardial effusion . neoplastic pericardial disease . neoplastic pericarditis . pericardial metastases
Several tumors may metastasize to the heart causing neoplastic pericarditis. The tumors more frequently involved are lung cancer, lymphomas (mostly with supradiaphragmatic lymph nodes involvement), mesothelioma and breast cancer. Neoplastic pericardial effusion is one of the most frequent causes of cardiac tamponade, and may be the first clinical sign of neoplasm; however, about 30% of the cases of pericardial effusion in cancer patients are due to other causes: lymphatic engorgement (mostly in tumors involving the mediastinal lymph nodes), radiation therapy or even viral pericarditis [1,2]. In order to plan the most appropriate treatment a correct diagnosis is of paramount relevance. A particular form of neoplastic pericarditis is observed in patients with primary effusion lymphoma, which is related to the human herpes virus 8 and usually affects human immunodeficiency virus-infected patients, and causes pleural, pericardial and/or peritoneal effusion without solid masses or lymph node involvement. This particular type of lymphoma generally has a poorer prognosis compared with other non-Hodgkin’s lymphomas [3]. The pericardium may also be infiltrated directly by a mediastinal mass causing both
informahealthcare.com
10.1586/14779072.2015.1025754
external adhesion and pericardial space invasion by the tumor (FIGURE 1). Clinical aspects
Neoplastic pericardial disease may be suspected because of the appearance of symptoms (dyspnea, tachycardia or even cardiac tamponade), or may be an incidental finding during routine chest x-ray or CT scan. The most frequent symptoms are dyspnea and tachycardia. These symptoms, however, are non-specific; in cancer patients, they may be caused by anemia, pleural effusion or pulmonary lymphangitis, for instance. Compared with other forms of pericarditis, a large pericardial effusion and the appearance of signs of cardiac tamponade are more frequent in neoplastic pericardial disease as compared with other causes of pericarditis. This observation is explained by the fact that most pericardial metastases follow a lymphatic retrograde way: the engorged vessels cannot drain the effusion and a large amount of pericardial fluid may accumulate in few days, leading to cardiac tamponade [2,3]. Cardiac tamponade is a clinical syndrome, linked to the intrapericardial/intracardiac pressure: a slowly
2015 Informa UK Ltd
ISSN 1477-9072
377
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 07/29/15 For personal use only.
Review
Lestuzzi, Berretta & Tomkowski
information about the presence, entity and distribution of pericardial effusion and of intrapericardial neoplastic masses. Moreover, it is vey useful in assessing the hemodynamic impairment (cardiac tamponade or impending cardiac tamponade). Pericardial effusion is usually assessed in a semi-quantitative way, measuring the separation between the pericardial layers from several approaches. Both a rapid increase of pericardial effusion and the observation of spontaneous contrast within the pericardial fluid raises the suspicion of Figure 1. Mediastinal mass (lymphoma) infiltrating the pericardium. Left, diastole; a neoplastic component. Also the pericarright, systole. The anterior wall and the apex are fixed to the mass. dial neoplastic masses may be recognized accumulating effusion may become very large before causing by echocardiography. However, epicardial fat and fibrin strands tamponade, a rapid increase of intrapericardial fluid may lead to should not be misdiagnosed as neoplastic masses. Fat has usually cardiac tamponade with even small effusion, overcoming the abil- a low echogenicity and is more evident over the right ventricle ity of parietal pericardium to stretch [4]. Cardiac tamponade is and at the atrioventricular groove. Isolated masses with discrete characterized by engorged jugular veins, pulsus paradoxus dimensions and solid aspect (mostly if they infiltrate the underly(a decrease of >10 mmHg of systolic blood pressure during quiet ing myocardium) and/or with enhanced echogenicity after infuinspiration), tachycardia, low voltages and electric alternans at sion of ultrasonic contrast medium are very likely to be ECG and – in the more severe cases – hypotension, oliguria, syn- neoplastic (FIGURES 2 & 3) [8]. Echocardiographic signs of hemodycope or shock. Even the clinical signs typical of cardiac tamponade namic impairment are: right chambers collapse, changes in mitral may be confusing: the jugular veins may be engorged in patients flow velocities, dilation of the inferior vena cava, but these signs with obstruction of superior vena cava (either due to external com- are not always sensitive and specific. pression or thrombosis); pulsus paradoxus is frequent also in patients with obstructive lung disease or mediastinal masses. On Other imaging techniques the other hand, hypovolemia may masquerade a typical sign as Both CT and MRI are useful in assessing the entity of pericardial jugular vein distension [5,6]. Neoplastic pericardial disease, how- effusion and the presence of intrapericardial masses. These techever, may be represented mostly by solid neoplastic masses with niques are more reliable in the differential diagnosis between fat minimal or no effusion. The extreme condition is the so-called and tumor masses. PET has a high specificity: in fact, the pericartumor encasement of the heart: the epicardium is surrounded by a dium usually does not show any uptake; in case of inflammation, thick epicardial tumor mass that causes a constrictive pericarditis, a diffuse, low epicardial uptake may be observed; a single mass but may mimic clinically a cardiac tamponade [7]. It can be associ- with intense uptake is with very high probability neoplastic [9]. ated with a certain amount of pericardial effusion, but pericardio- On the other hand, it can also exclude a neoplastic pericardial centesis is usually not effective in relieving the hemodynamic involvement, if no uptake is detected (FIGURE 4). impairment. In some cases, the parietal pericardial layer is thickened, and even a small fluid accumulation may lead to constrictive Cytology & pathology hemodynamic (this is the so-called effusive-constrictive pericarditis). To confirm the neoplastic nature of the pericardial effusion, cytology and pathology are the gold standard. False negatives Diagnosis with the cytologic analysis of the pericardial fluid are possible. Chest x-ray One of the causes may be a low concentration of neoplastic Chest x-ray shows an enlarged cardiac shadow, with round cells; raising the probability of detecting the pathologic cells, all appearance. This finding may be missed in presence of large left the drained fluid (not only a small specimen) should be sent to pleural effusion, or of a large mediastinal mass. Other circum- the cytopathology laboratory and centrifuged. Also adding to stances which can limit the diagnosis are the displacement of cytologic fluid the analysis of epicardial or pericardial biopsies mediastinal structures after pneumonectomy, or an abnormal dia- obtained during pericardioscopy reduces the false-negative diagphragm elevation (as in the presence of large abdominal masses noses [10]. Another problem are the cytomorphologic changes and/or ascites). Thus, chest x-ray has a low sensitivity and low of mesothelial cells when stored, which can mimic carcinoma specificity in the diagnosis of neoplastic pericardial disease. or some kind of mesothelioma [11,12]. In the case of mesothelioma, the cytologic diagnosis is even more difficult: the sensitivEchocardiography ity has been reported to be as low as 38–50%; even the Echocardiography is the most used technique to define the differential diagnosis between mesothelioma, carcinomas and presence of neoplastic pericardial disease. It can give useful sarcomas may be challenging in some cases [13–15]. To improve 378
Expert Rev. Cardiovasc. Ther. 13(4), (2015)
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 07/29/15 For personal use only.
2015 update on the diagnosis & management of neoplastic pericardial disease
the reliability of cytologic examination, the fluid should be sent to the pathology laboratory immediately after drainage in the fresh state or refrigerated and stored at 2–8 C [16]. Cell block preparations, in addition to smears, and immunohistochemical markers are useful to make the diagnosis more accurate, and are most useful in rare tumors and in lymphoproliferative disorders [17–20]. Among the immunohistochemical markers, calretinin has been used for the differential diagnosis between mesothelioma and lung carcinoma; Claudin 4 has been reported as highly sensitive and specific in recognizing neoplastic effusions due to carcinomas; it is not tumor-specific, but is useful in differentiating between mesothelioma and carcinoma [21–23]. Also miRNA analysis of tissue samples is a promising tool in diagnosis of mesothelioma, with both sensitivity and specificity >90% [24]. The epithelial membrane antigen is the most widely accepted marker for distinction of benign and malignant proliferations in fluid, but it can give both falsepositive and false-negative results [25]. It should be noted that cytology requires some days to be completed; immediate wet preparations can be used for triage [26]. Pericardioscopy seems to be an effective method by which fragments of pericardial tissue can be obtained increasing the accuracy of diagnostic procedure of malignant pericardial involvement [27]. However, it requires a surgical approach with general anesthesia and special instruments, not available in every hospital; it should be applied in selected cases (if the diagnostic work-up failed to clarify the diagnosis) and requires a specific expertise. It is limited to the largest A referral centers.
Review
Figure 2. Neoplastic pericardial disease in a case of breast cancer, with moderate pericardial effusion and epicardial neoplastic masses (arrows).
a sensitivity of 97.6% and a specificity of 91.4%; a high value of CYFRA 21-1 with low CEA in pleural fluid can identify patients with mesothelioma [29]. Many other tumor markers have been tested, and some have shown promising results (alone or in combination): CA-19-9, CA-72-4, squamous cell
B
Biomarkers in the pericardial fluid
The dosage of tumor markers in the pericardial fluid is easier than cytology, and gives results even with a small amount of fluid and in a few hours. Several markers already used for screening and follow-up of cancer using serum samples have been tested, with variable results according with the marker tested. One of the markers best known and used for most years is carcinoembryonic antigen (CEA); its dosage is possible in most laboratories, and can be used for triage in patients with suspected neoplastic pericardial effusion. The diagnostic cutoff for serous effusion is 5 ng/ml, but usually much higher values are found; the higher the level, the higher the specificity. The other two most used neoplastic markers are serum cytokeratin 19 fragments (CYFRA 21-1) and neuron-specific enolase [28]. CEA is still the most accurate single diagnostic marker, followed by CYFRA 21-1, and the combination of a CEA >6 ng/ml and CYFRA 21-1 >60 ng/ml resulted in informahealthcare.com
C
D
Figure 3. Pericardial, epicardial and myocardial infiltration by lymphoma (same case of Figure 1). (A) Short axis view; (B) at M-Mode the thickening of the pericardial layers is evident, there are no signs of constriction (green line = breath); (C) the apical mass infiltrates the underlying myocardium in this image (arrow); (D) a solid mass is evident at the right ventricular apex.
379
Review A
Lestuzzi, Berretta & Tomkowski
B
echo-guided pericardiocentesis, the use of agitated saline through the needle before inserting the catheter is useful in confirming that the needle did not enter any cardiac chamber or to stop the procedure before inserting the catheter. Moreover, the position of the catheter in the pericardial space may be confirmed.
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 07/29/15 For personal use only.
Prevention of recurrence
Without any additional treatment, the rate of recurrence of neoplastic pericardiFigure 4. Pericardial effusion and epicardial thickening in a patient with relapstis after drainage is high (up to 40%) [38]. ing pleural mesothelioma. At PET (right) both the epicardial thickening (large arrow) To prevent recurrence of symptomatic 18 and the effusion (thin arrow) are evident. There is no FDG uptake, and a neoplastic effusion in patients with a medium-term involvement can be excluded. poor prognosis, three approaches have been used for many years: the use of carcinoma, osteoprotegerin (OPG), TNF-related apoptosis- extended drainage, or of sclerosing therapy or the creation of a inducing ligand, but the studies are still limited so far [30–32]. pericardial window. In patients without other metastatic sites, There is a great interest in the potential use of circulating or in cancer with otherwise good prognosis as regards complete miRNA as diagnostic tools in serous effusions [33,34]. On the recovery or long-term survival, an attempt to cure the metaother hand, pericardial cytokines seem not to be useful in dif- static site possibly prolonging survival is worthy. This can be ferentiating neoplastic from autoreactive and viral pericardi- achieved using local and/or systemic antineoplastic treatments. tis [35]. In patients with lung adenocarcinoma, EGFR mutation To prevent the reaccumulation of fluid, an extended drainage occurred more frequently in those with malignant pericardial may be attempted; the catheter is left in place, permanently or effusion; these patients should be managed with targeted anti- intermittently opened, until the daily drained fluid is reduced EGFR therapies. Thus, the presence of EGFR mutation should to
