Predictors of Normalization of Circulating Interleukin-6 after Cardiac Myxoma Resection.

OBJECTIVE: To disclose the relationships between the anatomic features of cardiac myxomas and plasma interleukin (IL)-6 levels. METHODS: Twelve patients undergoing cardiac myxoma resection at The First Hospital of Putian, Teaching Hospital, Fujian Medical University were enrolled into this study. Pre- and postoperative IL-6 levels were determined by an enzyme-linked immunosorbent assay method, and correlations between cardiac myxoma dimension or volume and plasma IL-6 levels were analyzed. C-reactive protein (CRP) levels were also evaluated. RESULTS: IL-6 and CRP levels were significantly decreased one month after cardiac myxoma resection in comparison to preoperative values. IL-6 and CRP levels did not differ between patients with a cardiac myxoma of irregular appearance and those with a myxoma of regular gross appearance, or between patients with a pedicled or a sessile myxoma. Decrement of IL-6 of patients with irregular cardiac myxomas was much higher than that of patients with regular ones, while no intergroup difference was noted in decrement of CRP. A close direct correlation was noted between IL-6 levels and maximal dimension (length) or volume of cardiac myxomas, whereas CRP levels only correlated with maximal dimension of cardiac myxomas. CONCLUSION: Anatomic features of cardiac myxomas (sessile, irregular appearance, maximal dimension, and volume) could be determinants of the patients' circulating IL-6 levels. IL-6 was likely to be a more sensitive biomarker than CRP in predicting the inflammatory status of patients with cardiac myxoma. Sessile and irregular cardiac myxomas might predict more severe inflammatory conditions for their more abundant endothelial cells and IL-6 overproduction.

Predictors of normalization of circulating interleukin-6 after cardiac myxoma resection

Abstract Objective: To disclose the relationships between the anatomic features of cardiac myxomas and plasma interleukin (IL)-6 levels. Methods: Twelve patients undergoing cardiac myxoma resection at The First Hospital of Putian, Teaching Hospital, Fujian Medical University were enrolled into this study. Pre- and postoperative IL-6 levels were determined by an enzyme-linked immunosorbent assay method, and correlations between cardiac myxoma dimension or volume and plasma IL-6 levels were analyzed. C-reactive protein (CRP) levels were also evaluated. Results: IL-6 and CRP levels were significantly decreased one month after cardiac myxoma resection in comparison to preoperative values. IL-6 and CRP levels did not differ between patients with a cardiac myxoma of irregular appearance and those with a myxoma of regular gross appearance, or between patients with a pedicled or a sessile myxoma. Decrement of IL-6 of patients with irregular cardiac myxomas was much higher than that of patients with regular ones, while no intergroup difference was noted in decrement of CRP. A close direct correlation was noted between IL-6 levels and maximal dimension (length) or volume of cardiac myxomas, whereas CRP levels only correlated with maximal dimension of cardiac myxomas. Conclusion: Anatomic features of cardiac myxomas (sessile, irregular appearance, maximal dimension, and volume) could be determinants of the patients' circulating IL-6 levels. IL-6 was likely to be a more sensitive biomarker than CRP in predicting the inflammatory status of patients with cardiac myxoma. Sessile and irregular cardiac myxomas might predict more severe inflammatory conditions for their more abundant endothelial cells and IL-6 overproduction.

Raised preoperative international normalised ratio (INR) identifies patients at high risk of perioperative death after simultaneous renal and cardiac surgery for tumours involving the peri-diaphragmatic inferior vena cava and right atrium.

OBJECTIVE: To identify preoperative factors that predict 30-day mortality in patients undergoing simultaneous cardiac and renal surgery for urological tumours involving the peri-diaphragmatic vena cava and right atrium- The ability to predict mortality and therefore avoid surgery in those patients likely to die would be valuable. PATIENTS AND METHODS: We retrospectively reviewed perioperative outcomes in patients managed between December 2007 and January 2016 by a single team. The relationships of outcome measurements were analysed using Fisher's exact and Mann-Whitney U-tests. RESULTS: Of the 46 patients identified, 41 (89%) underwent surgery (20 males and 21 females). The median (range) age was 65 (17-95) years. Histology confirmed 37 renal cell cancers, one adrenal cancer, two primitive neuroectodermal tumours, and one leiomyosarcoma. The overall 30-day mortality rate was 7% (three of 41 patients). The international normalised ratio (INR), age, and estimated glomerular filtration rate (eGFR) correlated significantly with 30-day mortality. The mortality rate was high in patients with an INR ≥1.5 and <1.5 (with three of the five patients dying) compared to those with an INR <1.5 (0/36 patients died; 30 day mortality 0%). The INR correlated with serious complications (≥Clavien-Dindo Grade III), which occurred in all five patients with an INR ≥1.5 and <1.5 vs 12/36 (33%) with an INR <1.5 (P < 0.002). The median (range) eGFR in those that died was 36 (26-37) mL/min/1.73 m2 compared to 52 (24-154) mL/min/1.73 m2 in those that survived (P = 0.018). CONCLUSIONS: In patients undergoing combined cardiac and renal tumour surgery raised preoperative INR is associated with a high risk of 30-day mortality when the patient is elderly (>70 years) and of significant post-operative complications in younger patients (<70 years). Surgery in patients with a normal INR is challenging but much safer.

Pericardial mass in a patient with rheumatoid arthritis.

A 65-year-old man presented with long-standing rheumatoid arthritis (RA), severe fatigue and mild arthritis of metacarpophalaneal joints. Physical examination revealed S3, II/IV decrescendo diastolic murmur and 2+ LL oedema. Anticyclic citrullinated peptide antibodies were >250 units. Echocardiogram showed an 8 cm pericardial mass with no atrial or ventricular collapse and mild to moderate aortic regurgitation. Cardiac MRI defined the mass as a heterogeneous entity attached to the right, anterior and inferior heart borders, with compression on right cardiac structures and the left ventricle. CT-guided biopsy demonstrated fibrinous material without granulomas or infection. Fatigue did not improve on immunosuppression with low-dose prednisone and leflunamide. Cardiac tamponade was confirmed by heart catheterisation and the mass was surgically excised with partial pericardiectomy. The patient had a dramatic improvement and, 4 years later, he remains asymptomatic cardiac wise. This case highlights the clinical significance of pericardial disease in RA and its response to therapy.

Interleukin-8-producing primary cardiac undifferentiated sarcoma in a child with sustained fever.

We report the case of a 12-year-old boy with primary undifferentiated sarcoma of the left atrium. He had sustained fever during the clinical course and multiple lung and brain metastases. Chemotherapy and irradiation were ineffective; he died 41 days after hospitalization. On retrospective analysis, interleukin-8 (IL-8) was elevated; this was supported by immunohistochemistry and gene expression analysis of tumor samples. IL-8 continued to increase with tumor progression accompanied by elevated neutrophil count and C-reactive protein. IL-8 is involved in malignant tumor proliferation, migration, and angiogenesis and may have been related to the clinical condition and prognosis in the present case.

Atrial myxoma: a rare but well-described cause of increased erythrocyte sedimentation rate and anaemia.

A 56-year-old woman visited her general practitioner 12 months prior with eczema. Blood samples showed anaemia, a haemoglobin level of 105 g/L and a high erythrocyte sedimentation rate (ESR) of 80 mm. Her eczema was diagnosed as discoid lupus erythaematosus but there were no signs of systemic lupus erythaematosus. Extensive investigations were made including testing of serial blood samples, repeated examinations by specialists in dermatology, rheumatology and gynaecology, and several X-rays including CT of the chest and the abdomen, all without finding a reasonable underlying diagnosis. One year later, the patient presented with dyspnoea associated with effort and body position; she was sent for echocardiography, which showed an atrial myxoma filling almost the whole left atrium and affecting the mitral valve. She was treated with urgent surgical removal and now, 6 weeks postsurgery, has fully recovered. She no longer has dyspnoea, her haemoglobin level and ESR have normalised, and the eczema has almost disappeared.

Serum malondialdehyde levels in patients with malignant middle cerebral artery infarction are associated with mortality.

OBJECTIVE: Malondialdehyde (MDA) is an end-product formed during lipid peroxidation, due to degradation of cellular membrane phospholipids. MDA is released into extracellular space and finally into the blood; it has been used as an effective biomarker of lipid oxidation. High circulating levels of MDA have been previously described in patients with ischemic stoke than in controls, and an association between circulating MDA levels and neurological functional outcome in patients with ischemic stoke. However, an association between serum MDA levels and mortality in patients with ischemic stroke has not been previously reported, and that was the objective of this study. METHODS: Observational, prospective and multicenter study performed in six Intensive Care Units. We included patients with severe malignant middle cerebral artery infarction (MMCAI) defined as Glasgow Coma Scale (GCS) lower than 9. We measured serum MDA levels in 50 patients with severe MMCAI at the time of diagnosis and in 100 healthy subjects. Mortality at 30 days was the end point of the study. RESULTS: We found that patients with severe MMCAI showed higher serum MDA levels than healthy subjects (p<0.001). We found higher serum MDA levels (p<0.001) in non-surviving MMCAI patients (n=26) than in survivors (n=24). The area under the curve for prediction of 30-day mortality for serum MDA levels was 0.77 (95% CI = 0.63-0.88; p<0.001). Serum MDA levels >2.27 nmol/mL were associated with 30-day mortality (OR=7.23; 95% CI=1.84-28.73; p=0.005) controlling for GCS and age on multiple binomial logistic regression analysis. CONCLUSIONS: To our knowledge, this is the first study showing that serum malondialdehyde levels in patients with MMCAI are associated with early mortality.

Risk factors for embolism in cardiac myxoma: a retrospective analysis.

BACKGROUND: Myxomas are the most common primary heart tumors and are closely associated with embolic events. Cardiac myxomas typically arise from the interatrial septum at the border of the fossa ovalis in the left atrium. Any other location is considered atypical. Embolism, one of the complications of myxoma, is associated with high morbidity and mortality. The aim of this study was to investigate the risk factors for embolism in patients with cardiac myxoma. MATERIAL AND METHODS: In this retrospective study, a cohort of 162 patients with cardiac myxomas was surgically treated between January 1998 and June 2014 at 3 cardiac centers in China. Preoperative data, including platelet count, sex, age, and the tumor (size, location, surface, and attachment), were compared between embolic and non-embolic groups of patients. RESULTS: No significant differences in vascular risk factors were seen between the 2 groups. However, the percentage of higher platelet count (>300 × 10(9)/L) and mean platelet volume in the embolic group were significantly higher than in the non-embolic group (P=0.0356, and 0.0113, respectively). Irregular surface and atypical location of the myxomas were also independently associated with increased risk of embolic complications. CONCLUSIONS: Tumor location, macroscopic appearance, mean platelet volume, and high platelet count are strong risk factors for embolic events in patients with cardiac myxomas.

Self-limited effusion large B-cell lymphoma: two cases of effusion lymphoma maintaining remission after drainage alone.

We report two cases of human herpesvirus-8 (HHV-8)-negative large B-cell lymphoma involving pericardial and/or pleural effusion that regressed after drainage alone. Case 1 is a 70-year-old man showing massive pericardial effusion. Cytology of the drained effusion showed monotonous infiltration of CD3-, CD20+, CD79a+, and CD138- large B-cells. Monoclonality was shown by Southern blot analysis. Case 2 is a 70-year-old man with massive pericardial and bilateral pleural effusion. Cytology of pericardial effusion showed infiltration of CD20+, CD45RO-, CD138-, immunoglobulin lambda chain+, and kappa chain- large B cells. In both cases, effusion resolved after drainage and no relapse has been observed. HHV-8 was not demonstrated in either case. Clinical presentation of our two cases resembled primary effusion lymphoma (PEL), but cytomorphology, immunophenotype, and prognosis were clearly distinct from those of PEL. HHV-8-negative effusion lymphomas might include prognostically favorable self-limited tumors that could regress without any cytotoxic therapy.

[Tumor markers in the assessment of malignant and benign pericardial effusion]. / Tumormarker im Perikarderguss bei malignen und nichtmalignen Perikardergüssen.

BACKGROUND: The differential diagnosis of pericardial effusion is often challenging because different etiologies can be discussed. Of particular therapeutic and prognostic importance is the definitive differentiation of malignant pericardial effusion from benign effusions. The definitive diagnosis of malignant pericardial effusion is established by a positive cytological examination of the pericardial fluid. However, pericardial fluid cytology, although specific has variable sensitivity. Tumor markers are often investigated after pericardiocentesis but their utility as an aid for the diagnosis of malignant pericardial effusion is not well established. The aim of this study was to measure the concentrations of the tumor markers CEA, CA 19-9, CA 72-4, SCC and NSE in malignant and non-malignant pericardial effusions and to assess their diagnostic utility in differentiating malignant from benign pericardial effusion. METHODS: We investigated the pericardial fluid of 29 patients with proven malignant pericardial effusion and 25 patients with non-malignant pericardial effusion. The etiology of the pericardial effusion was defined by pericardial cytology, epicardial histology and PCR for cardiotropic viruses from pericardial and epicardial tissue acquired by pericardioscopy. The group with non-malignant pericardial effusion comprised 15 patients with autoreactive effusion and 10 patients with viral pericardial effusion. We analyzed the following tumor markers in the pericardial fluid: carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, carbohydrate antigen (CA) 72-4, squamous cell carcinoma (SCC) antigen and neuron-specific enolase (NSE). RESULTS: Of the tumor markers tested the mean concentrations of the CEA, CA 72-4 and CA 19-9 were significantly higher in malignant pericardial effusions than in non-malignant effusions (CEA 450.66 ±1620.58 µg/l vs. 0.72 ±1.49 µg/l, p<0.001; CA 19-9 1331.31 ±3420.87 kU/l vs. 58.85 ±17.53 kU/l, p=0.04; CA 72-4 707.90 ±2397.55 kU/l vs. 0.48 ±2.40 kU/l, p<0.001). ROC curve analysis showed that pericardial fluid CA 72-4 yielded an area under the curve (AUC) of 0.85 (95% confidence interval 0.74-0.95), followed by CEA with 0.80 (95% confidence interval 0.68-0.92). Pericardial fluid CA 72-4 levels >1.0 kU/l had 72% sensitivity (95% confidence interval 53%-87%) and 96% specificity (95% confidence interval 80%-99.9%) and CA 72-4 levels >2.5 kU/l had 69% sensitivity (95% confidence interval 49%-85%) and 96% specificity (95% confidence interval 80%-99.9%) in differentiating malignant pericardial effusions from effusions due to benign conditions. CONCLUSION: Malignant pericardial effusions are associated with significantly higher pericardial concentrations of the tumor markers CEA, CA 72-4 and CA 19-9. Of the tested tumor markers, measurement of CA 72-4 levels in pericardial fluid offered the best diagnostic accuracy. Based on our data evaluation of every patient with unexplained pericardial effusion and negative pericardial fluid cytology should include the measurement of pericardial fluid CA 72-4 levels. Under these circumstances the elevation of pericardial fluid CA 72-4 levels should include malignancy as a probable diagnosis.

Imaging and intervention of paraneoplastic effect of a right atrial myxoma on factor VII activity levels.

We present the case of a 64-year-old Pakistani man with right atrial myxoma, recently diagnosed with acquired severe factor VII (FVII) deficiency. The patient presented with a history of chronic hiccups and weight loss. Initial evaluation revealed an isolated prolonged prothrombin time, severely reduced FVII activity level, and a giant right atrial myxoma protruding into the right ventricle on computed tomographic thorax and echocardiography. After surgical resection, the patient maintained normal prothrombin time with increased FVII activity level in the immediate 24 hours postoperatively, and a dramatically high level of FVII activity at the 2-month follow-up. We believe that the paraneoplastic effect of myxoma on the FVII activity levels is previously unreported. In addition, we believe that hiccups as a presenting symptom for a myxoma with an atypical origin from the lateral wall of the right atrium has not been reported.

Comparison of plasma cardiac troponin I concentrations among dogs with cardiac hemangiosarcoma, noncardiac hemangiosarcoma, other neoplasms, and pericardial effusion of nonhemangiosarcoma origin.

OBJECTIVE: To determine whether plasma cardiac troponin I (cTnl) concentrations can be used to identify cardiac involvement in dogs with hemangiosarcoma, exclude cardiac hemangiosarcoma in dogs with noncardiac hemangiosarcoma, and identify cardiac hemangiosarcoma in dogs with pericardial effusion. DESIGN: Cohort study. ANIMALS: 57 dogs (18 with confirmed [5 dogs] or suspected [13] cardiac hemangiosarcoma, 14 with confirmed hemangiosarcoma involving sites other than the heart [noncardiac hemangiosarcoma], 10 with pericardial effusion not caused by hemangiosarcoma, and 15 with noncardiac nonhemangiosarcoma neoplasms). PROCEDURES: Plasma cTnl concentration was measured, and thoracic radiography, abdominal ultrasonography, and echocardiography were performed in each dog. The cTnl concentration was compared among groups. RESULTS: Median plasma cTnl concentration in dogs with cardiac hemangiosarcoma was significantly higher than the concentration in each of the other groups. A plasma cTnl concentration > 0.25 ng/mL could be used to identify cardiac involvement in dogs with hemangiosarcoma at any site (sensitivity, 78%; specificity, 71 %). A plasma cTnl concentration > 0.25 ng/mL could be used to identify cardiac hemangiosarcoma in dogs with pericardia effusion (sensitivity, 81%; specificity, 100%). CONCLUSIONS AND CLINICAL RELEVANCE: The median plasma cTnl concentration was higher in dogs with cardiac hemangiosarcoma, compared with the median concentration in dogs with hemangiosarcoma at other sites, dogs with other neoplasms, and dogs with pericardial effusion not caused by hemangiosarcoma. The plasma cTnl concentration may be used to identify cardiac involvement in dogs with hemangiosarcoma and to identify cardiac hemangiosarcoma in dogs with pericardial effusion.

Interleukin 6 activity associated with a cardiac lymphoma.

Primary cardiac B-cell lymphoma is an extremely rare heart tumor that may be difficult to diagnose because of nonspecific clinical manifestations. Cardiac myxomas and mediastinal lymphomas show increased levels of serum cytokines, which correlate with symptoms and tumor size. We present a case of an intracardiac large B-cell lymphoma in a 75-year-old woman who had high serum levels of interleukin 6 that decreased after tumor excision. These data suggest a possible correlation between cardiac B lymphoma symptoms and interleukin 6 overproduction.

Serological thymidine kinase 1 is a prognostic factor in oesophageal, cardial and lung carcinomas.

In this study we examine the use of the concentration of thymidine kinase 1 in serum (STK1) as a prognostic factor in routine clinical settings. For this purpose we used sera from patients with oesophageal (n=101) and cardial (n=39) carcinomas and nonsmall-cell lung carcinoma (NSCLC) (n=157). Sera from healthy individuals (n=95) were used as controls. STK1 was analysed by a chemiluminiscence dot blot assay. The mean STK1 concentrations and the STK1 positive rates of the patients with oesophageal and cardial carcinomas and with NSCLC were significantly higher as compared with healthy controls (P=0.01). The mean STK1 value of oesophageal carcinoma patients correlated with T-values (P=0.021) and with stage (P<0.005), but not with grade. The mean STK1 value of cardial carcinoma patients did not correlate with grade. No data on stage and T-values were available for these patients, due to advanced disease. The mean STK1 value of NSCLC patients with squamous cell carcinoma was significantly higher as compared with adenocarcinoma type (P=0.024). The mean STK1 value of the NSCLC patients correlated with clinical grade (P=0.006), T-values (P=0.001), stage (P=0.035) and to size of the tumour (P=0.030). The mean STK1 value and the number of STK1 positive patients were also higher in recurrent NSCLC patients. There was a tendency that stage I-II NSCLC patients with an STK1 level above 2 pmol/l showed a higher frequency of recurrence/death than patients below 1 pmol/l. Our results show that STK1 is a useful marker for prognosis in patients with oesophageal, cardial and lung carcinomas.

[Differentiation of malignant from nonmalignant, inflammatory pericardial effusions with biomarkers]. / Differenzierung von malignen und nichtmalignen, inflammatorischen Perikardergüssen mit Biomarkern.

Disorders of the pericardium are commonly associated with pericardial effusion. Its etiology comprises a broad spectrum of diseases including also malignancies. Pericardiocentesis, pericardioscopy and targeted epicardial biopsy with consecutive pericardial fluid and epicardial biopsy analysis by cytology, molecular biology and immunology establish the underlying etiology in the majority of cases. Of particular therapeutic and prognostic importance is the definite differentiation of malignant pericardial effusion from benign pericardial effusion. Biomarkers for cardiovascular diseases can be divided into biochemical, histological, immunologic, serologic and molecular markers as well as imaging biomarkers. Biomarkers have proven to be useful in the diagnosis, differential diagnosis and prognosis of ischemic heart disease and heart failure. With respect to pericardial disorders, a comprehensive approach combining clinical information, imaging biomarkers, biomarkers of pericardial effusion and analysis of epicardial biopsies often leads to the definite etiologic diagnosis of pericardial effusion. Computed tomography and magnetic resonance imaging allow further characterization of the effusion and, of note, also of the surrounding tissue, which is of particular interest in case of malignancies. Biomarkers of pericardial effusion include biochemical markers, autoantibodies, tumor markers, and cytokines. Analysis of pericardial fluid specific gravity, protein level and lactate dehydrogenase (LDH) separates transudates from exsudates. High adenosine deaminase levels (ADA) and low levels of carcinoembryonic antigen (CEA) in the pericardial effusion are observed in tuberculous pericarditis allowing the differentiation from malignant pericardial effusion. Additional markers, such as interferon and lysozyme, have also been suggested for the diagnosis of tuberculous pericarditis. Tumor markers in pericardial fluid have been used to diagnose malignant pericarditis. CEA levels are significantly higher in malignant than benign effusion. By a cutoff level of CEA > 5 ng/ml the diagnostic sensitivity and specificity are 75% and 100%, respectively, in the diagnosis of malignant pericardial effusion. Further analysis of cytokines and mediators, serologic, immunologic and inflammatory markers may help to understand the pathophysiology of the pericardial disease and provide useful diagnostic information.