Cardiac sarcoidosis underlies idiopathic dilated cardiomyopathy: importance of mediastinal lymphadenopathy in differential diagnosis.

BACKGROUND: Cardiac sarcoidosis is frequently overlooked or misdiagnosed as idiopathic dilated cardiomyopathy (DCM), primarily because of difficulties in its diagnosis. This is a crucial issue because appropriate therapy with immunosuppressive agents can be initiated if early diagnosis is achieved. METHODS AND RESULTS: Thoracic computed tomography (CT) was retrospectively analyzed in detail with special reference to lymph node swelling (LNS) in the mediastinum of 8 patients diagnosed with idiopathic DCM who underwent left ventriculoplasty (LVP), and were later proven to have active cardiac sarcoidosis by histological evaluation of the resected myocardium. Twenty age-matched patients with idiopathic DCM who also underwent LVP served as controls. On conventional chest radiographs, none of the cardiac sarcoidosis patients exhibited lymph node involvement, including bilateral hilar lymphadenopathy. However, CT demonstrated significant mediastinal LNS in 7 (88%) of them and in only 1 (5%) of the 20 controls. There was a significant difference in the incidence of LNS in the 2 groups (p=0.00005). CONCLUSION: Evaluation of mediastinal lymphadenopathy by CT is an easy and valuable initial screening method for distinguishing cardiac sarcoidosis from idiopathic DCM.     

High-resolution computed tomography patterns and immunopathogenetic findings in drug-induced pneumonitis

We tried to determine whether high-resolution computed tomography (HRCT) patterns correlate with the immunopathogenetic findings and whether they could provide helpful information for predicting the outcomes in non-neoplastic drug-induced pneumonitis. The HRCT images were classified as most suggestive of pneumonitis, diffuse alveolar damage (DAD), non-specific interstitial pneumonia, organizing pneumonia (OP), hypersensitivity pneumonitis, and acute eosinophilic pneumonia (AEP) in 34 patients with non-neoplastic drug-induced pneumonitis. The patients were analyzed for the bronchoalveolar lavage (BAL) cell findings and for the circulating levels of interferon-inducible protein 10 (IP-10) and macrophage-derived chemokine (MDC), which were measured by an enzyme-linked immunosorbent assay. The cumulative dose of corticosteroids received by the patients and the day when they required supplemental oxygen were calculated as outcome markers. There were no differences in the circulating chemokine levels and the BAL cell profiles except for the eosinophil percentages among the HRCT patterns. Most of the cases with pulmonary eosinophilia belonged to the OP and AEP groups, and the circulating MDC levels correlated with BAL eosinophil percentages. We could not find any relationship between the BAL cell profiles or the chemokine levels and the outcome markers. In contrast, the HRCT patterns rather predicted the outcomes because larger cumulative dose of steroids and longer oxygen supply were required for the patients in the DAD and OP groups. In contrast, all patients with AEP recovered without steroid administration. The present study suggests that HRCT does not predict cellular pathophysiology but it may predict the corticosteroid use in non-neoplastic drug-induced pneumonitis.     

Primary high-grade myofibroblastic sarcoma arising from the pericardium.

Primary pericardial sarcomas are very rare. A 62-year-old Japanese man presented with cardiac tamponade. Echocardiography, computed tomography and magnetic resonance imaging revealed massive pericardial effusion and a large tumor in the pericardial cavity, attached to the pericardium of the left ventricular posterolateral free wall. Surgical excision of the tumor was performed and histopathological and immunohistochemical examinations identified high-grade myofibroblastic sarcoma. Because of local recurrence soon after surgery, the patient received adjuvant chemotherapy, including doxorubicin and ifosfamide, and subsequent radiotherapy. As of 6 months after completing radiotherapy, the patient was alive and no disease progression or distant metastases were evident. This may be the first report of primary high-grade myofibroblastic sarcoma arising from the pericardium.     

Anti-myeloma effect of homoharringtonine with concomitant targeting of the myeloma-promoting molecules, Mcl-1, XIAP, and β-catenin

Since a variety of cell intrinsic and extrinsic molecular abnormalities cooperatively promote tumor formation in multiple myeloma (MM), therapeutic approaches that concomitantly target more than one molecule are increasingly attractive. We herein demonstrate the anti-myeloma effect of a cephalotaxus alkaloid, homoharringtonine (HHT), an inhibitor of protein synthesis, through the induction of apoptosis. HHT significantly reduced Mcl-1, a crucial protein involved in myeloma cell survival, in all three myeloma cell lines examined, whereas certain BH3-only proteins, such as Bim, Bik, and Puma, remained unchanged following HHT treatment, and their expression levels depended on the cell type. HHT also reduced the levels of c-FLIP(L/S), activated caspase-8, and induced active truncated-Bid. Thus, HHT-induced apoptosis appears to be mediated via both intrinsic and extrinsic apoptosis pathways, and the resultant imbalance between BH3-only proteins and Mcl-1 may be pivotal for apoptosis by HHT. In addition, HHT treatment resulted in reduced levels of beta-catenin and XIAP proteins, which also contribute to disease progression and resistance to chemotherapy in MM. In combination, HHT enhanced the effects of melphalan, bortezomib, and ABT-737. These results suggest that HHT could constitute an attractive option for MM treatment though its ability to simultaneously target multiple tumor-promoting molecules.     

Successful Transcatheter Embolization of Pseudoaneurysm Associated with Pancreatic Pseudocyst

Hemorrhage into a pancreatic pseudocyst is a rare event, but is the most rapidly lethal complication of chronic pancreatitis. Visceral-vessel aneurysms are an unexpectedly common finding in arteriography of patients with chronic pancreatitis. This case report describes bleeding from an anterior superior pancreaticoduodenal artery aneurysm, caused by chronic pancreatitis. The aneurysm was successfully treated by embolization with a steel coil.