Rare case of epithelioid hemangioendothelioma in the right innominate vein-An innovative diagnostic approach.

BACKGROUND AND AIMS: Epithelioid hemangioendothelioma is a rare malignant vascular tumor with limited literature. AIMS: We reported an innovative endovascular biopsy of the right innominate vein tumor. MATERIALS AND METHODS: Endovascular suction thrombectomy was performed with multipurpose catheter and constant negative pressure under fluoroscopic guidance. RESULTS: Epithelioid hemangioendothelioma was diagnosed preoperatively and a complete margin-free tumor resection with patch repair of the right innominate vein was achieved via sternotomy. DISCUSSION: Preoperatively diagnosis is usually not available due to lesions' location. Identifying malignant vascular tumors becomes valuable to guide the surgical treatment. CONCLUSIONS: In this case report, this innovative endovascular approach led to a rare preoperative diagnosis of EHE and subsequent margin-free resection.

Serum syndecan-1, hyaluronan and thrombomodulin levels in patients with lupus nephritis.

OBJECTIVES: We investigated circulating syndecan-1, HA and thrombomodulin levels in patients with biopsy-proven Class III/IV ± V LN and their clinico-pathological associations. Patients with non-renal SLE or non-lupus chronic kidney disease, and healthy subjects served as controls. METHODS: Serum syndecan-1, HA and thrombomodulin levels were determined by ELISAs. RESULTS: Syndecan-1, HA and thrombomodulin levels were significantly higher during active LN compared with remission (P < 0.01, for all), and correlated with the level of proteinuria, estimated glomerular filtration rate, anti-dsDNA antibodies, complement 3 and serum creatinine. Longitudinal studies showed that syndecan-1 and thrombomodulin levels increased prior to clinical renal flare by 3.6 months, while HA level increased at the time of nephritic flare, and the levels decreased in parallel with treatment response. Receiver operating characteristic curve analysis showed that syndecan-1 and thrombomodulin levels distinguished patients with active LN from healthy subjects, LN patients in remission, patients with active non-renal lupus and patients with non-lupus chronic kidney disease (receiver operating characteristic area under curve of 0.98, 0.91, 0.82 and 0.95, respectively, for syndecan-1; and area under curve of 1.00, 0.84, 0.97 and 0.79, respectively, for thrombomodulin). HA level distinguished active LN from healthy subjects, LN patients in remission and non-lupus chronic kidney disease (receiver operating characteristic area under curve of 0.82, 0.71 and 0.90, respectively) but did not distinguish between renal vs non-renal lupus. Syndecan-1 and thrombomodulin levels correlated with the severity of interstitial inflammation, while HA level correlated with chronicity grading in kidney biopsies of active LN. CONCLUSION: Our findings suggest potential utility of serum syndecan-1, thrombomodulin and HA levels in clinical management, and their potential contribution to LN pathogenesis.

Adenofibromatous Solitary Fibrous Tumor: An Unusual Morphologic Variant Occurring in the Sinonasal Tract.

BACKGROUND: Solitary fibrous tumor can exhibit a broad morphologic spectrum, such as presence of epithelioid tumor cells, adipose cells and multinucleated giant cells. This report describes an unusual morphologic variant characterized by adenofibromatous features, all occurring in the sinonasal region. METHODS: Four cases of the adenofibromatous variant of solitary fibrous tumor were retrieved from the surgical pathology and consultation files in Queen Elizabeth Hospital, Hong Kong. Histologic examination, immunohistochemical study and reverse-transcription polymerase chain reaction (RT-PCR) were performed. RESULTS: The patients were adults who presented with an obstructive mass of the nasal septum, nasal cavity or nasolacrimal sac. Histologic examination showed a circumscribed biphasic tumor with intermingling of glandular structures and spindle cells, reminiscent of mammary fibroadenoma. Bland-looking spindle cells formed short, irregularly oriented fascicles, admixed with variable amount of collagen fibers. The glandular component comprised ducts and seromucinous acini with a lobular architecture, indicating that it represented exuberant hyperplasia of indigenous glands rather than part of the neoplastic process. Demonstration of CD34 and STAT6 immunoreactivity in the spindle cells and NAB2::STAT6 gene fusion by polymerase chain reaction supports the diagnosis of solitary fibrous tumor. CONCLUSION: This study reports four cases of sinonasal solitary fibrous tumor with adenofibromatous features, furthermore expanding the morphologic spectrum of this tumor.

Long-term outcomes of add-on direct renin inhibition in igA nephropathy: a propensity score-matched cohort study.

INTRODUCTION: The long-term clinical outcomes in biopsy proven IgAN patients treated with aliskiren on top of a maximally tolerated dose of ACEi/ARB remain unknown. METHODS: Patients with IgAN treated with a direct renin inhibitor and ACEi/ARB for at least 6 months were compared with a 1:1 propensityscore-matched cohort (including MEST-C score and the 12-months pre-exposure slope of eGFR matching) who received ACEi/ARB without aliskiren exposure to compute the hazard ratio of reaching the primary endpoint of a composite of 40% reduction in eGFR, initiation of KRT and all-cause mortality. Secondary outcome measures included changes in mean UPCR, blood pressure, eGFR, incidence of hyperkalemia and other adverse events during follow-up. RESULTS: After a median follow-up of 2.5 years, 8/36 (22.2%) aliskiren-treated patients and 6/36 (16.7%) control patients reached the primary composite outcome (HR = 1.60; 95% CI 0.52-4.88; P = 0.412). Aliskiren treatment increased the risk of ≥ 40% eGFR decline (HR = 1.60; 95% CI 0.52-4.88; P = 0.412), and hyperkalemia (HR = 8.60; 95% CI 0.99-73.64; P = 0.050). At 10.8 years, renal composite outcome was reached in 69.4% vs 58.3% (HR = 2.16; 95% CI 1.18-3.98; P = 0.013) of patients in the aliskiren and control groups, respectively. The mean UPCR reduction between treatment and control was not statistically different (52.7% vs 42.5%; 95% CI 0.63-2.35; P = 0.556). The mean intergroup difference in eGFR decline over 60 months was 7.75 ± 3.95 ml/min/1.73 m2 greater in the aliskiren group (12.83 vs 5.08; 95% CI - 0.17 to 15.66; P = 0.055). CONCLUSION: Among patients with IgAN, add-on aliskiren was associated with less favorable long-term kidney outcomes despite an initial anti-proteinuric effect.

Suppression of ACADM-Mediated Fatty Acid Oxidation Promotes Hepatocellular Carcinoma via Aberrant CAV1/SREBP1 Signaling.

Lipid accumulation exacerbates tumor development, as it fuels the proliferative growth of cancer cells. The role of medium-chain acyl-CoA dehydrogenase (ACADM), an enzyme that catalyzes the first step of mitochondrial fatty acid oxidation, in tumor biology remains elusive. Therefore, investigating its mode of dysregulation can shed light on metabolic dependencies in cancer development. In hepatocellular carcinoma (HCC), ACADM was significantly underexpressed, correlating with several aggressive clinicopathologic features observed in patients. Functionally, suppression of ACADM promoted HCC cell motility with elevated triglyceride, phospholipid, and cellular lipid droplet levels, indicating the tumor suppressive ability of ACADM in HCC. Sterol regulatory element-binding protein-1 (SREBP1) was identified as a negative transcriptional regulator of ACADM. Subsequently, high levels of caveolin-1 (CAV1) were observed to inhibit fatty acid oxidation, which revealed its role in regulating lipid metabolism. CAV1 expression negatively correlated with ACADM and its upregulation enhanced nuclear accumulation of SREBP1, resulting in suppressed ACADM activity and contributing to increased HCC cell aggressiveness. Administration of an SREBP1 inhibitor in combination with sorafenib elicited a synergistic antitumor effect and significantly reduced HCC tumor growth in vivo. These findings indicate that deregulation of fatty acid oxidation mediated by the CAV1/SREBP1/ACADM axis results in HCC progression, which implicates targeting fatty acid metabolism to improve HCC treatment. SIGNIFICANCE: This study identifies tumor suppressive effects of ACADM in hepatocellular carcinoma and suggests promotion of ß-oxidation to diminish fatty acid availability to cancer cells could be used as a therapeutic strategy.