Ethacrynic Acid Inhibits Sphingosylphosphorylcholine-Induced Keratin 8 Phosphorylation and Reorganization via Transglutaminase-2 Inhibition

Sphingosylphosphorylcholine (SPC) is significantly increased in the malicious ascites of tumor patients and induces perinuclear reorganization of keratin 8 (K8) filaments in PANC-1 cells. The reorganization contributes to the viscoelasticity of metastatic cancer cells resulting in increased migration. Recently, we reported that transglutaminase-2 (Tgase-2) is involved in SPC-induced K8 phosphorylation and reorganization. However, effects of Tgase-2 inhibitors on SPC-induced K8 phosphorylation and reorganization were not clearly studied. We found that ethacrynic acid (ECA) concentration-dependently inhibited Tgase-2. Therefore, we examined the effects of ECA on SPC-induced K8 phosphorylation and reorganization. ECA concentration-dependently suppressed the SPC-induced phosphorylation and perinuclear reorganization of K8. ECA also suppressed the SPC-induced migration and invasion. SPC induced JNK activation through Tgase-2 expression and ECA suppressed the activation and expression of JNK in PANC-1 cells. These results suggested that ECA might be useful to control Tgase-2 dependent metastasis of cancer cells such as pancreatic cancer and lung cancers.

Lymph Node Metastases in Thyroid Carcinomas: CT Diagnosis

PURPOSE: To determine the usefulness of CT for diagnosing metastases to primary and secondary echelon lymph nodes (LNs) and to investigate various CT findings of metastatic LNs in thyroid carcinomas. MATERIALS AND METHODS: We retrospectively reviewed the CT and histologic findings in 59 patients with thyroid carcinomas who had undergone thyroidectomy and neck dissection. Primary echelon LNs (Level VI) were removed by central neck dissection in all patients, and in 21, a total of 136 levels of secondary echelon LNs (Level II-V) were excised away by lateral neck dissection. CT criteria of metastatic LNs included large size, significant homogeneous enhancement, calcification, and cystic change. We evaluated the ability of CT to detect primary and secondary echelon LN metastasis and tried to determine which CT features were useful for the diagnosis of LN metastasis. RESULTS: Histologically, LN metastasis was found in 31 (53%) of 59 patients, including 30 with metastasis to primary echelon LNs. Of the 136 levels of secondary echelon LNs resected in 21 patients, 44 were found at histology to harbor metastatic foci. The sensitivities, specificities, positive and negative predictive values, and accuracies of CT in the diagnosis of metastasis to primary and secondary echelon LNs, respectively, were 27% and 93%, 100% and 93%, 100% and 87%, 57% and 97%, and 63% and 93%. While all secondary echelon LNs with at least one of the following CT criteria-large size (n=19), cystic or necrotic change (n=14), or calcifications (n=8)-were histologically proven to be metastatic, six (24%) of 25 such LNs with a sole sign of significant enhancement at CT were found to be due to reactive lymphadenopathy. CONCLUSION: Although CT was unable to detect metastasis to primary echelon LNs, it was useful in the detection of secondary echelon LN involvement. Large size, cystic change, and calcification are considered highly reliable signs of metastatic LNs.

Comparison of Fast FLAIR and Echo-Planar FLAIR Imaging in Cere b ral Lesions

PURPOSE: To evaluate the usefulness of echo-planar FLAIR imaging in various cerebral lesions as compared with fast FLAIR imaging. MATERIALS AND METHODS: We obtained consecutive fast FLAIR and echo-planar FLAIR images in 33patients in whom MR imaging had revealed ischemic infarction (n=11), acute infarction (n=5), brain tumor (n=3), other conditions (n=3) or no abnormality (n=11). On both sets of images, percentage contrast and contrast to noise ratio (CNR) were calculated for white matter-gray matter and white matter-lesion. RESILTS: White matter-gray matter percentage contrast and CNR were lower on echo-planar FLAIR imaging than on fast FLAIR imaging (percentage contrast, 19 +/- 2 % vs 28 +/- 3 %, CNR, 2.77 +/- 0. 5 vs 4.86 +/- 0.7). White matter-lesion percentage contrast on echo-planar FLAIR imaging was similar to or greater than that on fast FLAIR imaging; 75 +/- 12 % vs 45 +/- 11 % in ischemic infarction, 80 +/- 12 % vs 78 +/- 11% in acute infarction, and 121 +/- 25 % vs 102 +/- 15 % for tumors. White matter-lesion CNR was similar on both sets of images: 8.3 +/- 0.9 vs 7.9 +/- 0.8 in ischemic infarction, 11 +/- 1.5 vs 9.5 +/- 1.2 in acute infarction, and 24 +/- 4 vs 27 +/- 3 for tumors. Due to high susceptibility to magnetization, echo-planar FLAIR imaging showed image degradation at the interface of the paranasal sinus and adjacent to the temporal bone. CONCLUSION: Echo-planar FLAIR imaging may be a useful pulse sequence in the diagnosis of various cerebral lesions.

Diagnostic Usefulness of CT-guided Pe rcutaneous Biopsy of the Spine

PURPOSE: To evaluate the diagnostic value of CT-guided percutaneous biopsy of inflammatory and tumorous lesions of the spine and paraspinal soft tissue. MATERIALS AND METHODS: Twenty-three patients underwent CT-guided percutaneous biopsy of the spine and paraspinal soft tissue. Tentative clinical diagnoses determined before biopsy were tuberculous spondylitis (n=5), pyogenic spondylitis (n=4), butterfly vertebra (n=1), old compression fracture (n=3), discitis (n=1), hemangioma (n=1), metastasis (n=7) and multiple myeloma (n=1). Biopsy was performed at the following levels: cervical-(n=1), thoracic-(n=9), and lumbar-spine(n=13). The approach to biopsy of the spine and paraspinal soft tissue lesions was posterolateral (n=11), posterior (n=2), or transpedicular (n=10). RESULTS: Tissue considered adequate by the pathologist involved was obtained in 21 (91%) of the 23 cases. In 19 cases, pathologic findings supported the clinical diagnoses determined before biopsy. In two cases, pathologic and clinical diagnoses differed. Complications such as severe pain, bleeding, infection, neurologic deficit or damage to internal organs were detected neither during or after the procedure. CONCLUSION: CT-guided percutaneous biopsy is a safe and reliable method of obtaining a diagnosis in many cases involving different spinal and paraspinal lesions.

Radiologic evaluation of adriamycin induced toxic cardiomyopathy in childhood leukemia

The cardiomyopathy associated with Adriamycin is frequently fatal and full clinical recovery is uncommon. To evaluate the radiological manifestation and the outcome of Adriamycin induced cardiac toxicity, we retrospectively reviewed the serial chest X-ray films of children treated with Adriamycin. Among 154 children with leukemia, fourteen patients developed clinical and radiologic evidence of congestive heart failure(CHF), Six out of 14(43%) died of CHF within 2 weeks after attack and eight children survived after their acute episodes of CHF, were controlled following digoxin and diuretic therapy. Despite the improving clinical evidence of heart failure, the follow-up chest roentgenograms of these 8 children showed definite cardiomegaly as compared with the pre-treatment chest X-ray. Three children among 8 had minimal cardiomegaly and the remaining five children showed persistent, marked cardiomegaly during the period of 9-25 months of follow up. In summary, when CHF develops during chemotherapy in leukemic children, the possibility of Adriamycin induced cardiac toxicity should be suspected. Our findings showed that persistence of cardiomegaly represented significant cardiomyopathy despite clinical improvement of CHF.

Computed tomographic features of tuberculous arthritis

The sparsity of publication concerning CT findings of tuberculous arthritis prompted authors to retrospectively evaluate 12 patients with tuberculous arthritis for characteristic CT findings. In each patient, the diagnosis of tuberculous arthritis was confirmed by surgery or biopsy. The CT examinations were evaluated by two radiologists retrospectively. Involved joints were the hip joint in seven patients, the sacroiliac joint in three parients, and the shoulder and ankle joint in one patients each. CT features included subchondral bony erosion(12 patients), soft tissue mass in the joint space(nine), widenining of the joint space(eight), ipsilateral muscle atrophy(eight), thickening of the joint capsule(seven), intra-articular effusion(six), soft tissue abscess(five),and bony sclerosis(four). In seven patients with the duration of symptoms less than 1 year, thickening of joint capsule and intra-articular effusion were the predominent findings, while bony sclerosis, gross bone destruction, and soft tissue mass in joint space were seen in five patients with the duration of symptoms longer than 1 year. Our results indicate that CT is useful in the diagnosis of tuberculous arthritis by demonstrating characteristic pathologic changes of the joint space, soft tissue abnormality and bony involvement.