A new liquid embolic material for liver tumors

Purpose: To evaluate the feasibility of a new liquid embolic material, Onyx, for treating liver tumors.Material and Methods: Onyx is a mixture of 6% (w/v) ethylene-vinyl-alcohol copolymer dissolved in anhydrous dimethyl sulfoxide (DMSO) with 28% (w/v) tantalum powder. In addition to 6% Onyx, we also tried 4%, 2% and 1% solutions, prepared by adjusting the amount of DMSO. We used 15 white rabbits with liver tumors created by percutaneous injection of VX2 tumor cells. In 4 groups with 3 rabbits in each, the liver arteries were embolized with 6%, 4%, 2% and 1% Onyx, respectively, and in 3 rabbits DMSO alone was injected. The injections were performed just proximal to the bifurcation of the proper hepatic artery, followed by celiac arteriography. Post mortem, the livers were examined by soft-tissue radiography, and liver-tissue section microscopy.Results: The maximum number of arterial branching points passed by embolic material in either the right or left hepatic arteries was 11, 15 and 16, for 6%, 4% and 2% Onyx, respectively, but was non-measurable for 1% Onyx. Minimum diameters of arteries reached by 6%, 4%, 2% and 1% Onyx in tumorous areas were 40 μm, 35 μm, 20 μm and 10 μm, respectively, and in non-tumorous areas 35 μm, 5 μm, 5 μm and 5 μm, respectively.Conclusion: This study suggests that Onyx may be feasible for treatment of hepatic tumors.     

Preoperative diagnosis of lymph node metastases in gastric cancer by magnetic resonance imaging with ferumoxtran-10

Background Knowledge regarding the presence and location of lymph node metastasis in gastric cancer is essential in deciding on the operative approach. Lymph node metastases have been diagnosed with imaging tests such as computed tomography (CT) and ultrasonography (US); however, the accuracy of such diagnoses, based on size and shape criteria, has not been adequate. Ferumoxtran-10 (Combidex; Advanced Magnetics) is a lymphotropic contrast agent for magnetic resonance imaging (MRI) whose efficacy for the detection of metastatic lymph nodes in various cancers has been reported by several investigators; however, its efficacy for this purpose has not been reported for gastric cancer. We investigated the efficacy of ferumoxtran-10-enhanced MRI for the diagnosis of metastases to lymph nodes in gastric cancer. Methods Seventeen consecutive patients who were diagnosed with a nonearly stage of gastric cancer were enrolled in the study. All the patients were examined by MRI (Signa Horizon 1.5 T; GE Medical; T2*-weighted images) before and 24 h after the intravenous administration of ultrasmall particles of superparamagnetic iron oxide — ferumoxtran-10 (2.6 mg Fe/kg of body weight) — and the presence or absence of metastasis was determined from the enhancement patterns. The imaging results were compared with the corresponding histopathological findings following surgery. Results Of 781 lymph nodes dissected during surgery, the imaging results of 194 nodes could be correlated with their histopathological findings. Fifty-nine lymph nodes from 11 patients had histopathological metastases. In nonaffected normal lymph nodes, we observed dark signal intensity on MRI caused by the diffuse uptake of the contrast medium by macrophages resident in the lymph nodes, which phagocytose the iron oxide particles of ferumoxtran-10. The number of phagocytic macrophages was decreased in metastatic lymph nodes, and they showed various patterns of decreased uptake of ferumoxtran-10. Three enhancement patterns were observed in lymph nodes: (A) lymph nodes with overall dark signal intensity due to the diffuse uptake of ferumoxtran-10; (B) lymph nodes with partial high signal intensity due to partial uptake; and (C) no blackening of lymph nodes due to no uptake of ferumoxtran-10. Patterns (B) and (C) were defined as metastatic. The sensitivity, specificity, positive predictive value, negative predictive value, and overall predictive accuracy of postcontrast MRI were 100% (59/59), 92.6% (125/135), 85.5% (59/69), 100% (125/125), and 94.8% (184/194), respectively. These parameters for predictive accuracy were much superior to these parameters previously evaluated by CT or US. Nodes in the retroperitoneal and paraaortic regions were more readily identified and diagnosed on the MR images than those in the perigastric region. Conclusion The present study confirmed that ferumoxtran-10-enhanced MRI is useful in the diagnosis of metastatic lymph nodes and that the use of this modality will be helpful in treatment decision-making for gastric cancer patients.     

Elevated level of plasma basic fibroblast growth factor in multiple myeloma correlates with increased disease activity.

Recent reports that bone marrow angiogenesis is increased in multiple myeloma prompted us to examine plasma concentrations of angiogenic growth factors and to elucidate their clinical and biological significance. In 45 cases including 36 cases of multiple myeloma and 9 cases of monoclonal gammopathies of undetermined significance (MGUS), plasma concentrations of basic fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF) were evaluated. FGF-2 was significantly elevated in 25 out of 45 (56%) of the patients with multiple myeloma compared with control subjects (median 9.01 pg ml vs. 1.58 pg/ml, P < 0.0001). The 25 cases were all active multiple myeloma, and none of the non-active myeloma and MGUS patients showed a high FGF-2 level. VEGF level was also elevated in 26 out of 45 patients (58%) compared with control subjects (median 42.0 pg/ml vs. 15.8 pg/ml, P < 0.0001 for VEGF). VEGF concentration was high in 20 active myelomas, but also in one non-active myeloma and five MGUS. Elevation of FGF-2 level was associated with beta2-microglobulin level, anemia and bone marrow plasma cell percentage, which represent disease activity. Interestingly, none of five Bence-Jones type myelomas, including four clinically active cases, revealed a high plasma FGF-2 level, while all of them showed a high VEGF level. In all five responders, the plasma FGF-2 levels were significantly decreased after chemotherapy. FGF-2 was immunohistochemically detected in the bone marrow myeloma cells of the patients with high plasma FGF-2 level. We conclude that plasma concentration of FGF-2 can be a useful indicator of disease activity.     

Reperfusion injury in liver transplantation

Reperfusion injury occurring in the transplanted liver is a complex lesion and has been the focus of considerable research over the past decade. This section will review recent major developments in understanding the mechanisms involved and their application to clinical transplantation.     

Effect of epinephrine on GLUT2 protein content in mouse liver

The intraperitoneal administration of epinephrine (EP) to mice caused a significant increase in the blood glucose level and a significant decrease in the liver glycogen content 1 h after its administration at 0.6 mg/kg (blood glucose; p < 0.01, liver glycogen; p < 0.01). The liver type glucose transporter (GLUT2) mRNA expression and protein content from mouse liver significantly increased in the intraperitoneally EP-treated mice when compared to that in normal mice (mRNA; p < 0.01, protein; p < 0.01). These results suggest that the hyperglycemic effect of EP is due, at least in part, to the increase of GLUT2 protein synthesis.     

Elevated levels of soluble interleukin-2 receptor in serum of patients with hematological or non-hematological malignancies

We measured the levels of soluble interleukin-2 receptor (sIL-2R) in the serum of 53 patients with hematological malignancies (14 with acute leukemia, 10 myeloproliferative disorders, 21 non-Hodgkin's lymphoma and 8 multiple myeloma), 40 with non-hematological solid malignancies (24 with lung cancer, 11 digestive system cancer and 5 other cancers) and 95 healthy subjects as a control using an enzyme-linked immunosorbent assay. Both hematological and non-hematological neoplasms showed significantly higher sIL-2R levels than normal subjects (p<0.01). However, compared to solid malignancies, hematological neoplasms displayed a wide range of sIL-2R levels and extremely elevated values of sIL-2R were seen in certain cases. These results seem to suggest that sIL-2R levels may serve as one of non-invasive markers of differential diagnosis for patients with bulky mass lesions between hematological and solid malignancy.