Detection and characterization of focal hepatic lesions: mangafodipir vs. superparamagnetic iron oxide-enhanced magnetic resonance imaging

PURPOSE: To compare the mangafodipir-enhanced magnetic resonance (MR) and superparamagnetic iron oxide (SPIO)-enhanced images for their ability to detect and characterize focal hepatic lesions. MATERIALS AND METHODS: Unenhanced, mangafodipir-enhanced, and SPIO-enhanced hepatic MR images obtained from 64 patients were analyzed. A total of 121 hepatic lesions were included: 66 hepatocellular carcinomas (HCCs), 26 metastases, 14 hemangiomas, 5 cysts, 3 cholangiocarcinomas, 4 focal nodular hyperplasias (FNHs), 2 abscesses, and 1 adenoma. Two radiologists independently reviewed the two sets of images in a random order: 1) the unenhanced and mangafodipir-enhanced images (the mangafodipir set) and 2) the unenhanced and SPIO-enhanced images (the SPIO set). This study compared the accuracy of lesion detection, the ability to distinguish between a benign and malignant lesion, and the ability to distinguish between the hepatocellular and nonhepatocellular origins of the lesions using the areas (Az) under the receiver operating characteristic (ROC) curve. RESULTS: The overall accuracy for detecting focal lesions was significantly higher (P < 0.05) with the SPIO set (Az = 0.846 and 0.871 for readers 1 and 2, respectively) than with the mangafodipir set (Az = 0.716 and 0.766). Most of the lesions detected only with the SPIO-enhanced MR images by the readers were small HCCs. For lesions larger than 15 mm, the sensitivities of the two contrast enhancement techniques were similar for both readers. The accuracy of the mangafodipir and SPIO sets in distinguishing between benign and malignant lesions was comparable. The accuracy for distinguishing between the hepatocellular and nonhepatocellular origins of the lesions was significantly higher (P < 0.05) using the mangafodipir set (Az = 0.897 and 0.946) than using the SPIO set (Az = 0.741 and 0.833). CONCLUSION: SPIO- and mangafodipir-enhanced images were comparable for detection of focal hepatic lesions other than small HCCs, which were better detected on the SPIO-enhanced images. Mangafodipir-enhanced images are likely better than the SPIO-enhanced images for distinguishing between focal liver lesions with a hepatocellular or nonhepatocellular origin.     

Analysis of gene expression profiles of hepatocellular carcinomas with regard to 18F-fluorodeoxyglucose uptake pattern on positron emission tomography

Purpose ¹⁸F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan has been found to reflect tumour aggressiveness and prognosis in various types of cancer. In this study, the gene expression profiles of hepatocellular carcinomas (HCCs) were evaluated to determine whether HCCs with high ¹⁸F-FDG uptake have more aggressive biological potential than those with low uptake.Methods Surgical specimens were obtained from ten patients with HCC (six males and four females, age range 38–68 years). The tumour samples were divided into two groups based on the ¹⁸F-FDG PET scan findings: high ¹⁸F-FDG uptake (n=4) and low ¹⁸F-FDG uptake (n=6).Results The pathological tumour grade was closely correlated with the ¹⁸F-FDG uptake pattern: HCCs with high ¹⁸F-FDG uptake were pathologically Edmondson-Steiner grade III, while those with low uptake were either grade II or grade II with a focal area of grade III. The total RNA was extracted from the frozen tissues of all HCCs (n=10) and adjacent non-cancerous tissue (n=7). The gene expression profiles were evaluated using an oligoDNA microarray. The HCCs with high ¹⁸F-FDG uptake showed increased expression of 11 genes—including vascular cell adhesion molecule-1, vinexin beta and core 1 UDP-galactose:N-acetylgalactosamine-alpha-R-beta 1,3-galactosyltransferase and the natural killer cell inhibitory receptor—compared to those with low uptake (p<0.005). Nine genes, including regulator of mitotic spindle assembly 1, grb2-related adaptor protein and beta-1,3-n-acetylglucosaminyltransferase, were repressed.Conclusion Gene expression is closely related to cell survival, cell-to-cell adhesion or cell spreading; therefore, HCCs with high ¹⁸F-FDG uptake appear to have more aggressive biological properties than those with low uptake.     

Prognosis of thymic epithelial tumors according to the new World Health Organization histologic classification

Background

The aim of this study was to document the prognosis of thymic epithelial tumors (TETs) according to new the World Health Organization (WHO) classification.

Methods

We retrospectively reviewed 150 patients with TETs that were confirmed pathologically during 11 years (from 1992 to 2002) in Severance Hospital, Seoul, Korea.

Results

TETs were classified as type A, AB, B1, B2, B3, or C, tumors and these represented 7 (4.7%), 26 (17.3%), 13 (8.7%), 45 (30.0%), 26 (17.3%), and 33 (22.0%) cases, and the 5-year survival rates were 100%, 93%, 89%, 82%, 71%, and 23%, respectively. Their Masaoka stages were I, II, III, IVa, and IVb, with 53 (35.3%), 39 (26.0%), 20 (13.3%), 22 (14.7%), and 16 (10.7%) cases. Tumor invasiveness, recurrence, completeness of resection, and tumor-related death were more frequent in types AB, B2, B3, and C than in types A and B1. Multivariate analysis showed that Masaoka stage (p < 0.001) and the WHO classification (p = 0.019) were significant independent prognostic factors.

Conclusions

The WHO classification is associated with tumor invasiveness, recurrence, completeness of resection, and tumor-related death, and has good correlation with Masaoka stage. The WHO histologic subtypes are an independently significant prognostic factor with respect to survival in our multivariate analysis. Types AB, B2, B3, and C showed invasive behaviors and R1 or R2 resections were frequently performed. Postoperative adjuvant radiotherapy was effective, but long-term follow-up is recommended because of decreased survival after 5 years following operation. The WHO classification may be helpful in clinical practice for the assessment and treatment of TET patients.     

Early biliary complications of laparoscopic cholecystectomy: evaluation on T2-weighted MR cholangiography in conjunction with mangafodipir trisodium-enhanced 3D T1-weighted MR cholangiography

OBJECTIVE: Our aim was to assess preliminary experience with combined conventional T2-weighted and mangafodipir trisodium (MnDPDP)-enhanced T1-weighted MR cholangiography in evaluating early biliary complications of laparoscopic cholecystectomy. SUBJECTS AND METHODS: Conventional heavily T2-weighted MR cholangiography with MnDPDP-enhanced T1-weighted MR cholangiography and ERCP were performed in seven patients with high clinical suspicion of biliary complications after laparoscopic cholecystectomy. The final diagnoses of complications were classified according to the presence and degree of bile duct injury, bile leakage, and retained stones. RESULTS: The diagnoses on MR cholangiography were as follows: complete transection and occlusion of the common bile duct with bile leakage (n = 3), partial strictures of the common bile duct with bile leakage (n = 1), cystic duct leakage (n = 1), partial ligation of an aberrant right hepatic duct (n = 1), and hemorrhage without biliary complication (n = 1). The final diagnoses at surgery (n = 2) and ERCP (n = 5) were as follows: complete transection and occlusion of the common bile duct with bile leakage (n = 2), partial strictures of the common bile duct with bile leakage (n = 2), cystic duct leakage (n = 1), partial ligation of an aberrant right hepatic duct (n = 1), and hemorrhage without biliary complication (n = 1). MR cholangiography accurately yielded the same findings as the final diagnoses, except in one case with partial stricture of the bile duct with bile leakage (overdiagnosed as complete occlusion on MR cholangiography). CONCLUSION: Combined conventional T2-weighted and MnDPDP-enhanced T1-weighted MR cholangiography may eliminate the use of other studies for the imaging of biliary complications after cholecystectomy if this preliminary data can be verified in a larger study.     

Percutaneous sclerotherapy of lymphangiomas with acetic acid

PURPOSE: To evaluate the efficacy of percutaneous image-guided sclerotherapy of lymphangiomas with use of acetic acid. MATERIALS AND METHODS: Twelve patients with lymphangiomas were treated with acetic acid as the sclerosant. There were eight male patients and four female patients, ranging in age from 1 to 29 years (mean, 11 years). The lymphangiomas were located at the neck (n = 5), upper extremity (n = 3), axilla (n = 1), cervicomediastinum (n = 1), anterior chest wall (n = 1), and retroperitoneum (n = 1). Two patients had recurrent lymphangiomas after surgery and two patients had undergone failed sclerotherapy with another sclerosant. The acetic acid used as the sclerosant was 40%-50% in concentration, and the amounts used ranged from 2 mL to 70 mL (mean, 11.3 mL), which was equivalent to 4.6%-50% (mean, 30.6%) of the aspirated lymphatics. All procedures were performed under ultrasonographic and fluoroscopic guidance. The sclerosant was removed after sclerotherapy. All patients except one underwent one treatment session. RESULTS: Complete resolution of the lymphangioma was achieved in eight patients (66.7%), good resolution (>50% reduction) was achieved in three (25.0%), and poor resolution (<50% reduction) was seen in one (8.3%). Complications encountered included pneumonitis adjacent to the lymphangioma (n = 1), pain (n = 2), hematuria (n = 1), and tingling sensation in the forearm (n = 1). CONCLUSION: Percutaneous sclerotherapy of the lymphangiomas with use of acetic acid is an effective method without serious complications.     

Glycogen-rich clear cell mammary malignant myoepithelioma

Primary clear cell tumors of the breast are uncommon and often present a diagnostic challenge. We describe an extremely rare case of glycogen-rich clear cell malignant myoepithelioma in a 43-year-old woman. Histologically, this tumor is composed of clear cells with abundant cytoplasmic glycogen particles. Immunohistochemically, these tumor cells show co-expression of vimentin, smooth muscle actin, epithelial membrane antigen, S-100 protein, and cytokeratin as evidence of myoepithelial cell tumor. The pathological staging of the patient is IIB (pT3N0M0) and the nuclear grading is 2. The patient demonstrated no evidence of recurrence or metastasis over a period of 42 months. We suggest that glycogen-rich clear cell malignant myoepithelioma be included in the histological differential diagnosis of clear cell tumors of the breast.     

A retrospective study of the clinical outcomes and significant variables in the surgical treatment of temporal lobe tumor associated with intractable seizures

A retrospective study was performed assessing the preoperative evaluation, and the postoperative outcomes in 35 patients with a temporal lobe tumor with intractable seizures who were treated by our neurosurgery service between October 1995 and December 1999. The mean age of the patients at the time of surgery was 27.9 years. The period of follow-up after surgery was a mean of 33.0 months. Of the study group of 35 patients, 27 (77.1%) became completely seizure free after surgery (class I), and 2 patients (5.7%) had no more than 2 seizures per year (class II). Worthwhile seizure control was achieved in 29 patients (82.8%). There was a statistical significance between the extent of tumor resection and favorable seizure outcome (p = 0.014). The most frequent histopathological diagnoses were classic epilepsy-associated ganglioglioma in 16 (45.7%) patients and low-grade astrocytoma in 10 (28.6%) patients. Complete resection of tumor was the most significant factor in obtaining a favorable seizure outcome.     

Soluble Polyimide Containing a Photoreactive 2‐Styrylpyridine Derivative as the Side Group: Synthesis and Characterization

Summary: We describe the synthesis and characterization of a soluble photoreactive polyimide. The precursor of the polyimide was prepared from 2,2′‐bis{4‐(3,4‐dicarboxyphenoxy)phenyl}hexafluoropropane dianhydride and 3,3′‐hydroxy‐4,4′‐diaminobiphenyl; the photoreactive polyimide was then prepared by the polymer reaction of the hydroxyl groups in the precursor polymer with 2‐{2‐[4‐(6‐hydroxyhexyloxy)phenyl]ethenyl}pyridine as a photoreactive 2‐styrylpyridine derivative. The photoreactive polymer and its precursor polymer were soluble in various polar organic solvents, and their thin flexible films were easily formed by solution casting. The initial decomposition temperatures of the former and latter polymers were 350 and 470 °C, respectively. The extent of the photochemical reaction of the photoreactive polymer film was measured to be 65.8% at an exposure energy of 1.5 J/cm². The transmittance of the film was found to be approximately 92% at room temperature and approximately 85% at 200 °C. These results suggest that the polyimide is a photosensitive polymer with good photosensitivity and high optical transparency. The dichroic ratios of the film were between 0.023 and 0.025 when exposed to linearly polarized UV light (LPUVL). The liquid crystal in the film cell was perpendicularly oriented to the electric vector of LPUVL.

Polar diagrams of LC cells fabricated from polyimide 6FBPA‐HAB‐SP6 film after irradiation with LPUVL.     

Absorbable microparticulate cation exchanger for immunotherapeutic delivery

An absorbable microparticulate cation exchanger was synthesized as a versatile carrier for biologically active proteins. In this work, acid-terminated polyglycolide (or polyglycolic acid) microparticulates (PG-MP) were surface modified for either sustained release of cytokines or as a platform for immunomodulation. The intended goal was to achieve in situ recruitment/maturation of dendritic cells and activation of T cells for tumor immunotherapy. PG-MP were prepared with a volume weighted mean diameter of 7.02 micro (range: 2.09-14.58 micro). Accessible carboxylic acid groups were determined to be 0.3 mmol/g with a corresponding zeta potential of -21.87 mV in phosphate-buffered saline. Under low magnification, scanning electron microscopy (SEM) revealed a highly textured surface due to processing from repetitive jet milling. However, a moderately porous architecture was noted at higher magnification. Electron spectroscopy for chemical analysis was used to characterize the PG-MP surface before and after adsorption of human granulocyte-macrophage colony stimulating factor (GM-CSF). Adsorption of GM-CSF on PG-MP (PG-GMCSF) resulted in a modest increase in the surface atomic concentration of nitrogen (0.97%). Pretreating the surface with poly-L-lysine (PG/Lys-GMCSF) prior to adding GM-CSF produced a nearly threefold increase in the surface nitrogen concentration (4.20% compared to 1.47%). This manipulation not only increased loading content, but also prolonged the release of GM-CSF released from 6 days to 26 days. ESCA on the post-release PG-MP samples (PG-GMCSF and PG/Lys-GMCSF) revealed a similar residual surface nitrogen concentration (2.26% vs. 2.35%). The observation was consistent with irreversibly adsorbed GM-CSF. It is postulated that irreversibly bound GM-CSF is released over time as a function of microparticulate degradation. Biological activity of released GM-CSF was confirmed by the proliferation of a GM-CSF-dependent cell line (TF-1) in the presence of microparticulates. PG-MP mediated activation of T cells was achieved through irreversible adsorption of either antimouse cd3 plus antimouse cd28 monoclonal antibodies (alpha-cd3/cd28-MP) or antihuman CD3 plus antihuman CD28 monoclonal antibodies (alpha-CD3/CD28-MP) on PG-MP. Irreversibly adsorbed antibodies were capable of activating both resting mouse and human T cells. Intracellular flow cytometry on mouse T cells revealed that nearly 50% of the activated cells produced interferon-gamma (IFN-gamma). This was consistent with a TH-1 or cell-mediated response. In vivo efficacy was evaluated in a mouse flank tumor model showing a significant antitumor effect both alone and in combination. Combination therapy was most effective at preventing tumor implantation (8/8 mice) and was able induce tumor regression (4/7 mice) and/or stable disease (3/7 mice) in a regression model. In these studies, immunohistochemistry was used to confirm local recruitment of dendritic cells. In conclusion, the PG-MP represents a novel absorbable cation exchanger that can be readily manipulated to deliver biologically active proteins for immunotherapy.