Delineation of brain tumor extent with [11C]L-methionine positron emission tomography: local comparison with stereotactic histopathology.

PURPOSE: Methyl-[11C]L-methionine ([11C]MET) positron emission tomography (PET) in brain tumors reflects amino acid transport and has been shown to be more sensitive than magnetic resonance imaging in stereotactic biopsy planning. It remains unclear whether the increased [11C]MET uptake is limited to solid tumor tissue or even detects infiltrating tumor parts. EXPERIMENTAL DESIGN: In 30 patients, a primary or recurrent brain tumor was suspected on magnetic resonance imaging. Patients were investigated with [11C]MET-PET before stereotactic biopsy. The biopsy trajectories were plotted into the [11C]MET-PET images with a newly designed C-based software program. The exact local [11C]MET uptake was determined within rectangular regions of interest of 4 mm in width and length aligned with the biopsy specimen. Individual histologic specimens were rated for the presence of solid tumor tissue, infiltration area, and nontumorous tissue changes. RESULTS: Receiver operating characteristics analysis demonstrated a sensitivity of 87% and specificity of 89% for the detection of tumor tissue at a threshold of 1.3-fold [11C]MET uptake relative to normal brain tissue. At this threshold, only 13 of 100 tumor positive specimen were false negative mainly in grade 2 astrocytoma. In grade 2 astrocytoma, mean [11C]MET uptake in the infiltration area was significantly higher than in solid tumor tissue (P < 0.003). CONCLUSIONS: [11C]MET-PET detects solid parts of brain tumors, as well as the infiltration area at high sensitivity and specificity. High [11C]MET uptake in infiltrating tumor of astrocytoma WHO grade 2 reflects high activity in this tumor compartment. Molecular imaging, with [11C]MET, will guide improved management of patients with brain tumors.     

HMGA1 protein overexpression in human breast carcinomas: correlation with ErbB2 expression.

We measured, by immunohistochemistry, HMGA1 protein expression in 212 breast tissue specimens: 6 normal samples, 28 hyperplastic lesions (13 with cellular atypia), 11 fibroadenomas, 10 in situ ductal carcinomas, 144 ductal carcinomas, and 13 lobular carcinomas. HMGA1 was not expressed in normal breast tissue; HMGA1 staining was intense in 40% of hyperplastic lesions with cellular atypia and in 60% of ductal carcinomas and weak in fibroadenomas and in hyperplastic lesions without cellular atypia. Because HMGA1 expression was similar among ductal breast carcinomas with different histologic grading, we evaluated the association between HMGA1 expression and that of other markers of breast carcinoma invasion (estrogen and progesterone receptors, Ki-67 antigen, and ErbB2) in 21 cases of grade 3 breast ductal carcinomas and 7 cases of breast lobular carcinomas. We found that HMGA1 expression tended to be associated only with c-erbB-2 expression (Spearman rho: 0.36; P=0.065). Taken together, these results suggest that HMGA1 expression might be a novel indicator for the diagnosis and prognosis of human breast cancer.     

Prognostic value of CD40 in adult soft tissue sarcomas.

PURPOSE: The purpose is to evaluate the expression of CD40, a membrane protein predominantly expressed on B cells, dendritic cells, and macrophages, in a series of adult soft tissue sarcomas and to test its possible prognostic value. EXPERIMENTAL DESIGN: CD40 expression was studied by immunohistochemistry. Correlations with other baseline characteristics of patients and tumors were analyzed with chi(2) test. The prognostic value was studied with univariable and multivariable analysis adjusted by age, sex, tumor size, grade, location, and distant metastases. RESULTS: Eighty-two patients, between January 1994 and May 2001, were analyzed. Membrane or cytoplasmic staining for CD40 protein was absent in 30% of the tumors but present in <10% of cells in 22 (27%), in 10% to 50% in 23 (28%), and in >50% of cells in 12 (15%) tumors. There was no correlation between CD40 expression and age, sex, size, grade, and location of the primary tumor and distant metastases. With 61 patients (74.4%) progressed and 31 (37.8%) dead, CD40 expression was a significant prognostic factor for disease-free and overall survival at univariable and multivariable analysis. Patients with tumors expressing CD40 in >50% of cells had a dramatically unfavorable prognosis with median disease-free and overall survival of 7 and 17 months, respectively, and hazard ratios of relapse and death as compared with patients with CD40-negative tumors of 2.89 (95% confidence interval: 1.26-6.60) and 6.92 (95% confidence interval: 2.18-22.0), respectively. CONCLUSIONS: These data suggest that expression of CD40 protein in >50% of cells might indicate an unfavorable prognosis in adult soft tissue sarcomas.     

Conservative surgery for Stage I ovarian carcinoma in women of childbearing age

Objective To assess the results of a policy of tailored conservative surgical management for young women with stage I ovarian carcinomas.
Design Retrospective study.
Participants Ninety-nine women aged 40 years or younger who underwent either primary surgery in our department or were referred after primary surgery performed elsewhere.
Methods Of the 99 women in our study, 56 underwent fertility-sparing surgery and 43 more radical surgery. Minimal requirements for conservative management were adequate staging and complete information about the therapeutic options. Factors important in the choice of the treatment were, age, wish to preserve fertility, histologic type and grade, and the stage of the tumour.
Results Conservative treatment was conducted in 84% of nulliparous and in 33% of parous women; 62% of grade 1 tumours, 48% of grade 2, and 50% of grade 3 were treated conservatively. With a median follow up of seven years, we observed five recurrences (9%) of carcinoma in women treated conservatively and five (12%) in those treated more radically. Two women (one in each treatment arm) were saved after recurrence. Two recurrences after conservative surgery involved the residual ovary (3.6%). Two women developed borderline tumour in the contralateral ovary and both were treated by surgery.
Conclusion After adequate staging and accurate information is given to the patient, conservative treatment may be safe in some women with early ovarian cancer. The risk of recurrence in the contralateral ovary is low. Conservative surgery may be also considered in some Stage I grade 3 tumours and in some women with stage IC tumours.     

Differences in myocardial and peripheral VEGF and KDR levels after acute ischemia

Background. Recent clinical use of vascular endothelial growth factor (VEGF) in the treatment of both myocardial and peripheral ischemia has suggested the possibility of tissue specific coregulation of VEGF and its receptors (eg, kinase domain region [KDR]). The present study was performed to detect the relationship between VEGF and KDR protein levels after acute myocardial and peripheral ischemia.

Methods. Eleven dogs were divided into two groups: peripheral ischemia (n = 6, ligation of major limb arteries) and myocardial ischemia (n = 5, circumflex artery ligation). Muscle biopsy specimens were taken from the perfusion territories of the occluded circumflex artery and limb arteries 3 hours and 6 hours after ligation. Protein levels were determined using Western blot analysis.

Results. In myocardium, VEGF levels increased on average eightfold from baseline (p < 0.05) both 3 hours and 6 hours after occlusion, whereas myocardial KDR levels dropped by about 60% at 3 hours and 80% at 6 hours (p < 0.05). With limb ischemia, both VEGF and KDR levels were significantly elevated at 3 hours.

Conclusions. In acute ischemia, regulation of VEGF and KDR may be controlled differently in cardiac and skeletal muscle. Myocardial KDR levels showed a significant decrease from baseline compared with a significant rise with peripheral ischemia.     

Dynamic contrast-enhanced MR angiography from the distal aorta to the ankle joint with a step-by-step technique

OBJECTIVE: The aim of this study was to visualize the arteries from the distal aorta to the ankle joint and to determine the accuracy of MR angiography for detecting stenoses and occlusions. SUBJECTS AND METHODS: Twenty-four patients with peripheral arterial occlusive disease underwent digital subtraction angiography and were examined on a 1.5-T MR scanner. The transit time for contrast material was determined with a test bolus injection. A T1-weighted three-dimensional gradient-echo sequence with short TR and TE was used for a dynamic measurement at the level of the iliac arteries, the upper leg, and the lower leg arteries. For each level a single dose of gadolinium was injected into an antecubital vein with an MR power injector. Maximal-intensity-projection reconstructions were calculated after subtraction of the first measurement at each level. Two experienced MR radiologists who were unaware of the digital subtraction angiography results interactively evaluated both the MIP reconstructions and the single slices on a workstation, first independently and then in a consensus interpretation. RESULTS: With digital subtraction angiography, 80 hemodynamically significant stenoses and 39 occlusions were detected. For the stenoses and occlusions, a sensitivity of 100% was found for MR angiography. The specificity for the assessment of stenoses and occlusions was 98% and 94%, respectively, for the iliac arteries; 98% and 94%, respectively, for the upper leg arteries; and 94% and 95%, respectively, for the lower leg arteries. Most false-positive findings of occlusion were due to metal stents present in the iliac (n = 3) and upper leg (n = 4) arteries. CONCLUSION: The MR imaging technique that we used revealed the arteries from the distal aorta to the ankle and proved to be reliable at showing arterial stenoses and occlusions.     

Synergistic antinociceptive interaction between acetaminophen or metamizol and B vitamins in the formalin test

There is evidence that B vitamins produce antinociception in animals. However, potentiation of NSAID‐induced antinociception by B vitamins is unclear. The current study was designed to investigate the antinociceptive interaction between a mixture of B vitamins and either acetaminophen or metamizol. Acetaminophen (56–316 mg/kg), metamizol (32–178 mg/kg), and the mixture of B vitamins (32–178 mg/kg of thiamine, pyridoxine, and cyanocobalamin in a 100:100:1 proportion, respectively) or a combination of each drug with the B vitamins mixture was administered orally to female Wistar rats, and the antinociceptive effect determined in the formalin test. Isobolographic analyses were used to define the nature of the interaction between NSAIDs and B vitamins. Oral administration of either drug produced a dose‐related antinociceptive effect. Isobolographic analyses revealed that both acetaminophen or metamizol and the B vitamins mixture interacted synergistically in the formalin test, suggesting that these two combinations could be useful in treating inflammatory pain states. Drug Dev. Res. 66:286–294, 2006. © 2006 Wiley‐Liss, Inc.     

Albendazole and its derivative JVG9 induce encystation on Giardia intestinalis trophozoites

In the present study, we evaluated the effect of an albendazole (ABZ) derivative JVG9 on cultured Giardia intestinalis. To assess the JVG9 effects, we evaluated the tubulin cytoskeleton by confocal microscopy, and we found that the characteristic staining was modified. The scanning electron microscopy images revealed extremely damaged trophozoites and cyst-like cells. The confocal images revealed that this drug triggered the expression of cyst wall protein 1 and encystation. We also found that at low doses, AL triggered the encystation process too.