Magnetic fluids (MF) have a potential for hyperthermia due to their good power absorption capabilities. Recent in vitro experiments with the so-called 'Magnetic Fluid Hyperthermia (MFH)' have shown that human tumours cells are homogeneously inactivated after AC magnetic field excitation of extracellular MF. The aim of the present study was the evaluation of a high dose MFH on intramuscularly implanted mammary carcinoma of the mouse. The tumours originated from initial in vivo passages of a spontaneous parent tumour. Because of larger variations of tumour growth in this rather primary model, logistic regression of non-averaged volumes was performed for each treatment modality. All growing tumours were randomized 30 days after transplantation (day of treatment) with an overall size distribution between 120-400 mm3. An intratumoural steady state temperature of 47 +/- 1.0 degrees C was maintained for 30 minutes with whole-body AC magnetic fields of 6-12.5 kA/m at 520 kHz. The magnetic fluid was #P6, which is a high biocompatible dextran magnetite. #P6 was given intratumourally (1.5 x 10(-2) mg ferrite/mm3) 20-30 minutes before excitation and was combined with magnetic targeting (50 mT), which yielded a 2.5-fold enhancement of the intratumoural iron concentration. Histological examinations of tumour tissue after intralesional ferrofluid administration alone indicated deep infiltration of the fluid into the carcinoma tissue, but no evidence of tissue damage as compared with untreated controls. In contrast, widespread tumour necrosis was observed after MFH. After application of either dextran or ferrofluid alone (no difference, p = 0.665), tumour growth was slightly delayed in comparison with untreated controls (p < 0.001). In contrast to the good fit of the controls (R = 0.92-0.87), tumour growth after MFH was much more heterogeneous; some tumours showed no evidence for regrowth at 50 days whereas others had grown quite readily. This most probably reflected the critical problem of homogeneity of the intratumoural MF distribution, which was also confirmed qualitatively by Magnetic Resonance Imaging (MRI), heterogeneous pigmentation of MFH treated tumours, and up to 1 degree C differences between temperature probes in the same tumour during AC magnetic field application. However, a quantitative comparison between intratumoural MF-heterogeneity and tumour response could not be performed in this study. Despite these current limitations, the regression analysis of the MFH data yielded a smaller tumour volume of about 1000 mm3 at 50 days growth time in contrast to all three controls. In conclusion, encouraging results have been obtained, which show, that one single high dose MFH is already able to induce local tumour control in many cases within 30 days after treatment. To overcome the uncertainties of intratumoural MF heterogeneity, advanced intralesional application methods are currently under development.
An unusual case of granulocytic sarcoma presenting in a pericardial effusion following trauma and preceding acute myelogenous leukemia (AML) by 8 months is presented. Five additional cases of granulocytic sarcoma preceding leukemia collected by the author are also tabulated. Granulocytic sarcoma in a nonautopsy population of myelogenous leukemic patients was found to be 2.9%. When presenting in an extramedullary site, especially preceding peripheral blood and bone marrow manifestations of leukemia, a misdiagnosis of histiocytic lymphoma may result. In questionable cases, other techniques including the naphthol-ASD-chloroacetate stain, touch imprints, immunoperoxidase stain for lysozyme, and electron micros-copy should be utilized. Although only a small series, the most recent cases have shown inductionhemission and survival characteristics of AML patients without granulocytic sarcoma.
One hundred twenty-six effusion samples from 102 patients were examined by cytology and flow cytometry (FCM). Overall, there was an 84% correlation between cytologic and FCM results. Of the 36 malignant cases determined by cytologic examination, FCM revealed an aneuploid peak in 20 (56%). Image analysis (IA) performed on the malignant cytologic cases with a diploid flow pattern detected two additional aneuploid peaks. In addition, FCM indicated three aneuploid cases in which cytologic characteristics were initially interpreted as benign (false negative). Aneuploidy was therefore detected in 64% of the malignant effusion specimens by FCM and IA. Twenty-three of the total of 24 aneuploid cases detected by FCM were associated with malignancy (predictive value = 96%). The one nonmalignant case was that of hemorrhagic pancreatitis with infected pseudocyst. FCM is an excellent tool when moderate to large numbers of tumor cells are present, whereas use of IA is advantageous for specimens containing smaller numbers of malignant cells because these can be directly analyzed. When an aneuploid peak is present, a diagnosis of malignancy must be suspected, and, if the initial cytologic screen is negative, a critical review of the cytology slides is justified. In those cases with an equivocal atypical cytology report and an abnormal cytometric histogram, additional investigation is warranted. In some malignancies the tumor cells will be diploid (in this study 36%) and neither FCM nor IA will add to tumor detection, leaving cytologic examination as the definitive technique.
A 6-year experience with bone marrow aspirates and biopsies (96 cases) positive for metastatic carcinoma is reviewed. Marrow examination detected secondary carcinoma in 58 cases (60%) despite negative roentgenographic and/or bone scan examinations. Breast carcinoma was the most frequent primary site. The bone marrow biopsy was superior to the aspirate in finding carcinoma (97% vs. 72%). However, in an occasional case, tumor was found only in aspirate preparations. Both procedures should be considered complementary and are recommended in the marrow evaluation of patients with carcinoma.
We report a case of extranodal NK/T-cell lymphoma, nasal type, which is rare in the United States and Europe. It is more prevalent in Asians and Native Americans of Mexico, Central America, and South America. A 30-year-old Southeast Asian man with facial swelling, fever, and unintentional weight loss was found to have leukopenia and thrombocytopenia. He underwent endoscopic sinus surgery, which confirmed extranodal NK/T-cell lymphoma, nasal type, and a blood and bone marrow examination, which was negative for involvement but yielded the diagnosis of alpha-E thalassemia. The patient received chemotherapy, radiotherapy, and a stem cell transplant with 100% engraftment.
A short review is given on current conventional hyperthermia technology. As an alternative, heat can also be generated by a magnetic fluid, which is excited by an externally applied AC magnetic field. In contrast to regional Radiofrequency (RF-) systems, Magnetic Fluid Hyperthermia (MFH) is not limited by electric (E-)field boundary effects and heterogeneous tissue conductivity. MFH may become interesting especially for tumors which currently cannot, or only with highly invasive procedures, be treated with hyperthermia, e.g. bone tumors, intrathoracal tumors, tumors of the base of the scull and of the brain. Current physical and biological results of MFH with carcinoma cells in vitro and experimental tumors in vivo are presented. Deeper insights into the mechanism of magnetic fluid power absorption, the use of Magnetic Resonance Imaging (MRI) for treatment planning, advancements of AC magnetic field applicator technology, intracellular hyperthermia, and options for magnetic fluid conjugates with isotopes and drugs are tasks for future research.
Serologic testing shows that hepatitis C virus (HCV) may have a role in the pathogenesis of B-cell non-Hodgkin lymphomas (B-cell NHLs). We tried to demonstrate HCV RNA sequences in paraffin-embedded tissue from B-cell NHLs by reverse-transcription double polymerase chain reaction (RT-PCR) and Southern blotting. We studied 31 consecutive cases of B-cell NHLs; lymph nodes from 32 patients with diseases other than B-cell NHL were negative controls. Positive-strand HCV RNA was tested with primers for the 5' untranslated region. Replicative negative strand HCV RNA was tested with strand-specific RT-PCR for the 5' untranslated region. Immunohistochemical staining for HCV was done using an antibody to HCV core protein. Positive-strand HCV RNA was detected in 8 patients with B-cell NHL; negative-strand HCV RNA was detected in 6 of these cases, indicating viral replication. All control cases were negative for HCV RNA. Immunohistochemistry showed no staining of lymphoma cells for HCV core proteins in any case. HCV and B-cell NHLs may be associated. RT-PCR on paraffin-embedded lymphoma tissue is an alternative method of testing for HCV. The value of immunohistochemistry could not be ascertained. The exact role of HCV in the pathogenesis of B-cell NHL needs to be studied further.
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