Leptomeninges as a site of relapse in locally controlled,diffuse pontine glioma with review of literature

Case report Leptomeningeal involvement in diffuse intrinsic brain stem gliomas is rarely diagnosed clinically and in majority of the instances diagnosed only on postmortem examination. We report two cases of diffuse pontine glioma diagnosed clinicoradiologically and treated with conventional radiotherapy.Observations On follow-up, both patients showed clinical features suggestive of meningeal spread although imaging for pontine tumor showed stable disease. Leptomeningeal disease in the spine was confirmed on imaging and in one case by cerebrospinal fluid examination also. During the follow-up of patients with pontine glioma, the possibility of leptomeningeal involvement must be borne in mind.     

ETV6/RUNX1 fusion at diagnosis and relapse: some prognostic indications

This study was undertaken in order to compare the interphase and metaphase cytogenetics of 28 patients with ETV6/RUNX1 positive acute lymphoblastic leukemia, at diagnosis and relapse. The median time to relapse was 26 months. The significant fusion positive population heterogeneity revealed at interphase by a commercial probe for ETV6/RUNX1 fusion has not been described before. Six diagnostic samples had a single abnormal population; others had up to five each, which differed in the numbers of RUNX1 signals, and in the retention or loss of the second ETV6 signal. In contrast, the number of fusion signals was more constant. At relapse, there were fewer populations; the largest or unique clone was sometimes a re-emergence of a minor, diagnostic one, with a retained copy of ETV6 and the most RUNX1 signals. Abnormal, fusion negative clones were identified in bone marrow samples at extra-medullary relapse. Variant three or four-way translocations, which involved chromosomes 12 and 21, were prominent among the complex rearrangements revealed by metaphase FISH. The frequency of their occurrence at diagnosis and reappearance at relapse, sometimes accompanied by minor clonal evolution, was another new observation. Other recurrent cytogenetic features included a second copy of the fusion signal in six cases, partial duplication of the long arm of the X chromosome in two cases, and trisomy 10 in three cases. In comparing our data with previously reported cases, a picture is beginning to emerge of certain diagnostic features, which may provide circumstantial evidence of an increased risk of relapse.     

A Strain Device Imposing Dynamic and Uniform Equi-Biaxial Strain to Cultured Cells

The objective of this study is to design a new apparatus to allow the control of the magnitude and frequency of dynamic stretch applied uniformly to cells cultured on a silicon elastic membrane. The apparatus is designed to produce equi-biaxial dynamic stretches with area changes ranging from 0% to 55% and frequencies ranging from 0 to 2 Hz. Homogeneous finite strain analysis using triangles of markers was performed to compute the symmetric two-dimensional Lagrangian strain tensor on the membrane. Measurements of strain in both static and dynamic conditions showed that the shear component of the strain tensor (E_rc) was near zero, and that there was no significant difference between radial (E_rr) and circumferential (E_cc) components, indicating the attainment of equi-biaxial strain. Bovine aortic endothelial cells were transiently transfected with a chimeric construct in which the luciferase reporter is driven by TPA-responsive elements (TRE). The transfected cells cultured on the membrane were stretched. The luciferase activity increased significantly only when the cells were stretched by 15% or more in area. Cells in different locations of the membrane showed similar induction of luciferase activities, confirming that strain is uniform and equi-biaxial across the membrane. © 1998 Biomedical Engineering Society. PAC98: 8780+s, 8745-k, 8722-q     

Genotypic and phenotypic characterization of "Streptococcus milleri" group isolates from a Veterans Administration hospital population.

Because identification of the species within the "Streptococcus milleri" group is difficult for the clinical laboratory as the species share overlapping phenotypic characteristics, we wished to confirm biochemical identification with identification by 16S rRNA gene sequence analysis. Ninety-four clinical isolates previously identified as the "Streptococcus milleri" group were reclassified as S. anginosus, S. constellatus, or S. intermedius with the API 20 Strep system (bioMerieux Vikek, Hazelton, Mo.) and the Fluo-card (Key Scientific, Round Rock, Tex.). In addition, we determined the Lancefield group, hemolysis, colony size, colony texture, repetitive extragenic palindromic PCR (rep-PCR) pattern, and cellular fatty acid (CFA) profile (MIDI, Newark, Del.). 16S rRNA gene sequence analysis with 40 selected representative strains showed three distinct groups, with S. constellatus and S. intermedius found to be more closely related to each other than to S. anginosus, and further distinguished a biochemically distinct group of urogenital isolates within the S. anginosus group of isolates. Except for strains unreactive with the Fluo-card (8%), all S. anginosus and S. intermedius strains identified by sequencing were similarly identified by biochemical testing. However, 23% of the selected S. constellatus isolates identified by sequencing (9% of all S. constellatus isolates) would have been identified as S. anginosus or S. intermedius by biochemical tests. Although most S. anginosus strains formed one unique cluster by CFA analysis and most S. constellatus strains showed similar rep-PCR patterns, neither method was sufficiently dependable for identification. Whereas Lancefield group or lactose fermentation did not correspond to sequence or biochemical type, S. constellatus was most likely to be beta-hemolytic and S. intermedius was most likely to have a dry colony type. The most frequent isolate in our population was S. constellatus, followed by S. anginosus. There was an association of S. anginosus with a gastrointestinal or urogenital source, and there was an association of S. constellatus and S. intermedius with both the respiratory tract and upper-body abscesses.     

Influence of cold ischemia time, pretransplant anti-porcine antibodies, and donor/recipient size matching on hyperacute graft rejection after discordant porcine to cynomolgus kidney transplantation

Organs transplanted between phylogenetically disparate species, such as from the pig into the primate, are subject to hyperacute rejection (HAR). This form of xenograft rejection is mediated by preformed natural antibodies and is believed to occur invariably in discordant xenografts thus leading to rapid destruction and complete thrombosis of the graft. Recent data, however, have shown that in the porcine to cynomolgus monkey setting, HAR is not inevitably seen after porcine kidney transplantation. The influence of preoperative antiporcine antibody levels in the recipient, cold ischemia time, and donor organ weight on the onset of HAR was investigated by using unmodified large white pigs (aged 3-12 weeks) as organ donors and adult cynomolgus monkeys (aged 1.5-3.5 years) as recipients. Porcine kidney xenotransplantation was performed in either a non-life-supporting model (n=7) or in a life-supporting model (n=8). In both models, no correlation was found between cold ischemia time and HAR. When preoperative anti-porcine antibody levels were investigated, a significant increase in incidence of HAR was observed in animals with elevated anti-porcine IgM (P<0.05) but not IgG levels (P=NS). Interestingly, although 5 of 12 grafts with an organ weight of less than 50 g underwent HAR, none of three grafts with a donor organ weight of more than 70 g showed signs of HAR. In addition, all three larger grafts showed intraoperative and postoperative urine production, although only in 1 (48 g) of the 12 grafts weighing less than 50 g primary graft function was observed. In one animal, a second porcine kidney (23 g) was successfully transplanted (without HAR) immediately after HAR and subsequent removal of a first porcine kidney (20 g). These results indicate that in the porcine to cynomolgus monkey setting anti-porcine IgM rather than IgG anti-porcine antibody levels seem to be of predominant importance for the induction of HAR. By increasing the donor organ size and weight the frequency of the onset of HAR can be at least reduced. This is most likely due to immunoabsorption of the recipients preformed antibodies in the porcine kidney without lethal damage for the graft.     

Effect of tertiary multileaf collimator (MLC) on foetal dose during three-dimensional conformal radiation therapy (3DCRT) of a brain tumour during pregnancy.

BACKGROUND AND PURPOSE: The aim of this work was to measure the dose to foetus both in vivo and in vitro during three-dimensional conformal radiation therapy (3DCRT) in a pregnant patient with a pituitary adenoma. The study was then extended to assess the components contributing to the foetal dose such as collimator scatter, internal scatter, head leakage, wedge scatter and multileaf collimator (MLC) effect. PATIENTS AND METHODS: A 30-year-old pregnant woman with a non-functioning pituitary macroadenoma was planned for 3DCRT with 6MV X-ray using four equally weighted MLC-shaped non-coplanar wedged portals. In vivo dosimetry was carried out using thermoluminescent (TL) phosphor powder, which was placed at different positions on the patient, corresponding to different locations in the uterus and also at external os. In vitro measurements were also performed on a simulated phantom using the same set-up parameters and beam arrangement to verify the in vivo measured dose. Experiments were carried out to measure the respective contributions of different components towards peripheral dose. RESULTS: In vitro measured dose to foetus was found to be slightly more than that of in vivo measurement with a maximum of 0.044% of the prescribed dose of 45Gy, which corresponded to 0.0199+/-0.0008Gy. Thermoluminescence dosimeter (TLD) kept at the external os of the patient showed a dose of 0.031% of the prescribed dose. Among the various components of the peripheral dose (foetal dose) measured, head leakage was found to be the leading cause contributing 52%, followed by wedge scatter (31%), collimator scatter (14%) and internal scatter (13%). The use of MLC reduced not only the volume of normal brain irradiation as compared to open fields but also the peripheral dose by 10%. CONCLUSION: Radiotherapy of brain tumours during pregnancy poses a unique clinical situation and decisions to deliver radiotherapy should be taken after detailed in vitro and in vivo dosimetric measurements. Our findings suggest that the beam arrangement using 3-4-fields generally used for 3DCRT of brain tumour with MLC for optimal coverage can be employed for pregnant patients even in early trimester. A possible increase in foetal dose from wedges to a large extent can be compensated with the use of MLC.     

Solitary extramedullary plasmacytoma of the premaxilla

Solitary extramedullary plasmacytoma is a rare tumour with radiotherapy playing an important role in its management. This report describes the case history of a man with a solitary extramedullary plasmacytoma at an extremely rare site, the premaxilla, that posed certain diagnostic and therapeutic dilemmas. The patient underwent surgery followed by postoperative radiotherapy. The use of two modalities of treatment for this localized tumour has been justified by briefly reviewing the literature and defining the various prognostic factors. These prognostic factors in turn should guide the treatment of these uncommon tumours.     

High precision conformal radiotherapy employing conservative margins in childhood benign and low-grade brain tumours.

BACKGROUND AND PURPOSE: To report local control and follow up outcome data of high precision conformal radiotherapy in childhood brain tumours. MATERIALS AND METHODS: Between December 1999 and December 2002, 26 children (17 boys and 9 girls, median age 11.5 years) with incompletely excised or recurrent benign and low-grade brain tumours [13 craniopharyngiomas, 11 low-grade gliomas (LGG) and 2 others] were treated with three-dimensional (3D) conformal radiotherapy (CRT) (12 patients) and stereotactic conformal radiotherapy (SCRT) (14 patients). Gross tumour volume (GTV) included neuro-imaging based visible tumour and/or resected tumour bed. Clinical target volume (CTV) consisted of GTV+ 5 mm margin and planning target volume (PTV) consisted of additional 5 mm margin for CRT and 2 mm for SCRT. Treatment was delivered with 3-9 conformal fixed fields to a median dose of 54 Gy/30 fractions. RESULTS: The actuarial 2 and 3 year disease free and overall survival was 96 and 100%, respectively (median follow up: 25 months, range 12-47 months). Radiological follow up available in 25 patients revealed complete response in 1, partial regression in 10, stable disease in 13 and progression in 1 patient (within the CTV). One patient with craniopharyngioma on a routine imaging revealed a mild asymptomatic cyst enlargement, which resolved with conservative management. A patient with chiasmatic glioma developed cystic degeneration and hydrocephalus 9 months after SCRT requiring cyst drainage and placement of a ventriculoperitoneal shunt. CONCLUSION: High-precision conformal techniques delivering irradiation to a computer generated target volume employing 7-10 mm 3D margins beyond the visible tumour and/or resected tumour bed appear to be safe in children with incompletely resected or recurrent benign and low-grade brain tumours, based on these data.