Biomedical subjects
Publications and source records attributed to A Trindade.
The 2BN bremsstrahlung cross section is a well-adapted distribution to describe the radiative processes at low-electron kinetic energy (E(k) < 500 keV). In this work a method to implement this distribution in a Monte Carlo generator is developed.
Positron emission mammography (PEM) can offer a non-invasive method for the diagnosis of breast cancer. Metabolic images from PEM using 18F-fluoro-deoxy-glucose, contain unique information not available from conventional morphologic imaging techniques like X-ray radiography. In this work, the concept of Clear-PEM, the system presently developed in the frame of the Crystal Clear Collaboration at CERN, is described. Clear-PEM will be a dedicated scanner, offering better perspectives in terms of position resolution and detection sensitivity.
Although rarely, the usually benign, supratentorial, grade II astrocytic tumour pleomorphic xanthoastrocytoma (PXA) may arise from the cerebellum. A review of the published cases of these PXAs is made including the author's own case of a 40 years-old man with a right cerebellopontine angle tumour, which recurred after a gross total resection. The major clinical and histopathological features of cerebellar PXAs are discussed, and factors playing a role in their biological behaviour, like post-surgical medical treatment, genetics and extent of leptomeningeal seeding are stressed.
In this paper, we present a novel implementation of a dose calculation application, based on the GEANT4 Monte Carlo toolkit. Validation studies were performed with an homogeneous water phantom and an Alderson-Rando anthropomorphic phantom both irradiated with high-energy photon beams produced by a clinical linear accelerator. As input, this tool requires computer tomography images for automatic codification of voxel-based geometries and phase-space distributions to characterize the incident radiation field. Simulation results were compared with ionization chamber, thermoluminescent dosimetry data and commercial treatment planning system calculations. In homogeneous water phantom, overall agreement with measurements were within 1-2%. For anthropomorphic simulated setups (thorax and head irradiation) mean differences between GEANT4 and TLD measurements were less than 2%. Significant differences between GEANT4 and a semi-analytical algorithm implemented in the treatment planning system, were found in low-density regions, such as air cavities with strong electronic disequilibrium.
Monte Carlo (MC) methods are nowadays often used in the field of radiotherapy. Through successive steps, radiation fields are simulated, producing source Phase Space Data (PSD) that enable a dose calculation with good accuracy. Narrow photon beams used in radiosurgery can also be simulated by MC codes. However, the poor efficiency in simulating these narrow photon beams produces PSD whose quality prevents calculating dose with the required accuracy. To overcome this difficulty, a multiple source model was developed that enhances the quality of the reconstructed PSD, reducing also the time and storage capacities. This multiple source model was based on the full MC simulation, performed with the MC code MCNP4C, of the Siemens Mevatron KD2 (6 MV mode) linear accelerator head and additional collimators. The full simulation allowed the characterization of the particles coming from the accelerator head and from the additional collimators that shape the narrow photon beams used in radiosurgery treatments. Eight relevant photon virtual sources were identified from the full characterization analysis. Spatial and energy distributions were stored in histograms for the virtual sources representing the accelerator head components and the additional collimators. The photon directions were calculated for virtual sources representing the accelerator head components whereas, for the virtual sources representing the additional collimators, they were recorded into histograms. All these histograms were included in the MC code, DPM code and using a sampling procedure that reconstructed the PSDs, dose distributions were calculated in a water phantom divided in 20000 voxels of 1 x 1 x 5 mm3. The model accurately calculates dose distributions in the water phantom for all the additional collimators; for depth dose curves, associated errors at 2sigma were lower than 2.5% until a depth of 202.5 mm for all the additional collimators and for profiles at various depths, deviations between measured and calculated values were less than 2.5% or 1 mm.
In radiosurgery narrow photon beams, the depth of maximum dose d(max), in the beam central axis increases as the size of the additional collimator increases. This behavior is the opposite of what is observed in radiotherapy conventional beams. To understand this effect, experimental depth dose curves of the additional collimators were obtained for a Siemens KD2 linear accelerator in 6 MV photon mode and the shift of d(max) varied from 11.0 +/- 0.6 mm for the 5 mm collimator to 14.5 +/- 0.6 mm for the 23 mm collimator. Monte Carlo simulations showed that the photons that had no interactions in the additional collimators, contributing more than 90% to the total dose in water, were responsible for the shift in d(max). Monte Carlo simulations also showed that electrons originated from these photons and contributing to the dose deposit in water in the beam central axis could be divided in two groups: those that deposit energy far away from their point of origin (the point of the first photon collision in water) and those that deposit energy locally (originated at more than one photon collision in water). Applying a simplified model based on the fact that the photons originating Compton electrons (at the first and subsequent collisions) have similar characteristics in air for all the additional collimators, it was shown that these electrons were also responsible for the shift of d(max) in the beam central axis. Finally, it was shown that the changes in the initial gradients of the depth dose curves of the additional collimators were mainly due to electrons originated from the first photon collision in water.
Central neurocytomas are a well-characterized group of neuronal tumors usually arising in the supratentorial ventricular cavities. We describe the anatomical and clinical study of seven of these neoplasms. Patients were in the first four decades of life, and tumors were usually located in one of the lateral ventricles. Surgical resection was subtotal in 6 cases. Light microscopic examination revealed predominantly benign lesions with morphological features similar to the so-called ependymoma of the foramen of Monro, of the oligodendrogliomas, and of the neuroblastomas. Immunohistochemistry and electron microscopy confirmed the diagnosis in each case, showing expression of neuron specific enolase and synaptophysin and containing microtubuli, neurosecretory granules, and presynaptic vesicles. In agreement with the literature, the authors stress the benign behaviour of most of these tumors and the need for systematic immunohistochemical and ultrastructural study. The actual roles of the extent of resection and of postoperative radiotherapy are still a matter of discussion.
The clinical importance of the cerebral aneurismatic lesion in well known. In Portugal we still do not have reliable statistics regarding the occurrence of the subarachnoid hemorrhage, however we can make a comparison through Kassel's and Drake's studies where they refer that annually 28,000 North-Americans suffer from subarachnoid hemorrhage attributed to the rupture of the cerebral aneurysm. This is a clinical situation that needs to be analyzed, more so because if it is not diagnosed and treated in time, it can cause a high level of morbidity and mortality. From 1984 to 1990, the authors studied 208 clinical cases of in-patients at the Santa Maria Hospital who had been diagnosed as having subarachnoid hemorrhage-cerebral aneurysm. They analyzed 172 cranium-encephalic Tomographies and 190 cerebral Angiographies. They found levels that overlapped the series already published with respect to the location of the lesion, dimensions and age groups involved. They tried to relate the presence aneurysm in the willis arterial circle with the occurrence of locoregional anatomic variants that were detected in 51% of the patients with aneurysm of the anterior communicating artery and in 33% of the cases in the posterior communicating artery. The high occurrence of serious forms of tomodensitrometric presentation should also be emphasized. As a matter of fact, 42.6% of the patients studied were grouped in degree IV of the Fisher Scale. This result translates the effort that is still required towards an early clinical and imaging diagnosis of warning hemorrhage to avoid or prevent a catastrophic hemorrhage recurrence.
A case is reported of acquired aphasia in a 15-year-old right-handed boy, secondary to a right occipitotemporal tumour. He had aphasia, alexia, agraphia and visuospatial disturbances, which persisted after partial removal of the neoplasm. 15 days after surgery he had an episode of left focal seizures, after which the aphasia worsened. One month later he developed severe (global) aphasia associated with rostral extension of the tumour. Although crossed aphasia was previously considered common in children, there are few reports with anatomical confirmation. In the authors' own series of 31 children with acquired aphasia this is the only case of crossed aphasia, an incidence similar to that found in adult cases.
Crossed aphasia is reported to be more frequent in traumatic series than in series of patients with other pathologies. A right-handed young man suffered a closed-head trauma and became aphasic and hemiparetic on the left. CT scan revealed a right frontal-lobe hematoma. Neuropsychological examination revealed a fluent aphasia and a Gerstmann syndrome. These signs were compatible with left supramarginal gyrus syndrome. However, the presence of a right frontal-lobe lesion suggested that this patient could be a crossed aphasic. Subsequent EEG study showed a left occipitotemporal focus and a right frontal one. Aphasic signs could thus be due to the left lesion, which was the result of a contrecoup mechanism. Fluent aphasias have been reported in closed-head trauma with right frontal impact. Attention is called for the possible bias of including cases like this in series of traumatic crossed aphasia.
A retrospective study was undertaken to determine the prognostic significance of endodermal sinus tumor (EST) elements in 56 patients with Stage III nonseminatous germ cell tumors of the testes (NSGCTT). The study patients were treated with conventional vinblastine, bleomycin and cisplatinum chemotherapy prior to our recognition of EST as a distinct entity. Twenty-one (37.5%) of the patients had EST elements in their tumors. Nineteen patients had EST in their primary testis tumor, whereas two had EST in metastatic sites only. Prognostic criteria (tumor volume, Dixon-Moore classification and chemotherapy vinblastin and bleomycin [VB] and VB plus cisplatin [VB + P] ) were similar in EST and non-EST patients. Long-term disease-free survival was significantly poorer for patients with Stage III NSGCTT containing EST (38%) compared with those not containing EST (71%) (P = 0.04). All 12 patients with small volume disease (III-B1-III-B2), independent of the presence of EST, are alive and free of disease for more than 2 years. Only 6 of 18 patients (33%) with advanced disease and EST are alive and free of disease, whereas 17 of 26 (65%) of patients with advanced disease not containing EST are alive and free of disease (P = 0.074). The addition of single agent bolus cisplatin to the treatment of patients with advanced disease achieved no improvement in survival. Endodermal sinus tumor must be included in future studies of advanced Stage III NSGCTT as an important prognostic variable.
After curative chemotherapy 58 patients with metastatic germinal tumors and 2 with extragonadal germinal tumors underwent an operation either to confirm a clinical complete response or to remove a residual mass. Biomarker status was converted to negative in all patients. Retroperitoneal lymphadenectomy was done in 22 patients after a complete clinical response was achieved and in 23 after an apparent complete response was achieved except for a residual retroperitoneal mass. Thoracotomy was done for a residual mass in 13 patients, while 2 underwent bilateral thoracotomy. Scarring was found in 25 patients (42 per cent), teratoma in 14 (23 per cent) and active tumor in 17 (28 per cent). One patient with scarring and primary seminoma died of disseminated seminoma, while 1 with primary teratocarcinoma died of disseminated disease, for a false negative rate of 3 per cent. Four patients with a residual mass showed unexpected findings: 2 had granulomas in the lung, 1 had carcinoid of the lung and 1 had retroperitoneal neurofibroma. Thus, there was a 7 per cent incidence of a mass being other than scar, teratoma or residual tumor. There was 1 operative death and 10 deaths of tumor, for an 18 per cent death rate. Of the 17 patients with active tumor 9 responded to salvage chemotherapy with stable complete remission and a minimum followup of 18 months. In addition to the 60 patients the advanced disease in 10 was surgically debulked after failure of chemotherapy and this procedure was followed by salvage chemotherapy. All 10 patients died, with a median survival of 7 months. The lack of responsiveness to chemotherapy was not improved by incomplete removal of tumor.
Sixty-two patients with metastatic hormonal refractory adenocarcinoma of the prostate received a combination of doxorubicin, mitomycin-C, and 5-fluorouracil (DMF). Thirty (48%) of the patients achieved an objective response. Response criteria excluded disease "stabilization" as a manifestation of response. Four clinical prognostic categories were identified: osseous I (OI) had metastatic axial skeletal involvement (23 patients); osseous II (OII) had axial and extremity skeletaL involvement (18 patients); visceral I (VI) had pulmonary metastasis (9 patients); and visceral II (VII) had pulmonary metastasis and involvement of other viscera (12 patients). The 20 responding patients survived a median of 47.5 weeks, whereas the 32 nonresponding patients survived a median of 23.8 weeks (n = 0.002). Response rates were highest among patients with OI (52%) and VI (88%) disease; response rates were lower amont patients with OII (33%) and VII (33%) disease. Responding patients in each clinical category survived longer than nonresponding patients except for those patients with VII disease. The median duration of response for patients with OI disease was 11 months, for OII 9.5 months, for VI patients it was 6.5 months, and VII patients it was 5 months. DMF is an effective treatment of metastatic hormonal refractory prostate cancer, resulting in consistent objective responses. The staging system employed identifies four clinical categories of metastatic prostate cancer and allows for accurate comparison of diet and stratification of study populations.
Partially purified human leukocyte (alpha) interferon was administered i.m. at a dose of 3 x 10(6) units/day to 19 patients with metastatic renal cell carcinoma. Five patients (26%) showed partial responses; two patients (10.5%), objective minor responses; three patients (16%), mixed effects (evidence of biological effect with regression of some lesions but concomitant progression); two patients (10.5%), disease stabilization; and seven patients (37%), progressive disease. All tumor responses were seen in lung or mediastinal metastases. Tumor response significantly correlated with interferon-induced leukopenia and granulocytopenia and with pretreatment performance status. Antibodies to interferon were found in one patient prior to treatment. We concluded that interferon is a potential active antitumor agent in patients with renal cell carcinoma.
Six patients with metastatic mixed germ-cell tumors who had been treated successfully with chemotherapy had recurring solitary enlarging masses. Four had enlarging pulmonary masses and two patients had enlarging abdominal masses. Each had the presumed chemotherapy refractory mass surgically resected and was found to have mature teratoma with absence of malignant histologies. The growth in two patients can be attributed to tense and expansile cysts; the remaining four had firm masses. All patients remain free of disease without further therapy at 5, 13, 14, 25, 66, and 108 months. Early recognition of this previously unreported and unusual clinical circumstance of a benign teratoma to grow after chemotherapy will allow for surgical salvage.
Cytogenic studies were performed on the direct chromosome preparations of the renal cell carcinoma cells and the cultured peripheral blood lymphocytes of a patient with familial renal cell carcinoma. The results revealed a specific, acquired translocations (3p;11p) present in the majority of metaphases of the tumor, indicating that the development of renal cell carcinoma is associated with a deletion in the proximal end of 3p. Renal cell carcinoma is thus the third example--the first two being retinoblastoma and Wilms' tumor--of a chromosomal deletion occurring germinally or somatically in association with a specific tumor. This finding adds further support to the existence of specific human cancer genes.
Twelve patients, with brain metastases from germ cell tumors were treated with combined whole brain irradiation and systemic chemotherapy. Two prognostic categories were identified. Patients with single brain metastases had a mean survival of 29.9 months, while patients with multiple brain lesions had a mean survival of 13.7 months. Four of the six patients with single brain lesions remain alive at 13, 14, 35 and 41 months following the clinical diagnosis of brain metastasis. The improved survival among patients with single lesions can be attributed to the sensitivity to chemotherapy of their tumors. Meningeal carcinomatosis, a previously unreported complication of metastatic germ cell tumor, developed in two patients who were initially treated for single brain metastasis. Both patients developed a clinical picture suggesting meningeal invasion by tumor and both had cytologic evidence in the cerebrospinal fluid of malignant cells.
Twenty-nine patients with local-regional pelvic recurrences of malignant urothelial tumors were treated with combined intra-arterial and iv chemotherapy. 5-FU (1 g/m2) was infused daily for 5 days via bilateral percutaneously placed hypogastric catheters. Doxorubicin (25 mg/m2) was infused iv on Days 1 and 2 and mitomycin (5 mg/m2) was infused iv on Days 3 and 4 of each course. Seventeen patients (58%) demonstrated an objective decrease in the size of the pelvic mass. All four patients with one of the adenocarcinoma variants of malignant urothelial tumors responded to therapy, while the three patients with squamous transformation of a transitional cell carcinoma failed to respond. The median survival of the responding patients was significantly longer (52 weeks) than that of nonresponding patients (28 weeks) (P = 0.002). Patients with initial low-volume pelvic disease demonstrated durable control of local residual tumors, with four of six patients having negative repeat cystoscopic examinations.