Interferon-alpha2a and 13-cis-retinoic acid with radiation treatment for high-grade glioma.
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Interferon-alpha (IFN-alpha) has been safely given concurrently with radiation therapy (RT) in treating gliomas. As single agents, both IFN-alpha and cis-retinoic acid (CRA) have produced objective tumor regressions in patients with recurrent gliomas. In vitro, IFN-alpha2a and CRA enhance radiation therapy effects on glioblastoma cells more than either agent alone. This trial was conducted to determine the clinical effects of IFN-alpha2a and CRA when given concurrently with radiation therapy to patients with high-grade glioma. Newly diagnosed patients with high-grade glioma received IFN-alpha2a at a dosage of 3 to 6 million IU s.c. 4 times a day for 3 days per week and 1 mg/kg CRA by mouth 4 times a day for 5 days per week during the delivery of partial brain radiation therapy at 180 cGy x 33 fractions for 5 days per week for a total of 59.4 Gy during the 7-week period. Use of the antiepileptic phenytoin was prohibited after observing that the combination of IFN-alpha2a, CRA, and phenytoin was associated with a high rate of dermatologic toxicity not seen in a previous study with concurrent IFN-alpha2a and radiation therapy. Forty patients (26 men and 14 women) with a median age of 60 (range, 19 to 81 years) were enrolled between August 1996 and October 1998. Histopathologic diagnoses were glioblastoma multiforme or grade 4 anaplastic astrocytoma in 36 patients, and grade 3 anaplastic astrocytoma in 4 patients. Only 4 patients (10%) underwent a gross total resection of tumor prior to this therapy; 50% were asymptomatic when treatment was initiated. The planned 7-week course of concurrent therapy was completed by 75% of patients; 30% completed the 16-week course of IFN-alpha and CRA alone. At a median follow-up of 36 months, there were 37 deaths, with a median overall survival of 9.3 months and a 1-year survival rate of 42%. There was no improvement in survival compared with a similar group of 19 patients treated with concurrent IFN-alpha2a and radiation therapy in a previous trial. In the high-risk group of patients in the present study, concurrent treatment with IFN-alpha2a, CRA, and RT was feasible, but was not associated with a better outcome compared with a similar patient population treated with radiation therapy and IFN-alpha2a, or compared with radiation therapy alone in other trials. (+info)
Salivary and lacrimal gland dysfunction (sicca syndrome) after radioiodine therapy.
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Salivary gland dysfunction has been described in patients undergoing radioiodine therapy but associated lacrimal gland dysfunction (sicca syndrome) has never been reported. We conducted a prospective cohort study with follow-up for up to 3 y in a tertiary care university center to determine the prevalence of sicca syndrome in patients after high-dose radioiodine treatment. METHODS: From January 1990 to December 1995, all patients undergoing radioiodine therapy (n = 79) with a standard dose of 925 MBq to 18.5 GBq (25-500 mCi) were interviewed using a standardized questionnaire to determine subjective ocular and oral dryness and were examined for objective lacrimal and salivary gland dysfunction. RESULTS: After radioiodine treatment, 32.9% of the patients reported subjective xerostomia and 25.3% reported subjective xerophthalmia in the first year of follow-up. Xerostomia persisted to the second year of follow-up in 20.3% of cases and was still present >3 y after the last dose of radioiodine in 15.2% of cases. Xerophthalmia persisted to the second year of follow-up in 17.7% of cases and was still present in the third year of follow-up in 13.9% of cases. Severe xerostomia occurred in 4 patients. Reduced salivary and lacrimal gland function was documented in 40 (50.6%) and 14 (17.7%) of the 79 cases, respectively, in the first year of follow-up. Objective xerostomia persisted in 13.9% of cases to the second year of follow-up and was still present in all patients >3 y after the last radioiodine application. Keratoconjunctivitis sicca persisted in 11 patients (13.9%) to the second year of follow-up but was only present in 6 patients (7.6%) >3 y after the last radioiodine application. Additionally, 28/79 patients (35.4%) who had a normal salivary gland scintigraphy previously showed reduced salivary gland function in the third year of follow-up. No significant dependence on cumulative treatment was found for objective xerostomia or xerophthalmia, but doses >11.1 GBq (300 mCi) were related to stage 3 dysfunction on salivary gland scintigraphy. CONCLUSION: Salivary and lacrimal gland dysfunction (sicca syndrome) is relatively frequent after radioiodine therapy. In most cases this is a transient side effect, but in some patients it may persist for a long period or appear late. (+info)
Gastric dysplasia-like epithelial atypia associated with chemoradiotherapy for esophageal cancer: a clinicopathologic and immunohistochemical study of 15 cases.
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Preoperative chemotherapy combined with radiotherapy (chemrad) is a common type of neoadjuvant treatment for esophageal adenocarcinoma or squamous cell carcinoma. The purpose of this study was to describe the clinical, histologic, proliferative (MIB-1), and oncogenetic (p53) features of 15 patients with gastric dysplasia-like epithelial atypical changes associated with preoperative chemrad for esophageal cancer. Two of these cases were initially misinterpreted as dysplasia, which led to partial gastrectomy. The findings were compared with 12 age- and sex-matched patients with known gastric dysplasia. Cases with gastric dysplasia-like epithelial atypia were significantly associated with a flat gross appearance, a patchy distribution, foveolar and gland involvement, surface maturation, an open nuclear chromatin pattern with prominent nucleoli, retention of nuclear polarity, mitoses confined to the pits, lack of atypical mitoses, cytoplasmic hypereosinophila and/or vacuolization, a lack of association with intestinal metaplasia, and finally, irregular glandular microcystic change, in comparison to the dysplasia controls. Furthermore, the study cases showed MIB-1 positivity restricted to the deep foveolar epithelium and an absence of p53 staining in 14 of 15 cases, in contrast to the dysplasia controls, in which MIB-1 stained both the deep and superficial foveolar epithelium and surface epithelium, and p53 was positive in all cases (100%). In summary, a number of histologic and immunohistochemical features may distinguish gastric dysplasia-like epithelial atypia associated with chemrad for esophageal cancer from true dysplasia. Pathologists should be aware of this entity and its histologic and immunohistochemical features to avoid misinterpretation and prevent unnecessary treatment. (+info)
Differential radiosensitivity of hypothalamo-pituitary function in the young adult rat.
(68/1791)
Cranial irradiation in children and adults often results in irreversible hypopituitarism. The earliest and most common endocrine abnormality is GH deficiency, often followed by other pituitary hormone deficits. We investigated whether a similar pattern of progressive hypopituitarism could be reproduced in an animal model. Different doses of cranial irradiation were delivered to the hypothalamo-pituitary region of normal adult male rats, and the effects on their subsequent growth, pituitary weight and hormone contents were studied. Animals received cranial irradiation with 300 kV X-rays at doses of 0, 20, 22 or 24 Gy (n=15 per group) and five animals from each group were killed at 8, 14 or 20 weeks after irradiation. Their anterior pituitary glands were weighed and assayed for GH, LH, TSH, ACTH and prolactin (PRL) content. All three doses of irradiation reduced body weight compared with that in non-irradiated controls and compromised growth between 8 and 20 weeks. Pituitary weight increased between 8 and 20 weeks in control rats, whereas it decreased significantly in the irradiated animals. Irradiation induced time- and dose-dependent changes in pituitary hormone contents. GH and PRL were most sensitive and decreased by more than 90% after irradiation; TSH contents were unaffected 8 weeks after the lowest dose of irradiation, but were reduced at 14 and 20 weeks. LH and ACTH were the slowest to be affected, and only at the greater doses of radiation. Thus progressive multiple pituitary endocrine deficits can be induced differentially in rats by increasing doses of cranial irradiation. This model should prove useful for defining the sites and mechanisms by which cranial irradiation induces neuroendocrine dysfunction. (+info)
Radioprotection to the eye during CT scanning.
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BACKGROUND AND PURPOSE: The lens of the eye is sensitive to radiation. Children undergoing CT of the head and patients undergoing repeated CT scanning of the head are vulnerable to this complication. The purpose of this study was to test the ability of a heavy metal, bismuth, in reducing radiation to the lens of the eye during routine cranial CT. METHODS: Both phantom and human studies were done. Using a standard head-attenuating phantom, scanning was performed with detectors placed over the eye, first without the protectors, and then with shielding by one (1T), two (2T), or three thickness (3T) of bismuth-coated latex. The patient study included 30 patients randomized into one of three groups with eye protection provided by 1T, 2T, or 3T of the bismuth-coated latex. Control measurements were done using thermoluminescent dosimeters over the forehead above each eye. Image artifact from the bismuth shields was assessed. RESULTS: The phantom study demonstrated that the use of bismuth-coated shielding over the eyes decreased radiation dosage by 48.5%, 59.8%, and 65.4% using 1T, 2T, and 3T, respectively. The effect of eye shielding in decreasing radiation dosage to the eye was highly significant for all three thicknesses (P = 2.9 x 10(-81) to 1.9 x 10(-89)). In the patient study, the use of 1T, 2T, and 3T of bismuth-coated latex saved an average radiation dose of 39.6%, 43.5%, and 52.8%, respectively. While the use of shielding was statistically significant in saving radiation for all thicknesses (P = 2.2 x 10(-10) to 1.4 x 10(-21)), there was no statistical difference between 1T, 2T, and 3T of bismuth-coated latex shielding found in patients. However, the trend was for increased radiation savings to the eye with increased thickness of shielding used. A review of all 30 studies showed no significant artifact caused by the eye shielding, regardless of thickness. CONCLUSION: Bismuth-coated latex shielding of the eye during cranial CT is simple to apply, inexpensive, and causes up to a 50% reduction in radiation to the lens of the eye. (+info)
New insights into the role of endothelin-1 in radiation-associated impotence.
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The objectives of this work were to: (1) Determine if prostate and penile tissue levels of endothelin-1 (ET-1) are increased in a rat following pelvic irradiation. (2) Determine if an ETa receptor antagonist (BQ-123) potentiates erectile function in these irradiated animals. Rats were divided into three study groups: control, 1000 cGy and 2000 cGy. The experimental groups received a single dose of radiation to the pelvic region. A time course was established to measure the effects of irradiation on prostate and penile tissue levels of endothelin-1 (ET-1)-like immunoreactivity. The effect of intracavernous injection of BQ-123 (25 microg/30 microl) was evaluated by measuring intracavernous pressure (ICP) following cavernous nerve electrical field stimulation. In the 2000 cGy group, a significant rise in ET-1-like immunoreactivity tissue levels was observed at 20 days. A significant decrease in ICP was recorded in the 1000 and 2000 cGy irradiated rats compared to the control group. Only the 2000 cGy group had a significant improvement in erectile function following BQ-123 administration. A significant improvement was observed 20 min post-administration, lasted 90 min, and was back to pre-administered levels at 120 min. The conclusion made was that radiation-induced impotence in irradiated rats is associated with an increased production of ET-1. Preliminary results are suggestive that ETa receptor antagonist may be of use to reverse such radiation-induced impotence in these irradiated animals. (+info)
Ionising radiation (medical exposure) regulations (Northern Ireland) 2000 and their implications for Accident and Emergency (A&E) doctors in training.
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With the introduction of the Ionising Radiation (Medical Exposure) Regulations (Northern Ireland) 2000 (IRMER) the medical practitioner faces greater accountability when requesting radiological investigations. The referrer (usually a doctor or dentist) must supply sufficient medical data to justify radiation exposure to a patient. These regulations can lead to criminal prosecution if breached. Our objectives were to identify the level of unjustified requests for plain abdominal radiography among A&E doctors and whether there is a statistically significant difference in the justification of request between doctors of differing experience. We reviewed and prepared statistical analysis of 100 A&E request forms for plain abdominal radiography. Royal College of Radiologist Guidelines were used as a "Gold standard" for justification of the investigation. A&E doctors of less than six months experience are at greater risk of breaching these regulations when requesting plain abdominal films, when compared to more experienced doctors. This is a serious issue which should be addressed at undergraduate and pre-registration level in addition to ongoing audit. (+info)
Accurate assessment of patient effective radiation dose and associated detriment risk from radiofrequency catheter ablation procedures.
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BACKGROUND: Radiofrequency (RF) cardiac catheter ablation procedures may require extended fluoroscopic exposure resulting in elevated radiation risk. The aim of the present study was to accurately establish RF ablation radiation risk levels and to provide means for accurate patient risk estimation from studies performed in any electrophysiology laboratory. METHODS AND RESULTS: Fluoroscopy required during cardiac ablation was classified into 4 types identified by beam orientation and irradiated tissue: (1) posteroanterior exposure during catheter advancing from the groin to the heart, (2) posteroanterior heart exposure, (3) left anterior oblique heart exposure, and (4) right anterior oblique heart exposure. The duration of each exposure was monitored in 24 patients undergoing RF cardiac ablation. Dose per minute of fluoroscopy was measured at 15 organs/tissues for each projection with the use of anthropomorphic phantom and thermoluminescence dosimetry. The effective dose rate was 219, 144, 136, and 112 mu/min for groin-to-heart posteroanterior, posteroanterior, left anterior oblique, and right anterior oblique exposure, respectively. A typical ablation procedure results in a total effective dose of 8.3 mSv per hour of fluoroscopy. The average excess of fatal cancers was estimated to be 650 and 480 per million patients undergoing RF ablation requiring 1 hour of fluoroscopy for US and UK populations, respectively. The average risk for genetic defects was determined to be 1 per million births. CONCLUSIONS: Radiation risk from RF cardiac ablation is moderate compared with other complications, but it may highly exceed radiation risk from common radiological procedures. Efforts should be made toward minimization of patient radiation risk from RF ablation procedures. (+info)