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Biomedical subjects

A Widmark

Publications and source records attributed to A Widmark.

At least 19 recordsLinked to original sources

Measurements of finger doses in x-ray guided surgery, nuclear medicine and research.

The Norwegian Radiation Protection Authority has performed measurements of finger doses to nuclear medicine staff exposed to 99Tc(m), researchers handling 32P, surgeons performing X-ray guided orthopaedic surgery and surgeons and radiologists performing X-ray guided endovascular treatment of abdominal aortic aneurysms (AAA). Calibrations were done with X-ray qualities N-40, N-60 and N-300 and with the beta source 90Sr + 90Y. Annual doses were estimated for the nuclear medicine staff and the orthopaedic surgeons. The mean annual finger dose to nuclear medicine staff exposed to 99Tc(m) was estimated to be 18.8 mSv, and the mean annual finger dose to surgeons performing X-ray guided orthopaedic surgery was 13.7 mSv. The surgeons and radiologists performing X-ray guided endovascular treatment of AAA received a mean finger dose of 0.35 mSv per treatment. The majority of researchers handling 32P received no finger dose at all, and the maximum reading was 1.65 mSv. All occupational groups received finger doses well below the annual finger dose limit of 500 mSv.

Aortic Aneurysm, Abdominal↗

Does prophylactic breast irradiation prevent antiandrogen-induced gynecomastia? Evaluation of 253 patients in the randomized Scandinavian trial SPCG-7/SFUO-3.

OBJECTIVES: To examine the development of antiandrogen-induced gynecomastia and breast tenderness in the first 253 patients in a randomized Scandinavian trial (SPCG-7/SFUO-3) with a 12-month complete follow-up evaluation performed by both doctors and patients. METHODS: In this study, the treating doctor and patient decided whether prophylactic irradiation (RT) of the breast should be given to prevent antiandrogen-induced gynecomastia. At each visit, the doctor evaluated the occurrence of gynecomastia and breast tenderness. Questions about gynecomastia and breast tenderness were also included in the study quality-of-life questionnaire (Prostate Cancer Symptom Scale). RESULTS: Mammary RT with mostly single fraction (12 to 15 Gy) electrons was given to 174 (69%) of the 253 evaluated patients. At the 1-year follow-up visit, the doctor evaluations indicated some form of gynecomastia in 71% and 28% (P <0.001) of the nonirradiated (no-RT) and irradiated (RT) patients, respectively. The patient evaluations at 1 year showed some form of breast enlargement in 78% and 44% (P <0.001) of the no-RT and RT patients, respectively. The doctors reported some form of breast tenderness at 1 year in 75% and 43% (P <0.001) of the no-RT and RT patients, respectively. The patient evaluations of breast tenderness show an expected significant increase in the RT arm at the 3-month follow-up, which was probably due to skin reactions. At 1 year, significantly more patients who marked "very much" on the Prostate Cancer Symptom Scale were seen in the no-RT group. A weak correlation between the doctors' and patients' detection of breast problems was observed. CONCLUSIONS: The results show that, with high significance, prophylactic RT of the breast decreases the risk of antiandrogen-induced gynecomastia and breast tenderness.

Androgen Antagonists↗

Treatment of patients with clinical T3 prostate cancer.

OBJECTIVE: To describe and evaluate treatment alternatives for patients with clinical T3 prostate cancer. MATERIAL AND METHODS: Literature review with main focus on recent studies in order to include the impact of prostate specific antigen (PSA). The possibility of using neoadjuvant/adjuvant hormonal therapy in combination with surgery or radiation was assessed. Results were related to life expectancy, tumour grade and serum PSA. RESULTS: M and N-staging is mandatory before treatment with curative intent. Watchful waiting is an option for selected patients but early hormonal therapy seems to offer some survival advantages. Standard 65-70Gy external beam radiation is not sufficient for these patients with extracapsular disease but better results are obtained with dose-escalation (beyond 70Gy) and/or adjuvant hormonal therapy. Radical prostatectomy may be an option for patients with long life expectancy and "early" tumours, neoadjuvant hormonal withdrawal is of no proven value. CONCLUSIONS: Patients with a long life expectancy should not be denied treatment with curative intent solely based on the finding of extracapsular disease.

Antineoplastic Agents, Hormonal↗

Quality of life and symptoms in a randomized trial of radiotherapy versus deferred treatment of localized prostate carcinoma.

BACKGROUND: Treatment of localized prostate carcinoma (LPC) using radiotherapy (RT) can induce disturbances in a patient's quality of life (QOL) and urinary and intestinal function. Late symptoms and QOL were evaluated in a randomized trial between RT and deferred treatment (DT). METHODS: Quality of life was evaluated with European Organization for Research and Treatment of Cancer's QLQ-C30 (+3) formula. Urinary and intestinal problems were evaluated with a validated symptom specific self-assessment questionnaire, QUFW94. The questionnaires were sent to 108 randomized patients with LPC and to an age-matched control group (n = 68). Mean age was 72 years. Mean total dose was 65 grays (Gy; 62.3-70 Gy). The median follow-up time from randomization was 40.6 months for the RT group and 30.4 months for the DT group. RESULTS: Social functioning was the only QOL scale in which a significant difference was found between the two patient groups and compared with the control group. Multivariate regression analysis showed that hematuria, incontinence, mucus, and planning of daily activities in response to intestinal problems caused this decrease in QOL in the RT group. A significant increase of intestinal problems was observed in the RT versus DT groups regarding mucus, stool leakage, intestinal blood, and planning of daily activity in response to intestinal problems. CONCLUSIONS: The RT patients showed increased levels of minor intestinal side effects compared with the DT patients and the controls, but the RT patients reported no decreased QOL except for decreased social functioning. This could be because this group developed coping skills or because of a low magnitude of side effects to influence the QOL.

Adaptation, Psychological↗

Radioimmunoscintigraphy using an anti-prostate monoclonal antibody (E4): a dosimetric evaluation.

The aim of this study was to evaluate different strategies to increase the tumour radiation dose for experimental radioimmunotherapy using 125I-labelled monoclonal antibody (MAb) E4 in a nude mice model xenografted with DU-145 tumours. The effects from a single injection of the 125I-labelled MAb E4, the same total amount of radiolabelled MAb E4 divided into three repeated injections, and the effect of pre-targeting with non-labelled MAb E4 for reducing the amount of shed antigen were investigated. Based on repetitive quantitative radioimmunoscintigraphies, calculation of the tumour radiation dose delivered from the 125I-nuclide was performed for each strategy. The single injection strategy without pretargeting rendered the highest mean tumour radiation dose, i.e. 0.23 Gy/MBq. Pretargeting with non-labelled MAb E4 before a single injection of [125I]E4 resulted in a slightly lower mean tumour radiation dose, i.e. 0.19 Gy/MBq, compared to the single injection alone. An even lower mean tumour radiation dose, i.e. 0.14 Gy/MBq, was obtained when the same total administered amount of activity was divided into three separate injections given in 10-day intervals. We concluded that the single injection strategy is the most efficient when using MAb E4 in this tumour model. The tumour radiation doses were not increased by dividing the same amount of activity into three injections or by pretargeting with non-labelled MAb E4.

Animals↗

Reliability and responsiveness of a prostate cancer questionnaire for radiotherapy-induced side effects.

Few self-assessment cancer-specific questionnaires/modules have yet been developed for radiotherapy-induced side effects. The aim of the present study was to test the reliability and responsiveness of a prostate cancer (PC)-specific questionnaire. Thirty-one patients with PC graded their urinary and intestinal symptoms and their sexual function on the questionnaire. A doctor and a nurse performed a structured interview and graded the patient's symptoms with the same questions. The procedure was performed at both the start and the end of the treatment. A high concordance regarding symptom detection was seen between the patient, nurse and the doctor. The inter-rater test shows intraclass correlation coefficient (ICC) values above 0.60 in all scales. The internal reliability exceeded the lower limit (Cronbach a >0.70) for all scales. The test-retest gave acceptable reliability for all scales (ICC > or = 0.60). All scales indicated increased problems during radiotherapy. The questionnaire was proven to be valid for the evaluations of urinary and intestinal problems and for sexual function in PC patients.

Aged↗

Acute side effects after dose-escalation treatment of prostate cancer using the new urethral catheter BeamCath technique.

Acute side effects after dose-escalated radiotherapy for prostate cancer with different treatment techniques were evaluated, using a daily diary recorded by the patients. Dose escalation was performed using the urethral catheter BeamCath' technique. Side effects were evaluated in 267 patients by means of a daily diary during the treatment and at 3-months' follow-up. The patients' evaluations were compared with those of patients treated with conventional or conformal techniques. Looser stools were reported in the conventional (placebo) and 76 Gy groups at 3-months' follow-up compared with at week 1. No other obvious increase in rectal or bladder morbidity was seen in the 76 Gy group. The catheter did not increase the urinary frequency in comparison to the other groups. The reported urgency and starting problems at the beginning of treatment seemed to improve in all groups at 3-months' follow-up. External beam radiotherapy dose escalation using the BeamCath technique did not result in a dose-dependent increase in acute side effects.

Adult↗

Guidance levels in the Nordic countries: a preliminary report for selected interventional procedures.

The Nordic radiation protection authorities have already published recommended guidance levels for patient doses for six conventional radiological examinations. Over the past two years a similar protocol has been in progress for three interventional procedures. Measurements have been performed in 22 different hospitals in the Nordic countries on patients in the weight range 40-100 kg. The selected procedures are percutaneous transluminal coronary angioplasty (PTCA), percutaneous transluminal angioplasty (PTA) and endoscopic retrograde cholangio- and pancreatio-graphy (ERCP). A total of 281 PTCA procedures, 304 PTA procedures and 147 ERCP procedures are included in the study. The results from this survey are presented as a first attempt to set guidance levels.

Angioplasty, Balloon↗

Rye bran and soy protein delay growth and increase apoptosis of human LNCaP prostate adenocarcinoma in nude mice.

BACKGROUND: In this study, we investigated whether dietary intervention could inhibit tumor growth of an androgen-sensitive human prostatic cancer. METHODS: LNCaP cells were transplanted subcutaneously in nude-mice. The animals were then put on different diets and tumor take, tumor growth and prostate specific antigen (PSA) secretion were studied during 9 weeks. RESULTS: Palpable tumors developed in 75% of the tumor-cell injected sites in animals fed a control diet (corn starch, sucrose, etc.) whereas, for animals given rye bran (RB), ethyl acetate extraction from rye bran supplemented cellulose based diets (CCEE), palpable tumors were seen in only 30% and for soy protein based diets (SCC) 50% of the transplantation sites, respectively. The tumors that grew to palpable size in the rye (RB) and soy (SCC) groups were smaller and secreted less PSA than those in the control group. In the rye and soy groups tumor cell apoptosis was increased, but cell proliferation was unaffected. Addition of fat to the rye diet reduced its effect on prostate cancer growth. CONCLUSIONS: Factors in rye bran and soy protein may inhibit prostate cancer growth. The effect is more apparent for rye than for soy. Further studies are needed to identify the effective substances and to explore the mechanism of action.

Adenocarcinoma↗

Fractionated radiotherapy of rat prostatic adenocarcinoma (Dunning R3327-PAP) in nonanesthetized animals.

BACKGROUND: The dose-response effect of fractionated external beam radiotherapy on nonanesthetized rats bearing the androgen-sensitive prostatic adenocarcinoma Dunning R3327-PAP was studied. METHODS: The radiation was given with a photon beam from a 4-MeV linear accelerator in doses from 4 to 11 Gray per fraction during 5 consecutive days. When the tumors with low and intermediate radiation doses relapsed into regrowth, the rats were castrated. Tumor volumes and rat weights were followed, and at the end of the study a morphometric analysis of the tumors was done. RESULTS: Fractionated irradiation induced a dose-dependent delay in tumor growth in hormonally intact rats. Castration stopped the tumor regrowth, showing that some of the tumor cells were still hormone-sensitive. The study was facilitated by the nonanesthesia procedure. CONCLUSIONS: The Dunning R3327-PAP hormone-sensitive rat tumor is sensitive to radiotherapy in a dose-dependent way. Regrowing, irradiated tumors contain hormone-sensitive cells. This work provided basic knowledge for further experimental studies of the effects of radiation on prostatic adenocarcinoma.

Adenocarcinoma↗

Late side effects unchanged 4-8 years after radiotherapy for prostate carcinoma: a comparison with age-matched controls.

BACKGROUND: The authors of this study previously evaluated pelvic irradiation-induced late side effects in patients with localized prostatic carcinoma 4 years after external irradiation by administering a validated self-assessment questionnaire (QUFW94), and compared the results with those of age-matched controls. The current study was designed to evaluate prospectively the patients' problems 8 years after radiotherapy and to compare them with those reported by the same controls. METHODS: The questionnaire was sent out at a mean of 8 years (range, 72-104 months) after irradiation to 120 patients and 125 controls. For analysis of sexual function, the patient group was divided into two subgroups, one treated with radiotherapy only (RT) and one group treated with radiotherapy plus castration (RT+A). A value of >1 on a 0-10 scale indicated that the patient was having a problem. RESULTS: The mean age was 73 years for both patients and controls. No changes in urinary problems were seen between the 4-year and the 8-year follow-up in the 2 groups. Sixty percent and 54% of the patients (P = 0.096) and 24% and 31% of the controls (P = 0.988) reported urinary problems at the 4-year and 8-year follow-ups, respectively. No changes in gastrointestinal late side effects in the patient group were seen between the 4-year (65%) and the 8-year (62%) follow-ups (P = 0.490). However, there was a decrease in intestinal problems in the control group between the 4-year (12%) and the 8-year (9%) follow-ups (P = 0.001). The sexual problems did not change during the two periods, in the patient groups or in the control groups. Fifty-six percent and 65% of the RT group (P = 0.052), 67% and 54 % of the RT + A group (P = 0.555), and 27% and 33 % of the control group (P = 0.243) indicated some kind of sexual problem at the 4-year and 8-year follow-ups, respectively. CONCLUSIONS: The amount of pelvic irradiation-induced urinary late side effects, intestinal late side effects, and sexual function, evaluated with a self-assessment questionnaire, did not change between 4 and 8 years after RT. The age-matched controls reported no change in urinary or sexual problems despite advanced age, but there was a reported decrease in intestinal problems.

Activities of Daily Living↗

After radiotherapy testosterone stimulation is unable to increase growth in the dunning R3327-PAP prostate tumour.

A study was carried out to investigate whether testosterone treatment is able to influence tumour growth in a rat prostatic adenocarcinoma previously treated with castration and high-dose fractionated irradiation. Copenhagen x Fisher rats bearing the androgen-sensitive, well-differentiated Dunning R3327-PAP tumour were castrated and thereafter treated with external beam radiation with photons from a 4-MV linear accelerator. One month after irradiation, substitution with subcutaneous testosterone was started. Tumour volumes and rat weights were monitored up to 256 days after castration, and at the end of the study a microscopic analysis of the tumours was performed. Irradiation delayed tumour growth as compared with untreated tumours. Castration delayed tumour growth, but a hormone-refractory relapse to doubled tumour volume was seen within 45 days. If testosterone was added after castration, the tumours grew rapidly. However, testosterone failed to increase tumour growth when given to rats treated with orchiectomy and irradiation. Histological examination showed that the irradiated tumours still contained tumour epithelial cells, but these cells apparently do not respond to testosterone stimulation. The well-differentiated and androgen-sensitive rat prostatic adenocarcinoma did not grow after irradiation despite stimulation with testosterone. This indicates that the malignant cells lose their androgen sensitivity after high-dose irradiation.

Adenocarcinoma↗

Effects of radiotherapy and estramustine on the microvasculature in malignant glioma.

Tumour angiogenesis is essential for progression of solid tumours and constitutes an interesting target for therapy. However, impaired tumour blood supply may also be an important obstacle for treatment by radiotherapy and chemotherapy. Estramustine has been shown to increase tumour blood flow and potentiate the effect of radiotherapy in experimental glioma. This study investigated the effects of fractionated radiotherapy and estramustine on angiogenesis in malignant glioma. The intracerebral BT4C rat glioma model was used and the animals were given whole brain radiotherapy 4 Gy x 5 days alone or in combination with estramustine 20 mg kg(-1) i.p. daily. Tumour microvascular density (MVD) was assessed by manual and computerized morphometrical analysis. Expression of vascular endothelial growth factor (VEGF) was studied by in situ hybridization. Radiotherapy decreased MVD to 157 vessels per mm2 compared to 217 vessels per mm2 in controls. Estramustine counteracted this anti-angiogenic effect and potentiated the anti-tumoural effect of radiotherapy. In addition, vessel size increased after estramustine treatment. Five days after completion of radiotherapy the expression of VEGF was increased in the centre of the tumours. In conclusion, fractionated radiotherapy decreases microvascular density in experimental malignant glioma. This effect was abolished by estramustine. The anti-vascular effect of irradiation is important to recognize when combining radiotherapy with cytotoxic drugs.

Animals↗

Radioimmunotherapy of DU-145 tumours in nude mice--a pilot study with E4, a novel monoclonal antibody against prostate cancer.

The anti-tumour effect of the 131I-labelled antiprostate monoclonal antibody (MAb) E4 was studied in an experimental model with 41 nude mice, subcutaneously xenografted with a human prostate cancer cell line (DU-145). The mice were divided into four study groups, i.e. one receiving single and another repeated injections of the radiolabelled MAb. A third group was injected with non-labelled MAb, and the fourth served as an untreated control group. The tumour volumes increased similarly in all groups during the 27-day observation period. The tumour tissue was morphologically disintegrated in the group that received repeated radioimmunotherapy (RIT). The tumours from this group contained large fluid-filled cystic parts and demonstrated pronounced cellular and subcellular polymorphism in the remaining viable tumour tissue. The untreated control tumours and single therapy tumours remained solid. The proportion of the total tumour volume that consisted of viable tumour cells, as determined by morphometric techniques, was significantly lower in the 131I-E4-treated groups. The use of 131I-labelled E4 MAb has thus demonstrated a promising therapeutic potential.

Animals↗

High-precision conformal radiotherapy (HPCRT) of prostate cancer--a new technique for exact positioning of the prostate at the time of treatment.

PURPOSE: Biopsies taken 2 years after radiotherapy of localized prostate cancer indicate residual tumor cells in 20-60% of cases, and the prognosis for these patients is unfavorable. More precise methods of localization of the prostate are desirable to increase the dose to the prostate tumor and minimize the volume of adjacent sensitive tissues that are currently included in the planning target volume. We have sought a method to more accurately locate the prostate at the time of treatment, allowing a reduction of the volume of rectum and bladder included in the high dose region during dose escalation. METHODS AND RESULTS: We have developed a new technique using a special urethral catheter (patent pending), containing markers that can be visualized by the radiotherapy machine for accurate positioning of the prostate. The catheter is used throughout the treatment planning procedure and the isocenter is placed on one of the markers. On the treatment couch the markers are visualized on port-films and with portal imaging immediately before dose delivery. A beam-center-marker on the accelerator makes it possible to adjust the isocenter position to within 1 mm, giving very high precision, independent of external fixation. The technique involves a simple patient setup. The method has been tested in five patients with conventional dose level (70 Gy) and in 24 patients in the first Scandinavian dose escalation study with external beam radiotherapy. No increase in acute side-effects was observed. CONCLUSION: With the new high precision conformal radiotherapy (HPCRT) technique we have developed a technique that allows us to increase the dose to the prostate without excessive side effects. The method reduces the uncertainties in prostate localization, is easy to handle, and feasible in routine treatment.

Equipment Design↗

Distribution of estramustine in the BT4C rat glioma model.

Estramustine (EaM), a carbamate ester of 17beta-estradiol and nor-nitrogen mustard, is a cytotoxic compound with antitumoral effect in malignant glioma in vitro and in vivo . However, knowledge of the pharmacokinetics of EaM in experimental glioma is limited. The objective of this study was therefore to investigate further the distribution of EaM in the BT4C rat glioma model. Assessment of EaM uptake and distribution was performed by quantitative whole-body autoradiography. In addition, the uptake of EaM and its metabolites estromustine (EoM), estradiol, and estrone were analyzed by gas chromatography. EaM was taken up from the circulation and was found to be the main product in glioma tissue. Whole-body autoradiography after [14C]-EaM administration revealed a strong 14C label simultaneously in tumor and normal brain tissue at 0.5 h after drug administration. In tumor tissue, sustained high levels of 14C label were detected at 12 h after drug administration. In contrast to the tumor, radioactivity in normal brain tissue rapidly leveled off, indicating a retention of radioactivity in the tumor. The tumor/brain radioactivity ratio reached a peak of 4.5 at 12 h after drug administration. High levels of 14C label were also found in pulmonary tissue. By gas chromatography, EoM was found to be the main metabolite in plasma. However, EaM reached higher levels in tumor tissue, with the mean tumor/plasma ratio being 11.7 as compared with 2.0 for EoM. Only low plasma levels of the estrogen metabolites were detected. In conclusion, EaM is taken up in the BT4C rat glioma tissue and is retained in the tumor as compared with normal brain tissue and plasma. EaM showed a greater selectivity for tumor tissue, exhibiting a high tumor/plasma ratio as compared with EoM. The distribution pattern after administration of EaM, as evaluated by both whole-body autoradiography and gas chromatography, supports the earlier suggestion that the uptake is related to a protein with EaM-binding characteristics.

Animals↗