Estimation of foetal brain dose from I-131 in the foetal thyroid

The ingestion of I-131 by pregnant women can have consequences for the developing foetus, in particular brain function. As the foetal thyroid accumulates iodine from the twelfth week of gestation onwards, the determination of foetal brain dose resulting from such I-131 accumulation is essential. Normal dosimetric methods fail to treat the case of foetus. Using an approximation method based on the MIRD approach, a foetal dose estimation scheme is developed to allow the determination of foetal brain dose from foetal thyroid irradiation. Dose values are obtained for the foetus based on the maternal intake of I-131. It was found that the choice of biokinetic model for the mother/foetus has a large impact on the determined dose estimate.     

Percent 131I uptake and post-therapy 131I scans: their role in the management of thyroid cancer

Renal disease in patients infected with human immunodeficiency virus (HIV) often presents with significant proteinuria and progressive renal failure; focal glomerulosclerosis is the most common renal pathology identified. To our knowledge, we report the first case of nephrotic-range proteinuria and preserved renal function in an HIV-infected patient in association with disseminated histoplasmosis. The initial level of proteinuria was 12.5 g/24 h. The patient developed a concomitant lesion on his neck, which was biopsied and identified as Histoplasma capsulatum by fungal stains and culture. The serum CF titer of antibody against yeast antigens of H. capsulatum was 1:8. The level of serum albumin decreased to 2.0 g/dL, and the level of serum cholesterol increased to 284 mg/dL. Immunohistochemical staining of renal biopsy tissue demonstrated immune complexes within the mesangium; H. capsulatum antigen was also demonstrated in the mesangium. Therapy with oral itraconazole resulted in marked clinical improvement. The findings in this case emphasize the need to rule out treatable causes of the nephrotic syndrome in AIDS, especially in cases of immune-complex glomerulonephritis.     

131I therapy for pediatric thyroid cancer

Azido-3'-deoxy-thymidine (AZT) is a drug extensively used in the treatment of AIDS. AZT was incubated in vitro either with the pituitary-hypothalamus complex (PHc) or the intact pituitary (PI) of male rats. The PHc is comprised of the hypothalamus and the attached pituitary gland. After a preincubation period, the PHc or PI was incubated for 1 or 2 h with Krebs-Ringer bicarbonate buffer or either of two different concentrations of AZT (1 and 10 microM). In the control incubations, the PHc released less prolactin (PRL) and more follicle-stimulating hormone (FSH) and luteinizing hormone (LH) than the PI, indicating that hypothalamic control of the pituitary was exerted in vitro, presumably by diffusion of releasing and inhibiting hormones from the neurohypophysis to the anterior lobe of the hypophysis. Both concentrations of AZT evoked a significant increase in release of PRL and a decreased release of LH and FSH from the PHc. In the case of LH, the higher concentration of AZT partially suppressed LH release within 1 h. The other effects were not dose-related and were observed after incubating the tissue with AZT for 2 h. However, incubation of the PI with AZT failed to alter anterior pituitary hormone release, illustrating that the site of action of AZT is in the hypothalamus. We hypothesize that AZT blocks DNA synthesis resulting in suppression of synthesis and consequent release of hypothalamic hormones that control release of pituitary hormones in vitro. The results raise the possibility that AZT may alter hypothalamic-pituitary function in vivo.     

Fatty acid composition of breast adipose tissue in breast cancer patients and in patients with benign breast disease

In this study, we report on the cell adhesion properties of marrow stromal cells to extracellular matrix components such as collagen and noncollagenous proteins. The osteoblastic cells and their non-osteoblastic counter-parts (MBA series) from the marrow stroma differentially recognized a spectrum of extracellular matrix proteins. The osteoblastic cells, MBA-15, preferentially attached to bone matrix proteins, whereas fibroendothelial MBA-2.1 and adipocytic 14F1.1 cells did not. The MBA-15 cells demonstrated a preference in their attachment to fibronectin > mixture of collagens > bone matrix extracts > collagen type I > noncollagenous proteins. Clonal subpopulations derived from the MBA-15 cell line representing various stages along the osteogenic lineage expressed differential attachment preference. MBA-15.4, a less differentiated clonal line, was compared to MBA-15.6, a mature cell line.     

Screening for microalbuminuria by RIA in 131I-treated thyroid cancer patients

Thyroid cancer patients are treated with up to 9.9 GBq of 131I to ablate remnant thyroid tissue and/or any functioning metastases that may be present. Radioiodine therapy is repeated as often as required. However, only a small fraction of the 131I is taken up by remnant thyroid and metastases, the remainder being eliminated by the kidneys, which are therefore subject to irradiation. External radiation therapy to the kidneys is known to lead to nephritis and albuminuria. The study included 113 patients treated with one to four doses of 131I (1.1-9.9 GBq each dose) and followed up 1 month to more than 8 years later. Spot samples of urine were collected and microalbuminuria measured by in-house radioimmunoassay. Twelve patients had elevated levels (normal range up to 34 micrograms ml-1), but their clinical history revealed such predisposing factors as diabetes and/or hypertension and proteinuria before therapy commenced. The remaining patients had normoalbuminuria. Grouping the patients based on the total dose of 131I administered resulted in a median microalbuminuria of 2.4-12.9 micrograms ml-1. Hence, this study showed that the dose of 131I normally used in treating thyroid cancer does not increase microalbuminuria to any significant extent.     

Leukaemias and cancers following iodine-131 administration for thyroid cancer

We studied 1771 patients treated for a thyroid cancer in two institutions. None of these patients had been treated with external radiotherapy and 1497 had received (131)I. The average (131)I cumulative activity administered was 7.2 GBq, and the estimated average dose was 0.34 Sv to the bone marrow and 0.80 Sv to the whole body. After a mean follow-up of 10 years, no case of leukaemia was observed, compared with 2.5 expected according to the coefficients derived from Japanese atomic bomb survivors (P = 0.1). A total of 80 patients developed a solid second malignant neoplasm (SMN), among whom 13 developed a colorectal cancer. The risk of colorectal cancer was found to be related to the total activity of (131)I administered 5 years or more before its diagnosis (excess relative risk = 0.5 per GBq, P = 0.02). These findings were probably caused by the accumulation of (131)I in the colon lumen. Hence, in the absence of laxative treatment, the dose to the colon as a result of (131)I administered for the treatment of thyroid cancer could be higher than expected from calculation of the International Commission on Radiological Protection (ICRP). When digestive tract cancers were excluded, the overall excess relative risk of second cancer per estimated effective sievert received to the whole body was -0.2 (P = 0.6).     

Endoscopic surveillance of Barrett's esophagus: a cost-effectiveness comparison with mammographic surveillance for breast cancer

OBJECTIVE: Endoscopic surveillance of Barrett's esophagus is commonly practiced to detect malignancy in an early and curable stage. However, the cost-effectiveness of this practice has been questioned. To clarify this issue, we undertook a cost analysis of endoscopic surveillance to detect adenocarcinoma in Barrett's esophagus compared with mammography used to detect occult carcinoma of the breast, a widely accepted cancer surveillance technique. METHODS: The rate of esophageal adenocarcinoma detected by endoscopic surveillance was calculated for Duluth Clinic patients with Barrett's esophagus seen from 1980 to 1995 and compared with published rates. The rate of occult breast cancer detection was calculated for all women undergoing surveillance mammography at the Duluth Clinic for the year 1994 and compared with published rates. Costs for screening studies and therapy for cancer treatment for both cancers were calculated based on clinical results and assumptions regarding outcomes derived from published reports, and the costs were compared. RESULTS: Endoscopic surveillance of 149 patients with benign Barrett's esophagus was performed for a total of 510 patient-yr, during which time seven patients developed adenocarcinoma, an incidence of one case per 73 patient-yr of follow-up. Occult breast cancer was detected in 50 of 12,537 mammograms, a detection rate of 0.4%. The incidences in both cases were comparable to published figures. The costs of detecting a case of adenocarcinoma in Barrett's esophagus and occult breast cancer were $37,928 and $54,513, respectively, and those for treatment resulting in cure were $83,340 and $83,292. Cost per life-yr saved was $4,151 for adenocarcinoma in Barrett's esophagus and $57,926 for breast cancer. CONCLUSION: Endoscopic surveillance of patients with Barrett's esophagus compares favorably with the common practice of surveillance mammography to detect early breast cancer, and should therefore be considered to be as cost-effective as surveillance mammography.     

Radioimmunotherapy of medullary thyroid cancer with iodine-131-labeled anti-CEA antibodies

This study evaluates the pharmacokinetics, dosimetry, toxicity and therapeutic potential of radiolabeled NP-4 and MN-14 anti-CEA antibodies in medullary thyroid cancer (MTC). METHODS: Eighteen patients with advanced MTC entered exploratory clinical studies with therapeutic doses of 131I-labeled NP-4 and MN-14 murine monoclonal antibodies (MAbs) reactive with carcinoembryonic antigen (CEA). Doses administered ranged from 46 mCi for 131I-MN-14 lgG to 195 mCi for 131I-MN-14 F(ab)2 in patients negative for human anti-mouse antibodies (HAMA). RESULTS: The radioconjugate blood half-life (T1/2) for the whole lgG was 42.5+/-5.0 hr compared to 18.8+/- 4.1 hr for the bivalent fragments. Tumor doses of 17.5+/-11.0 and 11.4+/-6.3 cGy/mCi were estimated for 131I-MN-14 lgG and F(ab)2, respectively. Tumor/red marrow dose ratios exceeded 3:1 for most lesions. Red marrow doses of up to 350 cGy generally could be delivered with < grade 4 toxicity. Seven of 14 evaluable patients showed evidence of anti-tumor effects lasting up to 26 months, based on physical exam, tumor markers or computed tomography. CONCLUSION: This study demonstrates that anti-CEA MAbs may be suitable for radioimmunotherapy of metastatic or recurrent MTC.     

Redifferentiation therapy-induced radioiodine uptake in thyroid cancer

Due to a dedifferentiation of tumor cells, some thyroid carcinomas lose their capability for radioiodine (RI) concentration. This phenomenon is associated with a worse prognosis and prevents effective treatment. Retinoic acid (RA) is known to induce redifferentiation in various kinds of tumors and has been used recently in thyroid cancer. METHODS: Twelve patients (9 women, 3 men) with 6 papillary, 4 follicular and 2 mixed-cell type tumors (including 4 Hurthle cell carcinomas) were treated orally with RA (dose: 1.18 +/- 0.37 mg/kg body weight) for at least 2 mo before RI therapy. None of the patients could be treated with any other modality (RI, surgery, external radiation) when RA administration was started. Initially, clinically important tumor sites did not take up significant amounts of RI. Changes of RI uptake and thyroglobulin (Tg) serum values were determined. Glucose metabolism was followed with fluorodeoxyglucose (FDG) PET imaging in 10 patients before and in 5 patients after RA treatment. RESULTS: In 2 patients, a significant RI uptake was induced by RA, and in another 3 patients a faint RI uptake was achieved (responder group). In 7 patients, no change of RI uptake was observed (nonresponder group). Median Tg was increased from 105-840 microg/liter during RA therapy in the responder group, which was significantly higher than the nonresponder group (173-134 microg/liter). FDG PET was positive in all 10 patients before RA therapy. PET showed variable patterns of changes (increase/decrease/disappearance) in glucose consumption related to RA response. CONCLUSION: RA can induce RI uptake in some patients with RI negative thyroid carcinoma tumor sites. Response to RA is associated with a significantly higher increase of Tg, suggesting that a restoration of Tg synthesis can be addressed as a redifferentiation parameter in these patients.     

Telomerase activity in benign proliferative breast disease and breast cancer

The application of telomerase activity is expected to serve as a reliable indicator of biological malignancy in breast tumors. We performed a study to quantify telomerase activity, the results of which revealed that this activity tends to be unexpectedly low in scirrhous carcinoma having low histological differentiation. It is therefore felt that additional studies at the tissue level using in situ hybridization will be required in the future. Although we think that atypical cystic duct is a true pre-cancerous lesion in the sense of having a high possibility of progressing into breast cancer, it will be interesting to determine whether or not the tissue is composed of cells having telomerase activity.     

Radioiodine I-31 therapy in the management of thyroid cancer. A prospective study

The therapeutic value of I-131 ablation therapy following thyroidectomy for thyroid cancer was evaluated in 54 patients in a prospective study of 25 years. Thirteen (24%) patients had follicular, 24 (44%) papillary, 13 (24%) mixed papillary-follicular, two (4%) Hurthle cell and two (4%) had undifferentiated cell type tumor. Twenty-four (44.5%) patients had metastases at the time of I-131 therapy mainly to cervical and mediastinal lymph nodes, and less frequently to bone, brain, lung, and liver. After surgical thyroidectomy, the mean cumulative dose of I-131 required to achieve therapeutic ablation of functioning post-surgical remnants or tumor metastases was 163.4 mCi. The recurrence rate for patients with metastases was 56% and those without metastases was 25%. Ten patients showed recurrence of I-131 accumulating tissue five to 10 years after initial total ablation. The total mean cumulative dose of I-131 administered for both followup diagnostic studies, and initial and follow-up therapy was 245.3 mCi. Seven deaths were attributable to thyroid cancer, five with differentiated and two with anaplastic cell type tumors. Three of the four patients with differentiated cell type tumors had metastases to brain or bone. Their response to therapy was similar to those patients with anaplastic cell type tumors. In contrast, there were no deaths due to thyroid cancer when total ablation was achieved and maintained. After ablation, all patients were maintained on maximum tolerated doses of thyroid extract or thyroxin. No significant complications attributable to the therapeutic doses of I-131 employed in this series were noted.     

Delayed massive soft tissue uptake of Tc-99m MDP after radiation therapy for cancer of the breast

A patient with a history of breast cancer and known lung metastases was referred for a bone scan to investigate the cause of severe neck and right shoulder pain. The bone scan showed massive uptake of the radiopharmaceutical in the soft tissue surrounding the right shoulder. A review of the patient's history indicated that the patient had undergone radiation therapy to the right upper thorax and breast area 14 months previously and an acute radiation dermatitis of the proximal right arm and should had developed. This had long since resolved. Physical examination and plain radiographs of the right shoulder and humerus failed to demonstrate any abnormality.     

Comparison of 18FDG-PET with 131iodine and 99mTc-sestamibi scintigraphy in differentiated thyroid cancer

Based on sequence analyses of 17 complete centromeric DNA monomers from ten different deer species, a model is proposed for the genesis, evolution, and genomic organization of cervid satellite I DNA. All cervid satellite I DNA arose from the initial amplification of a 31-bp DNA sequence. These 31-bp subrepeats were organized in a hierarchical fashion as 0.8-kb monomers in plesiometacarpalia deer and 1-kb monomers in telemetacarpalia deer. The higher-order repeat nature of cervid centromeric satellite DNA monomers accounts for their high intragenomic and intraspecific sequence conservation. Such high intraspecific sequence conservation validates the use of a single cervid satellite I DNA monomer from each deer species for interspecific sequence comparisons to elucidate phylogenetic relationships. Also, a specific 0.18-kb tandem duplication was observed in all 1-kb monomers, implying that 1-kb cervid satellite I DNA monomers arose from an unequal crossover event between two similar 0.8-kb ancestral DNA sequences.     

Elevated CEA in breast cancer patients with overlooked medullary thyroid carcinoma

After mastectomy and radiation for breast cancer, two patients were found to have persistent elevated CEA in their serum. This finding was erroneously attributed to occult metastases for the first patient and to local recurrence for the second. Overlooked medullary thyroid carcinoma (MTC) was the causal disease in both patients. A review of the literature stresses the frequency of CEA elevation in serum of MTC patients. A thorough search for any possible cause of elevated levels of CEA is advocated, particularly by thyroid sonogram with a needle aspiration biopsy when a nodule is discovered and by calcitonin assay in the serum.     

Effect of postoperative 131I treatment on thyroglobulin measurements in the follow-up of patients with thyroid cancer

Correlation of serum thyroglobulin (Tg) levels with recurrent cancer was performed in 200 patients who had undergone a subtotal thyroidectomy for well-differentiated thyroid carcinoma. Patients were divided into three groups: (1) those not treated postoperatively with radioactive iodine, (2) those treated with low dose (30 mCi) radioactive iodine, and (3) those treated with high dose (50-250 mCi) radioactive iodine. Tg levels proved to be reliable in detecting recurrent thyroid cancer regardless of the dose of radioactive iodine given postoperatively. These results reinforce the recommendation of using the Tg assay as the primary method of following these patients postoperatively, even when there was less than a total thyroidectomy and ablation with radioactive iodine.     

Radioiodine ablation of residual tissue in thyroid cancer: relationship between administered activity, neck uptake and outcome

A retrospective review was performed to evaluate the effectiveness of radioiodine in the ablation of residual thyroid tissue after surgery for differentiated thyroid cancer. 121 patients were treated at the Princess Margaret Hospital, Toronto, Canada between 1977 and 1989, with the activity of radioiodine determined empirically. Ablation of residual thyroid was determined by 131I nuclear scans, using absent visible uptake (compared with background) as the criterion for successful ablation. 97 patients (80%) had successful ablation of residual thyroid tissue after the first administration of radioiodine. Patients with higher iodine uptake in the neck had a tendency to receive higher activities of 131I. There were no statistically significant differences in age, sex, type of surgery, initial iodine uptake in the neck and administered radioiodine activity between those successfully ablated and those that were not. Patients receiving less than 3.7 GBq (100 mCi) tended to have lower iodine uptake (< 5% at 24 or 48 h), but their rate of thyroid ablation was just as high as those given 3.7 GBq or more. In order to take advantage of this, we have formalized our approach by deriving guidelines to the empiric determination of radioiodine activity based on the iodine uptake in the neck. Among the 11 patients treated with lobectomy only, the ablation rate was 64%. Although this was not significantly lower than for other forms of surgery, we continue to recommend completion thyroidectomy for this group of patients, if the goal of treatment is to ablate all thyroid tissue.     

Incidence of primary malignancies other than breast cancer among women treated with radiation therapy for benign breast disease

In addition to left ventricular pump failure and low cardiac output, structural and metabolic alterations of skeletal muscle are thought to contribute to exercise intolerance seen in patients with CHF. Studies using cardiac myocytes have implicated nitric oxide elaborated by inducible nitric oxide synthase (iNOS) as a potential agent associated with the genesis of dilated cardiomyopathy. The present study was designed to locate iNOS in the working skeletal muscle of patients with congestive heart failure. Specific antibodies were used to detect iNOS by immunohistochemistry in skeletal muscle biopsies (m. vastus lateralis) of 37 patients with left ventricular pump failure and 8 normal controls. The expression was restricted to skeletal muscle myocytes and was increased five- to ninefold in patients with chronic heart failure. There was no statistically significant difference in iNOS expression between patients with dilated cardiomyopathy and those with ischemic cardiomyopathy. The finding of a locally increased expression of iNOS and the experimental evidence that NO attenuates the contractile performance of the skeletal muscle suggest that the expression of iNOS may be responsible for the exercise intolerance seen in patients with chronic heart failure.     

Physical symptoms, distress, and breast cancer risk perceptions in women with benign breast problems.

Physical symptoms, general and breast cancer-specific distress, and perceived breast cancer risk were assessed in 66 women with benign breast problems (BBP) and 66 age-matched healthy comparison (HC) women. BBP women reported significantly greater worry about breast cancer than HC women. Breast symptom incidence and breast cancer risk perceptions were found to mediate group differences in breast cancer worry. Hierarchical regression analyses indicated that perceptions of control over a potential breast cancer prognosis moderate the impact of breast symptoms on reports of breast cancer worry. Implications for risk counseling with BBP women are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)