Changes in QT dispersion during adenosine infusion.

BACKGROUND: QT dispersion (QTd) measurement during treadmill stress testing has been to shown to improve the accuracy of exercise electrocardiogram (ECG) in the detection of significant coronary artery disease (CAD). HYPOTHESIS: The aim of this study was to determine whether adenosine-induced changes in QTd could predict significant CAD and to assess its efficacy as a diagnostic index in patients undergoing adenosine stress test. METHODS: QT interval measurements were made in 57 consecutive patients undergoing adenosine sestamibi stress test. Patients with an abnormal stress test underwent coronary angiography. Patients with significant disease by coronary angiography (> 70% stenosis) were classified as having CAD (Group 1), and those with normal stress images and/or normal coronaries by angiography were classified as having no CAD (Group 2). RESULTS: QT dispersion increased from 28.2 +/- 4.5 to 43.8 +/- 4.5 ms with a delta QTd of 15.53 +/- 3.68 in Group 1 (p = 0.001) and from 28.4 +/- 2.6 to 34.8 +/- 2.8 ms with a delta QTd of 6.58 +/- 2.21 ms in Group 2 (p = 0.006). Patients in Group 1 had a significantly higher increase in QTd (delta QTd) than the patients in Group 2 (p < 0.03). Addition of delta QTd (> 10 ms) to the ST depression during adenosine infusion would increase the sensitivity of the ECG from 23 to 65% and decrease the specificity from 91 to 70% for diagnosis of significant CAD. CONCLUSIONS: delta QTd is significantly more prolonged in patients with CAD during adenosine infusion. It increases the sensitivity of the stress ECG in diagnosis of CAD during adenosine infusion when used as an adjuvant index.

Thyroid nodules in the follow-up of irradiated individuals: comparison of thyroid ultrasound with scanning and palpation.

In 1974 we began a prospective study of a cohort of 4296 individuals exposed to therapeutic head and neck irradiation during childhood for benign conditions. To define the role of thyroid ultrasonography in following irradiated individuals, we studied a subgroup of 54 individuals. They all had been screened between 1974-1976 and had normal thyroid scans and no palpable nodules at that time. Thyroid ultrasonography, thyroid scanning, physical examination, and serum thyroglobulin measurements were performed. One or more discrete ultrasound-detected nodules were present in 47 of 54 (87%) subjects. There were a total of 157 nodules, 40 of which were 1.0 cm or larger in largest dimension. These 40 nodules occurred in 28 (52%) of the subjects. Thirty (75%) of these 1.0-cm or larger nodules matched discrete areas of diminished uptake on corresponding thyroid scans. The 10 that did not match (false negative scans for > or = 1.0-cm nodules) were the only nodules of this size in 7 subjects. Of 11 nodules 1.5 cm or larger, only 5 were palpable. Serum thyroglobulin correlated to the number (P = 0.04; r2 = 0.10), but not the volume of the thyroid nodules (P = 0.07; r2 = 0.08). We conclude that thyroid nodules are continuing to occur and are exceedingly common in this irradiated cohort of individuals. The results confirm that thyroid ultrasonography is more sensitive than physical examination and scanning. However, thyroid ultrasound is so sensitive and nodules so prevalent that great caution is needed in interpreting the results.

Improved detection of hepatic lesions using MoAb B72.3 and a modified 111In labelling technique in patients with recurrent colon cancer.

In this study, the clinical usefulness of 111In-SCN-Bz-diethylenetriaminepentaacetic acid (DTPA) monoclonal antibody (MoAb) B72.3 in patients with recurrent colorectal carcinoma was evaluated. In previous studies with radiolabelled MoAb B72.3, metastatic liver lesions in patients with colon cancer appeared as areas of either increased (hot lesions) or decreased (cold lesions) activity, and extrahepatic lesions appeared as areas of increased activity. Eleven patients were enrolled in this study, and 12 MoAb imaging study results were correlated with computed tomography/magnetic resonance imaging findings. The improved detection rates (number of hot lesions) in MoAb imaging were 48% (14/29) for hepatic metastases and 60% (6/10) for extrahepatic metastases. This represents a significant improvement in the rate of detection of metastatic disease of the liver in patients with recurrent colon cancer when compared to the rate in previous reports. Seventeen clinically unsuspected hepatic and extrahepatic areas of increased uptake were also identified on MoAb studies, and two of these areas were confirmed as metastatic disease at surgery. The rate of detection of extrahepatic metastases with 111In-SCN-Bz-DTPA MoAb B72.3 was also compared and found to be equal to the detection rates with other radiolabelled immunoconjugates. No major adverse side effects were noted during the administration of the MoAb. Four of nine patients tested had a positive anti-mouse antibody (HAMA) response 3 months after injection. These preliminary data indicate that this 111In-labelled immunoconjugate of MoAb B72.3 demonstrates an improvement in hepatic lesion detection rate than did previously reported preparations in patients with recurrent colon cancer.

Noninvasive staging of lung cancer. Indications and limitations of gallium-67 citrate imaging.

The results of evaluation of the hila and mediastinum with 67Ga scans are contradictory, as are the recommendations by different investigators on the use of 67Ga scintigraphy in the clinical evaluation of patients with primary lung carcinoma. Nevertheless, the economy and logistic simplicity of evaluating local and distant metastases with a single imaging procedure are attractive, especially because the symptoms may not enable the physician to make a correct identification of the organ systems affected by metastases. Neumann and Hoffer state that "at present conventional Ga-67 scanning techniques cannot be recommended for preoperative staging of mediastinal lymph node metastases in lung cancer patients." According to Waxman, 67Ga scintigraphy, relative to other imaging modalities, is a sensitive indicator of hilar spread of a tumor. However, because of the normally high background activity within the sternum and spine, mediastinal abnormalities may be poorly detected. Since most pulmonary tumors metastasize via regional nodes to the pulmonary hilum and then to the mediastinum, the high sensitivity for the detection of pulmonary hilar abnormalities and the high specificity for detection of mediastinal lesions suggest that gallium scintigraphy is a valuable adjunctive test when used appropriately. The results obtained locally are probably the best guide for individual physicians in the selection of diagnostic tests for their patients. Gallium scans may thus be helpful in the clinical evaluation of patients with lung cancer. Although gallium scans identify mediastinal node involvement, there is considerable controversy over the relationship between the sensitivity and specificity of the method. By detecting distant extrathoracic metastases, the 67Ga scan may identify a small group of patients who can be spared a needless operation. Gallium scanning fails specifically for metastases within the brain; thus, it does not supplant CT scans of the brain and it is less sensitive than bone scans in detecting osseous metastases. Gallium scanning of patients with small-cell lung cancer is not useful in the selection of therapy but does become important from a prognostic standpoint. Patients with extrathoracic involvement by small-cell carcinoma of the lung are known to have limited survival times compared with those of patients with thoracic involvement alone. In identifying patients with extensive disease, the oncologist is thus provided with prognostic information that may be useful in the counseling of the patient and the patient's family.

Detection of pulmonary metastases in a patient with synovial cell sarcoma using In-111 labeled monoclonal antibody 19-24.

A 35-year-old man was diagnosed in 1984 as having a synovial cell sarcoma of his right wrist without evidence of metastatic spread. The patient underwent regional hyperthermic chemoperfusion, wide-field excision, post-operative radiation therapy and systemic adjuvant chemotherapy. In 1986 and in 1987, because of new lesions found on chest radiographs, the patient underwent bilateral staging thoracotomies with resection of pulmonary metastases, followed by chemotherapy and radiotherapy. Later in 1987, a chest radiograph showed a large left hilar mass and multiple bilateral pulmonary nodules. Computerized tomography of the chest demonstrated a left hilar mass and two nodules in the right lower lung, raising the possibility of recurrent pulmonary metastatic cancer. As a diagnostic procedure, In-111 labeled monoclonal antibody (Mab) 19-24, produced against a human malignant fibrous histiocytoma, was infused intravenously, and 48-hour images revealed focal areas of increased uptake corresponding to the lesions seen on CT. At surgery, the lesions were confirmed to be synovial cell sarcoma. Imaging with Mabs specific for sarcoma may be particularly useful in sarcoma patients in whom there is clinical uncertainty regarding the nature of pulmonary lesions. In this case, the Mab was useful in distinguishing tumor deposits from postsurgical scarring and helped to guide subsequent surgery and treatment.

Preoperative imaging in primary hyperparathyroidism. Role of thallium-technetium subtraction scintigraphy.

Primary hyperparathyroidism, although often silent clinically, may lead to significant morbidity if it remains untreated. In more than 95% of all cases the cause is a parathyroid adenoma or glandular hyperplasia. Regression of disease follows successful surgical excision of the abnormal parathyroid gland. Recurrent or persistent hyperparathyroidism is most commonly caused by solitary adenomas, which may have an ectopic location. Preoperative localization of lesions may improve postoperative cure rates and decrease morbidity. Thallium T1 201 chloride-technetium Tc 99m pertechnetate subtraction scintigraphy was performed on 15 patients with primary hyperparathyroidism. The sensitivity and specificity for detection of abnormal glands were 90% and 95%, respectively. False-positive or false-negative results were minimize by strict adherence to a protocol and by the use of well-defined diagnostic criteria. Because of the superior sensitivity and specificity, this modality should be the primary imaging method of choice for preoperative evaluation of primary hyperparathyroidism. The relative role of other imaging modalities is also discussed.

Recurrence of thyroid nodules after surgical removal in patients irradiated in childhood for benign conditions.

To determine the incidence of benign thyroid nodules and the risk factors for their recurrence after surgical removal, we followed 511 patients for 1 to 40.6 years (median, 11.2) after surgery for benign thyroid nodules arising after local irradiation for unrelated benign diseases in childhood. Recurrent thyroid nodules developed in 100 patients (19.5 percent). The risk of recurrence correlated inversely with the amount of thyroid tissue removed. Women had a higher recurrence rate than men (28.4 percent vs. 10.3 percent; P less than 0.05). Among the 299 patients who had been treated with thyroid hormone at the discretion of their physicians to suppress thyroid-stimulating hormone, 25 had recurrences (8.4 percent), as compared with 72 of 201 patients who did not receive thyroid hormone (35.8 percent) (hazard ratio taking into account the extent of surgery and the patient's sex, 2.5; 95 percent confidence interval, 1.5 to 4.1). Histologic analysis of the 73 tissue samples from patients with recurrences showed that 14 samples (19.2 percent) were malignant. Thyroid hormone treatment had no effect on the rate of thyroid cancer. We conclude that radiation-associated benign thyroid nodules have a high recurrence rate, similar to that reported among nonirradiated patients with benign thyroid nodules. We also conclude that treatment with thyroid hormone decreases the risk of benign recurrences, particularly in women, but not the risk of cancer.

Radiation-induced thyroid carcinoma. Clinical course and results of therapy in 296 patients.

Of 5379 patients who had received radiation treatment at our institution for benign conditions of the head and neck, 318 developed thyroid cancer 3 to 42 years later. We report follow-up observations (median interval from diagnosis to recurrence or last contact, 10 years; longest interval, 31) for 296 of these patients. Three patients died of thyroid cancer and 40 had recurrences. The rate of recurrence during the 10 years after the detection of thyroid cancer, determined by life-table analysis, was 1.1%/yr. Factors that correlated with the risk of recurrence were tumor size, histologic type, number of lobes involved, vessel invasion, and lymph node metastases. The time from radiation exposure to the discovery of thyroid cancer (latency) and the age at diagnosis both inversely correlated with recurrence. The administration of thyroid hormones reduced the number of recurrences in patients with combined papillary and follicular cancer, but no reductions could be associated with the extent of surgery done or the prophylactic use of radioactive iodine ablation. We conclude that the course of radiation-induced thyroid cancer is the same as that of thyroid cancer found in other settings. We advocate a conservative approach to the treatment of small tumors that have no associated risk for thyroid cancer other than that they developed many years after the patient had been exposed to radiation.

Prospective serum thyroglobulin measurements in assessing the risk of developing thyroid nodules in patients exposed to childhood neck irradiation.

We examined 327 patients with a history of cervical radiation treatment for benign conditions and followed them for an average of 5.6 yr. These patients were selected because they initially had normal examinations and normal serum thyroglobulin levels. Of the 327 patients, 48 developed thyroid nodules, and an additional 30 had other clinical changes in their thyroids. Serum thyroglobulin increased by 4.0 +/- 0.6 (+/- SEM) ng/ml in those who remained normal, by 13.4 +/- 5.2 ng/ml in those who were no longer normal, and by 17.1 +/- 8.2 ng/ml in those who developed nodules. We conclude that increasing levels of serum thyroglobulin identify patients who should be examined and followed more carefully for thyroid nodules and thyroid cancer.

Radiation-induced tumors of the head and neck following childhood irradiation. Prospective studies.

Nodules were found in 1108 subjects who received childhood radiation for benign conditions of the cervical area at our institution. This is 37.5% of 2958 subjects, out of a total of 5379, for whom there is follow-up information. Of the 848 subjects who have had thyroidectomies, 297 (35.0%) had thyroid cancer. In addition to thyroid tumors, salivary, neural, and probably parathyroid tumors also occurred as a late consequence of childhood radiation. Prospective studies of the subjects indicate that thyroid nodules are continuing to occur at a constant rate. The measurement of serum thyroglobulin is helpful in identifying individuals for whom the risk of developing a nodule is increased. Follow-up of patients with nonsurgically-treated nodules indicates that some of their nodules are progressive. At the present time there is no indication that radiation-induced cancers behave differently than ones in other settings. However, some of their characteristics, especially their multicentricity and occurrence in younger individuals, indicate that continued follow-up is necessary. On the basis of the data generated by the follow-up program at our institution and programs elsewhere, recommendations for screening, treatment, and follow-up are made. The recommendations stress the importance of estimating risk based on radiation dose, previous tumors, and serum thyroglobulin, in arriving at clinical decisions for these subjects.

The role of gallium-67 in the clinical evaluation of cancer.

This review is based primarily on historic data, and it examines the indications for and limitations of gallium-67 scanning in the evaluation of patients with neoplasms. The use of gallium-67 scans is discussed according to tumor type, and data from the most representative and comprehensive studies are included. The results described, some of which were obtained primarily with older imaging techniques, should be regarded as representing the minimum that can be expected from application of this imaging procedure.

Complementary role of chest roentgenogram in interpretation of Tc-99m sulfur colloid liver scan.

Correlation of a chest roentgenogram and a radionuclide scan facilitated the interpretation of a liver scan with a defect in the dome that was due to an extrinsic compression and photon attenuation by a metastatic tumor in the right lung base.

The effects of inadvertent administration of antineoplastic agents prior to Ga-67 injection: concise communication.

Alteration of the gallium-67 (Ga-67) distribution after administration of chemotherapeutic agents has been demonstrated in experiments on both normal and tumor-bearing animals. We have encountered eight patients who had Ga-67 scintigrams in which the findings were similar to those in the animals experiments: markedly increased uptake in bone, with suppressed uptake in liver, muscle, and tumor. Five of the patients had hematologic neoplasms, and three had solid tumors, and each had received one or more chemotherapeutic agents during the 24 hr preceding Ga-67 administration. In three patients while not on antineoplastic medication subsequent Ga-67 images showed a return to the usual Ga-67 distribution pattern. The altered Ga-67 distribution may result from inhibition of protein synthesis or of a serum-binding agent for Ga-67, or from competitive blockage of specific Ga-67 organ receptors by the antineoplastic agents.

Is routine hepatic flow study cost effective? A case of hepatic cavernous hemangioma evaluated with dynamic flow study and delayed blood pool images.

A case of hepatic hemangioma was evaluated with radionuclide hepatic flow study, static scans, blood pool images, and angiography. The hemangioma appeared "avascular" on the hepatic flow study. Blood pool image with technetium 99m human-serum albumin was diagnostic in findings and quality for cavernous hemangioma.

Scintigraphic thyroid abnormalities after radiation. A controlled study with 99mTc pertechnetate scanning.

We did 99mTc-pertechnetate thyroid scintigraphy on 99 subjects with no history of therapeutic irradiation to the head or neck. They were compared with 198 irradiated patients selected from a group of over 1700 who were evaluated because of radiation treatment for benign head and neck conditions during childhood. The two groups were similar with respect to age and sex distribution. There were significantly more abnormal scintigrams in the irradiated group (55 of 198 patients versus one of 99 controls). Even after patients and controls with palpable nodules were excluded from the analysis there were still more abnormal scintigrams in the irradiated group (16 of 150 irradiated versus one of 97 control subjects). We conclude that thyroid nodules, including the smaller, nonpalpable nodules discovered by scintigraphy, are related to previous radiation therapy. For persons at substantial risk, such as those who received high-dose treatment (greater than 700 R) during childhood, the data support the use of screening scintigraphy, even with normal findings on palpation.