Management of the hot thyroid nodule.

BACKGROUND: Solitary hyperfunctioning nodules of the thyroid gland are usually viewed as benign. They may present with autonomous euthyroidism but are of concern for potential progression to hyperthyroidism. Various methods of treatment are worthy of consideration. PATIENTS AND METHODS: Forty-five patients with solitary hot thyroid nodules verified by radioisotope scintiscanning were selected for treatment. Thirty-one underwent surgery, usually partial thyroidectomy. Eight euthyroid patients received no treatment, 5 underwent therapy with radioactive iodine (RAI), and 1 received thyroid suppression treatment. The cases were assessed retrospectively. RESULTS: Thyroidectomy patients had no morbidity, were well, and showed 1 Hürthle cell tumor and 5 coincidental small malignancies associated with benign hot nodules, including a contralateral cancer. Untreated patients showed continuance of good health, but nodules persisted and 1 Graves' orbititis occurred. The RAI-treated patients had persistent nodularity, improved function, and 1 case of hyperparathyroidism. Thyroid feeding only caused iatrogenic toxicity and was discontinued. CONCLUSIONS: There are various techniques for managing the hot nodule. Nonsurgical methods may be effective, but can result in persistent nodularity and iatrogenic sequelae. Excision had no morbidity in this series and was effective in providing immediate relief of problems present and potential.

Scintigraphic flare in skeletal lymphoma.

The authors describe the bone scan flare phenomenon in a patient with treated skeletal lymphoma. This was confirmed by both gallium scanning and computed tomography. If serial bone scintigraphy is used for assessing the treatment response of lymphoma, the flare phenomenon must be recognized.

Immunoscintigraphy of human colon cancer xenografts in nude mice using a second-generation TAG-72 monoclonal antibody labelled with 99Tcm.

Monoclonal antibody CC83 is a second-generation high-affinity antibody directed against the TAG-72 antigen in colorectal cancer. Our objectives were to evaluate the biodistribution, pharmacokinetics and imaging properties of CC83 labelled with 99Tcm via a modified Schwartz technique. The immunological integrity of 99Tcm-CC83 was evaluated by size-exclusion FPLC and by determining the immunoreactive fraction in vitro against bovine submaxillary mucin. The biodistribution of 99Tcm-CC83 up to 24 h postinjection was evaluated in nude mice bearing subcutaneous LS174T human colon cancer xenografts. Blood radioactivity data was fitted to a one-compartment pharmacokinetic model. Images of tumour-bearing mice were obtained at 17-24 h postinjection with 99Tcm-CC83. 99Tcm-CC83 was eluted as intact immunoglobulin by FPLC analysis and the mean immunoreactive fraction was 0.49 +/- 0.15. Tumour uptake at 24 h postinjection was 11.2 +/- 4.1% i.d.g-1. Radioactivity in the blood was eliminated rapidly with a half-life of 8 h and tumour:blood ratios were > 2:1 at 24 h postinjection. LS174T tumours were successfully imaged in 3/3 mice. In vitro studies showed instability of 99Tcm-CC83 when challenged with cysteine and glutathione but not metallothionein, suggesting a metabolic route for the 99Tcm antibody in vivo. We conclude that CC83 labelled directly with 99Tcm retains its immunological integrity and capability specifically to target subcutaneous LS174T human colon cancer tumours hosted in nude mice. These results further suggest that 99Tcm-CC83 may have potential for imaging colorectal cancer in humans.

Iodine-123-IBZM dopamine D2 receptor and technetium-99m-HMPAO brain perfusion SPECT in the evaluation of patients with and subjects at risk for Huntington's disease.

Huntington's disease (HD) is pathologically characterized by neuronal loss and neuroreceptor alterations in the striatum, including a reduction in dopamine receptor density. We evaluated the clinical usefulness of 123I-iodobenzamide (IBZM) D2 receptor SPECT imaging and 99mTc-hexamethylpropyleneamineoxime (HMPAO) brain perfusion SPECT imaging by studying four early symptomatic HD patients, 20 asymptomatic subjects at risk for HD and 22 controls. Striatal D2 receptor binding and perfusion were measured semiquantitatively by calculating striatum-to-frontal cortex IBZM and HMPAO uptake ratios, respectively. The control IBZM ratio (1.58 +/- 0.06) declined with age at 1.5% per decade (r = -0.58, p < 0.005), whereas the HMPAO ratio (1.15 +/- 0.05) did not. All four symptomatic patients had decreased IBZM ratios and three patients also had decreased HMPAO ratios. Five of 20 at-risk subjects had decreased IBZM ratios and two subjects also had decreased HMPAO ratios. Three of the five at-risk subjects showed subtle nonchoreic neurological abnormalities. Decreased striatal D2 receptor binding thus may be detected by IBZM-SPECT in the asymptomatic as well as symptomatic groups, and these changes were more marked than perfusion deficits detected by HMPAO-SPECT. IBZM-SPECT thus appears to be a promising method for early diagnosis and preclinical detection of HD.

Dopamine D2 receptor SPECT imaging: basic in vivo characteristics and clinical applications of 123I-IBZM in humans.

The purposes of this study are to evaluate the utility of kit formulation, the basic in vivo characteristics, and clinical usefulness of dopamine D2 receptor imaging with 123I-(S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrodinyl)m ethyl]- benzamide (123I-IBZM). We studied 22 normal controls, 3 early symptomatic Huntington's disease patients, and 1 patient with visual hallucination on and off neuroleptics. 123I-IBZM could be conveniently prepared with a high degree of purity from a kit, but with relatively low radiochemical yield. We demonstrated 123I-IBZM receptor binding equilibrium by performing serial SPECT scanning in a normal volunteer. The basal ganglia/frontal cortex (BG/FC) ratios plateaued after the specific binding reached equilibrium approximately 60 minutes after injection. The BG/FC ratio declined significantly with age. The ratios for the Huntington's disease patients were significantly lower than those for normal controls. The images of the patient off neuroleptic therapy showed dramatically increased BG activity compared with those obtained while on therapy. The BG/FC ratio provides an estimate of Bmax/Kd and hence the receptor density. It appears important to perform SPECT early in the equilibrium phase and at a fixed time after injection to obtain significantly high signal to noise ratios. 123I-IBZM is an ideal tracer for SPECT including a rotating gamma camera type which can provide estimates of the receptor density objectively by calculating the BG/FC ratio, and is a promising agent for the investigation of dopamine D2 receptors in clinical conditions.

Comparative dual label study of first and second generation antitumor-associated glycoprotein-72 monoclonal antibodies in colorectal cancer patients.

Radiolabeled first-generation anti-tumor-associated glycoprotein-72 (TAG-72) monoclonal antibody (MAb), B72.3, has proven useful in detecting primary and secondary colorectal carcinoma. It has been anticipated that the development of second-generation, higher affinity, anti-TAG-72 MAbs, CC49 and CC83, would be of greater use in cancer detection and of value in radioimmunotherapy of human cancer. We compared the pharmacokinetics, biodistribution, and immune responses of 131I-labeled CC49 and CC83 to 125I-labeled B72.3 by preoperatively coninjecting dual-labeled MAbs into 16 colorectal cancer patients. The imaging properties of radiolabeled CC49 and CC83 were also assessed. Pharmacokinetics of all three MAbs were identical, and there were no differences in the uptake of any of three MAbs in tumor and normal tissues. Maximum tumor uptake was 0.0041% of the injected dose/g for 125I-B72.3, 0.0024% for 131I-CC49, and 0.0029% for 131I-CC83. Radiolabeled CC49 and CC83 detected most known tumor sites on scintigrams without any clear advantage for either MAb. Nonspecific splenic and testicular uptake was frequently observed. Anti-idiotypic human anti-mouse antibody responses were seen more frequently with B72.3 than with CC49 or CC83. We conclude that higher affinity, radiolabeled anti-TAG-72 MAbs can detect colorectal cancer but do not penetrate these tumors more effectively than B72.3. Improvements in tumor detection and radioimmunotherapeutic strategies will likely require the administration of smaller fragments of MAb molecules or novel delivery systems rather than the continued development of higher affinity MAbs.

Neuroanatomical localization for clinical SPECT perfusion brain imaging: a practical proportional grid method.

For the purpose of facilitating anatomical localization in interpretation of 99Tcm-hexamethylpropyleneamine oxime (HMPAO) brain single photon emission tomographic (SPECT) scans, a stereotaxic proportional grid system was applied in the form of an interactive computer program. This method takes advantage of a rotating gamma camera system which permits planar scout imaging for the determination of anatomical reference lines, and standardization of tomographic slices for brain size. Using measurements made on a lateral planar HMPAO image, proportional grids were constructed onto standardized transaxial images. This method was implemented for 33 clinical HMPAO SPECT studies. It required less than 15 min of an operator's time. This simple and practical neuroanatomical localization technique can be instrumental as an aid to the interpretation of routine clinical HMPAO SPECT images.

Assessment of regional cerebral perfusion by 99Tcm-HMPAO SPECT in chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is a severely disabling illness of uncertain aetiology. It is characterized by a chronic, sustained or fluctuating sense of debilitating fatigue without any other known underlying medical conditions. It is also associated with both somatic and neuropsychological symptoms. Both physical and laboratory findings are usually unremarkable. Regional cerebral blood flow (rCBF) was assessed in 60 clinically defined CFS patients and 14 normal control (NC) subjects using 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) single photon emission computed tomography (SPECT). Compared with the NC group, the CFS group showed significantly lower cortical/cerebellar rCBF ratios, throughout multiple brain regions (P < 0.05). Forty-eight CFS subjects (80%) showed at least one or more rCBF ratios significantly less than normal values. The major cerebral regions involved were frontal (38 cases, 63%), temporal (21 cases, 35%), parietal (32 cases, 53%) and occipital lobes (23 cases, 38%). The rCBF ratios of basal ganglia (24 cases, 40%) were also reduced. 99Tcm-HMPAO brain SPECT provided objective evidence for functional impairment of the brain in the majority of the CFS subjects. The findings may not be diagnostic of CFS but 99Tcm-HMPAO SPECT may play an important role in clarifying the pathoaetiology of CFS. Further studies are warranted.

'Reverse crescent pattern' on SPECT brain perfusion scan in chronic subdural hematoma.

A SPECT brain perfusion scan was performed on a patient who had symptoms of dementia. The SPECT scan showed marked crescentic medial displacement of the left cerebral hemisphere ("reverse crescent pattern"), and mildly decreased cortical perfusion in the affected hemisphere. Crossed cerebellar diaschisis was not present. On x-ray CT, the underlying abnormality was found to be a unilateral chronic subdural hematoma causing a significant mass effect. A reverse crescent pattern without crossed cerebellar diaschisis on SPECT brain perfusion scan in patients with dementia may suggest the diagnosis of chronic subdural hematoma.

Parotid gland and parapharyngeal space imaging--the surgical significance.

Wise head and neck surgeons, for whom parotid gland surgery constitutes a substantial portion of their case load, make full use of the radiologist and cytologist in arriving at a rational pre-operative diagnosis. They utilize the skill of these allied consultants to qualify (by histology) and quantify (by staging) diffuse and mass lesions of the parotid gland (and subjacent parapharyngeal space) in order to evolve an effective surgical, radiation or other treatment plan. They understand the basic principles of diagnostic imaging and apply them to the clinical problem at hand. They minimize diagnostic and intra-operative "surprises", reduce intra-operative and post-operative complications and generally have a more "informed" patient and patient's family. The purpose of this manuscript is to discuss a contemporary role for diagnostic imaging in neoplastic (and other) diseases of the parotid gland and subjacent parapharyngeal space. Not all lesions of the parotid gland require imaging, although a pre-operative clinical photograph, including evidence of facial nerve function, is always welcome. Other lesions may need diagnostic imaging, from simple to complex and sophisticated, depending upon the problem. Properly used, effective and selective diagnostic imaging can improve the surgeon's confidence by providing a more realistic provisional diagnosis and a better pre-operative staging process and treatment plan, thereby avoiding the surgically unexpected and facilitating prognosis.

Decision making in thyroid and parathyroid surgery: the influence of imaging.

Surgical decision making is essentially based on experience, augmented by a management philosophy. In this manuscript we review concepts of thyroid and parathyroid surgical decision making in relation to diagnostic imaging input. These two endocrine glands have crucial anatomic associations, but very different pathologic conditions; it is the specific pathologic considerations that ultimately determine the decision-making process. For us, diagnostic imaging has enabled a more effective surgical decision-making process through thorough pre-operative planning. The strategy for parathyroid surgery is based upon the pathologic localization obtained by high resolution ultrasound. Thyroid surgical strategy is more heavily influenced by experience, and our policy is total thyroidectomy for all malignant and benign tumors with airway compression.

Contribution of nuclear medicine to the diagnosis and management of extracranial head and neck diseases (excluding thyroid and parathyroid).

Nuclear medicine contributes to the diagnosis and management of extracranial head and neck diseases through the physiological information it provides. In addition to thyroid and parathyroid indications, radionuclide studies, i.e., bone and 67Gallium citrate scans are helpful in diagnosing and treating head and neck malignancies. Positron emission tomography with 18F-fluorodeoxy-glucose evaluates tumor glucose metabolism before and after treatment. Triphase bone scintigraphy enables early detection of osteomyelitis of the skull base, and its management requires 67Gallium-citrate or 111Indium-WBC scintigraphies. Salivary gland scintigraphy is the only functional imaging test of salivary tissue and should be utilized more in the diagnosis of submandibular duct obstruction and in the evaluation of preserved parenchymal function after recurrent infections.

Technetium-99m-HMPAO SPECT in the evaluation of patients with a remote history of traumatic brain injury: a comparison with x-ray computed tomography.

The functional imaging modality has potential for demonstrating parenchymal abnormalities not detectable by traditional morphological imaging. Fifty-three patients with a remote history of traumatic brain injury (TBI) were studied with SPECT using 99mTc-hexamethylpropyleneamineoxime (HMPAO) and x-ray computed tomography (CT). Overall, 42 patients (80%) showed regional cerebral blood flow (rCBF) deficits by HMPAO SPECT, whereas 29 patients (55%) showed morphological abnormalities by CT. Out of 20 patients with minor head injury, 12 patients (60%) showed rCBF deficits and 5 patients (25%) showed CT abnormalities. Of 33 patients with major head injury, 30 patients (90%) showed rCBF deficits and 24 patients (72%) showed CT abnormalities. Thus, HMPAO SPECT was more sensitive than CT in detecting abnormalities in patients with a history of TBI, particularly in the minor head injury group. In the major head injury group, three patients showed localized cortical atrophy by CT and normal rCBF by HMPAO SPECT. In the evaluation of TBI patients, HMPAO SPECT is a useful technique to demonstrate regional brain dysfunction in the presence of morphological integrity as assessed by CT.

Comparative biodistribution and antibody-dependent cellular cytotoxicity of native and heavy chain chimeric antibody.

We have recently chimerized the heavy chain of the pan-carcinoma monoclonal antibody (mAb) B72.3. Studies were undertaken to compare the IgG1 chimeric antibody, B72.3-1-3 with native murine B72.3 (nB72.3). Using fluorescence-activated cell sorting analysis, B72.3-1-3 demonstrated specific binding to fresh LS174T tumor cells. Biodistribution of 131I B72.3-1-3 was similar to 131I nB72.3 in nude mice bearing LS174T xenografts. Peak radiolocalization indices were noted on day 6 for B72.3-1-3 and day 8 for nB72.3. Both antibodies were capable of imaging LS174T tumors by radioimmunoscintigraphy. Antibody-dependent cellular cytotoxicity of LS174T by human peripheral blood lymphocytes was tested in 8h 51Cr release assays. With either no antibody or nB72.3, lymphocytes were not capable of killing LS174T cells. However, B72.3-1-3 at a concentration of 5 and 50 micrograms/ml mediated significant lysis of tumor cells by human lymphocytes. These results suggest that chimeric antibodies retain their binding properties to tumor cells and display biodistribution patterns similar to their unmodified counterparts. Such modifications may reduce the deleterious human antimouse antibody response to murine mAbs as well as augment antibody-dependent cellular cytotoxicity of tumor cells by human effectors.

Radionuclide imaging in otolaryngology-head and neck surgery.

Radionuclide imaging provides both qualitative and quantitative information that can have dramatic effects on patient management in diseases of the head and neck. The general concepts of nuclear medicine imaging, including radiopharmaceuticals and radiation effects, are discussed. The principles and techniques of thyroid, parathyroid, bone, and salivary radionuclide imaging studies will be reviewed. The intent of this article is to provide a concise and current review of head and neck radionuclide imaging that will be useful in the day-to-day practice of otolaryngology-head and neck surgery.

Red blood cell scan in cavernous hemangioma of the larynx.

Cavernous hemangioma of the larynx is an uncommon, difficult-to-diagnose vascular tumor for which there is no significant imaging literature to date. The possibility of improved diagnosis through RBC scanning might obviate injudicious biopsy and potential hemorrhage within the airway. Utilizing the radionuclide RBC scan, which labels the patient's own RBCs initially with cold pyrophosphate, and subsequently with technetium 99m as pertechnetate, we have identified successfully four patients with cavernous hemangioma of the larynx. All presented with a supraglottic mass involving at least the aryepiglottic fold and arytenoid region unilaterally. This report describes our satisfactory diagnostic imaging experience with the radionuclide RBC scan and suggests both its imaging specificity and its role in the management of this lesion.

Radionuclide bone scan in frontal sinus osteoma.

Frontal sinus osteomas, whether cortical or cancellous by morphologic radiologic appearance, appear to represent metaplasia rather than neoplasia occurring at the frontal-ethmoid suture line. These osteomas are not infrequently found completely or partially within the frontal sinus or adjacent ethmoid complex. Regardless of specific anatomic site, they occur at the embryologic junction of enchondral and membranous frontal bone. Those osteomas which produce mechanical complications (ostial obstruction or facial deformity or proptosis) give clear indication for surgical intervention. A much larger group of osteomas, however, is detected on routine plan radiographic examinations carried out for other reasons. Unfortunately, the singular conventional radiographic finding of an osteoma has, in the past, frequently been the sole and primary indication for surgical intervention. The purpose of the present paper was to review the experience with 10 frontal sinus osteomas managed expectantly over the past 11 years. All were imaged serially with morphologic studies, including conventional X-rays and computerized tomography scans. A radionuclide bone scan was carried out in all patients at the time of initial presentation. Those identified as producing mechanical complications clinically, or a 'hot' bone scan by radionuclide study, were regarded as appropriate for osteoplastic frontal sinusectomy for removal of the osteoma; three cases were approached in this way. On the other hand, utilizing this physiologic imaging parameter, a 'cold' bone scan indicated the presence of a relatively insert osteoma, in terms of biologic growth activity. Thus, adopting a non-operative approach, and following these patients over the 4-11 year period appears to have been validated.(ABSTRACT TRUNCATED AT 250 WORDS)

The parathyroid adenoma: an imaging/surgical perspective.

The clinical picture of hyperparathyroidism has changed since the implementation of routine serum calcium testing, resulting in more asymptomatic patients undergoing early surgical exploration. Although operative complications (e.g., recurrent laryngeal nerve paralysis, hypocalcemia, etc.) are not prevalent, the risk can be minimized by minimizing tissue dissection. For this reason, we feel that preoperative tumor localization is of great importance. We report our imaging results of parathyroid adenomas, utilizing ultrasonography, technetium-thallium subtraction scanning, digital subtraction angiography and magnetic resonance imaging. We also present an imaging protocol which, we have found, maximizes preoperative identification of these tumors.

Simultaneous occurrence of chylothorax and subarachnoid pleural fistula after thoracotomy.

A left chylothorax complicated elective left posterolateral thoracotomy and emergency decompressive laminectomy carried out on a 32-year-old woman with a benign neurofibroma. Failure of conservative therapy necessitated ligation of the thoracic duct and this in turn unmasked the concomitant subarachnoid-pleural fistula. Surgical repair and lumbar subarachnoid drainage were required to close the second fistula. The clinical setting, diagnosis and management of this uncommon condition are reviewed.