2-Deoxy-2-[F-18]fluoro-D-glucose positron emission tomography/computed tomography in the management of melanoma.

OBJECTIVES: 2-Deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) is widely available as a powerful imaging modality, combining the ability to detect active metabolic processes and their morphologic features in a single exam. The role of FDG-PET is proven in a variety of cancers, including melanoma, but the estimates of sensitivity and specificity are based in the majority of the published studies on dedicated PET, not PET/CT. Therefore, we were prompted to review our experience with FDG-PET/CT in the management of melanoma. METHODS: This is a retrospective study on 106 patients with melanoma (20-87 years old; average: 56.8 +/- 15.9), who had whole-body FDG-PET/CT at our institution from January 2003 to June 2005. Thirty-eight patients (35.9%) were women and 68 patients (64.1%) were men. Reinterpretation of the imaging studies for accuracy and data analysis from medical records were performed. RESULTS: All patients had the study for disease restaging. The primary tumor depth (Breslow's thickness) at initial diagnosis was available for 76 patients (71.7%) and ranged from 0.4 to 25 mm (average: 3.56 mm). The anatomic level of invasion in the skin (Clark's level) was determined for 70 patients (66%): 3, level II; 13, level III; 43, level IV; 11, level V. The administered dose of (18)F FDG ranged from 9.8 to 21.6 mCi (average: 15.4 +/- 1.8 mCi). FDG-PET/CT had a sensitivity of 89.3% [95% confidence interval (CI): 78.5-95] and a specificity of 88% (95% CI: 76.2-94.4) for melanoma detection. CONCLUSION: This study confirms the good results of FDG-PET/CT for residual/recurrent melanoma detection, as well as for distant metastases localization. PET/CT should be an integral part in evaluation of patients with high-risk melanoma, prior to selection of the most appropriate therapy.

Merkel cell carcinoma: Is there a role for 2-deoxy-2-[f-18]fluoro-D-glucose-positron emission tomography/computed tomography?

PURPOSE: 2-Deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) is becoming widely available as a powerful imaging modality, combining the ability to detect active metabolic processes and their morphologic features in a single study. The role of FDG-PET/CT is proven in lymphoma, melanoma, colorectal carcinoma, and other cancers. However, there are rare malignancies such as Merkel cell carcinoma that can potentially be evaluated with PET/CT. We were therefore prompted to review our experience with FDG-PET/CT in the management of patients with Merkel cell carcinoma. PROCEDURES: This is a retrospective case series of six patients with Merkel cell carcinoma, 58-81 years old (average 69 +/- 8.3), who had whole-body PET/CT at our institution from January 1st, 2003 to August 31st, 2005. Two patients were women and four were men. Reinterpretation of the imaging studies for accuracy and data analysis from medical records were performed. RESULTS: Twelve examinations were acquired for the six patients (one patient had six PET/CT, one patient had two PET/CT, and four patients had one PET/CT). The injected FDG doses ranged 381.1-669.7 MBq (average 573.5 +/- 70.3). Four patients had the PET/CT as part of initial staging, and two patients had the exam for restaging (after surgery and XRT). A total of six Merkel lesions (pancreas, adrenal, lip, submandibular lymph nodes, cervical lymph nodes, and parapharyngeal soft tissue) were identified in three patients and confirmed on histopathological examination. The FDG uptake in these areas was intense, with maximum standardized uptake value (SUVmax) values of 5-14 (average 10.4 +/- 3.8). In one patient, the PET/CT scan identified abnormal focal distal sigmoid uptake that was biopsied and diagnosed as adenocarcinoma. Two patients had negative scans and had no clinical evidence of disease on follow-up office visits (up to one year after PET/CT). CONCLUSIONS: This case series suggests that FDG-PET/CT may have a promising role in the management of patients with Merkel cell carcinoma.

Long-term results of irradiation for patients with progressive Graves' ophthalmopathy.

PURPOSE: To determine the long-term outcome of radiotherapy (RT) in patients with progressively symptomatic thyroid eye disease and to evaluate the potential long-term sequelae. METHODS AND MATERIALS: Four hundred fifty-three patients provided written informed consent and received retrobulbar RT for Graves' ophthalmopathy at Stanford University Medical Center; 197 with 1 year of follow-up were retrospectively analyzed. Of the 197 patients, 189 received RT to the bilateral retrobulbar regions, and 4 received unilateral RT. The technical information was unavailable for 4 patients. Patients were assessed by chart review, telephone interview, questionnaire, and multidisciplinary physician examination. Eye impairment was scored using the SPECS system. The end point review included the before and after treatment SPECS score, surgical intervention, and patient satisfaction. Potential complications, including cataract development, retinopathy, and tumor formation, were investigated. Multivariate analyses were performed to assess the prognostic variables. RESULTS: Improvement or resolution was 89% for soft-tissue findings; 70% for proptosis; 85% for extraocular muscle dysfunction; 96% for corneal abnormalities; and 67% for sight loss. The response to RT may take >6 months to stabilize. Factors predictive of response varied in the individual SPECS categories but included the initial SPECS score, pretreatment thyroid status, female gender, a 20-Gy RT dose, and a history of hypertension. Nonpredictive factors included a history of tobacco use, diabetes mellitus, steroids, and prior cataracts. Only 16% required surgical intervention to preserve their vision or restore binocular vision. Twenty-two patients (12%) developed cataracts after irradiation (median 11 years). No patient developed a tumor within the RT field during the follow-up period (range 1-29 years). Ninety-eight percent of patients were pleased with their results, and 2% believed their symptoms progressed despite RT. CONCLUSIONS: Retrobulbar irradiation (20 Gy) is safe and effective treatment for progressive Graves' ophthalmopathy, with a 96% overall response rate, 98% patient satisfaction rate, and no irreparable long-term sequelae, with follow-up extending 29 years. The most common late effect observed was cataract development, which occurred more frequently in older patients and was reversible with extraction. Elective surgical intervention after RT should be withheld until patients have demonstrated a plateau in response.

Iodine and thyroid cancer risk among women in a multiethnic population: the Bay Area Thyroid Cancer Study.

Research on the relationship between iodine exposure and thyroid cancer risk is limited, and the findings are inconclusive. In most studies, fish/shellfish consumption has been used as a proxy measure of iodine exposure. The present study extends this research by quantifying dietary iodine exposure as well as incorporating a biomarker of long-term (1 year) exposure, i.e., from toenail clippings. This study is conducted in a multiethnic population with a wide variation in thyroid cancer incidence rates and substantial diversity in exposure. Women, ages 20-74, residing in the San Francisco Bay Area and diagnosed with thyroid cancer between 1995 and 1998 (1992-1998 for Asian women) were compared with women selected from the general population via random digit dialing. Interviews were conducted in six languages with 608 cases and 558 controls. The established risk factors for thyroid cancer were found to increase risk in this population: radiation to the head/neck [odds ratio (OR), 2.3; 95% confidence interval (CI), 0.97-5.5]; history of goiter/nodules (OR, 3.7; 95% CI, 2.5-5.6); and a family history of proliferative thyroid disease (OR, 2.5; 95% CI, 1.6-3.8). Contrary to our hypothesis, increased dietary iodine, most likely related to the use of multivitamin pills, was associated with a reduced risk of papillary thyroid cancer. This risk reduction was observed in "low-risk" women (i.e., women without any of the three established risk factors noted above; OR, 0.53; 95% CI, 0.33-0.85) but not in "high-risk" women, among whom a slight elevation in risk was seen (OR, 1.4; 95% CI, 0.56-3.4). However, no association with risk was observed in either group when the biomarker of exposure was evaluated. In addition, no ethnic differences in risk were observed. The authors conclude that iodine exposure appears to have, at most, a weak effect on the risk of papillary thyroid cancer.

Thyroid carcinoma after successful treatment of osteosarcoma: a report of three patients.

We report three cases of papillary thyroid carcinoma occurring after successful treatment of osteosarcoma. Only one of the three patients received radiation therapy (to the chest) as part of the primary treatment of osteosarcoma. The onset of thyroid carcinoma occurred between 8 and 16 years from the cessation of osteosarcoma therapy. All patients are alive and disease-free from both malignancies. Whereas the association between osteosarcoma and thyroid carcinoma has not previously been recognized, there have been five case reports of these two entities occurring in the same patient. Three of these cases occurred in patients with Werner syndrome. None of the patients reported here had physical stigmata of Werner syndrome or a family history consistent with a hereditary cancer syndrome. Thyroid carcinoma occurs infrequently in patients with osteosarcoma, but in view of the rarity of these two disorders, this association may represent an inherited predisposition to these malignancies.

Positron emission tomography of the thyroid, with an emphasis on thyroid cancer.

The role of Positron Emission Tomography (PET) using 18F-fluorodeoxyglucose (FDG) in the management of thyroid cancer is discussed. It is important to ensure that patients are relaxed because uptake of FDG in tense or active muscles in the neck and larynx can be misinterpreted as metastases. The major role for PET is in patients where the stage of disease is uncertain, usually the result of discordant negative 131I scan and a positive serum thyroglobulin (Tg) values. PET identifies the source of Tg production in 50-80% of patients. PET scan can be negative in well differentiated cancers which retain the ability to trap iodine. This can result in a 'flip/flop', with negative PET, positive radio-iodine scan, or positive PET, negative radioiodine scan. PET is also valuable in identifying the source of calcitonin production in patients with medullary thyroid cancer. When focal uptake is seen in the thyroid of patients who are scanned for non thyroidal reasons, the likelihood of primary thyroid cancer is high. In contrast diffuse uptake of FDG in the thyroid is usually the result of auto-immune thyroid disorders.

Intraoperative ultrasonography for localization of recurrent thyroid cancer.

Advances in measurement of thyroglobulin (Tg) and in imaging techniques including high resolution ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) scan have increased our ability to detect thyroid cancer recurrences at an earlier stage. (1,2) After thyroidectomy, patients are often treated with radioiodine, but the recurrent cancers may not image with radioiodine. In these instances, the only definitive treatment is surgical resection. Reoperative neck surgery can be challenging, especially when trying to find a small cancer nodule within the central neck that contains dense fibrotic scar tissue. Herein we describe the use of intraoperative ultrasonography to identify the location of recurrent thyroid cancer. This technique can aid in tumor localization and may help to avoid complications such as recurrent nerve injury.

Recombinant human thyrotropin in the management of thyroid cancer.

Radioiodine has been shown to reduce recurrences and improve survival in well-differentiated thyroid cancer. To maximize the effectiveness of radioiodine therapy, patients are first treated by total thyroidectomy and then allowed to become hypothyroid. The elevation of thyroid-stimulating hormone, or thyrotropin (TSH), that occurs with hypothyroidism stimulates uptake of radioiodine in normal and cancerous thyroid tissues. A recent advance has been the introduction of recombinant human TSH (rhTSH), which is administered intramuscularly prior to testing with radioiodine. Phase III trials have demonstrated that rhTSH stimulates both uptake in and production of thyroglobulin by thyroid cells and the results are comparable to those of hypothyroid protocols in the majority of patients. Patients prefer the rhTSH protocol because they continue to ingest exogenous thyroid hormone and the symptoms of hypothyroidism are avoided. The rhTSH protocol is preferable in patients with pituitary dysfunction and in those who cannot tolerate hypothyroidism. RhTSH can also allow treatment of patients who have not had an adequate thyroidectomy and who are poor candidates for reoperation.

Dramatic parotid uptake of I-131 on a diagnostic whole-body scan.

Radiation sialadenitis is a complication of I-131 therapy for thyroid cancer. They authors report a case of intense uptake by parotid glands in a diagnostic I-131 scan (2 mCi) in whom sialadenitis had developed previously after a 100-mCi dose of I-131. Similar examples of images could not be found in the literature.

Recombinant human thyrotropin (rhTSH) in the management of differentiated thyroid cancer.

Recombinant human thyrotropin (rhTSH) has been evaluated in 38 patients with differentiated thyroid cancer. The patients had all been treated previously by operation and 31 had received radioiodine 131I. The patients continued to take thyroid hormone and changed to a low iodine diet for 14 days before and throughout the week of testing. The rhTSH was injected intramuscularly on two consecutive days, 74 MBq 131I was administered on the next day and scintigraphy completed 48 h after that. TSH was measured before administration of 131I, and thyroglobulin after the scan. All patients preferred this method to withdrawal of thyroid hormone, but 45% had mild symptoms including headache and nausea. The average TSH was 127 mU x l(-1), and was inversely related to the weight of the patients. Thirty-four had negative scans with a mean uptake of 0.06%. Thyroglobulin values above 10 ng x ml(-1) were found in seven patients, of whom four had similar findings when scanned after withdrawal of thyroid hormone. Of four with positive scans, two had undetectable thyroglobulin. The rate of clearance of 131I was compared in patients studied at 72 h who were hypothyroid and at 48 h in euthyroid patients given rhTSH and was found to be longer in the latter. We conclude that rhTSH can be used to stimulate thyroid tissue to trap 131I and secrete thyroglobulin. Both scan and thyroglobulin should be obtained. The method is well tolerated.

How frequently is the thymus seen on whole-body iodine-131 diagnostic and post-treatment scans?

The purpose of the study was to determine how often the thymus is visualized on whole-body radioiodine scans. One hundred and seventy-five patients had 325 diagnostic scans and 200 post-treatment scans. Activity in the mediastinum possibly consistent with the thymus was seen on seven scans in six patients. Four of these were diagnostic scans (three were second follow-up scans, and the fourth, a third follow-up scan). Three post-treatment scans demonstrated mediastinal uptake. Only one patient had persistent mediastinal uptake on both a post-treatment scan and a subsequent follow-up diagnostic scan. None of these six patients were treated as a result of this finding and none has clinical or biochemical evidence of metastatic disease.

Systemic radiation therapy with unsealed radionuclides.

Systemic unsealed radiation therapy is achieved when a radioactive substance is administered orally or parenterally and that material is concentrated in an organ or site for sufficient time to deliver a therapeutic dose of radiation. The radioactive material usually emits beta particles. In general, there is intense local radiation of the abnormal tissues, and normal organs, which do not trap the radioactive material, are exposed to a small radiation dose. The most frequent treatments involve radioiodine (131)I for hyperthyroidism and differentiated thyroid cancer. Other applications include treatment of painful skeletal metastases, polycythemia vera, malignant cysts, and neuroendocrine tumors. The treatments are usually well tolerated and not associated with long-term effects, such as cancer or infertility.

Parathyroid localization with high-resolution ultrasound and technetium Tc 99m sestamibi.

HYPOTHESIS: High-resolution ultrasound and technetium Tc 99m sestamibi scanning can be used for preoperative localization of abnormal parathyroid glands in patients with hyperparathyroidism. DESIGN: Ultrasound and sestamibi scanning were performed in patients undergoing neck exploration for hyperparathyroidism. If the 2 scans agreed in identifying a single adenoma, and surgery confirmed the location of a single adenoma and an ipsilateral normal gland, a unilateral exploration was performed. SETTING: University tertiary care center. PATIENTS: Sixty-one consecutive patients undergoing surgery for hyperparathyroidism from September 1, 1994, through September 30, 1997. INTERVENTIONS: High-resolution ultrasound was performed in 59 patients and sestamibi scanning in 58 patients; all patients underwent neck exploration by a single surgeon. MAIN OUTCOME MEASURES: The results of preoperative ultrasound and sestamibi scanning were compared with operative and histological findings. RESULTS: All patients were cured of hypercalcemia. Specificity of ultrasound and sestamibi scanning was 98% and 99%, respectively; however, their sensitivity was only 57% and 54%, respectively. Both imaging modalities had lower sensitivities in the setting of multigland disease. If both imaging studies were considered as a single test, sensitivity for imaging in patients with primary hyperparathyroidism reached 78%. Our localization protocol allowed a unilateral approach in 43% of patients (23 of 53). CONCLUSIONS: These results confirm the value of preoperative localization in patients with hyperparathyroidism. A unilateral approach can be used with a high degree of success in cases when ultrasound and sestamibi scanning agree in the identification of a single adenoma confirmed by surgical exploration with the identification of a normal ipsilateral gland.

Comparison of the clearance of radiolabelled nose drops and nasal spray as mucosally delivered vaccine.

The distribution and nasal clearance of 99Tcm-labelled albumin (18.5 MBq), used as a mucosal vaccine surrogate for FluMist, was determined in three volunteers. The subjects were randomized in a cross-over clinical study design to receive either large-particle aerosal (nasal spray) followed by nose drops, or nose drops followed by the nasal spray, 1 week apart. Gamma scintigraphy was used to measure the distribution and clearance. The 'vaccine' delivered as drops was cleared from the nose into the oesophagus and upper stomach at very variable rates. In contrast, the nasal spray was uniformly distributed and cleared from the nasopharynx with a 50% mean clearance time of 50 min (range 40-60 min) and was not detected in the lungs.

Uptake of I-131 in the biliary tract: a potential cause of a false-positive result of scintiscan.

Focal uptake of I-131 in the region of the liver was seen on whole-body scans in a 22-year-old asymptomatic woman who had invasive papillary cancer. Hepatic metastases were unlikely because of the clinical risk factors, and a CT scan of the liver was normal. By superimposing the I-131 scintiscan and a hepatobiliary scan, the site of the uptake was shown to be in the biliary tract, and it had migrated to the gallbladder on more delayed images. No pathologic cause was found.

Ultrasound-guided fine-needle aspiration biopsy of thyroid masses.

The purpose of this study was to determine the impact of ultrasound-guided fine-needle aspiration biopsy (USFNA) in the cytological diagnosis of nodular thyroid disease. It remains unclear exactly what role USFNA should play in the cytological diagnosis of nodular thyroid disease. All patients who underwent fine-needle aspiration (FNA) for nodular thyroid disease at Stanford University Medical Center from 1991 to 1996 were included in the study. Histopathologic diagnoses were compared to cytological diagnoses for those patients who underwent surgery. FNA was performed on a total of 497 thyroid nodules. Palpation-guided FNA (pFNA) was performed on 370 nodules, and USFNA was done on 127. The USFNAs were performed for the following reasons: 95 (75%) for nonpalpable or difficult-to-palpate nodules; 14 (11%) for previously failed FNA; and 18 (14%) for incidentally detected nodules. FNA had an unsuccessful biopsy rate of 16% and a sensitivity and specificity of 89% and 69%, respectively. USFNA had an unsuccessful biopsy rate of 7% and a sensitivity and specificity of 100% and 100%, respectively. The cancer yield at surgery for pFNA was 40%, and the cancer yield at surgery for USFNA was 59%. The complementary use of USFNA with pFNA improves the diagnostic approach to nodular thyroid disease. The use of USFNA has increased the cancer yield at surgery and the sensitivity of thyroid biopsy at our institution.