The impact of the multifocality and subtypes of papillary thyroid carcinoma on central compartment lymph node metastasis.

OBJECTIVE: Papillary thyroid carcinoma (PTC) may often appear as multifocal disease. Few studies demonstrated a higher rate of central compartment lymph node metastasis (CCLNM) in multifocal PTC patients. Therefore, the effect of different histological subtypes of multifocal PTC on CCLNM is another subject for further examination. The aim of the present study is to evaluate the rate of central lymph node positivity in multifocal PTC as compared to unifocal disease, and to identify the role of different histologic subtypes of PTC on central neck lymph node positivity. PATIENTS AND METHODS: Patients with PTC who underwent total thyroidectomy (TT) + central cervical lymph node dissection (CCLND) at authors' institution between January 2012 and June 2016 were included (n=274). Independent Samples t-test, Mann-Whitney U test and Chi-square tests were used to determine univariate associations, and multivariate analysis was conducted by logistic regression. RESULTS: The rate of CCLND positivity in multifocal PTC is higher than unifocal tumors and the difference is significant (p < 0.05). The univariate analysis demonstrated significant relation with male sex, lymphovascular invasion and size of dominant nodule > 10 mm regarding of CCLND positivity in multifocal PTC patients. The comparison between solitary and mixed histologic subtype of multifocal PTC is also significant (p < 0.05). CONCLUSIONS: Multifocality is an important risk factor for CCLNM. Male sex, dominant tumor size >10 mm and mixed histological subtype in multifocal PTC may play an important role in CCLND positivity.

The risk of hypoparathyroidism after central compartment lymph node dissection in the surgical treatment of pT1, N0 thyroid papillary carcinoma.

OBJECTIVE: The role of central compartment lymph node dissection (CCLND) in the treatment of papillary thyroid carcinoma (PTC) is still controversial. The benefits of CCLND should be weighed against its potential risks. We aim to evaluate the positivity of central lymph nodes in pT1, N0 PTC and to establish the complication rates of total thyroidectomy (TT)+CCLND. PATIENTS AND METHODS: This is a retrospective study on prospectively collected data over a 45-month period. A total of 329 patients were included. Total thyroidectomy was performed in 130 (39.5%) of these patients due to benign thyroid pathologies, and 199 (60.5%) pT1, N0 PTC patients had TT+CCLND. Our TT technique was applied in the same way in both groups. Central lymph node positivity, the number of lymph nodes removed during CCLND and the operative complications were evaluated. T-test and chi-square analysis were conducted in independent groups for statistical evaluation. RESULTS: The rate of central lymph node positivity in TT+CCLND group was 38%. The average number of lymph nodes removed by CCLND is 10.2 (1-36). Complication rates between TT and TT+CCLND groups were statistically significant (3.8% vs. 11.1%, respectively) (p<0.05). The difference was found to be particularly more pronounced for transient hypocalcemia. Although there was no significant relation between the number of lymph nodes removed during CCLND and the number of parathyroid glands detected in the pathology specimens (p>0.05), the relation between the development of symptomatic hypocalcemia and the number of the parathyroid glands removed during surgery was significant (p <0.05). CONCLUSIONS: Central compartment lymph node metastasis in PTC is common. CCLND may increase the rate of transient hypocalcemia.

Rosai Dorfman disease of the parotid and submandibular glands: salivary gland scintigraphy and oral findings in two siblings.

Rosai-Dorfman disease (RDD) is an unusual clinical entity characterized by benign pseudolymphomatous proliferation with significant histiocytic infiltration. In the present paper, extranodal RDD of the major salivary glands causing salivary hypofunction and the results of salivary gland scintigraphy and ultrasound are presented in two siblings. Case 1: a 10-year-old boy with bilateral painless masses around the parotid and submandibular glands was referred. Ultrasound examination showed bilateral, well-defined, hypoechoic solid mass lesions within both parotid glands with minimal normal parenchyma in the upper poles. Both submandibular glands were markedly hypoechoic and heterogeneous. Mass lesions within the parotid glands appeared as cold lesions with regular contours on scintigraphy. Dynamic images showed normal uptake and normal response to secretion in the upper poles of the parotid glands, corresponding with ultrasonographically normal parenchyma. Both submandibular glands showed markedly diminished uptake and secretion. Case 2: a 9-year-old boy presented with mass lesions around the submandibular glands. Ultrasound examination showed normal parotid glands and markedly hypoechoic and heterogeneous submandibular glands. Salivary gland scintigraphy showed normal uptake and secretion of parotid glands with markedly diminished uptake and secretion in both submandibular glands. There were severe carious lesions in both patients due to salivary hypofunction. Treatments of the two patients' teeth were performed. Major salivary gland involvement of RDD is important for dentists as it may cause xerostomia and can mimic dental abscess. Functional evaluation of salivary glands with scintigraphy, besides radiological and pathological techniques, will help to explain whether salivary glands are affected or not and improve the diagnostic effectiveness.

A practical approach to glomerular filtration rate measurements: creatinine clearance estimation using cimetidine.

Determination of creatinine clearance (Ccr) is not a reliable indicator of glomerular filtration rate (GFR), owing to tubular secretion of creatinine. It has been reported that Ccr measurements can approximate true GFR after cimetidine (Ci) administration. In this study, GFR was estimated by Cockcroft and Gault's equation (C(C-G)) based on measurement of plasma creatinine, and Ccr was determined by the standard clearance equation using 4- and 24-hr urine samples (Ccr4 and Ccr24, respectively) in 17 patients and 10 healthy controls. After cimetidine administration (800 mg, 3 times daily), GFR values were recalculated at the same time periods (C(CiC-G), CcrCi4 and CcrCi24, respectively). The results were all compared to those obtained by the 99mTc-DTPA protein-free double-sample method (C(DTPA)), which is a reference method for GFR determination. The coefficient of variation (CV%) for Ccr24/C(DTPA) was high before cimetidine administration; Ccr24 and CcrCi24 values were significantly different from C(DTPA) (CV 23.1%, Ccr24/C(DTPA) = 1.17, p 0.005; and CV 14.1%, CcrCi24/C(DTPA) = 0.92, p 0.006, respectively). Ccr4 values obtained before cimetidine ingestion showed large variation and were significantly different from C(DTPA) (CV 15.5%, Ccr4/C(DTPA) = 1.11, p 0.001). CcrCi4 values after cimetidine were similar to CDTPA (CV 6.9%, CcrCi4/C(DTPA) = 1.01, p 0.28). C(C-G) estimates were higher before cimetidine intake (CV 12.4%, C(C-G)/C(DTPA) = 1.21, p <0.001), whereas C(CiC-G) values were not significantly different from C(DTPA) values (CV 7.0%, C(CiC-G)/C(DTPA) = 1.01, p 0.67). This study shows that GFR estimations by C(C-G), Ccr4, Ccr24, or CcrCi24 are insufficiently reliable. On the other hand, C(CiC-G) and CcrCi4 results are acceptable for true GFR estimations.

Post-surgical ablation of thyroid remnants with high-dose (131)I in patients with differentiated thyroid carcinoma.

The aims of this study were to evaluate the efficacy of an empirically determined "fixed" high ablative dose of radioiodine ((131)I) therapy and to determine the utility of ultrasonography (US) in dose determination. A retrospective analysis was performed of 242 thyroid cancer cases treated with "fixed" high-dose (131)I for ablation of thyroid remnants without a pre-ablative (131)I diagnostic scintigraphy or radioiodine uptake study. Treatment doses ranged from 1850 MBq (50 mCi) to 7.4 GBq (200 mCi). The selection of the treatment dose was based on the surgical and pathological findings as well as the remnant thyroid volume calculated by US. A successful ablation was defined as the absence of activity in the thyroid bed on subsequent imaging studies. Successful ablation was obtained in 218 of the 242 patients (90%). In 162 of the 218 patients (74.3%), successful ablation was achieved after a single (131)I treatment. The remnant thyroid volume calculated by US was significantly different (P=0.04) between those who were successfully ablated and those who were not. The total (131)I dose needed for successful ablation was significantly higher in males (P=0.003). Patients with higher post-operative thyroglobulin (Tgb) levels and patients with a higher stage of disease required higher doses (P=0.036 and P=0.021 respectively). Serum Tgb levels were under 10 ng.ml(-1) in 220 of the 242 patients (90%) following radioiodine ablation while not receiving L-thyroxine suppression. Nineteen patients (7.8%) showed metastases on post-therapy scan and successful treatment was achieved in 11 of 19 (57.8%). Four of the 19 patients with distant metastases (revealed on post-treatment scan) were found to have been given a treatment dose of less than 200 mCi based on the proposed empirical approach. These results indicate that "fixed" high-dose (131)I treatment is clinically feasible with an acceptable dose underestimation rate, and the utilization of US in the determination of the thyroid remnant volume provides more accurate and reproducible results.

Comparison of In-111 octreotide and Tc-99m (V) DMSA scintigraphy in the detection of medullary thyroid tumor foci in patients with elevated levels of tumor markers after surgery.

PURPOSE: In this retrospective study, the authors evaluated the utility of In-111 octreotide (OctreoScan) and Tc-99m (V) DMSA scintigraphy for the localization of recurrent metastatic tumor foci in patients with medullary thyroid cancer (MTC) and compared the findings with those of conventional radiologic imaging methods. METHODS: The scintigraphic images were compared with computed tomography (CT) and magnetic resonance imaging (MRI) and ultrasonography (US) in 14 patients (8 men, 6 women; age range, 22 to 74 years) with elevated calcitonin and carcinoembryonic antigen levels after total thyroidectomy. All scintigraphic image findings were evaluated qualitatively as mild uptake (+) and moderate to marked uptake (++). RESULTS: In-111 octreotide may be superior to Tc-99m (V) DMSA for the detection of tumor foci of patients with MTC on a patient basis (78.5% versus 57.1%) and on a lesion basis (44.1% versus 30.2%). The sensitivity rate for In-111 octreotide (78.5%) was also similar to that of CT and MRI on a patient basis. Conversely, the combined use of Tc-99m (V) DMSA and In-111 octreotide revealed the best sensitivity rate (85.7%) on a patient basis, whereas the combined use of CT and MRI showed the best sensitivity rate (81.3%) on a lesion basis. CONCLUSIONS: These findings suggest that In-111 octreotide is superior to Tc-99m (V) DMSA and has a similar sensitivity rate to CT and MRI for the diagnosis of recurrent or metastatic MTC. Although the combined use of In-111 octreotide and Tc-99m (V) DMSA was most sensitive, the combined use of CT and MRI with radionuclide imaging methods may better detect more metastatic tumor foci.

Utility of ventilation and perfusion scan in the diagnosis of young military recruits with an incidental finding of hyperlucent lung.

Swyer-James-MacLeod syndrome (SJMS) is considered to be a relatively uncommon disease presenting with unilateral hyperlucent lung due to hypoplasia of a pulmonary artery and bronchiectasis of the affected lung. In this report, we describe the ventilation-perfusion (V/Q) scan findings of nine male recruits (aged 20-29 years, mean 24.4+/-2.96 years) with SJMS in whom the diagnosis was first established in adulthood. V/Q scan findings of all patients were compared with those on planar radiographs, pulmonary function studies, high resolution computed tomography (HRCT) and digital subtraction angiography (DSA). The ventilation (133Xe) and perfusion (99Tcm-macro-aggregated albumin) scans showed the characteristic pattern of a matched V/Q defect and marked air trapping on the washout phase on 133Xe scintigraphy. HRCT displayed hypodense lung with integrity of main airways, and markedly diminished vasculature on the affected side in all patients. A smaller pulmonary artery on the affected side with poor peripheral vasculature was observed with DSA in all patients. All patients had features of obstructive airway disease in varying degrees on pulmonary function studies. In contrast to other imaging methods, bronchiectasis as an etiological factor was displayed on HRCT. Some pulmonary areas, which were normal on HRCT and planar radiographs, showed air trapping on V/Q scan. Although a V/Q scan was more helpful in determining the extent of the disease and correlates well with conventional imaging methods, HRCT was the most valuable imaging method for the evaluation of aetiology in unilateral hyperlucent lung.

Use of CA15-3, CEA and prolactin for the primary diagnosis of breast cancer and correlation with the prognostic factors at the time of initial diagnosis.

The main goals of the clinical use of tumor markers are to evaluate the adequacy of the treatment, monitor recurrence and follow up response to the treatment applied. For this purpose a baseline level for the commonly used tumor marker must be known at the time of initial diagnosis, before any therapy, in order to compare with the tumor marker levels which will be obtained after the treatment and during the clinical follow-up. The aim of this study was to investigate the correlation, if there is any, of the baseline levels of CA15-3, CEA and prolactin (PRL) in patients with breast cancer with the most commonly used prognostic factors, i) the presence of distant metastasis, ii) the presence of axillary lymphatic invasion, iii) the number of invaded axillary lymph nodes, iv) tumor size and v) stage of the disease, for breast cancer. Baseline serum CA15-3, CEA and PRL levels of 172 patients with breast masses were determined prior to biopsy. The sensitivity and specificity of baseline CA15-3, CEA and PRL were; 23.2% and 95.3%, 17.41% and 83.7%, 5.8% and 97.6%, respectively. At least one of the three tumor markers was high in 36% (31/86) of the breast cancer patients. Baseline CA15-3 levels were frequently higher than CEA in patients with bone metastasis (60% vs. 20%) and axillary lymphatic invasion (31.8% vs. 25%), and showed a better correlation with the stage of disease. Baseline tumor marker levels showed no statistically significant correlation with either the number of invaded axillary lymph nodes or tumor size. In conclusion, sensitivities and negative predictive values for baseline CA15-3, CEA and PRL were not satisfactory for primary diagnosis of breast cancer. Correlation of baseline CA15-3 was found superior to CEA and PRL in terms of stage of disease, presence of axillary invasion and distant metastasis.

The comparison of dual phase Tc-99m MIBI and tc-99m MDP scintimammography in the evaluation of breast masses: preliminary report.

The aim of this prospective study was to determine the diagnostic value of Tc-99m MDP scintimammography (SMG) for the detection of breast cancer in patients with breast masses and to compare the results with Tc-99m MIBI scintimammography. Twenty patients, categorized as suspicious, positive or benign for breast cancer according to the mammographic findings were included in the study. Dual phase Tc-99m MIBI and Tc-99m MDP SMG were performed in the prone lateral position within 5 days of each other. Although early and late Tc-99m MIBI SMG showed equal (90.4%) sensitivity, the specificity of late Tc-99m MIBI (87.5%) was found superior to early (62.5%) imaging. The overall sensitivity and specificity of early Tc-99m MDP SMG were 71.4% and 62.5%, respectively. Although late Tc-99m MDP imaging showed 100% specificity, its sensitivity was only 23.8%. In the patients with palpable masses, both early Tc-99m MDP and Tc-99m MIBI showed equal sensitivity (100%), but the sensitivity of early Tc-99m MIBI (37.5%) was found slightly higher than Tc-99m MDP (25.0%) for nonpalpable breast lesions. The sensitivity of Tc-99m MIBI and Tc-99m MDP SMG in detecting metastatic axillary involvement was 66.6% and 50%, respectively. High sensitivity and specificity together with its low cost, easy availability and the possibility of detecting bone metastases seems to make Tc-99m MDP a contributive agent in the evaluation of breast lesions as an alternative to Tc-99m MIBI.

The role of Tc-99m (V) DMSA scintigraphy in the evaluation of superscan on bone scintigraphy.

PURPOSE: This study evaluated the biodistribution of Tc-99m (V) DMSA in patients with superscans on bone imaging and defined its role in differentiating the underlying cause. METHODS: Nine patients (five with metastatic and four with metabolic bone disease) with classical superscans were entered into the study. All patients had the necessary radiologic and biochemical studies and a final diagnosis was reached accordingly. Tc-99m (V) DMSA scintigraphy was performed 1 week after Tc-99m MDP whole-body bone imaging. RESULTS: In four of five patients with widespread skeletal metastases, Tc-99m (V) DMSA scan showed diffusely increased bone uptake. In the remaining patient, the Tc-99m (V) DMSA scan showed a normal distribution pattern. All patients with metabolic bone disease had increased bone uptake on Tc-99m (V) DMSA scans. CONCLUSION: Tc-99m (V) DMSA shows increased bone uptake in patients having a superscan appearance in metastatic or metabolic bone disease. Tc-99m (V) DMSA imaging may play a role in the evaluation of patients with equivocal bone scan findings for a superscan.

Synthesis of [99mTc]ethylenedicysteine-colchicine for evaluation of antiangiogenic effect.

Angiogenesis is in part responsible for tumor growth and the development of metastasis. Radiolabeled angiongenesis inhibitors would be useful to assess tumor microvasculature density. Colchicine (COL), a potent antiangiogenic agent, is known to inhibit microtubule polymerization and cell arrest at metaphase. This study aimed to develop 99mTc-labeled COL (EC-COL) using ethylenedicysteine (EC) as a chelator to assess tumor microvascular density. EC was conjugated to trimethylcolchicinic acid using N-hydroxysuccinimide and 1-ethyl-3-dimethylaminopropyl carbodiimide as coupling agents with a yield of 50-60%. In vivo stability was analyzed in rabbit serum at 0.5-4 h. Tissue distribution and planar imaging studies of [99mTc]EC-COL were evaluated in breast tumor-bearing rats at 0.5, 2 and 4 h. The data was compared to that using [99mTc]EC (control). The radiochemical yield of [99mTc]EC-COL was greater than 95%. [99mTc]EC-COL was stable in rabbit serum. In vivo biodistribution of [99mTc]EC-COL in breast tumor-bearing rats showed increased tumor-to-blood (0.52+/-0.12 to 0.72+/-0.07) and tumor-to-muscle (3.47+/-0.40 to 7.97+/-0.93) ratios as a function of time. Conversely, tumor-to-blood values showed a time-dependent decrease with [99mTc]EC over the same time period. Planar images confirmed that the tumors could be visualized clearly with [99mTc]EC-COL from 0.5 to 4 h. [99mTc]EC-COL may be useful to assess antiangiogenic and therapeutic effects during chemotherapy.

Noninvasive assessment of tumor hypoxia with 99mTc labeled metronidazole.

PURPOSE: The assessment of tumor hypoxia by imaging modality prior to radiation therapy would provide a rational means of selecting patients for treatment with radiosensitizers or bioreductive drugs. This study aimed to develop a 99mTc-labeled metronidazole (MN) using ethylene-dicysteine (EC) as a chelator and evaluate its potential use to image tumor hypoxia. METHODS: EC was conjugated to amino analogue of MN using Sulfo-N-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-HCl as coupling agents, the yield was 55%. Tissue distribution of 99mTc-EC-MN was determined in breast tumor-bearing rats at 0.5, 2, and 4 hrs. Planar imaging and whole-body autoradiograms were performed. The data was compared to that using 99mTc-EC (control), [18F]fluoromisonidazole (FMISO) and [(131)I] iodomisonidazole (IMISO). RESULTS: In vivo biodistribution of 9mTc-EC-MN in breast tumor-bearing rats showed increased tumor-to-blood and tumor-to-muscle ratios as a function of time. Conversely, tumor-to-blood values showed time-dependent decrease with 9mTc-EC in the same time period. Planar images and autoradiograms confirmed that the tumors could be visualized clearly with 99mTc-EC-MN from 0.5 to 4 hrs. There was no significant difference of tumor-to-blood count ratios between 99mTc-EC-MN and [(131)I]IMISO at 2 and 4 hrs postinjection. From 0.5 to 4 hrs, both 9mTc-EC-MN and [(131)I]MISO have higher tumor-to-muscle ratios compared to [18]FMISO. CONCLUSIONS: It is feasible to use 9mTc-EC-MN to image tumor hypoxia.

99Tcm-MIBI scintimammography in the evaluation of breast lesions and axillary involvement: a comparison with mammography and histopathological diagnosis.

The aim of this prospective study was to determine the diagnostic value of prone lateral 99Tcm-MIBI scintimammography in the detection of primary breast cancer and axillary lymph node involvement in patients with breast lesions. We evaluated 83 palpable and 22 non-palpable lesions in 77 consecutive patients with a clinically palpable mass and/or suspicious mammographic finding. Early and late scintimammograms were performed after the intravenous injection of 740 MBq 99Tcm-MIBI. The overall sensitivity of both scintimammography and mammography in the detection of primary breast cancer was 94%. The overall specificity was 84% and 56% for scintimammography and mammography respectively. In the patients with palpable masses, the sensitivity of scintimammography was 97% and the specificity was 84%; in those with non-palpable masses, the sensitivity was 35% and the specificity 100%. For the detection of axillary lymph node involvement, the sensitivity and specificity of scintimammography were 68% and 93% respectively. However, conventional mammography showed 37% sensitivity and 86% specificity. In conclusion, scintimammography is an accurate and clinically valuable tool for evaluating palpable and non-palpable breast abnormalities. In addition to its high sensitivity, it improves the specificity of mammography both in the evaluation of breast masses and in the detection of axillary involvement.

Biodistribution and scintigraphy of [111In]DTPA-adriamycin in mammary tumor-bearing rats.

The aim of this study was to develop an 111In-labeled diethylenetriamine pentaacetic acid-adriamycin (DTPA-ADR) conjugate to image breast cancer. DTPA-ADR was synthesized by reacting adriamycin with DTPA anhydride in the presence of carbonyldiimidazole. After dialysis (MW cut off was 500), the product was freeze-dried (yield 40-50%). An in vitro cell culture study was performed using cells from the 13,762 Fischer rat mammary tumor line. Drug concentrations tested were 0.1-100 microM. Biodistribution studies were conducted at 0.5, 2, 24 and 48 h in mammary tumor-bearing rats (n = 3/time interval, 10 microCi/rat, i.v.) with 13,762 cells (10(5) cells/rat, s.c.). Planar imaging and autoradiograms were obtained at the same intervals. In vitro cell culture assays showed an IC50 of 0.1 +/- 0.01 microM for ADR and 7.2 +/- 0.29 microM for DTPA-ADR, respectively. In biodistribution studies, tumor/blood uptake ratios of [111In]DTPA-ADR at 0.5, 2, 24 and 48 h were 0.55 +/- 0.17, 0.94 +/- 0.17, 3.06 +/- 0.53 and 3.66 +/- 0.35, respectively, whereas those for [111In]DTPA (control) were 1.19 +/- 0.69, 0.84 +/- 0.07, 0.56 +/- 0.10 and 0.60 +/- 0.03, respectively. The tumor uptake value (%ID/g) of [111In]DTPA-ADR at 0.5 h was 0.20 +/- 0.06. Planar images and autoradiograms showed good visability of tumors. Biodistribution, autoradiography and radionuclide imaging of [111In]DTPA-ADR in breast tumor-bearing rats showed that tumor-to-blood ratios increased steadily between 30 min and 48 h. These results indicate that DTPA-ADR, a new cancer imaging agent, might be useful in the diagnosis of breast cancer and may predict a therapeutic effect prior to treatment.

Discordance of sialography and scintigraphy in unilateral chronic sialadenitis.

A Tc-99m pertechnetate salivary gland scintigraphy, digital subtraction sialography (DSS) and cytological findings of a 48-year-old female who received I-131 therapy for the treatment of follicular carcinoma of thyroid are presented. Post radioiodine therapy sialoscintigraphy showed increased blood flow and uptake with decreased secretion in the left parotid gland suggesting acute inflammation. In contrast, DSS and fine needle aspiration biopsy (FNAB) findings were consistent with chronic sialoadenitis. Follow-up scintigraphy one month later showed normal blood flow and decreased uptake and confirmed the diagnosis of chronic sialoadenitis. In right of this case, we conclude that since management of sialoadenitis depends on the stage of inflammation scintigraphic findings should be interpreted together with radiology and FNAB findings if necessary. When chronic sialoadenitis is followed by acute exacerbations, diagnosis based exclusively on sialoscintigraphic findings may result in inadequate patient management.