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Percutaneous ethanol injection therapy in benign solitary solid cold thyroid nodules: a randomized trial comparing one injection with three injections.

The aim of the present study was to evaluate the efficacy of percutaneous ethanol injection therapy (PEIT) with special reference to dose response and symptom score and to describe side effects in a parallel-group randomized clinical trial with 6 months of follow-up, comparing 2 different treatment strategies. Sixty euthyroid outpatients with a benign solid and scintigraphically solitary cold thyroid nodule causing local discomfort were assigned to 1 session with a single intranodular injection of sterile 98% ethanol (PEIT-1, n = 30) or 3 weekly sessions with 1 injection of sterile 98% ethanol (PEIT-3, n = 30). In the PEIT-1 group, the pretreatment nodule volume was 9.9+/-5.7 mL (mean +/- SD). It decreased to 7.0+/-4.7 mL after 1 month, and 5.6+/-5.9 mL after 6 months (p = 3.2x10(-6)), and the ethanol dose given was 24.7%+/-7.5% of the pretreatment nodule volume. The overall reduction in nodule volume was 46%. In the PEIT-3 group the pretreatment nodule volume was 9.4+/-4.2 mL. It decreased to 5.9+/-3.5 mL 1 month after the last session, and 4.6+/-2.6 mL after 6 months (p = 4.0x10(-10)), and the cumulative ethanol dose given was 47.9%+/-21.3% of the pretreatment nodule volume. The overall reduction in nodule volume was 51%, and the difference between the 2 treatment regimens was 5.3%+/-5.5% (mean +/- SE of difference, p = 0.3). A satisfactory treatment dose, defined as a total intranodular spread of ethanol visualized on the monitor screen, was achieved in only 50%-60% of the sessions. This was due to pain that necessitated premature discontinuation of the injection and was apparently severe enough in 3 patients in the PEIT-3 group that they refused additional treatment. Twenty-two of 30 (73%) patients in the PEIT-1 group and 19 of 30 (63%) in the PEIT-3 group had a marked effect on symptoms at 6-month follow-up (p = 0.6). Side effects comprised transient thyrotoxicosis in 2 patients, permanent ipsilateral facial dysesthesia and increased flow of tears in 1 patient, paranodular fibrosis impeding subsequent surgery in 1 case and various degrees of pain and tenderness related to PEIT in nearly all. Major side effects were dose dependent. We conclude that PEIT is effective in inducing necrosis and reducing the volume of benign solid cold thyroid nodules. The additive effect of 2 additional doses compared with 1 dose is insignificant. The optimum management strategy has yet to be clarified. Limitations relate to the procedure being quite painful despite local anesthesia and the fact that side effects are in no way negligible, and therefore, a word of caution in routine use is advisable.

Adult↗

Comparison of palpation-guided fine-needle aspiration biopsy to ultrasound-guided fine-needle aspiration biopsy in the evaluation of thyroid nodules.

OBJECTIVE: Although fine-needle aspiration biopsy (FNAB) of thyroid nodules is a reliable and simple method, the diagnostic value may be limited by inadequate and false-negative results. In this prospective study, we compared palpation-guided FNAB (PGFNAB) with ultrasound-guided FNAB (UGFNAB) to establish the rates of inadequate material and cost-effectiveness. DESIGN: A total of 285 thyroid nodules in 215 patients were included in the study. Palpable nodules with the greatest diameter between 1 and 2.5 cm were included in the study. PGFNAB and UGFNAB techniques were applied to the same nodule by the same operator. Cytologic evaluations were performed by the same cytologist in a blinded fashion. To provide cost analysis, the prices obtained from different hospitals were evaluated. MAIN OUTCOME: The rates of inadequate material for PGFNAB and UGFNAB were significantly different as 32.3% and 21.4%, respectively (p = 0.004). There was significantly higher inadequate material rate in PGFNAB group for small-sized nodules (greatest nodule diameter between 10 and 15 mm) (p = 0.009), despite inadequate material rate was not significant for both procedures for larger sized nodules. False-negative results were 15.8% for PGFNAB and 5.6% for UGFNAB. Regarding cost analysis, the difference between the two methods was 20 dollars on average for each patient. CONCLUSIONS: We consider UGFNAB to be superior to PGFNAB for obtaining adequate material especially for small-sized nodules, as well as providing more accurate cytologic evaluation. Indeed, the difference between the costs of two procedures might be acceptable.

Adolescent↗

Effect of ultrasound-guided interstitial laser photocoagulation on benign solitary solid cold thyroid nodules: one versus three treatments.

OBJECTIVE: Interstitial laser photocoagulation (ILP) is a safe and effective procedure when inducing thyroid nodule necrosis. In this prospective randomized study, we evaluated a possible dose-response relationship as well as patient satisfaction. DESIGN: Thirty euthyroid outpatients with a cytologically benign solitary solid and scintigraphically cold thyroid nodule causing local discomfort were assigned to one session of ILP (ILP-1) (n = 15) or three monthly ILP sessions (ILP-3) (n = 15) and followed for 6 months. ILP was performed under continuous ultrasound (US)--guidance and with an output power of 2.5-3.5 W. Thyroid nodule volume was assessed by US. Pressure and cosmetic complaints were evaluated on a visual analogue scale. MAIN OUTCOME: In the ILP- 1 group, thyroid nodule volume decreased from 10.1 +/- 4.3 mL (mean +/- standard deviation [SD]) to 5.7 +/- 3.2 mL (p = 0.0004), and in the ILP-3 group from 10.8 +/- 5.5 mL to 4.6 +/- 3.0 mL (p = 0.0005) during follow-up. The overall mean difference between the two groups was 13%, corresponding to an improved mean thyroid nodule volume reduction of 30% (p = 0.03). In both groups subjective symptoms were significantly reduced, and without difference between the two groups (p = 0.7). No major side effects were seen in either group. CONCLUSION: As a nonsurgical therapeutic option, ILP-1 approximately halves thyroid nodule volume with concomitant symptom relief. There is little incremental effect of additional ILP treatment, which should be limited to patients with large nodules or limited nodule reduction after the first treatment.

Adult↗

Thyroid nodules: diagnosis and therapy.

Less than 1% of all cancers are present in the thyroid, yet thyroid nodules are found in 4 to 10% of the adult population. Because thyroid nodules are relatively common, the diagnostic dilemma is to distinguish between a more common benign nodule, which usually does not require specific treatment, and a malignant nodule, which requires thyroidectomy and further treatment. Thyroid nodules usually are an incidental finding on a routine examination by a primary care physician. When patients seek treatment for symptomatic nodules, a more serious problem may be indicated, and thyroid cancer is suggested. However, additional studies have demonstrated the use of genetic markers and immunohistochemistry in the diagnosis of thyroid nodules, which may lead to a more rational approach to the treatment. This article reviews literature published in the last 12 months pertaining to the pathogenesis, diagnosis, and treatment of thyroid nodules.

Algorithms↗

Thyroid imaging with Tc-99m MIBI in patients with solitary cold single nodules on pertechnetate imaging.

Thyroid imaging was performed in 30 patients with the standard pertechnetate technique, as well as with Tc-99m MIBI using a double-phase acquisition protocol. All patients had normal thyroid function confirmed by hormone measurements and cold solitary thyroid nodules, which were evaluated by pertechnetate scanning. Tc-99m MIBI scans were reported as showing cold (N = 14), warm (N = 7), or hot (N = 9) nodules. Nodule classification was made according to fine needle aspiration biopsy findings in 20 patients. The remaining 10 proceeded to surgery and had histopathologic confirmation of their lesions. Although all cold nodules with Tc-99m MIBI were cystic, six of the warm nodules were benign lesions. No histologically proven benign nodule was hot with Tc-99m MIBI. Of the hot nodules, seven were suspicious for follicular carcinoma with fine needle aspiration biopsy (N = 3), or had histologically proven papillary carcinoma (N = 4). Delayed images in five of seven of these lesions showed nodular retention of the radiopharmaceutical. In conclusion, double-phase Tc-99m MIBI scanning of the thyroid gland could be helpful in the preoperative assessment of patients with cold solitary thyroid nodules in order to evaluate the malignancy probability of these lesions.

Adenocarcinoma, Follicular↗

Infectious pulmonary nodules in immunocompromised patients: usefulness of computed tomography in predicting their etiology.

PURPOSE: To review the high-resolution computed tomography (CT) findings in immunocompromised patients who had nodular opacities and a proven diagnosis to determine whether the various infectious pulmonary nodules have distinguishing features on CT. MATERIALS AND METHODS: The high-resolution CT scans obtained in 78 immunocompromised patients with solitary or multiple nodular opacities of proven infectious etiology were reviewed retrospectively by 2 independent thoracic radiologists. Patients whose predominant abnormality consisted of branching linear or nodular opacities (tree-in-bud pattern) characteristic of infectious bronchiolitis and endobronchial spread of tuberculosis were excluded. The CT scans were assessed for the presence, appearance, size, and distribution of parenchymal nodules. Relations between findings at CT and the different infectious etiologies of nodules were assessed with regression analysis. Agreement between the 2 observers was assessed using the kappa statistic. RESULTS: The infectious causes included mycobacteria (n = 24), fungi (n = 22), bacteria (n = 20), and viruses (n = 12). Multivariate analysis demonstrated that a diameter <10 mm was the only independent predictor of etiology (P < 0.0001) and that patients whose nodules all measured less than 10 mm in diameter were most likely to have a viral infection. Nodules limited in size to less than 10 mm in diameter were seen in 83% of viral infections compared with 5% of bacterial infections (odds ratio [OR] = 95.0; 95% confidence interval (CI): 6.08-4,321.5, P < 0.0001), 0% of mycobacterial infections (OR = 91.7; 95% CI: 7.21-4,090.22, P < 0.0001), and 14% of fungal infections (OR = 31.67; 95% CI: 3.56-375.09, P = 0.0003). CONCLUSION: Although some overlap exists, nodule size is helpful in the differential diagnosis of infectious causes of nodules in immunocompromised patients. Patients whose nodules are all less than 10 mm in diameter are most likely to have a viral infection.

Acquired Immunodeficiency Syndrome↗

Small incidental pulmonary nodules: how useful is short-term interval CT follow-up?

PURPOSE: To determine whether short-term (<6 month) follow-up imaging by thoracic CT is necessary to evaluate small (< or =4 mm) noncalcified nodules (NCN) in patients with no history of malignancy or acute lung disease. MATERIALS AND METHODS: We reviewed serial thoracic helical CT scans between 1999-2000 obtained for the evaluation or follow-up imaging of small NCNs. CT scans were performed at 5-mm collimation. Patients were excluded if they had a history of neoplasm, infection, pulmonary fibrosis, or immune deficiency; also excluded if nodule(s) > or =5 mm at intake, or no follow-up scan within 1 year. NCNs were evaluated for number, size, configuration, and change in size over time. Exact 95% Confidence Intervals were used to estimate chances of nodule growth in 3-, 6-, and 12- month intervals. RESULTS: A total of 1826 patients received a CT for NCNs. Four hundred fourteen patients met inclusion criteria (221 women, 193 men; mean age, 65.6 years). Eighty-five patients had a single NCN, 329 had multiple NCNs. One hundred seventy-three patients had additional > or =5 mm nodules. One hundred twenty-seven patients were lost to follow up within the 1-year period. Eight nodules cleared. None of the < or =4 mm NCNs grew on follow-up imaging within 12 months. Three patients developed lung cancer in other nodules > or =5 mm (5-10 mm). These nodules grew on follow up intervals of 3-13 months. One patient had a 19 mm benign hamartoma that grew in 9 months. The calculated chance that a NCN < or =4 mm will grow within 3, 6, and 12 months (95% CI) is < or =0.89%, 1.01%, and 1.28%, respectively. CONCLUSION: The chance of growth in < or =4 mm NCNs in a 3- to 6-month period in patients with no previous history of malignancy or immune disorder is small; therefore, short-term follow-up imaging (<12 month) for nodules < or =4 mm is not necessary.

Adult↗

Solitary pulmonary nodule: detection and management.

Pulmonary nodules are commonly detected at computed tomography (CT) of the chest. More than 95% are < or = 10 mm; of these more than 95% are benign. Visual detection of pulmonary nodules by human readers is suboptimal, particularly with small nodules < or =10 mm. Computer-assisted detection can improve sensitivity and diagnostic confidence. Due to the high proportion of malignant lesions in nodules >10 mm immediate, often invasive workup is required including contrast-enhanced dynamic CT, positron emission tomography (PET) or biopsy. However, in nodules < or =10 mm the high proportion of benign lesions requires a non-invasive work-up usually based on follow-up with unenhanced CT. Invasive procedures are only required for growing nodules. Stable nodules require further follow-up and decreasing nodules are considered benign.

Adenocarcinoma↗

On measuring the change in size of pulmonary nodules.

The pulmonary nodule is the most common manifestation of lung cancer, the most deadly of all cancers. Most small pulmonary nodules are benign, however, and currently the growth rate of the nodule provides for one of the most accurate noninvasive methods of determining malignancy. In this paper, we present methods for measuring the change in nodule size from two computed tomography image scans recorded at different times; from this size change the growth rate may be established. The impact of partial voxels for small nodules is evaluated and isotropic resampling is shown to improve measurement accuracy. Methods for nodule location and sizing, pleural segmentation, adaptive thresholding, image registration, and knowledge-based shape matching are presented. The latter three techniques provide for a significant improvement in volume change measurement accuracy by considering both image scans simultaneously. Improvements in segmentation are evaluated by measuring volume changes in benign or slow growing nodules. In the analysis of 50 nodules, the variance in percent volume change was reduced from 11.54% to 9.35% (p = 0.03) through the use of registration, adaptive thresholding, and knowledge-based shape matching.

Algorithms↗

Recommendations for the management of cystic thyroid nodules.

BACKGROUND: The management of cystic thyroid nodules has not been standardized with respect to an initial fine-needle aspiration cytology (FNAC) cystic change result, which is defined as fluid aspiration and a smear with numerous macrophages but scant or no follicular cells. In the present study the physical characteristics of cystic thyroid nodules predictive of the pathology were investigated, and recommendations made on their management. METHODS: The aspiration results of 1436 thyroid nodules managed between 1998 and 2000 were investigated. A total of 157 patients who had a subsequent operation or follow-up data with reaspiration were the subjects of the present study. Age, sex, nodule characteristics and others were examined as possible predictors of cancer risk. RESULTS: The malignancy rate was 8.9%. Ten cases (71%) of malignancy were not cytologically diagnosed. Male sex and a nodule size of > or = 4 cm were found to be statistically significant predictors of malignancy. The malignancy rate was highest (100%) when a cystic lesion had malignant cytology on reaspiration and local invasion on radiology. CONCLUSIONS: When a cystic change is observed by initial FNAC of thyroid nodules, nodules of > or = 4 cm must be reaspirated and a firm cytologic diagnosis made to rule out malignancy. Nodules should be considered for surgery having taken into account other characteristics, in particular male sex and radiologic findings of local invasion.

Adult↗

Solitary pulmonary nodules: Part I. Morphologic evaluation for differentiation of benign and malignant lesions.

The solitary pulmonary nodule is a common radiologic abnormality that is often detected incidentally. Although most solitary pulmonary nodules have benign causes, many represent stage I lung cancers and must be distinguished from benign nodules in an expeditious and cost-effective manner. Evaluation of specific morphologic features of a solitary pulmonary nodule with conventional imaging techniques can help differentiate benign from malignant nodules and obviate further costly assessment. Small size and smooth, well-defined margins are suggestive of but not diagnostic for benignity. Lobulated contour as well as an irregular or spiculated margin with distortion of adjacent vessels are typically associated with malignancy. There is considerable overlap in the internal characteristics (eg, attenuation, cavitation, wall thickness) of benign and malignant nodules. The presence of intranodular fat is a reliable indicator of a hamartoma. The presence and pattern of calcification can also help differentiate benign from malignant nodules. Computed tomography (CT) (particularly thin-section CT) is 10-20 times more sensitive than standard radiography and allows objective, quantitative assessment of calcification. Initial evaluation often results in nonspecific findings, in which case nodules are classified as indeterminate and require further evaluation to exclude malignancy. Growth rate assessment, Bayesian analysis, contrast material-enhanced CT, positron emission tomography, and transthoracic needle aspiration biopsy can be useful in this regard.

Biopsy, Needle↗

CT screening for lung cancer: suspiciousness of nodules according to size on baseline scans.

PURPOSE: To assess the frequency with which a particular, possibly optimal work-up of noncalcified nodules less than 5.0 mm in diameter identified on initial computed tomographic (CT) images at baseline screening leads to a diagnosis of malignancy prior to first annual repeat screening, compared with a possibly optimal work-up of larger nodules. MATERIALS AND METHODS: Two series of baseline CT screenings in high-risk people were retrospectively reviewed. The first series (n = 1,000) was performed in 1993-1998; the second (n = 1,897), in 1999-2002. In each series, cases in which the largest noncalcified nodule detected was less than 5.0 mm in diameter and those in which it was 5.0-9 mm were reviewed to determine whether diagnostic work-up prior to first annual repeat screening showed or would have shown nodule growth and led or would have led to a diagnosis based on biopsy or surgical specimens. RESULTS: The frequency with which malignancy was or could have been diagnosed when the largest noncalcified nodule was less than 5.0 mm in diameter was 0 of 378, whereas when the largest noncalcified nodule was 5.0-9 mm in diameter, the frequency was 13 or 14 of 238. If persons with only nodules smaller than 5.0 mm had merely been referred for first annual repeat screening without immediate further work-up, the referrals for such work-up would have been reduced by 54% (from 817 [28%] to 385 [13%] of 2,897). CONCLUSION: In modern CT screening for lung cancer at baseline, detected noncalcified nodules smaller than 5.0 mm in diameter do not justify immediate work-up but only annual repeat screening to determine whether interim growth has occurred.

Adult↗

Solitary pulmonary nodules: comparison of classification with standard, thin-section, and reference phantom CT.

Standard, thin-section, and reference phantom computed tomography (CT) were performed to evaluate 75 consecutive patients with solitary pulmonary nodules. Follow-up was available for 62 nodules in 59 patients; 53 of the nodules were benign and nine were malignant. Twenty-one of the 62 nodules were assessed as benign with thin-section CT, while 33 of the 62 nodules were assessed as benign with reference phantom CT. Two of the nodules classified as benign with both thin-section and reference phantom CT proved to be malignant (a peripheral, ossified carcinoid and a 3.5-cm-diameter calcified carcinoma). The sensitivity of reference phantom CT (58%) for classification of benign nodules was higher than the sensitivity of thin-section CT (36%). The sensitivity of standard CT was lowest (12%). The presence of fat at thin-section CT was a reliable criterion for benignancy in six hamartomas. While both thin-section and reference phantom CT were useful in the identification of benign pulmonary nodules, reference phantom CT increased sensitivity by 22% compared with thin-section CT.

Adult↗

Prevalence of thyroid nodules in an occupationally radiation exposed group: a cross sectional study in an area with mild iodine deficiency.

BACKGROUND: Thyroid nodules and thyroid cancer occur more frequently in people exposed to radiation for therapeutic purposes, and to nuclear fallout. Furthermore, it is known that a moderate degree of iodine deficiency may be responsible for an increased prevalence of thyroid nodules, while it is suspected that radiation exposure could induce changes in thyroid autoimmunity. The iodine intake of people resident in Bari, S. Italy, is mildly deficient, which could be presumed to cause a higher prevalence of thyroid pathology. This study was conducted to evaluate the prevalence of thyroid nodules in a population occupationally exposed to radiation, in an area of mild iodine deficiency. METHODS: A cross-sectional study was designed to evaluate the prevalence of thyroid nodules in radiation exposed workers, compared with a stratified sample of non exposed workers. After giving written consent to participate in the study, all the recruited subjects (304 exposed and 419 non exposed volunteers) were interviewed to fill in an anamnestic questionnaire, and underwent a physical examination, ultrasound thyroid scan, serum determinations of fT3, fT4 and TSH, fine needle aspiration biopsy. The sample was subdivided into one group exposed to a determined quantity of radiation (detected by counter), one group exposed to an undetectable quantity of radiation, and the non exposed control group. RESULTS: The prevalence of thyroid nodules < 1 cm in diameter, defined as incidentalomas, in the exposed group with detected doses, was 11.28% in males and 9.68% in females, while in the exposed group with undetectable dose the prevalence was 10.39% in males and 16.67% in females. In the non exposed group the prevalence of incidentalomas was 9.34% in males and 13.20% in females. These prevalences were not statistically different when analysed by a multiple test comparison with the bootstrap method and stratification for sex. Instead, the prevalence of thyroid nodules > 1 cm in diameter resulted statistically different in exposed and non exposed health staff: 18.68% in non exposed males vs exposed: 3.76% (determined dose) and 9.09% (undetectable dose) in males, and 20.30% in non exposed females versus 3.23% (detected dose) and 9.52% (undetectable dose) in exposed females. There was a higher proportion of healthy staff in the exposed group than in the non exposed: (80.45% vs 68.68% in males; 80.65% vs 57.87% in females). CONCLUSION: In our study, occupational exposure to radiation combined with mild iodine deficiency did not increase the risk of developing thyroid nodules. The statistically significant higher prevalence of thyroid nodules in the non exposed group could be explained by the high percentage (22%) of people with a familial history of, and hence a greater predisposition to, thyroid disease. The endemic condition of mild iodine deficiency, demonstrated in other studies, played a major role in determining the thyroid pathology in our study groups.

Adult↗

Morphological and functional polymorphism within clonal thyroid nodules.

Thirty-nine thyroid nodules, removed because of recent growth, were analyzed morphologically by serial histological sections for the classical histomorphological hallmarks of follicular cell replication and for immunohistochemically demonstrable overexpression of the growth-associated ras-gene product p21ras. Clonal analysis was performed using the highly informative probe M27 beta that detects polymorphisms on the locus DXS255 of the X-chromosome. Twenty-four nodules were of clonal and 15 nodules were of poly-clonal origin. Only 3 out of the 24 clonal nodules were histomorphologically uniform. In all others, the structural hallmarks of active growth and the P21ras growth-marker expression were remarkably heterogeneous throughout the tumors. There were no histomorphological characteristics distinguishing these clonal tumors from polyclonal nodules. Even if a clonal thyroid tumor may be originally homogeneous in respect to the parameters studied here, mechanisms must exist that create wide heterogeneity of growth and of morphogenetic potential among the individual follicular cells during further expansion of the nodule. Thus, clonal nodules are much more common in nodular goiters than hitherto assumed on grounds of the classical morphological criteria. The diagnosis of a true monoclonal nodule can no longer rely on morphological and functional criteria alone but requires molecular or cytogenetic analysis of clonality.

Adult↗

Effect of percutaneous ethanol injection therapy versus suppressive doses of L-thyroxine on benign solitary solid cold thyroid nodules: a randomized trial.

The results of studies using suppressive doses of L-T4 on benign solitary solid cold thyroid nodules have been conflicting. Recently, intranodular injection of absolute ethanol has been proposed as an effective treatment, but has been evaluated only in uncontrolled studies. Our objective was to evaluate the effect of two alternative medical treatment modalities, percutaneous ethanol injection therapy and L-T4, on the benign solitary solid cold thyroid nodule. In a prospective randomized clinical trial, 50 euthyroid patients with a single solid colloid thyroid nodule causing local discomfort were assigned to a single intranodular injection of sterile 98% ethanol (n = 25) or suppressive doses of L-T4 (n = 25). We aimed at an ethanol dose of 20-50% of the pretreatment nodular volume. The initial daily dose of L-T4 was 1.5 microg/kg BW and was adjusted monthly during the first 6 months to reduce serum TSH to subnormal levels (<0.40 mU/L). Thyroid nodule volume and total thyroid volume were assessed by ultrasound, and thyroid function was determined by routine assays before and during follow-up. Symptom scores before and at 12 months were evaluated by a questionnaire rating pressure symptoms and cosmetic symptoms. The median ethanol dose given was 21% [95% confidence interval (CI), 18;25] of the pretreatment nodule volume. In this group, the median reduction in nodule volume was 47% (CI, 33;57; P < 0.0001) compared to 9% (CI, -7;22; P = 0.09) in the L-T4 group. The difference between the two treatment regimens was statistically significant (P < 0.0001). The median reduction in perinodular thyroid volume was 20% (CI, 11;31; P = 0.03) in the L-T4 group, whereas no change was seen in the ethanol group (-2.5%; CI, -18;11; P = 0.9). Fourteen of 25 (56%) patients treated with ethanol injection and 8 of 25 (32%) treated with L-T4 had complete relief of symptoms at 12 months of follow-up (P = 0.09). No major side-effects were seen in either group. Percutaneous ethanol injection therapy administered as a single small dose results in a satisfactory clinical response in approximately 50% of patients by halving the nodule volume. The thyroid nodule-reducing effect of L-T4 suppressive therapy is insignificant, but a subjective satisfactory clinical response is seen in a subgroup of patients, probably explained by the concomitant reduction of perinodular thyroid volume.

Administration, Cutaneous↗

RET/PTC rearrangements in thyroid nodules: studies in irradiated and not irradiated, malignant and benign thyroid lesions in children and adults.

Rearrangements of the RET proto-oncogene may occur in both naturally occurring and radiation-induced papillary thyroid carcinomas. Conflicting results on the frequency and type of RET/PTC rearrangements have been reported in relation to age, radiation exposure, and histological tumor variant. We designed the present study to evaluate in a single laboratory, using the same methodologies, the pattern of RET/PTC activation in thyroid tumors from different groups of patients (exposed or not exposed to radiation, children or adults, with benign or malignant tumors) in relationship to the above mentioned variables. We studied 154 patients with benign nodules (n = 65) or papillary thyroid cancer (n = 89). In the last group, 25 were Belarus children exposed to the post-Chernobyl radioactive fallout, 17 were Italian adults exposed to external radiotherapy for benign diseases, and 47 were Italian subjects (25 children and 22 adults) with no history of radiation exposure. Among patients with benign thyroid nodules, 21 were Belarus subjects (18 children and 3 adults) exposed to the post-Chernobyl radioactive fallout, 8 were Italian adults exposed to external radiation on the head and neck, and 36 were Italian adults with naturally occurring benign nodules. The overall frequency of RET/PTC rearrangements in papillary thyroid cancer was 55%. The highest frequency was found in post-Chernobyl children and was significantly higher (P = 0.02) than that found in Italian children not exposed to radiation, but not significantly higher than that found in adults exposed to external radiation. No difference of RET/PTC rearrangements was found between samples from irradiated (external x-ray) or not irradiated adult patients, as well as between children and adults with naturally occurring, not irradiated, thyroid cancer. When analyzing the type of RET/PTC rearrangement (RET/PTC1 or RET/PTC3), no major difference was apparent. In addition, eight cases with an unknown RET/PTC rearrangement and three cases with the concomitant expression of RET/PTC1 and RET/PTC3 were found. No significant correlation was observed between the frequency and/or the type of RET/PTC rearrangement and clinical-epidemiological features of the patients such as age at diagnosis, age at exposure, histological variant, gender and tumor-node-metastasis (TNM) categories. RET/PTC rearrangements were also found in 52.4% of post-Chernobyl benign nodules, in 37.5% of benign nodules exposed to external radiation and in 13.9% of naturally occurring nodules (P = 0.005, between benign post-Chernobyl nodules and naturally occurring nodules). The relative frequency of RET/PTC1 and RET/PTC3 in rearranged benign tumors showed no major difference. In conclusion, our results indicate that the presence of RET/PTC rearrangements in thyroid tumors is not restricted to the malignant phenotype, is not higher in radiation-induced tumors compared with those naturally occurring, is not different after exposure to radioiodine or external radiation, and is not dependent from young age. Other factors, probably influenced by ethnic or genetic background, may act independently from or in cooperation with radiation, to trigger the DNA damage leading to RET proto-oncogene activation.

Adolescent↗

Efficacy of ultrasound-guided fine-needle aspiration biopsy in the diagnosis of complex thyroid nodules.

Cystic thyroid nodules are considered to be one of the major causes of nondiagnostic and false-negative results on conventional fine-needle aspiration biopsy, thus limiting the potential of this method for the evaluation of complex (solid-cystic) thyroid nodules. Although ultrasound-guided fine-needle aspiration biopsy has emerged as a highly effective diagnostic method for the assessment of nonpalpable and difficult to palpate nodules, its role in complex nodules has not yet been carefully evaluated. In this study, we report the efficacy of ultrasound-guided fine-needle aspiration biopsy in 124 complex nodules in 113 patients. This method proved to be highly effective, yielding a satisfactory specimen for cytological evaluation in 94% of the nodules, suggesting that it is an excellent modality for the evaluation of complex nodules and also for the reevaluation of those nodules with a nondiagnostic result on conventional fine-needle aspiration biopsy.

Adult↗