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A Prospective Study on 3,907 Patients with Thyroid Nodules. Sono-histological Comparison and the Controversial Significance of the Halo Sign in Predicting Thyroid Malignancy.

Solymosi T., Toth G.L., Nagy D., Gal I. British Journal of Medicine and Medical Research 2015; 5.8: 1053-1059. doi: 10.9734/BJMMR/2015/13743 FULL TEXT


Background: The aim of this study was a comparison of the ultrasonographic (US) and histopathological findings on patients with thyroid nodules (TNs) in a moderately iodine-deficient region.
Methods: The US properties (The echostructure, the presence of halo sign, microcalcification, blurred border, vascularization, and the taller-than-wide sign) of 7,180 TNs were assessed in 3,907 patients later underwent surgery.
Results: 411 malignant cases were found. The risk of malignancy was significantly higher in cases involving a hypoechogenic nodule, microcalcification, a blurred border, type 3 vascular pattern or the taller-than-wide sign. The presence of a halo sign was associated with a significantly lower risk of malignancy in cases with hypoechogenic TNs, but with a significantly higher risk in cases with moderately hypoechogenic TNs. As concerns hyperechogenic TNs, the presence of a halo sign had no influence on the risk of malignancy. Among the patients with microfollicular proliferation without atypia on cytology, the risk of malignancy was significantly lower in the absence than in the presence of a halo sign.
Conclusions: The US features of a malignant TN are in general the same in our iodine-deficient region as in iodine-sufficient areas. The significance of a halo sign depends considerably on the echostructure of the TN. A combined assessment of the US and cytological findings may help avoid unnecessary surgery in patients with suspected follicular tumor.


Influence of Iodine Intake on the Diagnostic Power of Fine-Needle Aspiration Cytology of the Thyroid Gland.

Solymosi T., Toth G.L., Gal I., Sajgo C., Szabolcs I. Thyroid 2002;12:719-723.
doi: 10.1089/105072502760258703


In order to determine whether the iodine intake influences the diagnostic power of ultrasound-guided fine-needle aspiration cytology (US-FNAC), patients with nontoxic nodular goiter from an area with sufficient iodine intake (IS) ( n = 938, median iodine excretion [MIE] = 103 µ g/L) and from an iodine-deficient (ID) area ( n = 3601, MIE = 75 µ g/L) were investigated. Elevated rates of multinodularity (59.6% vs. 49.6%, p < 0.001), nonpalpable nodules (47.6% vs. 37.3%, p < 0.001) and nondiagnostic US-FNACs (8.8% vs. 5.1%, p = 0.008), and a lower malignancy rate (1.2% vs. 2.3%, p = 0.006) were found in the ID area. Follicular tumors were encountered among positive findings. Cytohistologic comparison (ID, n = 416; IS, n = 97) revealed that the sensitivity, specificity, and diagnostic accuracy of US-FNAC were similar in the two areas (95.5% vs. 92.3%, 78.3% vs. 71.1%, 82.4% vs. 80.6%, IS vs. ID area, respectively), while a lower malignancy rate and a higher ratio of benign to malignant tumors were observed in the ID than in the IS area (10.1% vs. 22.6%, p < 0.001, and 4.38 vs. 1.50, p < 0.001, respectively). This resulted in a lower positive predictive value of US-FNAC in the ID (36/106) than in the IS area (21/36, p = 0.001), because the rate of false US-FNAC was higher in benign (67/184) than in malignant tumors (4/61, p < 0.001).


The Clinical and Pathological Presentation of Thyroid Nodules in Children and the Comparison with Adult Population: Experience of a Single Institution.

Solymosi T., Lukacs Toth G., Budai L., Gal I. Int J Endocrinol. 2016; ID 1256189
doi: 10.1155/2016/1256189 FULL TEXT


The clinical and pathological presentation of thyroid nodules among younger and adult patients was compared in an iodine-deficient (ID) region. Data of 3,010 consecutive patients younger than 20 years and 3,010 patients older than 20 years were compared. The proportion of nodular goiters (22.8% versus 39.3%), the ratio of surgically treated nodules (33.2% versus 15.2%), and the proportion of malignant nodules (4.3% versus 2.1%) among diseased patients differed significantly between the two groups (younger versus adult). Nine papillary and 1 medullary carcinoma were found among children, while 15 papillary, 2 follicular, 1 insular, 1 anaplastic, and 1 medullary carcinomas occurred among adults. The ratio of follicular adenoma to hyperplastic nodules (3?:?1 to 1?:?1.67), the proportion of follicular variant (77.8% versus 26.7%), T4 tumors (77.8% versus 33.3%), and tumors with lymph node metastasis (88.9% versus 66.7%) were significantly higher among younger papillary carcinoma patients. No malignancies occurred among spongiform and central type cysts. Similarly to iodine-sufficient regions, more nodules are malignant and carcinomas have a clinically more aggressive presentation in children in comparison with adult patients in ID. Taking the significantly greater proportion of adenomas and the lack of follicular carcinoma into account, a conservative approach has to be considered in follicular tumors among children.


Twenty Years of Experience with the Preoperative Diagnosis of Medullary Cancer in a Moderately Iodine-Deficient Region.


Solymosi T., Toth G.L., Nagy D., Gal I. International Journal of Endocrinology 2013, ID 571606
doi: 10.1155/2013/571606 FULL TEXT


Background. There is a current debate in the medical literature about plasma calcitonin screening in patients with nodular goiter (NG). We decided on analyzing our 20-year experience with patients in an iodine-deficient region (ID). Patients and Methods. 22,857 consecutive patients with NG underwent ultrasonography and aspiration cytology (FNAC). If FNAC raised suspicion of medullary cancer (MTC), the serum calcitonin was measured. Results. 4,601 patients underwent surgery; there were 23 patients among them who had MTC (0.1% prevalence). Significantly more MTC cases were diagnosed cytologically in the second decade than in the first: 11/12 and 6/11, respectively. The frozen section was of help in 2 cases out of 3. Two patients suffered from a 3-year delay in proper therapy, and reoperation was necessary in 1 case. FNAC raised the suspicion of MTC in 20 cases that were later histologically verified and did not present MTC. The diagnostic accuracy of FNAC in diagnosing MTC was 99.2%. Two false-positive serum calcitonin tests (one of them in a hemodialyzed patient) and one false-negative serum calcitonin test occurred in 40 cases. Conclusion. Regarding the low prevalence of MTC in ID regions, calcitonin screening of all NG patients does not only appear superfluously but may have more disadvantages than advantages.

Minimally invasive video-assisted thyroidectomy and conventional thyroidectomy: a prospective randomized study.


Gal I., Solymosi T., Szabo Z., Baint A., Bolgar G. Surg Endosc 2008;22:2445-2449.
doi: 10.1007/s00464-008-9806-2.


BACKGROUND. Since the first description of the minimally invasive totally gasless video-assisted thyroidectomy (MIVAT) technique in 1998, relatively few studies have evaluated the outcome of this procedure. The authors review their experiences based on a prospective randomized trial comparing the potential advantages of MIVAT over conventional thyroidectomy.
METHODS. Patients undergoing surgery for either thyroid nodule or diffuse thyroid disease with hyperthyroidism were randomly selected for either MIVAT or conventional thyroidectomy. The exclusion criteria specified nodules larger than 35 mm, thyroid lobe volume greater than 20 ml, thyroiditis, and previous neck irradiation or surgery. Operative time, postoperative complications, and cosmetic results were evaluated using both a verbal response scale and a numeric scale.
RESULTS. Both the MIVAT group and the conventional thyroidectomy group included 15 patients. No significant differences were noted between the two groups in terms of age, sex, or indication for operation. The mean operative times were 65.5 +/- 18 min. for MIVAT and 43.3 +/- 14 min. for conventional thyroidectomy (P = 0.001). No postoperative complications were detected in either group. The cosmetic results, evaluated by both verbal response and numeric scales, were respectively as follows: MIVAT (3.7 +/- 0.2 and 7.9 +/- 1.2) and conventional thyroidectomy (2.3 +/- 0.7 and 4.9 +/- 1.3). The differences significantly favored MIVAT (P = 0.028 and P = 0.015, respectively) despite the small number of patients enrolled in this study, and consequently, its limited statistical power.
CONCLUSION. Although the complications are comparable between the two approaches, conventional thyroidectomy involves less operative time. However, MIVAT offers distinct advantages to selected patients in terms of very good to exellent cosmetic results and reduced postoperative distress.


Diagnostic Accuracy of Fine Needle Aspiration Cytology of the Thyroid. Impact of Ultrasonography and Ultrasonographically Guided Aspiration.


Solymosi T., Toth G.L., Bodo M. Acta Cytologica 2001;45:669-674.


OBJECTIVE: To determine the impact of ultrasonography on the diagnostic accuracy of fine needle aspiration cytology (FNAC) of the thyroid. STUDY DESIGN: We compared two FNAC series. In period 1 we used neither ultrasonograph nor ultrasonographically - guided FNAC in the evaluation of thyroid nodules, while both tools were routinely applied in period 2. Moreover, in the former period all cellular follicular lesions were encountered among suspicious findings, while in period 2 we advised regular follow-up examinations instead of immediate surgery for patients with no significant atypia. The basis of follow-up examinations was ultrasonographic volumetry of the nodule and repeat FNAC on growing nodules. RESULTS: The number of FNAC, positive predictive value of FNAC, number of malignancies, sensitivity, the specificity and diagnostic accuracy were higher in period 2 as compared with period 1: 3,446 vs. 1,448; 45% vs. 16%, 39 vs. 29, 92% vs. 76%, 65% vs. 87% and 66% vs. 87%, respectively. CONCLUSION: The introduction of ultrasonography permits higher diagnostic accuracy of the evaluation process. This is achieved not only by lessening false negative reports but, more important, by decreasing false positive results.

Percutaneous ethanol sclerotherapy of symptomatic nodules is effective and safe in pregnant women: A study of 13 patients with an average follow-up of 6.8 years.


Solymosi T., Melczer Zs., Szabolcs I., Nagy E.V., Goth M. International Journal of Endocrinology 2015, ID 765950
doi: 10.1155/2015/765950 FULL TEXT


Background. Because of the increased risk of surgery, thyroid nodules causing compression signs and/or hyperthyroidism are concerning during pregnancy. Patients and methods. Six patients with non-toxic cystic, four with non-toxic solid and three patients with overt hyperthyroidism caused by toxic nodules were treated with percutaneous ethanol injection therapy (PEI). An average of 0.68 mL ethanol per 1 mL nodule volume was administered. Mean number of PEI treatment for patient was 2.9. Success was defined as the shrinkage of the nodule by more than 50% of the pre-treatment volume (V0) and the normalization of TSH and FT4 levels. The average V0 was 15.3 mL. Short-term success was measured prior to labor, whereas long-term success was determined during the final follow-up (an average of 6.8 years). Results. The pressure symptoms decreased in all but one patient after PEI and did not worsen until delivery. The PEI was successful in 11 (85%) and 7 (54%) patients at short-term and long-term follow-up, respectively. Three patients underwent repeat PEI which was successful in 2 patients. Conclusions. PEI is a safe tool and seems to have good short-term results in treating selected symptomatic pregnant patients. Long-term success may require repeat PEI.


Treatment of Recurrent Nodular Goiters with Percutaneous Ethanol Injection: A Clinical Study of Twelve Patients.


Solymosi T., Gal I. Thyroid. 2003, 13: 273-277.
doi:10.1089/105072503321582079. FULL TEXT


Twelve patients who had previously undergone thyroid surgery received percutaneous ethanol injection (PEI) treatment because of recurrent nodular goiter (3 with a toxic [TN], 2 with a nontoxic cystic [NCN], and 7 with a nontoxic solid nodule [NSN]). Two of the 12 had recurrent nerve palsy contralateral to the nodule. Each patient received a mean total dose of 0.88 mL of ethanol per milliliter of nodular volume. Ethanol was injected in a mean of 3.5 sessions for solid and 3 sessions for NCN. In most cases, a slight to moderate burning pain was experienced during and for 12–48 hours after PEI treatment, and one patient experienced temporary hoarseness. One patient with TN and 2 patients with NSN became hypothyroid, 7 patients with nontoxic nodules remained euthyroid, 1 with TN became euthyroid, and a previously hyperthyroid patient with TN became subclinically hyperthyroid 1-year posttherapy. The nodule shrank by more than 50% of the pretreatment volume in all patients (8.6 ± 2.6 vs. 2.9 ± 1.2 mL in TN, and 12.3 ± 4.9 vs. 4.16 ± 2.54 mL in nontoxic nodules, pretreatment vs. 1 year posttreatment volume, respectively). With regard to the increased risk of reoperation, PEI treatment can be proposed for patients with recurrent nodular goiter requiring surgery.


Evaluation of the Long-term Growth Potential of Benign Non-toxic Thyroid Nodules by the AgNOR Method; an 11-year Follow-up Study.


Solymosi T., Gal I., Bodo M., Toth G.L., Nagy E.V. J Cytol Histol S3:008. 2015
doi: 10.4172/2157-7099.S3-008 FULL TEXT


Objective: The classification of benign thyroid nodules as stable or as fast growing may have clinical and economical relevance. The proliferative activity of thyroid cells determined by argyrophilic staining of the nucleolar organizer region (AgNOR) displays significant differences between benign and malignant thyroid lesions. We tested if that parameter can predict the growth potential of benign nodules.
Methods: On cytological samples of 106 benign nodules of 89 euthyroid patients, the mean AgNOR number per cell (AgNORc), the mean AgNOR area per cell (AgNORa) and the mean nuclear area were determined. The mean follow-up period was 11.9 years. The initial (V1) and the final (V2) nodule volumes and respective TSH values (TSH1 and TSH2) were determined.
Results: 66 nodules (62.2%) increased in volume. The median of V2/V1 was 1.31. V2/V1 correlated significantly with AgNORa, AgNORc, nuclear area and TSH-1. There was no significant correlation between V2/V1 and either age, duration of follow-up or TSH-2. No correlation was found between V2 and any of the parameters. We found on both forward and backward stepwise analysis that AgNORc values and initial TSH levels were significant determinates of the increase in volume size, i.e. both higher AgNORc values and higher initial TSH levels carry a greater risk for nodule growth.
Conclusions: The determination of AgNORc during FNA evaluation may contribute to the estimation of growth potential of thyroid nodules. Further studies using other enzyme techniques or new molecular methods are justified to achieve a better discrimination between stable and growing nodules.

Diagnostic value of AgNOR method in thyroid cytopathology: Correlation with morphometric measurements.


Solymosi T., Toth V., Sapi Z., Bodo M., Gal I., Csanadi L. Diagnostic Cytopathology 1996, 14: 140-144. doi: 10.1002/(SICI)1097-0339(199603)14:2


A silver staining technique was applied to 51 thyroid smears. The numbers of silver-stained nucleolar organizer regions (AgNORs) were counted, and the mean AgNOR and nuclear area per cell were determined with an image analyzer. The mean AgNOR count per cell was significantly higher in malignant than in benign lesions, but there was a considerable overlap. The mean AgNOR area and the mean SD of the AgNOR area per cell were significantly higher in carcinomas than in benign lesions (P = 10–9 and P = 5 × 10–10, respectively) and there were only two and one benign cases, respectively, of overlap. A strong correlation was observed between the mean AgNOR area and the mean nuclear area (r = 0.88), the former being a better discriminator between benign and malignant lesions. The AgNOR technique may contribute to routine thyroid cytopathology.

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