Differential diagnostic technique for high differentiated cancer in patients with nodular forms of thyroid diseases

FIELD: medicine.

SUBSTANCE: fine-needle aspiration of nodular thyroid growths is controlled by ultrasonic examination. A puncture needle containing an aspirate is washed twice in normal saline 1 ml, centrifuged; a supernatant is selected, and thyroglobulin is measured by enzyme immunoassay. If the thyroglobulin content is less than 272.5 ng/ml, the absence of high differentiated cancer is stated; the value falling within the range of 272.5-355.5 ng/ml shows a risk of high differentiated thyroid cancer; if the thyroid value is more than 355.5 ng/ml, high differentiated thyroid cancer is suspected.

EFFECT: invention provides the pre-operative differential diagnostics of high differentiated cancer in the patients suffering nodular forms of thyroid diseases, and also enables the further selection of an adequate method of treating.

3 ex

 

The invention relates to medicine, namely to Oncology, surgery, laboratory diagnostics, and can be used preoperatively to improve the differential diagnosis of well-differentiated cancer in patients with nodular forms of thyroid diseases to select the appropriate method of treatment.

To nodular forms of thyroid diseases according to the who classification (1988) include the following: I. Nodular colloid in varying degrees of proliferating goiter; II. Tumor: 1. Epithelial: a) benign, (b) malignant; 2. Non-epithelial benign and malignant [1, 2]. Nodular diseases of the thyroid gland combines the presence in the parenchyma of the thyroid gland "nodular" or "node". The term "education hub" or "hub" means multiple focal lesions of the thyroid gland, as determined by palpation or by any imaging method, characterized by different morphological features [1, 2]. Because of the heterogeneity of the histostructure of nodules difficulties in their differential diagnosis in the preoperative period, which may lead to wrong selection of treatment tactics. For the differential diagnosis of cancer and benign diseases tumor markers are used, these include thyreophora�in [3, 4, 8].

Thyroglobulin is synthesized exclusively by thyrocytes (follicular A - and B-cells) of the thyroid gland and malignant tumors originating from follicular cells [3]. Well-differentiated malignant tumors actively secrete thyroglobulin in the thyroid gland and its lymph node metastases [3]. However, the identification of thyroglobulin in the serum has no independent diagnostic value, since no differences in the levels in benign disease and well-differentiated thyroid cancer [4].

However, immunocytochemical study revealed that the expression of thyroglobulin increases directly in tissue of a malignant tumor of the thyroid gland, and in this case, the thyroglobulin can be considered a diagnostic indicator for well-differentiated thyroid cancer [5].

The known method of the study of thyroglobulin in the washout with the puncture needle from the lymph nodes to detect metastatic thyroid cancer [6, 7]. However, this method is intended to diagnose only metastases, but not for the differential diagnosis of well-differentiated cancer and benign nodular forms of thyroid disease and not provide guidance on Diagne�forecast thyroglobulin values.

The known method of determination of thyroglobulin by ELISA in the serum [8]. Method [8] is characterized in that 1) the content of thyroglobulin is determined in the serum and not directly in the tissue of the nodules of the thyroid gland; 2) on the basis of this method it is impossible to carry out the differential diagnosis of well-differentiated cancer and benign nodular forms of thyroid diseases; 3) these diagnostic indices of thyroglobulin have only values of the serum.

The known method of the study of thyroglobulin in the washout aspirate with needle aspiration biopsy of nodules of the thyroid gland [9, 10]. The known method has the following disadvantages: 1) not disclosed technique of the method; 2) is specified, only the mean values of thyroglobulin in different clinical groups, but there are no diagnostic value of thyroglobulin, which is necessary for the differential diagnosis of well-differentiated cancer and benign nodular forms of thyroid diseases. As presented, the known method [9, 10] cannot be used as a diagnostic method. This method will use as a prototype.

Object of the invention is to provide a method of differential diagnosis wysokotemperaturowe�of fucking cancer in patients with nodular forms of thyroid diseases to select the appropriate method of treatment.

The invention consists in that in the method of differential diagnosis of well-differentiated cancer in patients with nodular forms of thyroid diseases, including fine needle aspiration biopsy of a nodule of the thyroid gland under ultrasound, a needle puncture with the contained aspirator washed twice with 1 ml of isotonic sodium chloride solution, then centrifuged, take supernatant and enzyme immunoassay to determine the thyroglobulin, and if the content of thyroglobulin less 272,5 ng/ml suggests the absence of well-differentiated thyroid cancer, in the interval 272,5-355,5 ng/ml - risk well-differentiated thyroid cancer, above 355,5 ng/ml suggest a highly differentiated thyroid cancer.

The proposed method is developed as a result of the research content of thyroglobulin in a cellular aspirate obtained by needle aspiration biopsy of a nodule of the thyroid gland, in 80 patients. Of these, 37 were patients with well-differentiated thyroid cancer and a 43 - benign forms of nodular disease (nodular colloid goiter, adenoma thyroid gland). The thyroglobulin was determined by enzyme immunoassay used with�eat an automated analyzer "Multiscan EX (Finland) and the reagent kit for immunoassay determination of thyroglobulin tiroid ELISA-TG (Russia, St. Petersburg). As a diagnostic threshold for well-differentiated thyroid cancer, there is a level of thyroglobulin more 355,5 ng/ml. the sensitivity of the method in the differential diagnosis of nodules of the thyroid gland was 64.9% and the specificity was 95.3 per cent. The area under ROS-curve (AUC) was 0.85±0.04) was that based on the expert scale for AUC values, refers to very good results [11]. Application of the proposed method in addition to standard research methods (ultrasound and Cytology) has improved the sensitivity in the differential diagnosis from 64.9% to 86.5% and specificity - from 62.8% to 92,9%. Set the levels of thyroglobulin in the washout aspirate of the thyroid gland of the puncture needle for benign nodular disease of the thyroid gland (one-multinodular colloid goiter, benign tumors) - less 272,5 ng/ml, the risk of well-differentiated thyroid cancer - in the interval 272,5-355,5 ng/ml and well-differentiated thyroid cancer is higher 355,5 ng/ml.

The proposed method is as follows: 1) perform a fine needle aspiration biopsy of the thyroid gland under ultrasound and receive cellular aspirate; 2) the puncture needle (21G) containing the received TSA�Rath, washed twice with 1 ml of isotonic sodium chloride solution and the resulting mixture was placed in a special tube; 3) centrifuge and take the supernatant; 4) conduct the assay; 5) analyze the results: if the value of thyroglobulin less 272,5 ng/ml suggests the absence of well-differentiated cancer and the likelihood of benign disease of the thyroid gland, in the interval 272,5-355,5 ng/ml - risk well-differentiated thyroid cancer, above 355,5 ng/ml suggest a highly differentiated thyroid cancer.

Application of the method may have important diagnostic value with indeterminate cytological diagnosis refers to "follicular tumor" of the thyroid gland. "Follicular tumor" refers to the ability of cancer or adenoma of the thyroid gland without significant differences between these diseases, which can lead to a wrong choice of surgical treatment [12]. The true diagnosis is established only when postoperative histological examination of the removed drug based on the presence of tumor invasion of the capsule and blood vessels [12].

Give examples of the practical implementation of the proposed method.

Example 1.

Patient S., 53 years old (case history No. 2808/11), was admitted to the clinic with complaints about the presence of nodal education�ing in the neck. The anamnesis of disease for 9 months, when the examination by an endocrinologist revealed nodular formation of thyroid. The rapid growth of the site in the last 3 months. Comorbidities: diabetes mellitus type 2, hypertension. When you receive a satisfactory condition. Thyroid function - autores. Palpation of the thyroid gland is not enlarged, the right lobe is defined nodular formation, rounded, dense, with a diameter of 1.5 cm, displace when swallowing. Peripheral lymph nodes were not enlarged neck. The thyroid ultrasound: Right lobe 49×17×18 mm In the upper pole of the right lobe - hypoechoic node 16,8×10,8 mm with clear contours heterogeneous structure with PermitRootLogin the bloodstream. Left lobe 50×17×18 mm without nodules. Conclusion ultrasound: the nodular formation of thyroid. Produced by core needle aspiration biopsy under ultrasound with cytologic study and the enzyme immunoassay of the content of thyroglobulin in the washout of the needle aspirate of the needle.

Cytological diagnosis of follicular tumor.

The thyroglobulin in the washout aspirate - of 402.6 ng/ml.

Given the high level of 402.6 thyroglobulin ng/ml (<355,5 ng/ml), ultrasound data and cytological examination of the patient S. have cancer of the thyroid glands� T1N0MO. Patient S. is aimed at surgical treatment. Made with adequate oncological positions surgical treatment - extrafascial thyroidectomy.

Postoperative histological diagnosis (No. 2218/11): follicular thyroid cancer.

Such an example shows that on the basis of inclusion in a comprehensive diagnosis of nodules in thyroid research of the content of thyroglobulin in the washout aspirate of the thyroid gland can even with indeterminate cytological diagnosis, which is "follicular tumor", to more accurately diagnose the presence of thyroid cancer in the preoperative period and to perform an adequate volume of surgical treatment.

Example 2.

Patient S., 57 years old (case history No. 4666/10), was admitted to the clinic with complaints about the presence of nodules in the right lobe of the thyroid gland. The history of the disease within 10 years, periodically observed an endocrinologist, noted a gradual increase of the node. Thyroid function - autores. Palpation in the right lobe of the thyroid gland is determined by the nodal education rounded, normal density, with a diameter of 3 cm, displace when swallowing. Peripheral lymph nodes were not enlarged neck. Ultrasound of the thyroid: the entire right portion is hypoechoic node 25×13×19 mm with indistinct contours, rim, about�heterogeneous structure, with intranodular the bloodstream. Left lobe is not changed. Conclusion ultrasound: education hub of the right lobe of the thyroid gland. Produced by core needle aspiration biopsy under ultrasound with cytologic study and the enzyme immunoassay of the content of thyroglobulin in the washout of the needle aspirate of the needle.

Cytological diagnosis of follicular tumor.

The thyroglobulin in the washout aspirate - at 82.8 ng/ml.

Given the levels of thyroglobulin at 82.8 ng/ml (<272,5 ng/ml), the results of ultrasound and cytological studies in patient S. hypothesized that thyroid cancer is absent and there is a benign disease, most likely an adenoma of the thyroid gland. Patient S. is aimed at surgical treatment. Produced by the removal of the right lobe of the thyroid gland hemithyroidectomy.

Postoperative histological diagnosis (No. 4823/10): adenoma cells from Ashkenazi, nodular colloidal goiter.

Such an example shows that the study of the content of thyroglobulin in the washout aspirate in the complex diagnosis of nodules of the thyroid gland even with indeterminate cytological diagnosis ("follicular tumor") allows you to exclude thyroid cancer and assume adenoma. In this connection it is possible to solve organizarea�General surgery (hemithyroidectomy) with preservation of the left lobe of the thyroid gland.

Example 3.

Patient G., 66 years old (case history No. 8471/10), was admitted to the hospital with complaints of enlargement of the thyroid gland. In 1986 - resection of the thyroid gland. The recurrence of the disease after 8 years. The function of the thyroid gland - hypothyroidism. Palpation in the right lobe of the thyroid gland nodular formation up to 2 cm in diameter, in the left - 1,5 cm Nodes soft-elastic consistency, displace when swallowing. Peripheral lymph nodes were not enlarged. Ultrasound of the thyroid: in the left lobe is hypoechoic with a smooth contour nodal education 23×22 mm with PermitRootLogin the bloodstream. In the right lobe nodal education - 15×11 mm izoehogennaya, a vague outline, intranodular the bloodstream. Conclusion ultrasound: nodular thyroid.

Produced by core needle aspiration biopsy under ultrasound with cytologic study and the enzyme immunoassay of the content of thyroglobulin from the puncture needle.

Cytological diagnosis:

The node of the right lobe - follicular tumor; node left lobe - colloid goiter.

The thyroglobulin in the washout aspirate from a node of the right lobe - 288,6 ng/ml.

The thyroglobulin in the washout of the aspirate of the node of the left lobe - to 120.4 ng/ml.

Given the levels of thyroglobulin 288,6 ng/ml (range 272,5-355,5 ng/ml), ultrasound data and cytological studies in patient G. p�eprogen cancer of the right lobe of the thyroid gland, and benign disease (colloid goiter) of the left lobe.

Patient S. is aimed at surgical treatment. Produced thyroidectomy.

Postoperative histological diagnosis (No. 8728/10): papillary carcinoma of the right lobe of the thyroid gland, nodular makrofollikulârnaâ craw of the left lobe.

The mentioned example shows that in the complex diagnosis study the content of thyroglobulin in the washout of the aspirate of the nodule contributes to a more accurate differential diagnosis for multi-node diseases of the thyroid gland in the preoperative period and the choice of adequate surgical tactics.

The technical result of the invention is to improve the differential diagnosis of well-differentiated cancer in patients with nodular forms of thyroid diseases in the preoperative period to select the appropriate method of treatment.

The list of references

1. Petunina N. And., L. V. Trukhina thyroid Disease. - M.: GEOTAR-Media, 2011. - P. 151-156.

2. Endocrinology: the national guide / ed. by I. I. Dedov, G. A. Melnichenko. - M.: GEOTAR-Media, 2008. Pp. 504-519.

3. Spencer, A. C. Modern principles of assessment of the level of thyroglobulin in patients with well-differentiated cancer of the thyroid // Thyroid International (in Russian). - 2003. - №. 4. - S. 1-15.

4. Thyroid disease / Henry M. Kronenberg, Shlomo Melmed, Kenneth �. Polonsky, P. reed Larsen: per. from English. ed. by I. I. Dedov, G. A. Melnichenko. - M.: OOO "reed elsiver", 2010. - P. 80-81.

5. RF patent №2455517. Reshetov I. V., Slavnova E. N. A method for diagnosing the degree of malignant thyroid cancer, Byull. No. 17. - 20.06.2013.

6. Rumyantsev P. O. Comprehensive diagnosis and treatment of thyroid cancer based on etiopathogenic and prognostic factors: author. dis. ... doctor. honey. science / S. P. Kazakov. - Obninsk, 2009. - 37 p.

7. Romanchishen A. F., Gostomski V. A., Zaitseva I. V., E. V. Lipsky New opportunities puncture biopsy in the diagnosis of thyroid cancer and hyperparathyroidism // Modern aspects of surgical endocrinology: Mat. XIX ROS. Symp. - Chelyabinsk, 2010. Pp. 306-308.

8. Kamyshnikov B. C. tumor Markers: methods of determining reference values, interpretation of tests. - M.: Medpress-inform, 2011. Pp. 76-78.

9. Olifirova O. S. Kalyan S. V., Chalchenkova I.e., Trynov N. N. New opportunities in the preoperative diagnosis of nodular thyroid diseases // Bulletin of the division WITH the RAMS. - Irkutsk, 2012. - №4 (86), part 1. - P. 63-67.

10. Kalan S. V., Olifirova O. S., Trynov N. N., Chalchenkova I.e. the results of the study of tumor markers in nodular thyroid disease // Journal of Practical medicine". - Kazan, 2013. - №2 (67). - S. 149-152.

11. ] N. Logistic regression and ROS-analysis - mathematical apparatus. [E�my] Available at: http://www.basegroup.ru/library/analysis/regression/logistic/

12. Follicular thyroid neoplasia / E. A. Troshina, N. In. Mazurin, I. A. Abesadze et al. / / Problems of endocrinology. - 2006. - No. 1. - P. 23-25.

Method of differential diagnosis of well-differentiated cancer in patients with nodular forms of thyroid diseases, including fine needle aspiration biopsy of a nodule of the thyroid gland under the control of ultrasound, characterized in that the puncture needle with the contained aspirator washed twice with 1 ml of isotonic sodium chloride solution, then centrifuged, take supernatant and enzyme immunoassay to determine the thyroglobulin, and if the content of thyroglobulin less 272,5 ng/ml suggests the absence of well-differentiated thyroid cancer, in the interval 272,5-355,5 ng/ml - risk well-differentiated thyroid cancer, above 355,5 ng/ml suggest a highly differentiated thyroid cancer.



 

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