RU2493770C2 - Method of diagnosing cancer in patients with pre-operation cytological diagnosis "follicular neoplasm" of thyroid gland by means of mathematical modelling - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to oncology and surgery, and can be used for diagnostics of thyroid gland cancer in patients with pre-operation cytological diagnosis "follicular neoplasm". Cytological, ultrasound and clinical-anamnestic examination of thyroid gland is carried out. 13 parameters, constituting mathematical model, are determined. Parameters are introduced into mathematical model, in case if sign is present, value "1" is given, in case of its absence "0". Values Y1 and Y2 are calculated by claimed function. If Y1 is larger than Y2, diagnosis of thyroid gland cancer is stated. If Y2 is larger, than Y1, diagnosis of thyroid gland cancer is excluded.

EFFECT: method makes it possible to diagnose cancer of thyroid gland in pre-operation period for selection of adequate type of surgery.

2 ex

Description

The invention relates to medicine, namely to oncology and surgery, and can be used in the preoperative period for the diagnosis of cancer in patients with a preoperative cytological diagnosis of “follicular tumor” to select an appropriate type of surgical operation.

The term "follicular tumor" refers to an "indefinite" preoperative cytological diagnosis, which means the possibility of cancer or adenoma of the thyroid gland without significant differences between these diseases, which can lead to incorrect surgical treatment. A true diagnosis is made only by postoperative histological examination of a removed thyroid preparation based on the presence of invasion of the capsule and blood vessels.

For differential diagnosis in patients with “follicular tumors” of the thyroid gland, immunocytochemical methods are used (1, 4, 6), and the use of molecular biooncomarkers (2). These methods are characterized by the complexity of the implementation, the need to use special equipment and reagents, performed by specially trained doctors, are expensive.

The proposed diagnostic method using mathematical modeling is simple and fast, low cost, non-invasive, the possibility of repeated use in an outpatient setting by a surgeon.

Closest to the claimed is a method for the diagnosis of thyroid tumors using mathematical modeling (5). The known method has the following disadvantages: 1. the method is designed only for the diagnosis of thyroid tumors without dividing them into benign tumors and thyroid cancer; 2. the method is not applicable for the diagnosis of cancer in patients with a cytological diagnosis of "follicular tumor" of the thyroid gland.

A known method for diagnosing and predicting the number of new cases of highly differentiated cancer among nodules of the thyroid gland using a mathematical model (6). The known method has the following disadvantages: the method is designed for use in large groups of patients for a long period of time - 5-6 years and does not provide for individual use for the diagnosis and treatment of each particular patient.

The technical result is the diagnosis of thyroid cancer in the preoperative period using a mathematical model in patients with a preoperative cytological diagnosis of "follicular tumor" to select the appropriate type of operation.

The proposed method allows using a mathematical model in the form of classifying functions that were calculated during a step-by-step discriminant analysis using the statistical package STATISTICA 6.0 with stepwise inclusion of variables (Forward stepwise) in the analysis of 22 standard clinical and medical history and ultrasound parameters in 124 patients, as a result of which 13 most informative parameters were selected that made up the model, and their classification function coefficients were calculated, diagnosed with thyroid cancer in preoperative This period in patients with a preoperative cytological diagnosis of "follicular tumor" to select an appropriate type of operation:

Classifying functions for the diagnosis of thyroid cancer:

Cancer Y1 = -15.93 + 7.10 · X1 + 8.25 · X2 + 6.12 · X3 + 7.07 · X4 + 3.97 · X5 + 5.75 · X6 + 5.63 · X7 + 4.94 · X8 + 1.35 · X9 + 4.52 · X10 + 5.15 · X11-1.33 · X12 + 1.72 · X13

No cancer Y2 = -3.48 + 2.75 · X1 + 1.80 · X2 + 1.57 · X3 + 2.51 · X4 + 1.56 · X5 + 3.55 · X6 + 1.34 · X7 + 2.54; X8 + 0.77; X9 + 1.29; X10-2.43; X11 + 1.40; X12 + 1.28; X13,

where the ultrasound parameters: X1 is the hapoechogenicity of the nodular formation, X2 is the heterogeneity of the nodular formation, X3 is the absence of the rim of the halo, X4 is the uneven contour of the node, X5 is calcification in the nodular formation, X6 is the intranodular blood flow in the nodular formation, clinical parameters: X7 is male sex, X8 - the size of the nodular mass is more than 2 cm, X9 - rapid growth of the nodule in the thyroid gland (<1 year), X10 - increased density of the nodular mass, determined by palpation, X11 - enlarged cervical lymph nodes, X12 - thyrotoxicosis; anamnestic parameters: X13 - anamnesis of the disease ≤1 years.

A method for the diagnosis of thyroid cancer in patients with a preoperative cytological diagnosis of a follicular tumor, including clinical, anamnestic, cytological, and ultrasound examination of the thyroid gland, characterized in that they conduct a cytological examination of the thyroid nodule and diagnose a follicular tumor thyroid gland, perform an ultrasound of the nodular formation in the thyroid gland and determine the following parameters: hypoechoicity of the nodular formation - X1, eodnorodnost nodule - X2, the lack of rim «Halo» - the X3, uneven contour nodule - X4, calcifications in nodules - X5 intranodulyarny blood flow in the nodules - X6; determine the clinical and anamnestic parameters: male gender - X7, the size of the nodular formation is more than 2 cm - X8, the rapid growth of the node in the thyroid gland (≤1 years) - X9, the increased density of the nodular formation, determined by palpation, - X10, the enlarged cervical lymph nodes - X11, thyrotoxicosis - X12, disease history ≤1 years - X13, if there is a sign, set the value to “1”, if it is absent, set to “0”, calculate the values of Y1 and Y2 based on these functions

Y1 = -15.93 + 7.10 · X1 + 8.25 · X2 + 6.12 · X3 + 7.07 · X4 + 3.97 · X5 + 5.75 · X6 + 5.63 · X7 + 4 94 · X8 + 1.35 · X9 + 4.52 · X10 + 5.15 · X11-1.33 · X12 + 1.72 · X13

Y2 = -3.48 + 2.75 · X1 + 1.80 · X2 + 1.57 · X3 + 2.51 · X4 + 1.56 · X5 + 3.55 · X6 + 1.34 · X7 + 2 , 54 X8 + 0.77 X9 + 1.29 X10-2.43 X11 + 1.40 X12 + 1.28 X13,

if the Y1 value is greater than Y2, a thyroid cancer diagnosis is made; if the Y2 value is greater than Y1, the thyroid cancer diagnosis is excluded.

The method is as follows:

In patients with thyroid nodules in the preoperative period, the following standard parameters are determined: ultrasound - hypoechoic nodules (X1), heterogeneity of nodules (X2), lack of a rim of a halo (X3), uneven nodular contour (X4), calcifications in nodular formation (X5), intranodular blood flow in nodular formation (X6); clinical and anamnestic parameters - male gender (X7), the size of the nodular formation is more than 2 cm (X8), the rapid growth of the nodule in the thyroid gland is ≤1 years old (X9), the increased density of the nodular formation determined by palpation (X10), enlarged cervical lymph nodes ( X11), thyrotoxicosis (X12), medical history ≤1 year (X13), cytological parameter - “follicular tumor”. Parameters (X1-X13) are introduced into the mathematical model, if there is a sign, they put the value "1", in the absence of it - "0":

Cancer Y1 = -15.93 + 7.10 · X1 + 8.25 · X2 + 6.12 · X3 + 7.07 · X4 + 3.97 · X5 + 5.75 · X6 + 5.63 · X7 + 4.94 · X8 + 1.35 · X9 + 4.52 · X10 + 5.15 · X11-1.33 · X12 + 1.72 · X13

No cancer Y2 = -3.48 + 2.75 · X1 + 1.80 · X2 + 1.57 · X3 + 2.51 · X4 + 1.56 · X5 + 3.55 · X6 + 1.34 · X7 + 2.54 · X8 + 0.77 · X9 + 1.29 · X10-2.43 · X11 + 1.40 · X12 + 1.28 · X13.

The results are evaluated as follows, the patient belongs to the group for which the calculation of the function will give a greater value. If the value of the classification function for Y1 is greater than the value of the function Y2, the patient should be assigned to the group Y1 - thyroid cancer. If the value of the classification function for Y2 is greater than the value of the function Y1, the patient should be assigned to group Y2 - there is no thyroid cancer.

Examples of the claimed method

Example 1

Patient M., 59 years old (medical history No. 13740/10), was admitted to the clinic with complaints of the presence of nodular formation in the neck, identified during a preventive examination. An anamnesis of the disease is 1.5 months. Upon receipt, the condition is satisfactory. The function of the thyroid gland is euthyroidism. On palpation in the left lobe of the thyroid gland, a nodular formation is determined, roundish, very dense, with a diameter of up to 1.5 cm, displaced when swallowed. Peripheral lymph nodes of the neck are not enlarged. Ultrasound of the thyroid gland: in the left lobe - hypoechoic nodular formation with a diameter of 1.5 × 1.7 mm, with an uneven contour, of a homogeneous structure with a rim, having an intranodular type of blood flow. The right lobe is not changed.

Cytological examination: follicular tumor.

Calculation of classification functions for nodular thyroid gland formation.

Among the parameters included in the model were the following: hypoechogenicity of nodular formation (X1), uneven nodular contour (X4), intranodular blood flow in nodular formation (X6), male gender (X7), increased density of nodular formation determined by palpation (X10), medical history of disease ≤1 year (X13).

Options X1 X2 X3 X4 X5 X6 X7 X8 X9 X10 X11 X12 X13 Value one 0 0 one 0 one one 0 0 one 0 0 one

We calculate the classification functions:

Y1 = -15.93 + 7.10 · 1 + 8.25 · 0 + 6.12 · 0 + 7.07 · 1 + 3.97 · 0 + 5.75 · 1 + 5.63 · 1 + 4 , 94 · 0 + 1.35 · 0 + 4.52 · 1 + 5.15 · 0-1.33 · 0 + 1.72 · 1 = 15.86 or

Y1 = -15.93 + 7.10 · 1 + 7.07 · 1 + 5.75 · 1 + 5.63 · 1 + 4.52 · 1 + 1.72 · 1 = 15.86

Y2 = -3.48 + 2.75 · 1 + 1.80 · 0 + 1.57 · 0 + 2.51 · 1 + 1.56 · 0 + 3.55 · 1 + 1.34 · 1 + 2 , 54 · 0 + 0.77 · 0 + 1.29 · 1-2.43 · 0 + 1.40 · 0 + 1.28 · 1 = 9.25 or

Y2 = -3.48 + 2.75 · 1 + 2.51 · 1 + 3.55 · 1 + 1.34 · 1 + 1.29 · 1 + 1.28 · 1 = 9.25

Thus, Y1 = 15.86> Y2 = 9.25, i.e. there is thyroid cancer.

Therefore, the patient M. was diagnosed with thyroid cancer. Patient M. is directed to surgical treatment. An adequate surgical treatment was performed from an oncological point of view, involving the complete removal of the thyroid gland, extrafascial thyroidectomy.

Postoperative histological diagnosis (No. 10652/10): follicular thyroid cancer.

This example indicates that on the basis of 6 standard parameters determined in a patient with a cytological diagnosis of a “follicular tumor” of the thyroid gland, in an outpatient setting using the method of mathematical modeling, you can diagnose the presence of thyroid cancer in the preoperative period, which allows you to perform an adequate type of surgical treatment.

Example 2

Patient B., 30 years old (medical history No. 3038/10), was admitted to the hospital with complaints of the presence of nodular formation in the neck, cosmetic defect, difficulty swallowing. Nodular goiter was diagnosed 4 years ago, within 0.5 years noted a rapid growth of the node with a visible cosmetic defect. Upon receipt, the condition is satisfactory. The function of the thyroid gland is euthyroidism. On palpation in the right lobe of the thyroid gland, a nodular formation is determined, round, soft-elastic consistency, painless, with a diameter of up to 4 cm, displaced by swallowing. Peripheral lymph nodes of the neck are not enlarged. Ultrasound of the thyroid gland: in the right lobe - hyper-echogenic nodular formation with a diameter of 3.2 × 4 cm, with a smooth contour, a heterogeneous structure with a rim, having an intranodular type of blood flow. There are no nodules in the left lobe.

Cytological examination: follicular tumor.

Calculation of classification functions for nodular thyroid gland formation:

Among the parameters included in the model were the following: heterogeneity of the nodular formation (X2), intranodular blood flow (X6), the size of the nodular formation is more than 2 cm (X8), rapid growth of the node in the thyroid gland ≤1 year (X9):

Options X1 X2 X3 X4 X5 X6 X7 X8 X9 X10 X11 X12 X13 Value 0 one 0 0 0 one 0 one one 0 0 0 0

We calculate the classification functions:

Y1 = -15.93 + 7.10 · 0 + 8.25 · 1 + 6.12 · 0 + 7.07 · 0 + 3.97 · 0 + 5.75 · 1 + 5.63 · 0 + 4 94 · 1 + 1.35 · 1 + 4.52 · 0 + 5.15 · 0-1.33 · 0 + 1.72 · 0 = 4.36 or

Y1 = -15.93 + 8.25 · 1 + 5.75 · 1 + 4.94 · 1 + 1.35 · 1 = 4.36

Y2 = -3.48 + 2.75 · 0 + 1.80 · 1 + 1.57 · 0 + 2.51 · 0 + 1.56 · 0 + 3.55 · 1 + 1.34 · 0 + 2 , 54 · 1 + 0.77 · 1 + 1.29 · 0-2.43 · 0 + 1.40 · 0 + 1.28 · 0 = 5.18 or

Y2 = -3.48 + 1.80 · 1 + 3.55 · 1 + 2.54 · 1 + 0.77 · 1 = 5.18

Thus, Y2 = 5.18> Y1 = 4.36, i.e. no thyroid cancer.

Therefore, patient B. does not have thyroid cancer, nodular formation is a follicular adenoma of the thyroid gland. Patient B. is directed to surgical treatment. Performed hemithyroidectomy on the right.

Postoperative histological diagnosis (No. 9712/10): follicular thyroid adenoma.

This example indicates that on the basis of 4 standard parameters determined in patients with a cytological diagnosis of a “follicular tumor” of the thyroid gland in an outpatient setting, using the mathematical modeling method, it is possible to establish the absence of thyroid cancer and diagnose follicular thyroid adenoma in the preoperative period. As a result, an organ-saving operation was performed while preserving the left lobe of the thyroid gland.

The proposed method allows using mathematical modeling that takes into account ultrasound and clinical and anamnestic signs of thyroid cancer in patients with a preoperative cytological diagnosis of follicular tumor, to increase the efficiency of differential diagnosis of cancer in the preoperative period to select an appropriate type of surgical operation.

The source of information

1. Abesadze I.A. Differential diagnosis of follicular tumors of the thyroid gland: author. dis ... cand. honey. Sciences / Abesadze I.A. - M., 2008 .-- 32 p.

2. Kazakov S.P. Molecular biological markers in the diagnosis, pathogenesis and prognosis of thyroid diseases: abstract. dis ... doctor honey. sciences / S.P. Kazakov - M., 2010 .-- 48 p.

3. Nazarochkin Yu.V. An individual approach to the diagnosis and surgical treatment of patients with thyroid nodular diseases: abstract. dis ... doctor honey. sciences / Yu.V. Nazarochkin. - Volgograd, 2005 .-- 38 p.

4. Patent No. 2293524 Method for differential diagnosis of follicular adenoma and follicular thyroid cancer / Poloz T.L., Demin A.V., Shkurupy V.A. publ. 02/20/2007.

5. Patent No. 240742 Method for the diagnosis of thyroid tumors using mathematical modeling / Beloborodov VA, Olifirova OS, Ilyushonok AS publ. 12/27/2010 Bull. Number 36.

6. Sokolova OV Differential diagnostic criteria for follicular thyroid tumors of varying degrees of malignancy: author. dis ... cand. honey. Sciences / Sokolova O.V. - St. Petersburg., 2009 .-- 22 p.

Claims (1)

A method for the diagnosis of thyroid cancer in patients with a preoperative cytological diagnosis of a follicular tumor, including clinical, anamnestic, cytological, and ultrasound examination of the thyroid gland, characterized in that they conduct a cytological examination of the thyroid nodule and diagnose a follicular tumor "The thyroid gland, perform an ultrasound of the nodular formation in the thyroid gland and determine the following parameters: hypoechoicity of the nodular formation - X1, heterogeneity of the nodular formation - X2, lack of a rim of “halo" - X3, uneven outline of the nodular formation - X4, calcifications in the nodular formation - X5, intranodular blood flow in the nodular formation - X6; determine the clinical and anamnestic parameters: male gender - X7, the size of the nodular formation is more than 2 cm - X8, rapid growth of the node in the thyroid gland, ≤1 years - X9, increased density of the nodular formation, determined by palpation, - X10, enlarged cervical lymph nodes - X11 , thyrotoxicosis - X12, disease history ≤1 years - X13, if there is a sign, set the value to “1”, in the absence of a sign - “0”, calculate the values Y1 and Y2 based on these functions
Y1 = -15.93 + 7.10; X1 + 8.25; X2 + 6.12; X3 + 7.07; X4 + 3.97; X5 + 5.75; X6 + 5.63; X7 + 4 94 · X8 + 1.35 · X9 + 4.52 · X10 + 5.15 · X11-1.33 · X12 + 1.72 · X13;
Y2 = -3.48 + 2.75 · X1 + 1.80 · X2 + 1.57 · X3 + 2.51 · X4 + 1.56 · X5 + 3.55 · X6 + 1.34 · X7 + 2 , 54 · X8 + 0.77 · X9 + 1.29 · X10-2.43 · X11 + 1.40 · X12 + 1.28 · X13,
if the value of Y1 is greater than Y2, a diagnosis of thyroid cancer is established; if the value of Y2 is greater than Y1, the diagnosis of thyroid cancer is excluded.