RU2738305C1 - Method for differential diagnosis of malignant and benign parathyroid gland formations in patients with primary hyperparathyroidism - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to ultrasonic diagnostics, and can be used for differential diagnosis of malignant and benign parathyroid gland (PTG) formation in a patient with primary hyperparathyroidism. A neoplasm is detected with the help of a gray-scale ultrasound, the size of the new growth is measured and the presence of calcinates is determined. Additionally, contrast-enhanced ultrasonography using an endovascular contrast agent (ECA) is performed and a degree of contrast is measured in the growth area, a contrast accumulation pattern, a contrast accumulation pattern, a maximum contrast accumulation intensity value determining, time from the beginning of the ECA entry into the new growth area to the maximum value of the contrast accumulation intensity. If observing: new growths measuring the greatest measured value of 3 cm and more are assigned 1 point, less than 3 cm - 0 points; calcinations (one and more) are assigned 1 point, absence of calcinates - 0 points; hyper-contrast growth is assigned 2 points, iso-contrast or hypocontrast - 1 point, absence of contrasting - 0 points; uneven accumulation of contrast is assigned 1 point, uniform - 0 points; chaotic accumulation of contrast is assigned 2 points, ordered accumulation of contrast from periphery to center - 0 points; values of maximum intensity of accumulation of contrast 900 AU and more are assigned 2 points, less than specified value - 0 points; time from the beginning of the ECA entry into the new growth area to the maximum value of the contrast accumulation intensity of 3 s and less is 2 points, more than 3 s - 0 points. Obtained points are summed up. If the total value is 1 to 4 points inclusive, a benign neoplasm is stated. If value is 9 to 11 points, malignant neoplasm is observed.

EFFECT: method provides differential diagnosis of malignant and benign parathyroid (PTG) formation by assessing quantitative and qualitative contrast enhancement values.

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Description

Technology area

The invention relates to medicine, namely to instrumental diagnostics, and can be used in therapeutic (endocrinological) and surgical departments (departments of endocrine surgery) in preparation for surgical treatment of various forms of primary hyperparathyroidism (PHPT), namely, when removing formations of the parathyroid glands ( OSH).

State of the art

Primary hyperparathyroidism (PHPT) is an endocrine disease characterized by excessive secretion of parathyroid hormone (PTH) due to tumor lesions or PTG hyperplasia. PGPT is manifested by a multisymptomatic clinical picture, involving various organs and systems in the pathological process with a predominant lesion of the kidneys and bones, which leads to a significant decrease in the quality of life, disability of patients, and an increased risk of premature death. In about 85% of cases, PGPT causes a solitary PTG adenoma, and only in 10-15% of cases it occurs with multiple adenomas or with their multiple hyperplasia, 1-5% with carcinomas. [Makarov, I.V. Experience in diagnostics and surgical treatment of primary hyperparathyroidism / I.V. Makarov, R.A. Galkin, N.A. Prokofiev, V.A. Boltovskaya, P.M. Romanov // Endocrine Surgery. -2017. - T. 11, no. 2. - from. 81-89; Mokrysheva N.G. Primary hyperparathyroidism. Epidemiology, clinic, modern principles of diagnosis and treatment. - Diss. doct. medical sciences - M. - 2011. - S. 253].

Currently known methods of visualization of formations of the PTG are ultrasound examination (ultrasound); planar scintigraphy; scintigraphy combined with single-photon emission computed tomography; multispiral computed tomography (MSCT); magnetic resonance imaging (MRI); Positron emission tomography does not allow for differential diagnosis at the preoperative stage between benign and malignant PTG lesions and, therefore, planning the optimal amount of surgical treatment.

Ultrasound is a widespread and affordable anatomical topical diagnostic method. According to various data, the sensitivity of ultrasound in the case of solitary formation of the PTG varies from 76 to 91% and largely depends on the qualifications of the specialist. The specificity of the method can reach 96%. A high positive predictive value and diagnostic accuracy of PTG ultrasound was established (93.2% and 88%, respectively) [Cheung, K., et al, A meta-analysis of preoperative localization techniques for patients with primary hyperparathyroidism. Annals of surgical oncology, 2012.19 (2): p. 577-583].

Scintigraphy with technetril is considered the most informative functional method for topical diagnosis of PTG masses in PGPT. However, the accuracy of the study - from 50 to 90% - varies depending on the experience of specialists and the center where the study is conducted [Johnson NA, Tublin ME, Ogilvie JB. Parathyroid imaging: technique and role in the preoperative evaluation of primary hyperparathyroidism. AJR. 2007; 188: 1706-1715; Civelek AC, Ozalp E, Donovan P, Udelsman R. Prospective evaluation of delayed technetium-99m sestamibi SPECT scintigraphy for preoperative localization of primary hyperparathyroidism. Surgery 2002; 131: 149-157].

Single-photon emission computed tomography allows you to obtain not just a projection of the distribution of isotopes in organs and tissues on a plane, but a series of tomographic sections of an organ or part of the body, which significantly increases the accuracy and clarity of diagnosis [Takagi H., Tominaga Y., Uchida K. et al. Subtotal Versus Total Parathyroidectomy with Forearm Autograft for Secondary Hyperparathyroidism in Chronic Renal Failure. Ann. Surg. 1983; 198: 74-79; Kasai ET, da Silva JW, Mandarim de Lacerda CA et al. Parathyroid glands: combination of sestamibi- (99m) Tc scintigraphy and ultrasonography for demonstration of hyperplasic parathyroid glands. Rev Esp Med Nucl. - 2008. - 27: 8-12].

MSCT with contrast makes it possible to accurately assess the size and localization of the PTG, both in the case of their normal number and location, and in the presence of additional PTGs and their ectopia, including in the mediastinum. The diagnostic sensitivity of CT is 46-87%.

The use of positron emission tomography (PET) is recommended in some cases in patients with persistent disease or recurrent hyperparathyroidism in the absence of PTG imaging using first and second line methods. The use of PET is limited by the lack of tissue-specific radiopharmaceuticals and the high cost of the study [Bilezikian JP, Khan AA and Potts Jr JT. Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Third International Workshop. J Clin Endocrinol Metab. 2009 Feb; 94 (2): 335-339; Bilezikian JP, Brandi ML, Eastell R, Silverberg S, Udelsman R, Marcocci C and Potts Jr JT. Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Fourth International Workshop. J Clin Endocrinol Metab. Oct; 99 (10): 3561-9. doi: 10.1210 / jc. 2014-1413]. A common drawback of all computer methods is radiation exposure.

From the prior art, there is a method for preoperative diagnosis of PTG formation (RU2537213) using multiphase multispiral computed tomography (MSCT) with a radiopaque contrast agent (RC), which is carried out at the arterial and venous phases of the study - respectively, at 25 and 50 seconds after the RC injection. In this case, PK is injected once, after its administration, physiological saline is injected intravenously, and the funds are injected through the catheter at a rate of 4 ± 1 ml / s. The radiation attenuation coefficient in all formations of the research area is determined as the research parameters. When the X-ray attenuation coefficient is fixed to + 180 + 200 HU in the early arterial phase and a decrease in density of at least 80 HU is detected at the venous stage, the presence of an adenoma is diagnosed. EFFECT: method provides high quality diagnostics of PTG adenomas due to more accurate fixation of neoplasm location, optimal distribution and retention of contrast agent in the study area in healthy and pathogenic zones. However, radiation exposure, a number of disadvantages of the contrast agents used, mainly associated with their toxic-allergic reactions, the absence of a dynamic assessment of the microvasculature in real time and the impossibility, if necessary, of reintroducing the contrast during one study are the limiting factors of the method. In addition, the method does not allow for differential diagnosis between benign and malignant PTG lesions.

From the prior art, a method for diagnosing PTG changes (RU2169526) is known, including ultrasound examination of the neck area with a 5 MHz surface sensor, while the patient examines: the echogenicity of the formation - parameter A and evaluate it by 1 point with low echogenicity, 2 points - with reduced echogenicity; contours of education - parameter B: with clear contours of education, they are assessed by 1 point, with blurred contours of education - 2 points; the size of the formation - parameter B: if the size of the formation is less than 7 mm, it is evaluated by 1 point, if the size of the formation is 7 mm or more - 2 points; the number of formations - parameter D: when one formation is detected, 1 point is assessed, in the presence of several formations - 2 points, the points of all parameters are summed up, with a total of 4 to 6, PTG adenoma is diagnosed, with a total of 7 or more - PTG hyperplasia. However, this method does not allow at the preoperative stage to assess the risk of the presence of malignancy of the formation, as well as to carry out differential diagnostics with the formations of another organ belonging. The method does not imply the use of contrasting, which, accordingly, makes it impossible to analyze the microcirculation of the formation and determine the topographic and anatomical relationship of the tumor with the surrounding structures.

From the prior art, a method for diagnosing PTG masses using ultrasound with contrast is known (A. Agha, M. Hornung, C. Stroszczynski, et al. Highly Efficient Localization of Pathological Glands in Primary Hyperparathyroidism Using Contrast Enhanced Ultrasonography (CEUS) in Comparison with Conventional Ultrasonography J. Clin. Endocrinol. Metab. 98: 2019-2025, 2013. A. N. Sencha. Ultrasound examination of the parathyroid and salivary glands. From simple to complex. M.: MEDpress-inform, 2020-232s.), Including quantitative and a qualitative assessment of the vascularization of the PTG microvascular bed, which makes it possible to identify their tumors. Contrast-enhanced ultrasound has particular advantages in the presence of concomitant goiter, cervical lymphadenopathy, and polyglandular thyroid gland lesions, even after previous neck surgery. However, the known method does not allow differential diagnosis of malignant and benign PTG lesions.

The closest to the claimed solution is a method for diagnosing malignant and benign formations of the parathyroid glands in patients with primary hyperparathyroidism, including performing a gray-scale ultrasound, as a result of which the size, contour, echogenicity, and the presence of calcifications are assessed. There are no clear ultrasound signs of malignant PTG lesions. However, suspicious for PTG cancer are heterogeneous structure, irregular shape, lesion size more than 3 cm, uneven edges, reduced echogenicity [Nam, M., H.-S. Jeong, and J.H. Shin, Differentiation of parathyroid carcinoma and adenoma by preoperative ultrasonography. Acta Radiologica, 2017.58 (6): p. 670-675.] The known method also does not provide an accurate differential diagnosis of malignant and benign lesions of the PTG.

Thus, to date, there is no instrumental method that allows with high accuracy to carry out the differential diagnosis between benign and malignant PTG lesions at the pre- and intraoperative stage.

The technical problem solved by the claimed invention is to eliminate all of the above disadvantages of the known methods.

Disclosure of invention

The technical result of the claimed invention is the development of a method for the differential diagnosis of malignant and benign formations of the parathyroid glands in patients with primary hyperparathyroidism, characterized by high sensitivity (97%) and specificity (98%), which significantly exceeds those in gray-scale ultrasound examination with high statistical reliability (p. 0.05).

The technical result is achieved by implementing a method for differential diagnosis of malignant and benign formation of the parathyroid gland in a patient with primary hyperparathyroidism, including performing a gray-scale ultrasound, detection of a neoplasm, measuring the size of a neoplasm and determining the presence of calcifications; conducting contrast-enhanced ultrasound using an endovascular contrast agent (ECV), measuring in the neoplasm (area of interest) the degree of contrast, the nature of contrast accumulation, the pattern of contrast accumulation, determining the value of the maximum intensity of contrast accumulation, determining the time from the beginning of the ECV entering the area of interest to reaching the maximum value of the intensity of the accumulation of contrast, and in case of detection:

neoplasms with a size (according to the largest measured value) of 3 cm or more are assigned 1 point, less than 3 cm - 0 points;

calcifications (one or more) are assigned 1 point, the absence of calcifications - 0 points;

hypercontrast education is assigned 2 points, isocontrast or hypocontrast - 1 point, no contrast - 0 points;

uneven accumulation of contrast is assigned 1 point, uniform - 0 points;

chaotic accumulation of contrast is assigned 2 points, ordered accumulation of contrast from the periphery to the center - 0 points;

values of the maximum intensity of contrast accumulation 900 AU (arbitrary units) and more are assigned 2 points, less than the specified value - 0 points;

the time from the beginning of the arrival of ECV in the area of interest until the maximum value of the intensity of contrast accumulation of 3 s or less is assigned 2 points, more than 3 s - 0 points;

the obtained points are summed up, and when the value of the sum is from 1 to 4 points inclusive, they make a conclusion about the benign nature of the formation, when the value of the sum is from 9 to 11 points - about the malignant nature of the formation.

It was experimentally revealed that it is the complex of the listed indicators, including the parameters of gray-scale ultrasound, qualitative and quantitative contrast analysis, that ensures the achievement of the technical result - high accuracy of differential diagnosis of malignant and benign tumors at the preoperative stage. A gray-scale study by the sum of signs before the start of contrast enhancement reveals the risk of PTG carcinoma in this patient. A qualitative analysis of tumor microcirculation allows for differential diagnosis, and in some cases, when certain data are combined with high accuracy and specificity, a group of benign pathologies can be distinguished (for example, when hypocontrast or isocontrast with uniform accumulation and the correct pattern is combined), and a malignant formation can be diagnosed by a chaotic pattern of contrast accumulation and carry out differential diagnostics with the formation of another organ accessory. However, the qualitative analysis of contrasting has a degree of subjectivity, moreover, it depends on the state of the thyroid parenchyma with which the comparison is made. To objectify the data, the qualitative analysis was complemented by a quantitative assessment of the time-intensity curve. At baseline, the following quantitative measures were assessed: time of arrival (WIT), time to peak intensity (TTP), peak intensity (PI), mean transit time (MTT), and area under the curve (AUC). Of these, the indicators of peak intensity (PI) and the time for which the intensity of accumulation reaches its maximum value (TTP) were statistically significant for the diagnosis of malignant formation. For other indicators, there was no statistically significant difference in the differential diagnosis of tumors.

The inventive method allows you to identify a risk group of patients with malignant neoplasms of the thyroid gland by assessing a set of quantitative and qualitative indicators based on the results of gray-scale ultrasound and ultrasound with contrast enhancement. In addition, in addition to the high accuracy and reliability of the differential diagnosis, the proposed method is characterized by the absence of radiation exposure and minimal invasiveness. The method makes it possible to quantitatively and qualitatively assess the functional ability of the parathyroid parenchyma and to carry out differential diagnostics of tumor lesions of the organ, which is especially important at the stage of preoperative planning, since the result directly affects the volume of primary surgery and, thereby, the patient's survival.

The method is carried out as follows.

The method includes a preparatory stage, a stage of direct carrying out of gray-scale ultrasound and ultrasound with contrast enhancement, and a stage of qualitative and quantitative processing of the obtained data. A catheter with a diameter of 20-22G is inserted into the patient's ulnar vein, an adapter is connected to the catheter - a device for regulating infusion flows. A syringe with saline in a volume of 10 ml and a syringe with the required volume (2.4 ml) of a contrast agent prepared immediately before administration according to the manufacturer's instructions are attached to the device. For contrasting, an endovascular contrast agent (ECV) is used - a preparation based on sulfur hexafluoride (for example, SonoVue), which is a gas microbubbles encapsulated in a phospholipid membrane with a diameter of 2-6 nm. Such a small size determines the exclusively intravascular distribution of the drug and the impossibility of its penetration through the endothelium. At the same time, these vesicles easily pass into the microvasculature of the pulmonary capillaries, which ensures safe excretion through the lungs.

The endovascular contrast agent used in this study is fundamentally different from other contrast agents used in various instrumental methods for examining the PTG (CT and MRI). ECVs are intravascular substances with insufficient interstitial distribution; their half-life in blood is usually several minutes. ECVs can be injected several times before they are removed, CT and MRI contrast agents (being significantly less than ECV) penetrate the vessel wall and spread into the interstitium. Another difference between CT and MRI contrast agents: ECV changes under the influence of an ultrasound wave. The final significant difference relates to the rendering phases. While the scan phases for CT and MRI are noted at the peak of the increase for each phase, this is not the case for contrast-enhanced ultrasound (CUUS). The arterial phase for ECV begins when microbubbles enter the arterial pedicle of the scanned organ (10-15 seconds after intravenous injection) and lasts about 40 seconds. The venous and late phase lasts 3 to 6 minutes, depending on the parenchyma scanned. Due to the possibility of conducting QUUS in real time with a low mechanical index (MI), the desired organ is constantly scanned during each phase of contrasting. In contrast to the time of acquiring the image of the contrasting phases with CT or MRI, KUUSI allows you to continuously, in real time, one second to obtain images of lesions during all vascular phases (especially when analyzing a saved video clip).

At the initial stage of ultrasound, the area of interest is determined by ultrasound scanning in gray scale modes, color Doppler mapping and other modes that optimize the visualization of the organ. In transverse scanning, the zones behind the thyroid gland are examined along the entire length from the upper to the lower pole and partially retrosternal. Turning the head improves visualization of the PTG located behind the trachea. The state of the thyroid gland is assessed for subsequent comparison of the qualitative parameters obtained as a result of contrasting with the intact parenchyma of the thyroid gland. A study using gray-scale ultrasound can be performed according to the standard technique (Jin Young Sung. Parathyroid ultrasonography: the evolving role of the radiologist. Ultrasonography. 2015 Oct; 34 (4): 268-274. EV Polukhina. Ultrasound diagnosis of parathyroid pathology glands. Monograph. 2019 AN Sencha. Ultrasound examination of the parathyroid and salivary glands. Monograph 2020), while according to the claimed method determine the size of the formation, its structure, contour and the presence of calcifications. After determining the zone of interest, without changing the position of the sensor, the device is switched to the contrast study (CHI) mode with a low mechanical index (MI) of up to 0.14, for example, when using the Toshiba Aplio 500 ultrasound scanner. When using this device, automatically after the completion of the gray-scale ultrasound the sensor switches to a frequency of 5-8 MHz for ultrasound in contrast mode. A dual screen format appears on the machine's display, showing the image in B-mode and contrast mode. Render focus and label are set on the ROI.

At the next stage, contrast-enhanced ultrasound is performed directly. Into the venous catheter through an adapter in a bolus mode, an echocontrast preparation prepared immediately before the injection is injected in a volume of 2.4 ml, followed by a bolus injection of saline in a volume of 10 ml. In case of multiple lesions, if the screen format and the peculiarities of the topical location allow, it is possible to simultaneously assess the contrast indicators of several parathyroid glands. If necessary (for the study of another formation), a contrast agent can be injected 20 minutes later in the same volume.

Simultaneously with the start of the administration of a contrast agent, a stopwatch is turned on on the apparatus and a cine loop is recorded until the drug is completely washed out of the area of interest during visual assessment (not less than 180 sec). For the thyroid gland and parathyroid glands, contrast enhancement occurs within two time intervals: the arterial phase - from the moment the contrast enters the supplying vessel of the formation (usually 10-15 seconds after intravenous administration) lasts on average up to 30-45 seconds, the venous phase - from 30-45 seconds from the receipt of contrast in the supply vessel.

After the completion of contrast-enhanced ultrasound, a qualitative and quantitative analysis of the data obtained is performed. A qualitative analysis is carried out according to the following parameters: the degree of contrast, the nature of the accumulation of contrast, the pattern of accumulation, the rate of accumulation, and the rate of washout. The assessment of these parameters can be carried out according to a well-known technique (Sencha A.N., M.S.Mogutov, Yu.N. Patrunov and others. Ultrasound examination using contrast agents. Moscow: VidarVidar-M, 2015.-142s .; Sencha A.N. Ultrasound examination of the parathyroid and salivary glands. From simple to complex. M.: MEDpress-inform, 2020-232 pp .; Sencha E.A. Contrast-enhanced ultrasound examination in the diagnosis of thyroid tumors. KUOK 2017; 7 ( 3): 44-52; E. Karakas, S. Kann, H. Hoffen et al. Does Contrast-Enhanced Cervical Ultrasonography Improve Preoperative Localization R and Reesults In Patients With Sporadic Primary Hyperparathyroidism? J. Clin. Imaging Sci $ 2012; 2 : 64; F. Piscaglia, C. Nolsee, CF Dietrich et al. The EFSUMB Guidelines And Recommendation On The Clinical Practice Of Contrast Enhanced Ultrasound (CEUS): Update 2011 On Non-hepatic Applications. Ultrashall in der Medizin / European Journal of Ultrasound 2012 issue 1).

In particular, when determining the degree of contrasting of the formation (in comparison with the tissue of the thyroid gland) according to the indicated method, formations with the absence of contrast are revealed; hypercontrast; isocontrast; hypocontrast.

When determining the nature of the accumulation of contrast in the formation of the parathyroid gland, uniform or uneven accumulation is revealed, while the accumulation of contrast can be either diffusely uneven, associated with diffuse heterogeneity of the parenchyma of an organ or formation, or locally uneven, associated with the presence of fluid loci or calcifications in the formation.

When determining the pattern of accumulation, either the accumulation of the contrast agent from the periphery to the center, or chaotic accumulation is detected.

The rate of contrast accumulation and contrast washout can be fast, comparable to the thyroid parenchyma, slow. In this case, in the process of studying these parameters, the value of the peak of the intensity of the accumulation of contrast and the time to reach the peak of intensity from the beginning of the administration of the contrast agent to the patient are determined.

The quantitative assessment of the measured parameters based on the results of gray-scale ultrasound and ultrasound with contrast enhancement is carried out in the post-processing mode of the obtained data. A fragment of a cine loop is used for analysis, capturing the moment of arrival and the moment of washing out the contrast agent. With the help of the survey zone (ROI), the zones of interest in the parathyroid gland and in the thyroid parenchyma are distinguished. The intensity-time curves (TIC) are automatically displayed on the screen, where the X-axis shows the recording time of the cine loop in seconds, and the Y-axis shows the intensity of the displayed echo signal in absolute intensity units. The quantitative characteristics of contrasting are also duplicated on the screen in the form of tables.

It should be noted that the claimed complex of evaluation criteria was identified in the course of the study, in which the sizes, shape, contours of the neoplasm, the presence of calcifications, as well as the following parameters obtained from the curves and contrasting tables were used:

1. Zero time (T0, s) - the time interval from the injection of a contrast agent to the first appearance of microbubbles in the area of interest

2. Time of admission (WIT, s) - time interval from intensity 5% to intensity 95%

3. Time to reach the peak intensity (TTP, s) - the time interval from zero time (TO) to the point with maximum intensity (PI)

4. Peak intensity (PI, AU (maximum intensity units) - maximum point of PIV

4. Average transit time (MTT, s) - the time interval from zero time to complete washout.

5. Area under the curve (AUC) - the area under the curve from the beginning of the arrival of the contrast to the moment of its complete removal

At the same time, accurate and reliable data on the diagnosis of the histological variant of the tumor were obtained using the following set of parameters: the size of the formation (more than 3 cm), the presence of one or more calcifications, the degree of contrasting (hypercontrast formation), the uneven nature of accumulation, the chaotic pattern of accumulation, the value of the peak contrast accumulation intensity (Peak intensity, PI, AU) and time to peak intensity (TTP, s) with threshold values of 900 AU and 3 sec, respectively.

To predict the histological variant of the tumor, a scoring assessment of qualitative and quantitative indicators, as well as data from a gray-scale study, was developed. 1. formations of 3 cm or more were assigned 1 point, less than 3 cm - 0 points; 2. formations with calcifications (1 or more) were assigned 1 point, without calcifications - 0 points; 3. According to the degree of contrasting, the formations with the absence of contrasting were not assigned points (0 points), 1 point was assigned to isocontrast, 1 point to hypocontrast, 2 points to hypercontrast; 4. by the nature of accumulation, formations with uniform accumulation did not receive points, with uneven accumulation - 1 point; 5. according to the pattern of accumulation, formations with chaotic accumulation were assigned 2 points, with ordered accumulation from the periphery to the center - 0 points; 6. Formations with a peak intensity of 900 AU and more were assigned 2 points. Formations with an intensity peak below the cutoff threshold were not scored; 7. Formations with a time of reaching the peak of intensity less than 3 s were assigned 2 points, more than 3 s - 0 points.

The total number of points 1-4 indicates the benign nature of the process, the number of points 9-11 is typical for parathyroid cancer.

If the value of the sum of points is 5-8, the surgeon makes the decision on the scope of the intervention based on the intraoperative characteristics of the tumor.

The proposed method has passed clinical trials on the basis of the Federal State Budgetary Institution "National Medical Research Center of Endocrinology" of the Ministry of Health of Russia. A total of 32 patients with primary hyperparathyroidism were examined. In 24 patients, parathyroidectomy was performed, followed by histological examination of the surgical material. In 22 patients, the contrast intensity of the formations exceeded the contrast intensity of the thyroid tissue, in 6 patients the contrast pattern was uneven. The time to reach the peak intensity was 1.8-10.4 s, the peak intensity was 5.1-1104 AIU. At the stage of the preoperative study, a group of 3 patients was identified with pronounced uneven hypercontrast of the lesions, with a violation of the correct contrasting pattern, the time to reach the peak intensity of 1.8-3.0 s and the peak intensity of 903-1104 AIU. The total number of points on a point scale for assessing ultrasound signs for this group of patients was 9-11. Based on these indicators, an assumption was made about the likelihood of thyroid cancer, which was confirmed by subsequent histological examination. Thus, the sensitivity and specificity of the proposed method at the threshold values of the peak intensity of 900 AIU and the time to reach the peak intensity of 3.0 s was 100% for parathyroid cancer. From another group of patients (21 people), 19 patients had hypercontrast formations, 2 - hypocontrast, 1 - isocontrast, 19 people had a uniform accumulation pattern, 3 - uneven, which was associated with the presence of liquid zones, the accumulation pattern in all patients was orderly. The time to reach the peak intensity in patients of this group was 3.6-10.4 s, the peak intensity was 5.1-428. The total number of points in this group was 1-4, which at the preoperative stage made it possible to conclude that the lesions were benign.

Example 1. Patient A., 68 years old. Grayscale ultrasound revealed behind the middle segment of the right lobe, lateral to the esophagus and partially behind it, the formation of reduced echogenicity, homogeneous, without additional inclusions and calcifications, p 0.8x0.5x0.4 cm (0 points). In the study with contrasting in the indicated localization, a hypercontrast formation (2 points) was visualized with a uniform distribution of the contrast agent with an accumulation pattern from the periphery to the center (0 points). Quantitative contrast indicators were as follows: Peak intensity (PI) - 134.2АU (0 points), time to peak intensity (TTP) - 7.3 seconds (0 points).

The total number of points on the attribute assessment scale was 2 points. The conclusion was made about a benign tumor of the parathyroid gland. The histological conclusion: adenoma of the main cells.

Example 2. Patient L., 42 years old. During gray-scale ultrasound, a hypoechoic heterogeneous formation with multiple calcifications (1 point), size 3.9x2.3x1.4 cm (1 point) was visualized above the upper pole of the left lobe. In the study with contrasting in the indicated localization, a hypercontrast formation (2 points) was visualized with a chaotic pattern (2 points) and an uneven distribution of the contrast agent (1 point). Quantitative contrasting indices were as follows: Peak intensity (PI) - 903.0АU (2 points), time to reach peak intensity (TTP) - 3.0 sec (2 points). The number of points on the scale for assessing signs was 11 points, which made it possible to draw a conclusion about the malignant nature of the process. The histological conclusion: in the material under study, cancer of the parathyroid gland of a solid-microfollicular structure is found, mainly from the main cells, with the presence of areas of oxyphilic cells with pronounced polymorphism, with signs of capsular and vascular invasion.

The described set of qualitative and quantitative parameters makes it possible to carry out an accurate topical diagnosis of the formation of the parathyroid glands, to suggest the nature of the formation (adenoma or cancer), and also to distinguish them from other visually similar structures of the neck (lymph nodes, thymus remnant) and subsequently plan the appropriate amount of surgical intervention.

Claims (9)

A method for the differential diagnosis of malignant and benign formation of the parathyroid gland in a patient with primary hyperparathyroidism, including the detection of a neoplasm using gray-scale ultrasound, measuring the size of the neoplasm and determining the presence of calcifications, characterized in that contrast-enhanced ultrasound is additionally performed using an endovascular contrast medium (ECV) and by measuring the degree of contrast in the area of the neoplasm, the nature of the accumulation of contrast, the pattern of accumulation of contrast, determining the value of the maximum intensity of the accumulation of contrast, the time from the beginning of the arrival of ECV in the area of the neoplasm until the maximum value of the intensity of accumulation of contrast is reached, and in case of detection: neoplasms with the largest measured value of 3 cm or more are assigned 1 point, less than 3 cm - 0 points; calcifications (one or more) are assigned 1 point, the absence of calcifications - 0 points; hypercontrast neoplasm is assigned 2 points, isocontrast or hypocontrast - 1 point, no contrast - 0 points; uneven accumulation of contrast is assigned 1 point, uniform - 0 points; chaotic accumulation of contrast is assigned 2 points, ordered accumulation of contrast from the periphery to the center - 0 points; values of the maximum intensity of contrast accumulation 900 AU and more are assigned 2 points, less than the indicated value - 0 points; the time from the beginning of the arrival of ECV in the neoplasm until the maximum value of the intensity of contrast accumulation is 3 s or less is assigned 2 points, more than 3 s - 0 points; the obtained points are summed up, and when the value of the sum is from 1 to 4 points inclusive, the conclusion is made about the benign nature of the neoplasm, when the value of the sum is from 9 to 11 points - about the malignant nature of the neoplasm.