RU2822984C1 - Method for differential diagnosis of focal hepatic steatosis and solid hepatic growths in patients with burdened oncoanamnesis - Google Patents

Abstract

FIELD: medicine; hepatology; oncology.

SUBSTANCE: invention can be used for differential diagnosis of focal hepatic steatosis and solid hepatic masses in patients with a burdened oncoanamnesis. Ultrasound examination of the focal mass is performed in B-mode, and after visualization of the area of interest, the mode of point shear wave elastography is activated. If lesion is 10 to 15 mm in size, measurements are taken in the central part of the lesion, and if the lesion is more than 16 mm, in the peripheral part of the lesion. Method comprises quantitative assessment of liver tissue stiffness in 10 points in area of interest, and if the average value of tissue stiffness in the area of interest is higher than the range of reference values of liver tissue stiffness, a solid formation is diagnosed, and if the obtained value does not go beyond the range of reference values of liver tissue stiffness, focal steatosis is diagnosed.

EFFECT: method enables detecting changes in the liver at the screening stage, conducting continuous non-invasive monitoring of cancer patients, determining the patient management approach by identifying the most significant scanning area of the focal mass and using the B-mode ultrasound scanning and point shear wave elastography.

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Description

The invention relates to medicine, namely to methods for the differential diagnosis of focal liver pathology in oncology, and can be used for the differential diagnosis of focal liver steatosis and solid liver formations in patients with a burdened history of cancer.

Oncological diseases occupy one of the leading positions in morbidity and mortality throughout the world. According to world statistics, in 2020 the number of new cases exceeded 19 million, and the mortality rate from cancer was more than 1.0 million people ([1] - Sung N., 2021).

Due to its anatomical structure and blood supply characteristics, the liver is a highly tropic organ for metastasis; according to the literature, every third cancer patient, regardless of the location of the primary tumor, has metastases in the hepatobiliary zone ([2] - Rykov O.V., 2017).

According to the literature, benign neoplasms are found with the same frequency (5-20%) in the liver affected by metastases as in healthy individuals ([3] - Katrich A.N. 2019), therefore it is extremely important to have an accurate imaging method to determine further patient management tactics. Moreover, continuous monitoring of cancer patients requires an easily accessible, reliable, cost-effective and, most importantly, dose-free diagnostic tool for detecting and characterizing liver damage ([4] - Battaglia V., 2017).

Currently, the most commonly performed non-invasive diagnostic methods are native ultrasound (US) and contrast-enhanced ultrasound (CEUS), contrast-enhanced computed tomography (CT with CT), magnetic resonance imaging with contrast enhancement (MRI with CU). .

Greyscale ultrasound is a screening method and the first line in identifying changes in the liver. The presence of a focal lesion on ultrasound is considered an indication for the use of other diagnostic methods with contrast, such as CEUS, CT, or MRI with CE. However, these techniques require the use of a contrast agent, which carries a potential risk of an allergic reaction, increases the cost of the study and takes more time ([8] - Akdogan E., 2018).

Attempts to increase the information content of native ultrasound have led to the use of shear point elastography for differential diagnosis of lesions ([5] - Borsukov A.V., 2022).

Previously, this technique was used only to assess diffuse liver damage, in particular in patients with viral hepatitis ([7] - Pimanov S.I., 2021).

The technical result of the invention is the non-invasive determination of the type of lesion (focal steatosis of the liver or solid formation), reducing the time for assessing focal liver formation, due to the absence of the need to perform other methods of radiation visualization, the possibility of differential diagnosis at the primary stage and reducing the costs of further research.

The specified technical result is achieved using a method for differential diagnosis of focal hepatic steatosis and solid liver formations in patients with a burdened oncological history, including ultrasound examination of the focal formation in B-mode, characterized in that after visualization of the area of interest, the mode of point shear wave elastography is activated and with the size of the focal formation from 10 to 15 mm, measurements are carried out in the central part of the focal formation, and if its size is more than 16 mm in the peripheral part of the focal formation, then a quantitative assessment of the stiffness of the liver tissue is carried out at 10 points in the zone of interest, and with an average value of tissue stiffness in the zone of interest higher range of reference indicators of liver tissue stiffness, a solid formation is diagnosed, and if the obtained value does not fall outside the range of reference indicators of liver tissue stiffness, focal steatosis is diagnosed.

The method is illustrated in Figs. 1-4, where:

figure 1 is a graphical representation of the distribution of quantitative indicators of stiffness (m/s) in accordance with the final diagnosis;

figure 2 (example 1) - carrying out a quantitative measurement of the stiffness of the lesion in shear wave elastography mode. The value is higher than normal values for the stiffness of the liver parenchyma and is 1.47 m/s (6.44 kPa);

figure 3 (example 2) - quantitative measurements of hardness in the lesion correspond to normal hardness values in the liver parenchyma;

figure 4 (example 3) - increased tissue stiffness in a solid lesion.

Determination of lesion stiffness parameters was carried out in 64 patients with a burdened history of cancer, in whom focal liver lesions were visualized during gray scale ultrasound.

All patients in this group underwent ultrasound examination using expert-class devices with a software package for activating the shear wave spot elastography mode.

The study was carried out using a convex sensor with a frequency of 2-8 MHz. Before the study, to normalize hemodynamics, the patient was in a horizontal position on the couch at rest for 10 minutes. Next, the study was carried out with the patient lying on his back with his right arm thrown back behind his head.

To expand the ultrasound “window” of imaging, the patient’s legs were retracted to the left. After imaging in greyscale mode, the shear wave spot elastography mode was activated. The area of interest should be clearly visualized on the echogram, without artifacts from the tissue of the lung, intestinal loops, or stomach. The value of the control window was set to the minimum (1 cm × 0.5 cm), the zone of interest was located in the central part of the focal formation with sizes from 10 mm to 15 mm and in the peripheral part with focal sizes of more than 16 mm. At least 10 measurements were taken at various control points in the area of interest, then 10 measurements were taken in healthy liver parenchyma to exclude diffuse changes such as fibrosis. The study was carried out with a short breath hold during normal inspiration to ensure a static image and minimize respiratory artifacts. Then, for convenience, all studies were entered into an Excel 2018 table for further analysis using a special statistical software package Jamovi [10]. In order to level out false values in the lesion, this group did not include patients with fibrous liver disease, obtained by evaluation by shear elastography of the liver (F2 and higher in accordance with the METAVIR scale), as well as patients who, according to the results of a biochemical blood test, had the level liver transaminases were 5 or more times higher than the threshold values. The final clinical diagnosis of the nature of the lesion was made on the basis of anamnestic data, as well as in conjunction with contrast-enhanced computed tomography performed according to a standard scanning protocol.

If a malignant process was suspected, a morphological verification of the formation was performed; when benign signs were determined using radiological methods, the patient was under dynamic observation every 3 months in the first six months of observation, then monitoring was carried out every 6 months. Based on the results of the final clinical diagnosis, the following data were obtained: metastases were detected in 29 patients, hemangioma in 16 cases, and in 19 people focal changes in the liver were interpreted as an area of focal steatosis.

During statistical analysis and plotting, it was found that all lesions interpreted as areas of focal liver steatosis had stiffness values comparable to the stiffness of normal liver parenchyma, and the average stiffness value of hemangiomas and metastases was significantly higher. When analyzing the data obtained for three types of lesions, the median of the minimum, maximum and average stiffness values in the lesion was calculated based on the results of 10 measurements with determination of the standard deviation, as well as the interquartile range (M±STD (min; max). The obtained data are presented in Table 1.

In our study, the quantitative values recommended by the European Federation of the Society of Ultrasound and Medicine in Biology (EFSUMB) ([9] - Dietrich C.F., 2017, [6] - Borsukov A.V., 2017) were taken as reference indicators of the stiffness of normal liver parenchyma. where quantitative indicators of normal stiffness of the liver parenchyma (normal or clinically insignificant liver fibrosis - F0/F1) corresponded to values less than 1.2 m/s (4.32 kPa), indicators of clinically significant liver fibrosis (F2) fell within the range of 1.24 up to 1.34 m/s (4.32-5.4 kPa), for severe fibrosis (F3) the range of values was determined to be 1.34-1.55 m/s (5.4-7.2 kPa), for cirrhosis (F4) 1.55-2.0 m/s (7.2-12 kPa).

Thus, when comparing the quantitative values of hardness indicators in the lesions and the recommended values of hardness in accordance with the presence of diffuse changes in the liver, the area of focal fatty hepatosis in terms of quantitative values of hardness does not differ from healthy liver parenchyma, solid foci, such as hemangiomas and metastases, in terms of quantitative values have a significantly pronounced excess of the stiffness index in comparison with normal liver parenchyma.

The method is carried out, for example, as follows.

Before starting differential diagnosis, a survey scan of all liver segments is performed to identify pathological changes. Next, if there is a pathological zone in a gray scale mode, the liver with a focal formation is displayed on the monitor screen, and this zone is measured in millimeters in two planes. When a stable U3 picture of a focal lesion is obtained, the point shear elastography mode is activated, a measurement window for ultrasound point shear elastography is placed on the area of interest, followed by activation of this mode while holding the breath to avoid artifacts and obtaining false values. When the lesion size is from 10 to 15 mm, the measurement frame in the lesion is directed to the central part; when the lesion size is more than 16 mm, the lesion is assessed along the periphery without capturing visually healthy tissue. After obtaining 10 measurements in the lesion, an additional 10 measurements are taken in the intact liver parenchyma to exclude diffuse changes such as fibrosis and, thus, possibly avoid false values of stiffness in the lesion. Normal values of liver stiffness for most ultrasound devices are stratified and quantitatively correspond to the stage of fibrosis according to the METAVIR system, used to assess fibrotic changes in the liver ([9] - Dietrich C.F., 2017, [6] - Borsukov A.V. 2017).

The method is confirmed by the following clinical examples.

Example 1. Patient B., 46 years old. Main disease: SA of the right breast (pT2N1M0), condition after complex treatment from 2019, against the background of hormone therapy (Tamoxifen) to the present. The patient is under dynamic observation at the oncology center. Ultrasound in the right lobe of the liver visualizes a hyperechoic focal formation, up to 17 mm in size, with clear, uneven contours. According to the results of shear wave elastography, the stiffness of normal liver tissue without focal changes in accordance with clinical recommendations is equal to normal values (F0/F1), which corresponds to the absence of fibrotic changes. According to the results of shear wave elastography, all measurement values in the lesion (n=10) significantly exceeded normal values of liver tissue stiffness (Fig. 2), the average value of lesion stiffness for 10 measurements was 1.66 m/s (8.27 kPa) - data the values are outside the reference range of normal liver stiffness values; therefore, this formation was regarded as a solid neoplasm of the liver, and a hemangioma was suggested. A contrast-enhanced computed tomography scan was performed, where the enhancement patterns of the lesion were consistent with a hepatic hemangioma. According to the results of observation over time, the size of the lesion in the liver remained unchanged. Therefore, taking into account multimodal imaging, the focal lesion in the liver is regarded as a hemangioma.

Example 2. Patient K., 69 years old. Main disease: Breast cancer. Condition after organ-conserving surgery, radiation therapy in 2012. Hormone therapy with Tamoxifen for 5 years. According to the results of a control computed tomography of the abdominal organs with intravenous contrast enhancement 6 months ago, no evidence of metastases was obtained, and no ultrasound examination was performed. The real purpose of the appeal: routine follow-up in accordance with the recommendations of the oncologist.

During control ultrasound in B-mode, in the right lobe of the liver, near the portal vein, a hyperechoic focal formation measuring 15x10 mm, with clear uneven contours, is visualized. According to the results of shear wave elastography, the stiffness of intact liver tissue, in accordance with clinical recommendations, is equal to normal values (1.12 m/s; 3.79 kPa), that is, there are no diffuse changes such as fibrosis. When assessing the visualized lesion in the liver, the quantitative indicators in the lesion also correspond to normal stiffness values (0.92 m/s; 2.53 kPa) (Fig. 3), the average stiffness of the lesion for 10 measurements was 1.07 m/s ( 3.44 kPa), these values do not fall outside the reference range of normal liver stiffness values; accordingly, this formation was regarded as focal hepatic steatosis. In a control study after 3 months, these changes did not change; therefore, the lesion in the liver is not secondary and does not require invasive interventions.

Example 3. Patient F., 28 years old. Complaints of pain in the right leg for 6 months, increased pain after physical activity, increasing intensity and length over time. A CT scan at the place of residence revealed a tumor of the retroperitoneal space on the right, hepatomegaly, and simple renal cysts. For further examination I went to the oncology center. A trephine biopsy of the formation was performed; based on the histology results, a diagnosis was made: epithelioid sarcoma of the proximal type, Ki67-30%.

A repeat CT scan of the chest and abdominal cavity was also performed (carried out 3 months after the initial study), according to the results of which an enlargement of the main tumor with invasion into adjacent muscles and vessels was diagnosed, metastases in the lungs were additionally determined, and metastases appeared in the liver. Ultrasound of the abdominal organs in the liver visualizes a hypoechoic focus with fuzzy, uneven contours, measuring up to 15 mm in diameter. When assessing the stiffness of the unaffected liver parenchyma, no evidence was obtained for the presence of fibrotic changes. When studying the stiffness parameters of the lesion using the shear elastography technique, values were obtained whose stiffness was significantly higher than the stiffness of normal liver parenchyma (Fig. 4), the average stiffness of the lesion in 10 measurements was 3 m/s (18 kPa) - these values come out from the reference interval of normal liver stiffness values, accordingly, this formation was regarded as a solid neoplasm of the liver, more likely of a metastatic nature. According to the results of a comprehensive examination, the lesion in the liver was a metastasis; during treatment, this lesion tended to decrease in size.

Thus, the proposed method allows one to detect changes in the liver at the screening stage, conduct constant non-invasive monitoring of cancer patients, allows one to determine further tactics for patient management, is an easily accessible, reliable, economical and, most importantly, dose-free diagnostic tool for detecting and characterizing liver damage. The advantages of the method are a reduction in the time for assessing focal liver formation, the possibility of differential diagnosis at the primary stage and a reduction in the costs of further research.

Information sources

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2. Rykov O.B., Parshin D.V., Tskhovrebov A.T., Mirzoyan O.S., Fedorov D.N., Tarasova I.A., Shestakov A.L. Results of treatment of stomach cancer and metachromic metastases in the liver and lungs. Surgery. Journal named after N.I. Pirogov. 2017; (6): 69-71. https://doi.org/10.17116/hirurgia2017669-71

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5. A.V. Borsukov, Yu.K. Alexandrov, M.I. Arabachyan et al. Shear wave elastography. Analysis of clinical examples: A practical guide for postgraduate professional retraining of doctors / A. Borsukov, Yu.K. Alexandrov, M.I. Arabachyan et al. - 2nd edition, revised and expanded. - Moscow: SIMK, 2022. - 468 p. - ISBN 978-5-91894-102-7.

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Claims (1)

A method for the differential diagnosis of focal hepatic steatosis and solid liver formations in patients with a burdened oncological anamnesis, including ultrasound examination of the focal formation in B-mode, characterized in that after visualization of the area of interest, the shear wave spot elastography mode is activated and when the size of the focal formation is from 10 to 15 mm measurements are carried out in the central part of the focal formation, and if its size is more than 16 mm - in the peripheral part of the focal formation, then a quantitative assessment of the stiffness of the liver tissue is carried out at 10 points in the zone of interest, and if the average value of tissue stiffness in the zone of interest is above the range of reference stiffness indicators liver tissue is diagnosed with a solid formation, and if the obtained value does not fall outside the range of reference values for liver tissue stiffness, focal steatosis is diagnosed.