RU2707062C1 - Method for predicting optimal time of thermal ischemia accompanying organ-preserving operations in renal parenchymal tumors - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention refers to medicine, namely to urology, oncourology. Following diagnostic criteria are determined: number of arteries feeding the tumor (x), tumor volume (x), largest diameter of arteries feeding tumor (x), maximum tumor size (x), distance from nearest tumor edge to ureter or pelvis system (x), which is measured in points, wherein distance of more than 7 mm is assigned 0 points, 7 mm and less is 1 point; distance from tumor edge to main vessels (x), which is measured in mm, tumor growth pattern (x). Said indicators are assigned points. Based on the obtained points, calculating values of functions Dis ischemia time to 20 min and Dis ischemia time more than 20 minutes by original formulas. Then calculated values Dand D, wherein in case of obtaining a larger number in function Dconclusion is made on high probability of thermal ischemia for more than 20 minutes, with a greater value in function Dhigh probability of ischemia less than 20 min is stated.EFFECT: method enables predicting the ischemia time more or less than 20 min, which influences the determination of tumor resectability, obtaining an objective and accurate prediction.1 cl, 2 ex, 2 dwg, 3 tbl

Description

FIELD OF THE INVENTION

The invention relates to medicine, namely to urology, oncourology, and can be used for preoperative planning and predicting the time of thermal ischemia during organ-preserving operations for kidney tumors. The permissible time for thermal ischemia, in which there is no serious damage to the parenchyma, is considered 20 minutes. The developed method allows to predict the time of ischemia of more or less than 20 minutes, which affects the determination of tumor resectability.

State of the art

The prior art methods are known that can be used to predict the time of ischemia, the most famous among them are: PADUA (Interactive aspects and dimensions used for an anatomical), C-index is the ratio of the distance from the center of the tumor (cm) to the center of the kidney to the radius tumors (cm), as well as the RENAL scale [Simmons MN, Ching NE, Samplaski MK, Park CH, Gill IS. Kidney tumor location measurement using the C index method. J Urol. 2010; 183: 1708-13. [PubMed] Kutikov A, Uzzo RG. The R.E.N.A.L. Nephrometry score: A comprehensive standardized system for quantitating renal tumor size, location and depth. J Urol. 2009; 182: 844-53. [PubMed] Ficarra V, Novara G, Secco S, Macchi V, Porzionato A, De Caro R, et al. Preoperative aspects and dimensions used for an anatomical (PADUA) classification of renal tumors in patients who are candidates for nephron-sparing surgery. Eur Urol. 2009; 56: 786-93. [PubMed].

However, the known methods are subjective, because the assessment is based on data obtained on the basis of MSCT (multispiral computed tomography), which, in particular, does not provide detailed information on the ratio of the tumor to the pyelocaliceal system (CLS) and the connection with the vessels.

Closest to the claimed solution is the method used by the scale to assess the complications of R.E.N.A.L. [Kutikov A, Uzzo RG. The R.E.N.A.L. Nephrometry score: A comprehensive standardized system for quantitating renal tumor size, location and depth. J Urol. 2009; 182: 844-53. [PubMed]. The method is based on the determination of the following parameters: R (radius, tumor size, in cm), E (exophytic / endophytic - exophytic or endophytic nature of the tumor), N (nearness, proximity of the tumor to the cavity system of the kidney or its sinus, mm), A ( anterior, location of the tumor along the anterior or posterior surface of the kidney), L (location, localization of the tumor relative to the transverse lines drawn through the edges of the renal sinus), each of which is estimated by MSCT images in points, based on the sum of which a prognosis of the probability of intra- and early postoperative complications as well as time no thermal ischemia.

However, this method is based only on the interpretation of the image of MSCT (multispiral computed tomography), and does not take into account the complex of other significant anatomical parameters that can be obtained from 3D tumor modeling, which reduces the reliability and accuracy of obtaining predictive estimates. In addition, this method is difficult for preoperative planning carried out by a urologist / oncologist, since it requires the use of special knowledge in the field of radiation diagnostics and the possession of appropriate software, which increases the risk of erroneous conclusions.

Disclosure of invention

The technical problem solved by the invention is the creation of a method for predicting the time of thermal ischemia in organ-preserving operations for tumors of the renal parenchyma, which provides more reliable and accurate predictive estimates. The method is based on the construction of a 3D model of the pathological lesion with subsequent evaluation of the original complex of parameters on a 3D nephrometric scale.

The technical result, to which the claimed invention is directed, is the possibility of obtaining a more objective predictive assessment by using a set of criteria measured on a 3D model of the pathological focus obtained by the results of radiation research methods (for example, CT, micro CT, MRI, MSCT).

The technical result is achieved by implementing a method for predicting thermal ischemia during organ-preserving operations for kidney parenchyma tumors, including a study of the kidney parenchyma tumor by radiation methods with the construction of a 3D model of the pathological focus, determination of diagnostic signs, which are used as:

the number of arteries supplying the tumor - x ₁ , which is measured in points, while the absence of arteries is defined as 0 points, the presence of 1 to 3 arteries inclusive - 1 point, more than 3-2 points;

tumor volume - x ₂ , which is measured in points, while tumors with a volume of up to 20,000 voxel assign 0 points, 20000-40000 voxel - 1 point, 40001-60000 voxel - 2 points, more than 60,000 - 3 points;

the largest diameter of the vessels (arteries) supplying the tumor is x ₃ , which is measured in points, if the arteries are not visualized - 0 points, the diameter of the arteries 1-3 mm - 1 point, more than 3 mm - 2 points;

the maximum tumor size is x ₄ , which is measured in mm;

the distance from the nearest edge of the tumor to the ureter or the pyelocaliceal system is x ₅ , which is determined by the minimum distance from the edge of the tumor to the nearest of these structures, which is measured in points (more than 7 mm — 0 points, 7 mm or less — 1 point);

the distance from the edge of the tumor to the main vessels - x ₆ , which is measured in mm (the smallest distance between the tumor and the nearest main vessel, i.e. the distance from the nearest edge of the tumor to the nearest main vessel - arteries of the 1st or 2nd order);

the nature of tumor growth is x ₇ , which is measured in points: with an extrarenal nature of tumor growth equal to or more than 50%, 0 points are assigned, extrarenal less than 50% - 1 point, intrarenal with a distance to the kidney capsule 0-10 mm - 2 points, intrarenal with the distance from the tumor to the kidney capsule is more than 10 mm - 3 points.

According to the obtained values, the values of the functions D ₁ and D ₂ are calculated:

D ₁ = -11.512 + 2.165x ₁ - 2.216x ₂ - 0.283x ₃ + 0.287x ₄ + 2.399x ₅ + 0.205x ₆ + 1.751x ₇

D ₂ = -13.002+ 2.168x ₁ - 2.167x ₂ - 0.631x ₃ + 0.308x ₄ + 2.530x ₅ + 0.196x ₆ + 2.107x ₇ ,

Where

D ₁ - linear discriminant function characterizes the probability of thermal ischemia less than 20 min, D ₂ - linear discriminant function characterizes the probability of thermal ischemia more than 20 min;

x ₁ - x ₇ - values of features included in the model.

According to the method, the calculated values of D ₁ and D _{2 are} compared, while in the case of obtaining a larger number in function D ₂ , a conclusion is made that heat ischemia is more likely to be more than 20 minutes, with a larger value in function D ₁ , a conclusion is made that there is a high probability of ischemia less than 20 min.

Brief Description of the Drawings

The invention is illustrated by drawings, where in FIG. 1 presents ROC-curves for predicting the time of thermal ischemia in the treatment of kidney cancer, obtained using the proposed method and other existing methods; in FIG. Figure 2 presents the constructed 3D model of a kidney parenchyma tumor based on the obtained MSCT data.

The implementation of the invention

Below is a more detailed description of the proposed method.

264 patients were studied, which were divided into 2 groups: 46 patients - in whom the time of thermal ischemia was more than 20 minutes and 218 patients - with the time of thermal ischemia of less than 20 minutes. The study assessed the degree of connection of various indicators (signs) characterizing a tumor of the renal parenchyma with predictive conclusions about ischemia during surgery for more than 20 minutes and less than 20 minutes, using standard statistical methods (discriminant analysis method). As a result, we selected those that gave the correlation coefficients closest to 1, which indicates the strongest relationship between the indicators and the estimated event.

Based on the results of studies and discriminant data analysis with the aim of predicting the duration of ischemia before surgery for more than 20 minutes before surgery, 7 of the most significant classification features were selected. Signs included in the model were: the maximum tumor size (mm), the number of arteries supplying the tumor (0-0 points, 1-3 - 1 point, more than 3-2 points), the distance from the edge of the tumor to the great vessels (mm) , the largest diameter of the arteries that feed the tumor (not visualized - 0 points, 1-3 mm - 1 point, more than 3 mm - 2 points, if there is more than one artery, measure the diameter of the larger artery), the distance from the nearest edge of the tumor to the ureter or calyx pelvis system (more than 7 mm - 0 points, 7 mm or less - 1 point), tumor volume (in points, up to 20,000 voxel - 0 point fishing, 20000-40000 voxel - 1 point, 40001-60000 voxel - 2 points, more than 60,000 voxel - 3 points), the nature of tumor growth (extrarenal from 50% or more - 0 points, extrarenal less than 50% - 1 point, intrarenal with a distance to the kidney capsule of 0-10 mm - 2 points, intrarenally with a distance to the kidney capsule of more than 10 mm - 3 points).

To classify observation units according to the characteristics of one patient, linear discriminant functions were calculated with the coefficients of each group. The predicted case refers to the group for which the discriminant function takes the maximum value. To test the hypothesis about the homogeneity of the covariance matrices of the groups under study, the multidimensional Box M-test was used. The sensitivity and specificity of the set of criteria was evaluated using ROC analysis. Quantitative interpretation of the results was carried out according to ROC-curves with the assessment of the AUC indicator (Area under ROC curve - area under the ROC-curve).

The structural matrix of the correlation of discriminant variables with the canonical discriminant function, on the basis of which the variables were selected, are presented in table 1.

The canonical correlation describing the measure of the relationship between the discriminating function and the observation groups was 0.216, which accounts for 21.6% of the variance of the classified variable. The Wilks lambda in evaluating the canonical discriminant function was 0.953 (χ ² = 13.504; p = 0.041).

The largest contribution to the classification results from the selected variables is made by the indicators: the maximum tumor size, the nature of the tumor growth and the diameter of the vessels supplying the tumor.

For the studied groups, Fisher's classification functions were determined. The coefficients of linear models of the discriminant function, including classification features, are presented in table 2.

Based on table 2, the prediction of thermal ischemia up to 20 min and more than 20 min during surgical treatment of kidney cancer is carried out by determining D ₁ and D ₂ :

where D ₁ is the linear discriminant function for the duration of ischemia up to 20 min, D ₂ is the linear discriminant function modeling the ischemia for more than 20 min, x ₁ - x ₇ are the values of the attributes included in the model (table 2).

Upon receipt of two values of the functions D ₁ and D ₂ , they are compared and, if a larger number is obtained in the function D ₂ , a conclusion is made that heat ischemia is more likely to occur for more than 20 minutes; when a larger value in the function D ₁ , a conclusion is made that there is a high probability of ischemia less than 20 min .

Based on the obtained discriminant functions, a final classification was made, the results of which are presented in table 3.

The resulting predictive model has a specificity of 66.2%. The sensitivity of the model (correct predictions of ischemia for more than 20 minutes) was 65.2%. The overall accuracy of the model is 65.9%.

In the same sample, the discriminant model using the RENAL index as a predictor had a sensitivity of 59.1%, specificity of 50.8%, and overall accuracy of 52.4%. For the model using the PADOVA index, the sensitivity was 52.3%, specificity was 64.4%, and overall accuracy was 62.1%. When using the C-index as a predictor of ischemia duration of more than 20 min, the highest sensitivity was achieved - 68.2%, but significantly lower specificity - 42.6%, the overall accuracy of the model was 47.4% (Fig. 1).

To implement the proposed method, all patients undergo radiation diagnostics, for example, CT, micro CT, MRI, MSCT, before surgical treatment. According to the data obtained, they will build a 3D model of the pathological focus. The construction of a 3D model can be carried out using any software tools known from the prior art that provide adequate visualization of the anatomical structures, evaluated in the proposed scale (number of arteries supplying the tumor, tumor volume, diameter of the vessels supplying the tumor, maximum tumor size, distance to the ureter and / or TLS, distance to the great vessels, the nature of tumor growth).

As software, for example, Amira program version 5.4.5 can be used. (https://amira.software.informer.com/5.6/). If necessary, adjust the resulting 3D model - it can be implemented, for example, using Amira software (VisageImaging).

To build a 3D model in the Amira program, the obtained data (images) using CT, micro CT, MRI, 3D microscopy and other methods are loaded into the Amira program, filtered (artifact removal) and image preprocessing, and a 3D image is formed from the obtained data . On the resulting model, anatomical structures are distinguished that measure and analyze, visualize their spatial relationship.

3D modeling allows without distortion to effectively combine all four phases of visualization (contrasting) on a single integrated image: 1 - native examination, 2 - arterial phase, 3 - parenchymal, 4 - excretory, which gives comprehensive information about the anatomical features of the kidney affected by the tumor process, such as the number of vessels supplying the tumor, their diameter, the ratio of the tumor to the heart rate, etc.

The assessment of the time of thermal ischemia during organ-preserving operations for tumors of the renal parenchyma is carried out according to the above formulas using the measured parameters (see Table 1).

Below are examples of the implementation of the claimed invention.

Example. 1 Patient X., 57 years old.

Anamnesis: accidentally detected formation by ultrasound. According to MSCT, a tumor of the right kidney up to 50 mm in size was detected. Based on the obtained MSCT data, 3D modeling was performed (Fig. 2).

As a preoperative planning, the calculation of the time of thermal ischemia with organ-preserving benefits was performed.

According to 3D modeling, the patient revealed:

one artery feeding the tumor (x ₁ = 1 point);

the tumor volume was 62300 voxel (x ₂ = 3 points);

the diameter of the artery feeding the tumor was 2.17 mm (x ₃ = 1 point);

the maximum tumor size was 52.31 mm (x ₄ = 52.31);

the minimum distance from the PCS or ureter to the tumor was 1.4 mm (x ₅ = 1 point);

the minimum distance from the tumor to the great vessels (renal artery or first-order segmental arteries) was 1.37 mm (x ₆ = 1.37);

the nature of tumor growth - extrarenal more than 50% (x ₇ = 0 points).

Next, the values of the linear discriminant function were calculated for the duration of ischemia up to 20 min and more than 20 min, respectively:

D ₁ = -11.512 + 2.165x1-2.216x3-0.283x1 + 0.287x52.31 + 2.399x1 + 0.205x1.37 + 1.751x0 = 1.24

D ₂ = -13.002 + 2.168x1-2.167x3-0.631x1 + 0.308x52.31 + 2.530x1 + 0.196x1.37 + 2.107x0 = 1.25

The value of D ₁ was 1.24, the value of D ₂ was 1.25. The obtained value of D ₂ exceeded the value of D ₁ , the patient according to the calculations performed before the operation revealed a high probability of thermal ischemia for more than 20 minutes

According to the results of preoperative planning in a patient, the expected time of thermal ischemia is more than 20 minutes. The patient underwent laparoscopic enucleation of a kidney tumor. Intraoperative ischemia time was 27 minutes.

Example 2. Patient X, 63 years old.

Anamnesis: accidentally detected formation by ultrasound. According to MSCT, a tumor of the right kidney up to 20 mm in size was detected. Based on the obtained MSCT data, 3D modeling was performed.

As a preoperative planning, the calculation of the time of thermal ischemia with organ-preserving benefits was performed.

According to the 3D modeling of the patient:

no arteries feeding the tumor were identified (x ₁ = 0 points, x ₃ = 0 points);

the tumor volume was 45,000 (x ₂ = 1 point);

the maximum tumor size was 22 mm (x ₄ = 22);

the minimum distance from the PCS or ureter to the tumor was 30 mm (x ₅ = 0 points);

the minimum distance from the tumor to the great vessels (renal artery or first-order segmental arteries) was 40 mm (x ₆ = 40);

the nature of tumor growth - extrarenal more than 50% (x ₇ = 0 points).

The value of the linear discriminant function D ₁ was 0.588, the value of D ₂ was 0.562:

D ₁ = -11.512 + 2.165x0-2.216x1-0.283x0 + 0.287x22 + 2.399x0 + 0.205x40 + 1.751x0 = 0.588

D ₂ = -13.002 + 2.168x0-2.167x1-0.631x0 + 0.308x22 + 2.530x0 + 0.196x40 + 2.107x0 = 0562

The obtained value of D ₁ exceeded the value of D ₂ , the patient according to the calculations performed before the operation revealed a low risk of heat ischemia for more than 20 minutes.

According to the results of preoperative planning in a patient, the expected time of thermal ischemia is less than 20 minutes. The patient underwent laparoscopic enucleation of a kidney tumor. The intraoperative time of ischemia was 7 minutes.

Thus, the claimed method has shown its viability and the ability to use in practical work.

Claims (13)

A method for predicting the time of thermal ischemia during organ-preserving surgeries for tumors of the kidney parenchyma, including a study of the tumor of the kidney parenchyma by radiation methods with the construction of a 3D model of the pathological focus, the determination of diagnostic signs, which are used as: the number of arteries that feed the tumor (x ₁ ), which is measured in points, while the absence of arteries is defined as 0 points, the presence of 1 to 3 arteries inclusively - 1 point, more than 3-2 points; tumor volume (x ₂ ), which is measured in points, while tumors up to 20,000 voxel are assigned 0 points, 20,000-40000 voxel - 1 point, 40001-60000 voxel - 2 points, more than 60,000 - 3 points; the largest diameter of the arteries that feed the tumor (x ₃ ), which is measured in points, while if the arteries are not visualized, assign 0 points, if the diameter is 1-3 mm - 1 point, more than 3 mm - 2 points; maximum tumor size (x ₄ ), which is measured in mm; the distance from the nearest edge of the tumor to the ureter or pyelocaliceal system (x ₅ ), which is measured in points, while a distance of more than 7 mm is assigned 0 points, 7 mm or less - 1 point; the distance from the edge of the tumor to the great vessels (x ₆ ), which is measured in mm, the nature of tumor growth (x ₇ ), which is measured in points, where with an extrarenal nature of tumor growth equal to or more than 50%, 0 points are assigned, extrarenal less than 50% - 1 point, intrarenal with a distance to the kidney capsule 0-10 mm - 2 points, intrarenal with a distance from the tumor to the kidney capsule of more than 10 mm - 3 points; according to the obtained values, the values of the functions D ₁ and D ₂ are calculated: D ₁ = -11.512 + 2.165x ₁ -2.216x2-0.283x ₃ + 0.287x ₄ + 2.399x ₅ + 0.205x ₆ + 1.751x ₇ D ₂ = -13.002 + 2.168x ₁ -2.167x ₂ -0.631x ₃ + 0.308x ₄ + 2.530x ₅ + 0.196x ₆ + 2.107x ₇ , where the function D ₁ characterizes the time of ischemia up to 20 minutes, D ₂ - characterizes the time of ischemia more than 20 minutes; comparing the calculated values of D ₁ and D ₂ , in this case, if a larger number is obtained in the function D ₂ , a conclusion is made about a high probability of thermal ischemia for more than 20 minutes, with a higher value in the function D ₁ , a conclusion is made that a high probability of ischemia is less than 20 minutes.

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