A system for assessing the risk of complications after liver resection in subjects before surgery

Abstract

The present application provides a system for assessing the risk of complications after liver resection of a subject before surgery, which includes: a data acquisition module, which is used to obtain the Child-pugh level of the subject, the presence or absence of medical diseases requiring drug treatment, the number of liver segments to be removed, whether the subject has organ invasion, and the subject's preoperative hospitalization time; and a module for calculating the risk of complications after liver resection of the subject, which is used to calculate the above information obtained in the data acquisition module, so as to calculate the probability of the risk of complications after liver resection of the subject (P). The system described in the present application has good reliability, and the preoperative prediction of the incidence of liver surgery complications is consistent with the actual situation, and can be used to assess the risk of complications of liver surgery before surgery.

Description

Technical Field

[0001] The present invention relates to the technical field of pre-operative risk assessment, and in particular to a system for assessing the risk of post-operative complications of liver resection of a subject before surgery. Background Art

[0002] Liver resection has always been affected by its complexity, high complication rate and mortality rate, which affect the prognosis of surgery. However, in recent years, the safety of liver resection has been significantly improved by optimizing the selection of surgical patients, anesthesia and perioperative management, especially the establishment of hepatobiliary surgery as a specialty. Over the past half century, the safety of liver resection has always been at the top of liver surgery. Liver surgery has developed rapidly, and liver resection has evolved from a risky operation to a relatively safe operation. However, liver surgery still has a high complication rate and mortality rate, and appropriate preoperative prevention strategies must be considered to reduce the risk of postoperative complications. However, there is currently a lack of a complete system in this field to predict and evaluate complications of liver surgery through preoperative factors. Summary of the invention

[0003] In view of the above problems in the art, the inventor of this application has conducted in-depth research and attempted to establish a preoperative risk prediction and assessment system for liver surgery complications with strong clinical operability, so as to intervene in high-risk patients before surgery, thereby improving the safety of liver surgery, which has become a problem that urgently needs to be solved in clinical practice. The technical solution of this application designs a preoperative risk prediction and assessment system for liver surgery complications and analyzes and verifies it.

[0004] The technical solution of the present invention is as follows:

[0005] 1. A system for assessing the risk of complications after liver resection in a subject before surgery, comprising:

[0006] A data collection module, which is used to obtain the Child-Pugh grade of the subject, whether there are any medical diseases that require drug treatment, the number of liver segments to be removed, whether there is any organ invasion in the subject, and the preoperative hospitalization time of the subject; and

[0007] The module for calculating the risk of complications after liver resection of the subject is used to calculate the above information obtained in the data acquisition module, so as to calculate the risk probability (P) of complications after liver resection of the subject.

[0008] 2. The system according to claim 1, further comprising:

[0009] In the module for calculating the risk of complications after liver resection of the subjects, the Child-Pugh level of the subjects, the presence or absence of medical diseases requiring drug treatment, the number of liver segments to be resected, the presence or absence of organ invasion in the subjects, and the preoperative hospitalization time of the subjects obtained by the data acquisition module are converted into their respective corresponding values, and the assigned values ​​are entered into the formula model stored in the module for calculating the risk of complications after liver resection of the subjects to calculate the probability of risk of complications after liver resection of the subjects (P).

[0010] 3. A system according to item 2, wherein the Child-pugh grade of the subject is based on the presence or absence of hepatic encephalopathy, ascites, serum bilirubin, serum albumin concentration and prothrombin time, and the Child-pugh grade of the subject is determined as A, B or C based on the judgment of the clinician.

[0011] 4. A system according to claim 2, wherein:

[0012] The medical condition requiring drug treatment refers to one or more existing medical diseases requiring drug treatment other than surgical diseases requiring surgical treatment;

[0013] The number of liver segments to be resected refers to the parts that need to be resected among the 8 liver segments divided by the Couinaud segmentation method used clinically;

[0014] The organ invasion refers to the situation where the malignant tumor infiltrates and grows into adjacent organs other than the primary organ;

[0015] The subject's preoperative hospitalization time refers to the period from the time the patient is hospitalized for the surgery to before the surgery is performed.

[0016] 5. A system according to claim 2, wherein:

[0017] The assignment is determined based on the OR values ​​of the Child-Pugh grade of the subject, the presence or absence of medical diseases requiring drug treatment, the number of liver segments to be resected, the presence or absence of organ invasion in the subject, and the subject's preoperative hospitalization time parameters, which are pre-stored in a module for calculating the risk of complications after liver resection of the subject.

[0018] 6. A system according to item 2, wherein the formula model is a formula obtained by regression fitting based on the confirmed values ​​of each parameter including the subject's Child-Pugh grade, the presence or absence of medical diseases requiring drug treatment, the number of liver segments to be resected, the presence or absence of organ invasion in the subject, and the subject's preoperative hospitalization time.

[0019] 7. The system according to item 6, wherein the formula model is formula 1:

[0020] P=1 / {1+exp[-(α+β1χ1+β2χ2+β3χ3+β4χ4+β5χ5)]} (Formula 1),

[0021] Among them, χ1 is the value assigned to the Child-Pugh level of the subject;

[0022] χ2 is the value assigned to whether the subject has a medical condition that requires medication;

[0023] χ3 is the value assigned to the number of liver segments to be resected;

[0024] χ4 is the value assigned to whether the subject has organ invasion;

[0025] χ5 is the value assigned to the subject’s preoperative hospital stay;

[0026] P is the risk probability of complications after liver resection in the subjects;

[0027] Preferably, the value of α is -4.844;

[0028] The value of β1 is 0.737;

[0029] The value of β2 is 0.530;

[0030] The value of β3 is 0.673;

[0031] The value of β4 is 0.412;

[0032] The value of β5 is 0.464.

[0033] 8. A system according to item 6, wherein:

[0034] When the Child-pugh level of the subject is A, the Child-pugh level of the subject is assigned a value of 1.

[0035] When the Child-pugh level of the subject is B or C, the Child-pugh level of the subject is assigned a value of 2.

[0036] 9. A system according to item 6, wherein:

[0037] When the subject has no medical disease that requires drug treatment, the value of whether the subject has a medical disease that requires drug treatment is 1.

[0038] When the subject has a medical disease that requires drug treatment, the value assigned to the subject's medical disease status is 2.

[0039] 10. A system according to item 6, wherein:

[0040] When the subject has less than or equal to 2 liver segments to be resected, the value assigned to the number of liver segments to be resected is 1;

[0041] When the subject has 3 or more liver segments to be removed, the value assigned to the number of liver segments to be removed is 2.

[0042] 11. A system according to item 6, wherein:

[0043] When the subject does not have organ invasion, the value assigned to whether the subject has organ invasion is 1;

[0044] When the subject has organ invasion, the value assigned to whether the subject has organ invasion is 4.

[0045] 12. A system according to item 6, wherein:

[0046] When the subject's preoperative hospitalization time is less than or equal to 7 days, the subject's preoperative hospitalization time is assigned a value of 1;

[0047] When the subject's preoperative hospitalization time is greater than 7 days, the subject's preoperative hospitalization time is assigned a value of 2.

[0048] 13. A method for assessing the risk of post-hepatectomy complications in a subject prior to surgery, comprising:

[0049] Data collection steps, which are used to obtain the Child-Pugh grade of the subject, whether there are medical diseases requiring drug treatment, the number of liver segments to be resected, whether there is organ invasion in the subject, and the subject's preoperative hospitalization time; and

[0050] The step of calculating the risk of complications after liver resection of the subject is used to calculate the above information obtained in the data acquisition module, so as to calculate the risk probability (P) of complications after liver resection of the subject.

[0051] 14. The method according to claim 13, further comprising:

[0052] In the step of calculating the risk of complications after liver resection of the subject, the Child-Pugh level of the subject, the presence or absence of medical diseases requiring drug treatment, the number of liver segments to be resected, the presence or absence of organ invasion in the subject, and the preoperative hospitalization time of the subject obtained in the data collection step are converted into their respective corresponding values, and the assigned values ​​are entered into the formula model stored in the module for calculating the risk of complications after liver resection of the subject to calculate the probability of the risk of complications after liver resection of the subject (P).

[0053] 15. The method according to claim 14, wherein the Child-Pugh grade of the subject is determined as A, B or C based on the presence or absence of hepatic encephalopathy, ascites, serum bilirubin, serum albumin concentration and prothrombin time, based on the judgment of the clinician.

[0054] 16. The method according to claim 14, wherein:

[0055] The medical condition requiring drug treatment refers to one or more existing medical diseases requiring drug treatment other than surgical diseases requiring surgical treatment;

[0056] The number of liver segments to be resected refers to the parts that need to be resected among the 8 liver segments divided by the Couinaud segmentation method used clinically;

[0057] The organ invasion refers to the situation where the malignant tumor infiltrates and grows into adjacent organs other than the primary organ;

[0058] The subject's preoperative hospitalization time refers to the period from the time the patient is hospitalized for the surgery to before the surgery is performed.

[0059] 17. The method according to claim 14, wherein:

[0060] The assignment is determined based on the OR values ​​of the Child-Pugh grade of the subject, the presence or absence of medical diseases requiring drug treatment, the number of liver segments to be resected, the presence or absence of organ invasion in the subject, and the subject's preoperative hospitalization time parameters, which are pre-stored in a module for calculating the risk of complications after liver resection of the subject.

[0061] 18. The method according to claim 14, wherein the formula model is a formula obtained by regression fitting based on the values ​​confirmed by the Child-Pugh grade of the subject, the presence or absence of medical diseases requiring drug treatment, the number of liver segments to be resected, the presence or absence of organ invasion in the subject, and the preoperative hospitalization time of the subject.

[0062] 19. The method according to claim 18, wherein the formula model is Formula 1:

[0063] P=1 / {1+exp[-(α+β1χ1+β2χ2+β3χ3+β4χ4+β5χ5)]} (Formula 1),

[0064] Among them, χ1 is the value assigned to the Child-Pugh level of the subject;

[0065] χ2 is the value assigned to whether the subject has a medical condition that requires medication;

[0066] χ3 is the value assigned to the number of liver segments to be resected;

[0067] χ4 is the value assigned to whether the subject has organ invasion;

[0068] χ5 is the value assigned to the subject’s preoperative hospital stay;

[0069] P is the risk probability of complications after liver resection in the subjects;

[0070] Preferably, the value of α is -4.844;

[0071] The value of β1 is 0.737;

[0072] The value of β2 is 0.530;

[0073] The value of β3 is 0.673;

[0074] The value of β4 is 0.412;

[0075] The value of β5 is 0.464.

[0076] 20. The method according to claim 18, wherein:

[0077] When the Child-pugh level of the subject is A, the Child-pugh level of the subject is assigned a value of 1.

[0078] When the Child-pugh level of the subject is B or C, the Child-pugh level of the subject is assigned a value of 2.

[0079] 21. The method according to claim 18, wherein:

[0080] When the subject has no medical disease that requires drug treatment, the value of whether the subject has a medical disease that requires drug treatment is 1.

[0081] When the subject has a medical disease that requires drug treatment, the value assigned to the subject's medical disease status is 2.

[0082] 22. The method according to claim 18, wherein:

[0083] When the subject has less than or equal to 2 liver segments to be resected, the value assigned to the number of liver segments to be resected is 1;

[0084] When the subject has 3 or more liver segments to be removed, the value assigned to the number of liver segments to be removed is 2.

[0085] 23. The method according to claim 18, wherein:

[0086] When the subject does not have organ invasion, the value assigned to whether the subject has organ invasion is 1;

[0087] When the subject has organ invasion, the value assigned to whether the subject has organ invasion is 4.

[0088] 24. The method according to claim 18, wherein:

[0089] When the subject's preoperative hospitalization time is less than or equal to 7 days, the subject's preoperative hospitalization time is assigned a value of 1;

[0090] When the subject's preoperative hospitalization time is greater than 7 days, the subject's preoperative hospitalization time is assigned a value of 2.

[0091] Compared with the prior art, the technical effects of the present invention are:

[0092] The present invention establishes a binomial classification logistic regression model to obtain a formula for calculating the risk of complications of liver surgery (LORF formula). The area under the curve of the LORF formula is 0.782 (95% confidence interval is 0.749-0.815), the corresponding standard error is 0.017, P<0.001. The cutoff value for calculating the complication rate is 0.32 (32%). The LORF formula has good reliability, and the preoperative prediction of the incidence of liver surgery complications is consistent with the actual situation, and can be used to evaluate the risk of complications of liver surgery before surgery. BRIEF DESCRIPTION OF THE DRAWINGS

[0093] Figure 1 This is the prediction result curve of the five combined variables χ1-χ5. The AUC of the total score prediction of the five combined variables is 0.735;

[0094] Figure 2 This is the prediction result curve of LORF formula. The AUC of LORF formula is 0.782;

[0095] Figure 3 This is the verification result curve of the LORF formula. The AUC of the LORF formula is 0.727. DETAILED DESCRIPTION

[0096] The specific embodiments of the present invention will be described in more detail below. However, it should be understood that the present invention can be implemented in various forms and should not be limited by the embodiments set forth herein. On the contrary, these embodiments are provided to enable a more thorough understanding of the present invention and to enable the scope of the present invention to be fully communicated to those skilled in the art.

[0097] It should be noted that certain words are used in the specification and claims to refer to specific components. Those skilled in the art should understand that technicians may use different nouns to refer to the same component. This specification and claims do not use the difference in nouns as a way to distinguish components, but use the difference in the functions of the components as the criterion for distinction. As mentioned throughout the specification and claims, "including" or "comprising" is an open term, so it should be interpreted as "including but not limited to". The subsequent description of the specification is a preferred embodiment of the present invention, but the description is based on the general principles of the specification and is not intended to limit the scope of the present invention. The scope of protection of the present invention shall be determined by the attached claims.

[0098] Liver resection refers to the surgical removal of a part of the liver together with the liver lesion, while retaining normal liver tissue sufficient to maintain function. Liver resection is suitable for liver cancer, hepatic hemangioma, etc. The scope of surgical resection of the liver depends on the size and location of the tumor. The surgery requires the removal of the tumor together with a small amount of surrounding normal liver tissue. Liver resection is divided into regular and irregular types based on whether the resection is performed according to the anatomy of the liver segment. The liver has abundant blood flow, and effective control of bleeding during surgery is the key to a successful liver resection. Regular liver resection can control bleeding more effectively. According to the scope of liver resection, liver resection can currently be divided into: wedge resection, partial liver resection, lobectomy, hemihepatectomy, middle lobectomy and trisegmentectomy.

[0099] definition:

[0100] The perioperative period is the entire process surrounding the operation, starting from the patient's decision to undergo surgical treatment, to the surgical treatment and basic recovery, including the period before, during and after the operation. Specifically, it refers to the period from the time the surgical treatment is determined until the treatment related to this operation is basically completed, which is approximately 5-7 days before the operation to 7-12 days after the operation.

[0101] There are many factors that affect the incidence of perioperative complications, including patient age, gender, nutritional status, comorbidities, and surgical methods. The incidence of complications varies at different stages of the perioperative period.

[0102] Currently, the prediction and prevention of perioperative complications are determined by individual doctors based on their experience. Limited by the doctors' personal knowledge level and clinical experience, they are often unable to judge the probability of perioperative complications and whether active prevention is needed.

[0103] The Child-Pugh grade is a clinically commonly used grading standard for quantitatively evaluating the liver reserve function of patients with cirrhosis. The standard was first proposed by Child in 1964. At that time, Child divided the different states of the patient's five indicators (including general condition, ascites, serum bilirubin, serum albumin concentration and prothrombin time) into three levels, with 1 point, 2 points and 3 points respectively, and added the scores of the five indicators. The minimum total score was 5 points and the maximum score was 15 points. According to the amount of the sum, the liver reserve function was divided into three levels of A, B and C from low to high, indicating three different degrees of liver damage (the higher the score, the worse the liver reserve function). However, since the patient's general condition is often difficult to score, Pugh later proposed to replace the general condition with the presence or absence of hepatic encephalopathy and its degree, which is the Child-Pugh grade commonly used in clinical practice today.

[0104] In this application, based on the clinician's observation of the subjects, the presence or absence of hepatic encephalopathy, ascites, serum bilirubin, serum albumin concentration and prothrombin time are scored separately, each of which is divided into three levels, with the lowest level being 1 point and the highest level being 3 points. The scores of the five indicators are added together, and a score of 5-6 points is classified as Grade A, a score of 7-9 points is Grade B, and a score ≥10 points is Grade C.

[0105] The situation of medical diseases that require drug treatment in this application refers to: it refers to one or more other original medical diseases that require drug treatment in addition to the surgical diseases that require surgical treatment. Specifically, in addition to the surgical diseases that require surgical treatment, the patient usually also has one or more other original medical diseases, which are called comorbidities. Comorbidities are very common in surgical patients. Perioperative comorbidities may exist alone or occur simultaneously, often leading to the corresponding organ dysfunction of the heart, lungs, kidneys, etc., which reduces the reserve capacity to maintain the stability of the internal environment under stress, and is closely related to postoperative complications and mortality. If the patient's comorbidities are mild, no drug treatment is required. If they are severe, drug treatment is required. Therefore, these coexisting medical diseases that require drug treatment during the perioperative period are important factors affecting the effectiveness of surgery. For chronic medical comorbidities that require long-term drug treatment, such as hypertension and diabetes, the condition must be adjusted to a stable state before surgery can be performed; for diseases that can be cured with only short-term drug treatment, such as acute pharyngitis, unless the patient's surgical condition is urgent and requires immediate surgery, surgery should be performed after recovery. Therefore, during preoperative evaluation, such conditions should not be included in the category of medical diseases that require drug treatment.

[0106] The number of liver segments in this application is based on the Couinaud classification, which divides the liver into eight parts through the cross section of the bifurcation of the hepatic vein and the portal vein, specifically segment I, segment II, segment III, segment IVIV, segment V, segment VI, segment VII and segment VIII.

[0107] The number of liver segments to be resected in this application refers to the parts that need to be resected among the above eight parts, specifically: Segment I: caudate lobe; Segment II: upper segment of left lateral lobe; Segment III: lower segment of left lateral lobe; Segment IV: left medial lobe; Segment V: lower segment of right anterior lobe; Segment VI: lower segment of right posterior lobe; Segment VII: upper segment of right posterior lobe; Segment VIII: upper segment of right anterior lobe. The wider the range of lesions, the more liver segments need to be resected.

[0108] In this application, organ invasion refers to the situation where a malignant tumor infiltrates and grows into adjacent organs outside the primary organ. Specifically, a malignant tumor can not only grow in the primary organ, but also infiltrate and grow outside the primary organ, thereby invading adjacent organs. In this case, if a radical surgery is performed, in addition to removing the tumor in the primary organ, the adjacent invaded organs must also be removed during the operation.

[0109] The preoperative hospitalization time of the subject of this application refers to: the period from the time the patient is hospitalized for the operation to the time before the operation is performed, specifically, the period from the time the patient is admitted to the hospital to the time before the operation. Generally, if the patient's condition is complicated, the more time is spent on preoperative evaluation and treatment, and the corresponding preoperative hospitalization time is longer.

[0110] The OR odds ratio (or OR value) (Odds ratio), also known as the odds ratio, refers to the ratio of the number of exposed people to the number of non-exposed people in the case group divided by the ratio of the number of exposed people to the number of non-exposed people in the control group. It reflects the strength of the association between the disease and the exposure, and usually appears in case-control studies. To give a specific example, when studying the cause of myocardial infarction, 100 patients with myocardial infarction are selected as cases, and 100 patients who have not had myocardial infarction are used as controls to compare their possible causes of myocardial infarction. Suppose that among the people who have myocardial infarction, 40 people have hypertension, and among the people who have not had myocardial infarction, 20 people have hypertension. Then OR = (40 / 60) / (20 / 80) = 40*80 / 20*60 = 2.67. This 2.67 means that the risk of myocardial infarction in people with hypertension is 2.67 times that of people without hypertension. The OR value is a commonly used indicator in case-control studies (retrospective studies) to measure the strength of the association between exposure factors and disease factors; its practical meaning is: how many times the risk of disease in the exposure group is that in the control group. Risk = number of cases / number of non-cases. When the OR value is >1, it means that the exposure increases the risk of disease and is a risk factor for the disease; OR value = 1 means that the factor has no effect on the occurrence of the disease; OR value <1 means that the factor is a protective factor.

[0111] In the system or method constructed in the present application, the independent influencing factors of postoperative complications of liver surgery are Child-Pugh grade (B, C / A: OR value = 1.984, P = 0.002), medical diseases requiring drug treatment (yes / no: OR value = 1.883, P = 0.003), the number of liver segments to be resected (≥3 / ≤2: OR value = 1.947, P < 0.001), whether there is organ invasion (yes / no: OR value = 3.616, P = 0.023) and the number of days of hospitalization before surgery (>7 / ≤7: OR value = 1.565, P = 0.004).

[0112] In the above-mentioned system or method provided by the present invention, 1,732 patients undergoing liver surgery were retrospectively analyzed, and variables were screened by univariate and multivariate analysis, and the screened variables were graded and scored. The logistic regression equation was used to form a liver operation risk formula (LORF), referred to as the LORF formula, and the receiver operating characteristic curve (ROC curve) was used to verify the LORF formula.

[0113] Multivariate correlation analysis showed that independent influencing factors for postoperative complications of liver surgery were Child-Pugh grade (OR value = 1.984, P = 0.002), medical diseases requiring drug treatment (OR value = 1.883, P = 0.003), number of liver segments to be resected (OR value = 1.947, P < 0.001), organ invasion (OR value = 3.616, P = 0.023), and preoperative hospital stay (OR value = 1.565, P = 0.004). The area under the curve (AUC) of these five combined variables was 0.736, and the corresponding standard error was 0.015. The cut-off value of the total score was calculated by adding the values ​​of all risk factors to obtain a total score of 6.5. According to this threshold, the incidence of postoperative complications between the two groups was significantly different in ≤ 6 points and ≥ 7 points (χ2 = 59.217, P < 0.001). A binomial logistic regression model was established to obtain the formula for calculating the risk of complications (LORF formula). The area under the curve of the LORF formula was 0.782 (95% confidence interval: 0.749-0.815), the corresponding standard error was 0.017, P<0.001. The cutoff value for the estimated complication rate was 0.32 (32%).

[0114] The present invention provides a system for assessing the risk of post-hepatectomy complications in a subject before surgery, comprising:

[0115] A data collection module, which is used to obtain the Child-Pugh grade of the subject, whether there are any medical diseases that require drug treatment, the number of liver segments to be removed, whether there is any organ invasion in the subject, and the preoperative hospitalization time of the subject; and

[0116] The module for calculating the risk of complications after liver resection of the subject is used to calculate the above information obtained in the data acquisition module, so as to calculate the risk probability (P) of complications after liver resection of the subject.

[0117] In some embodiments of the present invention, in the module for calculating the risk of complications after liver resection of the subject, the Child-Pugh level of the subject, the presence or absence of medical diseases requiring drug treatment, the number of liver segments to be resected, the presence or absence of organ invasion in the subject, and the preoperative hospitalization time of the subject obtained by the data acquisition module are converted into their respective corresponding values, and the assigned values ​​are entered into the formula model stored in the module for calculating the risk of complications after liver resection of the subject to calculate the probability of the risk of complications after liver resection of the subject (P).

[0118] In some embodiments of the present invention, the Child-pugh grade of the subject is determined as A, B or C based on the presence or absence of hepatic encephalopathy, ascites, serum bilirubin, serum albumin concentration and prothrombin time at the clinician's discretion.

[0119] In some embodiments of the present invention, the Child-Pugh level of the subject in this application is scored based on the clinician's observation of the subject, the presence or absence of hepatic encephalopathy, ascites, serum bilirubin, serum albumin concentration and prothrombin time, each of which is divided into three levels, with the lowest level being 1 point and the highest level being 3 points. The scores of the five indicators are added together, and a score of 5-6 points is grade A, a score of 7-9 points is grade B, and a score ≥10 points is grade C.

[0120] Hepatic encephalopathy (HE) refers to a syndrome of central nervous system dysfunction caused by severe liver disease and based on metabolic disorders, and its main clinical manifestations are impaired consciousness and behavioral disorders. It varies depending on the type of liver disease, the degree of liver cell damage, the rapidity of onset, and the different causes. Due to the different underlying diseases that lead to hepatic encephalopathy, its clinical manifestations are also relatively complex and changeable. But there are also common manifestations: that is, reflected in neuropsychiatric symptoms and signs. There are both manifestations of primary underlying liver diseases and unique clinical manifestations, which are generally manifested as personality, behavior, intelligence changes and impaired consciousness. In the present invention, according to the West-Haven standard, hepatic encephalopathy is divided into 5 stages:

[0121] Stage 0 (no hepatic encephalopathy).

[0122] In patients with stage 1 (prodromal) hepatic encephalopathy, the clinical manifestations are characterized by mild personality changes and behavioral disorders. The patients' responses are still accurate, but their speech is unclear and slow, and most of the EEGs are normal.

[0123] In patients with stage 2 (pre-coma) hepatic encephalopathy, the clinical manifestations are mainly characterized by mental confusion, sleep disorders, and behavioral disorders, accompanied by tendon hyperreflexia, increased muscle tension, ankle clonus, positive Babinski sign, asterixis, and characteristic abnormalities in the electroencephalogram.

[0124] Patients with stage 3 (comatose stage) hepatic encephalopathy have clinical manifestations characterized by coma and mental confusion. Neurological signs persist or worsen, and they are often in a comatose state, but can be awakened and answer questions. However, they often have confusion and hallucinations, and the EEG has abnormal waveforms.

[0125] Patients with stage 4 (coma) hepatic encephalopathy have complete loss of consciousness, cannot be awakened, and have obvious abnormalities in the EEG.

[0126] In the present invention, three situations are divided based on the degree of hepatic encephalopathy, with the first situation (stage 0) being scored as 1 point, the second situation (stage 1-2) being scored as 2 points, and the third situation (stage 3-4) being scored as 3 points.

[0127] Ascites refers to the situation when the amount of fluid in the abdominal cavity increases by more than 200ml under any pathological state. Under normal conditions, there is a small amount of fluid (generally less than 200ml) in the abdominal cavity of the human body, which lubricates the peristalsis of the intestine. There are many causes of ascites, and more common ones include liver insufficiency, renal insufficiency, nutritional disorders, peritoneal metastasis of malignant tumors, connective tissue diseases, etc. In the present invention, the amount of fluid in the abdominal cavity caused by ascites is divided into three situations, and the first situation (no ascites) is recorded as 1 point, the second situation (mild ascites) is recorded as 2 points, and the third situation (moderate to severe ascites) is recorded as 3 points. The commonly used ascites grading standard in China is: mobile dullness is mild below the mid-axillary line, moderate between the mid-clavicular line and the mid-axillary line, and severe beyond the mid-clavicular line.

[0128] Serum bilirubin is produced by the release of hemoglobin from the lysis of aging red blood cells in the body. It includes indirect bilirubin and direct bilirubin. Indirect bilirubin is transported to the liver through the blood and generates direct bilirubin through the action of liver cells. Serum bilirubin is an indicator in liver function tests. The normal value is 0-21umol / L (Laboratory Department of General Hospital of the People's Liberation Army). The first level is serum bilirubin <34umol / L, with 1 point; the second level is serum bilirubin 34-51umol / L, with 2 points; the third level is serum bilirubin >51umol / L, with 3 points.

[0129] Serum albumin is a major protein in human plasma, accounting for 50% of the total plasma protein. For a normal person, 10-15 grams of serum albumin is synthesized in the liver every day, of which 40% is released into the blood vessels through the exchange between blood and interstitium. Serum albumin contains a polypeptide chain with 585 amino acid residues, a tryptophan residue, and a cysteine ​​aminothiol free radical, and its half-life in plasma is 15-19 days. Its secondary structure consists of three domains, each of which contains two subdomains. Due to its ability to bond lipopolysaccharides, bacterial products (teichoic acid, peptidoglycan), reactive oxygen, nitric oxide, other reactive nitrogen and prostaglandins, the main function of serum albumin in the blood is to regulate blood osmotic pressure, transport endogenous physiological metabolites (such as bilirubin, fatty acids) and exogenous ligands (such as warfarin, ibuprofen) to enhance their solubility in the blood, transport them to specific tissues or organs, and metabolize some toxic ligands. Serum albumin concentration has been used as an indicator to evaluate various diseases. The lower the concentration, the more serious the damage, which can lead to liver ascites in severe cases. The normal value of albumin is 35-50g / L (Laboratory Department of General Hospital of PLA). The present invention is divided into three situations according to serum albumin concentration. The first situation is >35g / L, with 1 point; the second situation is 28-35g / L, with 2 points. The third situation is <28g / L, with 3 points.

[0130] Prothrombin time (PT) refers to the time required for prothrombin to be converted into thrombin after adding excessive tissue thromboplastin and calcium ions to platelet-deficient plasma, resulting in plasma coagulation. Prothrombin time is an indicator reflecting the activity of coagulation factors I, II, V, VII, and X in plasma. Prothrombin time determination is a screening test to check whether there is any obstruction in the function of the body's exogenous coagulation system, and is also an important monitoring indicator for clinical anticoagulant treatment. The present invention is divided into three situations according to the prothrombin time. The first situation is that the prothrombin time is extended by <4 seconds, and 1 point is recorded; the second situation is that the prothrombin time is extended by 4-6 seconds, and 2 points are recorded; the third situation is that the prothrombin time is >6 seconds, and 3 points are recorded.

[0131] The scores of the above five indicators were added together, with scores of 5-6 being grade A, 7-9 being grade B, and scores ≥10 being grade C, thus obtaining the Child-Pugh level of the subject.

[0132] In some embodiments of the present invention, when the Child-pugh level of the subject is A, the Child-pugh level of the subject is assigned a value of 1, and when the Child-pugh level of the subject is B or C, the Child-pugh level of the subject is assigned a value of 2.

[0133] The presence or absence of medical diseases requiring drug treatment refers to the patient's existence of one or more existing medical diseases requiring drug treatment in addition to surgical diseases requiring surgical treatment, the specific description of which has been described above and will not be repeated here.

[0134] In some embodiments of the present invention, when the subject does not have a medical disease requiring drug treatment, the value assigned to whether the subject has a medical disease requiring drug treatment is 1; when the subject has a medical disease requiring drug treatment, the value assigned to whether the subject has a medical disease requiring drug treatment is 2.

[0135] The number of liver segments to be resected refers to the parts that need to be resected among the eight liver segments divided by the Couinaud segmentation method used clinically, the specific description of which has been described above and will not be repeated here.

[0136] In some embodiments of the present invention, when the number of liver segments to be resected of a subject is less than or equal to 2, the value assigned to the number of liver segments to be resected is 1; when the number of liver segments to be resected of a subject is greater than or equal to 3, the value assigned to the number of liver segments to be resected is 2.

[0137] Organ invasion refers to the situation in which a malignant tumor infiltrates and grows into adjacent organs outside the primary organ. The specific description has been described above and will not be repeated here.

[0138] In some embodiments of the present invention, when the subject does not have organ invasion, the value assigned to whether the subject has organ invasion is 1; when the subject has organ invasion, the value assigned to whether the subject has organ invasion is 4.

[0139] The subject's preoperative hospitalization time refers to the period from the time the patient is hospitalized for the surgery to before the surgery is performed, the specific description of which has been described above and will not be repeated here.

[0140] In some embodiments of the present invention, when the subject's preoperative hospitalization time is less than or equal to 7 days, the subject's preoperative hospitalization time is assigned a value of 1; when the subject's preoperative hospitalization time is greater than 7 days, the subject's preoperative hospitalization time is assigned a value of 2.

[0141] In some embodiments of the present invention, the above-mentioned assignment is determined based on the OR values ​​of the Child-Pugh level of the subject, the presence or absence of medical diseases requiring drug treatment, the number of liver segments to be resected, the presence or absence of organ invasion in the subject, and the subject's preoperative hospitalization time parameters obtained in advance and stored in a module for calculating the risk of complications after liver resection of the subject.

[0142] In the system constructed in this application, the independent influencing factors of postoperative complications of liver surgery are Child-Pugh grade (B, C / A: OR value = 1.984, P = 0.002), medical diseases requiring drug treatment (yes / no: OR value = 1.883, P = 0.003), the number of liver segments to be resected (≥3 / ≤2: OR value = 1.947, P < 0.001), whether there is organ invasion (yes / no: OR value = 3.616, P = 0.023) and the number of days of hospitalization before surgery (>7 / ≤7: OR value = 1.565, P = 0.004).

[0143] In the present invention, the above assignment is obtained by:

[0144] When the Child-pugh level of the subject is A, the Child-pugh level of the subject is assigned as 1; when the Child-pugh level of the subject is B or C, the OR value is 1.984, which is rounded to 2, that is, the Child-pugh level of the subject is assigned as 2;

[0145] When the subject has no medical disease requiring drug treatment, the value assigned to whether the subject has a medical disease requiring drug treatment is 1; when the subject has a medical disease requiring drug treatment, the OR value is 1.883, which is rounded to 2, that is, the value assigned to whether the subject has a medical disease requiring drug treatment is 2;

[0146] When the subject has less than or equal to 2 liver segments to be removed, the number of liver segments to be removed is assigned as 1; when the subject has more than or equal to 3 liver segments to be removed, the OR value is 1.947, which is rounded to 2, that is, the number of liver segments to be removed is assigned as 2;

[0147] When the subject does not have organ invasion, the value assigned to whether the subject has organ invasion is 1; when the subject has organ invasion, the OR value is 3.616, which is rounded to 4, that is, the value assigned to whether the subject has organ invasion is 4;

[0148] When the subject's preoperative hospitalization time is less than or equal to 7 days, the value assigned to the subject's preoperative hospitalization time is 1; when the subject's preoperative hospitalization time is more than 7 days, the OR value is 1.565, which is rounded to 2, that is, the value assigned to the subject's preoperative hospitalization time is 2.

[0149] In some embodiments of the present invention, the stored formula model is a formula obtained by regression fitting based on the values ​​confirmed by the Child-Pugh grade of the subject, the presence or absence of medical diseases requiring drug treatment, the number of liver segments to be resected, the presence or absence of organ invasion in the subject, and the subject's preoperative hospitalization time.

[0150] In some embodiments of the present invention, the formula model is the following formula 1:

[0151] P=1 / {1+exp[-(α+β1χ1+β2χ2+β3χ3+β4χ4+β5χ5)]} (Formula 1),

[0152] Among them, χ1 is the value assigned to the Child-Pugh level of the subject;

[0153] χ2 is the value assigned to whether the subject has a medical condition that requires medication;

[0154] χ3 is the value assigned to the number of liver segments to be resected;

[0155] χ4 is the value assigned to whether the subject has organ invasion;

[0156] χ5 is the value assigned to the subject’s preoperative hospital stay;

[0157] P is the risk probability of complications after liver resection in the subjects;

[0158] Among them, the value of α is -4.844;

[0159] The value of β1 is 0.737;

[0160] The value of β2 is 0.530;

[0161] The value of β3 is 0.673;

[0162] The value of β4 is 0.412;

[0163] The value of β5 is 0.464.

[0164] In some embodiments of the present invention, after obtaining the subject's χ1, χ2, χ3, χ4, and χ5 and substituting them into Formula 1, the subject's post-hepatectomy complication risk probability P can be calculated to assess the risk for the subject.

[0165] In another specific embodiment of the present invention, a method for evaluating the risk of post-hepatectomy complications of a subject before surgery is provided, which comprises: a data collection step for obtaining the Child-Pugh grade of the subject, the presence or absence of medical diseases requiring drug treatment, the number of liver segments to be resected, the presence or absence of organ invasion in the subject, and the pre-operative hospitalization time of the subject; and a step for calculating the risk of post-hepatectomy complications of the subject, which is for calculating the above information obtained in the data collection module, thereby calculating the probability (P) of the risk of post-hepatectomy complications of the subject.

[0166] In the step of calculating the risk of complications after liver resection of the subject, the Child-Pugh level of the subject, the presence or absence of medical diseases requiring drug treatment, the number of liver segments to be resected, the presence or absence of organ invasion in the subject, and the preoperative hospitalization time of the subject obtained in the data collection step are converted into their respective corresponding values, and the assigned values ​​are entered into the formula model stored in the module for calculating the risk of complications after liver resection of the subject to calculate the probability of the risk of complications after liver resection of the subject (P).

[0167] In addition, the contents described for the above-mentioned system of the present invention are all applicable to the method of the present invention.

[0168] Example

[0169] Example 1 Materials and Methods

[0170] 1.1 Case selection

[0171] A personal medical information file was established for patients undergoing perioperative liver surgery. The inclusion criteria for the cases were: (1) perioperative patients; (2) complete medical records; (3) patients who had not undergone a recent secondary surgery. A total of 1,732 cases were collected from January 1986 to December 2020.

[0172] Among them, the medical records include preoperative clinical medical records, pathological histological examination data and postoperative data; after admission, all patients were asked about their medical history in detail and underwent physical examination; routine preoperative clinical examinations included electrocardiogram, chest X-ray and laboratory tests such as blood routine, blood biochemistry, and coagulation function; imaging examinations included ultrasound, CT and / or magnetic resonance imaging, which were used as the basis for diagnosis; liver function assessment (Child-pugh) was performed on all patients; the preoperative factors analyzed included the patient's basic information (including gender, age, etc.), diagnosis, laboratory tests (bilirubin, albumin, HBsAg, AFP, etc.), Child grade, tumor size, tumor number, cirrhosis, etc.; intraoperative data came from surgical records and anesthesia records, including operation time, estimated blood loss, resection range, etc.; the postoperative data included the incidence of postoperative complications, mortality and follow-up data (including the patient's recurrence-free survival time, recurrence status and residual liver imaging data).

[0173] Non-recent second surgery refers to an unplanned second surgery due to the progression of the disease after surgery (such as recurrence and metastasis of the tumor after surgery), rather than a recent (mostly during the same hospitalization) unsuccessful first surgery or serious complications caused by special diagnostic and treatment operations.

[0174] 1.2 Selection of indicators to be screened

[0175] According to the commonly used surgical risk scoring systems at home and abroad and the previous clinical research experience of the inventors of this application, the perioperative factors analyzed include the patient's basic information, diagnostic information, laboratory test information, medical images and imaging examination information, operation name, accompanying medical diseases and medication history, resection range, etc.; postoperative conditions include complications / deaths, etc.

[0176] Specifically, the patient's basic information includes age, gender, height, weight, BMI, heart rate, respiratory rate, body temperature, blood pressure, etc.

[0177] The patient's diagnostic information includes imaging data and pathological data.

[0178] The patient's laboratory test information includes routine blood tests (white blood cell, neutrophil ratio, platelets, hemoglobin), coagulation function (APTT, PT, INR, D-dimer), blood biochemistry (alanine aminotransferase, aspartate aminotransferase, bilirubin, albumin, fasting blood glucose, urea, creatinine, blood lipids), arterial blood gas analysis (PH, PaO2, PaCO2, SaO2), cardiac function (myocardial enzyme spectrum, brain natriuretic peptide), infection indicators (CRP, PCT), blood type, eight blood transfusion items (five items of hepatitis B, hepatitis C, syphilis, AIDS), tumor markers (alpha-fetoprotein, etc.), etc.

[0179] The patient's medical images and imaging examination information include abdominal ultrasound, liver CT and / or MRI, chest X-ray / or chest CT, cardiac ultrasound, and, if necessary, PET-CT, lower limb venous ultrasound, etc.

[0180] The name of the patient's surgery is divided into anatomical and non-anatomical according to the resection method. If multiple resection methods are implemented at the same time, the number of resected liver segments is calculated as the sum. Re-resection refers to those who have undergone liver resection before. Liver resection with other major treatments is called "compound liver resection". Additional extrahepatic treatments for patients in this group include resection of other organs, bile duct resection / reconstruction or bile duct exploration, portal vein and / or vena cava resection / reconstruction, hilar lymph node dissection, etc. Additional intrahepatic treatments include radiofrequency, etc. Patients who only undergo simple liver resection without additional operations are called "simple liver resection."

[0181] The patient's concomitant medical diseases and medication history refers to the patient's need for long-term medication treatment due to coexisting medical diseases, including hypertension, coronary heart disease, arrhythmia, hyperlipidemia, diabetes, old cerebral infarction, chronic obstructive pulmonary disease, chronic renal insufficiency, etc.

[0182] The patient's resection range included extended liver resection (5 segments), right liver resection (4 segments), left liver resection (3 segments), middle liver resection (3 segments), left lateral lobectomy, right anterior lobectomy and right posterior lobectomy (2 segments), etc.

[0183] Common complications after liver resection include: bleeding, infection, liver dysfunction, bile leakage, etc. The most common complications after upper abdominal surgery related to liver cirrhosis, such as pleural effusion, ascites and perihepatic effusion, can be resolved after general treatment (such as transfusion of concentrated human albumin, adjustment of water and electrolyte balance, use of diuretics, etc.). The first important complications related to surgery are incision infection and intra-abdominal infection. Bile leakage is a serious complication after liver resection, which may affect the recovery of the disease. In this group of cases, 419 cases developed complications, with a total incidence of 24.19%. Among them, 164 cases had more than two complications (accounting for 39.14% of the total complications). There were 14 cases of fatal complications, accounting for 3.34% of the total complications, and the mortality rate was 0.81%.

[0184] 1.3 Research Methods

[0185] 1.3.1 Screen clinical risk factors based on whether postoperative complications occur in liver surgery. The dependent variable is postoperative complications, and the independent variable is all preoperative variables collected in the above 1.2; set variables for ordered categorical variables according to levels. For example: graded treatment of age, bilirubin, etc. All single factors that are significantly correlated with adverse postoperative outcomes are put into multivariate logistic regression analysis. The stepwise regression analysis method is used to obtain the main risk factors and their relative risk values. Set the risk score with reference to the risk parameter span in the multivariate analysis results of risk factors. Assign risk indicators to the nearest integer to facilitate clinical application. The sum of the risk scores of all risk factors of a single patient is the total risk score of the complication of the patient, and the risk index of all patients with complications is calculated, so as to establish an assessment system for the risk of complications.

[0186] The ordered categorical variables mentioned above specifically refer to the numerical variables collected in the above 1.2, and these numerical variables can be divided into different levels according to the corresponding thresholds. For example, the bilirubin value can be 21 μmol / L as the threshold, and values ​​below this threshold are normal values, and values ​​above this threshold are abnormal values.

[0187] The variable setting by level mentioned above specifically refers to setting different indicators according to their thresholds that have practical clinical value. For example, in addition to being divided into normal and abnormal values ​​based on 21 μmol / L as the threshold, the severity of jaundice can also be distinguished based on the value of this indicator, that is, a value within one times the upper limit of normal is called latent jaundice, and a value more than one times the upper limit of normal is called jaundice.

[0188] The univariate screening method for factors significantly correlated with adverse postoperative outcomes was as follows: Pearson correlation analysis was used to perform univariate analysis of perioperative factors, and multivariate logistic regression was used to screen the independent risk factors significantly correlated with adverse postoperative outcomes.

[0189] SPSS statistical software was used to obtain the main risk factors and their relative risk values. The independent risk factors were screened out through the Logistic regression method and the relative risk values ​​(OR values) were calculated.

[0190] The risk score is set according to the relative risk value parameter span of the independent risk factors calculated by the Logistic regression method, and the risk index is assigned to the nearest integer to facilitate clinical application. The sum of the risk scores of all risk factors of a single patient is the total risk score of the complication of the patient, and the risk index of all patients with complications is calculated, so as to establish an assessment system for the risk of complications.

[0191] 1.3.2 Establishment of the liver operation risk formula (LORF) for calculating the risk of complications after liver resection

[0192] According to the Logistic regression analysis, postoperative complications were defined as positive results, and no complications were defined as negative results. A Logistic regression model for complications was established, and the risk calculation formula was obtained:

[0193] P=1 / {1+exp[-(α+β1χ1+β2χ2+......β n χ n )]}

[0194] P represents the probability of complications. When P = 1, the probability of complications is 100%. α is a constant term, β1~β n are the regression coefficient values ​​corresponding to the risk indicators of complications risk factors, χ1~χ n They are the risk index level values ​​of complication risk factors, and corresponding values ​​are assigned according to the different standards of each indicator from normal to abnormal.

[0195] 1.3.3 Methods for verifying the LORF formula

[0196] The LORF formula was used to score and calculate the probability of complications. The receiver operating characteristic (ROC) curve was used to evaluate the resolution of the LORF formula. The larger the area under the curve, the higher the resolution. The cutoff value of the risk index was calculated at the same time.

[0197] 1.4 Statistical analysis

[0198] SPSS 25.0 statistical software was used for data analysis. The measurement data were expressed as Mean±SD. Pearson correlation analysis was used to analyze the relationship between complications and preoperative factors in patients undergoing elective surgery. Regression analysis was used to perform multivariate analysis of the factors affecting surgical complications. P < 0.05 was considered statistically significant.

[0199] Example 2 Preliminary Model Results Evaluation

[0200] 2.1 Incidence of complications after liver surgery

[0201] A total of 419 complications occurred, with a total complication rate of 24.19%, including 14 fatal complications, accounting for 3.34% of the total number of complications, and a mortality rate of 0.81%.

[0202] 2.2 Screening of preoperative clinical risk factors for postoperative complications

[0203] Univariate correlation analysis showed that the preoperative clinical risk factors for complications after liver surgery were previous surgery history (P = 0.006), non-liver surgery abdominal surgery history (P = 0.021), total bilirubin (P < 0.001), medical diseases requiring drug treatment (P < 0.001), Child-Pugh grade (P < 0.001), total number of liver segments to be resected (P = 0.001), nature of lesions (P = 0.001), resection method (P < 0.001), whether the resection margin is positive (P = 0.022), whether there is organ invasion (P < 0.001), and preoperative hospital stay (P = 0.040). These clinical factors were divided into grades. Since the factors of Child-Pugh grading include bilirubin, in order to make the evaluation system simple and easy to operate, bilirubin was merged into the Child-Pugh grading, as shown in Table 1.

[0204] Table 1 Univariate analysis of preoperative clinical risk factors associated with complications of hepatectomy

[0205]

[0206] *Pearson correlation analysis

[0207] In Table 1 , previous surgical history refers to the patient's previous surgery (including any type of surgery done previously), such as liver surgery, non-liver surgery (lung surgery, hernia surgery, gastrointestinal surgery, etc.).

[0208] Abdominal surgery history (non-liver surgery) refers to any abdominal surgery (including hernia surgery, gastrointestinal surgery, pancreatic surgery, kidney surgery, etc.) performed by the patient except liver surgery.

[0209] Total bilirubin concentration is the sum of direct bilirubin and indirect bilirubin in serum, and its unit of measurement is μmol / L. The determination of serum total bilirubin is an important test item in liver and gallbladder function examination. It can accurately reflect the degree of jaundice. The normal reference value of serum total bilirubin in our hospital's laboratory is: 0-21μmol / L;

[0210] The nature of the lesion refers to whether the lesion is benign or malignant, that is, whether the lesion is a benign lesion or a malignant tumor.

[0211] The liver resection methods here are divided into anatomical liver resection and non-anatomical liver resection. Anatomical liver resection refers to: liver resection according to the Couinaud segmentation of the liver, including single liver segment resection and multi-segment resection; anatomical liver resection generally does not require the Pringle method to block the first liver portal. The key is to dissect the hepatic pedicle and the hepatic vein entering the liver segment, ligate them respectively, and then resect the liver segment; non-anatomical liver resection refers to the complete resection of the tumor without considering the intrahepatic anatomy, generally requiring a resection margin of at least 1.0 cm. Non-anatomical liver resection generally requires the Pringle method to block the first liver portal or half the liver block.

[0212] A positive margin means that after tumor resection, pathology shows that the lesion has involved the margin (the edge of the incision where the tissue is cut), and the lesion is still visible at the margin. A positive margin means that there are still tumor cells at the edge of the incision, which means that the tumor tissue may not have been completely removed.

[0213] After the present invention uses Pearson correlation analysis to perform univariate analysis to preliminarily obtain potentially significant variables (as shown in Table 1), multivariate Logistic regression is then performed to eliminate the interference of other factors and screen out independent risk factors (as shown in Table 2).

[0214] After multivariate correlation analysis, the independent influencing factors for postoperative complications of liver surgery were Child-Pugh grade (OR value = 1.984, P = 0.002), medical diseases requiring drug treatment (OR value = 1.883, P = 0.003), the number of liver segments to be resected (OR value = 1.947, P < 0.001), whether there was organ invasion (OR value = 3.616, P = 0.023) and preoperative hospital stay (OR value = 1.565, P = 0.004). See Table 2 for details.

[0215] Table 2 Screening and assignment of independent influencing factors for complications after liver surgery by multivariate analysis

[0216]

[0217] *Logistic regression

[0218] Table 3 Multivariate analysis of screening independent influencing factors and assignment relationships for complications after liver surgery

[0219]

[0220]

[0221] 2.3 Establishment of a formula for calculating the risk of complications after hepatectomy

[0222] The risk score of each preoperative risk factor for liver surgery complications was used as the independent variable, whether the patient had complications was the dependent variable, and the occurrence of complications after surgery was defined as a positive result, while the absence of complications was defined as a negative result. A binomial classification logistic regression model was established. The specific intercept (regression coefficient value) is shown in Table 4, and the formula for calculating the risk of complications was obtained:

[0223] P=1 / {1+exp[-(-4.844+0.737χ1+0.530χ2+0.673χ3+0.412χ4+0.464χ5)]} (Formula 2)

[0224] Table 4 Calculation of regression coefficients of independent influencing factors of liver surgery complications

[0225]

[0226] *Logistic regression

[0227] The Child-Pugh score is used to determine the A, B, and C levels. A score of 5-6 is A, a score of 7-9 is B, and a score of ≥10 is C. The values ​​are assigned according to the A, B, and C levels in Table 3. n The regression coefficient value of is the intercept in Table 4.

[0228] 2.4 Verification of LORF formula

[0229] Depend on Figure 1 It can be seen that the area under the curve (AUC) of the above five combined variables is 0.736, and the corresponding standard error is 0.015. The cut-off value of the total score is 6.5 calculated by adding the values ​​of all risk factors. According to this threshold, the incidence of complications in the group with a score of ≤6 was significantly lower than that in the group with a score of ≥7 (χ2=59.217, P<0.001). A binomial classification logistic regression model was established to obtain the formula for calculating the risk of complications (LORF formula). By Figure 2It can be seen that the area under the curve of the LORF formula was 0.782 (95% confidence interval 0.749-0.815), the corresponding standard error was 0.017, P < 0.001. The cutoff value of the estimated complication rate was 0.32 (32%).

[0230] In addition, 100 consecutive new patients were included in the validation group to verify the LORF formula. The ROC curve was used to analyze its recognition ability. The area under the LORF formula curve was 0.727. Figure 3 shown.

[0231] The cut-off value provides a critical value for determining whether complications occur, and the LORF formula is validated by the ROC (area under the curve).

[0232] Liver failure after liver resection is an important cause of postoperative death. Accurate preoperative assessment of the patient's liver function is very important to reduce the incidence and mortality of postoperative liver failure. The Child-pugh score is currently the most widely used liver function assessment method. The system model constructed in this application shows that the Child-pugh score is an independent risk factor for complications after liver surgery (OR value = 1.984, P = 0.002). However, due to the shortcomings of some indicators being highly subjective, its single prediction of liver postoperative complications is still inaccurate and needs to be predicted in conjunction with other indicators.

[0233] Many patients who need surgery usually have one or more other pre-existing diseases in addition to the diseases that require surgical treatment, which are called comorbidities. This is more common in the elderly. The physiological functions of the elderly decline with age, and their height and body surface area decrease, muscles atrophy, metabolic activity and total cell count decrease. The functions of organs such as the heart, lungs, and kidneys decrease, which reduces the reserve capacity to maintain a stable internal environment under stress. Surgical stress adds a burden to the body's organs, increases the body's oxygen consumption by 30% to 70%, and myocardial oxygen consumption also increases accordingly. With the continuous breakthrough of traditional surgical taboos, a large number of high-risk surgical patients with liver, kidney, and lung dysfunction have been brought in, and the number of surgical patients with diseases such as diabetes, hypertension, and heart disease has also increased rapidly. These high-risk patients have perioperative comorbidities that exist alone or occur simultaneously, which are closely related to postoperative complications and mortality. This study shows that the medical diseases that patients have that require drug treatment are independent risk factors for postoperative complications of liver surgery (OR value = 1.883, P = 0.003).

[0234] In recent years, as liver surgery techniques have become increasingly mature, the success rate of giant liver tumor resection has increased, while postoperative complications and mortality have greatly decreased, making it possible to safely resect more giant liver tumors that were previously considered inoperable. The main reasons are: (1) improved understanding of the stereotactic positioning of liver tumors; (2) development of liver bleeding, hemostasis, and blood transfusion techniques; (3) more detailed liver surgery and vascular surgery techniques; (4) excellent anesthesia management; and (5) progress in perioperative management. However, the amount of liver resection (remaining functional liver volume) is still the main factor affecting the efficacy of liver resection. This study showed that the number of liver segments to be resected is an independent risk factor for postoperative complications of liver surgery (OR value = 1.947, P < 0.001). At the same time, many studies have shown that the larger the scope of surgery, the more surgical complications there are. This study also showed that if combined organ resection is performed simultaneously with extrahepatic organ invasion, there will be a greater risk of complications (OR value = 3.616, P = 0.023).

[0235] Preoperative hospitalization time is also related to the severity of the disease. Generally, the more serious the disease, the more complicated the preoperative preparation, and the longer the hospitalization time. On the contrary, if the disease is simple and there are few comorbidities, the preoperative preparation is also simple, and the preoperative preparation time is shorter. This study showed through multivariate analysis that preoperative hospitalization time is an independent influencing factor for postoperative complications of liver surgery (OR value = 1.565, P = 0.004).

[0236] Several preoperative scoring systems have been developed to assess the risk of death or complications after surgery. The most commonly used index is the American Society of Anesthesiologists Physical Status (ASA-PS) classification criteria, which is divided into I to V scores based on the patient's overall health status. The Revised Cardiac Risk Index (RCRI) is a simple and widely used index for predicting major cardiac complications. It contains six equally weighted indicators: coronary heart disease, heart failure, cerebrovascular disease, renal insufficiency, diabetes, and high-risk surgical procedures. However, the conclusions drawn by these assessment methods are vague and lack intuitiveness and precision. Recently, online web-based risk calculators have made it possible to implement more complex risk prediction tools in clinical practice, making the assessment results intuitive. An important example is the American College of Surgeons Risk Calculator (see http: / / riskcalculator.facs.prg). This risk calculator implements a series of clinical prediction models developed by applying the National Surgical Quality Improvement Program Registry (NSQIP) in the United States. The NSQIP risk calculator also has its limitations. Although this prediction model is derived from a large multicenter observational study, it has not been fully confirmed in countries outside the U.S. Moreover, surgical risks are different in China and the U.S., and risk adjustment should be made based on the actual situation in China.

[0237] In existing studies, prior art document 1 (Donadon M, et al. Individualized risk estimation for postoperative morbidity after hepatectomy: the Humanitas score. HPB (Oxford). 2017 Oct; 19 (10): 910-918.) disclosed that all patients who were scheduled to undergo hepatectomy from February 2012 to September 2015 were randomly assigned to a derivation or validation cohort. In this method, a scoring system was developed based on preoperative variables, and multivariate analysis was used to test it, and the OR value was used to construct the score. Results: Of the 340 patients, 240 were used for the derivation study and 100 for the validation study. Multivariate analysis showed that major hepatectomy (OR = 1.62; 95% CL 1.39-3.51), liver stiffness ≥ 9.7 kPa (OR = 2.46; 95% CL 1.16-5.28), BILCHE score (serum bilirubin and cholinesterase combined score) ≥ 2 (OR = 2.76; 95% CL 0.82-4.28) and esophageal varices (OR = 1.59; 95% CL 1.51-3.61) were independent predictors of complications. A 10-point scoring system was introduced. No complications occurred in patients with a score of ≤ 4, while the complication rate in patients with a score of ≥ 7 was as high as 54% (P < 0.001).

[0238] The application of prior art 1 has limitations, as shown in the following aspects: (1) liver stiffness in the independent predictor is not a commonly used examination item in clinical work, and some hospitals do not carry out this examination item. Therefore, this indicator makes the scoring system of document 1 unable to be widely promoted and applied; (2) BILCHE score in the independent predictor is not commonly used in clinical work, and the scope of cholinesterase detection in it is relatively limited, and its value is lower than Child-Pugh score; (3) the judgment of esophageal varices in the independent predictor requires upper gastrointestinal endoscopy to be clear, and upper gastrointestinal endoscopy is not only complicated but also causes great discomfort to patients during the examination process. Based on the above analysis, it can be seen that the application of document 1 is limited in application due to the indicators adopted by its technical solution itself.

[0239] Prior art 2 (Chen L, et al. Effective prediction of postoperative complications for patients after open hepatectomy: a simplified scoring system based on perioperative parameters. BMC Surg. 2019 Sep 5; 19 (1): 128.) discloses a study of patients who underwent open hepatectomy from 2015 to 2017, using univariate and multivariate analysis to determine the risk factors for postoperative complications. Specifically, a total of 207 patients were included in the study. For the experimental data set, multivariate analysis showed that diabetes, surgical scale, blood potassium, blood loss and weight were independent risk factors for postoperative complications. The area under the curve (AUC) of the scoring system for predicting postoperative complications of hepatectomy was 0.803, and in the validation data set, the corresponding AUC of the scoring system was 0.717.

[0240] The inventive concept of prior art 2 is very different from that of the present invention, which is reflected in the following aspects: the amount of blood loss among the independent risk factors is an intraoperative indicator, which can only be obtained at the end of the operation and cannot be accurately predicted before the operation, resulting in the inability of the scoring system to evaluate the occurrence of postoperative complications before the operation. The system of the present invention can predict the occurrence of postoperative complications through the indicators obtained before the operation, thereby providing a basis for preoperative intervention.

[0241] The scoring systems of prior art 1 and prior art 2 both rely only on the cutoff value to determine the risk of complications, and the conclusion is that the risk of complications is high when the total score is higher than the cutoff value, but there is no specific value for the probability of risk occurrence.

[0242] In summary, the various indicators used in the present invention are all commonly used inspection items in clinical work, which are not only easy to obtain, but also can be obtained before surgery. They can predict the occurrence of postoperative complications before surgery, so they have greater practical value. In addition, the present invention not only has a cutoff value, but also can calculate the probability of occurrence of postoperative complications, making the evaluation results more intuitive and quantitative.

[0243] In this study, a binomial classification logistic regression model was established to obtain a formula for calculating the risk of complications in liver surgery (LORF formula). The area under the curve of the LORF formula was 0.782 (95% confidence interval was 0.749-0.815), the corresponding standard error was 0.017, P < 0.001. The cutoff value of the estimated complication rate was 0.32 (32%). Another 100 consecutive patients were included in the validation group to verify the LORF formula, and the area under the curve of the LORF formula was 0.727. This shows that the LORF formula has good reliability, and the preoperative prediction of the incidence of liver surgery complications is consistent with the actual situation, which can be used to assess the risk of complications in liver surgery before surgery.

[0244] Although the embodiments of the present invention are described above, the present invention is not limited to the above specific embodiments and application fields, and the above specific embodiments are only illustrative and instructive, but not restrictive. A person skilled in the art can make many forms under the guidance of this specification and without departing from the scope of protection of the claims of the present invention, all of which belong to the protection of the present invention.

Claims

1. A system for assessing the risk of complications after liver resection in a subject before surgery, comprising: A data collection module is used to obtain the Child-Pugh grade of the subject, whether there are any medical diseases that require drug treatment, the number of liver segments to be removed, whether the subject has organ invasion, and the subject's preoperative hospitalization time; as well as A module for calculating the risk of complications after liver resection of a subject, which is used to calculate the above information obtained in the data acquisition module, so as to calculate the risk probability (P) of complications after liver resection of the subject; In the module for calculating the risk of complications after liver resection of the subject, the Child-Pugh grade of the subject, the presence or absence of medical diseases requiring drug treatment, the number of liver segments to be resected, the presence or absence of organ invasion of the subject, and the preoperative hospitalization time of the subject obtained by the data collection module are converted into their respective corresponding values, and the values ​​are brought into the formula model stored in the module for calculating the risk of complications after liver resection of the subject to calculate the risk probability (P) of complications after liver resection of the subject; The assignment is determined based on the OR values ​​of the Child-Pugh grade of the subject, the presence or absence of medical diseases requiring drug treatment, the number of liver segments to be resected, the presence or absence of organ invasion in the subject, and the subject's preoperative hospital stay parameters, which are pre-stored in the module for calculating the risk of complications after liver resection of the subject; The number of liver segments to be resected refers to the parts that need to be resected among the 8 liver segments divided by the Couinaud segmentation method used clinically; Wherein, the formula model is formula 1: P=1 / {1+exp[-(α+β1χ1+β2χ2+β3χ3+β4χ4+β5χ5)]} (Formula 1), Among them, χ1 is the value assigned to the Child-Pugh level of the subject; χ2 is the value assigned to whether the subject has a medical condition that requires medication; χ3 is the value assigned to the number of liver segments to be resected; χ4 is the value assigned to whether the subject has organ invasion; χ5 is the value assigned to the subject’s preoperative hospital stay; P is the risk probability of complications after liver resection in the subjects; Among them, when the subject's Child-pugh level is A, the subject's Child-pugh level is assigned a value of 1. When the Child-pugh level of the subject is B or C, the Child-pugh level of the subject is assigned a value of 2; Among them, when the subject has no medical disease that requires drug treatment, the value of whether the subject has a medical disease that requires drug treatment is 1. When the subject has a medical disease that requires drug treatment, the value of whether the subject has a medical disease that requires drug treatment is 2; Among them, when the subject has less than or equal to 2 liver segments to be resected, the value assigned to the number of liver segments to be resected is 1; When the subject has 3 or more liver segments to be removed, the value of the number of liver segments to be removed is 2; Among them, when the subject does not have organ invasion, the value assigned to whether the subject has organ invasion is 1; When the subject has organ invasion, the value assigned to whether the subject has organ invasion is 4; Among them, when the subject's preoperative hospitalization time is less than or equal to 7 days, the subject's preoperative hospitalization time is assigned a value of 1; When the subject's preoperative hospitalization time was greater than 7 days, the subject's preoperative hospitalization time was assigned a value of 2; Among them, the value of α is -4.844; the value of β1 is 0.737; the value of β2 is 0.530; the value of β3 is 0.673; the value of β4 is 0.412; and the value of β5 is 0.

464.

2. The system according to claim 1, wherein: The Child-Pugh grade of the subject is determined as A, B or C based on the presence or absence of hepatic encephalopathy, ascites, serum bilirubin, serum albumin concentration and prothrombin time at the clinician's discretion.

3. The system according to claim 1, wherein: The medical condition requiring drug treatment refers to one or more existing medical diseases requiring drug treatment other than surgical diseases requiring surgical treatment; The organ invasion refers to the situation where the malignant tumor infiltrates and grows into adjacent organs other than the primary organ; The subject's preoperative hospitalization time refers to the period from the time the patient is hospitalized for the surgery to before the surgery is performed.

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