1. Introduction

The problem of perioperative immunosuppression in cancer patients has been actively discussed in the scientific literature since the end of the 20th century, when it became obvious that surgical intervention, despite the radicality of tumor removal, is often accompanied by an increased risk of metastasis. Works of this period established that the tissue trauma itself, accompanying the operation, causes activation of the neuroendocrine stress axis and subsequent systemic immunosuppression [1,3,5].

The first observations of the relationship between anesthesia methods and changes in immune status date back to the 1990-2000s. It was shown that the use of inhalation anesthetics is associated with a more pronounced decrease in the activity of natural killers and an increase in the level of proinflammatory cytokines than total intravenous anesthesia. This marked the beginning of the search for optimal anesthetic approaches for cancer patients [2,4,6,12]. Subsequent studies in the early 2010s confirmed that the choice of anesthetic agent can have a significant impact on the level of perioperative immunosuppression. Work by J.P. Cata et al. and G.L. Snyder et al. showed that intravenous anesthetics, especially propofol, can have a protective effect on immune cells, reducing the severity of suppression of natural killer and cytotoxic T lymphocytes.

In parallel, the effect of perioperative analgesia, in particular the use of opioid analgesics, was studied. Studies by P. Sacerdote et al., M.P. Yeager et al. demonstrated that morphine and its derivatives can induce immunosuppression, contributing to a decrease in the activity of natural killers and an increase in the expression of PD-1/PD-L1 immune checkpoints on lymphocytes, which theoretically increases the risk of tumor recurrence. Along with this, special attention has been paid in recent years to the role of regional anesthesia in the prevention of perioperative immunosuppression. A number of studies have shown that the use of epidural or spinal anesthesia can reduce the level of systemic inflammation, reducing the release of catecholamines and cortisol, thereby maintaining the antitumor activity of the immune system [7,9]. Meanwhile, despite the results obtained, the question of the effect of different anesthetic methods on long-term survival of patients remains open. Systematic review by P. Forget et al. [1,10,11] showed that the evidence for the superiority of one type of anesthesia over another remains conflicting because studies vary significantly in design, tumor type, and patient characteristics.

The data accumulated to date have allowed us to put forward a hypothesis about the need for a comprehensive assessment of the immune status of patients in the perioperative period. In the studies of R. Kim et al. and S. Inoue et al., attempts were made to stratify patients by immune profile and select individualized anesthetic tactics to minimize immunosuppression. In recent years, special attention has been paid to the study of the molecular mechanisms of perioperative immunosuppression. It has been shown that stress-induced changes include activation of STAT3 signaling pathways and increased production of immune control molecules, such as PD-L1, on tumor and immune cells [6,8]. Such data open up new prospects for pharmacological correction of disorders.

Another relevant area is the study of the possibility of using stress protectors and immunomodulators in the perioperative period. Pilot clinical studies have shown that the use of β-blockers and cyclooxygenase-2 inhibitors (e.g., celecoxib) can help reduce the level of perioperative immunosuppression and improve long-term oncological outcomes.

Thus, the degree of study of the problem indicates recognition of the high significance of perioperative immunosuppression as one of the key factors of an unfavorable prognosis in cancer patients. However, the issues of individualization of anesthetic tactics, development of standards of immune correction and determination of reliable biomarkers of the risk of relapse remain unresolved, which determines the need for further targeted studies.

All of the above determined the main direction of this work.

The aim of the study is to develop a treatment and diagnostic algorithm for the correction of perioperative immunosuppression in cancer patients depending on anesthetic care.

2. Materials and Methods

The study included 120 oncological patients subject to planned surgical treatment for malignant neoplasms of various anatomical locations for the period from 2021 to 2025 in the Bukhara regional branch of the Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology.

All patients were divided into two equal groups-cohorts of 60 people each. This division of patients was planned in order to exclude differences in the statistical analysis. Group I (control) received standard anesthesia without immunocorrection, and Group II (main) was formed from patients for whom the choice of anesthesia tactics was carried out individually, based on the preoperative immunological assessment and the SIDAP acceptability scale developed by us, with subsequent implementation of a set of immunocorrective measures. Within the framework of the study, all patients included in the control and main groups were evenly distributed by the type of anesthesia used. In the control group, 33.3% of patients received general anesthesia (GA), regional methods (RM) and combined approaches (RM + RM), including a combination of general anesthesia with epidural, spinal or paravertebral block, were used equally. The structure of the main group is identical: 20 patients in each subgroup. Thus, the distribution by type of anesthetic intervention was completely balanced and ensured methodological purity of comparison of immunological parameters both between and within groups.

For an objective quantitative assessment of the results of immunosuppression correction in cancer patients undergoing surgery, the original unified scale of clinical assessment of the effectiveness of anesthesia care, developed within the framework of this methodological recommendation, was used in this study.

The scale is a structured tool consisting of six independent clinical and functional criteria reflecting the key aspects of the early postoperative period. A three-level assessment system is applied to each criterion: “good” (4 points), “satisfactory” (2 points) and “unsatisfactory” (0 points).

The following parameters were selected as the assessed: 1) hemodynamic stability, 2) need for analgesia, 3) awakening characteristics, 4) the presence and severity of side effects, 5) the need for postoperative observation in the intensive care unit, 6) the rate of early recovery of functional activity.

Each criterion was recorded during the first 72 hours after surgery and assessed by a committee of the attending physician, anesthesiologist, and applicant. The total score on the scale could range from 0 to 24. According to the established thresholds, the results were interpreted as follows: ≥20 points - clinically highly effective (excellent) anesthetic care; 12-18 points - satisfactory (acceptable); <12 points - unsatisfactory (questionable in terms of clinical viability). The scale was used in both the control and main groups. However, it was of particular importance in assessing the effectiveness of immunocorrection: it allowed us to record a decrease in the frequency of unfavorable functional outcomes, the transition of patients from the "unsatisfactory" category to "satisfactory" or "good", and to quantitatively prove the clinical effect of the proposed treatment and diagnostic tactics. In addition, the scale was used as the main tool for intergroup comparative analysis in the fourth stage of the study, where it demonstrated high sensitivity to changes in the patient's functional status when using various anesthetic approaches. It should be emphasized that the unified scale for assessing anesthetic care is an original development created in the course of this scientific work and registered in digital format.

3. Results and Discussion

The first stage of developing the diagnostic scale of immunological admissibility was the correlation analysis between the key parameters of the cellular component of the immune system in cancer patients. The overall profile of the obtained matrix demonstrates moderate mutual independence of most parameters. In particular, the CD3+ level did not demonstrate significant correlations with other indicators (maximum value ρ=0.093 with CD8+), which reflects its limited discriminatory value as a marker of functional differentiation. Moreover, the moderate negative relationship between CD3+ and Treg (ρ=-0.244) can be interpreted as a manifestation of cellular compensation in the form of an increase in the suppressor component against the background of a decrease in the total lymphocyte pool. CD4+ T-helpers showed a weak positive correlation with CD8+ (ρ=0.203) and with the CD4+/CD8+ ratio (ρ=0.126), which is physiologically explainable by the fact that both populations differentiate in parallel under normal T-cell regulation. However, the strength of the connection is insufficient to consider them statistically interdependent. There is virtually no correlation between CD4+ and Treg (ρ=-0.028), which emphasizes the difference in functional orientation: CD4+ act as a coordination center of adaptive immunity, while Treg implement a suppressive role.

CD8+ T-cytotoxic cells showed a moderate negative correlation with Treg (ρ=-0.285), which was one of the most pronounced values in the matrix. Such a relationship may indicate a real functional antagonism: when the regulatory link is strengthened, cytotoxic activity is suppressed, which was previously described as one of the mechanisms of tumor immunoevolution. The CD4+/CD8+ indicator demonstrated insignificant correlations with other variables, with the exception of a moderate negative relationship with NK cells (ρ=-0.191), which was apparently associated with the structural rearrangement of the immune response during surgical stress, when, with an imbalance of T populations, innate cytotoxicity is activated compensatorily. NK cells in general showed independent behavior with weak correlations with most parameters, only a small positive relationship with Treg (ρ=0.183). The key proinflammatory mediator IL-6, which in some cases was considered as a universal marker of surgical stress, showed no reliable correlation with either TNF-α (ρ=0.007), or IFN-γ (ρ=0.085), or IL-10 (ρ=0.087). In this case, IL-6 probably represents an autonomous marker of inflammatory load, reflecting the severity of the response to a greater extent than its integral direction. TNF-α, the second most important proinflammatory cytokine, demonstrated a weak positive correlation with IFN-γ (ρ=0.196) and IL-10 (ρ=0.134), which can be interpreted as a general tendency to activate the cytokine network, without pronounced functional connectivity. Such a configuration indicates that in the perioperative period TNF-α participates in the inflammatory cascade rather as a trigger than as a coordinating factor.

IFN-γ, on the contrary, was weakly correlated with almost all other parameters. This cytokine has a relative autonomy as a marker of cytotoxic functionality, which is especially important in the context of tumor immune control. Its weak relationship with IL-10 (ρ=0.008) and CRP (ρ=0.078) confirms that the antitumor cytokine link functions independently of the classical inflammatory axis. IL-10 is of interest. Its negative correlation with CRP (ρ=-0.187) may indicate an inhibitory effect of IL-10 on the synthesis of acute phase proteins, but the strength of the relationship is insufficient to conclude about a direct regulatory interaction, which also illustrates the general focus on restraining the systemic inflammatory response when the suppressive link is activated. CRP, as an integral marker of inflammation, was generally weakly associated with cytokine variables, which is probably due to its delayed kinetic profile and dependence on other, in particular, non-functional factors, such as age, BMI, tumor stage and preoperative load. The correlation matrix between cellular and cytokine parameters confirms the assumption of a multi-axial structure of the perioperative immune response, where each link can be activated independently.

Among the most notable relationships is the positive correlation between the level of Tregs and IL-6 (ρ=0.183), which is consistent with the literature data indicating the involvement of IL-6 in the induction and stabilization of regulatory T cells through the activation of the STAT3-dependent pathway. This dependence emphasizes the role of IL-6 as a mediator of not only inflammation, but also suppressor activity under surgical stress. Similarly, Tregs demonstrate a weak positive relationship with IL-10 (ρ=0.142), and although the coefficient does not reach the level of strong dependence, the presence of even a weak correlation may indicate a tendency toward suppressor dominance in some patients. Of interest is the negative value between NK cells and IL-10 (ρ=-0.187), which may potentially reflect biological competition between the active innate response and anti-inflammatory control. A decrease in NK cells with a simultaneous increase in IL-10 may be one of the mechanisms that ensure the weakening of cytotoxic surveillance in favor of inflammatory balance. CD4+ T helpers showed weak positive correlations with IFN-γ (ρ=0.196) and IL-10 (ρ=0.134), which reflects their central role in coordinating both proinflammatory and suppressor responses. However, low values of the coefficients confirm that in the acute postoperative period it is inappropriate to analyze CD4+ in isolation from Tregs and cytokines, since a comprehensive interpretation is important. Finally, the CD4+/CD8+ indicator demonstrated the highest negative value with CRP (ρ=-0.187), which may reflect the relationship between systemic inflammation and imbalance in the T-cell link.

In general, this stage of the analysis confirmed that the most promising for further modeling of the tolerance scale are: Treg (as a central suppressor node), IL-6 (as a trigger and marker of systemic inflammation), IFN-γ (as an indicator of cellular activity), as well as CD4+ and NK cells as key performers of adaptive and innate surveillance. Based on the data obtained, we constructed a multivariate logistic model to determine the contribution of each immunological indicator to the formation of the risk of an unfavorable clinical outcome. The integral unfavorable outcome, i.e. a low total score on the clinical scale, was considered as a dependent variable.

Among all the analyzed parameters, the highest AUC value was recorded for IL-6 (AUC=0.602), which reflects the moderate but stable discriminatory ability of this cytokine in identifying patients prone to the development of severe immunosuppression and complicated postoperative course. At the same time, the sensitivity of IL-6 was 81.2%, and the specificity was 40.9%, which indicates the predominant value of IL-6 as a "risk cutoff" parameter: it allows identifying the majority of vulnerable patients, albeit at the cost of reduced specificity. There are suggestions that its role as an early biochemical marker of stress-induced inflammatory response and a potential trigger of cellular dysregulation is very important. The Treg indicator demonstrated a weak, but potentially clinically significant prognostic ability (AUC=0.523). Despite the modest sensitivity level (37.5%), the specificity was 86.4%, which allows us to consider Treg as a parameter that allows us to confirm the already suspected immune inhibition, especially in combination with other markers. On the contrary, the CD4+, NK and IFN-γ indicators did not demonstrate high individual diagnostic value (AUC < 0.5). CD4+ and IFN-γ showed an inverse relationship with the risk, but their sensitivity level was extremely low (12.5% and 9.3%, respectively), while the specificity of CD4+ was high (95.5%), which allows us to potentially consider it as a clarifying criterion in a comprehensive assessment. NK cells showed hypersensitivity (100%) with extremely low specificity (13.6%), which makes them applicable only as an early signal of general activation of the immune axis, but not as a discriminatory risk predictor.

Thus, based on the totality of characteristics, only IL-6 and Treg have a conditional diagnostic value sufficient for inclusion in the immunological acceptability scale. The remaining indicators, despite their pathogenetic significance, did not demonstrate acceptable sensitivity/specificity characteristics and can only be used as auxiliary or modulating components in calculating the integral immune profile. Based on the data obtained, we developed a scoring scale "SIDAP" (degrees of immunological acceptability of the anesthetic approach) in cancer patients, implemented as a software module in digital format. The "SIDAP" program provides for patient assessment by five key immunological indicators, each of which is interpreted using a three-level system: 0 points - no deviations, 1 point - moderate changes, 2 points - severe impairment. Threshold values for each criterion are determined based on ROC analysis and confirmed by expert clinical interpretation. This scale forms an objective basis for personalized selection of anesthetic management method, reducing the risk of worsening postoperative immunosuppression and opening up opportunities for early correction of immune imbalance. The summary structure of the scale is presented.

I degree of immunological tolerance (0-4 points). This includes patients who do not have significant immune disorders. The CD4+ level is usually ≥36%, which corresponds to a fully coordinated adaptive immune response. NK cells remain within the physiological range (≥13%), ensuring the preservation of innate cytotoxic activity. The concentration of IL-6 in the blood serum does not exceed 30 pg / ml, indicating the absence of a systemic inflammatory response. Tregs do not exceed 6%, indicating a balance between activation and suppression in the T-cell link. The IFN-γ level remains ≥7.5 pg / ml, maintaining adequate cytokine support for cellular immunity. This profile allows us to speak of a high degree of immunological stability and functional compensation.

II degree of immunological tolerance (5-7 points). Patients in this group show individual but moderate disturbances of immune parameters, while the overall functional balance is maintained. CD4+ decreases to the range of 30-35%, indicating a limited coordination potential of the immune system. NK cells vary within 10-12.9%, which may indicate a decrease in innate protection. IL-6 increases to a level of 31-45 pg / ml, which reflects systemic stress, but does not yet require aggressive correction. Tregs fluctuate within 6.1-7%, indicating activation of the suppressor link without obvious immunosuppression. IFN-γ is at the border of 6.5-7.4 pg / ml - a moderate decrease, partial loss of cytotoxic potential is possible. This is an intermediate risk group that requires an individual approach to the choice of anesthesia method and, if necessary, gentle correction of the immune background.

III degree of immunological acceptability (≥8 points). Patients with severe immunological disorders reflecting the development of functional immunosuppression: CD4+ <30% - a sign of failure of the coordinating link of adaptive immunity; NK cells <10% - loss of innate cytotoxic activity associated with an increased risk of metastasis; Treg > 7% - increased suppressor activity and inhibition of the effector link; IL-6 > 45 pg/ml - high-intensity systemic inflammation with the participation of stress mediators; IFN-γ <6.5 pg/ml - decreased antitumor activity indicating suppression of the Th1 response. Such a profile requires either preoperative immunocorrection, or revision of anesthesia tactics towards the most gentle (regional), or temporary postponement of the intervention if there are risks.

A comparative analysis of the distribution of patients by degrees of immunological tolerance (I-III) in groups I and II at the stage of inclusion in the study demonstrated the comparability of the initial immune profile. The assessment was carried out before the immunocorrective measures and before the choice of anesthetic tactics, solely on the basis of laboratory parameters included in the SIDAP scale. In both groups, patients with a limited or low degree of immunological tolerance predominated, which reflects the high prevalence of immunosuppressive changes in cancer patients before surgery. The proposed method for correcting perioperative immunosuppression and choosing anesthetic tactics in cancer patients is based on a step-by-step clinical and immunological stratification of the risk of developing immune disorders in response to surgery. It is based on the author's scale of immunological tolerance to anesthetic care, taking into account five key indicators of the immune status.

The essence of the treatment and diagnostic algorithm is to select the most gentle anesthetic approach based on the overall immunological assessment, and if significant disorders are detected, to conduct a pre-directed immunological correction in order to transfer the patient to a more favorable risk category. Thus, the method is not only a diagnostic, but also a treatment and prognostic tool that allows influencing outcomes through preoperative intervention.

At the first stage of the treatment and diagnostic algorithm, a laboratory examination of the patient is carried out, including the determination of five main immunological indicators. The interpretation of the values is carried out according to the SIDAP scale developed by us. Further tactics are determined depending on the degree of SIDAP.

If the first degree of admissibility (SIDAP-1) is present, the patient is considered immunologically resistant. In this case, anesthetic tactics do not require restrictions: general, regional or combined anesthesia can be used depending on the scope of the operation, the anatomical zone and the preferences of the anesthesiologist. When the second degree of acceptability (SIDAP-2) is detected, the patient has moderate violations of one or more indicators: decrease in CD4+ to 30-35%, decrease in NK to 10-12.9%, increase in Treg to 6.1-7%, increase in IL-6 to 45 pg/ml and decrease in IFN-γ to 6.5-7.4 pg/ml. In this case, the patient is considered as conditionally acceptable for general anesthesia, but priority is given to combined or regional methods. At the same time, moderate immunocorrection is recommended, aimed at stabilizing the inflammatory background and supporting cellular immunity. Moderate and metabolically targeted immunocorrection is recommended, aimed at reducing the level of IL-6, supporting the function of NK cells and moderate inhibition of the proinflammatory cascade. These measures allow with a high probability to improve the immune profile indicators and reduce the risks during general or combined anesthesia. The correction program includes four main elements.

Celecoxib (COX-2 inhibitor), 200 mg 2 times a day for 3 days before surgery, in order to reduce the level of IL-6 and TNF-α by reducing the production of proinflammatory mediators.

In order to stabilize the cell membrane, neutralize free radicals, protect NK and CD4+ lymphocytes, antioxidant support is prescribed: N-acetylcysteine (NAC): 600 mg × 2 times a day, orally or parenterally; Vitamin C: 1000 mg / day orally, in 2 doses of 500 mg; Vitamin E: 100 mg / day, orally in capsules. The duration of therapy is 3 days before surgery. In order to stimulate IFN-γ synthesis, support lymphocyte function and cytotoxic activity, nutritional support (immunonutrition) is prescribed, which includes the use of L-arginine 2-3 g, Glutamine 2 g, Zinc 15-20 mg, Selenium 100-150 mcg, which can be taken in the form of ready-made mixtures (for example, Impact®, Nutridrink® Protein Plus), in a volume of 400-600 ml / day in 2-3 doses per day for 72 hours before surgery. The use of immunonutrition has been proven effective in preparing cancer patients for abdominal surgery. In order to reduce Treg activation, avoid immune inhibition caused by opioids (to achieve minimization of the opioid load), morphine and its derivatives (fentanyl, tramadol) are replaced with paracetamol (1 g × 4 times a day); meloxicam (15 mg orally once a day); ketorolac (30 mg intramuscularly); regional analgesia, if possible (blockade, infiltration, epidural analgesia); dexmedetomidine (0.2-0.7 mcg/kg/h intravenously in a perfusor, as indicated, especially in cases of high anxiety and unstable hemodynamics).

Patients with the third degree of immunological tolerance according to the SIDAP scale (a total of 8 points or higher) have pronounced immune disorders characterized by a persistent decrease in CD4+ and NK cells, an increase in IL-6 and Treg levels, and a decrease in IFN-γ. This profile is associated with a high risk of developing postoperative immunosuppression, delayed recovery, infectious complications, and worsening oncological outcomes. Therefore, general or combined anesthesia without preliminary immunological preparation is contraindicated in this group. In order to stabilize the immune status and transfer the patient to a safer category, a mandatory course of immunocorrection is carried out for at least 72 hours before the planned intervention, including: Celecoxib, NSAIDs and multimodal analgesia, nutritional support (immunonutrition), antioxidants (support of cellular homeostasis), immunomodulators (for the purpose of direct stimulation of the Th1 response and / or suppression of Treg) and the use of transfer factors, Reaferon-Lipint (IFN-α2b) 500 thousand IU, orally, 1 time per day.

After 72 hours from the start of immunocorrection, a repeated laboratory assessment of the immune profile is carried out, recalculation of points on the SIDAP scale and reassessment of the degree of admissibility. If the patient moves to stage II or I, combined or general anesthesia is acceptable; if stage III remains, the operation is performed under regional support or postponed until the immune status is stabilized.

Thus, the described course of mandatory immunocorrection allows transferring patients from the high-risk zone to the controlled one, reducing the likelihood of developing postoperative immunosuppression, complications and violations of antitumor surveillance. It provides the opportunity to choose an anesthesiological approach consistent with the state of the immune system and introduces the principle of immunological responsibility into the practice of oncoanesthesiology.

For an objective assessment of the effectiveness of the proposed treatment and diagnostic tactics, the dynamics of the distribution of patients in group II by degrees of immunological tolerance according to the SIDAP scale during 72 hours of preoperative immunocorrection was analyzed. The distribution was assessed at four control points: before the start of therapy, after 24, 48 and 72 hours.

At the initial stage (0 h), the proportion of patients with degree III tolerance was 65%, which reflected the high prevalence of severe immune disorders in the population under examination. Grade II was recorded in 35% of patients, and there were no patients with grade I (0-4 points on the scale), which is completely consistent with the logic of including group II as a clinically vulnerable category. Already 24 hours after the start of immunocorrection, a shift in distribution occurred: the share of grade III decreased to 43%, while grade II increased to 57%. Despite the fact that patients with grade I were still absent, this stage reflected the early positive effect of the therapy, primarily due to a decrease in IL-6 levels and partial stabilization of Treg and CD4+ indicators.

By the 48th hour, 8% of patients had achieved indicators corresponding to the first degree of immunological tolerance. They were mainly represented by patients who were on the border between the first and second degrees at the beginning of therapy and responded most favorably to the combination of nutritional support and inflammation inhibitors. The number of patients with the third degree continued to decrease to 30%, and the share of the second degree was 62%.

By the 72nd hour, the number of patients with the first degree increased to 17%, which confirms the stable effect of the intervention and the possibility of transferring some patients from the zone of conditional and critical immune intolerance to the functionally safe one. At the same time, the second degree remained dominant (63%), and the share of patients with the third degree decreased to 20%, which indicates resistance to standard correction of about a fifth of the sample.

Thus, the obtained data confirm the high efficiency of the proposed immunocorrection program. In more than 40% of patients who initially had grade III immunological tolerance, we were able to achieve a risk reduction to grade II or I. As a result, the dynamics allowed us to expand the range of acceptable anesthetic interventions, reduce the need for delays, and ensure the implementation of safer individualized tactics.

The developed treatment and diagnostic algorithm for choosing anesthesiological tactics and correction of perioperative immunosuppression in cancer patients is based on a quantitative assessment of the immunological status using the original scale of immunological admissibility (SIDAP). The scale takes into account five key indicators: CD4+, NK, Treg, IL-6 and IFN-γ, allowing to objectively determine the degree of risk of developing immunosuppression during general or combined anesthesia. The algorithm not only stratifies patients by risk, but also provides tactical recommendations regarding the form of anesthesia and the composition of preoperative immunocorrection. The use of a correction scheme including anti-inflammatory, antioxidant and nutritional components made it possible to transfer more than 40% of patients from the high-risk group to safer categories, which indicates the high efficiency and practical feasibility of the proposed method. Thus, a reproducible and clinically applicable system of personalized assessment and preparation for anesthesia care in oncological surgery was created.

The development and implementation of a treatment and diagnostic algorithm based on immunological stratification made it possible to implement the concept of personalized anesthetic tactics in cancer patients. To assess its clinical significance, a comparative analysis of two groups was conducted: group I, in which the anesthetic management tactics were formed in a standard way without taking into account the immune status, and group II, where the algorithm was implemented in full. As part of the assessment, immunological parameters were analyzed in dynamics, as well as clinical efficacy indicators. Analysis of cellular immunity in cancer patients who received immunocorrection before surgery showed a clear tendency to normalize the key parameters of the adaptive and innate links of immune protection. If at the stage of the primary examination (before correction), the immune profile was practically no different from that in the group without immunocorrection, then after intervention on the immune system (but before the start of the operation), significant positive shifts were noted.

Thus, the CD4+ level in patients after immunocorrection increased by an average of 7-10% compared to the initial values. This was accompanied by an increase in the CD4+/CD8+ index and a moderate increase in CD56+, reflecting the activation of NK cells. Thus, even before surgery, patients in Group II entered the surgical stress in a more functionally collected, immunologically mobilized state. After surgery, despite the expected decrease in a number of indicators, the dynamics turned out to be fundamentally different compared to the group without correction. Thus, the number of CD4+ T-helpers in patients who received general anesthesia decreased by an average of 1.2 times, while in a similar subgroup of Group I this decline reached almost 1.4 times (p <0.05). The decrease in NK cell activity (CD56+) was also less pronounced: the decrease was about 15%, while in patients without immunocorrection - more than 30% of the initial level (p <0.01). It is especially important to note the behavior of Treg cells. In group II, their level after surgery increased by only 10-15% of the post-correction level, while in group I the growth reached more than 40%, especially in patients who underwent general anesthesia. This indicator demonstrates the effectiveness of preventive intervention in preventing hyperregulation and subsequent inhibition of antitumor immune surveillance. Comparative analysis of the CD4+/CD8+ index confirms the general trend: after surgery, it decreased in both groups, but in the group with immunocorrection, the decrease did not exceed 10%, while in group I the index fell by more than 20% (p < 0.05). This means that patients in group II maintained a more balanced ratio of coordination and effector links of the immune response even under surgical stress.

In general, immunological correction performed before surgery ensured the formation of a more stable, adaptive immune phenotype in patients, which was expressed in a less pronounced postoperative decline in key lymphocyte populations, a more stable functional index and limited growth of the regulatory link. Against the background of general anesthesia, where the most pronounced immune shifts were observed in group I, in patients with immunocorrection they were mitigated by almost 1.5-2 times, which emphasizes the practical significance of the developed preparation algorithm. In comparison with group I, where such measures were not carried out, the dynamics of inflammatory and regulatory markers turned out to be not only more moderate, but also biologically more coordinated, reflecting a weakening of the proinflammatory response and the preservation of adaptive stability. At the stage of preoperative preparation, most patients in group II showed a moderate decrease in IL-6 and TNF-α levels, which can be interpreted as a preventive suppression of subclinical inflammation. After immunocorrection, the IL-6 level decreased by an average of 10-15% compared to the initial level, while in Group I similar stabilization was not observed, which is especially significant given that IL-6 is a key mediator triggering the cascade of hyperinflammation and Treg cell activation. In patients with regional and combined anesthesia, post-correction IL-6 levels were 25-30% lower than in Group I patients who entered surgery without immune preparation (p < 0.01).

Postoperative growth of IL-6 was observed in all patients, but its amplitude in Group II was significantly smaller. Thus, under general anesthesia, the IL-6 level increased approximately 1.6 times from the preoperative level, while in patients of Group I this increase reached 2.3 times (p < 0.01). Under regional anesthesia, the difference was even more pronounced: IL-6 increased no more than 1.5 times, while in the control group it almost doubled (p < 0.01). Immunocorrection does not so much eliminate the inflammatory response to surgery as limit its scale and neutralize hyperreactivity. The same trend was observed for TNF-α: in patients with immunocorrection, the postoperative increase did not exceed 20-25% of the preoperative level, while in Group I it reached 40% or more (p < 0.05). Moreover, the initial levels of TNF-α in both groups were comparable, which emphasizes the effect of the intervention rather than the difference in the initial background.

IFN-γ, on the contrary, demonstrated a relatively stable picture. In group II, after immunocorrection, its level increased by 5-8%, and after the operation, it decreased moderately, without going beyond the adaptive response. In group I, a drop in the IFN-γ level by more than 15-20% was observed, especially in the general anesthesia subgroup, which was accompanied by a parallel increase in IL-10 and Treg - a typical combination for the development of perioperative immunosuppression. Thus, patients with immunocorrection provided better preservation of the antitumor Th1 response, while in group I it failed. The dynamics of IL-10, a cytokine associated with immune tolerance and inhibition of inflammation, also differed significantly. In group II, its level after surgery increased only by 20-25%, while in group I - by more than 50% (p <0.05), especially against the background of general anesthesia, which allows us to assume that immunocorrection restrains the activation of inhibitory links of the immune network without disrupting the natural mechanisms of inflammation compensation. The CRP indicator in group II after surgery also demonstrated a less pronounced increase. If in group I its level increased more than twice, then in group II this growth was limited to 1.6-1.7 times (p <0.05). In patients with a combined anesthetic approach, the CRP values after surgery were almost a third lower than in a similar subgroup of group I, which is probably due to the synergistic effect of regional anesthesia and immunological correction.

Thus, the obtained data indicate that immunocorrection in the preoperative period is able to modulate the patient's inflammatory reactivity and form a more physiological cytokine response. A decrease in the amplitude of IL-6 and TNF-α, stabilization of IFN-γ and limitation of IL-10 and CRP hyperproduction create prerequisites for maintaining the immune balance under surgical stress. The correction effect was especially pronounced when using regional or combined anesthetic approaches, where the cytokine profile indicators demonstrated the best preservation. In patients of group I with OA, pronounced fluctuations in blood pressure requiring vasopressor support were observed in 40% of cases. After immunocorrection, this proportion among patients of group II decreased to 15%. The number of stably undergoing interventions increased 2-fold - from 4 to 8 patients, which confirms the strengthening of autonomic regulation and improvement of peripheral vascular resistance (p <0.05). In RA, even in group I, hemodynamics often remained within adaptive limits (only 2 patients required support). However, in group II, no patient showed instability, and positive results were assessed in all 10 cases (1.4 times more often, p <0.01). At the same time, the use of combined anesthesia (OA + RA) led to minor disturbances that persisted in some patients in group I (3 cases), but in group II, only 1 patient showed an unstable reaction. At the same time, the proportion of positive results increased by 40%, which is especially important for patients with combined pathology and a high risk of destabilization.

Among patients with OA, every third patient in Group I had severe pain syndrome requiring opioid support. After immunocorrection, the number of such cases decreased by 3.5 times. Most patients in Group II (40%) managed with the basic analgesia regimen, while in Group I there were only 20% of such cases (p <0.01). At the same time, regional anesthesia initially demonstrated a low need for additional analgesia: in Group I, there was only 1 case of ineffective pain relief. In Group II, all patients were in the controlled pain response zone, and in 55% of cases they were within the baseline level, which is 57% higher than in the control group (p <0.05).

The combined approach to choosing anesthesia (OA + RA) ensured a moderate need for additional analgesia in most patients in Group I. After immunocorrection, there were 17% fewer of such cases, and the number of patients who did not need pain relief correction almost doubled. Awakening delay in OA with signs of cognitive disorientation was recorded in 2 patients in Group II versus 6 in Group I. At the same time, 7 out of 20 patients in the main group woke up quickly and calmly, while in the control group there were less than a quarter of them.

The subgroup of patients with RA demonstrated the clearest contrast: all 10 patients in Group II woke up without delays and side effects. In Group I, a delay was recorded in one patient, but the total number of those who woke up perfectly was 20% lower (p < 0.05).

The use of combined (OA + RA) anesthesia after immunocorrection was assessed in 10 patients (1.4 times more often than in Group I). Clinically, this was accompanied by a reduction in the duration of post-anesthesia observation.

In OA in group I, a quarter of patients had severe adverse reactions (vomiting, chills, agitation). In group II, this figure decreased almost 5 times, while the proportion of patients without adverse effects increased by 30% (p <0.01). Adverse reactions in group I with RA were observed in half of the patients, but required intervention only in 1 case. In group II, there were virtually no side effects: 12 patients (60%) passed the postoperative period without complaints, which is significantly higher compared to the control subgroup.

The proportion of patients with clinically significant side effects in OA + RA decreased from 2 to 1 case, and the number of patients without symptoms increased by 1.6 times, which additionally confirms the protective effect of immunocorrection and the gentle neurovegetative profile of combined anesthesia.

6 patients in group I required observation for more than 24 hours after OA. After immunocorrection, there were only 1 such patients, which demonstrates a decrease in the severity of the postoperative period. The number of patients who did not require intensive care increased almost twofold (p <0.01). Even in group I, patients with RA generally did not require intensive care. But in group II, there was not a single case of even short-term intensive care control, which emphasizes that the regional component in combination with immune preparation almost completely eliminates the need for resuscitation support. Among patients in group I after OA + RA, 3 cases required observation for >24 hours. In group II - only 1. Good results were assessed in 9 patients versus 8 in group I, i.e. the improvement is pronounced, but moderate.

In Group I, 7 patients did not recover their activity within the first 48 hours after OA. In Group II, there were only 2 such patients. The number of patients who got up within the first day increased by 30%, reflecting both a decrease in inflammation and better autonomic adaptation. In Group II, 11 patients (55%) demonstrated complete recovery within 24 hours after RA, while in Group I there were only 8 such patients. Negative dynamics were not recorded in any patient in Group II. After immunocorrection, the proportion of patients with OA + RA who got up within the first 24 hours increased by 40%, and the number of late mobilizations (more than 48 hours) decreased threefold, which confirms the beneficial effect of the combination of techniques and immune intervention.

The summarized data on the integrated clinical scale for assessing the effectiveness of anesthesia, clearly demonstrate a significant improvement in the functional status of patients after the implementation of the developed immunocorrection algorithm. If in the group without correction an unsatisfactory result was recorded in every fourth patient, then in group II there were almost 2.2 times fewer such outcomes (p < 0.01). The decrease in the proportion of unsatisfactory assessments reflects not just a local improvement in individual parameters, but a systemic effect of stabilization of key physiological functions, from hemodynamics to restoration of activity. The proportion of patients with a satisfactory level of adaptation after surgery remained at a similar level (about 48-50%), but in group II there was a clear shift in emphasis towards the result of the "good" level. Thus, if in group I only 16 people (26.7%) received a total assessment of "good", then after immunocorrection there were 23 such people (38.3%), that is, almost 1.5 times more (p < 0.05).

In general, the introduction of immunocorrection allowed not only to reduce the number of clinically unfavorable scenarios, but also to significantly increase the proportion of patients with the most favorable postoperative status, which confirms the real clinical value of the approach. The effect is especially pronounced in patients who received regional or combined anesthesia, where stabilization of the immune background was supplemented by the physiological advantage of the method.

Thus, the comparative assessment of the effectiveness of the proposed treatment and diagnostic algorithm for the correction of perioperative immunosuppression in cancer patients showed its high clinical effectiveness. The use of immunocorrection before surgery provided a significant improvement in the indicators of both cellular and humoral immune response, with a limitation of the severity of the inflammatory cascade, a decrease in the level of proinflammatory cytokines and stabilization of the activity of regulatory links. Analysis using the integrated clinical scale for assessing effectiveness demonstrated a significant decrease in the proportion of unsatisfactory outcomes in the main group - more than 2 times, with a simultaneous increase in the proportion of good clinical profiles by 43% (p < 0.05). The most pronounced positive effect was recorded with regional and combined anesthesia, which emphasizes the synergism between immunological preparation and the physiological nature of the anesthetic approach.

4. Conclusions

1. The comparative evaluation of the effectiveness of the proposed treatment and diagnostic algorithm for the correction of perioperative immunosuppression in cancer patients showed its high clinical effectiveness. The use of immunocorrection before surgery provided a significant improvement in the indices of both cellular and humoral immune responses, with a limitation of the severity of the inflammatory cascade, a decrease in the level of proinflammatory cytokines and stabilization of the activity of regulatory links.

2. Analysis using the integrated clinical scale for assessing effectiveness demonstrated a significant decrease in the proportion of unsatisfactory outcomes in the main group - more than 2 times, with a simultaneous increase in the proportion of good clinical profiles by 43% (p < 0.05). The most pronounced positive effect was recorded with regional and combined anesthesia, which emphasizes the synergism between immunological preparation and the physiological nature of the anesthetic approach.