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0South Russian Journal of Cancer. 2024. Vol. 5, No. 1. P. 6-16 https://doi.org/10.37748/2686-9039-2024-5-1-1 https://elibrary.ru/gwafxm
ORIGINAL ARTICLE
Clinical and pathogenetic justification for the use of therapeutic plasma exchange in the complex of preoperative preparation
of patients with non-small cell lung cancer complicated
by the inflammatory process
N. D. Ushakova1,2, D. A. Rozenko1, S. N. Tikhonova1, D. A. Kharagezov1, N. N. Popova1,212
1 National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation
2 Rostov State Medical University, Rostov-on-Don, Russian Federation
12 natalyaanest@mail.ru
Purpose of the study. Determination of pathogenetic substantiation and indication criteria for the inclusion of extracorpo- real detoxification methods in preoperative preparation of patients with non-small cell lung cancer (NSCLC) complicated by inflammation.
Patients and methods. This study included the data on 222 patients with newly diagnosed stage I-IV NSCLC referred for elective surgical treatment to the Department of Thoracic Oncology, National Medical Centre for Oncology, in 2017-2019. Endogenous intoxication was evaluated in all patients depending on the leukogram results: leukocytic intoxication index (LII), body resistance index (BRI), reactive neutrophil response (RNR), and neutrophil-lymphocyte ratio (NLR). Indicators of the inflammatory response, i. e. interleukin 6 and procalcitonin, were also studied.
Results. 36.5 % of NSCLC patients developed inflammation. That over 70 % of the NSCLC patients showed pronounced clinical and laboratory signs of endogenous intoxication and inhibited protective systems of homeostasis. Initial sub- or decompensated endotoxicosis together with reduced overall reactivity of the body poses a high risk of systemic inflamma- tory response to antitumor surgical treatment. This justifies the inclusion of extracorporeal detoxification into preoperative preparation of this category of patients as an active preoperative therapy.
Conclusions. Simultaneous elevation of LII, RNR and NLR characterizing the presence of endotoxicosis in sub- and decom- pensation of endogenous intoxication by own physiological detoxification systems requires an active preoperative preparation with extracorporeal detoxification.
For citation: Ushakova N. D., Rozenko D. A., Tikhonova S. N., Kharagezov D. A., Popova N. N. Clinical and pathogenetic justification for the use of therapeutic plasma exchange in the complex of preoperative preparation of patients with non-small cell lung cancer complicated by the inflammatory process. South Russian Journal of Cancer. 2024; 5(1): 6-16. https://doi.org/10.37748/2686-9039-2024-5-1-1, https://elibrary.ru/gwafxm
For correspondence: Natalia N. Popova - Cand. Sci. (Med.), MD, anesthesiologist and resuscitator of the Anesthesiology and Resuscitation Department, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation; Assistant of the Department of Oncology, Rostov State Medical University, Rostov-on-Don, Russian Federation
Address: 63 14 line, Rostov-on-Don 344037, Russian Federation E-mail: natalyaanest@mail.ru
ORCID: https://orcid.org/0000-0002-3891-863X SPIN: 5071-5970, AuthorID: 854895
Scopus Author ID: 57215858399
Compliance with ethical standards: the ethical principles presented by the World Medical Association Declaration of Helsinki, 1964, ed. 2013 were observed in the study. The study was approved by the ethics committee of the National Medical Research Centre for Oncology (extract from the protocol of the meeting No. 19 dated 22/11/2021). Informed consent was received from all participants of the study
Funding: the work was carried out with the support of the National Medical Research Centre for Oncology
Conflict of interest: the authors declare that there are no obvious and potential conflicts of interest associated with the publication of this article
The article was submitted 02.06.2023; approved after reviewing 01.12.2023; accepted for publication 27.02.2024
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https://doi.org/10.37748/2686-9039-2024-5-1-1, https://elibrary.ru/gwafxm
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?????: 344037, ?????????? ?????????, ?. ??????-??-????, ??. 14-? ?????, ?. 63 E-mail: natalyaanest@mail.ru
ORCID: https://orcid.org/0000-0002-3891-863X SPIN: 5071-5970, AuthorID: 854895
Scopus Author ID: 57215858399
?????????? ????????? ??????????: ? ?????? ??????????? ????????? ????????, ????????????? ???????????? ??????????? ????????? ??????????? ?????????? (World Medical Association Declaration of Helsinki, 1964, ???. 2013). ???????????? ???????? ????????? ????????? ???? "???? ?????????" ????????? ?????? (??????? ?? ????????? ????????? ? 19 ?? 22.11.2021 ?.). ??????????????? ???????? ???????? ?? ???? ??????????
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INTRODUCTION
To date, lung cancer (LC) occupies a leading po- sition among all malignant neoplasms, representing a significant socio-economic problem in Russia and the world overall. In the Russian Federation, the in- crease in morbidity and mortality from LC is especial- ly noticeable among the male population in the age group over 60 years, while 85 % of detected cases are represented by non-small cell lung cancer (NS- CLC) [1]. Unfortunately, in more than 70 % of patients, a malignant neoplasm of the lung is diagnosed at the stage of a locally widespread process, or there is a metastatic lesion, including the pleura, the opposite lung, and the chest wall [2].
According to current data, the surgical method in combination with antitumor therapy significantly affects the prognosis of the disease, improving the survival of patients with NSCLC at virtually all stages compared with maintenance therapy [3]. At the same time, the nature of the course of the disease depends not only on the effectiveness of the method used, but also on the occurrence of severe complications that may cause the refusal of specialized care or restriction of full-fledged antitumor treatment.
It is fair to note that all cancer patients are sus- ceptible to various infectious complications, which is 4-8 times more common than in the general population. This is due to a defect in the immune system, provoked by both tumor development and increased catabolic processes against the back- ground of impaired physiological detoxification and excretion processes, as well as secondary changes in organs and tissues due to antitumor therapy [4]. In predicting complications, including septic ones, it is necessary to consider not only the primary infec- tion of the tumor, but also the aggressive tactics of extended operations, including total removal of the organ affected by the tumor and suspected meta- static spots [5]. According to some data, the inci- dence of inflammatory pulmonary complications in patients with progressive NSCLC ranges from 12 to 40 %, and the mortality rate reaches 26.5-33 % [6]. These indicators are due to several reasons. Thus, endobronchial tumor growth leads to the formation of a secondary inflammatory focus in the lung tis- sue and in most patients, LC presents as pneumoni- tis, pleurisy, pleural empyema or lung abscess with pneumonia [7]. In addition, the late stages of LC are
characterized by the disintegration of the tumor with the formation of necrosis and an inflammatory zone in the tissue of the affected lung. The necrotic focus becomes a source of intoxication, which is caused by the prolonged intake of cellular breakdown products into the blood [8].
The factors determining the prognosis of the func- tional state of patients with LC after radical surgical treatment, which involves total organ removal or ex- tended lung resection with regional lymphadenecto- my, should also include the features of ensuring gas exchange during surgery. The cessation of air cir- culation in the lung during surgery provokes a mas- sive release of inflammatory cascade mediators into the bloodstream, and inadequate gas exchange with a decrease in oxygen partial pressure and a decrease in cardiac output cause the development of hyper- capnia and tissue hypoxemia [9]. In addition, rota- tional surgical manipulations on a lung "turned off" from gas exchange contribute to aggravating the situation caused by the powerful release of tumor cell decay products into the general bloodstream, initiating the launch of a systemic inflammatory re- action, the development of acute lung damage in the early postoperative period [7].
In the conditions of the initial inflammatory pro-
cess, surgical stress, accompanied by functional disorders of the sympathetic nervous system, par- adoxical endocrine responses, as well as immuno- logical and hematological changes, it promotes the activation of leukocytes, fibroblasts, endothelial cells, and platelets, followed by massive release of biolog- ically active substances. A cascade of pathological changes and disruption of the normal functioning of the microcirculatory bed in patients with LC leads to the development and rapid progression of acute lung injury, as a result one in three patients dies [10]. Everything listed above determines the relevance of the concept of endotoxicosis correction and of prevention of acute respiratory distress syndrome in patients with NSCLC complicated by the inflam- matory process that is already happening in the pre- operative period. At the same time, the inclusion of extracorporeal detoxification in the complex of preoperative preparation, which ensures the removal of excessive concentrations of pathognomonic en- dogenous toxic substances, can probably contribute to improving the results of the inpatient period of
care for this category of patients.
The purpose of the study was to determine the pathogenetic validity and criteria of indications for inclusion of therapeutic plasma exchange in the complex of preoperative preparation of patients with NSCLC complicated by the inflammatory process.
MATERIALS AND METHODS
The study included data obtained from the medi- cal histories of 222 patients with primary NSCLC of stages I-IV who were admitted for elective surgical treatment at the Department of Thoracic Oncology of the National Medical Research Center of Oncology, in the period 2017-2019.
The median age in the study group was 61 years, the average age was 63.9 � 1.7 years, the range was 37-78 years, with 77 % men and 23 % women. The age categories according to the criteria of the World Health Organization were represented by people: under 45 years - 2.3 % (n = 5), 45-59 years - 30.6 % (n = 68),
60-74 years - 61.7 % (n = 137), over 75 years - 5.4 % (n = 12). According to preliminary data of clinical ex- amination and histological analysis of the surgical material, the staging of the tumor process was carried
out (TNM classification 8-edition, 2017) [11]: T1N0M0 in 6.3 % (n = 14), T2aN0M0 in 26.6 % (n = 59), T2bN0M0 in
8.1 % (n = 18), T3N1M0 in 14.9 % (n = 33), T3-4N1-2M0 in
36.5 % (n = 81), T3-4N3M0 in 6.7 % (n = 15), T3-4N2-3M1
in 0.9 % (n = 2) patients. Morphological parameters of the tumor: the largest number was squamous cell carcinoma of varying degrees of differentiation, which was detected in 80.1 % of patients. According to the clinical and anatomical classification of RL, the follow- ing were presented: central cancer - 27.45 % (n = 61), peripheral cancer - 64.9 % (n = 144), peripheral cancer with centralization - 7.65 % of cases (n = 17). Sur- gical treatment included: lobectomy and bilobecto- my - 67.9 % (n = 55), pneumonectomy - 8.7 % (n = 7), pleuropneumonectomy - 4.9 % (n = 4), combined pneu- monectomy - 17.3 % (n = 14), pneumonectomy with tracheal bifurcation resection - in 1.2 % (n = 1) to the patient. Clinically significant concomitant diseases were identified: ischemic heart disease - 63.5 %, ar- rhythmias - 27.5 %, hypertension - 51.7 %, postinfarc- tion cardiosclerosis - 22.9 %, chronic nonspecific lung diseases - 25.2 %, type 2 diabetes mellitus - 18.9 %, deep vein thrombophlebitis of the lower extremi- ties - 28.4 %, gastric ulcer or 12 duodenum - 35.1 % of patients.
The control group consisted of 24 relatively healthy men and women without cancer, comparable in age and gender to the study group.
To diagnose the presence and nature of the course of endogenous intoxication (EI) accompa- nying the development of the oncological process, all patients upon admission were assessed accord- ing to leukogram data for indicators of endogenous intoxication - leukocyte intoxication index (LII), body resistance index (BRI), neutrophil reactive response (NRR), neutrophil-lymphocyte ratio (NLR). The indi- cators of the inflammatory response - interleukin-6 (IL-6) and procalcitonin (PCT) - were also studied. Criteria for inclusion of patients: primary diagnosed NSCLC in persons over 18 years of age. The exclu- sion criterion was under the age of 18, small cell lung cancer.
This study was approved by the Ethical Committee of the institution, It was also carried out the prior consent of patients to the processing of their person- al clinical and laboratory data for scientific purposes (Protocol No. 19 of 11/22/2021).
The main material for this study was the blood (erythrocytes, plasma) of patients. Blood sampling was carried out in sterile vacuum tubes with pre- servative in the morning from the ulnar vein when patients were admitted to the hospital before any medical measures were carried out. A general clini- cal blood test was performed using the colorimetric method. The concentration of PCT was studied by the Brahms PCTQ test (Brahms Diagnostica, Germa- ny), IL-6 in blood serum was determined by enzyme immunoassay (Vector-Best reagents, Novosibirsk). Statistical verification of compliance with the nor- mal distribution was carried out according to the Shapiro-Wilk and Kolmogorov-Smirnov W-criterion, the results are presented in the form of M � m (M is the sample mean, m is the error of the mean, the median (Me), which in all groups practically did not differ from M, and the interquartile range in the form of a calculation of the lower and upper quartiles:
(Q25 and Q75).
STUDY RESULTS
A retrospective analysis of the data from 222 med- ical histories showed that in 81 patients (36.5 %), the manifestation of cancer manifested clinical signs of the inflammatory process and was diagnosed as
paracancerous pneumonia in 11, pneumonitis in 62, pleuritis and pleural empyema in 8 cases. These pa- tients formed the basis for further research.
An analysis of the data of 81 patients in whom the course of NSCLC was complicated by inflam- matory complications indicated that 58 patients (71.6 %) were initially diagnosed with central LC, 6 patients (7.4 %) had a peripheral form and 17 pa- tients (21.0 %) had peripheral cancer with centraliza- tion of the process. In the group with complications,
92.9 % (n = 75) of men and 7.1 % (n = 6) of women. According to age indicators, the group of patients in the age category 60-74 years prevailed 59.3 % (n = 48), then 45-59 years - 33.3 % (n = 27), at the age of 45 years and over 75 there were 3 patients (3.7 %). The complicated course was more often ob- served in patients with stage 3a - in 64.4 % (n = 52), then 2b - 21.1 % (n = 17), 3b - in 11.1 % (n = 9), stage 2a and stage 4 in 2 patients.
In 69 of 81 (85.2 %) patients, clinical signs of EI were noted, which had manifestations in the form of complaints of weakness and increased fatigue, fever with varying degrees of myalgia, sleep disor- ders and decreased psychoemotional activity, or a combination of these clinical signs of EI. When analyzing the white blood cell panel, it was revealed that upon admission, 63 out of 81 (77.7 %) patients had laboratory signs of EI due to tumor autolysis, and in some cases with the addition of bacterial in- fection - 22 (27.2 %) (Table 1).
It was noted that in 13 (16.0 %) patients with NS- CLC with the development of mild EI, stability of the general reactivity of the body with a compensated state of homeostasis was observed. In 19 (23.5 %) pa- tients, signs of mild EI were accompanied by inhibition of general reactivity, but the stability of homeostasis was ensured by detoxification systems of the body, the level of NRR was within physiological norms. In 10 (12.3 %) patients, a mild degree of EI was recorded with signs of inadequate compensation due to inhibi- tion of the general reactivity of the body and instability of homeostasis - in addition to an increase in LII, an increase in the level of NRR and NLR was observed. In 21 (25.9 %) patients, an average degree of severity of EI was revealed with a marked decrease in BRI, a man- ifestation of subcompensation or decompensation of physiological detoxification systems, which was manifested by a significant increase in relative to nor- mal values of neutrophil reactive response indicators.
Laboratory signs of initial systemic inflammation were revealed in 8 out of 81 (9.9 %) patients with initially diagnosed pleurisy and pleural empyema, according to IL-6 and PCT indicators. The serum concentration of PCT was 0.422 � 0.15 ng/ml, ex- ceeding the values of healthy people by 3.7 times (p < 0.001). The IL-6 values were 67.3 � 4.1 pg/ml, which exceeded the normal values by 14.3 times (p < 0.001).
The probability that a full-fledged and radical sur- gical treatment in these patients in conditions of failure of homeostasis and protective systems of the body can provoke a further decrease in compensa- tory reactions with the subsequent development of systemic and organ dysfunctions. An analysis of the nature of the course of the early postoperative period in these patients showed that 28 out of 81 (34.6 %) patients were diagnosed with complications in the first three days after surgery - acute respiratory dis- tress syndrome, pneumonia, sepsis, multiple organ failure. In all these patients, in the preoperative pe- riod, according to leukogram data, the presence of mild and moderate EI was recorded in combination with a decrease in overall reactivity and the state of sub- and decompensation of EI by physiological detoxification systems of homeostasis, an increase in NLR indicators, which amounted to 93.3 % of the total number of patients with initially identified dis- orders according to leukogram data (28 out of 30 patients). The hospital mortality rate in this cohort of patients was 28.6 % with a total mortality rate of 5 %. The severity of postoperative complications and high mortality have determined the relevance of the development and implementation of the concept of reducing the risk of early post-surgical complications
at the stage of the preoperative period.
DISCUSSION
In general, the data accumulated to date indicate that in the conditions of actively developing surgi- cal technologies, personalization of targeted and radiotherapy, the long-term results of treatment of patients with NSCLC remain disappointing [12]. It is obvious that a locally widespread tumor process with an inflammatory component is the cause of a number of pathological transformations that can lead to severe systemic complications in patients with LC. The data obtained in the study indicate ini-
tially pronounced changes in the functional state of patients with NSCLC. Thus, in the preoperative period, 71.55 % of patients registered the tension of non-specific protective systems of the body with si- multaneous detection of limited reserve capabilities of the immune system.
To obtain a complete picture of the initial state of protective, including physiological detoxification systems, we conducted a retrospective analysis of the medical histories of patients with NSCLC with
the determination of the level of integral intoxication indices LII, NRR, BRI, NLR. The leukocyte intoxica- tion index (LII is a characteristic indicator of tissue degradation processes and various levels of EI. In fact, the formula represents the absolute ratio of the number of neutrophilic leukocytes to lymphocytes, monocytes, eosinophils:
LII = (4 MC + 3 MMC + 2 RSN + SN) � (PC + 1) /
(Lf + M) � (E + 1), where MC are myelocytes, MMC - metamyelocytes, RSN - rod-shaped neutrophils, SN -
Table 1. LII, NRR, BRI, NLR values in patients with NSCLC prior to the surgical intervention (M � m)
Endogenous intoxication level
White blood cell panel indicators (U)
LII (with normal BRI (with normal NRR (with normal NLR (with normal range 1-1.6 � 0.2) range 50-100) range 10.6 � 2.1) range 1-2.1 � 0.1)
general body reactivity, (n =11)
2.812 (2.2; 5.435)
35.33
? = 0.010442
(n = 10)
Note: * - p < 0.05 compared to the indicators in healthy people. LII - Leucocytinc indicator of intoxicatin, NRR - neutrophil reactive response, BRI - body resistance index, NLR - neutrophil-lymphocytic ratio
segmented neutrophils, PC - plasma cells, Lf - lym- phocytes, M - monocytes, E - eosinophils.
LII is one of the most common intoxication indi- ces, the indicators of which are: norm - 0.62-1.6 U, mild degree of intoxication - 2.7-3.7 U; average degree 3.6-4.8 U; severe degree - 5.8-8.5; above
8.6 U - extremely severe degree of EI. An increase in LII indicators to 4-9 U indicates the presence of bac- terial toxins, the interval from 2 to 3 U is an indicator of intoxication by autolysis products. In addition to LII, the body resistance index (BRI) is considered as an objective indicator of EI, which is calculated as the ratio of the number of leukocytes to the product of the patient's age by the LII coefficient.:
BRI = L (thousand/l) / patient's age � LII.
BRI indicators vary from 50 to 100 U. At the same time, low BRI numbers indicate the development of an acute septic process.
The neutrophil NRR is also an EI index and is equal to the product of the sum of myelocytes, young (a co- efficient of 1 is added if the total is less than one) multiplied by the percentage of rod-shaped and seg- mented neutrophils divided by the product of the sum of the percentage of basophils, lymphocytes, and monocytes by the number of eosinophils.
NRR = ((MC + MMC +1) � RSN � SN) /
((Lf + B + M) � E), where MC are myelocytes, MMC - metamyelocytes, RSN - rod-shaped neutro- phils, SN - segmented neutrophils, E - eosinophils, Lf - lymphocytes, M - monocytes, B - basophils. The normal values of NRR are 10.6 � 2.2 rel. U. NRR level 15 -25 rel. U. compensation of EI is indicat- ed, 26 -40 rel. U - subcompensation, more than 40 rel. U - decompensation of the inflammatory process [13].
There is no doubt about the objectivism of evalu- ating EI indicators with the possibility of predicting the complicated course of the early postoperative period using integral intoxication indices calculated from a leukogram. Undoubtedly, this is an urgent and effective way that allows in a short time, according to a general blood test, to assess the initial state of the patient's homeostasis with the determination of EI and to develop tactics for necessary and timely treatment. In addition, according to modern data, the integral indicators of the neutrophil reactive re- sponse have a pronounced informative character. This criterion characterizes the effects of toxins on the change in the ratio index of cells with varying
degrees of nuclear differentiation (rod-shaped and segmented neutrophils). Numerous studies have determined the role of the neutrophil-lymphocyte ratio as a marker of prognosis and severity of chronic diseases such as cirrhosis of the liver, cholecystitis, pancreatitis, chronic obstructive pulmonary disease, as well as in determining the risk of cardiovascular complications in cardiac surgery. The Russian and foreign literature reflects aspects of the dynamics of NLR indicators in oncology, which shows the prog- nostic significance of this indicator [14]. The role of activated neutrophils in the reactivity of the body determines the restructuring of metabolic processes, migration and adhesion, the formation of regulatory and secretory functions. A number of authors be- lieve that an increase in NLR is one of the signs of activation of systemic inflammatory processes in patients with multiple organ dysfunction syndrome, in which, due to increased secretion of inflammatory mediators and cytokines, the role of neutrophils is important. Numerous clinical studies indicate a cer- tain sensitivity of NLR for stratification of the sys- temic inflammatory response of the body in infection and bacteremia, which has an important prognostic value [15].
In addition, it is generally recognized that the
course of the disease largely depends on the reac- tivity of the body, which is largely determined by the immune system. IL-6 and PCT levels are true and chronologically valuable biomarkers of the develop- ment of an inflammatory response. These indicators demonstrate a pronounced stimulation of immune reactions in the structure of the inflammatory re- sponse of the patient's body, which makes it possible to choose a rational and timely therapy tactic. The prognostic significance of the markers is determined by the fact that the increase in indicators indicates the development of an unfavorable course of the disease [16].
The coexistence of tumor and inflammatory pro- cesses in patients with NSCLC is associated with a significant increase in the number of postoper- ative complications, including inflammatory gene- sis, which, accordingly, worsens the prognosis and treatment outcomes of the hospital period of this category of patients. In the studied group of patients, the incidence of purulent-septic complications was
36.5 % of cases. We studied the nature of early post- operative complications in patients with NSCLC.
Of the 222 patients, 141 (63.2 %) had an uncompli- cated course, and 81 (36.5 %) patients had a com- plicated course. Early postoperative complications were diagnosed in 28 (34.5 %) patients. At the same time, 34.6 % of these patients in the early postoper- ative period (the first 3 days after surgery) revealed the development of life-threatening complications: acute respiratory distress syndrome, pneumonia and others. It was revealed that the course of cancer in 81 patients with a complicated course of the malig- nant process was accompanied by the development of endogenous intoxication, determined by an in- creased level of LII and NLR. At the same time, only in 28 patients with a complicated course of the early postoperative period, a significant increase in the indicators of the neutrophil reactive response was recorded, characterizing the inadequacy of compen- sation for EI by physiological detoxification systems of homeostasis, in some cases in combination with a decrease in the reactivity of the body. In patients with severe postoperative complications, the values of inflammatory markers turned out to be indicative: the PCT content exceeded the normal limits by 3.7 times, and IL-6 by 14.3 times, which indicated sys- temic inflammation.
Taking into account the presence of endotoxicosis
and systemic inflammatory response in the stud- ied patients, the complex of standard preoperative preparation should be supplemented with extracor- poreal detoxification. The choice of the therapeutic plasma exchange (TPE) method is justified by its maximum detoxification potential, which allows re- moving all types of toxic substances from the blood- stream, including those associated with proteins. During the TPE procedure, inflammatory mediators actively adhere from the systemic bloodstream to the filter membrane, which reduces the risk of gener- alized systemic inflammation and, as a result, acute damage to the lung parenchyma [17].
The study made it possible to establish that the manifestation of cancer in patients with stage I -IV LC is characterized by the presence of en- dogenous intoxication of varying degrees of com- pensation. In this regard, it is justified to conduct detoxification therapies in the preoperative period in patients with the manifestation of EI in combination with inhibition of the general reactivity of the body and instability of homeostasis. It is most likely that full-fledged and radical surgical treatment in these
conditions can provoke a further decrease in the compensatory potential of homeostasis with the sub- sequent development of systemic disorders, which justifies the need for active preoperative preparation of patients with NSCLC aimed at preventing severe inflammatory complications.
An example of the development of life-threatening complications in this category of patients is the clini- cal case of treatment of a patient with acute damage to a single lung after radical surgery - pneumonec- tomy, described by us in 2020 [18]. The presented clinical example demonstrates the severe course of the postoperative period in a patient 67 years after radical surgical treatment for cancer of the lower
lobe of the left lung cT3N0M0 art. II, with disintegra- tion and abscessing paracancerous pneumonia, a condition after 3 courses of polychemotherapy.
The scope of the operation included an extended combined pneumonectomy on the left, resection of the left atrium, resection of the pericardium, partial pleurectomy, plastic pericardium with polypropylene mesh. The severity of the patient's condition was due to the development of generalized inflammation with acute damage to a single lung on the 1st day of the postoperative period. Respiratory function was com- pensated by artificial lung ventilation (LV) (Hamilton G5 device). Ventilation parameters: respiratory rate - 16 v min.; airway pressure - 10 cm of water; positive pressure at the end of exhalation (Positive pressure at the end of exhalation - PEEP) - 5 cm of water; frac- tion of oxygen in the inhaled air (Fraction of Inspired Oxygen - FiO2) - 80 %; respiratory volume - 330 ml; minute volume of respiration - 5.5 l/min. Against this background, SpO2 is 90 %. Indicators of acid-base state: partial pressure of carbon dioxide in arterial blood (pCO2) 36.5 mmHg; partial pressure of oxy- gen in arterial blood (pO2) 114 mmHg; pH 7.43; base
deficit (BE) 0.2; bicarbonate (HCO3-) 32.4 mmol/L.
According to blood tests: leukocytosis 32 � 109/l; neutrophilosis 80 %; leukocyte activity of endotoxin -
0.67 (Response - 0.92); PCT - 46 ng/ml; IL-6-1860
pg/ml. X-ray examination data: inflammatory infil- tration in the lower lateral sections of the only lung. The probability of death on the MPM II scale (Mor- tality prediction model) was 75.3 %, which required a complex of high-tech intensive treatment with the inclusion of an extracorporeal detoxification program. In this case, the outcome of the hospital treatment period was favorable, the patient was discharged
from the hospital. Saving the life of this patient be- came possible with full-fledged treatment, timely in- clusion in the treatment complex of extracorporeal detoxification. At the same time, it is possible that active preoperative preparation aimed at relieving the severity of EI and optimizing the functional state of the body's own physiological detoxification sys- tems in the preoperative period could prevent the development of such a formidable complication in the postoperative period. However, this dictates the need for confirmation and, therefore, further research.
CONCLUSIONS
It was revealed that the development of inflam- matory complications in patients with NSCLC is ob- served in 36.5 % of cases. In conditions of a com- bination of a tumor disease and an inflammatory component, a decrease in the compensatory capa- bilities of the patient's body can be expected with a high degree of probability and, as a result, the de- velopment of inflammatory complications of varying
severity in the early postoperative period. The data obtained demonstrate that in more than 70 % of pa- tients with newly diagnosed NSCLC, the course of cancer is accompanied by pronounced clinical and laboratory signs of EI with inhibition of protective homeostasis systems.
The presence of initial endotoxicosis in a sub- or decompensated form against the background of a decrease in the general reactivity of the body poses a high risk of developing a generalized inflammatory response to antitumor surgical treatment. This actu- alizes the inclusion of extracorporeal detoxification as an active preoperative therapy in the complex of preoperative preparation of this category of patients. The simultaneous increase in the indicators of LII, NRR and NLR, characterizing the presence of endotoxicosis in conditions of sub- and decompen- sation of EI by their own physiological detoxification systems, determine the need for active preoperative preparation with the inclusion of a component of extracorporeal detoxification, i. e. therapeutic plasma
exchange.
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Information about authors:
Nataliya D. Ushakova - Dr. Sci. (Med.), professor, anesthesiologist and resusticator, National Medical Research Centre for Oncology, Rostov-on- Don, Russian Federation; professor of the Anesthesiology and Resuscitation Department, Rostov State Medical University, Rostov-on-Don, Russian Federation
ORCID: https://orcid.org/0000-0002-0068-0881, SPIN: 9715-2250, AuthorID: 571594, ResearcherID: L-6049-2017, Scopus Author ID: 8210961900
Dmitriy A. Rozenko - Cand. Sci. (Med.), chief of the Anesthesiology and Resuscitation Department, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation
ORCID: https://orcid.org/0000-0002-5563-484X, SPIN: 4658-5058, AuthorID: 917988
Svetlana N. Tikhonova - MD, anesthesiologist and resuscitator, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0001-6919-3523, SPIN: 5141-1656, AuthorID: 1077917
Dmitriy A. Kharagezov - Cand. Sci. (Med.), MD, chief of the Thoracic Surgery Department, National Medical Research Centre for Oncology, Rostov- on-Don, Russian Federation
ORCID: https://orcid.org/0000-0003-0640-2994, SPIN: 5120-0561, AuthorID: 733789
Natalia N. Popova 12 - Cand. Sci. (Med.), MD, anesthesiologist and resuscitator of the Anesthesiology and Resuscitation Department, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation; assistant of the Department of Oncology, Rostov State Medical University, Rostov-on-Don, Russian Federation
ORCID: https://orcid.org/0000-0002-3891-863X, SPIN: 5071-5970, AuthorID: 854895, Scopus Author ID: 57215858399
Contribution of the authors:
Ushakova N. D. - performed writing of the draft; Rozenko D. A. - performed scientific editing;
Tikhonova S. N. - initiated formulation of the research goal, analysis of the results; Kharagezov D. ?. - carried out the development of the research design;
Popova N. N. - provided with clinical support of the study.
