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ASSESSMENT OF THE STATE OF IMMUNITY IN PATIENTS WITH
TUMORS
Said Abdurakhmanovich Babayev
Shavkat Satiboldievich Bekturdiev
Nodir Mahammatkulovich Rakhimov
Dilfuza Zuhriddinovna Jalalova
Dildora Zuhriddinovna Yusupova
Shakhnoza Shavkatovna Shakhanova
Received 15
th
Apr 2021,
Accepted 17
th
May 2021,
Online 6
th
June 2021
1
PhD, Associate Professor, Department
of Ophthalmology, Samarkand Medical
Institute, Uzbekistan
2
PhD, Head of the Department of
Ophthalmology at Samarkand Medical
Institute
3
Associate Professor of Oncology
Department of Samarkand Medical
Institute
4
PhD, Head of Ophthalmology
Department of the 1st Clinic of
Samarkand Medical Institute
5
Senior lecturer, Department of
diseases and traumas of maxillofacial
area of Tashkent
Institute of Dentistry
6
Assistant of Department of Oncology
of Samarkand Medical Institute
ABSTRACT
:
Cellular immune status provides information
on the relative and absolute numbers of cell populations
(monocytes,
granulocytes
and
lymphocytes)
and
subpopulations of lymphocytes in the blood. The human
div is equipped with a complex defence mechanism whose
primary function is to distinguish foreign antigens from the
div's own antigens and initiate an appropriate immune
response. Historically, innate immunity differs from
adaptive immunity, and these systems work closely
together. The immune response is mediated by both
cellular components (B- and T-lymphocytes, NK cells,
macrophages/monocytes,
granulocytes
and
antigen-
presenting cells) and humoral components (antibodies,
complement factors, cytokines and other soluble effector
molecules). [12,13].
Keywords
:
immunity, orbital tumors, leukocyte formula
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Both external factors (climatic, physical, mechanical, etc.) and the state of the organism itself
(inflammatory processes, metabolic disorders, regulatory nervous influences, changes in connective
tissue) play a role in the emergence and development of neoplasms [1].
Tumor transformation of one or several cells causes the div to respond to the elimination of foreign
information. The div's response to a developing tumor is carried out using humoral and cellular
mechanisms, which can be determined by counting the number of peripheral blood leukocytes [2,3].
The leukocyte blood count is an indicator of the div's nonspecific response, which quite fully reflects
the typical processes in the immunity system in health and disease. Leukocytogram outside the
expanded immunogram can serve as an immunologically informative component and guideline for
determining the functional state of immunity in general and in some diseases: toxic infection, sepsis,
hypo- and avitaminosis, rheumatism, alimentary exhaustion, etc. [4].
Changes in the leukocyte formula in the dynamics of the pathological process, the level of leukocytes,
lymphocytogram contribute to assessing the severity of the patient's condition, determining the amount
of therapy, assessing the patient's response to surgery, predicting the effectiveness of therapy and the
course of the rehabilitation period [5].
The choice of the ratio of certain cellular elements is due to their closest functional relationship in the
system of cellular cooperation [6,7,8]
From the point of view of various authors, the most significant of the many integral hematological
indicators are: leukocyte index (LI), leukocyte intoxication index (LII), leukocyte shift index (LSI),
leukocyte to ESR ratio, lymphocyte-granulocyte index (LGI), general index (GI), the index of the
ratio of neutrophils and lymphocytes (IRNL), the index of the ratio of neutrophils to monocytes
(IRNM), the index of the ratio of lymphocytes to monocytes (IRLM), the index of the ratio of
lymphocytes and eosinophils (IRLE), the coefficient of redundancy (CR) [9, 10,11]
Objective
: to study changes in hematological indices in patients with various types of orbital tumors.
Materials and methods
:
Integral hematological parameters were determined in 179 patients with primary orbital tumors.
Men were 42.5%, women - 57.5%, mainly (42.9%) of the most working age: from 40 to 60 years.
Benign tumors accounted for 69.2%, malignant - 30.8% of cases.Among the primary benign tumors of
the orbit, tumors of neurogenic origin predominated - 19.5%. Vascular tumors accounted for 15.4%,
epithelial tumors (mainly of the lacrimal gland) - 9.4%. Less common were fibrous histiocytoma -
3.4%, fibroma - 1.5%, osteoma and lipoma - 1.2% each, etc. Congenital cysts and false tumors
considered in the group of primary tumors were observed in 16.5% and 32, 2% of cases (Diagram 1).
Table 1 Patient characteristics
Parameter
Numbers of patients Percentage (%)
Age
mean
50 year
-
Range
25–85 year
-
Gender
male
76
42,5
female
103
57,5
Tumortype
malignant
56
31,2
benigntumors 123
68,8
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Diagram 1 distribution of patients with benign tumors
Among malignant neoplasms, lymphomas prevailed
rhabdo-myosarcomas - 4.80% are much less common.
(adenocarcinoma, adenocarcinoma in pleomorphic adenoma) were observed in 22.80%, malignant
paraganglioma - 4.70%, malignant histiocytoma
Diagram 2 distribution of patients with malignant tu
All patients underwent standard clinical and instrumental studies, including visometry, biomicroscopy,
ophthalmoscopy, exophthalmometry, perimetry. Removed neoplasms were examined by
morphological methods.
39.50%
0.00%
5.00%
10.00%
15.00%
20.00%
25.00%
30.00%
35.00%
40.00%
45.00%
MALIGNANT NEOPLASMS
Lymphomas
adenocarcinoma
19.50%
15.40%
0.00%
5.00%
10.00%
15.00%
20.00%
25.00%
BENIGN NEOPLASMS
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Diagram 1 distribution of patients with benign tumors
Among malignant neoplasms, lymphomas prevailed - 39.50%, undifferentiated sarcomas
4.80% are much less common. Malignant tumors of the lacrimal gland
(adenocarcinoma, adenocarcinoma in pleomorphic adenoma) were observed in 22.80%, malignant
4.70%, malignant histiocytoma - 3.8%, etc. (Diagram 2).
Diagram 2 distribution of patients with malignant tumors
All patients underwent standard clinical and instrumental studies, including visometry, biomicroscopy,
ophthalmoscopy, exophthalmometry, perimetry. Removed neoplasms were examined by
11.20%
4.80%
22.80%
4.70%
1
MALIGNANT NEOPLASMS
undifferentiated sarcomas
rhabdo-myosarcoma
malignant paraganglioma
histiocytoma
15.40%
9.40%
3.40% 1.50% 1.20%
1
BENIGN NEOPLASMS
May-June2021
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Diagram 1 distribution of patients with benign tumors
39.50%, undifferentiated sarcomas - 11.20%,
Malignant tumors of the lacrimal gland
(adenocarcinoma, adenocarcinoma in pleomorphic adenoma) were observed in 22.80%, malignant
mors
All patients underwent standard clinical and instrumental studies, including visometry, biomicroscopy,
ophthalmoscopy, exophthalmometry, perimetry. Removed neoplasms were examined by
3.80%
myosarcoma
Neurogenic tumors
Vascular tumors
Epithelial tumors
histiocytoma
fibroma
lipoma
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Research results
.Based on the calculation of the leukocyte formula, it was found that LII
significantly (P <0.05) increases in all patients with orbital tumors, regardless of genesis, indicating
the development of endogenous intoxication of a nonspecific nature.
Table 2 Comparative characteristics of leukoformula indicators for various orbital tumors
Malignant
tumor
Benign tumor
Parameter
HR (95% CI)
HR (95% CI)
Leukocyte index (LI)
1,088 (0,745 -
1,589)
0,895 (0.77-1,02)
Leukocyte intoxication index (LII)
1,244 (0,928 -
1,669)
1,18 (0,86-1,5)
Leukocyte shift index (LSI)
1,921 (1,19 3–
3,092)
3,155 (2,168 -
4,591)
Lymphocyte – granulocyte index (LGI)
2,492 (1,876 -
3,310)
1,715 (1.200 -
2.451)
Lymphocyte to eosinophil ratio (LTER)
1,558 (1,190 -
2,040)
1,385 (1,049 -
1,829)
Lymphocyte to Monocyte Ratio Index (LTMR)
0,81 (0,70-0,92)
1,352 (1,037 -
1,764)*
Index of the ratio of neutrophils and lymphocytes (IRNL)
1,676 (1,271 -
2,209)
1,392 (1,045 -
1,855)
Neutrophil to monocyte ratio (NTMR)
0,5 (0,34-0,7)
1,348 (0,954 -
1,904)*
General index (GI)
0,924 (0,712–
1.200)
0,67 (0,51-0,83)
Index of the ratio of leukocytes and ESR (erythrocyte
sedimentation rate, sed rate)
3,54 (2,85 – 4,22) 2,93 (2,56-3,3)
Abbreviations: CI, confidence interval; Heart rate, hazard coefficient.
* Significantly (p <0.05).
An increase in LII in pseudotumor by 1.5 times is associated with an inflammatory reaction in the
tissues. A significant 1.8-fold increase in this indicator in individual patients (16%) with malignant
tumors of the orbit (malignant lymphoma-lymphoma-lymphocytic type and rhabdomyosarcomas) is, in
our opinion, a sign of an increase in the process of tissue decay of tumors.
An increase in LIESR in malignant ones up to - 3.54 ± 0.45 compared with benign neoplasms - 2.93 ±
0.32 - indicates an increase in the concentration of antibodies and autointoxication associated with the
autoimmune process. This is also confirmed by an increase in GI by 1.4 times in patients with
malignant tumors (malignant lymphomas, adenocarcinomas).
The simultaneous increase in LII and LIESR, revealed by us, speaks of the depletion of the T-
lymphocytic link of immunity. The absence of changes in the indicators of LI and IRNL (the ratio of
lymphocytes and segmental-nuclear neurophils), indicating a positive correlation of their content in the
peripheral blood, may be associated with damage to the specific and nonspecific defense of the div,
regardless of the type of tumor. The data of changes in the integral hematological parameters in
patients with orbital tumors are presented in Table 2.
A significant 2-2.5-fold increase in NTMR in all types of tumors is considered by us as an increase in
the activity of the microphage system against the background of a pronounced effector response. A
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1.2-fold increase in LTER, which is more typical for patients with benign orbital tumors, is considered
by us as a manifestation of delayed-type hypersensitivity.
An increase in LSI (by 2.2-2.6 times), also more pronounced in benign tumors, indicates, as we
believe, the predominance of the affector link in the immunological process. CI is a generalizing
indicator of the quantitative composition of peripheral blood leukocytes increased by 1.2-1.1 times
compared to the norm, which, in our opinion, speaks of the adaptation of the div to the tumor process
in the orbit. As our studies have shown, in the leukocytogram of patients who applied in the initial
period of development of malignant tumors (1-3 months) and in the period from 2 to 4 years, the
highest LIESR is noted, and with a long-term illness - more than 10 years - these indicators decrease to
normal level, which may be associated with the chronization of the process and adaptation of the
organism, or with the characteristics of a long-existing tumor.
With pseudo tumor, the indicators of LIESR, LSI, GI reach the norm in patients who are sick for more
than a year, with benign tumors - more than 2-4 years, that is, during this period, according to these
indicators, pseudotumor and benign tumors differ from malignant neoplasms, which also indicates, in
our opinion, on the adaptation of the div, but at an earlier date.
We did not reveal a significant difference in indicators in the groups of patients with various types of
orbital tumors depending on age, only in patients over 60 years old with malignant tumors we noted a
decrease in LI and an increase in CI, which apparently characterizes a decrease in the activity of
polynuclears and the development of breakdown in the peripheral blood cell system. In benign
tumors, we found an increase in ISLM, with pseudotumor, an increase in addition to ISLM, and
ISNM, which is associated with inhibition of the macrophogenic and effector links of immunity.We
did not reveal any gender dependence in patients with malignant tumors in comparison with the initial
data, but in women LIESR and GI were higher in benign tumors, LII and LSI in pseudotumor, which,
in our opinion, indicates a decrease in the cellular component of immunity in these types tumors in
female patients.
Integral hematological indices of benign tumors were significantly higher than normal (P <0.05), with
the exception of LI, ILH, IRNL; in patients with false and malignant do not differ from the norm LI,
ILH, LTER; the rest of the indices were significantly higher than the norm.
Significant differences (P <0.05) between benign and false tumors are noted in the LII and LTER
indicators, between benign and malignant there are differences in the NTMR and ISLM indicators (P
<0.05). There were no statistically significant differences (P> 0.05) in hematological parameters
between false and malignant tumors. The correlation coefficient between LII, LTER, NTMR and
ISLM and the diagnosis “benign tumor” is 0.291, 0.265, 0.238 and 0.197, respectively; between the
indicated indices and the diagnosis “false tumor” - 0.114, 0.276, 0.192 and 0.278, respectively, and
between the listed indices and the diagnosis “malignant tumor” the correlation coefficient was 0.363,
0, 273, 0.269 and 0.283, that is, between the indicated indices and the diagnosis, according to our data,
mainly a weak correlation.
Discussion.
To predict a marker of infection and inflammation, the indicators of total and differential
leukocyte count are historically considered. Despite this, its role has gone beyond the assessment of
infectious processes, and today it is used as a prognostic marker to measure the results of the course
and treatment of a tumor. The association between inflammation and tumors has long been known,
compelling recent evidence suggesting a strong association between peripheral inflammatory cells
before treatment and prognosis in different types of tumors [12,13,14,15].
Inflammatory processes lead to a chronic oxidative process and generate oxygen free radicals that
stimulate the emergence, development and progression of tumors [16]. Here, we retrospectively
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studied orbital tumors, based on medical records, to assess the prognostic values of the total number
of leukocytes, neutrophils, lymphocytes, monocytes in a comparative aspect with other clinical factors.
Our results confirmed the conclusions that factors such as the lymphocyte-to-monocyte ratio (ISRM
and the neutrophil-to-monocyte ratio (ISNR)) were associated with benign tumors, while the leukocyte
intoxication index (LII) was an unfavorable prognosis for patients with orbital tumors. More
importantly, we found that an increased ratio of neutrophil lymphocytes and monocyte counts were
significantly associated in benign tumors, while at the same time in malignant processes had a poor
prognosis, which is confirmed by SaurabhBobdey (2017) with lower overall survival and did not
depend on other variables to predict prognosis for patients with oral cancer [11].
These results are consistent with other published studies that indicate a role for monocyte counting
(Tsai et al, n = 213) [12] and Perisanidis et al, n = 97 in predicting oral cancer patients [17].
There is evidence that in advanced cancer, the systemic host immune response is an important
independent predictor of outcome, and measurements of the systemic inflammatory immune response
before treatment can be used to independently predict cancer survival [17].
Sasaki A (2007) and colleagues studied the preoperative absolute monocyte count in patients who
underwent liver resection for hepatocellular carcinoma and in patients who underwent liver surgery for
colorectal metastasis and found that the absolute monocyte count before treatment was independent a
prognostic indicator of tumor recurrence and survival [18].The monocyte index as an independent
prognostic indicator has been obtained in breast cancer [19], Hodgkin's lymphoma [20], rectal cancer
[18], and ovarian cancer [21].
Some authors have reported that neutrophils and other cells such as macrophages secrete factors that
promote tumor growth, including vascular endothelial growth factor [22], IL-8 [23], matrix
metalloproteinases and elastaseare likely to contribute to stimulation of the tumor microenvironment.
Conclusion
Thus, on the basis of calculating the ratios of the elements of the general blood test in patients with
orbital tumors, it was revealed that, regardless of the origin of the neoplasm in the patient's div,
against the background of suppression of the functions of effector cells, complex disorders of the
microphage-macrophage system, endogenous intoxication develops, accompanied by delayed-type
hypersensitivity. The duration of the tumor process, the age and gender of the patients have no
significant effect on the level of integral hematological indices. A correlation has been established
between some indices and a tumor diagnosis (benign, false, malignant), which allows us to
recommend the determination of integral hematological indices as additional diagnostic tests for
various types of orbital tumors, especially benign and malignant ones.
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