COMORBID PATHOLOGY IN WOMEN WITH BENIGN AND MALIGNANT TUMORS OF THE UTERINE BODY Текст научной статьи по специальности «Клиническая медицина»

UDC: 618.14-006

COMORBID PATHOLOGY IN WOMEN WITH BENIGN AND MALIGNANT TUMORS OF THE UTERINE BODY

A.A. Firman1, A.V. Efremov1, O.J. Uzakov2, A.A. Masybaeva3

!INCO, the Hyperthermia research institute, Novosibirsk, Russian Federation international Higher School of Medicine, Bishkek, Kyrgyz Republic 3Kyrgyz Scientific Center for Human Reproduction, Bishkek, Kyrgyzstan

Abstract

The aim of the work was to analyze comorbidpathology in women with benign and malignant uterine diseases. 436 women were examined, of which thefirst group consisted of 101 patients diagnosed with uterine fibroids. The second group included 290 women with uterine body cancer. Control group - 45 healthy women of the sa age. Anamnestic, instrumental and laboratory research methods were used. In the group of sick women, significantly more frequent occurrence of gynecological pathology was revealed; the frequency of hypertension, chronic cholecystitis, obesity and type 2 diabetes mellitus was higher. The highest incidence of these somatic diseases was recorded in the group of women with uterine body cancer.

Keywords: cancer of the uterine body, uterinefibroids, comorbidpathology.

АЯЛДАРДЫНКОМОРБИДДИК ПАТОЛОГИЯСЫНДАГЫ ЖАТЫН ДЕНЕСИНИН ЗАЛАЛСЫЗ ЖАНА ЗАЛАЛДУУ

ШИШИКТЕРИ

А.А. Фирман1, А.В. Ефремов1, О.Ж. Узаков2, А.А. Масыбаева3

Сибирь гипертермия илим изилдее институту АКэУ, Новосибирск, Россия Федерациясы

2Эл аралык Жогорку Медициналык Мектеби, Бишкек, Кыргызстан

3Адамдын репродукциясы боюнча Кыргыз илимий борбору, Бишкек, Кыргызстан

Аннотация

Иштин максаты аялдардын жатынынын залалсыз жана залалдуу оорулары менен коштолгон коморбиддик патологиясын талдоо болгон. 436 аял текшерилди, анын ичинен биринчи топко жатындын миомасы диагнозу коюлган 101 бейтап кирет. Экинчи топко жатынрагы менен ооруган 290 аял кирген. Контролдук - бирдей курактагы 45 дени сак аялдар. Анамнездик, аспаптык жана лабораториялык изилдее ыкмалары колдонулган. Оорулуу аялдардын тобунда гинекологиялык патологиянын, гипертониянын, енекет холециститтин, семирYYHYн жана 2-типтеги кант диабетинин квп кездешкени байкалган. Бул соматикалык оорулардын эц жогорку керсеткYЧY жатынын денесининрагы менен ооруган аялдардын тобунда катталган.

Ачкыч свздвр: жатын денесинин рагы, жатын денесинин миомасы, коморбиддик патология.

КОМОРБИДНАЯ ПАТОЛОГИЯ У ЖЕНЩИН С ДОБРОКАЧЕСТВЕННЫМИ И ЗЛОКАЧЕСТВЕННЫМИ ОПУХОЛЯМИ ТЕЛА МАТКИ

А.А. Фирман1, А.В. Ефремов1, О.Ж. Узаков2, А.А. Масыбаева3

!АНО НИИ гипертермии. Новосибирск, Российская Федерация Международная высшая школа медицина, Бишкек, Кыргызстан 3Кыргызский научный центр репродукции человека, Бишкек, Кыргызстан

Аннотация

Целью работы стал анализ коморбидной патологии у женщин с доброкачественными и злокачественными заболеваниями матки. Было обследовано 436 женщин, из которых первую группу составили 101 пациентка с диагнозом миома тела матки. Во вторую группу вошли 290 женщин с раком тела матки. Контроль - 45 здоровых женщин той же возрастной группы. Применялись анамнестические, инструментальные и лабораторные методы исследования. В группе заболевших женщин выявлена достоверно более частая встречаемость гинекологической патологии, выше частота гипертонической болезни, хронического холецистита, ожирения и сахарного диабета 2-го типа. Самая высокая частота встречаемости этих соматических заболеваний регистрировали в группе женщин, больных раком тела матки.

Ключевые слова:рак тела матки, миома тела матки, коморбидная патология.

Introduction

The ideas about oncogenesis have undergone a significant evolution over the past decades, and to a large extent not only due to fundamental theoretical generalizations, but also due to advances in the innovative technologies. The existing vision is based on the fundamental concept of the oncogene, and technological innovations largely reflect the progress associated with the study of DNA and the analysis of mutational mechanisms that cause damage to it. There are several such mechanisms. Firstly, oncogenes initiate LPO processes and produce active radicals and metabolites of oxygen and nitrogen (Klauning J.E., Kameldulis L.M., 2004); as a result, a decrease in the activity of the main

enzymatic antioxidants under conditions of oxidative stress, which are the basis of intracellular protection against free radical damage ( Menshikova E.B. et al., 2008). Secondly, these are disorders in microelement balance, a number of which are coenzymes of various enzyme systems, including pro-/antioxidant ones, and, moreover, the activity of these enzymes directly depends on the content of microelements (Barandier C., Leiris J ., 1998). Thirdly, this is an imbalance between the secretion of protumor (IL-6), antitumor (IL-2), and regulatory (IFN-) cytokines (Antonov V.G., Kozlov V.K., 2004). Uterine body cancer and myoma are the tumors with a complex mechanism of tissue transformation, in the occurrence of which

endocrine and metabolic disorders play a role, conditioned by damage to the ne uro humo ral s ys te ms , whic h are responsible for the correlation between various organs of the reproductive and endocrine systems in particular. (Bershtein L.M. , 2004; Emons G. et al., 2010).

At the same time, the analysis of concomitant pathology, which is detected in the process of diagnosing an oncological disease, can help in the interpretation of initiating mechanisms and direct preventive measures in the right direction.

The aim of this work was to analyze comorbid pathology in women with benign and malignant uterus diseases.

Research methods used were, first of all, anamnestic, and the necessary instrumental and laboratory methods.

In accordance with the goal, 436 women were examined, of which the first group consisted of 101 patients with a diagnosis of uterine fibroids (UF). In 63.4% of patients in this group, ultrasound revealed single myomatous nodes, in 36.6% -multiple. The overall size of the uterus corresponded to 5-6 weeks of pregnancy in 59.4% of patients, 7-9 weeks - in 41.6%. More than 50% of patients did not present complaints typical for patients with UF; 30.6% noted painful menstruation, and 26.7% noted heavy and prolonged menstruation.

The second group included 290 women with uterine body cancer (UBC). According to the de gree of tumo r differentiation (Pathological Anatomical Diagnosis..., 1993), the group consisted of 34.5% of patients with highly differentiated, 33.8% with moderately differentiated and 31.7% with poorly differentiated adenocarcinoma.

Clinical examination of patients with

uterine body cancer and fibroids was carried out in accordance with the traditional scheme, including a thorough history taking, ge neral and sp ecial gynec ological examination. As additional methods of examination, echography of the pelvic organs (M-echo), hysteroscopy, separate diagnostic curettage of the mucous membrane of the cervical canal and mucous membrane of the uterine body were conducted, and if medically indicated -laparoscopy. The final diagnosis was made taking into account the data of histological examination of tissues removed during the uterus operation. The group with DS: "uterine fibroids" included patients with the size of the tumor lesion from 6 to 9 weeks of pregnancy - 41 women, with sizes from 10 to 11 weeks - 20 women, from 12 and more weeks - 40 women.

The distribution by morphological stages of the disease showed that 67.6% of patients have stage I of the disease; 20.6% -stage II, 7.4% - stage III and 4.4% - stage IV.

The control group included 45 women of the same age as the patients of the first and second clinical groups, but without a history of tumor diseases of the uterus and other internal organs.

All studies were performed in accordance with the Declaration of Helsinki of the World Medical Association "Ethical principles for medical research involving human subjects" and "Rules of clinical practice in the Russian Federation", approved by the Order of the Ministry of Health of the Russian Federation №266 dated June 19, 2003.

Research outcomes

The age of UBC patients varied from 38 to 69 years; patients with UF - from 33 to 67 years; women in the control group - from 34 to 65 years (table 1).

Table 1. Age characteristics of patients with the uterine boc y cancer and fibroids

Age (years) UBC (n=290) UF (n=101) Control (n=45)

Average age 63,0 ± 5,5 58,0 ± 4,0 57,0 ± 5,0

under 40 3,0% 15,0% 7,0%

from 41 to 50 17,0% 35,0% 26,0%

from 51 to 60 39,0% 40,0% 58,0%

Older 61 41,0% 10,0% 9,0%

It should be noted that the majority of UBC patients were in the postmenopausal period. It was observed that in patients of older age groups (51-60, older than 61 years), low-differentiated forms of UBC were significantly more often recorded, which is consistent with the data of other researchers who note a high frequency of UBC against the background of a long period of postmenapause and pronounced atrophic processes of the endometrium (Polyakova V.A., 2001).

The maximum number of UBC was observed in the age groups of 51-60 years and older than 61 years, the minimum - in

the groups under 40 years, in the group of patients with UF, respectively: the maximum - in the age groups from 41 to 60 years, and the minimum - in the groups older than 61 years.

UBC was diagnosed before surgery in 264 (91.0%) patients; after surgery - in 26 (8.9%) patients. The division of patients with UBC according to the morphological stages (signs) of the disease was carried out according to the International Classification (Pathological Anatomical Diagnosis of Human Neoplastic Diseases, 1993). In most patients with UBC, the first and the second stage of the disease were diagnosed (table 2).

Table 2. Distribution of patients with UBC by the stages of the disease

Stage I Stage II Stage III Stage IV

(n = 98) (n = 30) (n = 11) (n= 6)

IA IB IC IIA IIB IIIA IIIB IVA IVB

n, n, n, n, n, n, n, n, n,

% % % % % % % % %

64 108 24 25 34 16 7 6 6

22,1% 37,2% 8,3% 8,9% 11,7% 4,8% 2,6% 2,2% 2,2%

The assessment of the relationship between the stage of the disease and the age of women did not reveal significant statistical patterns.

Among the risk factors for intrauterine tumor processes, many researchers name primary infertility, no

history of childbirth, previous abortions, anovulatory uterine bleeding in premenapause, late menapause, genital endometriosis, postmenopausal estrogen intake, aggravated heredity for cancer of the reproductive system, obesity, hyperlipidemia, diabetes, hypertension

(Bohman Ya.V., 2002).

When evaluating the features and nature of changes in menstrual and reproductive functions in patients with UBC and UF, certain patterns were identified in the disorder of these functions (table 3).

It was established that in the group of

patients with UBC and UF, menstrual irregularities were noted in the anamnesis significantly more often than in the control group. In the group of women with UBC, there was a later onset of menopause than in other groups.

Table 3. Features of menstrual function in patients with uterine cancer and fibroids

Indicators UBC (n=290) UF (n=101) Control group (n=45)

Age at menarche (years) 13,3± 2,1 12,8 ±1,3 12,7 ± 1,4

Menstrual disorders (%) 46,2% 64,2% 22,1%

Age at menapause (years) 53,2 ± 2,7 50,4 ± 1,8 48,9 ± 2,3

Duration of menstrual 28,1 ± 0,3 26,5 ± 0,5 27,4 ± 0,4

cycle (years)

Duration of 0,8 ± 0,1 0,6 ± 0,2 0,7 ± 0,1

perimenapause (years)

Duration of menapause (years) 9,6 ± 4,2 7,7 ± 3,4 10,4 ± 3,4

When assessing the factors characterizing the state of reproductive health, other features were also revealed (Table 4).

Table 4. Features of reproductive function in patients with uterine body cancer and fibroids

Indicators UBC (n=290) UF (n=101) Control group (n=45)

Average number of deliveries 2,3±0,4 1,6 ± 0,3 2,2 ± 0,3

Average number of abortions 8,1 ± 1,4 5,6 ± 2,0 4,2 ± 1,5

One delivery 63 (21,7%) 29 (28,7%) 22 (49,0%)

2 - 3 deliveries 161 (55,5%) 47 (46,5%) 16 (35,5%)

4 and more deliveries 14 (4,8%) 17 (16,8%) 4 (8,9%)

1 - 4 abortions 31 (10,7%) 25 (24,8%) 18 (40,0%)

5 - 9 abortions 149 (51,4%) 37 (36,6%) 12 (26,6%)

10 - 15 abortions 30 (10,3%) 29 (28,7%) 6 (13,3%)

More than 15 abortions 21 (7,2%) 7 (6,9%) 3 (6,7%)

Criminal abortions 9 (3,1%) 6 (5,9%) 2 (4,4%)

Spontaneous miscarriages 35 (12,1%) 28 (28,0%) 3 (6,7%)

It is known that the susceptibility of the uterine receptor apparatus to the estrogens and progesterone exposure plays a significant role in the pathogenesis of UBC. Abortions lead to significant violations of this link of pathogenesis. In our studies, the majority of patients with UBC and UF had a history of abortion. On average, 1 patient with UBC accounted for 8.1 1.4 abortions, in 61.7% of women this number was from 5 to 15, and in 7.2% it exceeded 15. It should be noted that in the groups of women with UBC and UF, the average number of abortions per woman was higher than that of women in the control group. In general, the revealed pathology testifies to the insufficient attention of women to their

Table 5. The frequency and nature of gynecological diseases in patients with UBC and UF

health.

The most severe consequences for the uterus receptor apparatus occur after criminal abortions. In anamnesis, 3.1% of women suffering from UBC had criminal abortions, and 12.1% of women had spontaneous miscarriages.

Data on previous gynecological diseases are important for the identification of UBC risk factors. Thus, it was found that among women of the two main clinical g r o u p s ( U B C a n d U F ) c h r o n i c salpingoophoritis and endometritis were found much more often than in the control group (Table 5).

Gynecological diseases UBC (n=290) UF (n=101) Control group (n=45)

Cervical erosion 81 (28,0%) 32 (31,7%) 12 (24,0%)

Colpitis, vaginosis 41 (13,5%) 29 (28,7%) 10 (22,2%)

Chronic salpingoophoritis 125 (42,3%) 47 (46,5%) 14 (28,0%)

Chronic endometritis 37 (12,7%) 8 (7,9%) 3 (6,7%)

Benign ovarian tumors 13 (4,1%) 10 (9,9%) -

Uterine fibroids 110 (37,9%) 101(100%) -

Genital endometriosis 30 (10,5%) 10 (9,9%) 4 (8,9%)

Primary infertility 41 (14,2%) 4 (3,9%) 1 (2,2%)-

Secondary infertility 15 (5,1%) 10 (9,9%) 3 (6,7%)

The incidence of diseases such as uterine fibroids and genital endometriosis in women in the main clinical group was significantly higher (p < 0.05) than in women in the control group. This once again testifies to the unity of pathogenetic mechanisms in hormone-dependent gynecological diseases, which include UBC.

It is believed that the presence of uterine fibroids in postmenopausal women is a kind of tumor marker (Bohman Ya.V.,

2002). Thus, in the group of women with UBC, the incidence of uterine fibroids was 37.9%, which significantly differed from that in the control group (p < 0.05).

When studying the nature of chronic somatic pathology occurring in the anamnesis of UBC and UF patients (Table 6), it was found that the frequency of diseases of the respiratory, digestive, urinary and nervous systems did not have statistically significant differences in the compared groups (p > 0, 05).

Table 6. The frequency and nature of chronic somatic diseases in patients with UBC and

UF

Chronic diseases UBC (n=290) UF (n=101) Control group (n=45)

Cardio-vascular system 140 (48,3%) 25 (24,7%) 7 (15,5%)

Hypertonic disease 108 (37,2%) 30 (29,7%) 11 (24,0%)

Respiratory organs 42 (14,5%) 20 (19,8%) 9 (20,0%)

Gastroenteric tract 60 (20,7%) 12 (11,9%) 8 (17,7%)

Liver disease 58 (20,1%) 18 (17,8%) 5 (11,1%)

Urinary system 74 (25,5%) 29 (28,7%) 10 (22,2%)

Endocrine system 12 (4,1%) 5 (4,9%) 5 (11,1%)

Obesity 249 (85,8%) 59 (58,4%) 15 (37,5%)

Diabetes mellitus 45 (15,5%) 7 (6,9%) 1 (2,2%)

Diseases of the nervous system 24 (8,2%) 10 (9,9%) 5 (11,1%)

At the same time, in the main clinical groups of women with UBC and UF, the incidence of such diseases as hypertension, chronic cholecystitis, obesity, and type 2 diabetes mellitus was significantly higher (p < 0.05) than in the control group. The etiology of these diseases is based on systemic disorders of hormonal and metabolic regulation, and there is a state of chronic stress and / or non-compliance with recommendations for a healthy lifestyle: overeating and eating disorders, low physical activity, psycho-emotional stress. And again, neglect of one's health, low sanitary and hygienic literacy are revealed. At the same time, it should be noted that the highest incidence of these somatic diseases was recorded in the group of women with

UBC, which allows us to consider the presence of these diseases as a risk factor in the development of UBC.

When assessing the clinical indicators of fat metabolism, we found that in women suffering from benign and malignant uterus neoplasms, the incidence of obesity is higher than in women in the control group (p < 0.05). Among patients with UBC, pathological excess of body weight was observed significantly more often than among patients with UF - in 85.8% and 58.4% of cases respectively.

Analysis of anamnestic data on the existing oncogynecological pathology in close relatives revealed the following results (Table 7).

Table 7. Hereditary predisposition to the uterus oncological diseases in patients with

UBC and UF

Oncological pathology in close relatives UBC (n=290) UF (n=101) Control group (n=45)

uterine fibroids 35 (12,1%)0 25 (24,7%) 5 (10,0%)

UBC 25 (8,6%) 10 (9,9%) 2 (4,4%)

Cancer in another location 50 (17,2%) 6 (5,9%) 3 (6,6%)

NA 180 (62,1%) 60 (59,4%) 35 (77,7%)

For example, differences were found in the incidence of uterine fibroids in patients with UBC and UF, with a predominance in the latter group (12.1% and 24.7%, respectively; p < 0.05); the frequency of cases of cancer of other localization was significantly higher in patients with UBC (17.2% and 5.9%, respectively; p < 0.05). UBC was also registered more often in the group of patients with UBC and UF than in the control group (8.6%, 9.9% and 4.4%, respectively).

Thus, patients with intrauterine benign and malignant diseases quite often had a hereditary burdened history of tumor pathology. At the same time, a hereditary burdened anamnesis was more often observed in the group of patients with UBC than in the group of patients with UF and the control group.

Conclusions

1. In the development of benign and malignant neoplasms, a gynecological history is of a primary importance: the number of abortions, including criminal ones, chronic salpingoophoritis and endometritis were indicated more often in the group of sick women.

2. In women with diagnosed uterine body cancer and uterine fibroids, compared with women in the control group, the incidence of hypertension, chronic cholecystitis, obesity and type 2 diabetes was higher. The highest incidence of these somatic diseases was recorded in the group of women with uterine body cancer.

3. The hereditary history of the uterine body cancer was burdened in the group of diseased women significantly more often than in the control group.

4. Comorbid pathology may be a predisposing factor in the development and

manifestation of neoplasm diseases of the uterine body, especially of the uterine body cancer.

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