Vol 51, No 6 (2023)

Background: Cervical cancer is the most common type of female genital malignancies. In Russia, its incidence is 17 to 19 cases per 100,000 of female population. Cervical cancer is characterized by high activity, rapid development of radio/chemoresistance and unfavorable prognosis. To assess the risk of recurrence, metastasis and choice of the optimal treatment strategy, factors related to the disease progression are under study. Vascular endothelial growth factor (VEGF) overexpression is related to tumor angiogenesis and poor outcome in various cancer types, including cervical cancer.

Aim: To study an association between the rs2010963 polymorphism of the VEGFA gene and risk of development and progression of cervical cancer.

Materials and methods: This case-control study included 120 women (aged 49 [42; 65] years) with cervical cancer stage I-II and 112 women without cervical or other types of cancer. Based on the results of histological examination, two subgroups were formed: the one with tumor emboli (TE+) in the tumor vasculature and surrounding tissues (n = 41, 34.17%) and the other without tumor emboli (TE-) (n = 79, 65.83%). The polymorphic DNA loci of the rs2010963 VEGFA gene were analyzed by real time polymerase chain reaction.

Results: In the patients, cervical cancer has associated with the VEGFA gene allelic polymorphism rs2010963 (χ² = 5.47; p = 0.021). The minor C allele increased risk of cervical cancer by 1.6-fold (odds ratio (OR) 1.58, 95% confidence interval (CI) 1.08-2.31), and the ancestral G allele reduced the cervical cancer probability (OR 0.63, 95% CI 0.43-0.93). The genotypes distribution in the dominant model (GG and GC + CC) confirmed the association of the rs2010963 VEGFA gene polymorphism with cervical cancer (χ² = 4.73; p = 0.031), specifically, if there was a minor C allele in the genotype (GC + CC). We found that the association of the rs2010963 VEGFA gene polymorphism with TE in the tumor vessels and surrounding tissues was a predictor of unfavorable progression and metastasis of cervical cancer (χ² = 3.94; p = 0.049). The minor C allele increased the risk of TE by 1.7-fold (OR 1.72, 95% CI 1.004-2.98), whereas the ancestral G allele reduced this chance (OR 0.58, 95% CI 0.34-0.996).

Conclusion: The C allele of the rs2010963 polymorphism of the VEGFA gene is a risk factor for cervical cancer, as well as a risk factor for the development of tumor emboli.

Background: With the evolution of hormonal contraception, such as implementation of low dose agents, new regiments and administration routes of contraceptives, the risk of thrombotic complications persists, although is decreasing. The search for an available test for hemostasis assessment, which would allow for the prediction of thrombotic complications in high risk patients, remains relevant. Global tests for hemostasis assessment, such as thrombin generation test and thrombodynamics test, are attracting the specialists' attention due to the possibility of a quick integrative assessment of plasma hemostasis, especially during choice and tailoring of an optimal version of hormonal therapy.

Aim: To assess the value of the integral thrombodynamics test in the multifactorial assessment of hemostasis system in women of reproductive age using hormonal contraceptives.

Materials and methods: This observational prospective comparative study included 408 women aged 18 to 49 years followed from 2018 to 2022 in The Nikiforov Russian Center of Emergency and Radiation Medicine and Centre of Miscarriage Prevention and Treatment of the Maternity Hospital No. 1, St. Petersburg. From these, 208 women (mean age, 38.0 ± 7.0 years) were taking hormonal contraceptives (HC+ group), and 200 women (mean age, 37.5 ± 9.2 years) were in the control group (HC-). In the HC+ group, 163 women were taking combination oral contraceptives, 24 had an intrauterine levonorgestrel-releasing system, 8 used vaginal rings, and 13 were using progestin only oral contraceptives. Multifactorial clinical and laboratory assessment included taking past history, measurement of pro- and anticoagulation blood parameters, fibrinolysis, and endothelial function parameters (automatic coagulometer ACL TOP 500, Instrumentation Laboratory, USA). The integral assessment of the hemostasis system was performed with Thrombodynamics Registrator T-2 (Hemacor, Russia).

Results: The groups were similar as per their age, chronic venous insufficiency and smoking. The HC+ group had significantly higher proportion of women with cardiovascular disorders (p = 0.0037), obesity (p = 0.0004), and headache (p < 0.0001), compared to the HC- group. The thrombodynamics test showed a significantly higher rate of clot formation in the women taking hormonal contraception, compared to that in the HC- group (36.2 [30.1; 43.6] and 30.3 [28.0; 33.6] mcm/min, respectively, p < 0.001). Hypercoagulation identified by the thrombodynamics test was associated with slowing down of XIIa-dependent fibrinolysis (6 [5; 8] min in the HC- and 12.8 [8; 16] min in the HC+ group, p < 0,001) and higher levels of endothelial dysfunction markers (FVIII, 113 [85; 156] and 150 [107; 180]%, p = 0.015; vFW, 98 [85; 133] and 146 [95; 168]%, respectively, p = 0.003). The analysis of plasma hemostasis parameters depending on the presence of thromboembolic risk factors has shown that higher number of the risk factors is associated with higher velocity parameters in the thrombodynamics test in the range of chronometric hypercoagulation.

Conclusion: The integral thrombodynamics test for the assessment of plasma hemostasis allows for identification of hemostasis dysfunction in women taking hormonal contraceptives. To prevent the risk of thromboembolic complications, it is desirable to assess blood coagulation system parameters before administration of hormonal agents.

The prevalence of diabetes mellitus in acromegaly is significantly higher than that in the general population. Carbohydrate metabolism abnormalities often precede other phenotypic manifestations of acromegaly. The review presents data on the prevalence of carbohydrate metabolism disorders in acromegaly and describes their pathophysiological characteristics and approaches to treatment.

Growth hormone (GH) excess is recognized as a key factor of glucose homeostasis abnormalities due to decreased insulin sensitivity (resulting from active lipolysis) and direct stimulation of insulin secretion. Insulin-like growth factor 1 (IGF1) improves insulin sensitivity; however, the GH diabetogenic effects prevail over the insulin-sensitizing impact of IGF1. Surgical and radiation treatment for somatotropinoma may indirectly improve carbohydrate metabolism, because they decrease the GH levels. Treatment with first generation somatostatin analogues can both improve glycemic control due to decreased GH levels and worsen it due to deterioration of postprandial insulin release, especially in patients with already manifest carbohydrate metabolism disorders. The GH receptor antagonist pegvisomant blocks the effects of excess GH on the target tissues without suppressing insulin secretion, which results in better glucose control; treatment with this agent can be preferred in patients with acromegaly and diabetes mellitus. Management of carbohydrate metabolism disorders in acromegaly is done in accordance with general treatment principles for type 2 diabetes mellitus.

Takayasu arteritis (TA) is a type of chronic large vessel vasculitis, which most often affects the aorta and its main branches as a kind of destructive-productive segmental aortitis and subaortic panarteritis, with possible obliteration of their orifices. Clinical picture of TA may be different depending on the nature and localization of the pathological process.

We present a clinical case of ischemic injury of the colon mucosa in TA in a young (21 year old) female patient after she had a novel coronavirus infection (COVID-19). Due to ineffectiveness of out-patient treatment of ulcerative colitis, as well as complaints that were not meeting the diagnosis of ulcerative colitis, the patient was referred for additional examination and treatment modification in inpatient settings. Taking into account her diarrheal syndrome at the disease onset, the ileocolonoscopy results (rectal and colonic erosions), the results of histological examination (diffuse leukocytic infiltration of the mucosa, lymphoid infiltration of submucosa of the colon), elevation of proinflammatory markers, involvement of the inferior mesenteric artery at ultrasound dopplerography, the differential diagnosis was made between the TA overlap syndrome with inflammatory bowel diseases and TA-associated ischemic colitis. The assessment results made it possible to exclude inflammatory bowel diseases, to establish the diagnosis of TA and to consider colonic mucosa abnormalities as ischemic with underlying disease.

The clinical case described is a rare event of intestinal ischemia as a first TA manifestation. Given the increasing worldwide prevalence of TA, especially after the new coronavirus infection pandemic, it is necessary to include this rare cause of gastrointestinal vasculitis to the differential diagnostic search, since mesenteric ischemia is one of the main causes of death in AT patients.