MAMMOLOGY. ORIGINAL REPORTS
Background. One of the most common methods of breast reconstruction after mastectomy for malignant tumors is reconstruction using an endoprosthesis. However, this technique is associated with the risk of developing periprosthetic complications. The classic solution to this problem is to remove the endoprosthesis, achieve complete remission of the infectious process and repeat the cycle of reconstructive measures. In this work we present a new approach to the treatment of periprosthetic complications.
Aim. To evaluate the effectiveness of the controlled negative pressure system (CNP) in the treatment of periprosthetic breast complications.
Materials and methods. From 2019 to 2023, the study included 23 patients who underwent combined/complex treatment for breast cancer, including reconstructive plastic surgery with the installation of endoprostheses, and 1 patient who underwent aesthetic surgery was included. All patients experienced various complications after the reconstructive stage: protrusion of the endoprosthesis, ischemia of the flap and/or local inflammation. To relieve the complications that arose, treatment was carried out using a flushing system and a CNP.
Results. The duration of therapy with the sequential installation of a flushing system followed by replacement with a СNP averaged 15 days. In 7 cases out of 24, it was not possible to preserve or reinstall endoprostheses due to thinning of the musculocutaneous flap, resistance of the microflora to the treatment, or relapse of the infectious process. In 17 cases, no complications were recorded after re-installation of endoprostheses for 2 years. As a result of the work, in most cases, within one hospitalization, it was possible to preserve the skin sheath, achieve complete regression of complications and perform repeated reconstructive intervention
Conclusion. In most cases, the use of a CNP allows you to save the bed for the full installation of a new endoprosthesis. To do this, a number of conditions must be met: absence of microflora growth; presence of granulation after treatment; full thickness and integrity of the musculocutaneous flap. Systemic treatment and a history of radiation therapy are not a contraindication to retaining endoprostheses.
Background. One of the causes of complications in breast cancer patients after immediate breast reconstruction (IBR) is postmastectomy radiation therapy (PMRT).
Aim. Retrospective analysis of the results of IBR, and evaluating the effect of PMRT on the frequency and type of complications.
Materials and methods. Between 2015 and 2021, 798 patients underwent IBR with tissue expander or implant in N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia. PMRT was performed in 375 patients (group 1). The remaining 423 patients did not receive PMRT (group 2). Complications, including reconstructive failure (RF), Baker grade III/IV capsular contracture (CC), were recorded and analyzed.
Results. Finally, cosmetic result analyzed in 521 patients. In 281 patients of PMRT group (group 1) IBR with expander or implant were performed in 144 and 137 cases, respectively. In the 240 patients without PMRT (group 2), IBR with expander was performed in 81 patients, with implant – in 159 cases. Pooled analysis revealed that overall rate of complications in the PMRT group was 33.8 % (in 95 of 281 patients), in non-irradiation patients – 22.9 % (in 55 of 240 patients), p <0.01. In group 1, RF were recorded in 67 (23.8 %) patients, in group 2 – in 44 (18.3 %) patients, p >0.05. CC in group 1 were detected in 28 (10 %) patients, in group 2 in 11 (4.6 %) patients, p <0.05. In patients with permanent implants RF were detected in 21 (14.6 %) of irradiation patients and in 22 (13.8 %) non-irradiation patients (p >0.2). On the contrary, CC were mentioned in 22 (16.1 %) of irradiated patient and in 8 (5 %) patients that didn’t receive PMRT, p <0.005. After reconstruction with expander RF were diagnosed in 46 (31.9 %) patients after PMRT and in 22 (27.2 %) non-irradiation patients, p >0.2. CC were observed in 6 (4.2 %) patients from PMRT group and in 3 (3.7 %) patients treated without PMRT, p >0.2.
Conclusion. PMRT in patients after IBR with simultaneous installation of a permanent implant is characterized by a decrease in the incidence of RF, but an increase in the incidence of CC.
Background. Increasing the survival rate of breast cancer patients is a problem all over the world and directly depends on the early detection of a malignant tumor. Genome-wide associative studies (GWAS) as a minimally invasive method may be used in determining risk of breast cancer or detection at an early stage. The increase in the number of patients with disseminated breast cancer in the Republic of Kazakhstan makes it necessary to search for molecular genetic markers of breast cancer for their use in the diagnosis and treatment of patients with this pathology.
Aim. To retrospectively estimate the correlation of the effectiveness of drug antitumor therapy for breast cancer with gene polymorphism.
Materials and methods. The study included the results of genotyping biomaterial samples on high-density DNA chips (venous blood of 1,277 Kazakh patients (in the third generation) with a verified diagnosis of breast cancer with locally advanced and disseminated breast cancer who received anticancer therapy), clinical data of patients, data on the clinical efficacy and toxicity of drug therapy. GWAS data (genotypes) associated with identified responses to chemotherapy drugs were compared with similar data recorded in international databases.
Results. The family history study showed 16.52 % of women in the questionnaires had a family history of various types of ESR, and 86.25 % of them had a burden of breast cancer in women of the first degree of kinship. The average age of patients with breast cancer was 48.79 ± 11.44 years. According to the TNM classification, cancer in situ was detected in 4.78 % of patients, stage I of the disease was recorded in 15.27 %, stage II in 63.43 %, stage III in 12.60 %, stage IV in 3.92 % of patients. The vast majority of the patients (96.9 %) had a nodular form of breast cancer. The distribution of the patients by tumor phenotype: luminal type A was found in 20.4 % of patients, luminal type B in 38.3 %, luminal type B with HER2 overexpression in 14.3 %, HER2 positive form in 11.9 % of cases, 12.4 % of patients had an aggressive form – triple negative breast cancer. 18 main genotypes were identified in the Kazakh population as a result of the analysis of associations of the effectiveness of neoadjuvant chemotherapy (its individual components, according to chemotherapy regimens) and individual gene polymorphisms.
Conclusion. An associative relationship between different types of gene polymorphism and the characteristics of response to various chemotherapeutic drugs used in the treatment of breast cancer has been confirmed. The obtained results formed the basis for the development of recommendations for making changes to the clinical practice of the Republic of Kazakhstan in order to use them in identifying a genetic predisposition to breast cancer and the effectiveness of drugs used in treatment.
Aim. To identify population characteristics of the PIK3CA gene mutation among breast cancer patients in the Krasnoyarsk region.
Materials and methods. The study included 140 patients with breast cancer with a certain mutation status of the PIK3CA gene, observed at the Krasnoyarsk Regional Clinical Oncology Center named after A.I. Kryzhanovsky. Determination of PIK3CA gene mutations (exons 2, 5, 8, 10 and 21) was carried out using commercial kits on equipment from Roche (Germany). Statistical processing of the obtained data was carried out using Microsoft Excel and Statistica 12 software products. The assessment of the factor of influence on the relapse-free and overall survival was carried out by constructing and comparing Kaplan–Meier curves. The result was considered statistically significant at a significance level of p <0.05.
Results and conclusion. The overall frequency of occurrence of PIK3CA gene mutations is 38.6 %. The most common mutations are H1047X (55.4 %) in exon 21 and E545K (27.8 %) in exon 10. The median age of breast cancer patients with mutation status in the PIK3CA gene was 58.9 [49.0; 67.0] years, median time to relapse or progression was 62.2 [27.0; 84.0] months. There were no statistically significant differences in relapse-free survival between the presence and absence of mutations (p = 0.8). The effect of changes in PIK3CA on a decrease in overall survival rates (p = 0.047) in breast cancer patients was shown.
Background. Reducing malignant mortality to 185 cases per 100,000 by 2030 is one of goals of the state program “Healthcare development” in Russia.
Aim. To assess potential impact of using trastuzumab deruxtecan in patients with breast cancer on reducing cancer mortality.
Materials and methods. Three indications of trastuzumab deruxtecan were considered: adult patients with HER2-positive unresectable or metastatic breast cancer that were previously treated with trastuzumab and a taxane in the advanced or metastatic setting (referred as “Second line”); adult patients with HER2-positive unresectable or metastatic breast cancer who previously received at least two lines of therapy in the metastatic setting including trastuzumab emtansine (referred as “Third line”); adult patients with HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy (referred as “HER2-low metastatic breast cancer”). The set of comparators for each clinical situation was formed based on the clinical guidelines and clinical trials of trastuzumab deruxtecan. Overall survival and treatment duration were modelled on the clinical trials basis. The model was used to estimate number of lives saved in case of transitioning all eligible patients to trastuzumab deruxtecan within a three-year horizon.
Results. Up to 3,609 patients p. a. in the “Second line” situation, 1,300 patients p. a. in the “Third line” situation and 2,260 patients p. a. in the “HER2-low breast cancer” situation can initiate trastuzumab deruxtecan treatment. In that case mortality from neoplasms could be reduced by 1,461 deaths in case of “Second line”, by 427 deaths in case of “Third line” and by 801 deaths in case of “HER2-low metastatic breast cancer” over three years. Reduction in mortality will contribute to achieving the target mortality rate from neoplasms of 21.61–24.81 %, 4.31–12.57 % and 5.91–20.89 %, respectively.
Conclusion. Using trastuzumab deruxtecan for breast cancer treatment in different clinical situations leads to quantitate reduction in cancer mortality in Russia.
MAMMOLOGY. REVIEWS
The main problem of breast reconstruction after a mastectomy is the complete destruction of all structural elements of the breast and the lack of integumentary tissues that do not allow carrying out one-stage breast reconstruction. To solve this problem, usually performing a two-stage reconstruction, which today is the most commonly used method of breast reconstruction. The peculiarity of this method is that after removal of the expander, during the second stage of reconstruction, some retraction of the skin and a decrease in the area of the prepared skin cover are observed. Thus, after installing a permanent implant and suturing the surgical wound, the skin sheath is tightened around the installed endoprosthesis, while the greater the retraction of the skin, the more pronounced the tension appears and, accordingly, the load on the sutured wound increases. As a result, the risks of developing diastasis of the wound edges with the exposure of the endoprosthesis increase, which leads to the need to remove the implant. Therefore, when carrying out the second stage of breast reconstruction, a very important moment of the operation is the suturing of the postoperative wound, the competent implementation of which allows the prevention of implant extrusion.
MAMMOLOGY. CLINICAL CASE
This article provides a review of studies analyzing the etiology, diagnosis, and treatment of Peitz–Jeghers syndrome, as well as the risk of cancer of different locations in patients with this genetic disorder. We report a case of Peitz–Jeghers syndrome associated with breast cancer in young women in two generations (mother and daughter). Despite specific clinical manifestations (multiple hamartomatous polyps developing in childhood and ink-black mucous pigmentation in the woman and her immediate relatives), Peitz–Jeghers syndrome was diagnosed only after breast cancer development and consultation with oncologists. This confirms the need for informing both oncologists and general practitioners about this genetic disorder.
GYNECOLOGY. ORIGINAL REPORTS
Aim. To evaluatethe role tumour budding (TB), MELF-pattern and tumour-infiltrating lymphocytes (TILs) as possible prognostic factors of endometrioid adenocarcinoma of the uterine corpus.
Materials and methods. A single-centre, retrospective, observational study was conducted involving 188 patients with endometrioid adenocarcinoma of the uterine body. 40 patients who had disease recurrence or died directly from progression of endometrioid adenocarcinoma of the uterine body were the unfavourable outcome group, 148 patients without progression and death from this tumour were the favourable outcome group. Fisher, Yates exact two-sided criteria were used to analyze the data. Survival analysis was performed using log-rank test. The hazard ratio (HR) and its 95 % confidence interval (CI) were estimated using single-factor analysis with log-rank test and multivariate Cox proportional hazards analysis. p <0.05 was considered statistically significant.
Results. TB was observed predominantly in the group of patients with unfavourable outcome (р <0.0001) Survival analysis revealed statistically significant decreased survival in cases with TB (HR 5.3; 95 % CI 2.2–12.7; р <0.0001). MELF-pattern was statistically significantly more frequent in the group of patients with unfavourable outcome (р <0.0001), a decreased survival of patients was observed in the presence of MELF-pattern (HR 5.8; 95 % CI 2.1–16.2; р <0.0001). Comparison of groups according to the number of TILs revealed statistically significant differences (р = 0.0242). When analyzing survival relative to the threshold value of the number of TILs, statistically significant differences were also observed (HR 3.7; 95 % CI 1.7–7.9; р = 0.021). Multivariate Cox proportional hazards analysis revealed that only TB and MELF-pattern had prognostic significance for recurrence-free survival (HR 3.7; 95 % CI 1.8–7.4; р <0.001).
Conclusion. TB and MELF-pattern are specific changes in the stroma of endometrioid adenocarcinoma stroma of the uterine corpus that can be used as pathomorphological predictors of clinical outcome.
Background. Cervical cancer (CC) refers to cancer of visual localization and in women of reproductive age remains one of the most common oncological diseases. The carcinogenesis of CC is caused by the persistence of highly oncogenic types of human papillomavirus (HPV), the level of carcinogenicity of which is the highest based on the criteria of the International Agency for Research on Cancer. However, cervical carcinogenesis does not occur in all cases of persistence of highly oncogenic types of HPV. This, in turn, determines the need for a thorough search, study and analysis of possible cofactors that can lead to neoplastic changes in the cervix.
Aim. To develop a model for predicting the individual risk of CC in women of reproductive age, taking into account clinical, anamnestic, laboratory and histological data.
Materials and methods. The material for the study was retrospective examination data from 251 patients of reproductive age who were treated at the Center for Gynecology and Reproductive Technologies of the National Medical Research Center “Medical and Rehabilitation Center”, Ministry of Health of Russia in the period 2015–2022. Results. Highly oncogenic HPV types were significantly more common in the group of patients with verified СС who took combined oral contraceptives (COC), compared with patients who did not take COC (p = 0.035). Multifactorial analysis allowed us to determine that long-term use of СОС for a total of more than 7 years is associated with a tendency to increase the risk of developing СС (hazard ratio 1.68; 95 % confidence interval 1.1–2.5; p = 0.010). According to the results of statistical calculation, the values of regression coefficients were obtained and the tendency to increase the risk of developing CC was predicted in the presence of such factors as: HPV type 16 persistence, body mass index, and the duration of COC intake in years.
Conclusion. Thus, taking into account all possible risk factors for CC, the negative effect of cofactors, namely increased body mass index and prolonged intake of COC, on the course of HPV as the leading etiological factor of breast cancer, will allow us to identify groups at increased risk of developing CC, form an individual algorithm for monitoring and examination throughout the entire period of taking COC, as well as conduct individual cancer prevention by limiting the duration of taking COC.
Background. Uterine fibroid (UF) is a benign tumor of the myometrium and is considered as one of the criteria for the state of women’s reproductive health. Objective information about the incidence of UF in a modern megalopolis allows us to assess the level of health of the female population, characterize the availability and quality of medical care, and plan its development.
Aim. To analyze the incidence and prevalence of UF according to the data of medical organizations in Yekaterinburg in 2016–2022.
Materials and methods. An epidemiological study of the incidence and prevalence of the adult female population of the city of Yekaterinburg in 2016–2022 was conducted. For the analysis, we used Form No. 12 of the Federal Statistical Observation of Medical Organizations located in the city. The incidence rates were calculated for the average annual female population aged 18 years and over, expressed in 0/0000. Absolute growth (decrease), growth rate (decrease), growth rate (decrease), average growth rate (decrease) were studied. The long-term dynamics of the indicators was determined using the average growth rate.
Results. The incidence of UF was 130.890/0000, and the prevalence was 735.800/0000 in 2016. During the pre-pandemic period, the indicators increased significantly in 2019 compared to the baseline year 2016 (р < 0.001). The incidence increased by 1.96 times, the prevalence – by 1.39 times. The indicators decreased to the level of 2016 during the pandemic of new coronavirus infection (2020–2022) (р >0.05).
Conclusion. The obtained dynamics of incidence and prevalence of UF in the population of women in a modern megalopolis is considered as a criterion for the state of women’s health, accessibility and quality of preventive and planned medical care for gynecological patients. The results of the study are recommended for planning medical care for women and can form the basis for continuing epidemiological studies.
Background. Endometrial cancer (EC) dominates in the structure of gynecological cancer morbidity. There has been an increase in this nosology in women of reproductive age. The morphological precancerous form of endometrioid adenocarcinoma is endometrial intraepithelial neoplasia (EIN), or atypical endometrial hyperplasia (AEH), that is difficult to diagnose: there is a high percentage of underdiagnosis resulting in a wrong treatment strategy. To improve the accuracy of diagnosis, additional immunohistochemical markers are being studied that are not part of the physician»s routine practice. Extremely promising for the prognosis of endometrial malignancy is the assessment of the functioning of the genes of the DNA mismatched nucleotide repair system (DNA mismatch repair system, MMR).
Aim. To assess the diagnostic value of (microsatellite instability, MSI) in patients with AEH to rule out coexisting endometrial cancer.
Materials and methods. The study includes 72 histological samples: 36 cases of EIN and 36 cases of EC, 14 of which were combined with EIN. To assess the microsatellite status, immunohistochemical staining of specimens was done with the identification of 4 markers, i. e. MLH1, PMS2, MSH2, MSH6.
Results. It was found that out of 36 cases of EIN, only one sample showed loss of the PMS2 and MLH1 genes, which amounted to 3 %; the remaining EIN samples showed microsatellite stability. In 5 (36 %) out of 14 cases of combined EC and EIN pathology, MSI/dMMR was identified. Eight (36 %) out of 22 EC samples were found to have MMR deficiency. Loss of PMS2 increases the likelihood of being classified as EC 9-fold (odds ratio 9.1). With that, the presence of foci of adenocarcinoma in the case of AEH if MSI is confirmed can be asserted with a probability of 93 %. The detection of MSI in a histological sample is more often associated with the presence of EC, while the loss of the PMS2 and/or MLH1 genes increases the likelihood of a cancer diagnosis. If during additional immunohistochemical analysis a loss of these genes is observed, then EC can be diagnosed, even with an ambiguous histological pattern.
Conclusion. Detection of MSI/dMMR in AEH indicates the presence of foci of coexisting endometrioid adenocarcinoma with an extremely high degree of probability. Detection of MSI/dMMR in the treatment of EC is advisable at the stage of diagnosis.
GYNECOLOGY. REVIEWS
An indicator of the effectiveness of treatment of cancer patients, in addition to oncological results, is also the preservation of their quality of life. Quality of life assessment is a modern research method that allows identifying even minor changes in any spheres of human activity in order to comprehensively determine the effectiveness of treatment. The quality of life of cancer patients is a priority and promising area of modern medicine.
The article presents information about the current state of the problem of quality of life of patients with cervical cancer after organ-preserving treatment. The results of a number of foreign studies published on this topic are presented. In addition, the results of a prospective study conducted in the Department of Gynecology of the Tomsk Oncology Research Institute are presented. In conclusion, the need for additional study of reproductive results and determining which factors need to be further evaluated, speaking of a comprehensive assessment, is shown.
Ovarian germ cell tumors account for 30 % of germ cell tumors of other localizations and 70 % of all ovarian neoplasms. The aim of this review is to study and systematize clinical manifestations, diagnosis and treatment of ovarian germ cell tumors in childhood and adolescence on the basis of current foreign and domestic studies.
Ovarian neoplasms in children and adolescents are rare pathologies (2.6–3.0 per 100,000 patients a year), however, they are sufficiently relevant in pediatric gynecology nowadays. The age of the patients highly correlates with different histological types of ovarian neoplasms. And this is a reason for discussing this disease in different age groups apart. Unfortunately, there are a number of unresolved issues connected with the etiology, pathogenesis and diagnosis. This paper discusses recent information related with the subject “ovarian neoplasms in pediatric gynecology” and particularly questions which require further study.
The aim of the work is to conduct a review of recent literature which corresponds to this subject and to discover questions which require further study.
The analysis revealed that the etiology and pathogenesis of a number of rare neoplasms has not been discovered fully yet and that can be the cause of the delayed disease diagnostics. Apart from this there are no tools for the preoperative stratification of the risk of malignancy and that can lead to more frequent radical operations for benign tumors.
GYNECOLOGY. CLINICAL CASE
The article presents an analysis of the current state of the problem of background and precancerous diseases of the endometrium. The issues of etiology and pathogenesis of these conditions are reflected, as well as the features and difficulties of diagnosis, treatment and course in patients with pregnancy are presented. The experience of the Tomsk Oncology Research Institute in the treatment of this pathology is presented, as well as clinical cases that clearly demonstrate the possibility of successful treatment of both endometrioid intraepithelial neoplasia and initial uterine body cancer. It should be noted that the results of treatment of this category of patients are quite good, as well as the expediency of careful dynamic monitoring of this category of patients and the possibility of collegial decision-making in determining treatment tactics at all stages of therapy.
Article
ISSN 1999-8627 (Online)