Evolution of the CDK4/6 inhibitor abemaciclib: from palliative to adjuvant therapy. Clinical experience with abemaciclib in patients with hormone-receptor-positive, HER2-negative breast cancer

Introduction. Cyclin-dependent kinase 4/6 inhibitors are indicated in endocrine therapy for the treatment of hormone receptorpositive, HER2-negative, advanced, or metastatic breast cancer. In the recent past, abemaciclib made its debut as a combinatorial partner for adjuvant therapy in hormone-dependent breast cancer. This article demonstrates the analysis of our own experience of introducing abemaciclib into clinical practice.Aim. The aim of the study was to evaluate the preliminary results of treatment of patients with hormone receptor-positive HER2-negative metastatic breast cancer using abemaciclib outside the framework of clinical trials, in the real clinical practice of an oncological dispensary.Materials and methods. A retrospective analysis of the results of treatment was carried out in 27 patients who were prescribed abe-maciclib in various regimens and lines from April 2021 to January 2022 in the conditions of routine practice in the Krasnodar region.Results and discussion. Analysis of the total population of 27 patients at a median follow-up of 8 months showed that the median PFS was not reached. The one-year PFS was 68.8%. Treatment outcomes were independent of prescribing abemaciclib to treat baseline metastatic disease or breast cancer progression after previous radical treatment (p = 0.60). The PFS did not depend on the expression of progesterone receptors in the tumor tissue (p = 0.326) and the proliferative activity index Ki-67 (p = 0.618). Patients who received no more than 2 lines of previous drug treatment for a history of metastatic breast cancer had the greatest benefit from abemaciclib therapy (p = 0.001).Conclusions. Despite a relatively difficult group of patients (96% of patients with visceral metastases), abemaciclib has demonstrated efficacy and safety. The effectiveness did not depend on the analyzed factors: Ki-67, the level of expression of progesterone receptors, the type of metastatic disease (de novo metastatic or progressive breast cancer). In view of the best results, it is advisable to prescribe abemaciclib in the early lines of therapy

Surgical treatment of portal hypertension complications in patients with liver cirrhosis

Objective: Improving the results of surgical treatment of portal hypertension complications in patients with liver cirrhosis.Material and methods: The results of medical care for 328 patients with liver cirrhosis, who were treated in the surgical departments of the central district and city hospitals of the Krasnodar Region, were analyzed. The effectiveness of minimally invasive surgical treatment of portal hypertension complications in 832 patients with liver cirrhosis treated at the Regional Clinical Hospital no. 2 of the Ministry of Health of the Krasnodar Region were also evaluated.Results: The mortality rate in patients with liver cirrhosis, admitted in first-level institutions of medical care due to acute bleeding from esophageal varices, reached 26.3%. In conditions of surgical treatment of complications of portal hypertension in a third-level institution of specialized care it did not exceed 4.7%.Conclusion: The optimal approach to the surgical treatment of patients with liver cirrhosis is to stop the bleeding from esophageal varices at the first stage of medical care and to treat portal hypertension complications using minimally invasive technologies in a multidisciplinary clinic involving a multidisciplinary team of doctors

Pneumomediastinum as a predictor of negative prognosis in patients with coronavirus pneumonia

Aim of the study was to analyze the course of coronavirus pneumonia in patients with pneumomediastinum. Material and methods. The study included 139 patients, 71 of whom developed spontaneous pneumomediastinum against the background of coronavirus pneumonia. Laboratory, clinical and radiological data were analyzed and compared. Results. The relationship between the severity of viral pneumonia (3rd–4th degree of severity according to MSCT) and pneumomediastinum was revealed. It was found that spontaneous mediastinal emphysema in patients with COVID-19 signifcantly more often leads to the development of acute respiratory distress syndrome, multiple organ failure and can be a predictor of negative prognosis of the disease outcome. Conclusions. Pneumomediastinum in patients with viral pneumonia caused by a new coronavirus infection is a predictor of severe disease and poor prognosis. With an increase in spontaneous mediastinal emphysema without pneumothorax, it is recommended to perform mediastinotomy according to Razumovsky’s indications, and in case of clinically signifcant concomitant pneumothorax – drainage and revision of the mediastinum

Оценка эффективности локальной стероидной терапии у детей с олигоартикулярным вариантом ювенильного артрита: результаты ретроспективного исследования

 Background. Despite the progress in diagnosis and treatment of chronic rheumatic diseases in children, the choice of anti-inflammatory drugs in case of the onset of oligoarticular juvenile idiopathic arthritis (JIA) still remains relevant. Till present, pediatric rheumatologists have not reached a  consensus on this issue yet.The aim of this study was to search for predictors of early failure of local steroid therapy and assessment of its feasibility in patients with oligoarticular JIA.Materials and methods. In a retrospective study, 92 children aged 11 months – 9 years with chronic oligoarticular JIA without extra-articular manifestations were monitored. The features of the clinical, instrumental and laboratory diagnosis during the disease onset were studied, along with the dynamics of the articular syndrome and the effectiveness of intra-articular administration of corticosteroid drugs.Results and discussion. The data on 92 children with 164 active joints who received 218 local intra-articular injections of triamcinolone acetonide at the onset of the disease were analyzed. Intra-articular injections of triamcinolone acetonide at a dose of 20–40 mg were performed with an interval of 3, 6, and 12 months, depending on the intensity of the disease. In about one third of children with oligoarticular JIA, arthritis became inactive on average after two intra-articular injections of triamcinolone acetonide. The study did not reveal the predictors of early ineffective topical corticosteroid monotherapy in children. No clinical, instrumental, and laboratory signs were identified that would directly indicate the need for early therapy with  methotrexate.Conclusion. Triamcinolone acetonide is an effective and safe drug for children with oligoarticular JIA. Despite the widespread use of biological, gene, and other innovative therapies, application of local corticosteroids as  the firstline therapy in children with oligoarticular JIA should not be  neglected.  Актуальность. Несмотря на большой прогресс в диагностике и лечении ревматических заболеваний у детей, все еще остается актуальным вопрос выбора  противовоспалительной терапии в случае дебюта  хронического олигоартрита. Единого мнения на этот счет у  детских ревматологов нет и по настоящий день. Цель. Поиск предикторов ранней неэффективности и оценка целесообразности локальной стероидной  монотерапии у пациентов с дебютом олигоартикулярного  варианта ювенильного артрита. Материалы и методы. Основу ретроспективного  исследования составили 92 ребенка в возрасте от 11 мес до 9 лет с хроническим олигоартритом без экстраартикулярных  проявлений (олиго-ЮА). Были изучены  особенности клинико-инструментальной и  лабораторной диагностики в дебюте заболевания, динамика суставного синдрома и эффективность внутрисуставного  введения глюкокортикостероидного препарата.Результаты. Проанализированы данные 92 детей со 164 «активными» суставами, которые получили 218 изолированных внутрисуставных манипуляций по введению  стероидного препарата (триамцинолон ацетонид). Триамцинолон ацетонид вводился  внутрисуставно в дозе 20–40 мг с интервалом 3, 6, 12 мес в  зависимости от активности заболевания. Около одной трети  детей с олиго-ЮА достигли неактивной стадии болезни в среднем после двукратного введения данного  препарата. Исследование не позволило выявить предикторов ранней неэффективности монотерапии  локальными стероидными препаратами у детей. Не выявлено достоверных клинико-инструментальных и  лабораторных признаков, которые напрямую указывали бы  на необходимость начала ранней терапии препаратом  «Метотрексат».Заключение. Триамцинолон ацетонид является  эффективным и безопасным препаратом у детей с  олигоартикулярным вариантом ювенильного артрита.  Несмотря на популяризацию генно-инженерной  биологической терапии, не следует пренебрегать лечением  локальными стероидными препаратами как первой линией противоревматической терапии у детей.

Органосохраняющие операции на матке при врастании плаценты: клинический опыт

Introduction. The aim of our work was to improve surgical delivery procedures in patients with a true placenta accreta.Materials and methods. We analysed 17 childbirth histories of patients who underwent organ-preserving surgeries on uterus during placenta rotation in 2018-2019. The choice of an optimal tactic for managing patients in the department of pregnancy pathology at the BSMU clinic, as well as each case of the surgical treatment of placenta accrete, was carried out jointly with specialists from I.M. Sechenov First Moscow State Medical University.Results and discussion. All patients underwent surgery in a planned manner; their age and parity had no static differences (p > 0.1). The surgery performed according to the described technique did not lead to a significant increase in its duration. Additionally, the average blood loss of 2200 ml during surgery was not considered significant for this type of operations. We believe that these indicators will decrease with the accumulation of practical experience in performing such interventions.Conclusion. The applied method of surgical intervention using temporary occlusion of the common iliac arteries has shown a high efficiency and allowed the amount of intraoperative blood loss to be reduced. Despite performing a bottom incision on the uterus to remove the fetus and excise the area of placenta rotation, the examined patients did not experience significant complications both during the surgery and in the early and late postoperative period. The first results allow this technique to be recommended as a method of choice during placenta rotation The monitoring of patients will continue.Введение. Целью нашей работы явилось совершенствование хирургических методик родоразрешения при истинном приращении плаценты.Материалы и методы. Нами было проанализировано 17 историй родов пациенток, перенесших органосохраняющие операции на матке при вращении плаценты за 2018-2019 гг. Выбор оптимальной тактики для ведения пациенток в отделении патологии беременности клиники БГМУ и каждого случая оперативного лечения врастания плаценты производился совместно со специалистами ФГАОУ ВО «Первый МГМУ имени И.М. Сеченова» Минздрава России.Результаты и обсуждение. Все пациентки были прооперированы в плановом порядке, их возраст и паритет не имел статических различий (р > 0,1). Выполнение операции по данной методике не привело к существенному возрастанию ее продолжительности. Также средняя величина кровопотери 2200 мл не является значительной при данной операции. Полагаем, что эти показатели будут улучшены по мере накопления практического опыта выполнения таких вмешательств и в дальнейшем будут сокращены.Заключение. Примененный метод оперативной тактики с использованием временной окклюзии общих подвздошных артерий показал высокую эффективность и позволил снизить величину интраоперационной кровопотери. И несмотря на выполнение донного разреза на матке для удаления плода и иссечения области вращения плаценты, у обследованных больных не наблюдалось значительных осложнений во время операции, а также осложнений в раннем и позднем послеоперационном периоде. Первые результаты позволяют рекомендовать данную методику как метод выбора при вращении плаценты, наблюдение за пациентками будет продолжено

Клинические аспекты рака предстательной железы у больных с выявленными герминальными и соматическими мутациями в генах репарации ДНК путем гомологичной рекомбинации

Background. In clinical practice, there is a need to predict clinical behavior of prostate cancer with germinal and somatic mutations in DNA homologous recombination repair (HRR) genes due to an atypical response to standard treatment methods. Also, the expediency of testing the mutational status of HRR genes is dictated by the possibility of using the PARP-inhibition strategy in metastatic castration-resistant prostate cancer (mCRPC). In addition to expanding the possibilities for targeted therapy the necessity to inform the relatives of mutation carriers is underestimated. It is also important to realize the fact of accumulation of somatic changes both in the primary tumor and in the metastatic lesion during tumor evolution and under treatment, which dictates the possibility of repeated biopsy with exhausted therapy possibilities.Aim. Evaluation of prostate cancer clinical behavior features and response to drug therapy depending on the identified mutations in the HRR genes.Materials and methods. The study was performed at the Clinical Oncological Dispensary No. 1 (Krasnodar). Clinical and morphological data of 27 patients with prostate cancer and identified germinal and somatic mutations in HRR genes (BRCA1, BRCA2, ATM, BARD, BRIP1, CDK12, CHEK1, CHEK2, PALB2, RAD51B, RAD51C, RAD54L, FANCL) were retrospectively analyzed. Statistical analysis was performed using the IBM SPSS Statistics v.22 statistical package.Results and conclusion. The median age of patients was 61 years. The most frequent were mutations in the BRCA2 (37 %), CHEK2 (18.5 %), ATM (14.8 %) genes. More than half of the patients (69 %) had primary metastatic disease. The differentiation grade of G2 and G3 according to the classification of the International Society of Urological Pathologists (ISUP) with Gleason score of 7 (3 + 4) and 7 (4 + 3) were both detected in 27 % of cases. The type of mutation did not affect the time of castration resistance development (p = 0.216). The time to castration resistance increased close to statistical significance in the case of primary stage of T3–4N0M0 compared to other stages (log-rank p = 0.092). Progression-free survival (PFS) with docetaxel monochemotherapy was significantly longer when prescribed for metastatic hormone-sensitive prostate cancer with mutations in HRR genes compared to mCRPC (p = 0.061) and to primary metastatic disease (p = 0.04). At the same time, the risk of progression during therapy was higher for presence of regional lymph node metastases with primary advancement (p = 0.005; hazard ratio 1.167; 95 % confidence interval 2.765–267). There was also an advantage in PFS when prescribing docetaxel for BRCA1/2 and ATM mutations in comparison with other mutations (p = 0.038). When prescribing therapy with 2nd generation antiandrogens or abiraterone, progression-free survival is higher in the group of patients with prostate cancer with Gleason score of 7 (4 + 3) compared to cohort with other morphological types, and this difference is almost statistically significant (log-rank p = 0.091, Breslow p = 0.076, Taron-Ware p = 0.074). Targeted therapy with the PARP inhibitor Olaparib in the performed trial was received by 10 patients with HRR mutations. At the same time, according to the data of the PROfound trial, the advantage of Olaparib in radiological PFS was shown in germinal and somatic mutations in group A (BRCA1, BRCA2, ATM) and in the general group (A and B – other HRR mutations).Введение. В клинической практике наблюдается необходимость прогнозирования клинического течения рака предстательной железы (РПЖ) при наличии герминальных и соматических мутаций в генах репарации ДНК путем гомологичной рекомбинации (HRR) ввиду нетипичного ответа на стандартные методы лечения. Также целесообразность тестирования мутационного статуса генов HRR обусловлена возможностью применения стратегии PARP-ингибирования Олапарибом при метастатическом кастрационно-резистентном РПЖ (мКРРПЖ). Помимо расширения возможностей таргетной терапии недооценена необходимость информирования родственников о вероятности носительства герминальных мутаций. Также важно осознание факта накопления соматических изменений как в первичной опухоли, так и в метастатическом очаге в процессе эволюции опухоли и под влиянием лекарственного лечения, что диктует возможность повторной биопсии при исчерпанных вариантах терапии.Цель исследования – изучение особенностей клинического течения и ответа на лекарственную терапию РПЖ в зависимости от выявленных мутаций в генах HRR.Материалы и методы. Исследование выполнено на базе Клинического онкологического диспансера № 1 (Краснодар). Ретроспективно проанализированы клинико-морфологические данные 27 больных РПЖ с выявленными герминальными и соматическими мутациями в генах HRR (BRCA1, BRCA2, ATM, BARD, BRIP1, CDK12, CHEK1, CHEK2, PALB2, RAD51B, RAD51C, RAD54L, FANCL). Статистический анализ выполнен с использованием статистического пакета IBM SPSS Statistics v.22.Результаты и заключение. Медиана возраста пациентов составила 61 год. Чаще выявлялись мутации в генах BRCA2 (37 %), CHEK2 (18,5 %), ATM (14,8 %). Более половины пациентов (69 %) имели первично-метастатическое заболевание. Чаще выявлены опухоли с суммой баллов по шкале Глисона 7 (3 + 4), прогностическая группа 2 (G2) и 7 (4 + 3), прогностическая группа 3 (G3) по классификации Международного общества урологических патологов (ISUP) – по 27 % соответственно. На время до развития мКРРПЖ не влиял тип мутации (р = 0,216). Время до развития кастрационной резистентности близко к статистической значимости увеличивается в случае первичной распространенности T3–4N0M0 по сравнению с другой распространенностью (log-rank р = 0,092). Выживаемость без прогрессирования (ВБП) при монохимиотерапии доцетакселом значимо дольше при назначении по поводу метастатического гормоночувствительного РПЖ с мутациями в генах HRR по сравнению с назначением препарата при мКРРПЖ (р = 0,061) и первично метастатическом заболевании (р = 0,04). При этом риск прогрессирования на фоне терапии выше при наличии поражения регионарных лимфатических узлов при первичной распространенности (р = 0,005; отношение рисков 1,167; 95 % доверительный интервал 2,765–267). Также выявлено преимущество в ВБП при назначении доцетаксела при мутациях в генах BRCA1/2 и ATM по сравнению с другими мутациями (р = 0,038). При назначении терапии антиандрогенами 2-го поколения или абиратерона время без прогрессирования близко к статистической значимости выше в группе пациентов с РПЖ с мутациями в генах HRR прогностической группы G3 (ISUP) по сравнению с другими прогностическими группами (log-rank р = 0,091, Breslow p = 0,076, Taron-Ware p = 0,074). Таргетную терапию PARP-ингибитором Олапарибом в представленном исследовании получили 10 пациентов с мутациями HRR. При этом по данным регистрационного исследования III фазы PROfound показано преимущество Олапариба при мКРРПЖ в выживаемости без рентгенологического прогрессирования как при герминальных, так и при соматических мутациях в группе А (BRCA1, BRCA2, ATM) и в общей группе (А и В – других мутаций HRR)

Human papillomavirus-associated oropharyngeal carcinoma: trends in epidemiology and methods for detecting the virus in tumors

Oropharyngeal squamous cell carcinoma has been traditionally associated with tobacco and alcohol consumption. Nevertheless, latter 30 years have shown squamous cell carcinoma (OPSCC) incidence stagnation and increasing, despite the decrease in smoking prevalence. The incidence was recognized among white men of middle age, often non-smokers or former smokers in the investigations with smoking cessation data. It differs from traditional patient with OPSCC, older men, heavy smoker or alcohol drinker. The incidence of OPSCC is increased due human papilloma virus (HPV) infection. The infection transition is associated with sex and oro-genital contact may lead to HPV-infection of oropharynx and oral cavity. There are multiple types of HPV, but the majority of OPSCC is associated with HPV 16 type. Epidemiology of HPV-associated OPSCC, HPV-infection of oral cavity and/or oropharynx and HPV detection are discussed in the review

СOMPARATIVE ANALYSIS OF 10-YEAR RESULTS OF TREATMENT EFFICACY IN PATIENTS WITH COLORECTAL CARCINOMA

Aim. To study the dynamics of survival of patients with colorectal cancer in the Krasnodar region for the period of 2006-2015Materials and methods. Patients are divided into groups: registered in 2006, 2009, 2012, 2015. According to the Regional Population Cancer Registry, a comparative analysis of the long-term outcome of treatment of 9,741 patients was conducted by groups.Results. In patients with newly diagnosed colorectal cancer for the past 10 years, a significant increase in the three-year observed, as well as a three-year and five-year adjusted survival rate over the entire follow-up period, was obtained. For all stages of the disease and overall, the observed and adjusted survival rates declined for the first four years after the diagnosis was established, this result was most significant in patients with stage III and IV cancer. An unfavorable prognosis of survival was obtained in patients with stage IV: one-third survive less than a third of patients, the five-year life expectancy in this group was 9.8%.Conclusion. Improving the survival rates of patients with colorectal carcinoma indicates an increase in the effectiveness of providing specialized care for patients with colorectal cancer in the regio

TREATMENT OF HEAD AND NECK SQUAMOUS CELL CARCINOMA ACCORDING ON THE SPECIFIC MOLECULAR FEATURES OF THE TUMOR (A LITERATURE REVIEW)

Despite the achieved progress in radiotherapy, chemotherapy, and surgery, head and neck squamous cell carcinoma (HNSCC) still remains the sixth most common cause of death from cancer worldwide. The division of HNSCC into 2 large groups with different survival rates is a significant achievement made during the last decades in cancer research and treatment of head and neck cancer. In 45 % – 90 % of cases, oropharyngeal squamous cell carcinoma is presumably associated with human papillomavirus (HPV). A recent whole-exome sequencing study on HNSCC helped to develop new principles of treatment that will allow to increase the effectiveness of conventional therapy. The study demonstrated that inactivating mutations in the p53 gene trigger carcinogenesis. The majority of tumors have such mutations that inactivate the p53 tumor suppressor gene. According to the results of sequencing, HPV-positive and HPV-negative tumors have completely different mutation profiles. Intratumoral heterogeneity should be taken into account when implementing new treatment approaches. We present an overview of studies published between 1989 and 2014. Current review briefly describes molecular mechanisms of carcinogenesis in HNSCC in the light of genetic and biochemical features of the tumor, paying particular attention to the most significant scientific achievements in this field. Moreover, we outline the advancements of wholeexome sequencing in HNSCC and give an overview of recent studies devoted to new therapeutic approaches. The process of carcinogenesis in HNSCC is often initiated by tumor suppressors. In this case, the development of target-based drugs is problematic. Target therapy focused on the ways of tumor growth suppression is a much more serious challenge than inhibition of oncogenic signals, because it requires reactivation of tumor suppressors and restoration of their functions, which is more difficult than conventional chemical and biological blockage. Poor survival of patients with HNSCC, which is usually associated with a small size of recurrent tumors, their latent growth, and localization in various anatomical areas, shows that there is an urgent need for developing new therapeutic approaches for the disease. The study was aimed to analyze specific molecular features of head and neck tumors and to explore the opportunities of providing personalized care for these patients