Anton Anatoliyovych Burlaka

У статті розглянуто сучасні підходи до хірургічного лікування метастатичного колоректального раку з низьким пухлинним навантаженням печінки. Метою роботи є узагальнення наукових даних щодо ефективності та безпеки лапароскопічноЇ резекціЇ печінки й радіочастотноЇ абляціЇ, визначення перспектив Їх комбінуваного застосування. Проведено огляд наукових публікацій, представлених у базах даних PubMed/MEDLINE, Cochrane Library, Web of Science та Google Scholar за 2017–2022 рр. Проаналізовано результати рандомізованих контрольованих досліджень, когортних досліджень, систематичних оглядів і метааналізів щодо післяопераційних ускладнень, локального контролю пухлини, загальноЇ та безрецидивноЇ виживаності. Встановлено, що резекція печінки забезпечує кращий локальний контроль метастатичних вогнищ. Радіочастотна абляція характеризується меншою інвазивністю та може застосовуватися у ретельно відібраних пацієнтів із небеликими метастазами. Лаӱароскопічний доступ сприяє зменшенню післяопераційних ускладнень, скороченню тривалості госпіталізаціЇ та прискоренню відновлення пацієнтів. ОбӲрунтовано перспективність комбінуваного засТосування лаӱароскопічноЇ резекціЇ та радіочастотноЇ абляціЇ для злереження функціональноЇ паренхіми печінки й оптимізаціЇ локального лікування. Зроблено висновок, що вибір лікувальноЇ тактики має Ӳрунтуватися на індивідуальній оцінці пухлинного наТаванТаження, локалізаціЇ метастазів, резектабельності вогнищ і загального стану пацієнта.

У 2017 році лапароскопічна резекція лівої латеральної секції та малі резекції передніх сегментів печінки вважалися стандартом в світовій практиці. Однак у 2023 р. лише 5% резекцій печінки проводилися лапароскопічно в українських спеціалізованих центрах. Мета: дослідити, чи мають лапароскопічні малі резекції печінки (МРП) кращі фінансові, хірургічні та довгострокові онкологічні результати порівняно з відкритими резекціями печінки (ВРП) у двох державних спеціалізованих лікарнях України після початку повномасштабного вторгнення в 2022 р. Об’єкт і методи: у період з січня 2022 р. по червень 2025 р. 205 пацієнтів з колоректальними метастазами в печінку пройшли або малі відкриті резекції печінки (МВРП), або лапароскопічні малі резекції (ЛМР). Основними кінцевими точками були 30-денна післяопераційна частота ускладнень та хірургічні результати. Другорядними кінцевими точками були витрати на лікування та онкологічні результати. Результати: між групами спостерігалася різниця в післяопераційній частоті ускладнень на користь ЛМР: 3,8% (n = 4) проти 11,7% (n = 12) у групі ВРП (p = 0,04). 1,9% (n = 2) пацієнтів у групі ВРП мали важкі ускладнення. Смертність не була зареєстрована в жодній з груп. Загальна сума витрат на лікування 103 пацієнтів у групі ЛМР і 102 пацієнтів у групі ВРП склала 3,8 млн грн і 3,5 млн грн відповідно (p = 0,82). Дворічна безрецидивна виживаність становила 44% проти 54% та 19,6 місяців проти 24,0 місяців відповідно для груп ВРП та ЛМР (p = 0,62). Висновкок: лапароскопічні малі резекції печінки у пацієнтів з метастазами колоректального раку в печінку в державних спеціалізованих лікарнях зменшили період відновлення та рівень післяопераційних ускладнень при подібних онкологічних результатах та витратах.

Background. Extended epidural analgesia is widely used for postoperative pain control in oncological surgery. However, prolonged catheterization carries a risk of microbial colonization and infectious complications. In cancer patients, these risks are exacerbated by immunosuppression and impaired skin barrier function, underscoring the need to study the microbial spectrum and clinical implications of catheter colonization. Objective: to determine the frequency of bacterial colonization of epidural catheters, the spectrum of isolated microorganisms, and the clinical significance of these findings in patients undergoing oncological surgery. Materials and methods. A prospective study was conducted involving 51 patients who underwent prolonged epidural analgesia after oncological surgery. Demographic characteristics, somatic status, catheterization duration, incidence of infectious complications, and microbial culture results from catheter tips were analyzed. Statistical methods included descriptive analysis, Pearson’s test, Mann-Whitney U test, logistic regression, and Spearman correlation. Results. Positive cultures were found in 41.18 % of patients, with Staphylococcus epidermidis being the most common isolate. Clinical signs of infection were absent in 98 % of cases. No clinical-demographic variable showed a statistically significant association with colonization (p > 0.05), although body mass index had the strongest (nonsignificant) inverse correlation ( = –0.223). Colonization rates increased after more than 72 hours of catheterization. Conclusions. Epidural catheter colonization is common among cancer patients but rarely leads to clinically significant infections. Adherence to aseptic techniques and regular monitoring allow for the safe use of prolonged analgesia. Further research is needed to determine the optimal duration of catheterization and effective prevention strategies.

We searched for genes whose deletion affects mitochondrial heteroplasmy in the yeast Saccharomyces cerevisiae. In order to do this, we crossed a yeast knockout collection pool (rho⁺) with a rho^– strain containing a large deletion in its mtDNA. The resulting mixture of cells was plated onto selective media that made it possible to distinguish between diploid cells that had lost and retained wild-type mtDNA as a result of such crossing. From the resulting pools (initial one, cells that lose rho⁺ mtDNA, and those that retained it), we isolated DNA and determined the proportion of deletion strains using high-throughput sequencing. This made it possible to identify functional groups of genes that reduce the ability of yeast cells to maintain rho⁺ mtDNA in a state of heteroplasmy with rho^– mtDNA.

Background. The intermittent Pringle maneuver remains the major technique for controlling hemorrhage during liver surgery. Nevertheless, this procedure involves a risk of triggering a cascade of pathological changes resulting in the ischemia-reperfusion injury (I/R) effect. The pharmacological prevention of this I/R injury represents a promising approach. The aim of the study was to compare the effects of pharmacological preconditioning with sevoflurane and propofol-based intravenous anesthesia on the postoperative function of the liver as the primary end-point. Materials and Methods. A prospective cohort study includes the analysis of the data of 73 patients who underwent liver surgery. In the study group (n = 41), preconditioning with sevoflurane inhalation was provided 30 minutes prior to liver resection. In the control group (n = 32), sevoflurane preconditioning was not provided. The primary endpoints were blood lactate concentration shortly after the surgery and one day later; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities on postoperative Days 1, 3, and 5 as markers of hepatocyte damage. Results. On postoperative Day 1, in patients of the study group, lactate decreased to preoperative levels, while in the control group, lactate content increased as compared to both preoperative levels and the levels immediately after liver resection. A significant difference in AST activity levels between the groups was registered on Day 5, although this difference was not clinically relevant. The decrease in the prothrombin index in the study group on Day 3 was superior to that in the control group. The multiple regression analysis demonstrated a moderate positive association between the number of resected liver segments and the markers of the functional state of the liver in the study group while in the control group, such association was not significant. Conclusion. The protective effect of sevoflurane on the postoperative function of the liver is manifested by the lower level of blood lactate and the stable level of transaminase activity.

Summary. Prognosis of metastatic colorectal cancer (mCRC) patients nowadays is an important subject in the field of oncology. R0-resection of colon with primary tumor and liver metastasis remains the only treatment which significantly improves survival rate. However, recent experimental data show that surgical trauma can indirectly stimulate tumor growth due to mitochondrial dysfunction and unregulated superoxide radical (O2-) generation. Aim: To study the clinical significance of 8-oxo-2'-deoxyguanosine (8-oxodGu) marker, to assess the oncological effects of warm ischemia of liver parenchyma on disease prognosis in patients with mCRC. Material and Methods: 69 urine 24-hour volume tests of patients with mCRC and 17 healthy individuals were studied. Urine 8-oxodGu level was measured using spectrophotometric method with pre-solid phase DNA extraction. The energy system and hepatocyte detoxification system state, levels of O2- in tumor tissue were determined using the method of electron paramagnetic resonance (EPR) and SpinTraps technology at room temperature. Experiments were carried out on a computerized EPR spectrometer RE-1307. EPR spectra were recorded at temperature of liquid nitrogen (–196 °C) in paramagnetically pure quartz dewar on a computerized spectrometer PE-1307 with resonator H011. Error of the method of spectrum integration and spread of spectrum reproduction of one sample was not more than 3%. Results: The average level of marker in healthy individuals was 0.244 ± 0.063 nM/kg ∙ day, whereas before the resection and on day 3 after the R0-resection of liver in mCRC patients was 3.42 ± 0.18 nM/kg ∙ day and 2.12 ± 0.08 nM/kg ∙ day (p < 0.05), respectively. On day 3 after the liver resection due to its metastatic lesions with a total duration of warm ischemia period < 30 min and > 30 min have had marker at level 2.108 ± 0.13 nM/kg ∙ day and 2.9883 ± 0.159 nM/kg ∙ day (p < 0.0001), respectively. The volume of metastatic tissue significantly and directly correlated with the level of urine 8-oxodGu (R2 = 0.54, 95% CI 0.037–0.0991, p < 0.0001), also duration of surgical intervention (≥ 300 min) and duration of worm liver ischemia (> 30 min) during the surgery significantly increased urine level of 8-oxodGu (R2 = 0.54, 95% CI 0.001–0.004, p < 0.001). Conclusions: Warm liver ischemia (> 30 min), long-term surgical intervention (≥ 300 min) and metastatic tissue volume (≥ 12 cm3) in liver parenchyma in mCRC patients significantly increase urine 8-oxodGu levels. R0-resection of liver metastases in mCRC patients decreases urine 8-oxodGu levels already on day 3 after the surgery. 8-oxodGu is a new factor of oncological prognosis in patients with mCRC.

Summary. ­Background: The resection of metastases within healthy parenchyma improves significantly the long-term outcome in metastatic colorectal cancer. Until now, the resection technique involves Pringle maneuver, which allows reducing blood loss during transsection of liver parenchyma. However, the classical Pringle maneuver has restrictions due to ischemia/reperfusion (I/R) effect, in particular increasing risk of tumor recurrence after liver surgery. Aim: To study the pathological impact of surgical intervention and I/R effect on healthy liver tissue in the experimental setting by evaluating the markers of redox-homeostasis and oxidatively induced mutage­nesis, and also to assess the current possibilities of their correction by application of drag-reducing polymers (DRPs). Materials and Methods: MC38 mouse colon adenocarcinoma cells were transplanted intrahepatically to C57Bl/6 mice. The influence of warm ischemia on metastatic potential of MC38 cells, the speed of superoxide radicals (SR) generation and 8-hydroxydeoxyguanosine content were studied. Results: In case of modeled liver metastases, the surgery initiates an increase in the rate of SR generation into the remaining liver tissue and, consequently, provokes its ischemic injury. The application of DRPs protects liver tissue under I/R conditions. Conclusions: The warm I/R can promotes metastatic lesions in the healthy part of the organ with underlying increase in the rate of SR generation and oxidatively induced damage of guanine in DNA. The hemorheological effects of DRPs ensure increase of microcirculatory perfusion and oxygenation of liver tissues with the reduction of the rate of SR generation and decrease of 8-hydroxydeoxyguanosine as a marker of oxidatively induced mutations in DNA of hepatocytes. The intraperitoneal administration of nanomolar doses of DRPs prevents the activation of the growth of dormant metastatic MC38 cells in the liver. Further experimental and clinical study of these substances will allow reducing the risks of activation of uncontrolled tumor growth in the liver due to the pathological effect of post-operative I/R.

Background: For the last three decades, the world surgical community successfully adopted different surgical strategies for colorectal cancer (CRC) patients with liver metastases (LM), however, we are still seeing the evolution of treatment guidelines. The purpose of the study was to analyze a 20-year evolution of CRC patients with LM being treated in a specialized state Ukrainian oncological center. Materials and methods: The retrospective analysis of 1118 CRC patient cases using prospectively collected patient data from the National Cancer Institute registry. The time ranges between 2000–2010 and 2011–2022 and the LM manifestation – metachronous (M0)/synchronous (M1) were the two main grouping criteria. Results: The overall survival 5-year survival of patients who had surgery between 2000–2011 and 2012–2022 was 51.3 and 58.2% (P=0.61) for the M0 cohort and 22.6 and 34.7% at M1 (P=0.002), respectively. The results of the multivariate analysis in 1118 cases revealed that liver re-resection and regional lymph node dissection ≥D2 were associated with better overall survival [hazard ratio (95% CI)=0.76 (0.58–0.99) P=0.04] in the M0 cohort and receiving at least 15 courses of chemotherapy had better recurrence-free survival rates [hazard ratio (95% CI)=0.97 (0.95–0.99), P=0.03] for both M0 and M1. Conclusions: It was shown the improvement of the oncological prognosis for CRC patients with synchronous LM who were treated after 2012. The adaptation of world experience algorithms and the surgical strategy evolution have become the root cause of the above.

Background: Preliminary study results demonstrated parenchyma-sparing surgery (PSS) as an effective approach which allowed to remove colorectal cancer (CRC) metastatic lesions within the central liver cites and increased the probability of the liver re-resections. Methods: The prospective analysis re-evaluation of the 185 CRC patients surgical treatment has been performed. Results: An overall 5-year survival (OS) of the 185 enrolled patients was 43 ± 7%, and the mean and median value for OS was 48.7 ± 1.9% and 55.2 ± 5 (95% CI: 44.4–66.1) months. The 5-year OS for CRC patients whose metastatic lesions were predominantly located within peripheral and central liver segments was 56 ± 8% and 27 ± 9%, respectively (p = 0.08). A 5-year disease-free survival (DFS) rates of patients with peripheral and central liver cites metastatic lesions were 31 ± 7 % and 15 ± 7%, p = 0,12. And the DFS median was 34.2 and 46.5 months for R_1v and R0 cohorts, respectively, p = 0.62. Conclusions: Parenchyma-sparing surgery should be a priority pathway for complex treatment of patients with deeply located lesions of the right liver lobe. Trial registration: The study is registered in https://www.researchregistry.com/browse-the-registry#home/registrationdetails/5ed9f60863e9bf0016624456/, no. 5679.