ORIGINAL ARTICLES
Purpose of the study. Analysis of the possibility of using presepsin in the early diagnosis of sepsis in cancer patients after extensive surgical interventions for tumors of the thoraco-abdominal localization.
Materials and methods. The study included 27 people: 10 healthy individuals (control) and 17 patients who received surgical treatment at the National Medical Research Center of Oncology for malignant neoplasms of thoraco-abdominal localization. In the blood of all patients, studies of sepsis markers were performed: presepsin (P-SEP), highly sensitive CRP (hsCRP) (PATHFAST, Japan), procalcitonin (PCT), interleukin 6 (IL6) (Cobas e 411, Germany), as well as lactate, total leukocyte count (WBC) with a leukocyte formula, a blood culture test for suspected septic complications included in a routine examination. The studies were carried out before and on the 2nd day after the operation. Data were assessed by comparing P-SEP levels with hsCRP, PCT, IL6, lactate, WBC, blood culture test results, and the clinical status of patients. Depending on the data obtained, 2 groups were distinguished: I – patients with confirmed sepsis (3 people), II – without sepsis (14 people). Statistical processing was performed using STATISTICA 13.0.
Results. In the control group, the level of P-SEP was 182.7 ± 11.9 pg/ml. In patients before surgery, the marker values were 213.7 ± 47.7 pg/ml, which did not differ statistically from the control data and did not go beyond the reference values, as did the content of PCT, hsCRP, IL6. On the 2nd day after surgery, all patients showed unidirectional changes, characterized by an increase in the levels of the studied parameters, but with varying degrees of intensity. The most significant was the increase in the concentration of presepsin. At the same time, it was noted that the level of presepsin on the 2nd day after surgery in patients of group I patients with confirmed sepsis averaged 2577.5 ± 1762.5 pg/ml with a maximum level 4340.0 pg/ml, and in group II with In the absence of confirmed bacteremia, there was an increase in the level of presepsin 1205.0 pg/ml. The data obtained correlated with the dynamics of changes in the concentration of other sepsis markers – hsCRP, PCT, IL6. Thus, the study of the level of presepsin, along with widely used markers – hsCRP, PCT, IL6, allows diagnosing sepsis in the early postoperative period in cancer patients.
Conclusion. In patients with malignant neoplasms of thoracoabdominal localization, changes in the levels of sepsis markers in the early postoperative period can be used as a basis for prescribing antibiotic therapy. Presepsin may be recommended for use as an early marker of sepsis in patients with oncological pathology.
Purpose of the study. Creation and study of models of primary multiple malignant tumors (MMPT model) under experimental conditions.
Materials and methods. The study was carried out involving male and female BALB/c Nude mice (n = 42). Experimental groups of mice: with melanoma B16/F10 (B16/F10), males (control 1) and females (control 3) by n = 7; control 2 – with sarcoma 45 (C45), males n = 7; control 4 – with Guerin carcinoma (KG), females n = 7; basic: MMPT model No. 1 – B16/F10 and S45, males n = 7, and MMPT model No. 2 – B16/F10 and GC, females n = 7. 0.5 ml suspension of murine B16/F10 melanoma tumor cells diluted in the saline proportions 1:20 was injected under the skin of the left dorsal side to all animals with MMPT model, as well as 0.5 ml of a suspension containing 0.50 × 106 S45 or GC tumor cells in the saline under the skin on the right dorsum. Control groups received the same amount of tumors as the MMPT model.
Results. Tumors in male mice in MMPT model No. 1 appeared simultaneously and significantly earlier than in controls: В16/ F10 melanoma by 3 times, S45 by 2 times. Tumor zises in MMPT model No. 1 were larger than in the corresponding controls: by 8.5 times at the area of В16/F10 melanoma inoculation and by 2.2 times at the area of S45 inoculation. Melanoma metastasized under the S45 capsule. Tumor at the area of GC transplantation in MMPT model No. 2 grew 5 times faster than at the area of В16/F10 melanoma injection; both tumors appeared on average 3 times earlier than in control groups 3 and 4. Tumor volumes in MMPT model No. 2 were larger than in the corresponding controls: by 7.5 times at the area of В16/F10 melanoma inoculation and by 2.2 times at the area of GC inoculation. However, almost the entire volume of the tumor node in the area of B16/F10 melanoma transplantation was represented by GC tumor tissue due to metastasis from the primary GC tumor. Melanoma remained as a small black spot with a diameter of 5–6 mm at the area of its inoculation under the skin. The average survival of mice in MMPT models No. 1 and No. 2 was 1.5–2 times (p < 0.05) lower than in the corresponding controls.
Conclusions. Sequential subcutaneous transplantation of mouse B16/F10 melanoma and rat sarcoma 45 to BALB/c Nude mice increased the malignant potential of each tumor: the time of their onset was shorter, and the growth rate of tumors increased which decreased the survival of animals. Sequential subcutaneous transplantation of mouse B16/F10 melanoma and Guerin's rat carcinoma to female BALB/c Nude mice suppressed tumor growth of B16/F10 melanoma and increased the malignant potential of rat GC.
Purpose of the study. To analyze the physical and neuropsychiatric development of pediatric patients who underwent cranial irradiation in the period from 2015 to 2020 in the radiotherapy department of the National Research Center of Oncology and to assess the risk of post-radiation complications.
Materials and methods. 17 children aged from 3 to 17 years were hospitalized under medical supervision in the department of pediatric oncology of the National Medical Research Centre for Oncology. All the children underwent a course of conformal radiation therapy totally on the brain area and the first two cervical vertebrae in the radiotherapy department of the National Medical Research Centre for Oncology. 13 patients (76.7 %) underwent radiation therapy due to the prevention of neuroleukemia with a total dose of 12 Gy (a dose per fraction was 2 Gy), 2 patients with a confirmed relapse of acute lymphoblastic leukaemia (ALL) (11.65 %), 1 patient with a confirmed diagnosis of neuroleukemia (5.8 %) and 1 patient from the high-risk group (5.8 %) – with a total dose of 18 Gy (a dose per fraction was 2 Gy). Further 75 month regular medical checkup was carried out on the basis of the Regional Children's Clinical Hospital for.
Results. None of the surviving patients showed growth retardation. Two patients (11.65 %) complained of increased fatigue, decreased concentration; one patient (5.8 %) showed unmotivated irritability and aggression during the examination. Intellectual development corresponded to age in all patients (100 %). One patient (5.8 %) experienced episodes of nausea and vomiting (grade 1 on the CTCAE scale), three patients (17.7 %) suffered from headache (grade 2 on the CTCAE scale), three patients (17.7 %) complained of fever up to 38 °C (1 degree on the CTCAE scale). Two out of 17 ALL patients died due to disease progression.
Conclusion. Taking into account the different time intervals between treatment and the moment of the study (from 9 to 75 months), cranial irradiation demonstrates relative safety for patients undergoing treatment during critical periods of development of both physical and neuropsychic spheres. However, an objective assessment of the development prospects is difficult due to the relatively short time after undergoing therapy (from 9 to 75 months) and a small sample of patients.
REVIEWS
Malignant tumors of the head and neck are still one of the most challenging problems of treatment in modern oncology. The disease affects mainly the capable people (from 30 to 60 years old). Tumor lesions of the paranasal sinuses lead to disability and have a high mortality rate. Head and neck tumors comprise of 20–30 % of all cancer cases. People with early paranasal sinus cancer have minor complaints, their general condition doesn’t get affected so they don’t seek for medical care in a while. As a result, patients start on treatment at tumor grades III–IV. This article provides the most complete information about the causes, frequency and special features of the course of paranasal sinus cancer, as well as about modern methods of it’s diagnosis and combination treatment. Despite the great advances in the treatment of these malignant tumors the three and five year survival rates remain unsatisfactory, which requires a research for new effective treatments. Currently the main treatment methods for these malignant tumors are combination and complex (involving surgery, radiotherapy and chemotherapy) treatments. The standard treatment approach includes radical surgical removal of the primary tumor and metastatic lymph nodes followed by radiation or chemoradiation therapy. Chemotherapy as monotherapy is administered in non-resectable primary or recurrent tumors, distant metastases or when a patient refuses the radical surgery. Improvement of existing treatment methods and development of new ones are an essential need. Earlier detection of the disease requires primary care physicians to be trained to diagnose tumor lesions of the paranasal sinuses, and highly specialized physicians (dentists, otorhinolaryngologists, maxillofacial surgeons, dermatologists) to express their cancer alertness.
Lung cancer (LC) takes the first place in the structure of overall oncology in males. More than 1.8 million of new cases of lung cancer (LC) are registered each year worldwide. LC is the leading cause of cancer death in both developing and developed countries, and the 5 years survival rate is as low as 19 %. Many factors explain such unsatisfactory outcomes, including the LC diagnosis at an advanced stage, when the currently available treatments can rarely provide cure. Non-small cell lung cancer (NSCLC) with chromosomal rearrangement of anaplastic lymphoma kinase (ALK) is sensitive to targeted therapy with tyrosine kinase inhibitors (TKIs). Tumor cells containing ALK fusion are sensitive to TKIs – targeted drugs that have significantly improved the results of treatment of patients with ALK-positive NSCLC, half of whom survive more than 6.8 years after diagnosis. The number of patients with ALK-positive NSCLC varies, so ALK rearrangements are detected in about 3–7 % of lung adenocarcinomas, which accounts for up to 60.000 new cases of the disease annually worldwide. ALK-positive NSCLC is observed almost exclusively in adenocarcinomas associated with persons of younger age, male and never smoked or smoked a little. Patients with ALK-positive stage I–III NSCLC are shown treatment similar to patients with wild-type NSCLC, including surgery, radiation therapy, chemotherapy or multimodal treatment, depending on the stage of the tumor process. Numerous ALK TKIs have been developed in recent years, including alectinib, which is the current preferred first-line agent for patients who haven’t received therapy. The study of the mechanisms of resistance has led to the development of next-generation ALK inhibitors that better penetrate the central nervous system, actively affecting brain metastases. This review highlights the current state and prospects for the development of ALK-positive NSCLC therapy.
Abnormal gene copies, a special type of genetic polymorphism, is a hallmark of most solid tumors, including colorectal cancer. Abnormal copy number of genes leads to tumor-specific genomic imbalance, which manifests itself already in precancerous precursor lesions. The aim of this review was to systematize the scattered data on changes in gene copy number observed in colorectal cancer and their impact on the outcome of the disease and response to therapy. The data from 58 studies was analyzed on gene copy number changes and their expression in primary carcinomas, cell lines and experimental models. This review examines the spectrum of genetic changes that lead to colorectal cancer, describes the most frequent changes in the number of gene copies at different stages of the disease, and changes in the number of gene copies that can potentially affect the outcome of the disease of individual patients or their response to therapy. In fact, aberrant gene copy number as a form of chromosomal imbalance affects a number of genes that provide a metabolic selective advantage for a tumor cell. Changes in the genes copy number in colorectal cancer patients not only positively correlate with changes in their expression, but also affect the levels of gene transcription at the genome-wide scale. Aberrant gene copy numbers are closely related to disease outcome and response to treatment with 5 fluorouracil, irinotecan, cetuximab and bevacizumab. Nevertheless, the possibility of translating the genes copy number index into clinical practice requires further research.