Клинический случай легочной формы мукормикоза у ребенка с острым лимфобластным лейкозом

The article presents a clinical case of pulmonary mucormycosis in a 12‑year-old child at the stage of diagnosis of acute lymphoblastic leukemia. The first symptoms of the disease (headaches, malaise and weakness, pallor), changes in the general blood count (hyperleukocytosis up to 200 thousand cells/μl, single platelets). Based on the results of the examination, the main diagnosis was verified for acute lymphoblastic leukemia L2, IFT T-II, CD1a-. At the stage of diagnosis of acute lymphoblastic leukemia, the underlying disease was complicated by the development of right-sided pneumonia according to X-ray examination. To verify the etiology of infiltration of lung tissue, broncho-alveolar lavage was directed to microbiological diagnostics, which included studies: enzyme immunoassay, microscopic and cultural. On the aggregate of all the results obtained, invasive mucormycosis was diagnosed and antifungal therapy was started immediately.

The results of anterior rectal resection with the formation of a hardware anastomosis in cancer patients

Purpose of the study. A retrospective analysis of the immediate results of performing anterior rectal resections in cancer. Materials and methods. In the Department of Abdominal Oncology No. 1 with a group of X-ray vascular methods of diagnosis and treatment of the clinic of the National Medical Research Centre for Oncology of the Ministry of Health of Russia treatment for rectal cancer operations of anterior rectal resection were performed in 334 patients, while in 143 (42.8 %) cases they were low. As a standard, total mesenteric excision and lymphoid dissection in volume D2 were performed. Combined surgical interventions were performed in 68 (20.4 %) patients for locally spread tumors. As a rule, they were resection in nature and were performed with tumor infiltration of adjacent organs (bladder with ureters, ovaries, uterus, vagina, small intestine, abdominal wall). Colorectal anastomosis using crosslinking devices was formed in all cases, in 316 (94.6 %) cases it was a "side – to-end" junction, in 18 patients – "end-to-end". A preventive proximal intestinal stoma was formed in 73 (21.9 %) cases, where 67 cases it was an ileostomy, and 6 – a transversostomy. The preventive proximal intestinal stoma was not formed among 261 patients. Results. After performing anterior resections for rectal cancer operations, the complications developed in 75 (22.5 %) patients. The most threatening and dangerous complication was the failure of the colorectal anastomosis, which was noted in 12 (3.5 %) cases.This complication occurred in 8.2 % (6 patients out of 73) of preventatively stoma-treated patients, in 2.3 % of patients without a stoma (6 patients out of 261).Conclusion. The use of a preventive proximal intestinal stoma allows you to form a colorectal anastomosis even in the presence of complicated forms of rectal cancer. The number of complications directly referred to the formation of a preventive proximal intestinal stoma is relatively small, but when planning surgery for uncomplicated rectal cancer, the probability of their possible occurrence should be taken into account.

Methods for modeling tumor growth in mice in experimental studies of human gastric cancer

Gastric cancer (GC) is a group of malignant tumors originating from the gastric mucosa cells. The highest incidence of GC is recorded in Japan, China and Russia, and the lowest one in the USA and New Zealand. Extensive molecular genetic research of GC has revealed its heterogeneity associated with the genomic instability of the tumor and the complexity of its phenotype due to simultaneous changes in several oncogenes and suppressors. This was the basis for the creation of the GC classification by molecular subtypes. The creation of a realistic preclinical model is essential for translational GC studies. Cancer cell lines and xenografts derived from them are among the most common preclinical models. They are easy to generate, but they also have limitations, since these models cannot sufficiently reproduce the unique characteristics of each cancer patient. Patient-derived xenografts (PDX) are currently the best model for testing targets and predictors of response to therapy. PDX models are created by transplanting surgically resected human tumors into immunodeficient mice. These models maintain morphological similarity and replicate the molecular characteristics of parental tumors providing an indispensable tool for assessing anticancer drug response. Statistical data from preclinical studies with PDX models can significantly save the time and resources required for clinical trials. Transgenic and knockout mouse models are also widely used in scientific laboratories in order to study specific genetic pathways of oncogenesis and develop experimental therapy for GC. This review discusses the molecular classifications of GC and experimental murine models that reproduce cancer in situ and are a universal platform for preclinical research in experimental oncology.

A clinical case of pulmonary form of mucormycosis in a child with acute lymphoblastic leukemia

Mucormycosis of the lungs is a severe infectious complication in patients with acute lymphoblastic leukemia, which develops at the stage of high-dose cytostatic therapy. It is characterized by an extremely aggressive, rapidly progressive course and, without specific treatment, is fatal in a short time. Reliable verification of mucor is necessary due to its resistance to the most commonly used antifungal drugs, particularly to voriconazole.The article presents a clinical case of pulmonary mucormycosis in a 12‑year-old child at the stage of diagnosis of acute lymphoblastic leukemia. The first symptoms of the disease (headaches, malaise and weakness, pallor), changes in the general blood count (hyperleukocytosis up to 200 thousand cells/μl, single platelets). Based on the results of the examination, the main diagnosis was verified for acute lymphoblastic leukemia L2, IFT T-II, CD1a-. At the stage of diagnosis of acute lymphoblastic leukemia, the underlying disease was complicated by the development of right-sided pneumonia according to X-ray examination. To verify the etiology of infiltration of lung tissue, broncho-alveolar lavage was directed to microbiological diagnostics, which included studies: enzyme immunoassay, microscopic and cultural. On the aggregate of all the results obtained, invasive mucormycosis was diagnosed and antifungal therapy was started immediately.

The use of transdermal therapeutic systems for chemical pleurodesis in a patient with prolonged air leakage after lung resection for cancer

This clinical observation demonstrates a method of a motivated use of a transdermal therapeutic system (TTS) based on fentanyl for chemical pleurodesis in a patient with prolonged air leakage after lung resection for cancer. The most common complication after elective lung resections is an alveolar-pleural fistula or prolonged air leakage. This clinical phenomenon occurs as a result of communication between the alveoli of the lung parenchyma distal to the segmental bronchus and the pleural cavity. In most cases, air leakage through the drains is eliminated spontaneously, but the frequency of prolonged pneumostasis absence in the postoperative period can reach 25 %, which has a negative effect on the outcomes of surgical interventions due to the development of pneumonia and empyema. Long-term drainage of the pleural cavity does not always end with aerostasis and requires repeated invasive interventions. One of the ways to achieve the tightness of the lung tissue involves various methods of chemical pleurodesis, which is a surgical manipulation – the introduction of a sclerosing chemical substance into the pleural cavity by spraying medical talc through a trocar or a injecting tetracycline solution into the pleural drains. The chemical causes aseptic inflammation and adhesions between the visceral and parietal pleura, followed by obliteration of the pleural cavity. The sclerosant introduction is accompanied by severe pain that can provoke respiratory and/or hemodynamic deficits, up to apnea and life-threatening heart rhythm disturbances. Pain relief during chemical pleurodesis is obviously an important factor in the prevention of a number of complications in patients undergoing surgery for lung cancer. Bolus intravenous injections of narcotic analgesics lead to an analgesic effect, but a short-term one due to the absence of a depot in the body and a sharp drop in the drug concentration in the blood serum. Unfortunately, this method of introducing narcotic drugs can cause various complications in weakened and elderly cancer patients, such as respiratory depression and cardiac arrest. The TTS action is characterized with continuous dosing and the creation of a constant concentration of the narcotic drug over a certain period of time. This method provides a multilevel and systematic approach to pain relief, reduces toxicity and minimizes the inhibition of the central mechanisms of external respiration regulation without causing respiratory and cardiac disorders in patients who underwent lung resection.

Biomarkers for non-small cell lung cancer immunotherapy

The discovery of immune checkpoint inhibition has revolutionized the treatment of many solid malignancies, including non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICI) can restore the antitumor immune response by blocking the inhibition of T-cell activation. Anti-programmed death-ligand 1 (PD-L1) is currently the main biomarker of the effectiveness of anti-PD-1 / PD-L1 blockade in the treatment of NSCLC without driver mutations. High tumor mutational burden suggests an increased neoantigens load and has been associated with the effectiveness of ICI therapy. Microsatellite instability, a biomarker approved for immunotherapy across solid tumors, but it is uncommon in NSCLC. Primary resistance to ICIsis characteristic of NSCLC with driver mutations, acquired is associated with immunoediting resulting in the depletion of potentially immunogenic neoantigens. The review discusses recent advances and future directions for predicting the results of immunotherapy in patients with NSCLC.

The importance of developing new mannan tests in the diagnosis of invasive candidiasis in oncology patients

The regimens of anticancer therapy have been intensified and methods of high-dose chemotherapy (HDCT) have been introduced for recent years which made it possible to achieve significant progress in the results of tumor treatments. Intensification of chemotherapy regimens in cancer patients leads to the emergence of risk factors of invasive candidiasis (IC) development: agranulocytosis, disruption of the integrity of the mucous membranes, prolonged use of CVC, repeated antibiotic therapy, long-term parenteral nutrition. Thus, intensification of anticancer therapy may be accompanied by an increase in infection-mediated mortality.IC is the most common invasive mycosis in Russia. More than 11 thousand cases of IC occur in our country every year. The frequency IC in Russia is 8.29 per 100 thousand of the population, which corresponds to the results of the LIFE study in European countries where this indicator varies from 2.2 to 11 per 100 thousand of the population. There are no clinical signs or symptoms specific for IC. It develops in patients with concomitant diseases, which significantly complicates the diagnosis. In this regard, an urgent issue is to improve the diagnosis of candidal infectious complications in cancer patients in order to optimize treatment by studying serological markers that have the greatest value in the diagnosis of infectious complications in cancer patients.

Blood levels of growth and progression factors in patients with locally advanced breast cancer during neoadjuvant chemotherapy

Purpose of the study. An analysis of blood levels of TGF-β, TGFR2, TNF-α, TNF-αR1, TNF-αR2, CD44 and MMP9 in patients with various biological subtypes of breast cancer receiving neoadjuvant chemotherapy.Materials and methods. This article presents an analysis of levels of growth and progression factors (TGF-β, TGFR2, TNF-α, TNF-αR1, TNF-αR2, CD44 and MMP9) in the blood of 162 patients with various biological subtypes of locally advanced breast cancer receiving 8 cycles of neoadjuvant chemotherapy.Results. Levels of TGF-β, TGFR2, TNF, TNF-α, TNFR1, TNFR2, CD44, MMP9 in patients with all BC subtypes were high before the treatment. After chemotherapy cycles, the values decreased statistically significantly in all BC subtypes: CD44 decreased by 25.2 %, 30 % and 54.7 % in luminal A, luminal B and TNBC, respectively; TNFα– by 26.2 %, 48.3 % and 50.8 %, respectively; TNFα-R1 – by 52.1 %, 39.2 % and 50.3 % respectively; TNFα-R2 – by 31.7 %, 32.8 % and 41.9 % respectively; MMP9 – 35.3 %, 32.6 % and 43.3 % respectively.Conclusions. We identified a combination of growth and progression factors which determines the chemotherapy sensitivity and resistance in all subtypes of breast cancer; so, a decline in the levels of TGF-β, TNFα, MMP9 and CD44 after neoadjuvant chemotherapy predicts further remission for at least 3 years. On the contrary, stabilization or an increase of these indicators leads to the early tumor progression.

Functional state of cardiomyocyte mitochondria in malignant process in presence of comorbid pathology in experiment

Purpose of the study. An analysis of indices of free radical oxidation and respiration of mitochondria of heart cells in a malignant process in presence of diabetes mellitus and chronic neurogenic pain in experimental animals.Materials and methods. The study included outbred female rats (n=32) and С57ВL/6 female mice (n=84). Experimental groups of rats were: intact group 1 (n=8), control group 1 (n=8) with diabetes mellitus (DM), comparison group 1 (n=8) with standard subcutaneous transplantation of Guerin’s carcinoma, main group 1 (n=8) with Guerin’s carcinoma transplanted after 1 week of persistent hyperglycemia. Experimental groups of mice were: intact group 2 (n=21), control group 2 (n=21) with a model of chronic neurogenic pain (CNP), comparison group 2 (n=21) with standard subcutaneous transplantation of melanoma (B16/F10), main group 2 (n=21) (CNP+B16/F10) with melanoma transplanted 3 weeks after the CNP model creation. Heart mitochondria were isolated by differential centrifugation. Levels of cytochrome C (ng/mg of protein), 8-hydroxy-2'-deoxyguanosine (8-OHdG) (ng/mg of protein), and malondialdehyde (MDA) (μmol/g of protein) were measured in mitochondrial samples by ELISA. Statistical analysis was performed using the Statistica 10.0 program.Results. DM in rats upregulated 8-OHdG by 6.3 times and MDA by 1.9 times (р=0.0000) and downregulated cytochrome C by 1.5 times (р=0.0053) in heart cell mitochondria, compared to intact values. DM+Guerin’s carcinoma in rats increased 8-OHdG by 14.0 times and MDA by 1.7 times (р=0.0000) and decreased cytochrome C by 1.5 times (р=0.0000), compared to intact values. CNP in mice did not affect the studied parameters in mitochondria of the heart. CNP+B16/F10 in mice increased 8-OHdG by 7.1 times and MDA by 1.6 times (р=0.0000) and decreased cytochrome C by 1.6 times (р=0.0008).Conclusions. Comorbidity (diabetes mellitus, chronic neurogenic pain) together with malignant pathology aggravates mitochondrial dysfunction of heart cells with destabilization of the respiratory chain mediated by free radical oxidation processes.

Changes in the level of cardiomarkers in the development of acute myocardial infarction on the background of chemotherapy of a patient with tongue cancer

Cancer is one of the leading causes of death and disability worldwide. Timely diagnosis and the introduction of new effective treatments, including intensive radiation and chemotherapy regimens, have significantly improved survival forecasts in recent years. At the same time, the use of these types of treatment increases the risk of complications, one of which includes chemotoxic cardiopathies. In this regard, timely detection and treatment of complications from the cardiovascular system in patients receiving chemotherapy courses in combination with surgical methods of treatment is important. This paper presents an assessment of the significance of the use of cardiomarkers in the early diagnosis of acute myocardial infarction that developed during chemotherapy in a patient with tongue cancer with a complicated cardiac history. Patient M., 45 years old, was admitted for surgical treatment for cancer of the tongue St. IVA, T4aN1M0, cl. gr. 2. Planned laboratory and instrumental studies were performed. Contraindications for surgical treatment were not identified. A preoperative course of chemotherapy was performed, against the background of which the patient's condition worsened with symptoms of acute cardiopathy. A second ECG was urgently performed, as a result of which an increase in the ST segment in III, aVF was established, as well as a study of the concentration of cardiomarkers: highly sensitive troponin I, N-terminal propeptide of natriuretic hormone, creatine phosphokinase MB, myoglobin, the dynamics of changes in the level of which indicated the development of acute coronary syndrome. The complex application of diagnostic procedures, including the determination of the level of cardiomarkers, made it possible to timely diagnose the development of acute type 1 myocardial infarction in a patient with tongue cancer on the background of chemotherapy. When analyzing the entire array of clinical and laboratory data, the leading initiating factor that played a decisive role in the development of myocardial infarction in this case was, in our opinion, a preoperative course of polychemotherapy with paclitaxel and carboplatin, which have cardiotoxicity. Thus, the category of patients with an initial unfavorable background, due to a common malignant process and the presence of a history of cardiodisfunction, requires more careful preparation for preoperative courses of polychemotherapy, including cardiotropic therapy with mandatory monitoring of the level of the main cardiomarkers. The most significant changes were in the levels of creatine phosphokinase MB, troponin I, and myoglobin, which were recorded in the first hours of myocardial infarction. An association was found between an increase in troponin I concentration and an increase in the ST segment of the electrocardiogram.