КЛИНИЧЕСКИЕ НАБЛЮДЕНИЯ
Purpose: to study the role of virtual multislice-CT-bronchoscopy in the detection of bronchial tumors and assessment of bronchial tumor extension. Material and methods. Findings of the virtual multislice-CTbronchoscopy were analyzed in 61 patients with primary and secondary bronchial tumors. Virtual multislice-CTbronchoscopy was performed using the AquilionONE (320-slice) CT scanner. Results. Virtual bronchoscopy revealed 3 types of bronchial involvement: peribronchial, intrabronchial and mixed tumor infiltrations. The virtual fly through bronchoscopy was used to assess the macrostructure and tumor margins in patients with intrabronchial tumor growth. Broad-based polypoid masses causing the obstructing narrowing of the bronchus were visualized inside the bronchial lumen. The narrowing of the bronchial lumen and no visualization of the cartilaginous structures (the bronchus turned into the deformed tubular structure) were the signs of infiltration of the main bronchi and the trachea. In patients with lung and hilar lymph node metastases, infiltration of segmental and lobar bronchi led to the impaired ventilation of the affected segments or lobes of the lungs, thus resulting in the development of atelectasis. In patients with benign tumors, the lesion was characterized by the regular shape, smooth surface and homogeneous internal structure, as well as the absence of infiltration of the bronchial wall. Conclusion. Virtual multislice-CT-bronchoscopy with multiplanar and three dimensional reconstruction is a reliable noninvasive method for accurate diagnosis of bronchial involvement and the differential diagnosis between extrinsic pressure on the bronchial tree and bronchial tumor.
Purpose: To compare the possibility of using multiple-gated acquisition scan (MUGA) and 99mTc-MIBI GATE SPECT for evaluation and forecast of anthracycline–induced cardiotoxicity in breast cancer patients. material and methods. The study included 67 women (mean age – 44 ± 4.9 years) with breast cancer without significant pathology of the cardiovascular system. For the treatment of these patients used doxorubicin in dose of 50 mg/m2 per course in combination with various drugs. All patients were studied by MUGA (n=33) or GATE SPECT (n=34) before starting chemotherapy, at 1 hour after the first administration of doxorubicin and after the 4th course. results. After administration of doxorubicin at a dose of 50 mg/m2 was found that 11 patients according MUGA and 14 patients according GATE SPECT had a significant (10 % or more) reduction in left ventricular ejection fraction (LVEF). Significant inhibition of systolic function in this patient group remained after the 4th course treatment. In the individual analysis of the MUGA and GATE SPECT results, registered after the administration of doxorubicin at a dose of 200 mg/m2, was revealed that the criterion of LVEF reduction (10 % or more) in response to the first dose of doxorubicin can predict the development of chronic cardiotoxicity. Conclusion. The MUGA and GATE SPECT can be applied with equal effectiveness for evaluation of acute and chronic anthracycline–induced cardiotoxicity in breast cancer patients. The decrease in LVEF (10 % or more) in response to the first dose of doxorubicin can predict the development of chronic cardiotoxicity.
The study was undertaken to analyse molecular markers associated with clinical response to preoperative chemotherapy in patients with muscle-invasive bladder cancer. the purpose of the study was to determine the relationship between the expression of transcription factors, vascular endothelial growth factor (VEGF), activity of proteasomes and calpaines in tumors and the response to neoadjuvant chemotherapy of patients with muscle-invasive bladder cancer. material and methods. The study included 50 patients with histologically verified transitional cell carcinoma of the bladder T2a–3bN0M0 (G2-G3). The levels of transcription and growth factors were determined by an immunoenzymatic assay. Proteasome activity was measured using the fluorometric method. results. Patients who achieved partial tumor regression demonstrated higher levels of VEGF and transcription factors (NF-κB and HIF-1), but lower levels of the 26S proteasome compared to those observed in patients with stable disease. Conclusion. Additional molecular markers that can be considered as predictors of response to neoadjuvant chemotherapy for bladder cancer were identified.
LABORATORY AND EXPERIMENTAL STUDIES
The identification of women who are at high risk of developing breast cancer plays a key role in chemoprevention of breast cancer selective estrogen receptor modulators. purpose: To study specific immune responses to chemical carcinogens and sex steroid hormones associated with breast cancer in postmenopausal women. material and methods. Serum IgA-antibodies specific to benzo[a]pyrene, estradiol and progesterone were studied in 203 non-smoking healthy women and 469 non-smoking breast cancer patients (125 with ER– and 344 with ER+) using semi-quantitative enzyme immunoassay. results. The low levels of all three antibodies were revealed in 53.2 % of healthy donors, in 47.2 % of breast cancer patients with ER– and in 40.7 % of patients with ER+. The high levels of all three antibodies were found in 12.3 %, 18.4 % and 26.5 % of cases, respectively. In the studied groups, the levels of antibodies to estradiol and progesterone were correlated with the levels of antibodies to benzo[a]pyrene (rs=0.54–0.7, p<0.0001). Conclusion. Immunoassay of antibodies to exogenous and endogenous antigens could be useful for determining risk of developing ER+ breast cancer and preventing administration of tamoxifen and others selective modulators of estrogen receptors. Active immunization against exogenous chemical carcinogens could increase the levels of antibodies to endogenous steroids, thus stimulating breast cancer.
Introduction. Changes in the redox status of tumor cells can be used as one of the molecular mechanisms of apoptosis aimed at increasing the susceptibility of tumor cells to chemotherapeutic agents. Purpose: to study the mechanisms of dysregulation of apoptosis in P19 tumor cells under the conditions of redox status modulation. Material and methods. Apoptosis in P19 tumor cells was assessed by flow cytometry analysis. The number of annexin-positive cells, the expression of CD95 and CD120, as well as the intracellular calcium ion concentration and the percentage of cells with reduced mitochondrial transmembrane potential were measured. The protein-glutathione mixed-disulfide level and the GSH/GSSG ratio were determined by spectrophotometry. To modulate redox status of cells, the protector and blocker of SH-groups, or N-acetylcysteine were used. Results. Incubation of cultures in the presence of SH-group blocker resulted in the imbalance in the glutathione system with increased concentration of glutathionylated proteins. A decreased redox status led to an increased CD95 and CD120 expression levels on the membrane of P19 tumor cells, as well as to decreased mitochondrial potential and increased intracellular calcium ion concentration, thus contributing to the launch of a P19 tumor cells. The presence of SH-group blocker and N-acetylcysteine resulted in an increased number of annexinpositive cells. Conclusion. Along with the development of oxidative stress, the molecular redox-dependent mechanisms of apoptosis dysregulation through the mitochondrial and receptor-mediated pathways were identified in the P19 tumor cells.
The tumor niche in the microenvironment of the primary tumor is believed to reflect events occurring in the premetastatic niche. In our study, based on the assessment of the expression of cytokine genes associated with inflammation and invasive and metastatic phenotype of tumor cells in the tumor microenvironment, their contribution to the creation of favorable conditions for the development of tumor and metastases was described. Material and methods. The main clinical and pathological parameters in 12 patients with invasive breast carcinoma of non-specific type (IC NST) were studied. The expression of 13 genes encoding key cytokines and chemokines in the stroma of IC NST was assessed using the PALM laser microdissection system and real-time polymerase chain reaction. Results. A direct correlation between the size of the primary tumor and the expression levels of IL1b and CXCL8 genes was found. Furthermore, it was shown that the proliferative activity of tumor cells was inversely correlated with the expression CCL2 gene that attracted monocytes. The expression of IL6 and IL8 genes involves the differentiation of monocytes into M2 macrophages, which can stimulate tumor cell invasiveness. However, microenvironment cells were found not to express MST1, FGF7, EGF genes, protein products of which provide invasive and metastatic progression of tumor cells. In our study, no significant differences in gene expression levels between patients with and without lymph node metastases were found. Nevertheless, the use of the multivariate data analysis allowed us to reveal a close relationship between the studied parameters related to a high risk of lymph node metastasis. Conclusion. A wide range of cytokines involved in the development of inflammation, recruitment of monocytes, as well as secretion of factors promoting both tumor growth and lymphatic metastasis was identified. Similar events in premetastatic niche might contribute to the development macrometastasis.
ONCOLOGY PRACTICE
The purpose of the study was to evaluate the efficacy of preoperative embolization of the common hepatic artery in patients with pancreatic body and tail cancer invading the celiac trunk. Material and Methods. Twenty-two patients underwent distal subtotal pancreatectomy with resection of the celiac trunk and the common hepatic artery. Of these 22 patients, 6 underwent preoperative embolization of the common hepatic artery. Results. In spite of invasion of the celiac trunk, the hepatic arterial blood flow was completely blocked in all patients who underwent preoperative embolization of the common hepatic artery. No complications related to endovascular intervention were found. In all cases, control angiography showed an adequate blood supply to the liver due to collateral circulation from the superior mesenteric artery. No ischemic complications were observed in postoperative period. Conclusion. Preoperative embolization of the common hepatic artery appeared to be a safe procedure that could prevent the risk of ischemic complications in patients undergoing distal subtotal pancreatectomy with resection of the celiac trunk and the common hepatic artery without plastics.
Stoma surgery in patients with obstructive rectal cancer is not a rare case. That is why we studied a possibility of conservative treatment with large bowel obstruction (LBO) using the method of endoscopic recanalization. Material and methods. We enrolled 117 rectal cancer patients with acute or partial LBO. Fifty-eight patients were treated with endoscopic recanalization of lumen. After achieving intestinal decompression, the patients received preoperative chemoradiotherapy (40–60 Gy, tegafur 300 mg/м2, 1–28 days) followed by surgery. The control group consisted of 59 patients who were treated with surgery followed by chemoradiotherapy. Results. Decompression was successful in 48 patients (82.7 %). Partial recanalization was observed in 8 patients, but it was not obstacle to perform chemoradiotherapy. Two patients developed complications (paracolic abscess), requiring unplanned emergency surgery. The frequency of sphincter-preserving surgical procedures was 82.6 % in the study group and 28.8 % in the control group, p<0.001. Conclusion. The proposed method of intestinal decompression allowed the number of sphincter-sparing surgery to be increased without worsening the disease prognosis.
REVIEWS
Esophageal cancer is an aggressive form of cancer. Adenocarcinoma and squamous cell carcinoma are the most common histological types of esophageal cancer, with the incidence rate showing an upward tendency. Although endoscopic biopsy is considered the «gold standard» for diagnosis of esophageal cancer, both falsepositive and false-negative results can occur, therefore, the predictive and prognostic molecular markers in outcome of esophageal cancer are required. Although the molecular events involved in esophageal cancer pathogenesis are still poor understood, there have been reports on histological and genetic changes, such as DNA aberrant methylation and copy number variation, changes in DNA stability, its expression and etc. This review summarizes various investigations aimed at studying genomic instability (microsatellite instability, MSI), which predisposes the cell to malignant transformation. The mechanisms of interaction between the mismatch repair and miRNA expression in esophageal cancer have been studied. Recent advances in genomic and molecular studies of MSI+ cancers can successfully complement the histological assessment and help to develop novel therapeutic approaches to cancer treatment.
CASE REPORTS
Squamous cell ovarian and sigmoid colon carcinomas are extremely rare malignancies. Because of their rarity, it is difficult to investigate the clinical characteristics and prognosis of patients with theses malignancies, and therefore, the increased interest in each clinical case report is highly relevant. Multiple primary squamous cell ovarian and sigmoid colon carcinomas are the subject of discussion and differential diagnosis of sigmoid colon cancer with secondary ovarian cancer. Histopathological and clinical characteristics of the tumors were present and evidences in favor of the multiple primary malignancies were given. The association of squamous cell ovarian and sigmoid colon carcinomas with human papilloma virus type 16 was shown.
Benign tumors of the esophagus and stomach are rare lesions and they usually present as leiomyomas. There have been no published reports indicating high metabolic activity of leiomyomas, detected by PET-CT. In the present case, gastric leiomyoma extending into the esophagus was found to have a high 18F-FDG uptake.
We present a case report of locally advanced colorectal cancer that responded successfully to conservation chemotherapy allowing R resection to be performed. Morphological characteristics prior to and after chemotherapy have been described in detail. This case report demonstrates the feasibility of performing radical treatment for patients with locally advanced rectal cancer using neoadjuvant chemotherapy.
CHRONICLE. INFORMATION
ISSN 2312-3168 (Online)