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Siberian journal of oncology

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No 5 (2015)
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CLINICAL STUDIES

5-13 3006
Abstract

Background. Patients are referred to a specialized oncologic hospital with diagnosis of gastric cancer, which has been already established. Under this condition it is important to determine the clinical problems in which CT plays a crucial role. The aim of the study is the systematization of the major clinical challenges being addressed by CT in patients with gastric cancer treated at the radio-oncological hospital. Methods. A total 120 patients with gastric cancer at the different phases of combination therapy were included in our study: 91 patients underwent preoperative CT for the tumor staging; 70 patients underwent CT topometry; 40 patients were examined with CT in order to the post-therapy control. Results. The role of computed tomography in the study of gastric carcinoma is mainly represented by the staging of tumor according to the TNM system; CT topometry; assessment of response to neoadjuvant therapy; evaluation of postoperative complications and the post-therapy control. Conclusion. In a specialized hospital, CT plays a key role in the management of gastric cancer. CT has important impacts on clinical decisions and allows solving specific clinical problems.

14-20 1186
Abstract

Background and purpose. The purpose of this investigation was to evaluate feasibility, safety and efficacy of radiotherapy for inoperable non-small-cell lung cancer (NSCLC). Various radiotherapy planning methods have been proposed to decrease normal tissue toxicity. We compared 2D-RT with 3D-RT for NSCLC. Parameters assessed included dose to PTV and organ-at-risk (OAR), multiple conformity and homogeneity indices. Material and methods. Initial and re-simulation CT images from 52 consecutive patients with IIB – IIIB NSCLC were used to quantify dosimetric differences between 2D and 3D conformal radiotherapy. Contouring was performed on both CTs, and plans (n=104 plans) and dose-volume histograms were generated. Results. All plans provided comparable PTV coverage. Compared with 2D-RT, 3D-RT significantly reduced the maximum dose to heart (p<0.01), spinal cord (p<0.01), whole lung (p<0.01), esophagus (p<0.02) – Wilcoxon test.

21-29 1109
Abstract

The purpose of the study was to compare immediate surgical outcomes of low anterior resections (LAR) and intersphincteric resections (ISR) of the rectum. Materials and methods. Treatment outcomes of 42 patients operated on between March, 2014 and January, 2015 were presented. Group I consisted of 24 patients who underwent laparoscopic ultra-low anterior resection (uLAR) for rectal cancer. Group II comprised 18 patients who underwent laparoscopic ISR. Results. No significant differences in the median length of surgery and blood loss between two groups were observed. Circular and distal resection margins were negative in all cases. In 18 (75 %) patients of Group I and in 14 (77.7 %) patients of Group II, total mesorectumectomy(TME) was assessed as grade 3 (p=0.83). The frequency of postoperative complications in uLAR-treated group was 20.8 %, not requiring a secondary revision procedure, and 27.8 % in ISR-treated group, requiring repeated surgery. The mean value of the fecal incontinence according to the Wechsler scale in a month after surgery was significantly higher in group II than in Group I patients (9.3 versus 6.2, р=0.01). The average treatment cost for uLAR was higher by 45,000 rubles than that for ISR. Conclusion. Both surgical procedures were matched by the duration of operation, amount of blood loss and the quality of mesorectumectomy. The complication rate was not significantly different between two groups, however, 16.8 % of Group II patients required relaparotomy, likely due to the mastering of the ISR technique. Ultra-low anterior resections of the rectum are functionally preferred. When performing ISR, the technique of reservoir colo-anal anastomosis with preservation of the portion of the internal sphincter provides functional results comparable with those obtained using LAR.

30-36 711
Abstract

The goal of the research: to evaluate short-and long-term treatment outcomes in patients with superficial bladder cancer, who underwent transurethral en block resection of the bladder wall tumor. Material and methods. Surgical treatment results were assessed in 270 patients with bladder cancer from 2003 to 2012. All patients were divided into 2 groups. Group I consisted of 94 patients who underwent transurethral en block resection of the bladder wall tumor. Group II (the control group) composed of 176 patients who received the conventional transurethral resection. Results. Local recurrence occurred 1.4-fold less frequently in Group I than in Group II patients (47.7 versus 34.0 %, p<0.05), and disease progression occurred 4-fold less frequently in Group I than in the control group (8.5 versus 2.1 %, p<0.001). Moreover, the Group I patients had a longer time to disease progression than the Group II patients (6.1 ± 3.1 versus 32.5 ± 75 months, p<0.05). Conclusion. Transurethral en block resection of the bladder wall tumor allows the depth of invasion to be exactly measured and the incidence of recurrence to be decreased.

37-43 1776
Abstract

In this study 122 strains of strictly anaerobic gram-negative rods Bacteroides, Prevotella and Fusobacterium, isolated from cancer patients between 2004 and 2014 were analyzed. The most common strains were B. fragilis (55 %) followed by Prevotella (34.4 %) and Fusobacterium spp (10.6 %). The species identification was carried out by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). Among the B. fragilis group strains, B. fragilis, B. thetaiotaomicron, B. ovatus and B. vulgatus were isolated most frequently. Among Prevotella species, the most frequently isolated species were P. buccae, P. buccalis, P. oris, P. denticola and P. nigrescens, and 77 % of the Fusobacterium spp. were F. nucleatum. Susceptibilities of the isolates to antimicrobial agents were determined by the E-test methodology. The percentage of the susceptibility of B. fragilis group isolates were: metronidazole, 97 %; imipenem, 95.5 %; amoxicillin/clavulanate, 95.5 % and clindamycin, 77.6 %. Three B. fragilis isolates proved to be multidrug-resistant (simultaneously to imipenem, amoxicillin/ clavulanate and metronidazole or clindamycin). All Prevotella isolates were susceptible to imipenem and amoxicillin/clavulanate, whereas 78.6 % of the pigmented Prevotella species and 46.4 % of the non-pigmented species were resistant to penicillin. The number of strains susceptibility to metronidazole and clindamycin were 93 % and 88 %, respectively. All Fusobacterium strains were sensitive to all tested antibiotics, including penicillin.

LABORATORY AND EXPERIMENTAL STUDIES

44-50 690
Abstract

Background. Search for more informative prognostic parameters in patients with renal cell carcinoma is an actual problem of modern oncology. Purpose: to study the prognostic significance of expression of transcription factors, VEGF growth factors, its receptors, m-TOR protein kinase and the activity of intracellular proteinases in patients with disseminated renal cell carcinoma. Material and methods. Forty patients with metastatic renal cell carcinoma (T3–4N0–1M1) were included into the study. In accordance with the MSKCC scale, all patients were divided into 3 groups: with good prognosis (n=13), intermediate (n=26) and unfavorable prognosis (n=1). Further, the analysis included patients with good and intermediate prognosis (n=39). All patients received targeted therapy with pazopanib or everolimus. Palliative nephrectomy was performed after completion of preoperative treatment. The level of transcription and growth factors was studied using IFA method. The proteasome and calpain activities were assayed fluorometrically. Results. Initially high levels of the expression of HIF-1 transcription factor and VEGF growth factor in renal cell carcinoma were associated with good disease prognosis evaluated according to the MSKCC scale. The targeted therapy with pazopanib/ everolimus resulted in decrease in the expression of HIF-1, NF-κB р65, NF-κB and р50 transcription factors, VEGF growth factor and the proteasome activity. The increased calpain activity in patients with intermediate prognosis was associated with disease progression. Conclusion. Additional molecular parameters that increase the informative value of the MSKCC scale were identified, allowing for more precise prediction of the disease outcome in patients with metastatic renal cell carcinoma.

51-58 730
Abstract

Recent research revealed dendritic cells (DCs) to have direct antitumor cytotoxic activity and to inhibit the growth and proliferation of tumor cells in vitro. The aim of the present study was to investigate the association between the cytotoxic activity of dendritic cells generated in the presence of interferon alpha (IFN-DCs) and TNFα expression by IFN-DCs in patients with malignant lymphomas. It was shown that IFN-DCs of malignant lymphoma patients possessed low cytotoxic activity against tumor cell line HEp-2 associated with low expression of transmembrane TNFα (tmTNFα) and high level of soluble TNFα (sTNFα) secretion. Reduced DC cytotoxic activity and low tmTNFα expression on DC surface were observed mainly in Hodgkin’s lymphoma patients. In contrast, IFN-DCs of patients with non-Hodgkin lymphoma were endowed with the ability to lysis of HEp-2 cells and tmTNFα molecule expression was similar to that in IFN-DCs from healthy donors. It was determined that the increase of expression of tmTNFα molecule on lymphoma patient IFN-DCs induced by the addition of TNFα-converting enzyme inhibitor into IFN-DC cultures was associated with the enhancement of IFN-DC cytotoxic activity against HEp-2 cells. 

59-66 863
Abstract

The mechanism of regulation of ABC transporter gene expression, which is related to individual characteristics of the tumor-bearing organism and its tumor, defined by gene single nucleotide polymorphisms (SNP – Single Nucleotide Polymorphism) has not been extensively studied. We conducted large-scale genome studies of association of SNP with the level of ABC transporter gene expression. The study involved 68 patients with morphologically verified diagnosis of breast cancer treated with neoadjuvant chemotherapy (NAC). Using a quantitative Real-time PCR, the expression of 4 multidrug resistence (MDR) genes (ABCB1, ABCC1, ABCC2, ABCG2) was studied in surgical samples after NAC. Microarray analysis was performed using high density DNA microarrays, which contain more than 750.000 SNPs. Six SNPs significantly associated with postoperative expression levels of multidrug resistance genes, ABCB1, ABCC1, ABCC2, ABCG2, were identified. It was shown that in carriers of a rare genotype, the expression levels of all 4 examined genes in tumors after chemotherapy were either decreased (rs2680835, rs1951366 and rs12018988), or increased (rs4676478, rs6896596, rs1154121) compared to those observed in carriers of frequent and heterozygous genotypes of the SNP. The possible mechanisms of the effect of the identified SNPs and their genes on the expression of ABC transporters were discussed.

67-73 596
Abstract

Melanoma of the skin is considered as multiplex neoplastic system characterized by high tumor heterogeneity. MicroRNAs are a class of epigenetic regulators by which 90 % of human genome is controlled. At the present time more than 1 500 types of microRNAs is identified. Comparative analysis of microRNA expression profile is performed in melanoma, melanocytic nevi and tumor microenvironment in the present study. The differences of microRNA expression levels should be under further consideration to evaluate their functional significance in melanomagenesis and possible application as melanoma prognostic and diagnostic markers.

74-79 637
Abstract

The purpose of the study was to determine the informative value of р53, CD 138 and Кi 67 markers in mucosal stratified squamous epithelium of patients with precancerous laryngeal lesions and laryngeal cancer. Material and methods. Expression of the above markers was analyzed in 80 patients with chronic laryngeal diseases and in 37 patients with laryngeal cancer. Results. The level of proliferative activity was shown to be directly proportional to more severe dysplastic and neoplastic lesions of the laryngeal mucosa, thus indicating the increased proliferative activity in precancerous lesions and their subsequent malignant transformation. Our data clearly show that suppression of apoptosis is one of the mechanisms of malignant epithelial transformation of epithelial cells. In difficult cases, a sharp increase in the levels of p53 and KI 67 in patients with grade III dysplasia can be considered as an additional criterion for evaluation of risk of malignant transformation. Based on the results obtained, CD138, a cell differentiation marker, is recommended to be considered as an additional criterion for selecting patients with grade II dysplasia into the group being at high risk for laryngeal cancer development. Conclusion. Persistently increased Ki67 expression level serves as an additional criterion for inclusion of patients with precancerous lesions to the group at increased risk of cancer. Alterations in the expression levels of р53 in patients with grade III laryngeal dysplasia are the signs of possible progression of premalignant lesions. 

80-83 4951
Abstract

Microsatellite instability is associated with dysfunction of the MSH2, MLH1, PMS2 and MSH6 genes, which participate in the repair of unpaired nucleotides of DNA. It is known that microsatellite instability is an independent prognostic factor in determining the differentiation grade of colon cancer. The use of immunohistochemistry to study the repair system of unpaired nucleotides has its own characteristics and limitations. Materials and methods. The study included 39 patients with colon adenocarcinoma. Moderately-differentiated colon adenocarcinoma was the most common histological type (72 %). There were 8 % of well-differentiated and 12 % poorly-differentiated carcinomas. Immunohistochemical analysis of SH2, MSH6, PMS2 and MLH1 proteins was done according to the standard protocol. Results. Out of 39 cases, 6 (15 %) had loss of expression of at least one of the studied proteins. Out of these 6 cases with indirect signs of MSI-H, 3 were poorlydifferentiated, 1 was mucinous and 2 were moderately differentiated adenocarcinomas. Conclusion. Thus, immunohistochemical analysis of DNA repair genes can be used to determine the histological differentiation of colon adenocarcinoma.

ONCOLOGY PRACTICE

84-91 789
Abstract

Objective: to evaluate the ability of high-field MRI to assess tumor response to chemoradiotherapy in patients with locally advanced cervical cancer. Material and methods. The study involved 43 patients. MRI was performed using a 1.5 Tesla MAGNETOM ESSENZA scanner (SIEMENS, Germany) with a magnetic field strength of 1.5 T. Intravenous bolus injection of paramagnetic contrast agent was used to assess the tumor spread and determine the tumor boundaries and its structure. Dynamic series of sections and delayed scans in standard T1-weighted sequence were obtained. Results. Dynamic contrast-enhanced MRI was shown to be a highly informative method that can be used to monitor the process of combined chemotherapy and radiation therapy in the treatment of patients with cervical cancer. It permits the objective assessment of the dynamics of tumor regression, changes in tumor vascularity and regional lymph node status. 

92-94 782
Abstract

The paper presents the first experience of using a combination of radiosurgery and resection of the liver in patients with extensive metastatic disease treated at theChelyabinskRegionalOncologyCenter. This technique results no in postoperative liver failure, thus allowing R0 resection to be performed for unresectable patients.

REVIEWS

95-101 2054
Abstract

The review presents the worldwide data on the cancer incidence and mortality and risk factors for cancer.

102-109 1048
Abstract

Currently, there is a marked tendency towards improvement of early detection of breast cancer that allows patients at extremely low risk for developing recurrent disease to be identified. Therefore, it is necessary to search for biological markers of unfavorable prognosis for patients with hormone-dependent breast cancer. In order to introduce these markers into routine clinical practice, they should be validated in welldesigned clinical studies, provide additional predictive information and be easily reproducible. The standard immunohistochemical parameters (estrogen and progesterone receptors and Ki67 cell proliferation index) can be served as these markers. However, the dynamic changes in these parameters during hormone therapyrather than their initial expression levels in the tumor are of great significance for the individualized hormone therapy. 

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ISSN 1814-4861 (Print)
ISSN 2312-3168 (Online)