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Siberian journal of oncology

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Vol 18, No 5 (2019)
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https://doi.org/10.21294/1814-4861-2019-18-5

EPIDEMIOGICAL STUDIES

5-11 1110
Abstract

The purpose of the study was to compare data on the cancer incidence rates for 2016 between the official reports on cancer statistics and federal cancer registry, collected in December 2018.

Material and Methods. The study estimated the total data on 18 parameters from 35 regions of Russia, covering 66.3 million people (2016). The database of the Russian cancer registry and the database containing reports on the state cancer statistics were used. The cancer statistics/cancer registry ratio was assessed.

Results. No differences in cancer incidence between the official reports on cancer statistics and cancer registry data were found. In the official reports on cancer statistics, the mortality rate, the proportion of posthumously recorded patients per 100 newly diagnosed, the proportion of deaths from diseases not related to cancer per 100 deceased patients, the cancer prevalence and the prevalence rate of unspecified malignant tumors were slightly reduced (to 10 %, 9 %, 5 %, and 4 %, respectively), and the rate of cancer detection, the proportion of histologically verified diagnoses and the proportion of cancers detected in stage III were increased (to 19 %, 10 % and 14 %, respectively) compared to those in cancer registry data.

Conclusion. Improvement in the quality and completeness of information about cancer patients is associated rather with increasing the annual report length than with the need to improve the cancer registration system itself.

12-17 1036
Abstract

The purpose of the study was a comparative assessment of the cervical cancer incidence and mortality among females in urban and rural populations of the Omsk region.

Material and Methods. The study included females aged over 18 years from urban and rural areas of the Omsk region. According to population-based cancer registry data for the period 2004–16, the crude cancer incidence and mortality rates in urban and rural populations were calculated. The variational and correlation analyzes were used, the differences were assessed using Student t-test.

Results. During 2004–16, the cervical cancer incidence among females of the Omsk region showed an increasing tendency, reaching a peak incidence in women aged 35–54. Concerning the cervical cancer mortality rate, it tended to decrease. For rural females, the cervical cancer mortality rate decreased from 10.8 to 9.7 per 100,000 females (p>0.05). For urban females, the mortality rate decreased from 9.2 to 7.5 per 100,000 females (p>0.05). No significant differences in the mortality rates between urban and rural females were found (p>0.05). The tendency towards decreased incidence of advanced cervical cancer (the average decrease being 3.3 % for rural females and 2.8 % for urban females, p>0.05) and increased incidence of early stage cervical cancer (the average rise being 1.8 % and 1.9 %, respectively) was observed.

Conclusion. In the Omsk region, the cervical cancer mortality rate for both rural and urban females showed a tendency to decrease. During the study period, the incidence of cervical cancer had increased; however the incidence of advanced cervical cancer had decreased.

CLINICAL STUDIES

18-28 2276
Abstract

The objective of the study was to assess the feasibility of using CA -62 marker of epithelial carcinomas for monitoring treatment response and detecting cancer progression or recurrence during chemotherapy.

Material and Methods. A 12-month double-blind clinical trial was conducted by two independent groups: clinical oncologists and biochemists, and involved 89 patients with different cancers confirmed by histopathological findings. The other inclusion criteria were: the presence of at least one measurable lesion according to the RECIST criteria, ECOG performance status 0-2 and satisfactory laboratory parameters. The expression of CA -62 cancer marker was measured by immunochemiluminescent assay used for the detection of epithelial carcinomas.

Results. The elevated level of CA -62 marker was observed in 76 patients before starting the treatment. After completion chemotherapy, the level of this marker decreased to the normal reference ranges (<4600 U/ml) in 53 % of patients and remained increased in 24 % of patients. Of 24 % of patients with the initial low level of CA -62 marker (1000–4000 U/ml) before treatment, 12 % had no changes in the level of this marker during chemotherapy; however, 5 % of these patients had disease progression and 7 % had stable disease after starting the treatment. In 12 % of patients with an initial low CA -62 level, it increased during chemotherapy, indicating disease progression.

Conclusion. The changes in the level of CA -62 marker during chemotherapy in patients with gastric cancer, small-cell lung cancer, colorectal cancer, neuroendocrine cancer and ovarian cancer showed a high correlation (76–100 % depending on the tumor site) with the performance status of the patients according to RECIST criteria. The CA -62 marker was shown to be feasible for monitoring gastric cancer, small-cell lung cancer, colorectal cancer, neuroendocrine cancer and ovarian cancer as well as for assessing the response to chemotherapy.

29-37 1096
Abstract

Background. Lymphogenous metastasis in Ewing sarcoma is a relatively rare and poorly studied event associated with aggressive clinical course and poor prognosis. Until now, no risk factors for lymphogenous metastasis in patients with Ewing sarcoma are reported.

The purpose of the study was to evaluate tumor characteristics as predictors for lymphogenous metastasis and to create a mathematical model for assessing the risk of developing lymph node metastases in patients with Ewing sarcoma.

Material and Methods. Clinical characteristics of the tumor were studied in 88 patients with Ewing sarcoma: in 8 patients with lymphogenous metastasis and in 80 patients having no lymphogenous metastasis. The primary tumor in all patients with lymphogenous metastasis was found to have an extraskeletal origin. Morphological and immunohistochemical characteristics of the tumor were studied in 31 patients with Ewing sarcoma: in 8 patients with lymphogenous metastasis and in 23 patients without lymphogenous metastasis.

Results. Statistical analysis and comparative evaluation of the characteristics of the immunophenotype and histological pattern of the tumor in the two studied groups showed significant differences regarding several of them: the structure of nuclear crowding (fusion of nuclei), focal hemorrhages, nuclear normochromasia, and positive expression of cytokeratins by tumor cells. The above signs (except for nuclear normochromasia) were the basis for creating a mathematical model capable of predicting the risk of lymphogenous metastases in Ewing sarcoma.

Conclusion. The revealed association with lymphogenous metastasis of cytokeratin expression can be considered as indirect confirmation of the pathogenetic significance of the mesenchymal-epithelial transition in the mechanism of lymphogenous metastasis.

38-44 1109
Abstract

Many epidemiological studies have revealed the association between the risk of developing endometrial cancer (EС) and metabolic syndrome (MS) components. A large percentage of patients, especially elderly patients, may have one or more MS components at the time of cancer diagnosis.

Objective: to identify the clinical and morphological features of EС, depending on the number of MS components: three-, fourand five-components.

Material and Methods. The study included 60 patients with morphologically verified endometrial cancer (T1–3aN0–1M0). All endometrial cancer patients were divided into three groups. Group I included patients with MS, group II – patients with obesity or overweight (ICU ), and group III – patients without MS. Endometrial cancer patients with MS were divided into three subgroups: patients with 3 MS components, with 4 MS components and with 5 MS components.

Results. The proportion of endometrial cancer patients with MS was 53.3 %. The median age of the patients was 61.0 ± 2.1 years. The majority of patients had 4 components of MS. Moderately differentiated tumor was observed in 71.8 % of cases, and invasion of less than one-half of the myometrium was observed in 65.3 % of cases. Significant factors of relapse-free survival were: the presence/absence of MS, TG level and the fasting plasma glucose level, thus underlining the effect of MS not only on the development of EС, but also the survival of patients.

Conclusions. Our study and many previous studies indicate that the strategies for reducing the prevalence of the components of MS are needed to be developed.

LABORATORY AND EXPERIMENTAL STUDIES

45-53 1135
Abstract

Abstract Introduction. We have previously shown the feasibility of hormonal resistance horizontal distribution from cell to cell, with the joint cultivation of sensitive and resistant cells and/or through exosomes secreted by resistant cells. What is the mechanism of such resistance distribution, and how do cells with secondary resistance reproduce the characteristics of donor resistant cells? To answer these questions, we analyzed the overall level of DNA methylation in MCF-7 estrogen-dependent breast cancer cells and estrogen-independent sublinia.

The purpose of the study was to analyze DNA methylation profiles for the development of hormonal resistance by breast cancer cells and for resistant phenotype further accession.

Methods. DNA methylation was evaluated by the RRBS (Reduced Representation Bisulfite Sequencing) method in MCF-7 breast cancer cells and their resistant sublines.

Results. 19 CpG dinucleotides, differentially and generally unidirectionally methylated in cells with primary and secondary resistance to tamoxifen, were detected. Differential changes in methylation were found for DNA regions that regulated the expression of six protein-coding genes: PRKCZ, TRAPPC9, AS IC2, C2CD4A, ZNF787, CRTAC 1. Bioinformatics analysis showed that two of these six genes, PRKCZ (protein kinase C Zeta) and TRAPPC9 (Trafficking Protein Particle Complex Subunit 9) were directly involved in the regulation of NF-κB activity.

Conclusion. The data obtained indicate the existence of common DNA patterns, the methylation of which varies in the same direction in cells with primary and secondary resistance. The involvement of two of the identified genes in the regulation of NF-κB may indicate the inclusion of the latter in the formation of a resistant phenotype of tumor cells, even under conditions of horizontal transfer of resistance.

54-60 1120
Abstract

Because of the high risk of brain metastases from HER2-positive breast cancer, the study of the anticancer activity of drugs used to treat brain tumors, in particular lomustine, is of great importance. In the FVB/N Her-2 transgenic mice bearing HER2-positive breast cancer (BC HER2+), a single oral administration of lomustine at a dose of 50 mg/kg resulted in a significant tumor growth inhibition (up to 96 %, p<0.0001). The tumor growth index (TGI) expressed as a ratio between the areas under the kinetic curves of tumor growth in the study and control groups and amounted to 33 % (p<0.001) indicated the high activity of lomustine. However, the effect of lomustine on intramuscularly transplanted Ehrlich tumor was insignificant (tumor growth inhibition and tumor growth index were <39 % and 68 %, respectively). Lomustine administered orally at a single dose of 50 mg/kg 24 hours after intracranial transplantation of BC HER2+ increased the median survival time up to 30 days in FVB/N mice compared to 21 days in the control group mice (p<0.001). The high therapeutic effect of lomustine in HER2-positive breast cancer mice is likely can be explained by the biological characteristics of this tumor; therefore clinical trials of lomustine for HER2-positive tumors are needed.

61-67 1218
Abstract

 Introduction. Adjuvant systemic therapy remains one of the main options for treating breast cancer. Results of standard immunohistochemical studies are not always a criterion for selecting systemic therapy. Nowadays, multigene expression analysis is actively used to predict the response to chemotherapy in patients with earlystage breast cancer. We studied a 24-gene multi-gene panel for typing breast cancer.

Material and Methods. A prospective analysis of 199 breast cancer patients (T1–3N0–3M0) was carried out. Surgical specimens were studied using the standard immunohistochemistry (IHC) and RT-PCR for detecting expression of 24 genes.

Results. According to the IHC results, breast cancer was divided into 5 molecular subtypes: luminal A was detected in 59 (30 %) patients; luminal B (HER2-negative) in 52 (26 %); luminal B (HER2-positive) in 19 (9 %); triple-negative in 28 (14 %); HER2-positive 41 (21 %). RT-PCR showed that ST K15, MYC, MYBL2, BIRCC 5, BCL2, TERT, ESRP1, PGR, HER2, GBR7, MGB1 and MMP11 were the most significant genes in subtype distribution. The total percentage of matches between the two studies was 61.7 %.

Conclusion. Studies have shown the need to add additional typing methods for breast cancer to a standard IHC study, which will undoubtedly increase the information content of diagnostic measures and will improve the effectiveness of the treatment.

68-73 1037
Abstract

To understand the mechanism of the effect of 5 % 5-fluorouracil (5-FU) gel used simultaneously with ultrasound (US ) on a tumor in patients with cervical cancer, the level of DNA damage was studied in vitro. We used cervical adenocarcinoma HeLa CC L-2 cells cultured under standard conditions in RPMI-1640 medium with 10 % fetal bovine serum and 50 μg / ml gentamicin. Ultrasound exposure lasted 10 min. (frequency of 0.88 MHz and intensity of 0.2 W / cm2). The 5-FU dose was 0.7 мкМ, with the time of exposure of 24 hours. In 24 hours after starting exposure, the level of DNA damage to the cells of the culture was studied using the comet assay in the alkaline version and evaluated by the % DNA parameter in the comet tail (% TDNA). The statistical significance of the differences was evaluated using the Mann-Whitney U test and Fisher’s exact test. The combined exposure to ultrasound / 5-FU led to a 5.2-fold increase in % TDNA compared to the control culture, % TDNA was 1.9 times higher after exposure to 5-FU alone and 3.0 times higher after exposure to ultrasound alone. In 24 hours after the combined exposure, less than 50 % of the culture cells had a low level of DNA damage (<10 % TDNA), i.e. completed the repair process and could continue to proliferate, and more than 30 % of the culture cells still had a high level of damage (>30 % TDNA) and were probably in the process of apoptosis. Thus, the results of the study showed that the combined effect of ultrasound / 5-FU on the HeLa culture helped to overcome resistance to chemotherapy, having a synergistic effect.

ONCOLOGY PRACTICE

74-79 1875
Abstract

Background. There is a wide spectrum of metabolic and toxic disorders that can cause acute encephalopathy in cancer patients. In routine clinical practice, hypoglycemia, vitamin B1 (thiamine) deficit, fulminant liver failure, uremia, severe hypoand hypernatremia should be primarily excluded. Central neurotoxicity associated with hyperammonemia in patients receiving 5-fluorouracil (5-FU) and oral fluoropyrimidines should be considered in differential diagnosis. In this case, the analysis of the blood acid-base status and the detection of B-type hyperlactatemia can facilitate the diagnosis of the cause of encephalopathy.

Case description. We present two cases of hyperlactatemia and encephalopathy in stage IV cancer patients with continuous infusion of 5-FU via a portable infusion pump.

Conclusion. Diagnosis of the frequent fluoropyrimidin-related adverse effects, such as myelosuppression, anorexia, diarrhea, mucositis, and palm-plantar syndrome, are routine and mastered by an oncologist at the very beginning of his/her professional activity. Specific fluoropyrimidinerelated encephalopathy or hyperlactatemia are difficult to suspect and recognize. We hope our description will be useful to prevent possible diagnostic errors.

80-85 851
Abstract

The incidence of neuroendocrine tumors has significantly increased over the last years.

The purpose of the study was to analyze treatment outcomes in patients with pancreatic endocrine tumors (PETs) with regard to histopathologic diagnosis.

Material and Methods. The clinical records of 1077 patients with pancreatic tumors were retrospectively analyzed. Fifty patients were diagnosed with PET. Treatment outcomes were assessed with regard to tumor differentiation grade, tumor stage, extent of surgery and drug therapy.

Results. The most common histological grade was G1. Patients with G1 tumors had the best 1-and 3-year survival rates regardless of tumor stage. Factors influencing prognosis in patients with PETs were: radical surgery, Ki67 expression level, histological grade (G1–3), tumor stage at diagnosis.

REVIEWS

86-96 1545
Abstract

Objective: to conduct a systematic literature review of the published studies on retroperitoneal non-organ liposarcomas.

Material and Methods. A literature search was performed using Pubmed, Elibrary, COSMIC databases. The data of retrospective and prospective clinical trials were analyzed. Results. The article reviews contemporary data on epidemiology, classification, clinicalmorphological and molecular-genetic characteristics, as well as diagnosis and treatment of retroperitoneal non-organ liposarcomas. Conclusion. Retroperitoneal sarcomas account for about 13 % of all types of soft tissue sarcomas. Liposarcoma is the most common retroperitoneal mesenchymal tumor. Diagnosis and treatment of non-organ retroperitoneal liposarcoma remain challenging due to poor long-term treatment outcomes. As experience is gained with the diagnosis and treatment of retroperitoneal nonorganic liposarcomas, changes occur in the system of understanding the problem that determines the strategy for providing medical care in this category of patients. The article presents modern concept of retroperitoneal non-organ liposarcomas.

97-107 3002
Abstract

Background. Squamous carcinoma of the larynx is still the most common head and neck cancer in many Western countries. The larynx plays a key role for many essential functions, including breathing, voice production, airway protection, and swallowing. According to the world literature, 23,800 new cases of laryngeal cancer and 106,000 deaths from this disease are registered annually in the world. Laryngeal cancer treatment is aimed at achieving tumor control while optimizing functional outcomes.

Objective: to review available data on surgical and non-surgical treatment options for locally advanced laryngeal cancer, as well as the evidence supporting each of these, including oncological outcomes (overall survival, disease-free survival, local control of the disease, functional outcomes and quality of life).

Material and Methods. A systematic literature search was conducted in the electronic databases Medline, Cochrane Library, and Elibrary in the interval time between 1987 and 2016.

Conclusions. In recent decades, the treatment paradigm for advanced laryngeal cancer has shifted from surgery (total laryngectomy) as the gold standard of treatment to nonsurgical organ-preserving treatment using radiation therapy or chemoradiation therapy. However, concerns have arisen regarding functional outcomes after chemoradiation therapy, as well as a possible reduction in overall survival in laryngeal cancer patients, risk factors, laryngectomy.

CASE REPORTS

108-112 843
Abstract

Despite advances in the treatment of non-small cell lung cancer (NSC LC), prognosis of advanced lung cancer is extremely poor. The search for additional treatment options to prevent local recurrence and distant metastases is of great importance. Monoresistance genes, such as ABCC5, BRCA1, RRM1, ERCC1, TOP1, TOP2a, TUBB3, and TYMS play a significant role in tumor sensitivity to chemotherapy for NSC LC. The expression levels of these genes in tumor tissue should be assessed for personalization of adjuvant chemotherapy in patients with NSC LC.

Case description. We present a clinical case of a 65-year-old patient diagnosed with non-small cell lung cancer who underwent extended combined surgery followed by 4 courses of personalized adjuvant chemotherapy. The expression levels of monoresistance genes (ABCC5, RRM1, ERCC1, TOP1, TOP2a, TUBB3, BRCA 1 and TYMS) determined by reverse-transcriptase quantitative real-time PCR (RTqPCR) were used as predictive markers of response to adjuvant chemotherapy regimen.

Conclusion. Our case report demonstrated the feasibility of performing organ-preserving surgery followed by personalized adjuvant chemotherapy based on the expression levels of monoresistance genes as predictive markers of benefit from adjuvant chemotherapy.

113-117 1291
Abstract

Background. Solid pseudopapillary tumor of the pancreas is a rare neoplasm, accounting for only 1–2 % of all pancreatic neoplasms and having a tendency to affect mainly young women.

Material and methods. We report a case of a solid pseudopapillary tumor of the pancreas in a 28-year-old man treated with laparoscopic distal pancreatectomy in Moscow Botkin Hospital.

Results. The tumor was discovered incidentally by routine survey ultrasound or computed tomography of the abdomen. The patient underwent distal pancreatectomy with splenectomy. The immunohistochemical study showed a pronounced positive nuclear staining for β-catenin and progesterone and a negative staining for chromogranin A and synaptophysin, thus confirming the presence of solid pseudopapillary tumor of the pancreas.

Conclusion. In case of pancreatic tumor, even in male patients, a solid pseudopapillary tumor must be considered in the differential diagnosis. Surgical strategies should be based on the location, size of the tumor and the involvement of adjacent organs, because R0-resection with a solid pseudopapillary tumor leads to a good 5-year survival.

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