Клинические исследования. Рубрика в журнале - Сибирский онкологический журнал
50 лет клинико-эпидемиологических исследований острых лейкозов у детей Томской области
Статья научная
Представлены итоги 50-летних (1958-2007 гг.) клинико-эпидемиологических исследований по проблеме острых лейкозов у детей Томской области. Показано, что первичная заболеваемость острыми лейкозами детей на протяжении указанного периода сохраняется в пределах средних величин. Преобладающей формой является острый лимфобластный лейкоз. Уста- новлено статистически значимое преобладание пациентов с дигестивным типом телосложения.
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Статья научная
Currently the impact of autophagy on carcinogenesis remains understudied. On the one hand, autophagy acts as a tumor suppressor, as it activates degradation of oncoproteins, toxic proteins, and damaged cell organelles, that may be aggressive and lead to DNA damage. On the other hand, autophagy may promote tumor cell survival under hypoxia and in the presence of reactive oxygen species, which occurs primarily due to blocking of apoptosis mechanisms, raising the chances for maintaining tumor clone dynamics. Autophagy regulation is a complicated and multi-stage process. The main regulator here is a signaling pathway that activates serine/threonine protein kinase m-TOR (the mammalian target of rapamycin). Data on the impact of autophagic proteins ATg5, LC3A, LC3b, and beclin-1 on malignant cell survival as well as on tumor growth and progression have been reported in literature. However, studies aimed at seeking possible relationships between autophagy and pathogenetic mechanisms of carcinogenesis are of great interest. the aim of the study is to investigate a relationship between the expression parameters of autophagy regulatory proteins m-TOR and beclin-1 and the features of lymphogenic metastasis in colorectal cancer. materials and methods. The study included 105 patients with T1-4N0-3M0 colorectal cancer treated in the Thoracic and Abdominal Department of Cancer Research Institute of Tomsk Research Medical Center from 2012 to 2015. The average age of patients was 59.7±4.3 years. Morphological verification of the diagnosis was performed on the biopsy samples of primary tumor tissue. Staging of colorectal cancer was determined according to the TNM classification of malignant tumors (2002). results. Analysis of the frequency of lymphogenic metastasis depending on the presence or absence of m-Tor and beclin-1 expression in tumor cell cytoplasm revealed a statistically significant link between these variables. Conclusion. The obtained findings clearly exhibit that deceleration or loss of autophagic activity in the tumor is accompanied by implementation of lymphogenic dissemination, which is a predictor of an unfavorable outcome of the disease.
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CXCR4 expression in different subsets of CTCS and single (detached) breast cancer cells
Статья научная
The aim of this study was to assess CxCR4 expression in different subsets of CTCs and single (detached) breast cancer cells. materials and methods. Thirty five patients with invasive breast carcinoma of no special type (IC NST) (T1-4N0-2M0), between 29 and 69 years of age were included in this study. Different subsets of CTCs with CxCR4 expression were evaluated by flow cytometry. A confocal microscopy was used to assess CxCR4 expression in different subsets of single (detached) cancer cells in breast tissue. results. The CxCR4 was expressed in CTCs without stem-like and EMT phenotype, in CTCs with EMT but not stem markers and in stem-like CTCs without EMT features. In all blood samples, the CxCR4 expression in CTCs with stem-like and EMT phenotype was absent. In breast tumor the CxCR4 was expressed in the non stem-like single (detached) breast cancer cells with EMT features, in the single (detached) breast cancer cells with stem and EMT features. In all tumor samples the stem-like or non stem-like single (detached) breast cancer cells without EMT features were absent. Conclusions. Different subsets of the CTCs exhibited CxCR4. The CxCR4 expression did not depend on the presence or absence of stem or/and EMT features in tumor cells. We showed that some subsets of single (detached) breast cancer cells in the primary tumor were characterized by the ability to express CxCR4 and may be a source of the respective CTC subsets.
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Introduction. In accordance with UICC and AJCC 8th edition TNM classifications, there is a strong evidence for division of oropharyngeal squamous cell carcinoma (OPSCC) into 2 molecular subtypes by HPV-status with distinct prognosis depending on biological differences. Such a division leads to differences in staging OPSCC and in future it will lead to implementation of preventive measures and new therapeutic strategies against HPV-positive cancer. Aim of the study: to assess the clinical and prognostic significance of the combination of P16, a surrogate marker for HPV-positivity, and high proliferative activity in patients with oropharyngeal carcinoma. Material and Methods. Immunohistochemical (ICH) analysis with monoclonal antibodies specific for P16 and Ki67 proteins was used to detect expression patterns in the formalin-fixed, paraffin-embedded tumor samples obtained from 104 patients with squamous cell carcinoma of the tongue and oropharynx, treated at Oncological Dispencery № 1 in Krasnodar from 2011 to 2016. HPV-positive status was determined if more than 70 % of tumor cells had moderate or strong nuclear and cytoplasmic P16-staining. High index of proliferative activity (PA) was detected if more than 50 % tumor cells expressed Ki67 nuclear antigen. Results. P16-positivie status was associated with tonsillar cancer (р=0.002), female gender (р=0.015), age 70 % with high PA demonstrated correlation with tonsillar cancer (р50 % and clinicopathologid parameters and overall survival confirms the biological features of HPV-associated cancer. The evaluation of this IHC-complex can increase the diagnostic accuracy of IHC-analysis of HPV-status and predict the prognosis of patients with OPSCC.
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Статья научная
Целью исследования явилось изучение структурно-функционального состояния пристеночного слизистого слоя и полостного секрета оставшейся части желудка у 64 больных после субтотальной дистальной резекции по поводу рака в раннем послеоперационном периоде и влияния эндоскопической лазеротерапии (44 пациента) и медикаментозного лечения (20 человек) на коррекцию выявленных нарушений. Выявлено, что в ранние сроки после проведенного лечения произошло достоверное изменение состава как структурных, так и внеструктурных гликопротеинов, парциального состава отдельных моносахаров в обеих группах. Был сделан вывод о том, что лазерное лечение по сравнению с медикаментозной терапией оказывает более серьезное влияние на биосинтез полимеризованных гликопротеинов и приближает их состав к нормальным показателям.
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Feasibility of simultaneous integrated boost for high-dose treatment of high-risk prostate cancer
Статья научная
Background. Radiation therapy for high-risk prostate cancer presents a challenge for cancer radiotherapists. The improvement of treatment outcomes is associated with radiation dose escalation and prophylactic irradiation of lymph nodes, therefore, the development of the new treatment schemes is needed. Simultaneous integrated boost technique based on the volumetric modulated arc therapy is the most efficient treatment option. Material and Methods. The anatomical data of 10 patients with high-risk prostate cancer was used for dosimetry-based treatment planning. Both simultaneous integrated boost and sequential boost technique were considered. The treatment planning goal was to deliver the equivalent dose of 96 Gy at 2 Gy per fraction (EQD2=96 Gy) (α/β=1.5 Gy) to the prostate, EQD2=62.5 Gy to the seminal vesicles and EQD2=50 Gy to lymph nodes avoiding damaging the organs at risk, mainly the bladder and rectum. The irradiation was based on volumetric modulated arc therapy with two partially coplanar arcs and two rotations at each arc. The obtained dose distributions were compared with respect to dose-volume histograms and equivalent uniform doses (EUD). Results. In the case of sequential boost, the minimal dose delivered to the prostate was equal to2cc95.9 ± 2.1 Gy, EUD=104.9 ± 1.7 Gy. The dose delivered to 2 cm3 ( D ) bladder was 97.4 ± 2.0 Gy. Normal tissue2cccomplication probability (NTCP) was 1.64 %. The dose delivered to 2 cm3 ( D ) rectum was 103.4 ± 9.2 Gyand NTCP was 27.4 %. In the case of simultaneous integrated boost, the minimal dose delivered to the prostate was equal to 90 . 4 ± 2 . 3 Gy, EUD= 103 . 9 ± 1 . 3 Gy. The bladder dose was as high as D 2cc = 96 . 1 ± 5 . 2 Gy, NTCP= 0 . 176 ± 0 . 132 %, the rectum dose - D 2cc = 81 . 1 ± 6 . 0 Gy, NTCP= 2 . 34 ± 1 . 92 %. Conclusion. Volumetric modulated arc therapy along with simultaneous integrated boost have shown the feasibility of simultaneous irradiation of the prostate, seminal vesicles and lymph nodes up to the prescribed dose values without significant over irradiation of the organs at risk (OARs). Dose values in the tumor as high as EUD= 103 . 9 ± 1 . 3 Gy along with prophylactic irradiation of lymph nodes may result in higher tumor control probability value and should be considered for clinical trials.
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Hereditary diffuse gastric cancer: genetic aspects and prophylactic total gastrectomy
Статья научная
For patients with an identified germline E-cadherin-1 ( CDH1 ) mutation, prophylactic gastrectomy is the treatment of choice to eliminate the high risk of developing diffuse gastric cancer. The case report describes a rare case of hereditary diffuse gastric cancer (HDgC) associated with CDH1 gene mutation, which is reported in the Russian population for the first time. In 2013, a 28-year-old woman was referred to Clinical Oncogenetics Laboratory with a family history of gastric cancer. Molecular genetic analysis revealed CDH1 gene mutation. The lifetime risk of cancer in mutation positive members is more than 80. Histological examination of gastric biopsy specimens obtained during endoscopy revealed isolated signet ring cells in the lamina propria. Spleen-preserving D2-lymphodissection and total gastrectomy with Roux-en-Y reconstruction with a jejunal reservoir formation were performed at the Abdominal Oncology Surgery Department.
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Impact of transcription factors, VEGF and proteases on kidney cancer progression
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Introduction. The efficacy of anticancer treatment depends on biological factors of tumor. the aim of the study was to determine the activity of proteasomes and calpains and to reveal their association with VEgF, HIF-1α and NF-κΒ expressions in normal, primary and metastatic renal cell carcinoma (RCC) tissues. methods. Ninety-three patients with renal cell carcinoma were included into the study. The expression levels of transcription factor and VEgF were measured using ELISA kits. The levels of proteasome subunits were measured by Western blotting. Proteasome and calpain activities were determined using specific fluorogenic substrates. results. We revealed inactivation of proteolysis in patients with kidney cancer. Disease advance was associated with a significant depression of cellular proteolysis and increase in transcription and growth factor levels in primary kidney cancer tissues. The proteolysis activation was found in metastatic tissues. Conclusions. Our results suggest that NF-κΒ, HIF-1α and VEgF transcription factors and intracellular proteolytic systems are involved in kidney cancer progression.
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Статья научная
In vivo autofluorescence of normal and metaplastic epithelium of esophagogastric transition in patients with reflux-esophagitis was studied by local fluorescence spectroscopy under 532 nm excitation. It was shown that application of in vivo local fluorescence spectroscopy during gastroesophagoscopy makes it possible to improve a quality of diagnostics of Barrett's esophagus. Key words: gastroesophageal reflux disease, Barrett's esophagus, fluorescent diagnosis, local fluorescent spectroscopy.
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Objective. In accordance with clinical guidelines, neoadjuvant chemoradiotherapy (nCRT) is recommended as a beneficial option for treatment of thoracic esophageal squamous cell carcinoma (TESCC). However, some studies did not demonstrate potential benefits of nCRT. In this paper we compared treatment outcomes of surgery alone with preoperative CRT followed by surgery. Material and Methods Group 1 (n=147) consisted of patients who underwent surgery alone. Group 2 (n=3,337) was formed in the framework of the present systematic review and meta-analysis (15 publications captured 20 separate subgroups for analysis). Patients of group 2 received nCRT followed by esophagectomy. Overall survival (OS) and median OS were estimated.
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ABC-transporter family genes have been well studied and their involvement in the development of drug resistance has been assessed. The presence of aberrant conditions in these genes can affect the treatment and prognosis of the disease. Loss of heterozygosity (LOH) is one of these conditions; it is a common event in cancer development. Therefore, the aim of this study was to investigate the relationship between LOH in ABC transporter genes in breast cancer and response to chemotherapy and disease prognosis. Material and Methods. A total of 130 breast cancer patients were included in the study. Microarray analysis was performed on Affymetrix CytoScan™ HD Array high-density DNA chips to assess LOH status. Chromosome Analysis Suite 4.1 software (Affymetrix, USA) was used to process microarray results. Results. Forty-nine ABC transporter genes were evaluated for LOH. The frequency of LOH ranged from 6.9 % to 90 %. An association analysis identified two genes: ABCG5 and ABCG8, in which the presence of LOH was associated with a lack of objective response to neoadjuvant chemotherapy. The presence of LOH in the ABCA5, ABCA6, ABCA8, ABCA9, ABCA10 and ABCC3 genes was associated with high rates of metastasis-free survival (log-rank test, p
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Predictors of local recurrence of renal cell cancer. Our experience
Статья научная
Risk factors for renal cell cancer (Rcc) recurrence, including its local form, include stage and high Fuhrman grading system score, regional lymph node involvement, microvascular invasion, tumor necrosis, positive surgical margin, and sarcomatoid or rhabdoid tumor differentiation. Objective. the study analyzes data from moscow Research oncological institute named by pa Herzen to determine the predictors of local recurrence of kidney cancer based on the data from surgically treated patients with local recurrent Rcc. material and methods. We analyzed retrospectively data from 87 patients who were divided into 2 groups: 1-st, patients with detected local recurrence of kidney cancer (n=43), and 2-nd, control group (n=44). the following predictors were evaluated: tumor size, tumor histotype, tumor stage, Fuhrman grading system, surgical margin status, tumor necrosis, sarcomatoid and rhabdoid changes, microvascular invasion, hemorrhage and invasion of collecting system components (css), renal capsule, and perirenal cellular tissue and primary treatment. Results. the risk of local recurrence was higher in the primary tumor, over 40 mm in diameter (oR=5.8, p function show_abstract() { $('#abstract1').hide(); $('#abstract2').show(); $('#abstract_expand').hide(); }
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Статья научная
Purpose. to evaluate prostate specific antigen density (psad) as a predictor of overall (os) and cancer-specific survival (css) in patients with prostate cancer (pc) who have undergone combined hormonal-radiation therapy. material and methods. in order to assess the prognostic significance of psad we retrospectively analyzed outcomes of 714 pca patients who received combined hormonal-radiation therapy at the a.m. granov Russian scientific center of Radiology and surgical technologies, ministry of Healthcare of Russia, between January 1996 and december 2016. since the prognosis and management differ according to the extent of tumor involvement, patients were categorized into localized (n=272), locally advanced (n=231) and metastatic (n=211) pc groups. We equentially applied Roc-analysis, Kaplan-meier product limit estimator and cox proportional hazards model to assess the prognostic relevance and establish threshold values of psad that had a significant impact on survival rates. results. in the localized pc group, psad threshold values of 0.34 ng/ml/cc and 0.36 ng/ml/cc were associated with a decrease in os and css, respectively. patients with “low” psad had significantly better os and css survival rates in both uni- and multivariate analyses. in locally advanced pc group, psad threshold values were 0.28 ng/ml/cc and 0.63 ng/ml/cc for os and css, respectively. However, exceeding the specified values, in the locally advanced pc group, was not accompanied by a statistically significant decrease in survival rates. Finally, in the metastatic pc group, established psad threshold values were 2.25 ng/ml/cc and 2.30 ng/ml/cc for os and css, respectively. according to the results of univariate analysis, patients with “low” psa tend to demonstrate statistically significant better os and css rates. the results of multivariate analysis, however, failed to prove psad as an independent prognostic factor within the metastatic pc cohort. conclusion. psa density is a reliable tool for assessing survival rates in patients with localized pc who have undergone combined hormonal-radiation therapy.
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Psychological rehabilitation and life quality assessment for patients with thyroid cancer
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Life quality values of thyroid cancer patients are characterized by reduction in psychological vector in early postoperative period and greatly in social vector. The detected damages are completely resolved within 6 months. Compensation of physical characteristics of life quality occurs more completely. High level of personal anxiety having preferably psychical and neurovascular character is observed in patients of the studied group. Comprehensive systematic psycho-therapeutic correction in early postoperative period taking account individual characteristics of the patients significantly increases the treatment efficacy. A high social-labor adaptation of the studied group patients has been found.
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Radical prostatectomy and robotic radiosurgery as treatment options for localized prostate cancer
Статья научная
Purpose: to compare immediate, short-term and long-term treatment outcomes after radical prostatectomy and robotic radiosurgery in patients with localized prostate cancer. Material and Methods. The study included 2 groups of patients. Group I patients (n=80) underwent radical surgery (nerve-sparing prostatectomy). Group II patients (n=102) underwent KiberKnife stereotactic robotic radiotherapy. Results. Immediate treatment outcomes after both radical prostatectomy and robotic radiosurgery did not demonstrate increased number of postoperative complications and severe radiation-induced injuries. The PSA level decreased and reached a nadir PSA level immediately after radical prostatectomy. After stereotactic radiation therapy, the PSA level decreased gradually every three months, reaching a nadir within a year. In the group of patients receiving CyberKnife treatment, changes in the prostate volume affected the quality of urination, which was confirmed by the assessment of the volume of residual urine. When comparing the quality of urination in treatment groups using the IPSS scale, the values were comparable. No differences in the 1-year disease-free survival rates between groups were found. However, 60 months later, disease free survival rate was higher by 8.2 % in patients treated with radiosurgery than in patients who underwent radical prostatectomy (p function show_abstract() { $('#abstract1').hide(); $('#abstract2').show(); $('#abstract_expand').hide(); }
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Short-term results of surgical treatment of non-organic retroperitoneal tumors
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Comparative analysis of short-term results of combined operations and isolated removal of non-organic retroperitoneal tumors has been carried out. The study included 97 patients with malignant primary and recurrent tumors adjacent to surrounding organs. A total of 106 operations were performed, 56 of them were combined operations (52 patients were operated on), and isolated tumor removal was performed in 50 cases (45 patients were operated on). It has been found that the hemorrhage volume and surgery duration are significantly increased during the combined operations resulting in the increase in the rate of postoperative complications, however, these differences are not significant.
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Single vein resection in surgery for pancreatic ductal carcinoma as a criterion of resectability
Статья научная
Background. pancreatic ductal carcinoma (pdc) with involvement of the superior mesenteric vein (smV) or/and portal vein (pV) remains a discussible subject. We have evaluated vein invasion as a criterion of borderline resectability and long-term outcome. material and methods. in our center, 68 patients underwent either 65 standard pancreatoduodenal resections or 3 pancreatoduodenectomies for pdc. Resection of smV/pV was performed in 18 cases (26.5 %). three patients received neoadjuvant chemotherapy (Nact), and adjuvant chemotherapy (act) was assigned to 37 patients (54.4 %). Results. morbidity (42.0 vs 50.0 %, р=0.590) and mortality rates (4.0 vs 16.7 %, р=0.111) had no significant differences in groups of standard and angioplasty operations respectively. act was completed in 10 (16.7 %) patients only. there was true vein invasion in 12 of 18 patients with vein resection. рN+ (р=0.012) and angioplasty by itself (р
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Introduction. The purpose of this study was to evaluate the feasibility of using 99mTc-Tg SPECT in the detection and staging of malignant lymphoma. materials and methods. Fifteen patients with newly diagnosed malignant lymphoma underwent 99mTc-Tg SPECT. Six patients had Hodgkin’s lymphoma and 9 patients had aggressive forms of non-Hodgkin’s lymphoma (NHL) : diffuse large b-cell lymphoma (7 cases), b-cell follicular lymphoma (1 case), and lymphoma from b cells in the marginal zone (1 case). Stage IIA was diagnosed in 5 patients, stage IIb in 1, stage IIIA in 1, stage IVA in 4 and stage IVb in 4 patients. results. Pathological 99mTc-Tg uptake in lymph nodes was observed in 14 (93 %) of the 15 patients. In one patient, the enlarged submandibular lymph node (16 mm in size) detected by CT was not visualized by 99mTc-Tg SPECT. This false-negative result was likely to be associated with increased accumulation of 99mTc-Tg in the oropharyngeal region. There were difficulties in the visualization of paratracheal, para-aortic and paracardial lymph nodes. These difficulties were associated with a high blood background activity, which persisted even 4 hours after intravenous injection of 99mTc-Tg. Software-based SPECT and CT image fusion allowed visualization of these lymph nodes. The pathological 99mTc-Tg accumulation in axillary, supraclavicular, infraclavicular and cervical lymph nodes was observed most often. Extranodal involvement was seen in 9 patients. 99mTc-Tg SPECT identified extranodal hypermetabolic lesions in 7 (78 %) of these patients. In one patient, hypermetabolic lesion in the lung detected by 99mTc-Tg SPECT was not detected on CT image. CT identified bone marrow involvement in the pelvic and scapula in 1 patient. The use of 99mTc-Tg SPECT allowed the visualization of hypermetabolic bone tissue lesions in this patient (Figure 4). In addition, in a patient with intact bone tissue on CT, 99mTc-Tg SPECT detected hypermetabolic lesions in the iliac bone. Conclusion. 99mTc-1-Thio-D-glucose demonstrated increased uptake in nodal and extranodal sites of lymphoma. The results indicate that SPECT with 99mTc-1-Thio-D-glucose is a feasible and useful tool in the detection and staging malignant lymphoma.
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The aim of the study was to identify differences in the immune system parameters between metastatic melanoma patients who responded and did not respond to dendritic cell vaccination. Material and Methods. The study group included 20 patients with stage III-IV metastatic melanoma, who received vaccine therapy with dendritic cells (DC) in a prophylactic mode. The control groups included 13 patients who had symptoms of disease progression at the time of starting vaccine therapy, and 5 healthy donors. The DC-vaccine was prepared in the form of a suspension of the patient's autologous dendritic cells loaded with tumor antigens in vitro . A single dose had 2 million dendritic cells in 1 ml of phosphate buffer solution, which was administered intradermally in the nearest site to the regional lymphatic collectors. The immune system status was assessed before starting vaccination. The immune system status was evaluated according to the indexes of 25 peripheral blood cell populations using multicolor flow cytometry and integral characteristic in the form of the visual image generated by the visualization method of multidimensional data (NovoSpark, Canada). Results. The immune status in patients with metastatic melanoma at the start of DC-vaccination differed and was associated with the effectiveness of subsequent vaccine therapy. The response to vaccination was observed in patients whose immune system status was similar to that of healthy individuals. Low efficacy of DC-vaccine therapy was shown in patients whose immune system status corresponded to that of patients with disease progression. Alterations of the immune system in patients with metastatic melanoma were registered both at the level of individual immunological parameters and at the level of visualized integral characteristics. The integral characteristics of the immune system associated with the patient's immunocompromised status can be considered as a criterion for stratification of patients with metastatic melanoma for the effective DC-vaccine therapy. Conclusion. The effectiveness of vaccine therapy with dendritic cells in patients with metastatic melanoma is associated with the immune system state before starting this therapy.
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The inflammatory status and lymph node metastases in non-small cell lung cancer
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Introduction. The development of inflammation is characterized by changes in blood hematology parameters and indices. Various inflammatory parameters are used to assess the inflammatory status (iS) during cancer treatment. Recent studies have revealed a relationship between tumor progression and the presence of chronic inflammation. Consequently, there have been many attempts to predict the risk of tumor recurrence and distant metastases, as well as patient's survival assessing the various inflammatory markers. The relationship between iS parameters and lymph node metastasis remains poorly understood in non-small cell lung cancer (NSCLC). Material and Methods. The prospective study included 35 patients with NSCLC (T1-4N0-2M0). Seventeen patients received 2-3 cycles of neoadjuvant chemotherapy (NAC). A leukocyte formula was determined in the peripheral blood and inflammatory indices, such as neutrophils to lymphocytes ratio (NLR), platelets to lymphocytes ratio (PLR), lymphocytes to monocytes ratio (LMR) and systemic immuno-inflammatory index (Sii) were calculated. in addition, the concentrations of fibrinogen, C-reactive protein (CRP) and cortisol were evaluated. Results. NAC alone did not significantly change the parameters of patients' iS. Lymph node metastases were associated with changes in parameters indicating the enhanced iS. in the group of patients who did not receive NAC, lymph node metastasis was associated with fibrinogen blood levels (cut-off value 5.35 g/L), PLR index value (cut-off value 7.18) and cortisol blood concentration (cut-off value 414 nmol/mL). The confidence level was x2=10.118; р=0.018. in the group of patients who received NAC, lymph node metastasis was associated with the leukocyte count (cut-off value 7.1*109/L), PLR index value (cut-off value is 7.18) and CRP blood concentration (cut-off value is 8.5 mg/L). The confidence level was x2=8.193; р=0.042. Conclusion. Risk of lymph node metastasis in NSCLC is associated with iS. Parameters of iS can be used to predict the risk of lymph node metastases.
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