[Thoracoscopy in combined treatment of thymoma (in Russian only)]. / Videotorakoskopiia v kombinirovannom lechenii timom.

The experience of video-assisted thoracoscopic interventions for thymus tumors in the Research Institute of Oncology of Tomsk National Research Medical Center is presented. We also evaluate the features of postoperative management of these patients.

[Dynamics of LINE-1 Retrotransposon Methylation Levels in Circulating DNA from Lung Cancer Patients Undergoing Antitumor Therapy].

Malignant cell transformation is accompanied with abnormal DNA methylation, such as the hypermethylation of certain gene promoters and hypomethylation of retrotransposons. In particular, the hypomethylation of the human-specific family of LINE-1 retrotransposons was observed in lung cancer tissues. It is also known that the circulating DNA (cirDNA) of blood plasma and cell-surface-bound circulating DNA (csb-cirDNA) of cancer patients accumulate tumor-specific aberrantly methylated DNA fragments, which are currently considered to be valuable cancer markers. This work compares LINE-1 retrotransposon methylation patterns in cirDNA of 16 lung cancer patients before and after treatment. CirDNA was isolated from blood plasma, and csb-cirDNA fractions were obtained by successive elution with EDTA-containing phosphate buffered saline and trypsin. Concentrations of methylated LINE-1 region 1 copies (LINE-1-met) were assayed by real-time methylation-specific PCR. LINE-1 methylation levels were normalized to the concentration of LINE-1 region 2, which was independent of the methylation status (LINE-1-Ind). The concentrations of LINE-1-met and LINE-1-Ind in csb-cirDNA of lung cancer patients exhibited correlations before treatment (r = 0.54), after chemotherapy (r = 0.72), and after surgery (r = 0.83) (P < 0.05, Spearman rank test). In the total group of patients, the level of LINE-1 methylation (determined as the LINE-1-met/LINE-1-Ind ratio) was shown to increase significantly during the follow-up after chemotherapy (P < 0.05, paired t test) and after surgery compared to the level of methylation before treatment (P < 0.05, paired t test). The revealed association between the level of LINE-1 methylation and the effect of antitumor therapy was more pronounced in squamous cell lung cancer than in adenocarcinoma (P < 0.05 and P > 0.05, respectively). These results suggest a need for the further investigation of dynamic changes in levels of LINE-1 methylation depending on the antitumor therapy.

[Results of surgical and combined treatment of non-small cell lung cancer].

AIM: To study the results of surgical and combined treatment of non-small cell lung cancer stage III using preoperative chemotherapy and intraoperative radiotherapy. MATERIAL AND METHODS: The study included 152 patients with non-small cell lung cancer stage III. Overall and recurrence-free 5-year survival were 20.4% and 14.3% respectively. These values were significantly higher in case of combined treatment consisting of radical surgery and intraoperative radiotherapy (29.2% and 18.7% respectively, p<0.05). RESULTS: The best results were obtained in case of preoperative chemotherapy with paclitaxel/carboplatin, radical surgery and intraoperative radiotherapy on background of radiosensitization with cisplatin. Overall and recurrence-free 5-year survival were 47.9% and 41.7% respectively (p<0.05). Incidence of postoperative complications and mortality rate did not significantly differ between surgical and combined treatment (p>0.05).

Chemotherapy and intraoperative radiation therapy for operable stage III non-small cell lung cancer.

The study was undertaken to evaluate results of combined modality treatment including intraoperative radiation therapy (IORT) in 202 patients with stage III non-small cell lung cancer. The 5-year disease-free and overall survival rates in patients who underwent 15 Gy IORT were 18. 7% and 29. 2%, respectively. The overall response rate to preoperative chemotherapy with paclitaxel/carboplatin was 43. 7%, treatment was well tolerated. Preoperative chemotherapy with paclitaxel/ carboplatin in combination with 15 Gy IORT led to a significant increase in the 5-year disease-free and overall survival rates to 31. 4% and 39. 2%, respectively (p<0. 05). The 5-year disease-free and overall survival rates were respectively 32. 6% and 40. 8% in patients who received additional administration of cisplatin combined with 10 Gy IORT. Radiosensibilization with cisplatin in patients treated with 15 Gy IORT increased the 5-year disease-free and overall survival rates to 41. 7% and 47. 9%, respectively (p<0. 05).

[Chemoradiotherapy in combination with local hyperthermia for patients with non-small cell lung cancer].

Short-term treatment outcomes for 15 patients with stage IB-III non-small cell lung cancer (NSCLC) were present- ed. The patients were treated with thermochemoradiothrapy (TCRT). Hyperfractionated radiation therapy at a total dose of 40 Gy (1.3 Gy/fraction, twice daily, 5 days per week) was given concurrently with 2 courses of chemotherapy with pa- clitaxel (175 mg/m², i.v, on day 1) and carboplatin (AUC 6, i.v, on day 1). Ten sessions of local hyperthermia were deliv- ered using the Celsius TCS electro-hyperthermia system. Local hyperthermia was administered twice a week, 2 hours before radiotherapy or immediately after administration of chemotherapeutic agents, for 45-60 min at 41-43 °C. The overall, histologically confirmed, response rate was 93% with 3 (20%) patients achieving a complete response and 11 (73.3%) with a partial response. Stable disease was seen in 1 case (6.7%). No disease progression was found. Chemoradiotherapy and local hyperthermia were well tolerated. Twelve (88%) patients underwent radical surgery (RO): 8 (66.7%) lobectomy and 4 (33.3%) pneumonectomy (TCRT as an option of preoperative treatment). There were no postoperative complications and deaths. Radiation therapy was continued up to the total dose of 60-66 Gy in 3 cases (inoperable patients), and the number of local hyperthermia sessions was increased to 12-14 (TCRT alone). During the follow-up period of 12-14 months, no evidence of disease progression was observed. A prelimi- nary analysis of data obtained indicate that TCRT for patients with NSCLC is well tolerated, results in tumor regression, expand the indications for surgical treatment and demonstrates the encouraging results.

[The analysis of perioperative period in patients with lung cancer stage III, receiving the combined treatment].

The intra- and postoperative period was analyzed in 202 patients with non-small cell lung carcinoma, treated with the combined therapy and intraoperative radiotherapy. There were no intraoperative complications registered, in spite of complex antitumor treatment. 18.8% of patients developed postoperative complications, which has no substantial influence on the outcome and were determined by the volume of the operation. The postoperative lethality rate was 3.0%.

[Effect of combined modality treatment with intraoperative radiotherapy on the morphofunctional state of the myocardium in patients with stage-III lung cancer].

Epy influence of combined treatment including neoadjuvant chemotherapy, radical surgery and intraoperative radiotherapy with a single dose of 15 Gr or 10 Gr has been studied in conditions of radiosensibilization on morphological and functional status of myocardium in non-small lung cancer patients at stage III with by means of ECG-synchronized single-photon emission computed tomography of myocardium with 99mTc MIBI. It was shown that this kind of treatment does not worsen functional status of myocardium, besides the perfusion level of myocardium correlated with initial concomitant cardiovascular pathology and extent of surgical treatment.

[Assay of methylated gene RARbeta2 in circulating DNA of blood from patients with lung cancer as a potential prognostic marker].

Blood-based methylated DNA gene RARbeta2 in circulating plasma (cir DNA) and one associated with blood cell surface were assayed in patients with non small cell lung cancer before and after combined treatment. The levels in both appeared to be significantly higher than in healthy subjects. Enhanced levels prior to treatment were associated with greater advancement of the disease and unfavorable prognosis (overall survival). After two courses of neoadjuvant therapy plus surgery methylation indices fell down to match those in healthy subjects. Our data may be instrumental in working out additional criteria to be used in diagnosis, prognosis and follow-up of patients with non small cell lung cancer.

[Identification of proteins overexpressed in malignant gastric tumors: comparison of the results of 2-De and bioinformatics search].

Comparison of protein expression in intestinal and diffuse stomach tumors by 2D gel electrophoresis led to identification of three proteins (SOD2, S100A6, and TXN), which are overexpressed in tumors as compared to normal controls. It was shown, that overexpression of proteins SOD2 and TXN occurs much more frequently in diffuse tumors than in intestinal ones. A control panel of eleven proteins overexpressed in stomach tumors has been selected based on the data of comparative 2D analysis described in the literature. Bioinformatics search for mRNAs encoding proteins from the control panel in Oncomine database (which contains the results of determination of mRNA transcription level in tumor vs. normal samples) demonstrated the coincidence of proteomic and transcriptomic data for seven out of 11 proteins.

[Lung cancer: 25-year experience with surgical and combined treatment].

Data on surgical and combined treatment of 950 patients with non-small lung cancer are evaluated. After combined treatment of lung cancer stage III using intraoperative radiotherapy and adjuvant chemotherapy or radiosensitization, recurrence-free survival rose to 13.3 +/- 2.3 and 23.0 +/- 1.1 months, respectively; 5-year overall survival--32.8 +/- 3.2% and 40.3 +/- 4.2% respectively. Compare with 10.4 +/- 1.3 months and 20.8 +/- 8.5%, respectively, for surgery alone. Despite the prejudice against preoperative radiotherapy, postoperative one administered in TTD of 40-60 Gy (median 55 Gy) may be recommended for treatment of lung cancer spreading to mediastinal lymph nodes.

[Immunochemical and molecular-genetic markers in gastric cancer diagnostics].

Studies of molecular mechanisms of neoplastic transfromation are being under the thorough investigation, reveal the new genes involved into the tumor development. These genes and their products are potential tumor markers and levels of their expression can be detected using modem assays characterized by high specificity and sensitivity. The review highlights the current status of the molecular diagnostics of gastric cancer, including protein and nucleic acids biomarkers. The genetic and epigenetic changes, which are detected in the malignant and nonmalignant tumor tissue DNA and in the blood plasma DNA from tumor bearing patients, are summarized.

[Platelet functional status in patients with gastric cancer at combined treatment stages].

Platelets are active cells that excrete various humoral factors that contribute to thrombogenesis and inflammation. The investigation was undertaken to study induced platelet aggregation in patients with gastric cancer at combined treatment stages and to evaluate the impact of intraoperative radiotherapy (IOR). The study covered patients with gastric cancer (GC). Group 1 included Stage III GC patients who had undergone elective radical surgery; Group 2 comprised Stage III GC patients who had radical surgery with a session of IOR; Group 3 consisted of Stage IV GC patients who had undergone palliative surgery or explorative laparotomy. Induced platelet aggregation were explored from the BIOLA aggregometer (Russia) readings before, 30 minutes, 1, 3, 5, 7, and 14 days after surgery. Adenosine phosphate, adrenaline, collagen were used as inducers. It is concluded that there is a need for postoperative laboratory control and correction of platelet activity. In GC patients operated on with IOR, platelet activity should be monitored for at least 2 weeks after surgery.

[Postoperative features in lung cancer patients receiving intraoperative radiotherapy and radiosensitization].

Research Institute of Oncology, Research Center, Russian Academy of Medical Sciences, Siberian Branch, Tomsk. Postoperative course was studied of stage III non-small cell lung cancer (35) treated radically using intraoperative radiotherapy (15Gy) and cisplatin radiosensitization. Postoperative complications were reported in 11.4 +/- 5.4%. Reduction in complication rates was due to the use of a combined treatment complex. There were no postoperative lethalities.

[Radiologic follow-up and prognosis of efficiency of systemic Sr-89 Cl-2 therapy of bone metastases in prostate cancer]. / Kompleksnaia luchevaia otsenka i prognozirovanie éffektivnosti sistemnoi radioterapii 89SrCl2 pri kostnykh metastazakhraka predstatel'noi zhelezy.

We evaluated possibilities of bone scintigraphy with 99mTc-methylendiphosphonate (99mTc-MDP) and magnetic resonance imaging (MRI) in follow-up and prediction of effect in patients with extensive bone metastatic disease treated with betha-emitter 89SrCl2. 24 patients with prostate cancer and extensive metastatic involvement of skeleton were referred for the study. 89SrCl2 was injected as single injection of 150 MBq (4 mCi), in eighteen from Amersham plc., England, as Metastron, in six--from Medradiopreparat, Russia). In all patients bone scintigraphy with 99mTc-MDP and MRI study of metastatic regions were performed before and in 3 months after 89SrCl2 injection. Patients treated with Metsatron were also studied in 6 months after injection. Quantitative analysis of data comprised count and anatomic dimensions of metastatic areas and calculation of indices [metastasis/intact bone] both for scintillation count of 99mTc-MDP bone scans and signal intensity of T1-weighted MRI scan. Henceforth, we conclude the data of bone scanning with 99mTc-MDP and of MRI give evidencies for significant regress of bone metastases in patients treated with 89SrCl2 besides symptomatic suppression of pain syndrome. 99mTc-MDP bone scanning is also of predictive value for the prognosis of therapeutic effect of systemic radiotherapy with 89SrCl2 in prostate cancer.

[The combined treatment of locally disseminated stomach cancer with intra-arterial regional chemotherapy]. / Kombinirovannoe lechenie mestnorasprostranennogo raka zheludka s vnutriarterial'noi regionarnoi khimioterapii.

The method of a long-term celiac artery catheterization through the lumbar transaortic access is proposed. In 56 patients with a 3d stage gastric cancer regional intraarterial chemotherapy with 5-fluorouracil was used pre- and postoperatively. There was a decrease of postoperative complications from 47.8 + 6% in surgical treatment to 16.0 +/- 4% in combined treatment. Metastases and recurrence were observed in 11 (21.2 + 5%) patients with regional chemotherapy and in 34 (58.6 + 6%) patients with surgical treatment only.

[Intra-arterial regional chemotherapy in the combined treatment of stage-III cancer of the stomach]. / Vnutriarterial'naia regionarnaia khimioterapiia v kombinirovannom lechenii raka zheludka III stadii.

The report discusses a method of long-term catheterization of the celiac artery by lumbo-transaortal access. Intraarterial regional chemotherapy with 5-fluorouracil was administered to 56 cases of gastric cancer, stage III, before and after surgery. A significant drop in postoperative complication rate from 47.8 +/- 6% after surgery to 16.0 +/- 4% after combination treatment was recorded. During two years after operation, metastases and recurrences were registered in II out of 52 patients receiving intraarterial chemotherapy (21. +/- 5%), as compared with 34 out of 58 (58.6 +/- 6%) in controls without chemotherapy.

[The determination of the level of antibodies to Epstein-Barr virus antigens in organizing groups at high risk for lung cancer disease]. / Opredelenie urovnia antitel k antigenam virusa Epstaina--Bar pri formirovanii grupp povyshennogo riska zabolevaniia rakom legkogo.

Titers of antibodies against Epstein-Barr virus (EBV) antigen were measured in 450 subjects aged 40 years and older. The group included patients with lung cancer, cases of non-specific chronic lung pathology and healthy subjects (150 persons in each subset). A significant increase in the level of antibodies to capsid EBV antigen was established in patients with lung cancer and chronic non-specific lung pathology as compared to healthy controls. Parameters of specific immunologic response to Epstein-Barr virus may be recommended as additional criteria for inclusion into the group at risk for lung cancer.