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This article presents a method of organ-preserving surgical treatment of laryngeal cancer, which has been developed and used since 1991 at the Tsyba Medical Radiological Research Center, Branch of the National Medical Research Center of Radiology of the Ministry of Health of Russia. The indications for this method are tumors affecting the middle part of the larynx, limiting its mobility, extending to the anterior commissure, laryngeal ventricle, vestibular fold, lower larynx and one arytenoid cartilage, but retaining mobility in the scooper-cricoid articulation. OBJECTIVE: To increase the functional safety of the larynx and improve the quality of life of patients with laryngeal cancer by using the developed method of organ-preserving surgical intervention in combined treatment. MATERIAL AND METHODS: The study included 197 patients who were operated on by the same method for a primary tumor or in connection with a relapse of the disease. At the first stage, all primary patients underwent a course of radiation or chemoradiation therapy 40-50 Gy. In 78 patients with recurrent laryngeal cancer who underwent resection of the larynx, the previous treatment was carried out in the form of a full course of radiation or chemoradiation therapy with a above 60 Gy. RESULTS: Wound healing by primary intention in patients with preoperative irradiation was observed in 92.4% of cases. With resections for a primary tumor, restoration of functions was observed in 115 (96.6%) patients, and with resections of recurrent tumors - in 71 (91%) patients. Three-year disease-free survival in these patients was 74.4%. CONCLUSION: The presented data showed the high efficiency of the method. This is evidenced by the course of the postoperative period, functional and oncological results are comparable, and in some cases exceed those of other researchers.

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The authors consider the risk factors and the specific clinical symptoms of the malignant nasopharyngal neoplasms as well as the methods for instrumental, laboratory, and pathomorphological diagnostics of this pathology. The full scale implementation of the recommendations for the timely detection of the tumours using the aforementioned diagnostic procedures and tests makes it possible to reduce to a minimum the interval between the establishment of the diagnosis and the onset of the relevant treatment at the early stages of the disease and thereby to ensure the improvement of its long-term outcomes.

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The study is based on the results of treatment of 60 patients with locally advanced laryngeal cancer (T3-4N0-3M0) exposed to combined treatment: 31 with preoperative chemoradiothera-py, 29 thermochemoradiotherapy. Radiotherapy was performed in the hyperfractionated mode: "1 Gy +1 Gy" (every 4-5 hours) 5 times a week to 30-40 Gy in total. Local hyperthermia was performed 2 times a week before the second fraction of radiotherapy in 3-4 sessions. Eight-day courses of chemotherapy were administered in the beginning of radiotherapy by scheme: vincristine (1. 4 mg/m2 per 1day), cisplatin (20 mg/m2 2, 3, 4 days), bleomycetin (10 mg/m2 5, 6 days), cyclophosphamide (200 mg/m2 7, 8 days). Surgical treatment was performed through 2,5 3 weeks after completion of radiotherapy. Local hyperthermia intensified the course of radiation reaction on the mucous of the larynx but not significant influenced on healing of surgical wounds. Thermochemoradiotherapy compared with chemoradiotherapy raised local relapse-free survival from 75 to 93% (p = 0. 07), regional, for a group of patients with stage N1-3 from 33 to 70%, N1-2 from 40 to 78% (p = 0. 1), loco -regional from 67 to 87% (p = 0. 04). Our findings suggest the necessity for further research on the use of thermochemoradiotherapy in combined treatment of patients with locally advanced laryngeal cancer.

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The combined treatment with preoperative chemoradiotherapy (CRT) was performed in 28 patients with locally advanced laryngeal cancer (T3-4N0-3M0). Radiation therapy (RT) was carried out according to the scheme "1 + 1 Gy" (interval 4-5 hours) 5 times a week till 30-40 Gy. RT was accompanied by simultaneous polychemotherapy: vincristine (1.4 mg/m² per day), cisplatin (20 mg/m²--2-4 days) bleomicetin (10 mg/ m²--5, 6 days), cyclophosphamide (200 mg/m²--7, 8 days). Surgical treatment was carried out in 2.5-3 weeks after CRT. CRT allowed conducting organ-saving surgery on the larynx in 11 (52%) of 21 patients with T3 of primary tumor. All other patients underwent laryngectomy at a different volume. Five-year disease-free survival for the whole group in total (T3-4) was 88%. Relapses of regional metastases (MTS) occurred in 7 of 9 patients including in 4 of 5 patients after lymphadenectomy. The overall survival of patients with T3N02 was 71%, with T4N0-3--20%. Thus we have developed a method of treatment allowing to achieve high local relapse-free survival in patients with locally advanced laryngeal cancer. However organ-saving effectiveness of preoperative CRT and its effect on regional MTS remain low, which requires further research in this direction.

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Single chemoradiotherapy (CRT) was performed in 27 patients with laryngeal cancer (T3-4N0-3M0). Radiotherapy (RT) was carried out in hyperfractionated mode 1+1 Gy (every 4-5 hours), 5 times a week to CFD 60 Gy with a 2-week break after CFD 30-40 Gy. Courses of polychemotherapy (PCT) were performed simultaneously with RT at each stage of treatment. Overall 5-year survival of patients in the whole by the group (T3-4N0-3) was 44.6%, for patients with T3N0--72.7%, T3N1-20--42.9%, T4N1-2--40.0% with an average life expectancy 38.1; 50.8; 39.0 and 39.8 months respectively. During a 5-year follow-up the local control of the primary tumor at T3 was equal to 61%, T4--25% with a median remission of 40.6 and 13.5 months respectively. During this period the regional control at metastases N1 was 50%, with a median remission of 32.7 months. In 4 patients of 5 with N2 and in all 3 patients with N3 during the first year after CRT continued growth or tumor recurrence was diagnosed. Thus, conservative CRT provides relatively satisfactory 5-year outcomes in patients with tumors T3N0-1.

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Radioresistance of cancer stem cells (CSCs) is regarded as one of the possible causes of cancer recurrence after radiotherapy. Since the regularities and mechanisms of radiation effects on this population of cells have not been sufficiently studied, the aim of this work is to elucidate the changes in the CSC number after γ-irradiation in stable cultures of tumor cells in vitro and tumor tissue in vivo (in the course of radiation therapy of patients with cancers of the upper respiratory tract). CSCs were identified in the cell lines B16, MCF-7, HeLa by the ability to exclude the fluorescent dye Hoechst 33342 (SP method) 48-72 h after irradiation at the doses of 1-20 Gy and in biopsy material by immunophenotype CD44+CD24(-/low) before and 24 h after irradiation at the total dose of 10 Gy. The essential differences in the response of CSCs and other cancer cells were found after exposure to low-LET radiation. The absolute number of CSCs increased after a single exposure at the doses ranging from 1 to 5-10 Gy in different cell cultures, but a further dose increase maintained the current number of CSCs or decreased it. At the same time, the number of non CSCs significantly decreased with increasing doses of radiation exposure, as expected. Fractionated irradiation in vivo at a total dose of 10 Gy increased the relative amount of CSCs in most patients. The registered changes are an integral indicator of cell death, cell division delay immediately after irradiation, proliferation at a later time, possible dedifferentiation of non CSCs, etc. The exact contribution of each of them to the radiation-induced increase of the CSCs number is of considerable interest and requires further research.

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There were analyzed results of treatment of 58 patients with laryngeal cancer T3-4N0-3M0. Chemoradiotherapy (CRT) was carried out in 27 patients, thermochemoradiotherapy (TCRT)-in 31 patients. Radiotherapy (RT) was performed in hyperfractionated mode (1 Gy + 1 Gy with an interval of 4-5 hours) 5 times a week to CTD 52-60 Gy with a 2-week break after CTD 30-40 Gy. Local hyperthermia (LHT) was carried out 2 times a week before the second fraction of RT in an amount of 3-6 sessions. The first cycle of polychemotherapy was administered at the beginning of RT and the second one-after the break. The local control under the primary tumor category T3 after CRT was equal to 58% and after TCRT--88%, at T4--72% and 25%, respectively. Late radiation damage of the larynx in the form of mucosal edema and perichondritis after CRT was in 2 patients (7%) and after TCRT--in 3 patients (10%). Thus, TCRT for locally advanced laryngeal cancer allows obtaining a higher overall survival and a local control as compared to CRT and does not lead to a significant increase of frequency of perichondritis.

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Thermochemoradiation therapy was performed in 31 patients with laryngeal cancer (T3-4N0-3M0). Radiotherapy was performed in 2 stages 1+1 Gy (every 4-5 hours), 5 times a week to SOD 52-60 Gy with a 2-week break after SOD 30-32 Gy. Local hyperthermia was carried out two times a week before the second fraction in an amount of radiation therapy sessions 3-6. In the days of local hyperthermia second fraction of radiotherapy increased to 3 Gy. Courses of chemotherapy were combined with radiation therapy and local hyperthermia at the beginning of each stage of treatment. For the whole group a complete response of the primary tumor was diagnosed in 25 (80.6%) patients, partial - in 6 (19.3%). Of the 12 patients with N1-3 complete regression of metastases occurred in 5 (41.7%), partial - also in 5 (41.7%). Five-year overall survival was 88.2% T3N0, T4N1 in 3 - 62.1%. Local control of the primary tumor in these terms in the group T3 was detected in 88.2%, in the group T4 - 77.8%, regional control of metastases with N1-3 - 33.3%. Late swelling of the mucous membrane of the larynx developed in 4 (12.9%) patients, perichondritis - in 3 (9.7%). Thermochemoradiation therapy of locally advanced cancer of the larynx provides a fairly good results comparable with those of the combined treatment.

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This paper analyzes the results of combined treatment with preoperative thermochemoradiotherapy in 28 patients with locally advanced laryngeal cancer (T3-4N0-3M0). Radiation therapy (RT) 32 Gy was carried out 5 times a week with splitting the daily dose of radiation on the 2 factions (interval 4 hours) on a "1 Gy + 1 Gy," in the days of the local hyperthermia (LGT)--on a "1 Gy + 3 Gy". LGT in an amount of 3-4 sessions was performed two times a week before the 2nd fraction of RT. The course of polychemotherapy was administered concurrently with RT and LGT. In 2-3 weeks after completion of the course thermochemoradiotherapy patients were operated. Organ-saving operations were performed 10 (56%) of 18 patients with primary tumors categories T3 and 2 (20%) of 10 with T4. Postoperative wounds healed by first intention in 21 (75%) patients. The cumulative 5-year overall survival in the whole group (T3-4N0-3) was 89%, for patients without regional metastases (T3-4N0)--100%. Relapse-free survival time for those patients with a primary tumor T3 equaled 94%, T4--90%. Relapse metastases occurred in 20% of patients. Thus, preoperative thermochemoradiotherapy is a highly effective method of treatment for locally advanced cancer of the larynx and does not lead to the development of severe postoperative complications.

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Data on the treatment of 215 patients with locally advanced malignancies of the nasal cavity and accessory nasal sinus are presented. All patients received preoperative radiotherapy using different fractionation schemes under a total target dose (TTD) of 32-40 Gy. Surgery was carried out two weeks later. Whenever radicality of surgery was in doubt, postoperative gamma therapy included exposure to 2 Gy 5 times a week (TTD--30-40 Gy) (n=121). Group I (n-57) received radiation at standard fractionated dosage. In group II (n=66), fractionation, tentatively considered "dynamic" was used while, in group III, fractionation was dynamic in actual fact. In group IV (n=10), superfractionation (1+1 Gy) was employed in group V (n=6),--gamma-neutron therapy. Patients in group VI (n=51) were operated on as scheduled and received 5 Gy, twice a week (TTD--20 Gy). According to 5-year follow-up, the best results were obtained with the use of larger doses of preoperative radiation (groups II, III, VI). Postoperative radiotherapy proved ineffective and it would be useless unless ablative procedures were definitely faulty during surgery.

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The study deals with the results of examination and treatment of 1040 patients with cancer (T3-4N0-3M0) of larynx and laryngopharynx. Radiotherapy was given to 358 patients concurrently with systemic polychemotherapy and different means of radiomodification. The remaining patients (682) receiving the same treatment minus systemic polychemotherapy were in control. Relapse-free (72.6%) and overall survival (82.7%) in the study group was significantly higher than in controls (54.7% and 63.4%, respectively) (p < 0.001). Moreover, an organ's function was preserved in 57.1% compared with 28.5% in control (p < 0.001).

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Apoptosis in peripheral blood lymphocytes of healthy donors and cancer patients after gamma-irradiation with different doses was studied by the flow cytometry method. Wide intra- and interindividual variabilities of the lymphocyte radiosensitivity were observed. The radiosensitivity did not depend on the subpopulation composition of the lymphocyte pool. The persons with very low and high lymphocyte radiosensitivities were found significantly more often among the cancer patients than among the healthy donors. One can suggest that this method is useful as a biomarker of future cancer risk and prognosis of radiotherapy efficiency.

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Under observation there were 452 patients with chronic stenosis of hollow organs of the neck having cannulas during the period from 3 months to several years. During the tracheobronchoscopic examination it was found that 35 patients had trachea ulcers, 46 patients had erosive tracheobronchitis. The ulcers were localized on the anterior wall of the thoracic part of the trachea. Their diameter was from 1 to 2.5 cm. The ulcers were accompanied by diffuse bilateral bronchitis of the II-III degree of the inflammation intensity. 2-3 ml of ozonated sodium chloride solution with the concentration of ozone in it 5 mg/l were introduced into the ulcer edges, i.e. lymphotropically, into the submucous membrane. The same solution (40-60 ml) was used for daily sanitation of the tracheobronchial tree. Complete epithelization of the ulcers and cleansing of the bronchial tree took 3-4 curative bronchoscopies.

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85 patients aged 26-60 years with pulmonary chronic obstructive diseases (PCOD) and gastric and duodenal erosive-ulcerous lesions were investigated. In PCOD the increased bioamines level in endocrine cells of bronchial ciliated epithelium and gastric glandular epithelium was detected before the treatment. The complex treatment in the form of bronchoscopy with lymphotropic administration of antibiotic and immunomodulator against the background of intragastral ozonotherapy contributes to the decrease in tissue edema, restoration of their trophicity and inflammatory process resolution. Against the background of therapy the serotonin content in endocrine cells of bronchial ciliated epithelium and gastric mucosa decreased to the norm.

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Lung abscess was diagnosed during a complex examination in 115 patients. All the patients had local treatment through the bronchoscope. Cleansing of the abscess cavity takes place 1,3 times quicker in the patients who were given laser irradiation in addition to sanitation bronchoscopy or to whom immunomodulators and antibiotics were introduced lymphotropically intrabronchially, than in those with usual sanitation. The administration of 20 ml of glycerol in the abscess cavity allowed cleansing of the cavity to be 2-3 times quicker.

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An analysis of the data on the treatment of 91 cases of advanced cancer of the larynx showed that local UHF-hyperthermotherapy is more efficient than the SHF one as a component of radiotherapy. Use of the latter procedure was followed by a higher rate of late-onset radiation injuries. Moreover, combined application of hyper-fractionated irradiation and UHF-hyperthermotherapy involved practically no grave complications while 5-year survival increased.

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