[Cytogenetic and molecular genetic investigation of melanoma].
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Biomedical subjects
Publications and source records attributed to A S Barchuk.
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Video-assisted thoracoscopy for differential and improved diagnosis was successful in 245 out of 249 patients (98.3%) with various chest neoplasms. Video-assisted surgical procedures were performed in 50 (20%). Complications were reported in 4 (1.6%). The method proved highly-effective as well as fairly safe and sparing.
The published studies of onco-associated genetic polymorphisms are characterized by insufficient interlaboratory reproducibility. The inconsistency of the results can be partially attributed to some characteristics of patients and control groups, which are used for the comparison of allele frequencies. For instance, many investigations involve so-called "healthy donors" as a standard. However, the efficiency of such a comparison can be questioned; indeed, as an individual life-time risk of malignancy reaches as high as 40-50%, a significant part of "healthy donors" would soon or later become the oncological patients. Here we tested the advantage of using "true" oncologically tolerant individuals as an additional control, e.g. tumor-free people, who succeeded to achieve an elderly age without signs of any neoplastic disease. GSTM1 gene polymorphism was used as a "positive control" for this novel design of molecular epidemiological study, as the GSTM1-null genotype displays slight but reproducible association with lung cancer risk. In the present investigation, GSTM1-deficiency was detected in 45% elderly tumor-free individuals, 55% healthy middle-aged donors, and 59% lung cancer patients. The minimal frequency (43%) of GSTM1(-) genotype was detected in elderly tumor-free smokers, and the maximal one (100%) was found in never-smoking lung cancer patients. Thus, the comparison of lung cancer patients to the "true" oncologically tolerant cohort (elderly tumor-free individuals, especially smokers) revealed more demonstrative deviations for the unfavorable genotype, than the traditional comparative analysis between oncological patients and healthy donors.
Diagnostic potential of video-assisted thoracoscopy was evaluated in 66 patients (36 males and 30 females) with neoplasms (aged 24-68 yrs). When used in conjunction with biopsy, it confirmed the following diagnoses: lymph proliferative disease (23), mediastinal malignancies (11), sarcoidosis (21), benign mediastinal tumors (7), Castleman's benign lymphoma (2) and mediastinal cyst (2). Clinical diagnosis was substantially changed in 40 (61%) cases as a result of videothoracoscopy application. It has proved precise, fairly safe and conservative; it has a potential in diagnosis of mediastinal tumors.
The 12-year end-results of standard "wide" and sparing "narrow" excision of superficial skin melanoma are compared. The results were contributed by a joint study of the WHO Collaborating Centers for Evaluation of Methods of Diagnosis and Treatment of Melanoma headed by Dr. U. Veronesi and Dr. N. Cascinelli and 23 other centers in different countries (the Blokhin and Petrov Centers in Russia). The investigation comprised 612 patients. After randomization, "narrow" excision of primary tumor with 1 cm-wide margins was performed in 305 patients. In the remaining 307 patients, "wide" excision left margins within 3 cm. Tumor was identified as superficial on the basis of thickness (Breslow), the threshold being 2 mm-thick invasion. This same prognostic indicator was used in both groups. Another one was 12 year-long recurrence-free survival. The sparing excision of primary cutaneous melanoma with a thickness under 2 cm proved effective.
The results of an evaluation of thyroid homeostasis in 54 patients with thyroid cancer (TC), 12-thyroid adenoma (TA), 10-non-toxic nodular goiter (NTG) and 39 healthy controls are discussed. It was demonstrated that assays of blood serum levels of thyrotropic hormone (TTH), thyroxin (T4), triiodothyronine (T3) and thyroglobulin (TG) are useless in diagnosing TC. However, it was confirmed that routine assays of blood serum-TTH, T4 and T3 levels are needed to evaluate the effect of post-operative substitution hormone therapy. Furthermore, the presence of recurrence or metastasis was indicated by an elevated concentration of blood-TG post-operatively if it was high pre-operatively. Post-operatively, TTH levels soared up in thyroid cancer and adenoma patients, reached their peak one month after surgery and then came back to normal while blood-TG concentration dropped to normal within 6-12 months. Unlike TA patients, blood-TG showed a continuous rise in those with TC. Ten years after surgery, blood-TTH levels in TC patients, who had received substitution hormone therapy, were much lower than in those without it. Similarly, the recipients of hormone therapy showed relatively lower T3 (6 months after operation) and TG (5 years after surgery) levels. Blood-TTH in overweight (Broca index > 20%) patients with TC was much higher than in those overweight less than 20%, 2 years after surgery. Elevated concentrations of blood-TTH and T3 were recorded in radically-treated patients with TC recurrences and metastases.
A 45-year experience of diagnosis and treatment of lung cancer is presented. In groups at high risk of cancer, photoroentgenographic screening has proved effective. The use of out-patient complex pulmonologic examination serves to improve identification of central cancer. Early cancers of the lung can be reliably detected in 92.2% of patients with central cancer and in 92.6%-peripheral localizations of tumor. After radical surgery, 5-year survival in cases of stage I tumor was 63.5: stage II-43.5 and stage III-22.9%, mean 5-year survival (irrespective of stage) being 37%. Postoperative radiation was shown to be followed survival over 5 years in cases of non-small cell carcinoma (N2). Early diagnosis and combined therapy are key in raising efficacy of lung cancer treatment.
The study group included 104 patients with soft-tissue sarcoma and metastases into the lung, treated at the Institute Clinic in 1960-1992. Surgery for lung metastasis was given to 10 and chemotherapy-to 48 patients; the remaining 48 cases received treatment for symptoms only. Overall 5-year survival was 13.5% (after surgery-30.0%; chemotherapy-19.1%). All the 46 patients treated for symptoms died within two years after detection of lung metastasis. Chemotherapy proved effective in the treatment of multiple metastasis when detected shortly after removal of the first lesion.
The data on the morbidity, time of diagnosis and results of treatment of esophageal cancer in St. Petersburg and Leningrad Region (1992-1994) were analyzed. The morbidity rates were higher in women than in men, the predominant age being over 60. Morphological verification data were not available in almost half the cases. Stage I-II tumors were detected in 15.7-26.5%. Specialized treatment was given to 25%, combination one-to nearly 2%. To raise the standards of medical aid, it is suggested that measures be taken to ensure stable operation of the Cancer Register, St. Petersburg, and to offer treatment to esophageal cancer patients at specialized medical facilities.
Endoscopic laser photodestruction is regarded not only as an independent procedure of treatment but primarily as an important and effective component of combined therapy of lung cancer. Direct-contact destruction of carcinoma of the bronchus and distal segment of the trachea has been performed using YAG:Ne lasers in 32 cases. The procedure has proved highly effective, especially, in combination with radiation therapy. Lysis of tumor in areas remote from the exposed one has been observed. It is suggested that endoscopic laser treatment of tumors offers considerable advantage.
The study was concerned with evaluating the results of follow-up of 756 cases of complications of colorectal cancers urgently admitted for surgery to four hospitals of St. Petersburg. Most patients were hospitalized late when complications diagnosed as an acute disease of organs of the abdominal cavity were apparent. Frequent postoperative complications and poor results of treatment were due to advanced age of patients, their grave general condition, concommitant pathologies, frequent errors of diagnosis made before and during hospitalization and lack of a single strategy of therapy. No improvement in the results of treatment of these grave cases can be expected unless the quality of diagnosis and the standards of urgent surgical aid organization are improved and an efficient therapeutic strategy is developed.
Procedures for early diagnosis of primary skin melanoma have been developed on the basis of the data available on 1.500 cases. Symptoms of malignant transformation of long-term pigmented nevi have been analyzed. The problems involved in screening primary skin melanoma and differential diagnosis have been studied.
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Surgical treatment of 258 patients (1st group) with carcinoma of the lung whose hereditary case history was aggravated by the presence of malignant tumors in blood relatives was compared with treatment of 861 patients of the control group (2nd group). Lung cancer patients of the 1st group were less operable than those of the 2nd group, 60.0% and 71.2% (p < 0.001) correspondingly. Resectability was 84.1% and 93.7% (p < 0.001) correspondingly. Totally in early stages (I-II stages) operations were performed only on 118 patients (45.7%) with the aggravated heredity and 536 (62.2%) of patients of the control group (p < 0.001). The symptoms which characterize surgical treatment of lung cancer in patients with the aggravated heredity are much worse as compared with the control group of patients because of the biological features of the tumors characterized by extremely high potential of the regional and remote metastases.
Specific features of metastatic spreading of lung cancer have been compared in 258 surgical patients from families with a history of lung cancer incidence (group I) and in 861 controls (group II). Lesions in lymph nodes at various stages were more frequent in group I, metastatic spreading incidence increasing in step with stage. In is noteworthy that more frequent lesions in mediastinal lymph nodes (stage IV) were observed in group I (54.2%), as compared with 11.8% in controls (P < 0.001). Multiple lesions of lymph nodes at all stages of metastatic spreading featured prominently in 48.5% of group I, as compared with 17.0% in group II (P < 0.001). Metastatic spreading was studied versus such characteristics of primary tumor as size, histologic pattern and pattern of tumor growth.
An analysis of 67 cases of skin melanoma of feet and legs aggravated by the risk of regional metastatic spreading established a significant improvement in five-year survival (over 30%) in patients who had undergone prophylactic lymphadenectomy. Indications for preventive surgery are suggested and rationale of its extent is discussed.
Application of antihypoxant drugs in postoperative period has been investigated. Lithium oxybutyrate was administered to 30 lung cancer patients before and shortly after operation. The results were compared with the data on 26 patients in control. Major characteristics, and, primarily, its antihypoxic protective effect have been evaluated. Lithium oxybutyrate administration is recommended in lung cancer patients during and shortly after surgery.