Preoperative radiotherapy in combination with metronidazole for resectable gastric cancer: long-term results of a phase 2 study.

AIM: Surgery remains the main treatment of stomach carcinoma. Poor long-term survival mandates the study of other techniques. An original treatment scheme with preoperative radiotherapy and metronidazole as a radiosensitizer is reported here. METHODS: Between 1982 and 1988, MRRC RAMS carried out a prospective clinical trial of preoperative radiotherapy (20 Gy/5 days) in combination with metronidazole (given orally, 3 times, 5 gms per metre(2)). Of 91 patients who received preoperative radiotherapy, 67 patients were operated on with curative intent and were eligible for further analysis. RESULTS: Acute gastro-intestinal toxicity was significant but manageable without surgery delay in most cases. There were 4 postoperative deaths. Overall 5-year, 10-year survival and median survival were 46%, 36% and 46 months. Serosal and nodal involvement were the most significant adverse prognostic factors. Tumours confined to the gastric wall, node negative cases, middle and distal location, differentiated tumours, female sex and age more than 50 years were associated with relatively good long-term results: overall 5-year survival was 50% or better, overall 10-year survival was 40% or better. CONCLUSION: The combined treatment showed significant but manageable acute toxicity. The long-term results seem encouraging and support further investigations in multimodal treatment of gastric cancer.

[Fast neutrons in the treatment of malignant neoplasms]. / Bystrye neitrony reaktora v lechenii zlokachestvennykh novoobrazovanii.

More than 250 patients, mainly with locally advanced tumors of the head, neck and breast were treated with a I MeV beam of fast neutrons emitted from a BR-10 reactor. The fast neutron contribution to the total dose of the radical component of complex gamma-neutron therapy was 20-40%. Said modality was shown to improve the results of treatment for laryngeal and breast tumors. The 5-year actuarial survival following complex gamma-neutron therapy for laryngeal cancer was 89.25, while in controls--65.2% (p < 0.005). The 5-year actuarial overall survival in breast cancer patients treated with fast neutrons was 66.5%: gamma-neutron therapy alone--46.0% (p < 0.05).

[Pathomorphosis of laryngeal cancer after neutron and gamma-neutron therapy using fast neutrons of the reactor]. / Patomorfoz raka gortani pri neitronnoi i gamma-neitronnoi terapii s ispol'zovaniem bystrykh neitronov reaktora.

Studies of tumours and adjacent tissue were carried out in 29 patients with carcinoma of the larynx after preoperative irradiation with fast neurons at a total focal dose 5.6 Gy alone or in combination with gamma therapy. Pronounced pathomorphosis was established in all the cases, up to a full disappearance of the tumor in 2 patients, the degree of pathomorphosis did not depend on location, macroscopic form of growth, degree of dissemination. No changes were found in the wall of the larynx outside the tumor.

[Biological markers of precancer of the large intestine]. / Biologicheskie markery predraka tolstoi kishki.

Current views on focal defect in colorectal mucosa as a risk factor for development of tumours are presented. It is characterized by such phenotypical changes of the mucosa as cell proliferation activation, changes in ornithine decarboxylase activity and polyamine synthesis, changes in the expression of the blood group antigens and associated carbohydrate antigens as well as the development of small adenomas. All these changes may be biological markers of colonic precancer.

[Combination treatment of rectal cancer using preoperative combination radiotherapy]. / Kombinirovannoe lechenie raka priamoi kishki s predoperatsionnoi sochetannoi luchevoi terapiei.

The paper is concerned with analysis of the results of therapy of 122 rectal cancer patients divided into 2 groups by sex, age, tumor site, type of anatomical tumor growth, and stage of disease: I (72 patients)--combined therapy including preoperative radiotherapy and operation; II (50 patients)--surgery alone. Indications for combined therapy with preoperative irradiation were worked out. The results of histological investigation showed that this method brought about deep radiation injuries of tumors with minimum damage of the adjacent normal tissues. A conclusion was made that combined therapy including preoperative irradiation decreased the number of recurrences and metastases and increased (in combination with surgical intervention) the 5-year survival rate up to 79.6%.

[Thermoradiotherapy of rectal cancer]. / Termoradioterapiia raka priamoi kishki.

Methods of combined and multimodality therapy are widely used for the treatment of malignant rectal tumors. However radical operation cannot be performed in 50% of patients, in some cases patients refuse surgery. In such cases patients are given a split course of radiation therapy using local heating of a tumor and a method of daily dose fractionation. Altogether 58 patients with stage T2-4N0-1M0-1 were treated by this method: 38 received thermoradiotherapy, 20 were controls. At the 1st stage the summary focal dose (SFD) was 40 Gy, temperature in a tumor was 42-44 degrees C, interval 3-4 weeks. At the 2nd stage radiotherapy was given with daily dose fractionation (1 + 1.5 Gy at 4-5- h interval), the SFD was 35-40 Gy. The SFD over the entire therapeutic course was 75-80 Gy. Radiation rectitis in thermoradiotherapy was more frequent and severe. Complete tumor regression was observed in 7 (18.4%) patients, marked regression--in 24 (63.2%) patients, insignificant regression--in 5 (13.1%); 2 patients (5.3%) were treated without any effect. 29 (76.3%) patients lived over 2 yrs., 6 (25.8%) patients died of tumor progression.

[A rare case of rupture of a syphilitic aortic aneurysm into the esophagus]. / Redkii sluchai proryva sifiliticheskoi anevrizmy aorty v pishchevod.

A case of the rupture of a syphilitic aortic aneurysm into the esophagus in a woman aged 64 with cured breast cancer was observed. A clinical picture, autopsy and microscopy findings were described. The authors underlined the rarity of the case, difficulty of intravital and morphological diagnosis which could be attributed to syphilis pathomorphosis. Of great importance for diagnosis are a detailed life history, clinical symptoms, instrumental methods of investigation, especially in oncological practice where differential diagnosis with exophytic esophageal cancer seems difficult.

[Cellular apoptosis: its morphology, biological role and the mechanisms of its development]. / Apoptoz kletok: morfologiia, biologicheskaia rol', mekhanizmy razvitiia.

The literature review reports data on morphology, biological role and mechanisms of apoptosis as a special type of cell destruction. Apoptosis is very common in humans and animals in health and disease, and therefore needs further investigation.

[Theory and practice of the morphometry of human tumors]. / Teoriia i praktika morfometrii opukholei cheloveka.

It is stated that if adequate qualitative and quantitative knowledge of tumor development is to be gained, a systems approach must be used, in which a given process is considered as representing the sum total of hierarchically organized and interrelated parts, and that quantitative data on processes of tumor development are needed for cognitive, diagnostic, evaluative, and prognostic purposes.

[Morphometric cellular characteristics of the inflammatory infiltrate in nonirradiated and irradiated rectal cancer]. / Morfometricheskaia kharakteristika kletok vospalitel'nogo infil'trata neobluchennogo i obluchennogo raka priamoi kishki.

A morphometric analysis of the inflammatory infiltrate cells of the stroma and adjacent tissue of adenocarcinomas of the rectum was performed in 40 patients. As to therapeutic modality, the patients were divided into 4 groups of 10 patients in each. The 1st group was given surgery only, the 2nd group preoperative gamma-therapy at a dose of 19.5 Gy, the 3rd 30 Gy and the 4th 40 Gy. Integral fractions of lymphocytes, plasmocytes and eosinophils were determined on randomly selected sections using the point counting technique. It was shown that in adenocarcinomas of the rectum integral fractions of the above cells had similar values irrespective of tumor macroscopic shape, degree of differentiation and growth depth. Cellular reactions in the adjacent tissues were more noticeable than in tumor itself, and numerical values of the integral fractions of inflammatory infiltrate cells depended on growth depth. After irradiation a decrease in the lymphocyte integral fraction and an increase in the plasmocyte integral fraction were noted both in the stroma and adjacent tissues.

[Use of metronidazole in the preoperative irradiation of stomach cancer patients]. / Primenenie metronidazola pri predoperatsionnom obluchenii bol'nykh rakom zheludka.

Altogether 70 patients received combined therapy for stomach cancer. A course of gamma-beam therapy (a summary focal dose of 20 Gy) combined with metronidazole was given at the first stage. Three-five days after the discontinuation of radiation therapy the patients were operated upon. Forty-nine (70%) patients were subjected to radical operation. The area of surgical intervention ranged from subtotal resection of the stomach to combined gastrectomy. Lethality after radical operations was 7.5%. Pronounced and extensive dystrophic changes were found in tumors at microscopic examination of resected specimens.

[The Struktura apparatus for stereometric research]. / Pribor dlia stereometricheskikh issledovanii "Struktura".

An apparatus is proposed for the stereological analysis in medicine and biology. Its basic parts are as follows: a television microscope, video-control monitor with a morphometrical net, blocks of accumulation and original information processing.

[DNA level in the cell nuclei of rectal mucosa and rectal cancer during preoperative radiotherapy]. / Soderzhanie DNK v iadrakh slizistoi obolochki i raka priamoi kishki pri predoperatsionnoi luchevoi terapii.

A microspectrophotometric study was made of DNA in cell nuclei of the normal mucous membrane and rectal tumors in 47 patients prior to and after irradiation at doses of 20, 40 and 36 Gy together with the administration of 7 g of 5-fU. The work was done using biopsies (before the onset of therapy) and operative material. As to Felgen-DNA in cell nuclei the normal mucous membrane has been shown to consist of homogeneous cell population with diploid nuclei. Rectal adenocarcinoma is characterized by polyploidy, an increase in the "DNA accumulation index" that grows with a decrease in the degree of tumor differentiation. A slightly raised "DNA accumulation index" is noted in the unchanged rectal mucosa after radio- and chemotherapy, signs of noticeable poly- and heteroploidy of the nuclei of the preserved cells were established in adenocarcinomas.