[Current state of the problem of treatment and prognosis of colorectal cancer].

The article presents an overview of the current state of the problem of colorectal cancer based on the features of its various clinical forms. It was shown that despite the fact that the surgical method was the leading cancer treatment for colon and rectum cancer the preference should be given to the combined and complex methods and in the treatment of squamous cell carcinoma of the anal canal, the emphasis was on conservative treatment with chemoradiation, leading to stable remission that avoided traumatic surgery in most cases. Also current data are presented on the necessity to identify circulating and disseminated tumor cells to refine prognosis and further explore ways to improve long-term results.

Prognostic role of tumor-associated proteases in colorectal cancer.

The relationship between the tumor and plasma levels of tumor-associated proteases - components of plasminogen activation system (uPA, tPA, and PAI-1), matrix metalloproteinases (MMP) 2, 7, 9 and their inhibitor (TIMP-1) - and the survival rate of patients with colorectal cancer was analyzed in order to evaluate the clinical significance of these markers. The study was carried out in two groups of patients, observed for 5 and 10 years, in whom the levels of these proteins were previously measured by enzyme immunoassays. High level of PAI-1 in the tumor (≥4.0 ng/mg protein) was found to be a significant, but not independent unfavorable prognostic factor for overall 5- and 10-year survival. The role of this factor was mainly significant in patients with stage III disease. High preoperative plasma levels of MMP-7 and TIMP-1 (threshold values 4.0 and 347 ng/ml, respectively) were independent unfavorable prognostic factors, while in unifactorial analysis, high level of MMP-7 (≥7.8 ng/mg protein) in the tumors of patients with disseminated process was olso an unfavorable prognostic factor.

Tumor associated proteases -- prognostic markers of colorectal cancer.

Associations between matrix metalloproteinase (MMP) 2, 7, 9, tissue MMP inhibitor TIMP- I and plasminogen activation system components (uPA, tPA and PAl-1) plasma and/or tumor levels in colorectal cancer (CRC) patients were evaluated in order to reveal their potential clinical implications. Two groups of CRC patients monitored for 5 or 10 years were enclosed in the study. Earlier, corresponding markers 'levels were measured in their plasma and/or tumors by immunoenzymatic techniques. High tumor PAl-I (> or =1 4,0 ng/mg protein) was demonstrated to be a significant, but not independent unfavorable prognostic factor for 5 and I10 years overall survival. Its role was mostly pronounced in stage II1 patients. High preoperative plasma MMP-7 and TIMP-I levels (cut-offs - 4,0 and 347 ng/ml respectively) were shown to be independent unfavorable prognostic factors, and univariate analysis revealed unfavorable prognostic value of high tumor MMP-7 content (> or =7,8 ng/mg protein) in patients with disseminated process.

[Tissue inhibitor of metalloproteinase-1 (TIMP-1) in colorectal cancer: correlation with clinico-morphological factors].

Tissue inhibitor of metalloproteinase-1 (TIMP-1) was identified by enzyme-linked immunosorbent assay in tumor, histologically-unchanged mucosa, and plasma from 100 colorectal cancer patients. A significant increase in TIMP-1 production of up to 27.4-times as high as in adjacent mucosa was found in 92%. That was most pronounced in cases of tumor extension through adjacent tissues and organs. The marker's level was excessively high in 8% only. It remained unchanged in 71% after excision of tumor. Yet, plasma levels of TIMP-1 were significantly higher in patients with distant metastases than in those with locally advanced process. No significant correlation between tumor and circulating TIMP-1 levels was established.

Matrix metalloproteinases 2, 3, 13 and their type 2 tissue inhibitor in tumors and plasma of patients with colorectal cancer.

Enzyme immunoassay studies revealed increased content of matrix metalloproteinases 2, 3 and 13 in tumors compared to the adjacent histologically unchanged mucosa in 70-90% patients with colorectal cancer, while the increase in the content of type 2 metalloproteinase tissue inhibitor did not reach the level of statistic significance. Plasma concentrations of these proteins did not correlate with the corresponding values in the tumors and did not surpass the normal levels, while their decrease after removal of the primary tumor was observed only in patients with initially high levels of this parameter.

Matrix metalloproteinases 7 and 9 and their types 1 and 4 tissue inhibitors in tumors and plasma of patients with colorectal cancer.

Enzyme immunoassays showed significantly elevated content of matrix metalloproteinase 7 and type 1 tissue inhibitor of metalloproteinases in tumors compared to adjacent histologically unchanged mucosa of patients with colorectal cancer; the levels of metalloproteinase 9 and type 4 tissue inhibitor of metalloproteinases were virtually the same in the tumors and mucosa. Plasma concentrations of the studied proteins did not correlate with their levels in the tumor, did not surpass the normal, and did not decease after removal of the primary tumor in the majority of patients.

[The incidence and primary multiplicity of colon cancer].

Analysis of Moscow cancer register demonstrates a steady growth of colon cancer (CC) incidence and mortality in Moscow, also noted in all large industrial cities of economically developed countries. In Moscow between 1996 and 2001, the incidence of CC had grown 1.5 times (from 19.6 up to 30% per 100,000), and the CC-related mortality had grown twice (from 9.1 up to 19.5% per 100,000). The incidence of CC among women is 1.5 to 2 times higher than that among men. The burst of CC incidence is noted after age 55, and the peak incidence is noted at age 65. Not rare (2.9% of cases) are tumors that develop simultaneously in different divisions of the colon, which are diagnosed during the surgery or are omitted even then. Such synchronous large bowel tumors are found mostly in patients over 60. The analysis show that metachronous tumors (3.4% of cases) usually develop in the colon 8 to 10 years after the first surgery for CC, or some other cancer, and are found mostly in patients over 70. Unlike foreign statistics on multicentric CC cancer, according to which primary-multiple (synchronous and metachronous) cancers occur in 1.24 to 14% of cases, Moscow statistics demonstrate a lower likelihood of such a pathology in Muscovites. To sum up, patients who underwent treatment for CC or any other cancer should keep being under an oncologist's observation due to the likelihood of the development of a metachronous colon tumor 8 to 10 years later.

[The experience in the use of DNA flow cytometry to predict the natural history of malignant neoplasms]. / Opyt primeneniia protochnoi DNK-tsitometrii dlia prognozirovaniia techeniia zlokachestvennykh novoobrazovanii.

The aim is to study the pattern of a cell population (ploidy) and to evaluate the latter's significance in the prognosis of different carcinomas. A total of 467 patients with primary carcinomas of the breast (n = 177), lung (n = 88), head and neck (n = 140), and colon and rectum (n = 62) were examined. All the patients underwent surgery alone or in combination with radiotherapy (X-ray)/chemotherapy. A follow-up lasted 6 to 120 months. DNA was measured in the operative tumor tissue specimens by using an ICP-22 flow cytometer. Diploid and aneuploid cancers occurred in 20.4-53.6 and 43.6-79.6% of cases, respectively. The frequency of recurrences was mainly associated with aneuploidy and it was more than thrice higher than that with diploidy (21.0-43.2 versus 4.5-14.4%). Five-year survival was twice worse in patients with aneuploid tumors than in those with diploid ones. The survival rates after one operation, preoperative, and postoperative radiation therapy was greater in patients with diploid tumors than in patients with aneuploid ones. Thus, DNA-ploidy of the study neoplasms is of high informative value in predicting the course of a tumorous process and in choosing treatment policy on an individual basis.

Soluble Fas antigen in the serum of patients with colon cancer.

Serum concentration of soluble Fas antigen (sFas) was measured in 60 normal subjects and 33 patients with colon cancer. The incidence of sFas detection and its serum content were higher in patients with colon cancer compared to normal subjects. No relationships between the incidence and level of sFas and patient's sex, age, duration and stage of the disease were found. Serum content of sFas tended to increase in patients with metastases to regional lymph nodes, liver, and lungs. The role of sFas as a marker predicting clinical course and outcome of colon cancer is discussed.

[Intensive preoperative hypoxic radiotherapy in combined treatment of patients with cancer of the colon]. / Intensivnaia predoperatsionnaia gipoksiradioterapiia v kombinoravannom lechenii bol'nykhs rakom obodochnoi kishki.

Efficacy of combined treatment (203 patients) and surgical treatment (200 patients) alone was analyzed. In combined treatment either radiation therapy (RT) in the dose 20 Gy over 5 days (group 1) or hypoxyradiotherapy (HRT) in the same doses but in combination with hypoxia (10% oxygen and 90% nitrogen--hypoxic gas mixture HGM-10--group 2) were used in preoperative period. In group 3 HGM-9 (9% oxygen and 91% nitrogen) was used as radioprotector in preoperative period but in increased by 25% radiation doses: total 25 Gy, 5 Gy for 5 days. In the control group only radical surgical treatment was performed. Preoperative irradiation didn't increase the rate of postoperative complications. At the same time the 5-year survival rate was higher in all the groups of patients on combined treatment than in the group of patients on surgical radical treatment. In the group with HGM-9 and increased by 25% radiation doses postoperative complications rate was lower, recurrences and distant metastases occurred less frequently.

[Morphological aspects of intense preoperative hypoxyradiotherapy in combined treatment of patients with sigmoid colon carcinoma]. / Morfologicheskie aspekty intensivnoi predoperatsionnoi gipoksiradioterapii v kombinirovannom lechenii bol'nykh rakom obodochnoi kishki.

Morphological study has confirmed the advantage of using doses of single radiation doses 5 Gy (total dose 25 Gy) and inhalation of a hypoxic gas mixture vs other methods of treatment. The study of radiation pathomorphosis showed significants devitalization of the tumor cells realized clinically with a fall in the number of postoperative recurrences and metastases.

[DNA flow cytometry in the prognostication of certain malignant neoformations]. / Protochnaia DNK-tsitometriia v prognozirovanii techeniia nekotorykh zlokachestvennykh novoobrazovanii.

The study has been concerned with DNA ploidy and its significance for prognosis of different neoplasms. The investigation included 314 patients: primary cancer of the lung (96), head and neck (146) and large bowel (72). Patients received surgery alone or surgery plus either radiotherapy or chemotherapy; they were followed up for 6-20 months. DNA levels were assayed in resected material using an ICP-22 flow cytometer. Diploid and aneuploid cancers were detected in 20.4-53.6 and 43.6-79.6%, respectively. The recurrence rates in cases of aneuploid cancers were more than 3 times those of diploidy (21.0-43.2 and 4.5-14.5%, respectively). Overall 5-year survival in diploid patients was twice that in aneuploid ones. Similarly, survival after surgery alone, preoperative chemotherapy and postoperative radiotherapy among diploid patients was longer than in aneuploid ones. Hence, DNA ploidy examination of tumors is of great informative value in prognosing tumor process and working out individually-tailored approach to treatment.

[DNA ploidy of tumor cells in prognostication of the course of malignant neoformations]. / Ploidnost' DNK opukholevykh kletok v prognozirovanii techeniia zlokachestvennykh novoobrazovanii.

DNA flow cytometry (FCM) was used for the clinical prognosis in patients undergone surgical removal of a tumor. The relationship between the structure of the tumor cell population (ploidy) and the frequency, time of a relapse onset (recurrence, metastasis), and the survival length were analyzed. All the patients had presurgical treatment (chemo- and/or radiotherapy). The patients were followed up for 5 to 9 years after surgery. The groups under study included 177 cases of breast cancer, 81 cases of larynx cancer, and 62 cases of colon cancer. Among the patients, the onset of a relapse was earlier and occurred more frequently in cases of aneuploid tumors among the patients regardless of the tumor type. In patients with aneuploid tumors, the most unfavorable prognosis was inherent in the hyperdiploid and multiclonal ones. The probability of 5-year survival for patients with aneuploid tumors appeared to be 20-30% lower than that in cases of diploid ones.

[Preoperative hypoxia-radiotherapy in multimodal treatment of patients with stage III colonic cancer]. / Predoperatsionnaia gipoksiradioterapiia pri kombinirovannom lechenii bol'nykh rakom obodochnoi kishki III stadii.

The paper analyzes the results of surgical and multimodality therapies for 237 patients with Stage III colonic cancer, which were divided into 3 groups. Group 1 included 119 patients undergone only surgical management, Group 2 comprised 43 who were additionally treated with intensive radiation (4 Gy daily for 5 days) and Group 3 consisted of 75 patients who were irradiated in the presence of overall hypoxia evoked by breathing a gaseous mixture containing 9% oxygen. A five-year follow-up has indicated that there are significantly higher survival rates among those who have received a multimodality therapy rather than those merely operated on (82 +/- 5 and 53 +/- 9%, respectively). A short-term gaseous hypoxia has been found to reduce the incidence of systemic radiation reactions in patients during preoperative radiation and to fail to lower the efficiency of multimodality therapy.

[Scintigraphy with tumoritropic radiopharmaceutical preparations in the diagnosis of cancer of the large intestine]. / Stsintigrafiia s tumorotropnymi RFP v diagnostike raka tolstoi kishki.

The authors represented the results of scintigraphic investigation to define the spreading of colon cancer in 78 patients. Of 21 patients in whom the investigation with 67Ga-citrate was performed in the preoperative period, RP accumulation was noted in 18, false-positive results were noted in 3 patients. During the investigation of 41 patients with 111In-bleomycin false-positive results were noted in all the cases. These results permit recommending this method for defining colon cancer spreading.

[Use of preoperative intensive irradiation in the combined treatment of patients with colon cancer]. / Ispol'zovanie predoperatsionnogo intensivnogo oblucheniia v komibinirovannom lechenii bol'nykh rakom obodochnoi kishki.

The paper discusses the results of preoperative intensive irradiation used in combined treatment for cancer of the sigmoid colon. Diagnosis was verified morphologically. Patients were randomly assigned for irradiation+surgery (group 1-97 cases) or surgery alone (group 2-111). Those undergoing radical operations only (in both groups) were included into the analysis. No difference was found between the two groups in rate of postoperative complications development (frequency of intestinal anastomosis failure included). The frequency of recurrence and metastasis development was significantly higher in the surgery only group. In patients with metastasis into regional lymph nodes, five-year survival was significantly higher among those who had undergone irradiation.