[Combined treatment of rectal cancer with moderate risk of tumor progression]. / Rezul'taty primeneniya kombinirovannogo metoda lecheniya bol'nykh rakom pryamoi kishki so srednim riskom progressirovaniya opukholevogo protsessa.

OBJECTIVE: To increase the effectiveness of combined treatment in patients with rectal cancer and moderate risk of progression based on the concept of polyradiomodification (PRM). MATERIAL AND METHODS: The study included 337 patients with rectal cancer and moderate risk of tumor progression. A short course of radiotherapy (cRT) (5x5 Gy) combined with several radiomodifiers (cRT+PRM) was performed in 147 (43.6%) patients. Other 190 (56.4%) patients underwent cRT. The following radio modifiers were used: three-time application of local microwave hyperthermia (Yacht-3 or Yacht-4 devices), two-time intrarectal delivery of a biopolymer composition with Metronidazole before the 3rd and 5th irradiation sessions and two-week oral administration of Capecitabine (Xeloda) at a daily dose of 2.0 g/m2. Surgery was performed in 4-6 weeks after radiotherapy. RESULTS: CRT+PRM program increased 5-year relapse-free survival up to 81.3% compared to 60.3% after cRT alone (p=0.0003) due to significant reduction of the incidence of cancer recurrence from 8.4% to 0.7% (p=0.0013). More effective local growth control expanded the indications for sphincter-sparing surgery. These procedures were performed in 89.1% and 70.5% of patients, respectively (p=0.00001). In the cRT+PRM group, sphincter-sparing surgery reduced incidence of cancer recurrence from 13.7% to 0.8% (p=0.0110), distant metastases - from 23.9% to 13.7% (p=0.00349). CONCLUSION: Radiomodification in neoadjuvant radiotherapy is justified in patients with moderate risk of tumor progression, improves long-term results and increases the incidence of sphincter-sparing surgery.

[Effectiveness of neoadjuvant chemoradiotherapy of locally advanced rectal cancer in conjunction with local hyperthermia and metronidazole].

Our study included 36 patients with hard fixed rectal tumors (T3, T4) who had received combined treatment at the Center's Clinics. On irrigoscopic evidence, lesions were more than 10 cm long. Radiotherapy was conducted thrice a week, STD of 4 Gy--TTD of 40 Gy; capecitabine, per os, 650 mg/m2 twice a day, days 1-22; oxaliplatin, 50 mg/m2, intravenously, days 3, 10 and 17; metronidazole in polymer composition, intrarectally, 10 mg/m2, twice, days 12 and 17 of radiotherapy; local hyperthermia (the <> installation), 460 mHz, 41-45 deg. C, 60 min, days 8, 12, 15 and 17. Diarrhea (stage III) was reported in 3 (8.3%); no toxicity (grade IV). Radical surgery was carried out in 35 (97.2%); sphincter-saving operation--20 (55.5%). Therapy-related pathomorphism (grade III-IV) was detected in 15 (42.8%). Combined neoadjuvant chemoradiotherapy plus polyradiomodification featured low toxicity and good tolerability and immediate effect.

[Polyradiomodification as component of combined treatment of rectal cancer: rationale and results].

The report discusses our 30-year experience with surgical and combined treatment of rectal cancer. In cases of preoperative radiotherapy, loco-regional frequency of relapse dropped to 9.6% as compared with surgery (16.3%). After preoperative thermoradiotherapy it fell to 4.6%; polyradiomodification - 0.5% (3-year follow-up). Distant metastasis formation rates were: after polyradiomodification--1.5%, radiotherapy--9.6%, and thermo-radiotherapy--6%. Recurrence-free survival rates (3 years) were: polyradiomodification--97.3%, thermo-radiotherapy--75.9%, radiotherapy--71.1%, and surgery--58%. Data on regimens and dosage of polyradiomodification alongside radiation damage for different combinations of treatment are presented.

[Histogenesis of infantile fibrosarcoma].

Eight cases of infantile deep soft tissue fibrosarcoma were examined. The tumor consists of neoplastic fibroblasts and myofibroblasts which differ from each other ultrastructurally. Well-differentiated collagen-forming neoplastic fibroblasts form one-half of infantile fibrosarcoma. Immunohistochemically and ultrastructurally immature embryonic-like fibroblasts were also identified. The latter closely resemble an embryonic perichondrial fibroblast of the embryonic limb during 6 weeks of development.

[Infantile hemangiopericytoma: a clinico-morphological study of 10 cases].

Infantile hemangiopericytoma (IH) is a rare mesenchymal tumor of the extremity and trunk soft tissues with medium potential grade. Its clinical course and prognosis on the basis of morphological evidence are unpredictable. IH consists of CD34-positive fibroblasts forming around fissural vessels. Some tumors feature non-hemangiopericytic structures. IH is morphologically identifiable by comparing with other infantile fibroblastic tumors, such as myofibroma and solitary fibrous tumor. Immunomorphological examination is essential to assure proper diagnosis of IH.

[Combined treatment for rectal cancer using different radiomodification means].

The paper presents an evaluation of the results of surgical and combined treatment received by 961 patients at the Center's Clinics within 28 years. The analysis was based on 3 protocols of prospective randomized study. It dealt with assessment of the end results of surgical and combined treatment for operable rectal cancer using one preoperative hyperfractonated STD of 5-25 Gy. That was combined with local microwave hyperthermia and two radio modifiers--local microwave hyperthermia+intrarectal administration of a preparation containing metronidazolum. Due to the latter factor, the rate of 3-year relapse-free survival rose considerably. Also, loco-regional and distant metastasis incidence was cut down due to superior ablasticity of surgery.

[Diagnosis of micrometastases of alveolar rhabdomyosarcoma].

Alveolar rhabgomyosarcoma is a highly malignant, small blue cell pediatric soft tissue tumor. Identification of micrometastases in alveolar rhabdomyosarcoma is important because the poor prognosis associated with this subgroup necessitates a modified therapeutic regimen. Since the obtained lymph node specimen can be very small; rhabdomyosarcoma cells are not easily detected using conventional histological methods. To assess the value of myogenin staining in the diagnosis of micrometastases in alveolar rhabdomyosarcoma, the authors examined 36 lymph nodes from children bearing this tumor. Occult tumor cells were detected in 8 cases. The PAX3/7-FKHR gene fusion that resulted from chromosomal translocation in alveolar rhabdomyosarcoma provided potential molecular diagnostic markers. Reverse-transcriptase polymerase chain reaction (RT-PCR) was used to develop an assay capable of identifying RAX3/7-FKHR positive cells in the fresh lymph nodes. Thirty-six lymph nodes were examined and of them 17 lymph nodes had PAX3/7-FKHR fusion transcripts of alveolar rhadomyosarcoma cells. The study demonstrates that molecular RT-PCR detection of micrometastases is the most sensitive method for diagnosing alveolar rhabdomyosarcoma.

[Low-grade fibromyxoid sarcoma: analysis of 8 cases].

The diagnosis of low-grade fibromyxoid sarcoma was made in 8 patients. The lesions were 2-17 cm in the lower extremities and trunk. One patient had a long history of painless subcutaneous and intramuscular mass (median 1 year). All tumors showed predominantly the typical hypocellularity and cytologic features of typical low-grade fibromyxoid sarcoma; however, the areas of hypercellularity and nuclear enlargement and hyperchromatism were identified. No necrosis and mitotic activity less than 2 mf/50 HPF were present. Ultrastructurally, the tumor composed of neoplastic fibroblasts. No other cell differentiation was identified. Immunohistochemically, the neoplastic cells showed a positive response to vimentin and fibroblast antigen; no muscle-specific antigens were revealed. The Ki-67 labeling index with MIB-1 ranged 2-6%.

Prognostic significance of expression of matrix metalloproteinase in colorectal adenocarcinomas and their metastases.

Expression of matrix metalloproteinases 2 and 9 was studied in primary tumors and their metastases in patients with colorectal cancer. The correlation of immunoreactivity with clinical morphological signs, prognosis of the disease, and development of metastases in the liver was analyzed. The level of expression and distribution of markers in patients with colorectal cancer with metastases in the liver differed from that in control patients without metastases. Enhanced expression of matrix metalloproteinases 2 and 9 was detected in colorectal cancer patients with distant metastases. Increased expression of matrix metalloproteinase 9 was associated significantly with low histological differentiation of the tumor, deeper tumor invasion, and was more often observed in tumors of colorectal cancer patients with unfavorable prognosis. Thus, matrix metalloproteinase 9 is a valuable marker for clinical observation and prognosis in patients with this location of the tumor process.

[Signet ring cancer of the stomach: clinico-morphological features, postsurgical results and prognosis].

Clinico-morphological features of signet ring cancer of the stomach were evaluated in 372 out of 2,308 gastric cancer patients undergoing gastroectomy or stomach resection. Signet ring tumor pathology occurs mostly in young females and younger patients generally. It features high incidence of early cancers, low frequency of metastatic spreading to lymph nodes (T1-T2), high frequency of immediate involvement of perigastric fatty tissues, peritoneum and ovaries and infrequent spreading to the liver. Post-surgical survival rates among patients with T1-T2 were relatively high, yet declining in cases of extension through the serous membrane of the stomach. D2-lymphdissection failure to improve the end-results of surgical treatment of signet ring cancer might be accounted for by the predominance of peritoneal metastases of this morphological pattern. Histochemical assay of mucines might be contribute additional data on prognosis.

[The features of expression of cellular adhesion molecules in primary colorectal cancer and its metastases].

Features of expression, distribution and interaction of E-cadherin, beta-catenin and CD-44v6 were immunologically assayed in samples from primary colorectal tumors (129) and their metastases to the lymph nodes (35) and liver (92). Reduction or total absence of E-cadherin expression was significantly more typical of tumors metastasizing, at different stages, to the liver (64/84, 76%) than in metastasis-free ones (14/45, 31%) (p=0.014). Enhanced cytoplasmic immunoreactivity and beta-catenin nuclear translocation occurred in 80% of disseminated tumors. Such alterations of E-cadherin, beta-catenin expression may be regarded as unfavorable prognosis factors involved in colorectal cancer. No significant correlation between CD-44v6 expression and tumor cell ability to metastasize was recorded.

[Monophasic synovial sarcoma: comparison of immunohistochemical and ultrastructural phenotypes and problems of differential diagnosis].

Diagnostics of monophasic synovial sarcoma is highly complicated mostly due to a wide range of cellular and histologic variation. This calls for use of additional examination techniques such as immunohistochemical and electron microscopic.

Expression of E-cadherin, beta-catenin, and CD-44v6 cell adhesion molecules in primary tumors and metastases of colorectal adenocarcinoma.

Immunohistochemical analysis of the expression of E-cadherin, beta-catenin, and CD-44v6 proteins was carried out for evaluating the metastatic potential of colorectal cancer cells. Specific features of expression, distribution, and interactions of adhesive molecules in primary tumors of the large intestine and their metastases in the liver and lymph nodes were studied. Reduction and complete absence of E-cadherin expression were much more often observed in patients with colorectal cancer with metastases in the liver than in patients without metastases. Cytoplasmic immunoreactivity and nuclear translocation of beta-catenin were increased in more than 80% cases with colorectal adenocarcinoma with metastases. These changes in the expression of E-cadherin and beta-catenin in tumor cells can be regarded as factors of unfavorable prognosis of colorectal cancer. No significant relationship between expression of CD-44v6 protein and metastatic potential of cancer cells was detected.

[Immunohistochemical study of E-cadherin, beta-catenin and CD-44v6 expression in the cells of primary colon cancer and its metastases].

129 primary colon carcinomas, 35 metastases to the lymph nodes and 92 metastases to the liver are studied. Reduction or complete absence of E-cadherin was more frequently observed in cases with liver metastases (64/ 84 - 76%) than in patients without metastases (14/45 - 31%) (p = 0,014). Also, beta-catenin expression was more frequent in cases with metastases. These results of E-cadherin and beta-caterin expression, changes may be considered as factors of unfavourable prognosis. No links between CD44v6 expression and metastases was found.

[Expression of nm23 and c-erbB-2 proteins in cells of primary colorectal cancer and its metastases]. / Ekspressiia belkov nm23 i c-erbB-2 v kletkakh pervichnogo kolorektal'nogo raka i ego metastazov.

Expression of proteins nm 23 and c-erbB-2 is observed in many human carcinomas and is associated with the disease progression. Immunohistochemical study of nm23 and c-erbB-2 expression was performed on 64 primary tumours, 19 metastases in the lymph nodes and 37 liver metastases. More pronounced expression of these proteins in the primary tumour cells is observed in cases with liver metastases. Expression of nm 23 was observed in 66% and that of c-erbB2 in 59% of liver metastases. Thus, expression of these proteins may reflect biological behaviour of the tumour and may appear to be an important factor in development of colorectal cancer metastases.

Immunohistological study of NM 23 and C-erbB-2 expression in primary tumor and metastases of colorectal adenocarcinoma.

Immunohistochemical study of expression of nm 23 and c-erbB-2 protein markers in primary tumor and metastases of colorectal adenocarcinoma showed that the incidence and expression of both protein markers in primary tumor tissue tended to increase after the appearance of liver metastases. Peculiarities of protein expression in tumor metastases in lymph nodes and liver and the possibility of using these markers as additional prognostic criteria in colorectal cancer are discussed.

[Deletion of YNZ22 and ALU-VPA/MYCL1 loci in human colonic adenocarcinoma and postoperative prognosis]. / Deletsii lokusov YNZ22 i ALU-VPA/MYCL1 v adenokartsionomakh tolstoi kishki cheloveka i posleoperatsionnyi prognoz.

Since deletions of the short arm of chromosome 17 are the most common genetic defects in human colorectal carcinoma (CC), we tested the YNZ22 locus (D17S30, 17p13.3) for loss of heterozygosity (LH) in adenocarcinoma and in the normal colonic mucosa of 49 CC patients, and studied the association of LH with clinicomorphological features of the tumor. Allele frequency distribution of YNZ22 did not differ for the patients and healthy people. LH in YNZ22 in the tumor was found in 33% (13/39) of all informative cases, its frequency being thrice higher in men than in women (chi 2 = 5.21, p = 0.022). The defect was associated with moderate or poor histological differentiation (P2 = 0.0055) and polyploidy > 3n (P2 = 0.0035) of tumor cells and with high incidence of post-surgery relapse or metastasis. Analysis of both YNZ22 and Alu-VpA/MycL1 (1p34.3) loci in the tumor allowed reliable relapse prognosis in 76% of the CC patients. The probability of post-surgery relapse or metastasis was estimated at no less than 67% for patients with LH in at least one of the two loci in the tumor, and at somewhat more than 20% for patients without LH.

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.

[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.