Significance of expression of tumor-associated microRNA-21 and -375 for predicting the course of cancer of oral cavity.

AIM: To investigate the features of expression of miRNA-21 and miRNA-375 in tumor cells of patients with cancer of oral cavity (COC) and to determine the possibility of their use to predict the aggressiveness of COC course. MATERIALS AND METHODS: The work is based on the results of examination and treatment of 50 patients with stage II-IV COC. miRNA expression in tumor cells was analyzed by real time reverse transcription polymerase chain reaction. RESULTS: High levels of miRNA-21 expression (> 0.26 a.u.) and miRNA-375 (> 0.36 a.u.) were determined in 72.0% and 63.0% of cases. We revealed a tendency to decreased miRNA-21 expression and increased miRNA-375 expression in tumors of patients with recurrence-free survival less than 12 months and the presence of metastatic lesions in regional lymph nodes. In patients with COC of low differentiation grade, the level of miRNA-21 was 2.0 times lower compared with tumors of moderate differentiation grade (p < 0.05), while the expression of miRNA-375, on the contrary, was higher in tumors of low differentiation grade. A decreased expression of miRNA-21 (< 0.26 a.u.) against the background of decreased levels of miRNA-375 (< 0.36 a.u.) in tumor cells was associated with worse recurrence-free survival. CONCLUSIONS: The obtained results indicate the relation between the main clinical and pathological characteristics of patients with COC and the levels of miRNA-21 and -375 expression in tumor tissue, which indicates the involvement of these miRNAs in the formation of COC malignancy evidencing on their potential usefulness as additional prognostic markers.

Establishing of Peritoneal Surface Malignancy Treatment Program: Background in Ukraine, Patient Selection, Staff Schedule, Perioperative Outcomes of First 28 Patients.

A combination of cytoreductive intervention with the intrahepatic hyperthermic chemotherapy is a well-established treatment of peritoneal carcinomatosis. There are many challenges in establishing a new peritoneal surface malignancy program in a low-income country regarding perioperative safety and resource allocation. We analyzed the retrospective database to determine the immediate surgical outcomes of the first 28 patients with peritoneal carcinomatosis and the impact of the program on allocation of general hospital and human resources. During the preparatory stage, web conferences with international experts established the goals and general requirements of the program, formalized in a written document; and a peritoneal surface malignancy multidisciplinary team was established. The team created the patient selection criteria, perioperative management checklists, and suggested material and staff requirements for surgical and anesthesia services. Twenty-nine cytoreduction were carried out, of which 18 were followed by HIPEC. The average operative time was 6.2 h. The median blood loss was 350 mL, which did not result in additional blood transfusion requirements for the blood bank. No additional nursing and supportive staff were provided for the ICU and the surgical unit. The average postoperative stay was 8.7 days. One patient died with 30-day mortality rate of 3%. Ten patients (34.5%) developed postoperative complications, of which 6 (20.6%) had grade III and higher Clavien-Dindo complications. Establishing a peritoneal surface malignancy program is possible via staged planning, liberal use of international mentors, and thoughtful resource allocation. This new program did not result in a significant redistribution of resources among other service lines of cancer care within the same institution.

BILATERAL AVASCULAR NECROSIS OF SACRAL LATERAL MASSES AFTER A COMPLETE RADIOLOGICAL RESPONSE OF LOCALLY ADVANCED RECTAL CANCER TREATED WITH NEOADJUVANT CHEMORADIATION THERAPY. CASE REPORT. / BILATERAL'NYY̆ AVASKULIaRNYY̆ NEKROZ LATERAL'NYKh MAS KRYZhIV PRY POVNOMU KLINIKO-RADIOLOGIChNOMU REGRESI PISLIa NEOAD'IuVANTNOÏ KhIMIOPROMENEVOÏ TERAPIÏ MISTsEVO POShYRENOGO DYSTAL'NOGO RAKU PRIaMOÏ KYShKY. KLINIChNYY̆ VYPADOK.

We present a rare case report of a bilateral avascular necrosis of lateral sacral masses in a patient who developed a sustainable complete clinical and radiological response after chemoradiotherapy for locally advanced rectal cancer. It is shown that despite the standardized and precise planning and fractioning for neoadjuvant chemoradiation therapy for locally advanced rectal cancer, the biological effects of ionizing radiation on critical organs can be va- ried both in time of occurrence and in structure. Evaluating the effect of neoadjuvant chemoradiation therapy, one should take into account the possibility of the development of even very rare effects of ionizing radiation on criti- cal organs and include their early detection in the diagnostic algorithm.

Tumor-associated redox state in metastatic colorectal cancer.

The high incidence of recurrence and metastasizing in colorectal cancer (CRC) poses the challenge for the improvement in long-term treatment outcome. AIM: To determine the major indicators of redox-formative molecules in the tissue of metastatic CRC (mCRC), stages Т2-4N0-2M0G2-3, namely the rate of superoxide radical (SR) generation, nitric oxide (NO) content, the activity of matrix metalloproteinases (MMP), lactoferrin (LF) content, and "free" iron and their association with some clinical and pathological characteristics of the patients. MATERIALS AND METHODS: mCRC samples from 51 patients were analyzed (stage II, 31 patients; stage III, 20 patients). The LF and "free" iron were assessed by electron paramagnetic resonance (EPR) at the temperature of 77 °K. The rate of SR and NO generation was determined with spin traps (ТЕМРО-Н, diethyl dithiocarbamate). The activity of MMP-2 and -9 was measured by gelatin zymography using SDS-polyacrylamide gel electrophoresis. Ki-67 expression was analyzed by immunofluorescence technique. RESULTS: In tumors with metastases into the regional lymph nodes (N1-2 category), SR generation rate was 2.2-fold higher than in the tumors categorized as N0. In G3 mCRC, SR generation rate was 1.7-fold higher than in G2-tumors (p < 0.05). The rate of SR generation correlated inversely with differentiation grade of the tumor (r=-0.61; p < 0.05). MMP-2 and -9 activities in mCRC tissue correlated with SR generation rate and NO level (r = 0.44 ÷ 0.53, p < 0.05). The direct correlation between LF content and the stage of the disease (r = 0.42) and "free" iron content (r = 0.61) was demonstrated while the correlation between LF content and tumor differentiation grade was inverse (r = -0.57; p < 0.05). CONCLUSIONS: The altered tumor-associated redox state in mCRC tissue contributes to the increased cell proliferation and formation of aggressive phenotype of the tumor. The assays for the content of redox-formative components in mCRC may be used as additional prognostic markers of the course of the disease in CRC patients.

DNA oxidation in patients with metastastic colorectal cancer: clinical significance of 8-hydroxy-deoxyguanosine as an independent prognostic factor.

Prognosis of metastatic colorectal cancer (mCRC) patients nowadays is an important subject in the field of oncology. R0-resection of colon with primary tumor and liver metastasis remains the only treatment which significantly improves survival rate. However, recent experimental data show that surgical trauma can indirectly stimulate tumor growth due to mitochondrial dysfunction and unregulated superoxide radical (O2-) generation. AIM: To study the clinical significance of 8-oxo-2'-deoxyguanosine (8-oxodGu) marker, to assess the oncological effects of warm ischemia of liver parenchyma on disease prognosis in patients with mCRC. MATERIAL AND METHODS: 69 urine 24-hour volume tests of patients with mCRC and 17 healthy individuals were studied. Urine 8-oxodGu level was measured using spectrophotometric method with pre-solid phase DNA extraction. The energy system and hepatocyte detoxification system state, levels of O2- in tumor tissue were determined using the method of electron paramagnetic resonance (EPR) and SpinTraps technology at room temperature. Experiments were carried out on a computerized EPR spectrometer RE-1307. EPR spectra were recorded at temperature of liquid nitrogen (196C) in paramagnetically pure quartz dewar on a computerized spectrometer PE-1307 with resonator H011. Error of the method of spectrum integration and spread of spectrum reproduction of one sample was not more than 3%. RESULTS: The average level of marker in healthy individuals was 0.244 day, whereas before the resection and on day 3 after the R0-resection of liver in mCRC patients was 3.42 day and 2.12 day (p < 0.05), respectively. On day 3 after the liver resection due to its metastatic lesions with a total duration of warm ischemia period < 30 min and > 30 min have had marker at level 2.108 day and 2.9883 day (p < 0.0001), respectively. The volume of metastatic tissue significantly and directly correlated with the level of urine 8-oxodGu (R2=0.54, 95% CI 0.0370.0991, p < 0.0001), also duration of surgical intervention (300 min) and duration of worm liver ischemia ( 30 min) during the surgery significantly increased urine level of 8-oxodGu (R2=0.54, 95% CI 0.001 0.004, p < 0.001). CONCLUSIONS: Warm liver ischemia (> 30 min), long-term surgical intervention ( 300 min) and metastatic tissue volume ( 12 cm3) in liver parenchyma in mCRC patients significantly increase urine 8-oxodGu levels. R0-resection of liver metastases in mCRC patients decreases urine 8-oxodGu levels already on day 3 after the surgery. 8-oxodGu is a new factor of oncological prognosis in patients with mCRC.

Modelling of survival of patients with colon adenocarcinoma based on multivariable analysis of the state of cancer cell nuclear apparatus.

THE AIM: The creation of a mathematical model of survival in patients with colon adenocarcinoma based on multivariable analysis of the state of cancer cell nuclear apparatus. PATIENTS AND METHODS: The study was performed on 141 samples of biopsy materials or material obtained during surgical treatment of the patients with colon adenocarcinoma or benign colon neoplasms with the use of histological, morphometric, densitometric, immunohistochemical and mathematical methods. RESULTS: It has been shown that each discrete pattern of the state of adenocarcinoma cell nuclei (quantity of DNA, the number and volume of nuclear organizer regions, expression rates of Ki-67, Bcl-2 and p53) is prognostically invalid in the case of its separate use. Combination of these characteristics significantly enhances prognostic validity of the survival model. Based on equation of Cox proportional hazards, survival model of good quality for the patients with moderately and poorly differentiated adenocarcinoma and increased average DNA content in tumor cell nuclei has been created. CONCLUSION: The proposed survival model for colon adenocarcinoma demonstrates the quality twice superior to the model based on the use of tumor grade only (G) which in fact is presently used as a sole common independent histological criterion of prognosis.

[PREDICTING FACTORS OF THE LIFE SPAN IN PATIENTS, SUFFERING METASTATIC COLORECTAL CANCER AND SYNCHRONOUS HEPATIC AFFECTION AFTER SURGICAL TREATMENT].

The results of treatment of 125 patients, suffering metastatic hepatic affection in colorectal cancer (pT1--4N0--2M1--in colonic cancer and pT1--3N0--2M1--in cancer recti), to whom in 2008-2015 yrs a one-staged (Group 1) or two-staged (Group II) surgical treatment was done. In affection of 4 regional lymph nodes and more (pN2) late results were less favorable, than in pN1 or pN0, not depending from surgical approach choosed. In 48 (38.4%) patients with one syndromal hepatic metastatic focus, the indices of general three-year and five-year cumulative survival were the best, than in other groups--82 and 63% (p = 0.001) accordingly; in monolobar affection--68 and 49%, and in bilobar--23 and 0%, not depending from method of surgical treatment (p < 0.001) choosed. Predictive factors were established, which impact negatively the indices of general survival in patients, suffering metastatic hepatic affection in colorectal cancer: hepatic metastatic foci number 4 and more, bilobar hepatic metastatic affection.

[SURGICAL TREATMENT OUTCOME IN PATIENTS WITH COLORECTAL CANCER AND CONCOMITANT LIVER METASTASES].

Colorectal cancer with synchronous liver metastasis (sm-CRC) is extremely unfavorable prognostic factor. Surgery remains is most effective method, able to extend the life of these patients. The results of treatment of 126 patients with sm-CRC were analyzed, whom performed simultaneous (group I) or staged (group II) surgery. Simultaneous resection of 3 segments of liver or less with metastases and primary tumor is a safe surgical strategy (complicatios level was 4.8%); simultaneous resection of 3 segments of liver or more increase the complicatios level to 20.9%. Simultaneous resection ensure reduction of hospital stay terms in 58.1% and duration of surgery in 71.3% (p < 0.001). The average cost of treatment patient treating with staged strategy exceeded in simultaneous surgical treatment in 40.9%.

[Combination of in-situ hepatic split and portal ligation in patients with colorectal cancer and metastatic hepatic spread].

In up to 50% of patients, suffering colorectal cancer (CRC), a hepatic metastatic affection was revealed, in 20-34% of them the metastases have occurred synchroniously with primary tumor. The main problem in estimation of resectability of metastatic CRC (mCRC) is a possibility to preserve a sufficient volume of the organ parenchyma, because an acute hepatic insufficiency (AHI) constitute one of the main risk factors for occurrence of complications and mortality in early postoperative period after extended hemihepatectomy. The expediency of application in National Cancer Institute of the insitu hepatic split in conjunction with a portal ligation (ISHS-PL), elaborated by surgical group in Regensburg, was studied up. The results of treatment of mCRC, using ISHS-PL--in 3 patients and of a standard two-staged hepatic resection--in 3, were analyzed. Duration of a gap period between the ISHS-PL stages have constituted on average (10 +/- 1) days, and for a standard two-staged hepatic resection--(56 +/- 11.3) days (p = 0.001). The investigation results witness a safety of performance of the ISHS-PL in patients, suffering mCRC. Application of such a surgical tactics have permitted to reduce the risk of an AHI occurrence after performance of the extended hepatic resection in patients, suffering bilobar metastatic hepatic affection.

Screening of epigenetic and genetic disturbances of human chromosome 3 genes in colorectal cancer.

DNA microarray technology comprising NotI-linking clones was used in a large-scale study of genetic and epigenetic changes in colorectal cancer. Analysis of samples from 24 patients revealed methylation, deletions, and amplifications in 137 of 181 NotI clones. For 27 genes/loci, these changes occurred in more than 30% of the tumor samples, suggesting that these genes are involved in the development of colorectal cancer. An analysis of the methylation status of CpG island of the ITGA9 gene/loci by bisulfite sequencing confirmed the NotI microarray data on the gene/loci methylation in colorectal cancer. Aberrations in 19 genes/loci were unknown previously. Their characterization may help ascertain the mechanisms responsible for colorectal cancer development and identify novel diagnostic and prognostic markers.