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Purpose: To assess prognostic/predictive value of carcinoembryonic antigen (CEA), transthyretin (TRT), αenolase (NNE), β2-microglobulin (β2-micro), B-cell activating factor (BAFF) and circulating tumor cells (CTCs) in metastatic colorectal cancer (mCRC) patients treated with chemotherapy with or without bevacizumab., Methods: 72 histologically confirmed mCRC patients treated at Oncology Institute Cluj were included. Biomarker levels were measured through validated methods. A manual method was used for CTCs, involving hemolysis, cytospin centrifugation and immunocytochemical staining for pan-cytokeratin. Statistical endpoints were response, progression- free survival (PFS) and overall survival (OS)., Results: Initial chemotherapy was fluoropyrimidine/oxaliplatin-based in 93.1%; bevacizumab was added in 58.3% of the patients. Median PFS and OS were 16.4 and 24.4 months. Two-year OS for CR & PR vs SD vs PD were 90% vs 48% vs 12%, respectively (p<0.01). Two-year OS for chemo/ bevacizumab vs chemotherapy: 65% vs 42% (p=0.09). Baseline CEA ≥5 ng/ml had a negative prognostic impact on OS and PFS (p<0.01). High baseline CEA was predictive of improved OS when adding bevacizumab (2-year OS chemo/bevacizumab vs chemo: 60% vs 17%, p<0.01); adding bevacizumab in patients with normal CEA did not improve OS (p=0.29). Higher than cut-off values for TRT had a positive OS prognostic value (p<0.01); higher levels for NNE, β2-microglobulin and BAFF had a negative impact (p<0.01). Two-year OS for baseline <1 CTC/ml vs ≥1 CTC/ ml was 74% vs 64% respectively (p=0.15)., Conclusions: The evaluated biomarkers could be useful prognostic factors for survival. Baseline CEA also has predictive value, suggesting that patients with low levels do not benefit from bevacizumab. A non-statistically significant correlation was observed between the number of CTCs and outcome.

BACKGROUND & AIMS. The present study was designed to examine the combined effects of Oxaliplatin (OXA) and 5-Fluorouracil (5-FU) in the Colo320 cell line. METHODS. The antiproliferative effects were evaluated using the MTT assay, apoptosis by flow cytometry, and RT-PCR-array technology was used to determine the major effects of the two chemotherapeutic drugs upon the most important genes involved in apoptosis. RESULTS. The antiproliferative effects of the therapeutic agents, as individual therapy or combined, proved to be dose and time-dependent, with increased efficiency for the combined treatment. Flow cytometry data revealed increased apoptotic processes in the case of the combined treatment at 24 hours after administration. The RT-PCR-array data indicated that at 24 hours after OXA treatment, 49 genes were differentially expressed, of which 45 were up-regulated and 4 down-regulated. In the case of the 5-FU treatment, 35 genes were down regulated and 2 up regulated. In the combined treatment of 5-FU and OXA, 19 genes were up-regulated and 15 down-regulated. CONCLUSIONS. This study proved that drug resistance could be counteracted by combining OXA with 5-FU to form a tandem that is capable of reducing cell proliferation and to stimulate extrinsic apoptosis pathway by targeting death receptors on the cell surface.

Aim: To identify the risk, the host-related prognostic factors and their predictive value for anastomotic leakage after colorectal resections following cancer., Method: 993 patients who underwent large bowel resection and primary anastomosis above 12 centimeters from the anal verge, without a temporary or permanent stoma at the Surgical Hospital No.3 (Cluj-Napoca, Romania) were retrospectively reviewed., Results: 32 (3.22 percent) anastomotic leaks were confirmed. Univariate analysis showed that the preoperative variables significantly associated with anastomotic leakage included: weight loss, smoking, cardiovascular disease, lung disease, hypoproteinemia, diabetes, anemia, leukocytosis, presence of two or more underlying diseases. Alcohol use, cerebrovascular disease, bowel preparation, type of anastomosis, tumor location, stage and histology were not significant variables. Hypoproteinemia (total serum protein level < or = 6 g/dl) and anemia (serum hemoglobin level < or = 11 g/dl) remained significant in the logistic regression model. The prognostic role of serum hemoglobin and proteins for the anastomotic leak was assessed using ROC curve analysis. For the cut-off value of serum protein level = 5.5 g/dl, a sensitivity of 61.6 percent and a specificity of 84.2 percent were calculated. The area under the curve was 0.703 (p= 0.0024). The area under the curve for serum hemoglobin was 0.616 (p=0.028). A sensitivity of 64.0 percent and a specificity of 64.7 per cent were obtained for a cut-off value of 9.4 g/dl. CONCLUSION. A serum protein level lower than 5.5 g/dl and serum hemoglobin lower than 9.4 g/dl could be considered as host-related predictive markers for anastomotic leak in large bowel resections for cancer.

Purpose: We analyzed the clinical results of different techniques of resection for malignant colorectal (primary or staged) obstruction., Methods: The subjects of this retrospective nonrandomized clinical study were 165 patients with malignant colorectal occlusion who underwent surgery treatment in our Department between 2002-2006. Patients with peritonitis or treated by means of permanent colostomy, palliative anastomosis, primary Hartman resection and rectal excision were excluded., Results: Patients with large bowel obstruction caused by obstructive malignant colorectal lesions underwent either one-stage primary resection with anastomosis (77 patients) or staged interventions (88 patients). There were no differences in age, sex, comorbidities, tumor staging, serum preoperative levels of hemoglobin and proteins between the two groups of patients defined by the different surgical techniques. Regarding mortality and morbidity following surgical treatment for large bowel obstruction no significant difference among the two groups (p > 0.05) or the fistula rate (p = 0.435) was obtained. Moreover, results showed a higher incidence of mortality (11.8% vs 7.8%), morbidity (13.6 vs 10.4) and increased hospitalization period (p = 0.03) among the patients that undergone series resections., Conclusions: One stage primary resections with anastomosis of the large bowel can be performed safely in case of emergency whenever patient comorbidities and local conditions do not stand as major restrictions.

Background and Aim: Case selection criteria for resection of liver metastasis after colorectal cancer are still incompletely elucidated and represent a subject of great interest recently. Our aim was to evaluate 2-year survival after resection and to identify the survival risk and prediction factors in those cases., Methods: 63 patients diagnosed and undergoing liver resection for colorectal metastatic disease to the liver at the Surgical University Hospital No.3 (Cluj-Napoca, Romania) between 01.01.2002 and 31.12.2005 were included in the study. Exclusion criteria were: palliative treatment as well as surgical treatment performed in a different surgical centre. After the surgical treatment, patients were followed regularly using clinical assessment on a 3 monthly basis with abdominopelvic ultrasound or computerised tomography annually. The following variables were recorded: age, gender, coexisting medical diseases, blood tests results, tumour site, maximal tumour diameter after resection, duration of surgery, surgical procedure and the clinical outcome until last follow-up, including date of death where appropriate., Results: 2-year post-operative survival was 65.1%. In univariate analysis: age (< 65 vs > = 65 years, p = 0.041), metastasis number (< 3 vs > = 3 tumors, p = 0.049), maximal tumor dimension (< 3 vs > = 3 cm, p = 0.047), glutamine-oxaloacetic transaminase (GOT) preoperative level (< 42 vs > = 42 mg/dl, p = 0.018) were significant factors correlated to median survival time. However, non of the above mentioned factors presented independent prediction power in multivariate analysis (Cox regression, p < 0.05)., Conclusions: Our results support liver metastasis resection without prior case selection except for technically-operative criteria selection.