Neutrophil infiltration combined with necrosis in the primary tumor is a useful prognostic indicator for three-year disease-free survival time in patients with colorectal cancer.

Histopathological evaluation plays a key role in the diagnosis of colorectal cancer (CRC). Tumor-related local inflammation is regarded as a novel prognostic parameter. Neutrophils constitute one of the main types of inflammatory cells. The aim of the present study was to evaluate the prognostic value of intratumoral tumor-associated neutrophils (intraTANs), stromal TANs (stromaTANs) and necrosis, as well as their combined parametric value in formalin-fixed paraffin-embedded tissue sections from patients with CRC. For this purpose, a retrospective study of 160 patients with CRC who underwent surgery was conducted. The association of intraTANs, stromaTANs, necrosis and their combined parametric value with the clinicopathological features of patients with CRC was examined. The Kaplan-Meier method and the log-rank test were used to compare survival curves. To identify independent prognostic factors, uni- and multivariate Cox proportional hazards regression models were used. StromaTANs were associated with lymph node metastasis (P=0.049) and tumor deposits (P=0.041). In addition, necrosis was found to be associated with venous (P=0.003), lymphatic (P=0.007) and perineural (P=0.015) invasion, as well as with lymph node metastasis (P=0.033), the number of invaded lymph nodes (P=0.012), and lymph node pouch invasion (P=0.043). Furthermore, necrosis was found to be associated with the white blood cell count (P=0.030), neutrophil count (P=0.011), the combined neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (NLR-PLR) (P=0.038), and the combined platelet and NLR (PLT-NLR status) (P=0.030), as well as with the serum carcinoembryonic antigen (CEA) levels following surgery (P=0.011) and the monocyte-to-lymphocyte ratio (P=0.023). The combined parametric value was found to be associated with pT stage (P=0.049), venous (P=0.034) and lymphatic (P=0.026) invasion, and with serum CEA levels prior to surgery (P=0.029). The analysis of the 3-year disease-free survival (DFS) time revealed that tumor growth [hazard ratio (HR), 2.070; 95% CI, 1.837-3.808; P=0.003] and the combined parametric value (intraTANs, stromaTANs and necrosis, HR, 1.577; 95% CI, 1.372-3.032; P=0.028) were independent factors for patients with CRC. Taken together, the findings of the present study demonstrated that the combined value of neutrophils and necrosis examined in the cancerous tissue may be used as a prognostic factor for the 3-year DFS time in patients with CRC.

Tumor-infiltrating lymphocytes in tissue material combined with systemic lymphocyte inflammation in patients with colorectal cancer.

The efficacy of cancer immunotherapy has been actively explored in the treatment of various malignant neoplasms of the gastrointestinal tract. In light of recent reports, the present study aimed to investigate the combination of the absolute lymphocyte count (ALC), percentage of tumor-infiltrating lymphocyte (TILs) and tumor progression status in patients with colorectal cancer (CRC) who underwent surgery. The medical records of 160 patients diagnosed with CRC were retrospectively reviewed. TILs were determined as a percentage of mononuclear inflammatory cells in the total intratumoral or stromal area as determined in five high power fields (magnification, x200-400), at the invasive front and in the centre of the tumour. Blood samples were obtained within 3 days prior to and 7 days following the surgical treatment. The assessment of the TIL percentage was performed in the tissue at the invasive front and in the centre of the primary tumour mass in combination with the determination of ALC in whole blood samples. The samples were obtained prior to and after surgery from patients with CRC, and the tumour progression status was also assessed (TILs/ALC/tumour progression status). A significant association was observed between the percentage of TILs in the main mass of tumour and the tumour size (P=0.031), the pT stage (P=0.049) and the incidence of necrosis (P=0.037) following surgery. The histological type was associated with the evaluated combined parameters prior to surgery (P=0.046). Lymph node pouch invasion was associated with TILs at the invasive front of tumour and with ALC prior to and after surgery (P=0.006 and P=0.037). Furthermore, the data indicated that the percentage of TILs located on the invasive front and centre of the tumour, and the ALC prior to and following surgery correlated with the treatment status (P=0.032, P=0.018, P≤0.001 and P≤0.001). A significant association was noted between eight features and evaluated combined parameters following surgery. These included the tumour size (P=0.021), TNM stage (P<0.001), tumour deposits (P=0.001), incidence of necrosis (P=0.042) and lymph node metastasis (P<0.001). Furthermore, the degree of invasion of venous (P<0.001), lymphatic (P<0.001) and perineural (P<0.001) sites was also significantly associated with TILs, ALC obtained after surgical treatment and tumor progression status. The data demonstrated that local and systemic chronic inflammation was associated with tumour progression in patients with CRC.

Cancers Cells in Traps? The Pathways of NETs Formation in Response to OSCC in Humans-A Pilot Study.

The aim of the experiment was to evaluate the process of neutrophil extracellular traps (NETs) formation in patients with oral squamous cell carcinoma (OSCC) in response to direct or indirect contact with SCC cells in comparison to results obtained in the cells of healthy subjects. To fulfill study objectives CAL 27 cell line and blood were obtained from cancer patients and control subjects. Parameters related to NETs formation were analyzed utilizing flow cytometry, fluorescence microscopy, and ELISA-type tests. The expression of selected phosphorylated proteins of the PI3K/Akt/PBK pathway in neutrophils was evaluated using the Western blot method. An increase in NETs formation was observed in a coculture of neutrophils with SCC cells, with the largest amount of NETs formed after stimulation with a supernatant obtained from the SCC culture. The enhanced process of NETs formation was accompanied by changes in the expression of proteins from the PI3K/Akt/PBK pathway. The obtained results prove the existence of interactions between neutrophils and cancer cells resulting in NETosis with the participation of the PI3K/Akt/PBK pathway in patients with OSCC.

Monocyte-to-lymphocyte ratio as a prognostic factor in peripheral whole blood samples of colorectal cancer patients.

BACKGROUND: Colorectal cancer is the third most common malignancy worldwide. Therefore, it is critically important to identify new useful markers that can be easily obtained in routine practice. Inflammation is a crucial issue in the pathogenesis and development of cancer. AIM: To evaluate the prognostic value of absolute monocyte count, monocyte to lymphocyte ratio (MLR), the combination of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio (NLR-PLR), and combined platelet and neutrophil-to-lymphocyte ratio (PLT-NLR) in peripheral blood samples of patients with colorectal cancer undergoing surgery. METHODS: We conducted a retrospective study of 160 patients with colorectal cancer who underwent surgery, and 42 healthy controls. The status of absolute monocyte count, MLR, NLR-PLR and PLT-NLR was calculated on the basis of blood samples obtained before and after surgery. Haematologic factors were examined in correlation with the type of tumour growth, tumour size, histological type, percentage of mucinous component, grade of malignancy, Tumour-Node-Metastasis stage, venous, lymphatic and perineural invasion of cancer cells, status of lymph node invasion and the presence of cancer cell deposits. The Kaplan-Meier method and the long-rank test were used to compare survival curves. To determine independent prognostic factors, univariate and multivariate Cox proportional hazards regression models were applied. RESULTS: The PLT-NLR status was correlated with tumour size and the presence of perineural invasion (P = 0.015; P = -0.174, P = 0.037). Moreover, high NLR-PLR and PLR-NLR ratios in the blood samples obtained after surgery were positively associated with histological type of cancer and percentage of the mucinous component (NLR-PLR: P = 0.002; P = 0.009; PLR-NLR status: P = 0.002; P = 0.007). The analysis of 5-year disease-free survival showed that the MLR of whole blood obtained after surgery [HR = 2.903, 95%CI: (1.368-6.158), P = 0.005] and the status of lymph node metastasis [HR = 0.813, 95%CI: (0.653-1.013), P = 0.050] were independent prognostic factors in colorectal cancer patients. CONCLUSION: The postoperative MLR in whole blood samples can be used as an independent prognostic factor in patients diagnosed with colorectal cancer.

Pre- and postoperative neutrophil and lymphocyte count and neutrophil-to-lymphocyte ratio in patients with colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant cancers worldwide. Patients with CRC are diagnosed based on various predictors, including performance status, clinicopathological factors and TNM classification. The aim of the present study was to analyze the neutrophil and lymphocyte counts, as well as the neutrophil-to-lymphocyte ratio (NLR) in pre- and postoperative blood samples of patients with CRC in correlation with specific anatomical variables and disease- free survival (DFS). The variables pre- and postoperative neutrophil count (preNEU and postNEU, respectively), lymphocyte count and NLR were significantly higher in cancer patients than those noted in healthy subjects (all P<0.001). PreNEU count correlated with tumor size, necrosis and tumor budding (R=0.204, P=0.014; R=0.189, P=0.023; R=-0.174, P=0.036, respectively). Moreover, postNEU was associated only with the histological type (R=0.174; P=0.047). The PreLYMPH count was correlated with distant metastasis (R=-0.153, P=0.046). PreNLR and postNLR were associated with the expression of various histological markers of disease progression. Analysis of DFS indicated that the postNEU count in the low group exhibited a tendency to lower DFS duration, although the results were not significant (P=0.055). In conclusion, the present study indicated a significant correlation between the factors analyzed in blood samples of CRC patients and the disease progression markers.

Insulin receptor substrate 1 may play divergent roles in human colorectal cancer development and progression.

BACKGROUND: Despite effective prevention and screening methods, the incidence and mortality rates associated with colorectal cancer (CRC) are still high. Insulin receptor substrate 1 (IRS-1), a signaling molecule involved in cell proliferation, survival and metabolic responses has been implicated in carcinogenic processes in various cellular and animal models. However, the role of IRS-1 in CRC biology and its value as a clinical CRC biomarker has not been well defined. AIM: To evaluate if and how IRS-1 expression and its associations with the apoptotic and proliferation tumor markers, Bax, Bcl-xL and Ki-67 are related to clinicopathological features in human CRC. METHODS: The expression of IRS-1, Bax, Bcl-xL and Ki-67 proteins was assessed in tissue samples obtained from 127 patients with primary CRC using immunohistochemical methods. The assays were performed using specific antibodies against IRS-1, Bax, Bcl-xL, Ki-67. The associations between the expression of IRS-1, Bax, Bcl-xL, Ki-67 were analyzed in relation to clinicopathological parameters, i.e., patient age, sex, primary localization of tumor, histopathological type, grading, staging and lymph node spread. Correlations between variables were examined by Spearman rank correlation test and Fisher exact test with a level of significance at P < 0.05. RESULTS: Immunohistochemical analysis of 127 CRC tissue samples revealed weak cytoplasmatic staining for IRS-1 in 66 CRC sections and strong cytoplasmatic staining in 61 cases. IRS-1 expression at any level in primary CRC was associated with tumor grade (69% in moderately differentiated tumors, G2 vs 31% in poorly differentiated tumors, G3) and with histological type (81.9% in adenocarcinoma vs 18.1% in adenocarcinoma with mucosal component cases). Strong IRS-1 positivity was observed more frequently in adenocarcinoma cases (95.1%) and in moderately differentiated tumors (85.2%). We also found statistically significant correlations between expression of IRS-1 and both Bax and Bcl-xL in all CRC cases examined. The relationships between studied proteins were related to clinicopathological parameters of CRC. No significant correlation between the expression of IRS-1 and proliferation marker Ki-67, excluding early stage tumors, where the correlation was positive and on a high level (P = 0.043, r = 0.723). CONCLUSION: This study suggests that IRS-1 is co-expressed with both pro- and antiapoptotic markers and all these proteins are more prevalent in more differentiated CRC than in poorly differentiated CRC.

Candidaemia in polish hospitals - a multicentre survey.

Significant changes in the frequency of candidaemia and the distribution of causative species have been noted worldwide in the last two decades. In this study, we present the results of the first multicentre survey of fungaemia in Polish hospitals. A total of 302 candidaemia episodes in 294 patients were identified in 20 hospitals during a 2-year period. The highest number of infections was found in intensive care (30.8%) and surgical (29.5%) units, followed by haematological (15.9%), 'others' (19.2%) and neonatological (4.6%) units. Candida albicans was isolated from 50.96% of episodes; its prevalence was higher in intensive care unit and neonatology (61.22% and 73.33%, respectively), and significantly lower in haematology (22%; P < 0.001). The frequency of C. krusei and C. tropicalis was significantly higher (24% and 18%) in haematology (P < 0.02); whereas, the distribution of C. glabrata (14.1%) and C. parapsilosis (13.1%) did not possess statistically significant differences between compared departments. Obtained data indicates that species distribution of Candida blood isolates in Polish hospitals reflects worldwide trends, particularly a decrease in the prevalence of infections due to C. albicans.