B7H3 Role in Reshaping Immunosuppressive Landscape in MSI and MSS Colorectal Cancer Tumours.

The study aimed to assess the expression of B7H3 concerning clinicopathological and histological parameters, including MSI/MSS status, CD-8 cells, tumour-infiltrating lymphocytes (TILs), budding, TNM scale and grading. Moreover, we analyzed the B7H3-related pathways using available online datasets and the immunological context of B7H3 expression, through the 48-cytokine screening panel of cancer tissues homogenates, immunogenic features and immune composition. The study included 158 patients diagnosed with CRC. To assess B7H3 levels, we performed an immunohistochemistry method (IHC) and enzyme-linked immunosorbent assay (ELISA). To elucidate the immune composition of colorectal cancer, we performed the Bio-Plex Pro Human 48-cytokine panel. To study biological characteristics of B7H3, we used online databases. Expression of B7H3 was upregulated in CRC tumour tissues in comparison to adjacent noncancerous margin tissues. The concentrations of B7H3 in tumours were positively associated with T parameter of patients and negatively with tumour-infiltrating lymphocytes score. Additionally, Principal Component Analysis showed that B7H3 expression in tumours correlated positively with cytokines associated with M2-macrophages and protumour growth factors. The expression of B7H3 in tumours was independent of MSI/MSS status. These findings will improve our understanding of B7H3 role in colorectal cancer immunity. Our study suggests that B7-H3 is a promising potential target for cancer therapy. Further studies must clarify the mechanisms of B7H3 overexpression and its therapeutic importance in colorectal cancer.

Do Elevated YKL-40 Levels Drive the Immunosuppressive Tumor Microenvironment in Colorectal Cancer? Assessment of the Association of the Expression of YKL-40, MMP-8, IL17A, and PD-L1 with Coexisting Type 2 Diabetes, Obesity, and Active Smoking.

The influence of chitinase-3-like protein 1 (YKL-40 or CHI3L1) expression on the immunological properties of the tumor microenvironment, which may affect the effectiveness of immunotherapy, is currently not sufficiently understood in colorectal cancer (CRC). The aim of this study was to investigate the relationship between YKL-40 expression and the immunological properties of the tumor microenvironment in CRC. We performed in silico analysis, including analysis of immune cell infiltration scores and the immune landscape depending on YKL-40 expression, gene set enrichment analysis (GSEA), and analysis of three Gene Expression Omnibus (GEO) datasets. In 48 CRC tissue homogenates and the surgical margin, we analyzed the expression of YKL-40, MMP8, IL17A, and PD-L1. Moreover, we analyzed the expression of YKL-40 in tissue homogenates retrieved from patients with coexisting diabetes, obesity, and smoking. The expression of YKL-40 was significantly higher in CRC tumor tissue compared to healthy tissue and correlated with MMP-8, IL17A, and PD-L1 expression. In silico analysis revealed an association of YKL-40 with disease recurrence, and GSEA revealed a potential link between elevated YKL-40 expression and immunosuppressive properties of the tumor microenvironment in CRC.

Overexpression and Role of HHLA2, a Novel Immune Checkpoint, in Colorectal Cancer.

The study aimed to investigate correlations between HHLA2 levels and parameters, including microsatellite instability (MSI) status, CD8+ cells, and histopathological features: budding, tumor-infiltrating lymphocytes (TILs), TNM scale, grading, cytokines, chemokines, and cell signaling moleculesin colorectal cancer (CRC). Furthermore, the immune infiltration landscape and HHLA2-related pathways in colorectal cancer using available online datasets were analyzed. The study included 167 patients diagnosed with CRC. Expression of HHLA2 was detected by immunohistochemistry method (IHC) and enzyme-linked immunosorbent assay (ELISA). The IHC was used to evaluate the MSI and CD8+ status. The budding and TILs were measured using a light microscope. The concentrations of cytokines, chemokines, and cell signaling molecules were measured to analyze the data by the Bio-Plex Pro Human cytokine screening panel, 48 cytokine assay, and principal component analysis (PCA). Geneset enrichment analysis (GSEA) was conducted to identify HHLA2-related pathways. The biological function of HHLA2 was predicted by Gene Ontology (GO). Analysis of the immune infiltration landscape of HHLA2 in colorectal cancer was made by the web-based tool Camoip. High HHLA2 expression was detected in CRC tumor tissues compared to the adjacent noncancerous tissues. The percentage of HHLA2-positive tumors was 97%. GSEA and GO showed that HHLA2 upregulation correlated with cancer-related pathways and several biological functions. Tumor-infiltrating lymphocytes score correlated positively with IHC HHLA2 expression level percentage. There was a negative correlation between HHLA2, anti-tumor cytokines and pro-tumor growth factors. This study provides a valuable insight into the role of HHLA2 in CRC. We reveal the role of HHLA2 expression as well as a stimulatory and inhibitory immune checkpoint in colorectal cancer. Further research may verify the therapeutic values of the HHLA2-KIR3DL3/TMIGD2 pathway in colorectal cancer.

B7H4 Expression Is More Frequent in MSS Status Colorectal Cancer and Is Negatively Associated with Tumour Infiltrating Lymphocytes.

The immunotherapies based on ICIs in CRC are nowadays limited to microsatellite unstable tumours which are approximately 15% of all CRC cases. There are a few new immune checkpoints belonging to the B7 family, including B7H4. B7H4 expression is associated with so-called "cold tumours", and its function is linked to the downregulation of various immune cell populations. Our study aimed to investigate whether B7H4 expression is dependent on microsatellite status in CRC and on elucidating the immunological context in which the expression of B7H4 occurs. We enrolled 167 patients in the study. We prepared the homogenates from tumour tissues and healthy adjacent tissue to assess the B7H4 levels and the Bio-Plex Pro Human 48-cytokine panel. We assessed the microsatellite status of the tumour, B7H4 expression, CD8+ T cell population, and the TILs and budding in H + E stained slides by the IHC method. We used an online available database for further exploring the biological characteristics of B7H4. The expression of B7H4 was more frequent in microsatellite stable tumours, and was negatively associated with TILs. B7H4 is positively correlated with antitumour immunosuppressive iTME, thus contributing to the immunosuppressive environment in CRC.

Influence of Obesity on Anastomotic Leakage After Anterior Rectal Resectionperformed Due to Cancer.

UNLABELLED: Anterior resection for rectal cancer carries the risk of serious complications, especially fistulas at the site of anastomosis. Numerous factors have been shown to impact anastomotic leakage. The results of studies on the influence of obesity on the frequency of anastomotic leakage after rectal resection performed due to cancer have been contradictory. The aim of the study was to evaluate the relationship between body mass index (BMI) and frequency of anastomotic leakage after anterior rectal resection performed due to cancer. MATERIAL AND METHODS: This retrospective analysis included 222 subsequent patients who had undergone anterior resection due to cancer with an anastomosis formed with a mechanical suture. The patients were divided into 3 groups depending on their BMI quartile as follows: Group I, BMI < 23.8 kg/m2 (lower quartile); group II, BMI between 23.8 and 29.38 kg/m2 (middle quartile); and group III, BMI > 29.38 kg/m2 (upper quartile). RESULTS: Anastomotic leakage occurred in 8 (3.6%) patients. Fistulas occurred in 4 out of 61 patients (6.56%) in group I, which was the highest incidence of fistulas for all 3 groups. In group II, fistulas occurred in 2 out of 55 patients (3.63%), and similarly, in group III, they occurred in 2 out of 106 patients (1.87%). The differences found in the frequency of fistulas between groups were not statistically significant (p=0.31). The logistic regression analysis did not show any relationship between leakage and age (p = 0.55; OR = 1.02; 95% CI: 0.95 - 1.1), sex (p = 0.97; OR = 0.97; 95% CI: 0.22 - 4.25) or BMI (p = 0.27; OR = 0.58; 95% CI: 0.22 - 1.53). CONCLUSIONS: The results of our study show that BMI did not have any influence on the frequency of anastomotic leakage after anterior rectal resection performed due to cancer.

Transcutaneous intravascular transposition of a permanent dialysis catheter.

Permanent catheters are used to provide long-lasting access for long-term dialysis therapy in certain patients when creating an arteriovenous fistula between their own vessels is not possible, when there are contraindications for fistula creation or when the expected lifetime of the patient is short. We present the case of a patient with terminal renal insufficiency treated with hemodialysis for 5 years. Due to post-thrombotic changes and venous stenosis resulting from long-term cannulation with dialysis catheters, the replacement catheter was inserted through the previously used canal and transcutaneous intravascular catheter transposition was performed.

Mortality and anastomotic leakage after anterior resection for rectal cancer.

BACKGROUND/AIMS: The aim of the study was to analyze the mortality and symptomatic anastomotic leak following stapled anastomosis after anterior resection for rectal cancer. METHODOLOGY: We analyzed retrospectively 161 patients subjected to elective anterior resection of the rectum. There were 102 (63.3%) men and 59 (37.7%) women. The patients were divided into two groups according to tumor location: group I - 129 (80.1%) patients with tumor located >6 cm from the anal verge and group II - 32 (19.9%) patients with tumor located =6 cm. RESULTS: Anastomotic leak was found in 5 (3.1%) patients, three (2.3%) from group I and two (6.2%) from group II (p<0.26). Anastomotic leak was found more often in patients with renal failure (p<0.0023) and in those who had undergone RBC concentrate transfusion (p<0.0045). Seven (4.3%) patients died in the postoperative period. Deaths occurred more frequently in patients with valvular heart disease (p<0.00002), renal failure (p<0.0047) and in those given concentrates of RBC (p<0.045). CONCLUSIONS: Incidence of postoperative surgical complications after resection for rectal cancer is not high and is acceptable; however, there is an increased risk of leakage after low anterior resection. Renal failure as well as RBC concentrate transfusion have an influence on mortality and anastomotic leak.