FSP-1 expression in cancer cells is relevant to long-term oncological outcomes in nonmetastatic colorectal cancer.

Purpose: Recent studies have revealed that the expression of cancer-associated fibroblast (CAF) activation biomarkers in cancer cells is associated with clinical outcomes in patients with certain types of malignant tumors. However, whether the expression of CAF activation biomarkers affects the prognosis of colorectal cancer (CRC) has not been fully elucidated. This study aimed to evaluate the association between the expression of CAF activation biomarkers in cancer cells with cancer invasion and long-term oncological outcomes in patients with CRC. Methods: Cancer specimens obtained from 135 patients with stage I-III CRC were examined using immunohistochemical staining to evaluate the expression of fibroblast specific protein-1 (FSP-1), fibroblast activation protein α (FAPα), α-smooth muscle actin (α-SMA), and vimentin in cancer cells. Results: FSP-1 expression in cancer cells was significantly associated with lymphatic invasion, perineural invasion, tumor (T) status, and lymph node (N) status. FAPα expression in cancer cells was significantly associated with lymphatic invasion. On univariate and multivariate analyses, FSP-1 and α-SMA expression in cancer cells were associated with a short 10-year overall survival (OS) and high 10-year systemic recurrence (SR), respectively. Tumor budding was associated with a short 10-year OS. However, FAPα and vimentin did not contribute to the prognosis in this study. Conclusion: In this study, we found that FSP-1 expression in cancer cells was related to cancer invasion. Additionally, FSP-1 and α-SMA expression in cancer cells was associated with 10-year OS and SR, respectively. Therefore, these markers may be used as predictors of long-term oncological outcomes in patients with CRC.

Compression injury of the circular stapler for gastrointestinal end-to-end anastomosis: preliminary in-vitro study.

PURPOSE: This preliminary in-vitro study was designed to evaluate the risk factors of compression injury from use of a circular stapler for end-to-end anastomosis. METHODS: Transparent collagen plates were prepared in dry and wet conditions. Physical properties of collagen plates and porcine colon tissue were examined using a rheometer. Adjustable and fixed-type circular staplers were applied on the collagen plates and the gap distance and compressive pressure were measured during anvil approximation. Tissue injury was evaluated using a compression injury scale. Compression properties were accessed to optimal or overcompression based on gap distance. RESULTS: Unacceptable injuries were rarely observed on the dry collagens, regardless of compression device. In the adjustable compression, the compressibility ratio was similar between dry and wet collagen. Overcompression and unacceptable injury increased on the wet collagens. In the fixed compression, the compressibility ratio increased significantly and unacceptable injuries were observed in more than 50% of wet collagens. Peak pressure was significantly higher in the fixed-compression types than those of adjustable type. On bivariate correlation analysis, fixed-compression type and wet collagens were respectively associated with overcompression. On multivariate analysis, edematous collagen condition was the most important risk factor and proximal anvil side, fixed compression type, and overcompression were also independent risk factors for unacceptable compression injury. CONCLUSION: In the edematous tissue condition, unintentional overcompression could be increased and result in tissue injury on the compression line of the circular stapler.

Comparisons of cancer-associated fibroblasts in the intratumoral stroma and invasive front in colorectal cancer.

The aim of this study was to evaluate the cytomorphologic maturity and molecular activation of cancer-associated fibroblasts (CAFs) in the intratumoral stroma and invasive front in colorectal cancer and understand how they affect cancer invasion and long-term oncological outcomes.The cytomorphologic maturity of and α-smooth muscle actin (α-SMA), fibroblast activation protein α (FAPα), and fibroblast-specific protein 1 (FSP-1) expression in CAFs in the intratumoral stroma (CAF) and the invasive front (CAF) of colorectal cancer tissues were compared (n = 147). The correlations between CAF maturation, molecular activity markers, and cancer invasion were evaluated by network analysis. Overall survival and systemic recurrence were analyzed to assess the oncological effects of CAF properties.The cytomorphologic maturation rate was comparable between CAF and CAF. The presence of mature CAFs was related to epidermal growth factor receptor overexpression in cancer cells. Expression rates of α-SMA (96.6%-98.0%) and FAPα (18.6%-22.9%) were similar between CAF and CAF. FSP-1 expression was more frequent in CAF than in CAF (66.4% vs 58.2%, P = .038). There was a significant decrease in FSP-1 expression in CAF and CAF in higher stages. The infiltrating growth pattern of the tumor was more frequent in the immature CAF. In colorectal cancer with perineural invasion and lymph node metastasis, FSP-1 expression in CAF was significantly lower. On multivariate analysis using the Cox proportional hazards model, immature CAF was found to be an independent prognostic factor of overall survival. In non-metastatic (stage I-III) colorectal cancer patients, CAF maturity was not a prognostic factor for systemic recurrence.Cytomorphologic maturity and molecular activation markers were similar between CAFs in the intratumoral stroma and invasive front of colorectal cancer.

Cancer-Associated Fibroblasts and Desmoplastic Reactions Related to Cancer Invasiveness in Patients With Colorectal Cancer.

PURPOSE: We evaluated the relationship of cancer-associated fibroblasts (CAFs) and desmoplastic reactions with cancer invasiveness and long-term outcomes in patients with colorectal cancer (CRC). METHODS: Histologic evaluation of mature CAFs and desmoplasia was performed by observing the collagen fiber structure and fibroblast cytomorphology in the intratumoral stroma and invasive front of CRC tissues. Cancer-cell invasiveness was evaluated using lymphatic invasion, vascular invasion, perineural invasion, tumor budding, and tumor growth patterns. Overall survival and systemic recurrence were analyzed. A network analysis was performed between CAF maturation, desmoplastic reaction, and cancer invasiveness. RESULTS: The proportions of mature CAFs in the intratumoral stroma and the invasive front were 57.6% and 60.3%, respectively. Epidermal growth factor receptor (EGFR) overexpression was significantly higher in the mature CAFs in the invasive front as compared to immature CAFs. Lymphatic invasion increased as the number of mature fibroblasts in the intratumoral stroma increased. Tumor budding was observed in almost half of both mature and immature stroma samples and occurred more frequently in infiltrating tumors. On network analysis, well-connected islands were identified that was associated with EGFR overexpression, CAF maturation, and infiltrating tumor growth patterns leading to tumor budding. CONCLUSION: The maturity of CAFs and desmoplastic reactions were associated with cancer invasion. However, the cytomorphologic characteristics of CAFs were insufficient as an independent prognostic factor for patients with CRC.

Quantitative analysis of colon perfusion pattern using indocyanine green (ICG) angiography in laparoscopic colorectal surgery.

PURPOSE: This study aimed to quantitatively evaluate colon perfusion patterns using indocyanine green (ICG) angiography to find the most reliable predictive factor of anastomotic complications after laparoscopic colorectal surgery. METHODS: Laparoscopic fluorescence imaging was applied to colorectal cancer patients (n = 86) from July 2015 to December 2017. ICG (0.25 mg/kg) was slowly injected into peripheral blood vessels, and the fluorescence intensity of colonic flow was measured sequentially, producing perfusion graphs using a video analysis and modeling tool. Colon perfusion patterns were categorized as either fast, moderate, or slow based on their fluorescence slope, T1/2MAX and time ratio (TR = T1/2MAX/TMAX). Clinical factors and quantitative perfusion factors were analyzed to identify predictors for anastomotic complications. RESULTS: The mean age of patients was 65.4 years, and the male-to-female ratio was 63:23. Their operations were laparoscopic low anterior resection (55 cases) and anterior resection (31 cases). The incidence of anastomotic complication was 7%, including colonic necrosis (n = 1), anastomotic leak (n = 3), delayed pelvic abscess (n = 1), and delayed anastomotic dehiscence (n = 1). Based on quantitative analysis, the fluorescence slope, T1/2MAX, and TR were related with anastomotic complications. The cut-off value of TR to categorize the perfusion pattern was determined to be 0.6, as shown by ROC curve analysis (AUC 0.929, P < 0.001). Slow perfusion (TR > 0.6) was independent factor for anastomotic complications in a logistic regression model (OR 130.84; 95% CI 6.45-2654.75; P = 0.002). Anastomotic complications were significantly correlated with the novel factor TR (> 0.6) as the most reliable predictor of perfusion and anastomotic complications. CONCLUSIONS: Quantitative analysis of ICG perfusion patterns using T1/2MAX and TR can be applied to detect segments with poor perfusion, thereby reducing anastomotic complications during laparoscopic colorectal surgery.