Illumina's Infinium HumanMethylation450 BeadChip arrays were used to examine genome-wide DNA methylation profiles in 22 sample pairs from colorectal cancer (CRC) and adjacent tissues and 19 colon tissue samples from cancer-free donors. We show that the methylation profiles of tumors and healthy tissue samples can be clearly distinguished from one another and that the main source of methylation variability is associated with disease status. We used different statistical approaches to evaluate the methylation data. In general, at the CpG-site level, we found that common CRC-specific methylation patterns consist of at least 15,667 CpG sites that were significantly different from either adjacent healthy tissue or tissue from cancer-free subjects. Of these sites, 10,342 were hypermethylated in CRC, and 5,325 were hypomethylated. Hypermethylated sites were common in the maximum number of sample pairs and were mostly located in CpG islands, where they were significantly enriched for differentially methylated regions known to be cancer-specific. In contrast, hypomethylated sites were mostly located in CpG shores and were generally sample-specific. Despite the considerable variability in methylation data, we selected a panel of 14 highly robust candidates showing methylation marks in genes SND1, ADHFE1, OPLAH, TLX2, C1orf70, ZFP64, NR5A2, and COL4A. This set was successfully cross-validated using methylation data from 209 CRC samples and 38 healthy tissue samples from The Cancer Genome Atlas consortium (AUC = 0.981 [95% CI: 0.9677-0.9939], sensitivity = 100% and specificity = 82%). In summary, this study reports a large number of loci with novel differential methylation statuses, some of which may serve as candidate markers for diagnostic purposes.

Aim Our aim was to evaluate the efficacy of indocyanine green (ICG) fluorescence angiography (FA) in reducing the incidence of anastomotic leakage (AL) following colorectal anastomosis. Method A single-centre randomized trial was undertaken between 2018 and 2019. Those patients who underwent a stapled colorectal anastomosis were randomized 1:1 for ICG FA versus visual clinical assessment of blood perfusion of the anastomosed colon and rectal stump (non-ICG FA group). The primary endpoint was to assess whether ICG FA was associated with a reduction in the incidence of AL. Secondary outcomes were the rate of postoperative complications and change in the level of bowel resection. Results A total of 380 patients undergoing sigmoid and rectal resection were enrolled. After randomization, three patients were excluded. The results of 377 cases were available for analysis; 187 had ICG FA and 190 were in the non-ICG FA group. ICG FA identified impaired blood perfusion of the colon in 36 (19%) cases. An AL (grade A, B or C) developed in 48 patients: 17 (9.1%) in the ICG FA group and 31 (16.3%) in the non-ICG FA group (P = 0.04). ICG FA did not decrease the rate of AL of high anastomoses (9-15 cm from the anal verge), at 1.3% vs 4.6% in the non-ICG FA group (P = 0.37). In contrast, a decrease in AL rate was found for low (4-8 cm) colorectal anastomoses (14.4% in ICG FA vs 25.7% in the non-ICG FA group; P = 0.04). Conclusion ICG FA is associated with a reduction in AL following low anterior resection.

Intraoperative use of fluorescence with indocyanine green reduces anastomotic leak rates in rectal cancer surgery: an individual participant data analysis.

Purpose: Colorectal anastomotic leakage (AL) is a life-threatening complication, which increases morbidity, hospital stay and cost of treatment. The aim of this study is to identify risk factors, including intraoperative indocyanine green fluorescence angiography (ICG FA), associated with the leak of stapled colorectal anastomosis. Methods: Four hundred twenty-nine consecutive patients underwent surgery between 2017 and 2019 for benign (n = 10, 2.3%) or malignant (n = 419, 97.7%) and rectal (n = 349, 81.4%) or distal sigmoid (n = 80, 18.6%) lesions with double-stapling technique reconstruction were included into retrospective study. Univariate analysis and multivariate logistic regression of the tumor-, patient-and treatment-related risk factors of AL was performed. Results: An AL developed in 52 patients (12.1%). In multivariate analysis following variables were independently associated with AL; male sex (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.9−7.7; P < 0.01), anastomosis at ≤ 6.5 cm from anal verge (OR, 3.1; 95% CI, 1.3−7.5; P = 0.01), and age of ≤ 62.5 years (OR, 2.1; 95% CI, 1.1−4.1; P = 0.03). ICG FA was found as independent factor reducing colorectal AL rate (OR, 0.4; 95% CI, 0.2−0.8; P = 0.02). A nomogram with high discriminative ability (concordance index, 0.81) was created. Conclusion: ICG FA is a modifiable surgery-related risk factor associated with a decrease of colorectal AL rate. A suggested nomogram, which takes into consideration ICG FA, might be helpful to identify the individual risk of AL.