BACKGROUND: Colorectal anastomotic leakage remains one of the most frequent and dreaded postoperative complications after colorectal resection. However, limited research has been conducted on the impact of this complication on the quality of life of patients who have undergone colorectal cancer surgery. OBJECTIVE: The aim of this systematic review was to identify, appraise, and synthesize the available evidence regarding the quality of life in patients with anastomotic leakage after oncological colorectal resections to inform clinical decision-making. DATA SOURCES AND STUDY SELECTION: PubMed, Embase, and the Cochrane Library were searched for studies reporting quality of life using validated questionnaires in patients with anastomotic leakage after oncological colorectal resections. The literature search was performed systematically and according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. OUTCOMES: Outcomes from quality-of-life questionnaires of patients with and without anastomotic leakage were analyzed. RESULTS: Thirteen articles reporting on 4618 individual patients were included, among which 527 patients developed anastomotic leakage. Quality of life was evaluated using 10 distinct questionnaires administered at various postoperative time points, ranging from 1 month to 14 years. Quality-of-life outcomes differed across studies and time points, but overall scores were most negatively affected by anastomotic leakage up to 12 months postoperatively. LIMITATIONS: There was a high heterogeneity between the included studies based on the questionnaires used and the time of assessment. CONCLUSIONS: The published evidence suggests that anastomotic leakage after oncologic colorectal resection is associated with impaired quality of life, especially within the first postoperative year. The impact of anastomotic leakage on quality of life warrants further evaluation and discussion with patients.

Metastatic colorectal cancer (CRC) is a common cause of cancer-related mortality, of which peritoneal metastases (PMs) have the worse outcome. Metastasis-specific markers may help predict the spread of tumor cells and select patients for preventive strategies. This exploratory pilot study aimed to gain more insight into genetic alterations in primary CRC tumors, which might be a predictive factor for the development of PM. Forty patients with T3 stage CRC were retrospectively divided in three groups: without metachronous metastases during 5-year follow-up (M0, n = 20), with metachronous liver metastases (LM, n = 10) and with metachronous PM (PM, n = 10). Patients with synchronous metastases were excluded. Primary formalin-fixed paraffin-embedded tumor samples were analyzed via comprehensive genome sequencing (TSO500 analysis) to identify DNA alterations and RNA fusion transcripts in 523 genes and 55 genes, respectively. Thirty-eight samples were included for final analysis. Four M0 tumors and one PM tumor were microsatellite instable. BRAF mutations were uniquely identified in three microsatellite-stable (MSS) PM tumors (37.5%, p = 0.010). RNA analysis showed an additional FAM198A-RAF1 fusion in one PM sample. BRAF p.V600E mutations were only present in PM patients with MSS tumors. Greater attention should be paid to BRAF-mutated tumors in relation to the development of metachronous PM.

Background: As colorectal cancer (CRC) patients with peritoneal metastases (PM) have a poor prognosis, new treatment options are currently being investigated for CRC patients. Specific biomarkers in the primary tumor could serve as a prediction tool to estimate the risk of distant metastatic spread. This would help identify patients eligible for early treatment. Aim: To give an overview of previously studied DNA and RNA alterations in the primary tumor correlated to colorectal PM and investigate which gene mutations should be further studied. Methods: A systematic review of all published studies reporting genomic analyses on the primary tissue of CRC tumors in relation to PM was undertaken according to PRISMA guidelines. Results: Overall, 32 studies with 18,906 patients were included. BRAF mutations were analyzed in 17 articles, of which 10 found a significant association with PM. For all other reported genes, no association with PM was found. Two analyses with broader cancer panels did not reveal any new biomarkers. Conclusion: An association of specific biomarkers in the primary tumors of CRC patients with metastatic spread into peritoneum could not be proven. The role of BRAF mutations should be further investigated. In addition, studies searching for potential novel biomarkers are still required.

Background: Intraoperative near-infrared fluorescence imaging (NIRF) with preoperative optical dye administration is a promising technique for quick and easy intraoperative visualization of the ureter and for an improved, real-time assessment of intestinal perfusion. During colorectal surgery, there is a need for simultaneous non-invasive ureteral imaging and bowel perfusion assessment, using one single camera system. The purpose of this study is to investigate the feasibility of simultaneous intestinal perfusion and ureteral imaging using a single commercially available NIRF imaging system. Methods: Six Landrace pigs underwent laparotomy under general anesthesia in this experiment. An intravenous (IV) dose of 0.2 mg/kg indocyanine green (ICG) was given to assess bowel perfusion. Two pairs received a methylene blue (MB) iv injection of 0.75, 0.50 or 0.25 mg/kg respectively to investigate ureteral visualization. Quest Spectrum Fluorescence Camera (Quest Medical Imaging, Middenmeer, The Netherlands) was used for NIRF imaging. Results: Ureter visualization and bowel perfusion under NIRF imaging was achieved in all animals. All ureters were visible after five to ten minutes and remained clearly visible until the end of every experiment (120–420 min). A mixed model analysis did not show any significant differences neither between the three groups nor over time. Importantly, we demonstrated that bowel perfusion could be visualized with methylene blue (MB) as well. We observed no interference between ICG and MB and a faster washout of MB. Conclusion: We successfully demonstrated simultaneous fluorescence angiography with ICG and ureteral imaging with MB in the same surgical procedure, with the same commercially available NIRF imaging equipment. More importantly, we showed that the use MB is adequate for bowel perfusion assessment and ureter visualization with this NIRF imaging system. Besides, MB showed an earlier washout time, which can be clinical beneficial as a repeated dye injection may be necessary during a surgical procedure.

Background: Near-infrared fluorescence (NIRF) angiography with intraoperative administration of indocyanine green (ICG) has rapidly disseminated in clinical practice. Another clinically approved, and widely available dye, methylene blue (MB), has up to now not been used for this purpose. Recently, we demonstrated promising results for the real-time evaluation of intestinal perfusion using this dye. The primary aim of this study was to perform a quantitative analysis of bowel perfusion assessment for both ICG and MB. Methods: Four mature female Landrace pigs underwent laparotomy under general anesthesia. An ischemic bowel loop with five regions of interest (ROIs) with varying levels of perfusion was created in each animal. An intravenous (IV) injection of 0.25 mg/kg–0.50 mg/kg MB was administered after 10 min, followed by NIRF imaging in MB mode and measurement of local lactate levels in all corresponding ROIs. This procedure was repeated in ICG mode (IV dose of 0.2 mg/kg) after 60 min. The quest spectrum fluorescence camera (Quest Medical Imaging, Middenmeer, The Netherlands) was used for NIRF imaging of both MB and ICG. Results: Intraoperative NIRF imaging of bowel perfusion assessment with MB and ICG was successful in all studied animals. Ingress (i/s) levels were calculated and correlated with local lactate levels. Both MB and ICG ingress values showed a significant negative correlation (r = − 0.7709; p = < 0.001; r = − 0.5367, p = 0.015, respectively) with local lactate levels. This correlation was stronger for MB compared to ICG, although ICG analysis showed higher absolute ingress values. Conclusion: Our fluorescence quantification analysis validates the potential to use MB for bowel perfusion assessment besides the well-known and widely used ICG. Further human studies are necessary to translate our findings to clinical applications.

Near-infrared fluorescence (NIRF) image-guided surgery is a useful tool that can help reduce perioperative complications and improve tissue recognition. Indocyanine green (ICG) dye is the most frequently used in clinical studies. ICG NIRF imaging has been used for lymph node identification. However, there are still many challenges in lymph node identification by ICG. There is increasing evidence that methylene blue (MB), another clinically applicable fluorescent dye, can also be useful in the intraoperative fluorescence-guided identification of structures and tissues. We hypothesized that MB NIRF imaging could be used for lymph node identification. The aim of this study was to evaluate the feasibility of intraoperative lymph node fluorescence detection using intravenously (IV) administered MB and compare it to ICG via a camera that has two dedicated near-infrared (NIR) channels. Three pigs were used in this study. ICG (0.2 mg/kg) was administered via a peripheral venous catheter followed by immediate administration of MB (0.25 mg/kg). NIRF images were acquired as video recordings at different time points (every 10 min) over an hour using the QUEST SPECTRUM^® 3 system (Quest Medical Imaging, Middenmeer, The Netherlands), which has two dedicated NIR channels for simultaneous intraoperative fluorescence guidance. The 800 nm channel was used to capture ICG fluorescence and the 700 nm channel was used for MB. The target (lymph nodes and small bowel) and the background (vessels-free field of the mesentery) were highlighted as the regions of interest (ROIs), and corresponding fluorescence intensities (FI) from these ROIs were measured. The target-to-background ratio (TBR) was then computed as the mean FI of the target minus the mean FI of the background divided by the mean FI of the background. In all included animals, a clear identification of lymph nodes was achieved at all time points. The mean TBR of ICG in lymph nodes and small bowel was 4.57 ± 1.00 and 4.37 ± 1.70, respectively for the overall experimental time. Regarding MB, the mean TBR in lymph nodes and small bowel was 4.60 ± 0.92 and 3.27 ± 0.62, respectively. The Mann-Whitney U test of the lymph node TBR/small bowel TBR showed that the TBR ratio of MB was statistically significantly higher than ICG. The fluorescence optical imaging technology used allows for double-wavelength assessment. This feasibility study proves that lymph nodes can be discriminated using two different fluorophores (MB and ICG) with different wavelengths. The results suggest that MB has a promising potential to be used to detect lymphatic tissue during image-guided surgery. Further preclinical trials are needed before clinical translation.