Anastomotic leakage (AL) is a potentially life-threatening complication following colorectal cancer (CRC) resection. In this study, we aimed to unravel longitudinal changes in microbial structure before, during, and after surgery and to determine if microbial alterations may be predictive for risk assessment between sufficient anastomotic healing (AS) and AL prior surgery. We analysed the microbiota of 134 colon mucosal biopsies with 16S rRNA V1-V2 gene sequencing. Samples were collected from three location sites before, during, and after surgery, and patients received antibiotics after the initial collection and during surgery. The microbial structure showed dynamic surgery-related changes at different time points. Overall bacterial diversity and the abundance of some genera such as Faecalibacterium or Alistipes decreased over time, while the genera Enterococcus and Escherichia_Shigella increased. The distribution of taxa between AS and AL revealed significant differences in the abundance of genera such as Prevotella, Faecalibacterium and Phocaeicola. In addition to Phocaeicola, Ruminococcus2 and Blautia showed significant differences in abundance between preoperative sample types. ROC analysis of the predictive value of these genera for AL revealed an AUC of 0.802 (p = 0.0013). In summary, microbial composition was associated with postoperative outcomes, and the abundance of certain genera may be predictive of postoperative complications.

Host diet and gut microbiota interact to contribute to perioperative complications, including anastomotic leak (AL). Using a murine surgical model of colonic anastomosis, we investigated how diet and fecal microbial transplantation (FMT) impacted the intestinal microbiota and if a predictive signature for AL could be determined. We hypothesized that a Western diet (WD) would impact gut microbial composition and that the resulting dysbiosis would correlate with increased rates of AL, while FMT from healthy, lean diet (LD) donors would reduce the risk of AL. Furthermore, we predicted that surgical outcomes would allow for the development of a microbial preclinical translational tool to identify AL. Here, we show that AL is associated with a dysbiotic microbial community characterized by increased levels of Bacteroides and Akkermansia. We identified several key taxa that were associated with leak formation, and developed an index based on the ratio of bacteria associated with the absence and presence of leak. We also highlight a modifiable connection between diet, microbiota, and anastomotic healing, potentially paving the way for perioperative modulation by microbiota-targeted therapeutics to reduce AL.

There are many reports that preoperative oral antibiotics (OAs) are effective in preventing surgical site infections (SSIs) in colorectal surgery. However, there is no consensus on the optimal dose of OAs. In this study, we investigated the efficacy of OAs in preventing SSIs and the possibility that OAs induce enterobacterial alteration in the intestinal tract.

We performed a retrospective cross-sectional analysis of 389 patients who underwent R0 resection and stoma creation for colorectal cancer in our department between 2009 and 2020. We focused on the incidence of peristomal candidiasis (PSC) as an indicator of enterobacterial alteration and used kanamycin (KM) and metronidazole (MNZ) as the OAs. A low-dose group received 1000 mg/day of both KM and MNZ, and a high-dose group received 2000 mg/day of both KM and MNZ.

SSI occurred in 60 of the 389 cases (15.4%). Regardless of stoma type, SSI was significantly more common in the non-OA group, while PSC was significantly less common. When examined by OA dose, the incidence of SSI was not significantly different between the low-dose and high-dose groups. However, PSC was significantly more common in the high-dose group than in the non-OA and low-dose groups. Analysis of bacterial and fungal levels in stool samples showed that bacterial levels after OAs were significantly lower than before OAs, while fungal levels increased.

OAs significantly reduce SSI in colorectal cancer surgery. However, excess OAs were significantly associated with the occurrence of PSC without contributing to further reduction in SSI.

Intestinal microorganisms play a crucial role in shaping the host immunity and maintaining homeostasis. Nevertheless, alterations in gut bacterial composition may occur and these alterations have been linked with the pathogenesis of several diseases. In surgical practice, studies revealed that the microbiome of patients undergoing surgery changes and several post-operative complications seem to be associated with the gut microbiota composition. In this review, we aim to provide an overview of gut microbiota (GM) in surgical disease. We refer to several studies which describe alterations of GM in patients undergoing different types of surgery, we focus on the impacts of peri-operative interventions on GM and the role of GM in development of post-operative complications, such as anastomotic leak. The review aims to enhance comprehension regarding the correlation between GM and surgical procedures based in the current knowledge. However, preoperative and postoperative synthesis of GM needs to be further examined in future studies, so that GM-targeted measures could be assessed and the different surgery complications could be reduced.

Ileocecal resection (ICR) is frequently performed in Crohn's disease (CD). NOD2 mutations are risk factors for CD. Nod2 knockout (ko) mice show impaired anastomotic healing after extended ICR. We further investigated the role of NOD2 after limited ICR. C57B16/J (wt) and Nod2 ko littermates underwent limited ICR including 1-2 cm terminal ileum and were randomly assigned to vehicle or MDP treatment. Bursting pressure was measured on POD 5, and the anastomosis was analyzed for matrix turn-over and granulation tissue. Wound fibroblasts from subcutaneously implanted sponges were used for comparison. The M1/M2 macrophage plasma cytokines were analyzed. Mortality was not different between groups. Bursting pressure was significantly decreased in ko mice. This was associated with less granulation tissue but was not affected by MDP. However, anastomotic leak (AL) rate tended to be lower in MDP-treated ko mice (29% vs. 11%, p = 0.07). mRNA expression of collagen-1α (col1 α), collagen-3α (col3 α), matrix metalloproteinase (mmp)2 and mmp9 was increased in ko mice, indicating increased matrix turn-over, specifically in the anastomosis. Systemic TNF-α expression was significantly lower in ko mice. Ileocolonic healing is impaired in Nod2 ko mice after limited ICR by local mechanisms maybe including local dysbiosis.

Anastomotic leak, defined by the International Study Group of Rectal Cancer as "a communication between the intra- and extraluminal compartments owing to a defect of the integrity of the intestinal wall at the anastomosis," is one of the most devastating complications in colorectal surgery. Much work has been done to identify causes of leak; however, despite advances in surgical technique, the prevalence of anastomotic leak has remained at around 11%. The potential causative role of bacteria in the etiopathology of anastomotic leak was established in the 1950s. More recently, alterations in the colonic microbiome have been shown to affect rates of anastomotic leak. Multiple perioperative factors that alter the homeostasis of the gut microbiota community structure and function have been linked to anastomotic leak after colorectal surgery. Here, we discuss the role of diet, radiation, bowel preparation, medications including nonsteroidal anti-inflammatory drugs, morphine, and antibiotics, and specific microbial pathways that have been implicated in anastomotic leak via their effects on the microbiome.

Colorectal anastomosis is a sophisticated problem that demands an elaborate discussion and an elegant solution. "Those who forget the past are condemned to repeat it." George Santayana, Life of Reason , 1905.

Anastomotic leak (AL) is a life-threatening postoperative complication following colorectal surgery, which has not decreased over time. Until now, no specific risk factors or surgical technique could be targeted to improve anastomotic healing. In the past decade, gut microbiota dysbiosis has been recognized to contribute to AL, but the exact effects are still vague. In this context, interpretation of the mechanisms underlying how the gut microbiota contributes to AL is significant for improving patients' outcomes. This review concentrates on novel findings to explain how the gut microbiota of patients with AL are altered, how the AL-specific pathogen colonizes and is enriched on the anastomosis site, and how these pathogens conduct their tissue breakdown effects. We build up a framework between the gut microbiota and AL on three levels. Firstly, factors that shape the gut microbiota profiles in patients who developed AL after colorectal surgery include preoperative intervention and surgical factors. Secondly, AL-specific pathogenic or collagenase bacteria adhere to the intestinal mucosa and defend against host clearance, including the interaction between bacterial adhesion and host extracellular matrix (ECM), the biofilm formation, and the weakened host commercial bacterial resistance. Thirdly, we interpret the potential mechanisms of pathogen-induced poor anastomotic healing.

Antibiotics are deployed against bacterial pathogens, but their targeting of conserved microbial processes means they also collaterally perturb the commensal microbiome. To understand acute and persistent effects of antibiotics on the gut microbiota of healthy adult volunteers, we quantify microbiome dynamics before, during, and 6 months after exposure to 4 commonly used antibiotic regimens. We observe an acute decrease in species richness and culturable bacteria after antibiotics, with most healthy adult microbiomes returning to pre-treatment species richness after 2 months, but with an altered taxonomy, resistome, and metabolic output, as well as an increased antibiotic resistance burden. Azithromycin delays the recovery of species richness, resulting in greater compositional distance. A subset of volunteers experience a persistent reduction in microbiome diversity after antibiotics and share compositional similarities with patients hospitalized in intensive care units. These results improve our quantitative understanding of the impact of antibiotics on commensal microbiome dynamics, resilience, and recovery.

Digestive tract resections are usually followed by an anastomosis. Anastomotic leakage, normally due to failed healing, is the most feared complication in digestive surgery because it is associated with high morbidity and mortality. Despite technical and technological advances and focused research, its rates have remained almost unchanged the last decades. In the last two decades, stem cells (SCs) have been shown to enhance healing in animal and human studies; hence, SCs have emerged since 2008 as an alternative to improve anastomoses outcomes.

To summarise the published knowledge of SC utilisation as a preventative tool for hollow digestive viscera anastomotic or suture leaks.

PubMed, Science Direct, Scopus and Cochrane searches were performed using the key words "anastomosis", "colorectal/colonic anastomoses", "anastomotic leak", "stem cells", "progenitor cells", "cellular therapy" and "cell therapy" in order to identify relevant articles published in English and Spanish during the years of 2000 to 2021. Studies employing SCs, performing digestive anastomoses in hollow viscera or digestive perforation sutures and monitoring healing were finally included. Reference lists from the selected articles were reviewed to identify additional pertinent articles.Given the great variability in the study designs, anastomotic models, interventions (SCs, doses and vehicles) and outcome measures, performing a reliable meta-analysis was considered impossible, so we present the studies, their results and limitations.

Eighteen preclinical studies and three review papers were identified; no clinical studies have been published and there are no registered clinical trials. Experimental studies, mainly in rat and porcine models and occasionally in very adverse conditions such as ischaemia or colitis, have been demonstrated SCs as safe and have shown some encouraging morphological, functional and even clinical results. Mesenchymal SCs are mostly employed, and delivery routes are mainly local injections and cell sheets followed by biosutures (sutures coated by SCs) or purely topical. As potential weaknesses, animal models need to be improved to make them more comparable and equivalent to clinical practice, and the SC isolation processes need to be standardised. There is notable heterogeneity in the studies, making them difficult to compare. Further investigations are needed to establish the indications, the administration system, potential adjuvants, the final efficacy and to confirm safety and exclude definitively oncological concerns.

The future role of SC therapy to induce healing processes in digestive anastomoses/sutures still needs to be determined and seems to be currently far from clinical use.

Scarce data are available on differences among index colectomies for colon cancer regarding reoperation for anastomotic leakage (AL) and clinical consequences. Therefore, this nationwide observational study aimed to evaluate reoperations for AL after colon cancer surgery and short-term postoperative outcomes for the different index colectomies.

Patients who underwent resection with anastomosis for a first primary colon carcinoma between 2013 and 2019 and were registered in the Dutch ColoRectal Audit were included. Primary outcomes were mortality, ICU admission, and stoma creation.

Among 39,565 patients, the overall AL rate was 4.8% and ranged between 4.0% (right hemicolectomy) and 15.4% (subtotal colectomy). AL was predominantly managed with reoperation, ranging from 81.2% after transversectomy to 92.4% after sigmoid resection (p < 0.001). Median time to reoperation differed significantly between index colectomies (range 4-8 days, p < 0.001), with longer and comparable intervals for non-surgical reinterventions (range 13-18 days, p = 0.747). After reoperation, the highest mortality rates were observed for index transversectomy (15.4%) and right hemicolectomy (14.4%) and lowest for index sigmoid resection (5.6%) and subtotal colectomy (5.9%) (p < 0.001). Reoperation with stoma construction was associated with a higher mortality risk than without stoma construction after index right hemicolectomy (17.7% vs. 8.5%, p = 0.001). ICU admission rate was 62.6% overall (range 56.7-69.2%), and stoma construction rate ranged between 65.5% (right hemicolectomy) and 93.0% (sigmoid resection).

Significant differences in AL rate, reoperation rate, time to reoperation, postoperative mortality after reoperation, and stoma construction for AL were found among the different index colectomies for colon cancer, with relevance for patient counseling and perioperative management.

Development of an anastomotic leak (AL) following intestinal surgery for the treatment of colorectal cancers is a life-threatening complication. Failure of the anastomosis to heal correctly can lead to contamination of the abdomen with intestinal contents and the development of peritonitis. The additional care that these patients require is associated with longer hospitalisation stays and increased economic costs. Patients also have higher morbidity and mortality rates and poorer oncological prognosis. Unfortunately, current practices for AL diagnosis are non-specific, which may delay diagnosis and have a negative impact on patient outcome. To overcome these issues, research is continuing to identify AL diagnostic or predictive biomarkers. In this review, we highlight promising candidate biomarkers including ischaemic metabolites, inflammatory markers and bacteria. Although research has focused on the use of blood or peritoneal fluid samples, we describe the use of implantable medical devices that have been designed to measure biomarkers in peri-anastomotic tissue. Biomarkers that can be used in conjunction with clinical status, routine haematological and biochemical analysis and imaging have the potential to help to deliver a precision medicine package that could significantly enhance a patient's post-operative care and improve outcomes. Although no AL biomarker has yet been validated in large-scale clinical trials, there is confidence that personalised medicine, through biomarker analysis, could be realised for colorectal cancer intestinal resection and anastomosis patients in the years to come.

In recent years, more and more attention has been paid to intestinal microbiome. Almost all operations will go through the anesthesia process, but it is not clear whether the intervention of anesthesia alone will affect the change in the intestinal microbiome. The purpose of this study was to verify the effect of sevoflurane inhalation anesthesia on the intestinal microbiome. The animal in the experimental group was used to provide sevoflurane inhalation anesthesia for 4 hours. The control group was not intervened. The feces of the experimental group and the control group were collected on the 1st, 3rd, 7th and 14th days after anesthesia. Sevoflurane inhalation anesthesia will cause changes in the intestinal microbiome of mice. It appears on the 1st day after anesthesia and is most obvious on the 7th day. The specific manifestation is that the abundance of microbiome and the diversity of the microbiome is reduced. At the same time, Untargeted metabonomics showed that compared with the control group, the experimental group had more increased metabolites related to the different microbiome, among which 5-methylthioadenosine was related to the central nervous system. Subsequently, the intestinal microbiome diversity of mice showed a trend of recovery on the 14th day. At the genus level, the fecal samples obtained on the 14th day after anesthesia exhibited significantly increased abundances of Bacteroides, Alloprevotella, and Akkermansia and significantly decreased abundances of Lactobacillus compared with the samples obtained on the 1st day after anesthesia. However, the abundance of differential bacteria did not recover with the changing trend of diversity. Therefore, we believe that sevoflurane inhalation anesthesia is associated with changes in the internal microbiome and metabolites, and this change may be completed through the brain-gut axis, while sevoflurane inhalation anesthesia may change the intestinal microbiome for as long as 14 days or longer.

The gut epithelium is a habitat of a variety of microorganisms, including bacteria, fungi, viruses and Archaea. With the advent of sophisticated molecular techniques and bioinformatics tools, more information on the composition and thus function of gut microbiota was revealed. The gut microbiota as an integral part of the intestinal barrier has been shown to be involved in shaping the mucosal innate and adaptive immune response and to provide protection against pathogens. Consequently, a set of biochemical signals exchanged within microbes and communication between the microbiota and the host have opened a new way of thinking about cancer biology. Probiotics are living organisms which administered in adequate amounts may bring health benefits and have the potential to be an integral part of the prevention/treatment strategies in clinical approaches. Here we provide a comprehensive review of data linking gut microbiota to cancer pathogenesis and its clinical course. We focus on gastrointestinal cancers, such as gastric, colorectal, pancreatic and liver cancer.

Accurate intraoperative assessments of tissue perfusion are essential in all forms of surgery. As traditional methods of perfusion assessments are not available during minimally invasive surgery, novel methods are required. Here, fluorescence angiography with indocyanine green has shown promising results. However, to secure objective and reproducible assessments, quantification of the fluorescent signal is essential (Q-ICG). This narrative review aims to provide an overview of the current status and applicability of Q-ICG for intraoperative perfusion assessment.

Both commercial and custom Q-ICG software solutions are available for intraoperative use; however, most studies on Q-ICG have performed post-operative analyses. Q-ICG can be divided into inflow parameters (ttp, t0, slope, and T_1/2max) and intensity parameters (Fmax, PI, and DR). The intensity parameters appear unreliable in clinical settings. In comparison, inflow parameters, mainly slope, and T_1/2max have had superior clinical performance.

Intraoperative Q-ICG is clinically available; however, only feasibility studies have been performed, rendering an excellent usability score. Q-ICG in a post-operative setting could detect changes in perfusion following a range of interventions and reflect clinical endpoints, but only if based on inflow parameters. Thus, future studies should include the methodology outlined in this review, emphasizing the use of inflow parameters (slope or T_1/2max), a mass-adjusted ICG dosing, and a fixed camera position.

The gut microbiota seems to play a key role in tumorigenesis, across various hallmarks of cancer. Recent evidence suggests its potential use as a biomarker predicting drug response and adding prognostic information, generally in the context of immuno-oncology.

In this review, we focus on the modulating effects of gut microbiota dysbiosis on various anticancer molecules used in practice, including cytotoxic and immune-modulating agents, primarily immune-checkpoint inhibitors (ICI). Pubmed/Medline-based literature search was conducted to find potential original studies that discuss gut microbiota as a prognostic and predictive biomarker for cancer therapy. We also looked at the US ClinicalTrials.gov website to find additional studies particularly ongoing human clinical trials.

Sequencing of stool-derived materials and tissue samples from cancer patients and animal models has shown a significant enrichment of various bacteria such as Fusobacterium nucleatum and Bacteroides fragilis were associated with resistant disease and poorer outcomes. Gut microbiota was also found to be associated with surgical outcomes and seems to play a significant role in anastomotic leak (ATL) after surgery mainly by collagen breakdown. However, this research field is just at the beginning and the current findings are not yet ready to change clinical practice.

The dysbiosis is defined as a disturbed symbiotic relationship between microbiota and the host and can cause a pro-inflammatory imbalance impairing the healing process at anastomotic level. The aim of this study is to detect, in fecal samples collected in the preoperative time, a peculiar microbiota composition that could predict the onset of colorectal anastomotic leakage.

We compared gut microbiota of healthy patients (Group A) and patients with colorectal cancer eligible for surgery (Group B). Group B was divided into patients who developed anastomotic leak (Group BL) and patients who had uneventful recovery (Group BNL). Stool samples were collected before surgery and after neoadjuvant treatment.

We analyzed stool samples from 48 patients, 27 belonging to Group A and 21 to Group B. In Group B, five patients developed anastomotic leakage (Group BL). Compared to healthy subjects, Group B showed a moderate increase of Bacteroidetes and Proteobacteria, a moderate reduction of Firmicutes and Actinobacteria, and a statistically significant reduction of Faecalibacterium prausnitzii. Group BL patients showed an array of bacterial species which promoted dysbiosis, such as Acinetobacter lwoffii and Hafnia alvei. Group BNL patients showed that bacterial species like Faecalibacterium prausnitzii and Barnesiella intestinihominis have a protective function.

The bacterial flora in subjects with colorectal cancer is statistically different compared to healthy patients. The presence of preoperative aggressive bacteria and the lack of protective strains has strengthened the hypothesis that a peculiar microbiota composition could represent a risk factor for the occurrence of anastomotic leakage.