Modern approaches and technologies to prevent anastomotic leakage in the gastrointestinal tract

<h3>Background</h3> The standard of care of colorectal cancer (CRC) management consists of surgical resection of the colon or rectum, followed by a reconnection, or ‘anastomosis’, of the remaining bowel ends to re-establish gastrointestinal continuity. Up to 30% of patients may present poor healing of the anastomosis, and anastomotic leak (AL), a major complication that increases mortality and morbidity after surgery. Our objective is to investigate the possible role of the gut microbiome in anastomotic healing in patients with CRC. <h3>Methods</h3> Preoperative fecal samples were collected from CRC patients undergoing surgery. The gut microbiota of patients with AL and of others that presented optimal healing were analyzed and compared using the Anchor pipeline. Fecal microbiota transplantation (FMT) was performed in mice using preoperative fecal samples from CRC patients with and without AL. Mice were then subjected to colonic surgery using a colonic anastomosis model. After 6 days, anastomotic healing and the gut barrier were assessed. The gut microbiota composition was compared as well to detect potential differences between the groups of mice transplanted from donors with and without AL. <h3>Results</h3> Mice colonized by FMT with the microbiota of donors with AL displayed macroscopically poorer healing of the colonic anastomosis and a higher bacterial translocation to the spleen, suggestive of a weaker gut barrier after surgery. The anastomotic wounds of mice receiving the microbiota of AL donors displayed lower concentrations of collagen and fibronectin and higher inflammatory cytokines, indicating poor extracellular matrix formation after surgery. This was accompanied by a higher expression of collagenolytic enzymes, indicative of collagen degradation at the wound site. The beta diversity of the gut microbiota was significantly different between mice receiving the microbiota of donors with and without AL. Several bacterial species were differentially abundant between the two groups and were associated with the healing process. <h3>Conclusions</h3> The preoperative gut microbiota in CRC patients with poor postoperative healing induces poor healing in mice and a weaker gut barrier after surgery. These results suggest a causal role for the gut microbiota in colonic healing after surgery in patients with CRC.

Introduction Systematic reviews of retrospective studies suggest that indocyanine green (ICG) angiography reduces anastomotic leak (AL) and improves postoperative outcomes. This systematic review and meta-analysis evaluates colorectal surgery outcomes following ICG use with comparison of results found in randomized controlled trials (RCTs) and retrospective studies. Methods A systematic search was conducted of studies evaluating ICG in colorectal surgery with more than five patients. Systematic search of MEDLINE, Embase, Scopus, and Web of Science was conducted in August 2021 and this study followed PRISMA and MOOSE guidelines. Primary outcome was AL. Meta-analysis was conducted with RevMan 5.4. Results Overall, 2403 studies were retrieved with 28 total studies including three RCTs meeting criteria. RCTs included 964 patients, whereas other studies comprised 7327 patients with 44.6% receiving ICG. The ICG and non-ICG cohorts were similar with respect to age (62.6 vs 63.1 years), sex (45.1% vs 43.1% female), smoking (22.4% vs 25.3% smokers), and diabetes (13.4% vs 14.2%), respectively. Anastomotic height (6.5 vs 6.8 cm) and technique (78.7% vs 74.8% stapled) were also comparable. With retrospective studies included, ICG was associated with AL reduction (odds ratio [OR] 0.41; 95% CI, 0.32–0.53; p &amp;lt; 0.001) and reoperation for AL (OR 0.64; 95% CI, 0.43–0.95; p = 0.03), with pronounced effects for rectal anastomoses (OR 0.31; 95% CI, 0.21–0.44; p &amp;lt; 0.001). RCT evidence suggests a much smaller effect size (OR 0.64; 95% CI, 0.42–0.99; p = 0.04), and no reduction in AL reoperation (OR 0.72; 95% CI, 0.29–1.80; p = 0.48) or length of stay (LOS). Conclusion Retrospective studies suggest reduced AL, reoperation for AL, and LOS with ICG angiography. However, RCTs suggest a smaller effect size and do not demonstrate reduced reoperation or LOS. Additional RCTs are required before widespread ICG uptake.

Background Poor fundus perfusion is seen as the major factor for the development of anastomotic necrosis, leakage and strictures. Quantitative imaging of tissue perfusion during reconstructive surgery, therefore, may reduce the incidence of complications. Imaging the fluorescense of intravenously administered fluorophores is an optical, non-contact method to image blood flow in real-time. However, quantitative parameters for perfusion evaluation are stil lacking. The objective of this study is to test fluorescence imaging derived quantitative parameters for perfusion evaluation of the gastric tube during surgery and to correlate these parameters to patient outcome in terms of anastomotic leakage. Methods This study included 22 patients (October 2015 - June 2016). Indocyanine green (ICG) was injected intravenously and the fluorescense intensity of the gastric tube was imaged for 2–3 minutes. At 4 locations, quantitative analysis of the fluorescent intensity over time was performed to obtain perfusion related parameters: the maximal intensity, mean slope and influx timepoint. These parameters were tested for significant differences between the four perfusion areas of the gastric tube (from normal to decreased perfusion) with a repeated ANOVA test. Furthermore, these parameters and the distance of the end of the gastroepiploic artery to the fundus and distance of the demarcation of the fluorescent signal to the fundus were compared with patient outcome in terms of anastomotic leakage development. Results The fluorescent signal could be detected in all analyzed patients (n = 20). Maximal intensity, mean slope and influx timepoint were significantly different between the base of the gastric tube and the fundus (P &lt; 0.0001). While the distance of the watershed and the demarcation of ICG to the fundus varied between patients, the distance of the demarcation of ICG to the fundus was significantly higher in the three patients who developed anastomotic leakage (P &lt; 0.0001). No allergic reactions on ICG were witnessed. Conclusion Intra-operative fluorescence imaging is feasible to visualize perfusion quantitatively in gastric-tube surgery, using the parameters maximal intensity, mean slope and influx timepoint. A low slope and a large distance between the fluorescence demarcation and the fundus were seen in patients who developed anastomotic leakage and could therefore allow for early risk stratification of necrosis. Disclosure All authors have declared no conflicts of interest.

Commentary: Hand-sewn or stapled esophageal anastomosis: Ask not what your anastomosis can do for you, but what you can do for your esophageal anastomosis

Various anastomotic and reconstruction techniques are used for minimally invasive total (miTG) and distal gastrectomy (miDG). Their effects on postoperative morbidity have not been extensively studied. MiTG and miDG patients were selected from 9356 oncological gastrectomies performed in 2017-2021 in 43 centers. Endpoints included anastomotic leakage (AL) rate and postoperative morbidity tested by multivariable analysis. Three major anastomotic techniques [circular stapled (CS); linear stapled (LS); and hand sewn (HS)], and 3 major bowel reconstruction types [Roux (RX); Billroth I (BI); Billroth II (BII)] were identified in miTG (n=878) and miDG (n=3334). Postoperative complications, including AL (5.2% vs 1.1%), overall (28.7% vs 16.3%), and major morbidity (15.7% vs 8.2%), as well as 90-day mortality (1.6% vs 0.5%) were higher after miTG compared with miDG. After miTG, the AL rate was higher after CS (4.3%) and HS (7.9%) compared with LS (3.4%). Similarly, major complications (LS: 9.7%, CS: 16.2%, and HS: 12.7%) were lowest after LS. Multivariate analysis confirmed anastomotic technique as a predictive factor for AL, overall, and major complications. In miDG, AL rate (BI: 1.4%, BII 0.8%, and RX 1.2%), overall (BI: 14.5%, BII: 15.0%, and RX: 18.7%), and major morbidity (BI: 7.9%, BII: 9.1%, and RX: 7.2%), and mortality (BI: 0%, BII: 0.1%, and RY: 1.1%%) were not affected by bowel reconstruction. In oncologically suitable situations, miDG should be preferred to miTG, as postoperative morbidity is significantly lower. LS should be a preferred anastomotic technique for miTG in Western Centers. Conversely, bowel reconstruction in DG may be chosen according to the surgeon's preference.

Intraoperative fluorescence angiography with indocyanine green to prevent anastomotic leak in rectal cancer surgery (IntAct): an unblinded randomised controlled trial.

Ischemia is known to be a major contributor for anastomotic leaks and indocyanine green (ICYG) fluorescence angiography has been utilized to assess perfusion. Experienced esophageal surgeons have clinically assessed the gastric conduit with acceptable outcomes for years. We sought to examine the impact of ICYG in a surgeon's decision-making during esophagectomy. We queried a prospectively maintained database to identify patients who underwent robotic esophagectomy. Time to initial perfusion, time to maximum perfusion, and residual ischemia were measured and used as a guide to resection of residual stomach. During esophagectomy the surgeon identified the anticipated line of ischemic demarcation (LOD) prior to ICYG injection. The distance between the surgeon's LOD and ICYG LOD was measured. We identified 312 patients who underwent robotic esophagectomy, 251 without ICYG and 61 with ICGY. There were no differences in age, sex, race, body mass index, histology, stage, or neoadjuvant therapy use between groups. The incidence of anastomotic leak did not differ between groups (non-ICYG, 5.2% vs. ICYG, 6.6%), p = 0.67. The initial perfusion time was ≥ 10s and max perfusion was > 25s in all the patients in the ICYG that developed anastomotic leaks. All patients were noted to have at least 1cm of residual gastric ischemia. Fifteen patients underwent independent surgeon evaluation of the ischemic LOD prior to ICYG. Differential distances were noted in 12 (80%) patients with a mean distance between surgical line of demarcation and ICYG LOD of 0.77cm. While the implementation of ICYG during esophagectomy demonstrates no significant improvements in anastomotic leak rates compared to historical controls, surgeon's decision-making is impacted in 80% of cases resulting in additional resection of the gastric conduit. Elevated times to initial perfusion and maximum perfusion were associated with increased gastric ischemia and anastomotic leaks.

Background: Anastomotic leakage (AL) is arguably the most troublesome complication of anterior resection (AR). In recent years, however, indocyanine green (ICG) fluorescence imaging has been recently used to evaluate blood flow in the anastomosis site, and it has been suggested that AL may be predicted. We reported the effectiveness of predicting AL in colorectal cancer surgery by observing a quantitative laparoscopic ICG fluorescence imaging for the first time. The purpose of this study was to predict the risk of postoperative AL by quantitative laparoscopic ICG fluorescence imaging focused on the rectal stamp, which is one of the major causes of AL in AR, and to construct diverting stoma (DS) only in appropriate cases. Methods: We studied the 25 patients who underwent elective laparoscopic AR for rectal cancer at our hospital between July 2016 and June 2017. Before enforcing double-stapling technique anastomosis, we injected ICG intravenously, and laparoscopically evaluated blood flow on the rectal stump. We analyzed quantitatively the relationship between various parameters and AL. Results: Median T0, from when the ICG was injected intravenously and the ICG disappeared from the injection route to the rise of the histogram of intensity, in AL group was significantly longer than that in non-AL group (P = .03). There were no other significant differences between AL and non-AL groups. Conclusions: T0 was longer in patients with AL than in those without. If prolonged T0 can be recognized intraoperatively, it will be possible to construct DS for appropriate patients only.

We have previously demonstrated that the flow speed of indocyanine green (ICG) fluorescence in the gastric conduit wall could predict anastomotic leakage after esophagectomy. Surround organs via retrosternal route is considered to affect the blood flow in the gastric conduit and anastomotic leakage. In the study, we investigated the impact of the flow speed of ICG fluorescence in the gastric conduit wall and thoracic inlet space on anastomotic leakage after esophagectomy. Methods A total of 142 patients, who underwent esophagectomy with three-field lymph node dissection, simultaneous reconstruction using a gastric conduit, and cervical anastomosis via retrosternal route, were prospectively investigated. Using ICG fluorescence imaging, blood flow speed of the gastric conduit wall was assessed before and after anastomosis (pre speed and post speed (cm/s)) and correlated with clinicopathological findings. Parameters of thoracic inlet space was assessed using CT scan and correlated with blood flow speed of the gastric conduit wall and anastomotic leakage. Results Median pre speed was 2.54 (0.73–6.10) cm/s and median post speed was dropped by 1.77 (0.32–8.67) cm/s. Speed reduction (pre speed—post speed) and speed reduction rate ((pre speed—post speed)/pre speed) were negatively correlated with thoracic inlet area (TIA) (P = 0.004, P = 0.021). Pre speed and post speed of the patients with anastomotic leakage were significantly slower than those of the patients without anastomotic leakage, respectively (P &amp;lt; 0.001 and P = 0.050). In 115 patients with pre speed more than 1.98 cm/s, TIA was significantly associated with anastomotic leakage after esophagectomy (P &amp;lt; 0.001). Conclusion We clearly demonstrated that retrosternal route reduced the blood flow of the gastric conduit wall using ICG fluorescence imaging. Narrow thoracic inlet space might obstruct the blood flow of the gastric conduit wall and cause anastomotic leakage after esophagectomy.

BackgroundThe optimal technique for intrathoracic esophagogastric anastomosis in esophagectomy remains undetermined. This study evaluates different anastomotic techniques in robot-assisted minimally invasive esophagectomy (RAMIE) and their impact on anastomotic leakage rates.Materials and MethodsThis observational, retrospective, comparative cohort study analyzed data obtained from the Upper GI International Robotic Association (UGIRA) Esophageal Registry. All consecutive patients with a histologically proven esophageal malignancy who underwent RAMIE with intrathoracic esophagogastrostomy were included. The anastomotic technique was performed based on the clinical judgement and expertise of each individual surgeon. For comparison, the four most common techniques were included: circular end-to-side, linear side-to-side, handsewn end-to-side, and handsewn end-to-end. The primary endpoint of this study was the occurrence of anastomotic leakage, defined by the Esophagectomy Complications Consensus Group as a full-thickness gastrointestinal defect involving the esophagus, anastomosis, staple line, or conduit, regardless of its presentation or method of identification.ResultsBetween 2016 and September 2023, 1518 patients were included. Univariable analysis demonstrated that the linear stapled side-to-side anastomosis was associated with the lowest anastomotic leakage rate (14.0%), while the handsewn end-to-end anastomosis had the highest (32.8%) (p < 0.001). The anastomotic leakage rates for circular end-to-side and handsewn end-to-side anastomoses were 19.4% and 26.9%, respectively. Multivariable analysis confirmed that anastomotic technique was independently associated with anastomotic leakage. Specifically, handsewn anastomoses were associated with a higher risk of anastomotic leakage for both end-to-side (OR 1.675, 95% CI 1.195–2.348, p = 0.003) and end-to-end (OR 2.181, 95% CI 1.403–3.390, p < 0.001) techniques compared to circular end-to-side anastomoses.ConclusionsIn RAMIE, linear side-to-side and circular end-to-side stapled anastomoses are associated with lower anastomotic leakage rates compared to handsewn techniques. While acknowledging the multifactorial complexity of anastomotic leakage, these findings favor the use of mechanical stapling in clinical practice.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00464-025-11977-x.

Background: Indocyanine Green (ICG) is a promising technique for the assessment of gastric conduit and anastomosis perfusion during esophagectomy. ICG integration may be helpful in minimizing the risk of anastomotic leak (AL). Literature evidence is sparse, while the real effect of ICG assessment on AL minimization remains unsolved. The aim of this systematic review and meta-analysis was to compare short-term outcomes between ICG-guided and non-ICG-guided (nICG) esophagogastric anastomosis during esophagectomy for cancer. Materials and Methods: PubMed, MEDLINE, Scopus, Web of Science, Cochrane Central Library, and ClinicalTrials.gov were queried up to 25 April 2024. Studies that reported short-term outcomes for ICG versus non-ICG-guided (nICG) anastomosis in patients undergoing esophagectomy were considered. Primary outcome was AL. Risk ratio (RR) and standardized mean difference (SMD) were utilized as effect size measures, whereas to assess relative inference we used 95% confidence intervals (95% CI). Results: Overall, 1399 patients (11 observational studies) were included. Overall, 576 (41.2%) underwent ICG gastric conduit assessment. The patients' ages ranged from 22 to 91 years, with 73% being male. The cumulative incidence of AL was 10.4% for ICG and 15.4% for nICG. Compared to nICG, ICG utilization was related to a reduced risk for postoperative AL (RR 0.48; 95% CI 0.23-0.99; p = 0.05). No differences were found in terms of pulmonary complications (RR 0.83), operative time (SMD -0.47), hospital length of stay (SMD -0.16), or 90-day mortality (RR 1.70). Conclusions: Our study seems to indicate a potential impact of ICG in reducing post-esophagectomy AL. However, because of limitations in the design of the included studies, allocation/reporting bias, variable definitions of AL, and heterogeneity in ICG use, caution is required to avoid potential overestimation of the ICG effect.

PurposeThis experimental study verified the effect of adipose-tissue-derived stem cells (ASCs) on the healing of ischemic colonic anastomoses in rats.MethodsASCs were isolated from the subcutaneous fat tissue of rats and identified as mesenchymal stem cells by identification of different potentials. An animal model of colonic ischemic anastomosis was induced by modifying Nagahata's method. Sixty male Sprague-Dawley rats (10-week-old, 370 ± 50 g) were divided into two groups (n = 30 each): a control group in which the anastomosis was sutured in a single layer with 6-0 polypropylene without any treatment and an ASCtreated group (ASC group) in which the anastomosis was sutured as in the control group, but then ASCs were locally transplanted into the bowel wall around the anastomosis. The rats were sacrificed on postoperative day 7. Healing of the anastomoses was assessed by measuring loss of body weight, wound infection, anastomotic leakage, mortality, adhesion formation, ileus, anastomotic stricture, anastomotic bursting pressure, histopathological features, and microvascular density.ResultsNo differences in wound infection, anastomotic leakage, or mortality between the two groups were observed. The ASC group had significantly more favorable anastomotic healing, including less body weight lost, less ileus, and fewer ulcers and strictures, than the control group. ASCs augmented bursting pressure and collagen deposition. The histopathological features were significantly more favorable in the ASC group, and microvascular density was significantly higher than it was in the control group.ConclusionLocally-transplanted ASCs enhanced healing of ischemic colonic anastomoses by increasing angiogenesis. ASCs could be a novel strategy for accelerating healing of colonic ischemic risk anastomoses.

Imaging technology to assess tissue oxygen saturation of the gastric conduit in thoracic esophagectomy

Intestinal perfusion at the anastomotic site is thought to be one of the most influential risk factors for postoperative anastomotic leakage (AL). We evaluated the efficacy of indocyanine green (ICG) fluorescence imaging at the stump of the proximal colon in left-sided colectomy or rectal resection in terms of decreasing the incidence of AL. Prospectively collected data were retrospectively evaluated. Patients who underwent left-sided colectomy or rectal resection were enrolled (ICG group; n = 197), and patients who had undergone a similar procedure before the ICG group were enrolled from the charts as historical controls (HC group; n = 187). After ICG evaluation, anastomosis was performed where fluorescence was sufficient. The incidence of AL was compared between the ICG and HC groups. Propensity score (PS)-matched data were analyzed to clarify the risk of AL. AL occurred in 6 patients (3.3%) in the ICG group and 17 (10.7%) in the HC group. ICG evaluation revealed 179 patients with good fluorescence and 18 with poor/none perfusion (9.1%). The transection line was changed in all patients with poor/none fluorescence. Three of these 18 patients developed AL (16.7%), though transection line was changed at which is thought to be good. We hope AL in poor/none fluorescence can be prevented at the same rate of cases with good fluorescence. Actually, the rate of that was significantly higher compared with good fluorescence patients (P = 0.038). 93 patients in each group were compared by PS-matched data analysis, which showed the AL rate in the ICG group was significantly lower than that in the HC group (3.2% vs 10.8%, respectively; P = 0.046). Even though this study has limitations of comparison of data prospectively collected and retrospectively analyzed, intraoperative ICG fluorescence imaging evaluation could significantly decrease the incidence of AL.

Indocyanine green is a useful tool in colorectal surgery. Quantitative values may enhance and standardize its application. To determine whether quantitative indocyanine green metrics correlate with standard subjective indocyanine green perfusion assessment in acceptance or rejection of anastomotic margins. Prospective single-arm, single-institution cohort study. Surgeons viewed subjective indocyanine green images but were blinded to quantitative indocyanine green metrics. Tertiary academic center. Adults undergoing planned intestinal resection. Accepted perfusion and rejected perfusion of the intestinal margin were defined by the absence or presence of ischemia by subjective indocyanine green and gross inspection. The primary outcomes included quantitative indocyanine green values, maximum fluorescence, and time-to-maximum fluorescence in accepted compared to rejected perfusion. Secondary outcomes included maximum fluorescence and time-to-maximum fluorescence values in anastomotic leak. There were 89 perfusion assessments comprising 156 intestinal segments. Nine segments were subjectively assessed to have poor perfusion by visual inspection and subjective indocyanine green. Maximum fluorescence (% intensity) exhibited higher intensity in accepted perfusion (accepted perfusion 161% [82%-351%] vs rejected perfusion 63% [10%-76%]; p = 0.03). Similarly, time-to-maximum fluorescence (seconds) was earlier in accepted perfusion compared to rejected perfusion (10 seconds [1-40] vs 120 seconds [90-120]; p < 0.01). Increased BMI was associated with higher maximum fluorescence. Anastomotic leak did not correlate with maximum fluorescence or time-to-maximum fluorescence. Small cohort study, not powered to measure the association between quantitative indocyanine green metrics and anastomotic leak. We demonstrated that blinded quantitative values reliably correlate with subjective indocyanine green perfusion assessment. Time-to-maximum intensity is an important metric in perfusion evaluation. Quantitative indocyanine green metrics may enhance intraoperative intestinal perfusion assessment. Future studies may attempt to correlate quantitative indocyanine green values with anastomotic leak. See Video Abstract . ANTECEDENTES:El verde de indocianina es una herramienta útil en la cirugía colorrectal. Los valores cuantitativos pueden mejorar y estandarizar su aplicación.OBJETIVO:Determinar si las métricas cuantitativas de verde de indocianina se correlacionan con la evaluación subjetiva estándar de perfusión de verde de indocianina en la aceptación o rechazo de los márgenes anastomóticos.DISEÑO:Estudio de cohorte prospectivo de un solo brazo y de una sola institución. Los cirujanos vieron imágenes subjetivas de verde de indocianina, pero no conocían las métricas cuantitativas de verde de indocianina.AJUSTE:Centro académico terciario.PACIENTES:Adultos sometidos a resección intestinal planificada.PRINCIPALES MEDIDAS DE RESULTADO:La perfusión aceptada y la perfusión rechazada del margen intestinal se definieron por la ausencia o presencia de isquemia mediante verde de indocianina subjetiva y la inspección macroscópica. Los resultados primarios fueron los valores cuantitativos de verde de indocianina, la fluorescencia máxima y el tiempo hasta la fluorescencia máxima en la perfusión aceptada en comparación con la rechazada. Los resultados secundarios incluyeron la fluorescencia máxima y el tiempo hasta alcanzar los valores máximos de fluorescencia en la fuga anastomótica.RESULTADOS:Se realizaron 89 evaluaciones de perfusión, comprendiendo 156 segmentos intestinales. Se evaluó subjetivamente que 9 segmentos tenían mala perfusión mediante inspección visual y verde de indocianina subjetiva. La fluorescencia máxima (% de intensidad) mostró una mayor intensidad en la perfusión aceptada [Perfusión aceptada 161% (82-351) vs Perfusión rechazada 63% (10-76); p = 0,03]. De manera similar, el tiempo hasta la fluorescencia máxima (segundos) fue más temprano en la perfusión aceptada en comparación con la rechazada [10 s (1-40) frente a 120 s (90-120); p < 0,01]. Aumento del índice de masa corporal asociado con una fluorescencia máxima más alta. La fuga anastomótica no se correlacionó con la fluorescencia máxima ni con el tiempo hasta la fluorescencia máxima.LIMITACIONES:Estudio de cohorte pequeño, sin poder para medir la asociación entre las mediciones cuantitativas del verde de indocianina y la fuga anastomótica.CONCLUSIÓN:Demostramos que los valores cuantitativos ciegos se correlacionan de manera confiable con la evaluación subjetiva de la perfusión de verde de indocianina. El tiempo hasta la intensidad máxima es una métrica importante en la evaluación de la perfusión. Las métricas cuantitativas de verde de indocianina pueden mejorar la evaluación de la perfusión intestinal intraoperatoria. Los estudios futuros pueden intentar correlacionar los valores cuantitativos de verde de indocianina con la fuga anastomótica. (Traducción-Dr. Yolanda Colorado).