Abstract Topic Esophageal Cancer: Surgical Treatment of Esophageal Cancer – early outcomes and complications Background Endoscopic submucosal dissection (ESD) is recommended for early-stage esophageal squamous cell carcinoma (ESCC). Most data on the efficacy of ESD for ESCC comes from Asia. There are no studies from Scandinavia. The aim of this study was to evaluate the safety and efficacy of ESD for ESCC in Scandinavia. Methods A multicenter retrospective cohort study. All patients with ESCC treated with ESD at five specialized centers in Sweden, Norway, Denmark and Iceland between January 2010 - June 2024 were included. The primary outcome was technical success rate - complete resection and en bloc resection. The secondary outcomes were R0 and curative resection rates, adverse events, overall survival (OS), disease-specific survival (DSS). Results Fifty-four patients were included, with a median age of 73 (IQR 67-79). The tumors involved ≥ 75% of the lumen circumference in 50.0 % of cases. The procedures were performed under general anesthesia and median operation time was 120.5 (IQR 81-180) minutes. The median hospital-stay was 2.5 days. Regarding primary outcomes, complete resection and en bloc resection rates were 98.2 % and 96.3 %, respectively. As for secondary outcomes, R0 and curative rates were 69.8 % and 44.4 %. One patient (1.9 %) had a postoperative bleeding, and one had a perforation. Stricture occurred in 33.3 %. One patient died within 30-days due to a delayed gastric perforation caused by barotrauma. With median follow-up of 2.6 years, five patients (9.3 %) died of ESCC and 11 (20.4 %) of other causes. Five-year OS and DSS were 60.3 % and 83.4 %. Conclusion Even in Scandinavia, with a low incidence of ESCC, ESD is a safe and effective treatment. A large proportion of tumors were large circumferential lesions, which could be removed completely, and the hospital stay was short. Compared to Asian series, good rates of complete and en bloc resection rates were achieved, however with lower curative resection rates, indicating that more advanced tumors were resected. During follow-up, <10% of treated patients died due to ESCC.

Introduction The systematic review evaluates the impact of indocyanine green fluorescence angiography (ICG-FA) on surgical decisions, postoperative complications, and mortality in acute bowel ischemia. Methods Studies were included if they met the following criteria: patients ≥18 y undergoing ICG-FA for perfusion assessment in all-cause acute bowel ischemia; if they were human clinical studies with original data (n ≥ 5); and if they were published in English, Latin, or Nordic languages. The primary outcome was change of strategy; secondary outcomes included postoperative complications and mortality. Studies were excluded if they were reviews or meta-analyses, animal studies, or papers without original empirical data. Risk of bias was assessed with the Risk of Bias In Non-randomized Studies - of Interventions (ROBINS-I Tool). Outcomes were presented narratively, given the high clinical and methodological heterogeneity across studies. Results Seven studies met the following inclusion criteria: five retrospective cohort studies and two case series. No randomized trials were identified. A total of 356 patients undergoing fluorescence-guided surgery for suspected or confirmed acute bowel ischemia were included. Across studies, the reported change in surgical strategy ranged from 29% to 67%, postoperative complications from 0% to 24%, and mortality from 0% to 64%. Conclusions Our findings suggest that ICG-FA may influence surgical decision-making in acute bowel ischemia by guiding resection strategy, but no clinical benefit in regard to postoperative outcomes was shown. However, the evidence is limited to small, retrospective studies with significant risk of bias and low quality of evidence.

Abstract Topic Esophageal Cancer: Surgical Treatment of Esophageal Cancer Background Achieving an adequate proximal resection margin is considered essential for oncologic control in esophageal adenocarcinoma. However, the prognostic significance of margin length following neoadjuvant therapy remains uncertain, particularly in patients who don't complete adjuvant chemotherapy. This study evaluates the clinical impact of proximal margin distance and adherence to national guidelines. Methods This retrospective single-center study included 221 patients treated at a high-volume tertiary referral center. All patients received neoadjuvant therapy before esophagectomy for esophageal adenocarcinoma between 2019 and 2021. The year of the last follow-up was 2023. Two experienced upper gastrointestinal pathologists independently evaluated the oral tumor-free resection margins after formalin fixation. Adherence to the national guideline-recommended proximal margin of ≥38 mm was assessed. Results The mean proximal resection margin was 31.3 ± 17.4 mm, and 30.2% of patients achieved the national guideline-recommended margin of ≥38 mm. The mean margin was significantly lower than the recommended 38 mm (one-sample t-test, p < 0.001). Proximal margin distance, analyzed both as a continuous variable and as a dichotomous variable at clinically relevant and data-driven cutoffs, was not independently associated with overall or recurrence-free survival. However, in an exploratory subgroup analysis of patients who did not complete adjuvant chemotherapy, a non-significant trend toward inferior recurrence-free survival was observed for margins ≤16 mm (p = 0.078). Conclusion The achieved proximal resection margin was significantly lower than the national guideline-recommended threshold (p < 0.001). However, proximal margin length was not independently associated with overall or recurrence-free survival. Larger, adequately powered studies with longer follow-up are warranted to clarify the potential prognostic relevance of proximal margin distance in patients receiving neoadjuvant therapy.

BACKGROUND:Mesenteric traction syndrome (MTS) is characterized by tachycardia, hypotension, and facial flushing during abdominal surgery. Previous studies suggest that severe MTS is associated with increased complications as well as endothelial damage. Whereas MTS was previously diagnosed based on subjective flushing, a recent study has validated an objective measure of facial flushing using laser speckle contrast imaging. However, no studies have yet examined the association between objectively diagnosed severe MTS (qsMTS), endothelial dysfunction, and postoperative complications. METHODS:Patients underwent either open pancreatic surgery or open esophagectomy for non-disseminated cancer. qsMTS was measured using laser speckle contrast imaging. Blood samples for endothelial damage and activation (soluble Thrombomodulin, VEGFR1, and Syndecan-1) were collected at predetermined intervals before and after surgery. RESULTS:In total, 61 patients were included, of whom 19 (31%) had qsMTS. qsMTS was associated with a Comprehensive Complication Index ≥26.2 (p = 0.010). No association was found between qsMTS-status and plasma concentrations of soluble Thrombomodulin, Syndecan-1, or VEGFR1 at any time point (p > 0.13 for all). CONCLUSION:Severe MTS remains a significant risk factor for severe postoperative complications following major abdominal surgery when diagnosed objectively. Although we hypothesized that this association might be partly mediated by increased endothelial damage and activation, our findings do not support this, as no association was observed between circulating endothelial markers and qsMTS or postoperative complications.

Background/Objectives: Motion artifacts significantly distort fluorescence measurements during surgical perfusion assessment, potentially leading to incorrect clinical decisions. This study evaluates the efficacy of automated motion compensation (MC) in quantitative indocyanine green (q-ICG) imaging to improve the accuracy of perfusion assessment. Methods: Frames from ICG perfusion assessment during 17 pancreaticoduodenectomies were analyzed. Regions of interest (ROIs) were systematically placed on each frame series, and automated MC was applied to track tissue movement. Performance was evaluated by comparing MC with surgeon-adjusted placement using multiple image quality metrics and analyzing perfusion metrics on time–intensity curves. Principal Component Analysis (PCA) was applied to explore whether image patterns could distinguish between successful and unsuccessful motion compensation. Results: Automated motion compensation successfully corrected motion artifacts in 67.5% of frame sequences, achieving comparable performance to surgeon-guided adjustments. PCA demonstrated clear separation between sufficient and insufficient corrections (AUC = 0.80). At the population level, MC did not significantly change perfusion slope (t(59) = 1.60, p = 0.11) or time-to-peak (Tmax; t(58) = 0.81, p = 0.42). Bland–Altman analysis showed a mean bias of −0.54 (SD = 3.32) for slope and 24.95 (SD = 238.40) for Tmax. At the individual level, 86.7% of slope and 79.7% of Tmax values differed by ≥10% after MC, with mean absolute percentage changes of 108.5% (median 37.8%) and 431.5% (median 65.9%), respectively. Conclusions: MC effectively reduces motion artifacts in fluorescence-guided perfusion assessment. By improving the precision of ICG-derived parameters, this technology enhances measurement reliability and represents an enabler for accurate intraoperative perfusion quantification.

INTRODUCTION:Curative treatment of gastric cancer requires surgery combined with perioperative chemotherapy. Textbook outcome (TO) and textbook oncological outcome (TOO) have gained increasing attention as composite measures representing an ideal surgical and oncological course. We aimed to evaluate the rates of TO and TOO after gastrectomy and their association with long-term outcomes. MATERIALS AND METHODS:A single-center retrospective observational study was conducted. TO was defined as achieving all of the following: macroscopic radical resection, R0 resection, removal of ≥15 lymph nodes, absence of severe complications (Clavien-Dindo grade >II), no intraoperative complications, hospital stay <21 days, no 30-day mortality, and no unplanned intensive care unit admission, reintervention, or readmission within 30 days after surgery. TOO was defined as TO plus adherence to guideline-compliant chemotherapy. Univariate analyses and multivariable logistic regression were used to identify predictors for TO and TOO. Associations between TO, TOO, and long-term outcomes were analyzed using Kaplan-Meier and Cox regression. RESULTS:We included 141 patients. TO was achieved in 56.7% and TOO in 25.9% of patients. TO was significantly associated with improved overall survival (hazard ratio: 0.31, P < 0.001) and recurrence-free survival (hazard ratio: 0.31, P < 0.001). TOO was not significantly associated with improved survival outcomes. The most common reasons for failing to achieve TO were severe complications (24.8%), reintervention (22.0%), and readmission (17.7%). CONCLUSIONS:This study found TO and TOO rates of 56.7% and 25.9%, suggesting quality of care on an international level. TO was significantly associated with long-term survival, supporting its future use as an important quality metric.

The prognostic value of lymph node (LN) yield in esophageal and gastric cancer remains controversial, especially in the context of modern perioperative treatment. This multicenter Danish cohort study evaluates the association between LN yield and survival outcomes. This study included 3092 patients who underwent curative-intent resection for esophageal (n = 2402) or gastric cancer (n = 690) between 2013 and 2021 at four Danish upper GI centers. All cases were registered in the Danish Esophagogastric Cancer Group database, covering 99% of all Danish esophageal and gastric cancer cases. Patients were stratified by nodal status (pN0/pN+) and categorized into five LN yield groups. Survival analyses were performed using Kaplan-Meier curves and multivariable Cox regression. In node-negative esophageal cancer, higher LN yields (20-29, 30-39, and 40+) were significantly associated with improved survival (hazard ratio: 0.47-0.58, P < 0.001) compared with the reference group (16-19). No survival benefit was seen beyond 16-19 nodes in node-positive esophageal or gastric cancers. Perioperative chemotherapy improved survival in node-positive esophageal cancer but had no effect in node-negative esophageal and gastric cancer. Discrepancies between clinical and pathological nodal staging were frequent and influenced both survival estimates and treatment allocation. LN removal was associated with survival in esophageal and gastric cancer. Node-negative patients showed increased survival if ≥20 nodes were removed, while node-positive esophageal cancer and gastric cancer patients showed no difference in survival beyond 16-19. Lastly, discrepancies between clinical and pathological staging underscore the need for more accurate preoperative diagnostics and highlight the impact of modern perioperative chemotherapy.

Introduction Dumping syndrome (DS) is a well-known sequela after esophagectomy, yet its prevalence remains uncertain, with previously reported estimates varying greatly (0%-78%). Moreover, predictors of DS remain underexplored. This study aimed to determine the prevalence of DS following curatively intended esophagectomy for adenocarcinoma and to identify potential risk factors. Materials and methods This single-center retrospective cohort study included patients who underwent esophagectomy for adenocarcinoma between January 2021 and May 2024. Data were collected through structured nurse-led follow-up interviews at predefined postoperative time points up to 24 mo after surgery. DS was classified based on reported symptoms. The prevalence of DS was assessed, and potential predictors were investigated through logistic regression analyses. Weight change over time was compared between patients with and without DS. Results This study included 148 patients. In total, 78% [70.9-84.7%] experienced DS at least once during follow-up, while point prevalence at individual visits remained consistently around 40-45%. Male sex was associated with increased odds of DS (adjusted odds ratio 3.04, [1.11-8.17]). Both groups experienced postoperative weight loss, with a nonsignificant tendency toward greater weight loss in patients with DS, particularly at one and 12 mo. Conclusions DS is highly prevalent after esophagectomy. These findings highlight the need for standardized diagnostic criteria, routine structured symptom assessment, and evidence-based strategies for postoperative management. Prospective studies are warranted to better define risk factors and optimize care for affected patients.

Late effects after gastrointestinal surgery are persistent symptoms or functional impairments that affect patients' quality of life following both benign and malignant treatment. The article provides an overview of the most common late effects in typical procedures. Examples include chronic pain, defecation issues, nutritional deficiencies, dumping, stoma-related problems, sexual dysfunction, and chronic fatigue. Systematic follow-up, early detection, and multidisciplinary rehabilitation are key measures to reduce the burden of late effects and improve patients' function and quality of life, as argued in this review.

Abstract Topic Esophageal Cancer: Surgical Treatment of Esophageal Cancer Background Esophageal and gastroesophageal junction cancers have a poor prognosis despite improvements in curative treatment. Achieving microscopically cancer-free resection margins is essential for long-term outcomes, yet a substantial risk of microscopic positive margins remains. Neoadjuvant therapy can render tumors macroscopically undetectable, potentially increasing this risk. This study aimed to evaluate the performance and safety of a liquid fiducial marker for preoperative marking of the proximal resection margin before neoadjuvant oncological therapy. Methods This was a prospective cohort study. Participants scheduled for neoadjuvant oncological therapy and esophagectomy had the fiducial marker endoscopically implanted in the circumference of the esophagus, five cm proximal to the tumor, to mark the intended resection border. Marker placement was performed before the initiation of neoadjuvant therapy. During esophagectomy, the surgeon’s proposed proximal resection margin was marked, and intraoperative ultrasonography was used to locate the marker. The distance between the marking and the proposed resection line was measured. Results Ten participants were included. Technical success of marker injection was achieved in all cases, without adverse events. The mean implantation time was 214.6 seconds (±38.8). The marker was visualised intraoperatively in 70% of patients, and was seen as a hypodense, oval-shaped structure. The mean distance from the marker to the resection line was 30.7 mm (±22.1). Conclusion Preoperative placement of a liquid fiducial marker to delineate the esophageal resection margin was technically feasible and safe. In 70% of cases, the marker was identified intraoperatively using ultrasonography and was consistently located distal to or at the surgeon’s proposed resection line.

Anastomotic leakage (AL) is a significant complication following esophagectomy. AL affects 8%-17% of patients and is associated with increased morbidity, mortality, and hospital stay. To this date, no consensus exists on the most optimal treatment. This systematic review aimed to determine the most effective treatment approach. A systematic search of Medline, Web of Science, Cochrane, Scopus, and Embase databases was conducted. Only studies reporting on the treatment of intrathoracic anastomotic leakage after esophagectomy with gastric conduit reconstruction for cancer were included. Studies investigating other esophageal disorders or failing to report the location of the anastomosis were excluded. The methodological quality and risk of bias were assessed using the Newcastle-Ottawa Scale for cohort studies. Out of 12,966 identified studies, 38 were included for analysis after removing duplicates and screening titles, abstracts, and full texts. Of these, five were found to be of poor methodological quality and 33 were of moderate quality. The most researched treatment methods were Endoluminal vacuum therapy (EVT), naso-fistula tube drainage (NFTD), and stent treatment. The success and mortality rates for EVT were 82% and 10.7%, for NFTD, 94% and 5.2%, and, for stent treatment, 75.1% and 13.5%, respectively. AL can be effectively treated with EVT, stent treatment, and NFTD. The NFTD approach appeared to have a higher success rate and lower mortality than other treatment modalities. However, it requires a longer treatment duration. Due to limitations within the included studies, a definitive recommendation regarding the optimal treatment for AL cannot be made.

In recent years, the utility of positron emission tomography/magnetic resonance imaging (PET/MRI) has become increasingly significant in diagnostic settings. This study provides a five-year follow-up on a previous pilot study that demonstrated the feasibility of PET/MRI in predicting the resectability of adenocarcinoma of the esophagogastric junction (AEG). We aimed to evaluate whether this imaging modality could further serve as a prognostic tool for survival in AEG patients. A total of 22 patients were included in the initial pilot study, with 17 of them undergoing surgery. All patients underwent three series of neo-adjuvant chemotherapy (NT). This follow-up study retrospectively analyzed the correlation between the apparent diffusion coefficient (ADC) and standard uptake value (SUV) measurements of the primary tumor from the original study with overall survival and recurrence. ADC and SUV values were measured prior to initiation of NT, and again 17–21 days into the first cycle of NT-administration, and the differences between the scans were calculated as ∆SUVmax, ∆ADCb0, and ∆ADCb50. Early treatment response was assessed using the Response Evaluation Criteria In Solid Tumors (RECIST). Binary logistic regression was employed to evaluate the predictive values of ADC and SUV parameters, and receiver operating characteristic (ROC) curves were generated to determine sensitivity, specificity, and area under the curve (AUC). As of January 7, 2022, 8 of the 22 patients were still alive. The AUC was calculated to assess the association of imaging parameters with long-term survival: ∆SUVmax: AUC = 0.74, sensitivity, 87.5

Delayed gastric conduit emptying (DGCE) after esophagectomy is a major cause of morbidity and reduced quality of life. The reported incidence varies greatly (2.2-47%), partly due to a lack of consensus on the definition of DGCE. Recently, an international expert consensus proposed diagnostic criteria for Early-DGCE (E-DGCE) and Late-DGCE (L-DGCE) alongside a symptom severity score. Using these criteria, we investigated the incidence and predictors of DGCE in a large cohort. All patients undergoing esophagectomy with pyloroplasty at Rigshospitalet, Denmark, between 2016 and 2021 were reviewed. E- and L-DGCE were defined using the proposed criteria (5-14 days and > 14 days after surgery, respectively). Specialist nurses followed patients for up 2 years at predefined intervals. About 387 patients were included. The incidence of E-DGCE was 174/387 (45%), and 155/387 (40%) patients presented with L-DGCE at least once during follow-up. The highest prevalence of L-DGCE (19.6%) was identified at postoperative day 28 (POD28) but decreased to 2.9% at the 2-year follow-up. A BMI of ≥30 was a predictor of E-DGCE (P = 0.004) and L-DGCE at POD28 (P = 0.01). No association between E-DGCE and L-DGCE was identified. Using the proposed criteria, the incidence of E-DGCE and prevalence of L-DGCE at POD28 was high. The prevalence of L-DGCE was dynamic but decreased greatly during follow-up. Future prospective studies with multiple follow-ups are needed to validate our findings and the usefulness of the criteria in a clinical setting.

Background Although fluorescence guidance during various surgical procedures has been shown to be safe and have possible better clinical outcomes than without the guidance, the use of fluorophores in pancreatic surgery is novel and not yet well described. This scoping review involved a systematic methodology of the currently available literature and aimed to illuminate the use of fluorophores in pancreatic surgery from a clinical view. Methods The PRISMA and the PRISMA-ScR guidelines were used when appropriate and the following databases were searched: PubMed, Embase, Scopus, The Cochrane Collection, and Web of Science. Human original articles and case reports were included. Bias was assessed with the Newcastle-Ottawa Scale and the IDEAL framework was used for evaluation of surgical innovation. Results A total of 5,565 search hits were screened, and 23 original articles and 24 case reports consisting of 754 patients met the inclusion criteria. The use of indocyanine green was both the most prominent and the most promising method for securing sufficient perfusion of neighboring organs, enhancing the detection and distinguishing of neuroendocrine tumors, and assisting in the identification of hepatic micrometastases. Conclusion The included studies were generally heterogenic, exploratory, and small. Indocyanine green was used in several ways, and it may add clinical value in different settings during pancreatic surgery. Tumor-targeted probes are a rapidly developing and promising field of research.

Gastric cancer remains a major clinical challenge with poor prognosis. This study investigated survival outcomes based on treatment strategy, tumor stage, and histology in Danish gastric cancer patients. From January 2013 to December 2021, 2,156 gastric cancers were registered in the Danish Esophagogastric Cancer Group database, covering 99

BACKGROUND:Barrett's esophagus high-grade dysplasia (BE HGD) can transform into esophageal adenocarcinoma (EAC) in 19-28 % of the cases. Calcium electroporation (Ca-EP) is a novel anti-cancer therapy where electrical pulses are combined with a local injection of calcium to increase intracellular calcium levels leading to cell death. Calcium electroporation has shown effect on premalignant conditions, and a relative sparing of normal tissue. METHODS:The primary aim of this study was to establish safety with Ca-EP in patients with BE HGD. Six patients with BE HGD scheduled for an endoscopic submucosal dissection (ESD) were treated with Ca-EP six weeks before under general anesthesia in an outpatient setting. All adverse events (AEs) were registered, and patients were evaluated with gastroscopy within one week. RESULTS:AEs included retrosternal pain, throat irritation, coughing, and headache. No serious adverse events were registered. A hyperemic area was seen in four patients directly after Ca-EP. Fibrinous coatings (four patients) and ulcers (four patients) were observed up to one week after treatment. One patient underwent two CTA scans due to pain and a visually large fibrinous clot. CTA showed no sign of perforation. Six weeks after five patients had a partial visual response with new squamous epithelium. However, all patients still had BE HGD. CONCLUSION:Ca-EP was safe in patients with BE HGD. This study paves the way for more extensive studies to investigate the effect on dysplastic cells and its role in treating esophageal adenocarcinoma.

INTRODUCTION:Approximately 1 million people live with ileostomies and rely on stoma bags in their daily lives. They do not have access to alternative products. To address alternatives, InterPoc™, an absorbent intestinal tampon, has been developed. However, its safety and efficacy in humans have not yet been assessed. AIM:This study aimed to evaluate the safety and efficiency of InterPoc by assessing pain, vital parameters, mucosal lesions and tampon insertion/removal. METHOD:Eight adults with ileostomies were enrolled in a pilot safety study. InterPoc was inserted into the stoma and stayed in for a maximum of 6 hours; it was removed earlier if discomfort was reported. Over this period, all participants fasted but were allowed to drink up to 2 litres of clear fluids. Hourly examinations were conducted to assess vital signs, pain and discomfort. All patients received a follow-up phone call 24 hours after removal of InterPoc. RESULTS:Eight participants were included of 21 who were screened. The InterPoc tampon had a median insertion duration of 3 hours and a median removal weight of 58.5 grams. One participant had the InterPoc inserted for 6 hours. No mucosal lesions, ischaemia, bleeding or major complications were registered during the observation period. No pain or discomfort was reported 24 hours after InterPoc removal. Vital signs remained stable with no Early Warning Score (EWS) higher than 1. CONCLUSION:The study demonstrated that InterPoc was safe and well tolerated in adults with an ileostomy, with no reported complications during the 24-hour follow-up period.

BACKGROUND Neoadjuvant therapy can reduce the size of gastroesophageal tumors to the extent that they are no longer macroscopically visible. This may increase the risk of microscopic-positive resection margins. One potential method to reduce this uncertainty could be the preoperative endoscopic marking of proximal tumor margins with BioXmark®, a novel liquid fiducial marker. This study aimed to report the initial experiences of the first ten patients marked with BioXmark®. AIM To evaluate the visibility of BioXmark® on ultrasound after preoperative marking of the proximal resection line of an esophageal tumor. METHODS The circumference of the esophagus was endoscopically marked preoperatively with a fiducial marker in four quadrants, 5 cm proximal to the tumor. During the surgery, the surgeon’s proposed proximal resection line was marked. Next, an ultrasound probe was used to identify the previously placed fiducial markers, and its placement was marked. The difference between the surgeon’s proposed resection line and the fiducial marker was measured intraoperatively and subsequently examined with respect to the resection margin and status. RESULTS BioXmark® was implanted in ten patients, 5 cm proximal to the tumor. The surgeon’s proposed resection line was positioned 2-6 cm proximally to the surgical marker line. Technical success of injecting the fiducial marker was achieved in all ten patients. In six patients, the marker was successfully identified intraoperatively on ultrasound. No peri- or postoperative adverse events related to BioXmark® implantation were found. CONCLUSION Excellent technical success with the implantation of the fiducial surgical marker was achieved, but limited intraoperative visibility on ultrasound was achieved. Further studies are required to optimize its clinical application.

AIM:Although vital signs have a well-described 24-h cyclic variation (circadian rhythm), this variation is often not considered in clinical vital sign monitoring despite being influenced by physiologic stress from complications. This study aimed to evaluate the lowest heart rate at night (night-nadir) (NN-HR) as a novel risk marker for serious adverse events (SAE) in postoperative patients, rather than the average nocturnal heart rate. METHODS:This was a propensity-matched nested case-control study of continuously monitored vital sign data (heart rate (HR), respiration rate, oxygen saturation and blood pressure) for up to 5 days after major non-cardiac surgery. The primary outcome was any SAE that occurred up to 24 h after a circadian value calculation. We compared NN-HR between patients who developed SAE and those who did not during similar postoperative periods. RESULTS:Out of 588 patients, 104 (17.8 %) experienced an SAE during the monitored period and were matched with a median of 201 controls. The NN-HR was significantly higher in patients with impending SAE (median 74.0 bpm [IQR 68.2-81.8] vs. 68.3 bpm [IQR 61.5-76.0], p < 0.001). An NN-HR threshold of >67 bpm identified patients at increased risk (risk ratio 2.43, 99 % CI 1.24-5.00) for SAE, however with only moderate predictive performance (F1 score 0.58). CONCLUSION:Absence of HR below 67 bpm at night, was significantly associated with increased SAE risk, highlighting the potential value of NN-HR as a monitoring target.The potential clinical utility of monitoring NN-HR to prevent SAE warrants further prospective investigation.