Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Postoperative Ileus Following Minimally Invasive Colorectal Resection: A Single-Center Randomized Controlled Trial

Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Postoperative Ileus Following Minimally Invasive Colorectal Resection: A Single-Center Randomized Controlled Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Postoperative Ileus Following Minimally Invasive Colorectal Resection: A Single-Center Randomized Controlled Trial Tingting Wei, Jing Liu, Baoqiang Di, Ying Lei, Sirui Cheng, Fei Ge, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8241477/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Postoperative ileus (POI) is a common complication after colorectal surgery, leading to delayed recovery and prolonged hospitalization. Although vagus nerve stimulation has shown promise in enhancing gastrointestinal motility in preclinical and early clinical studies, evidence in the perioperative setting remains limited. This study evaluated whether perioperative transauricular vagus nerve stimulation (taVNS) could improve postoperative bowel recovery in patients undergoing minimally invasive colorectal resection. Methods In this randomized, sham-controlled trial, 79 patients scheduled for elective minimally invasive colorectal resection were assigned to receive either taVNS or sham stimulation. The primary outcome was time to first defecation (TFD). Secondary outcomes included time to first flatus (TFF), time to tolerance of semisolid food (TOF), postoperative pain scores, opioid consumption, postoperative complications, length of stay, 30-day readmission, and perioperative inflammatory markers. Analyses followed the intention-to-treat principle. Results Compared with the sham group, the taVNS group demonstrated significantly shorter TFD (71.5 [62.0–89.8] vs. 90.0 [63.5–114.5] hours; adjusted hazard ratio [HR] 2.04, 95% CI 1.22–3.40; p = 0.01) and TOF (116.0 [108.0–135.0] vs. 133.5 [114.0–161.5] hours; adjusted HR 1.85, 95% CI 1.12–3.07; p = 0.02). The taVNS group exhibited a smaller postoperative day-1 increase in white blood cell count (β = −0.14, 95% CI − 0.27 to − 0.01; p = 0.04). Conclusions Perioperative taVNS accelerated gastrointestinal recovery and attenuated early postoperative inflammation following minimally invasive colorectal surgery. These findings support taVNS as a promising noninvasive strategy to reduce POI, meriting confirmation in larger multicenter studies. Trial registration ChiCTR2400083015, registered April 13, 2024. Transcutaneous auricular vagus nerve stimulation Postoperative ileus Colorectal surgery Gastrointestinal recovery Neuromodulation Randomized controlled trial Figures Figure 1 Figure 2 Figure 3 Introduction Surgery remains the preferred treatment for colorectal cancer; however, 36%–78% of patients experience postoperative gastrointestinal dysfunction, including abdominal distension, irritation, constipation, and postoperative intestinal obstruction (POI). POI has a multifactorial etiology and is associated with prolonged hospital stay, increased risk of complications, and higher healthcare costs [ 1 ] . Although various strategies have been investigated to prevent POI and its clinical sequelae—such as early feeding or sham feeding (chewing gum), intravenous lidocaine, neostigmine, erythromycin, and cholecystokinin—none have demonstrated consistent or clinically significant efficacy [ 2 ] . In recent years, increasing attention has been given to the role of the autonomic nervous system in modulating gastrointestinal function and inflammation. Activation of the vagus nerve has been shown to promote gastrointestinal motility and exert anti-inflammatory effects through the cholinergic anti-inflammatory pathway [ 3 , 4 ] . Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) provides a feasible method to activate vagal pathways and has been tested in several perioperative and gastrointestinal settings with promising results [ 5 , 6 ] . However, evidence regarding its efficacy in preventing POI following colorectal surgery remains limited. Therefore, we conducted a randomized controlled trial to evaluate whether perioperative taVNS could accelerate gastrointestinal recovery and reduce inflammatory response in patients undergoing minimally invasive colorectal resection. Methods Ethics and governance This prospective, single-center, randomized, single-blind pilot trial was conducted between July 2024 and April 2025 at Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University. The study was registered at ClinicalTrials.gov (ChiCTR2400083015, https://www.chictr.org.cn/showproj.html?proj=219458 ) on April 13, 2024, and received approval from the hospital’s Ethics Committee. Written informed consent was obtained from all participants prior to enrollment. The trial was conducted and reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) 2025 guidelines. Participants All patients who were able to independently provide informed consent and were scheduled to undergo elective minimally invasive colorectal resection (either laparoscopic or robotic, without a planned stoma) were eligible for inclusion. Exclusion criteria included active opioid abuse; major cardiovascular conditions such as myocardial infarction within the past six months, NYHA class ≥ 3, second- or third-degree atrioventricular block, permanent atrial fibrillation/flutter, or a history of ventricular tachycardia/fibrillation; epilepsy; confirmed chronic gastrointestinal inflammatory diseases. Patients were also excluded if they had a history of abdominal surgery or intestinal obstruction, underwent total colectomy, or needed prolonged intensive care (> 1 day) due to intraoperative or postoperative complications. Specific exclusions included skin rash or ear infection and severe adhesive tape allergy. Randomization and Blinding After obtaining written informed consent, patients were randomly assigned in a 1:1 ratio to receive either active or sham stimulation. Randomization was conducted using computer-generated random sequence numbers, 1 hour prior to the first preoperative intervention. During the study, only the personnel responsible for randomization and those administering the intervention were aware of the group assignments. Participants, postoperative care providers, and data analysts remained blinded to the allocation throughout the study period. All patients were informed that they might or might not perceive any sensation during stimulation, regardless of group assignment. Study protocol In this study, a standardized perioperative management pathway based on the Enhanced Recovery After Surgery protocol was applied to all participants. All patients underwent general anesthesia with endotracheal intubation. Balanced crystalloids were administered as the primary infusion fluid to prevent both excessive fluid overload and inadequate perfusion. Nasogastric tubes were not routinely placed. Multimodal analgesia was employed in all cases. All patients underwent bilateral transversus abdominis membrane nerve block or local incision infiltration before the end of surgery. Postoperatively, patient-controlled analgesia (PCA) with a standardized sufentanil regimen was provided. Patients were encouraged to resume oral fluids as early as possible and to gradually progress to a regular diet, along with early mobilization. Interventions Patients were fitted with an auricular vagus nerve stimulator (tVNS501, Ruishen An Medical Devices Co., Ltd., Changzhou, Jiangsu Province, China), positioned on the right cymba conchae [ 7 ] . Patients in the stimulation group received low intensity taVNS with the following parameters: a frequency of 25 Hz, pulse width of 250 µs, and alternating cycles of 30 seconds on and 30 seconds off. Stimulation began at an initial current of 10 mA and was gradually increased. Once the patient reported a tingling sensation within 20 seconds of stimulation onset, the current was adjusted to a level just below the sensory threshold (typically 20–60 mA). In the sham group, the electrode placement and stimulation parameters were identical to those in the stimulation group; however, the stimulator was turned off after the patient reported a tingling sensation, ensuring blinding. Stimulation was administered for 1 hour in the morning before surgery and was continued intraoperatively and for 30 minutes postoperatively. On postoperative day (POD) 1 and 2, patients received 1 hour of stimulation each morning. Outcomes and measures Patient characteristics were collected, including age, sex, height, weight, and American Society of Anesthesiologists classification, as well as histories of hypertension, diabetes mellitus, ischemic heart disease, valvular heart disease, stroke, infectious diseases, and cancer. Information on preoperative medication use was obtained, covering statins, β-blockers, anticoagulants, antiplatelet agents, calcium channel blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, other antihypertensive drugs, corticosteroids, metformin, insulin, other antidiabetic agents, opioids, and probiotics. Preoperative laboratory variables included C-reactive protein (CRP), absolute white blood cell (WBC) count, absolute neutrophil count, hemoglobin, aspartate aminotransferase, alanine aminotransferase, creatinine, and albumin levels. Surgical variables were also recorded, including duration of surgery, surgical approach, specific procedure performed, conversion to open surgery, unplanned stoma formation, lesion length, TNM stage, intraoperative fluid volume, urine output, and blood loss. Primary outcome Time to first postoperative defecation (TFD) (in hours): the interval between the end of surgery and the first observed stool passage [ 8 ] . Secondary outcome Secondary outcomes included time to first flatus (TFF), defined as the interval from the end of surgery to the first passage of flatus, and time to oral tolerance of semisolid food (TOF), defined as the absence of significant nausea or vomiting within 4 hours after ingestion of semisolid food. Additional outcomes comprised postoperative pain scores on days 1 to 3, assessed using a 10-point visual analogue scale (VAS; 0 = no pain, 10 = worst pain imaginable), cumulative opioid consumption via PCA, length of hospital stay (LOS), and postoperative complications, including poor wound healing, intestinal obstruction, infection, bleeding, intestinal fistula, hepatic insufficiency, hypoproteinemia, and readmission within 30 days after surgery. Postoperative laboratory markers—CRP, absolute WBC count, and absolute neutrophil count—were recorded on POD 1 and 3. Sample size and statistics The sample size was estimated based on data from a pilot study, in which the mean TFD after laparoscopic or robotic colorectal surgery was 70.2 hours. taVNS was found to reduce the mean time to 69.0 hours, with a standard deviation (SD) of 2.0 in both groups. Using G*Power software (version 3.1.9.7) for a two-sided test with a significance level of α = 0.05 and a power (1 − β) of 0.80, the calculated sample size was 35 patients per group. To account for an anticipated 10% dropout rate in clinical studies, the total sample size was increased to 80 patients, with 40 patients allocated to each group. All analyses were performed on an intention-to-treat basis. Continuous variables were expressed as mean ± SD or median [interquartile range (IQR)], depending on data distribution assessed by the Shapiro–Wilk test. Categorical variables were summarized as counts (percentages). Between-group comparisons were conducted using the Chi-squared or Fisher’s exact test for categorical variables, and either the Student’s t -test or Mann–Whitney U test for continuous variables, as appropriate. Kaplan–Meier curves were generated for the primary outcome and for the secondary outcomes (TFF and TOF). Postoperative changes in inflammatory markers (CRP, WBC, and neutrophil count) and VAS were analyzed using linear mixed-effects models (LMMs). Because of non-normal distributions, inflammatory and VAS data were log-transformed prior to analysis. Each model included Group, Time, and their interaction (Group × Time) as fixed effects, with patient ID as a random intercept. A compound symmetry covariance structure was chosen, as it provided comparable model fit to an autoregressive AR (1) structure (ΔAIC < 2). If the treatment-by-time interaction did not meet the pre-specified significance threshold ( p ≥ 0.20), the interaction term was removed, and overall group effects were reported across all time points. When significant, treatment effects were reported separately for each time point, with Bonferroni-adjusted pairwise comparisons. A two-sided p value < 0.05 was considered statistically significant. All analyses were performed using R Studio (version 2024.09.0 + 375). Results Patient recruitment、baseline characteristics and surgical variables Patient recruitment is summarized in the flow chart (Fig. 1 ). Between July 2024 and April 2025, a total of 217 patients were screened, of whom 79 met the inclusion criteria and were randomized to the stimulation group (n = 39) and the sham stimulation group (n = 40). Only one patient in the stimulation group refused postoperative stimulation due to ear discomfort. All 79 patients completed the study with no loss to follow-up, and all were included in the intention-to-treat analysis. Baseline characteristics were well balanced between the two groups (Table 1 ). Surgical and intraoperative variables are summarized in Table 2 . The median operation time was 145.0 (115.0–182.5) minutes in the stimulation group and 152.5 (125.8–181.3) minutes in the sham stimulation group ( p = 0.28). The intraoperative volumes of crystalloid and colloid were 1500.0 (1000.0–1500.0) mL in the stimulation group and 1500.0 (1475.0–1500.0) mL in the sham stimulation group ( p = 0.25). Intraoperative urine output was 300.0 (200.0–450.0) mL in the stimulation group and 300.0 (200.0–525.0) mL in the sham stimulation group ( p = 0.22). The proportions of patients according to surgical approach, procedures performed, conversion to open surgery, unplanned stoma formation, and pathological TNM stage were similar between the two groups. No significant differences were observed in lesion length or estimated blood loss. Table 1 Demographic and clinical features of treated patients at entry Variables Stimulation group (n = 39) Sham stimulation group (n = 40) p -value Age, year, median (IQR) 64.0 (55.5–71.0) 62.0 (54.0–72.3) 0.68 Sex, n (%) 0.53 Male 27 (69.2%) 24 (60.0%) Female 12 (30.8%) 16 (40.0%) Height, cm, mean ± SD 165.2 ± 9.4 163.9 ± 7.1 0.52 Weight, kg, mean ± SD 62.9 ± 9.9 64.3 ± 13.0 0.59 ASA classification, n (%) > 0.99 II 36 (92.3%) 37 (92.5%) III 3 (7.7%) 3 (7.5%) History of hypertension, n (%) 12 (30.8%) 14 (35.0%) 0.87 History of diabetes mellitus, n (%) 3 (7.7%) 4 (10.0%) > 0.99 History of ischemic heart disease, n (%) 0 (0.0%) 1 (2.5%) > 0.99 History of valvopathy, n (%) 1 (2.6%) 1 (2.5%) > 0.99 History of stoke, n (%) 0 (0.0%) 1 (2.5%) > 0.99 History of infectious diseases, n (%) 0 (0.0%) 0 (0.0%) > 0.99 History of cancer, n (%) 4 (10.3%) 4 (10.0%) > 0.99 Statins, n (%) 3 (7.7%) 4 (10.0%) > 0.99 Beta blockers, n (%) 3 (7.7%) 4 (10.0%) > 0.99 Anticoagulant, n (%) 1 (2.6%) 0 (0.0%) 0.49 Antiplatelet, n (%) 2 (5.1%) 2 (5.0%) > 0.99 Calcium channel blocker, n (%) 8 (20.5%) 10 (25.0%) 0.84 ACEI/ARB, n (%) 3 (7.7%) 5 (12.5%) 0.71 Other antihypertensive agents, n (%) 0 (0.0%) 4 (10.0%) 0.12 Corticosteroids, n (%) 0 (0.0%) 1 (2.5%) > 0.99 Metformin, n (%) 3 (7.7%) 3 (7.5%) > 0.99 Insulin, n (%) 0 (0.0%) 1 (2.5%) > 0.99 Other antidiabetic agents, n (%) 3 (7.7%) 2 (5.0%) 0.68 Preoperative opioid use, n (%) 0 (0%) 0 (0%) > 0.99 Probiotics, n (%) 0 (0%) 0 (0%) > 0.99 Hb, g/L, mean ± SD 126.3 ± 22.6 127.2 ± 24.1 0.87 AST, U/L, median (IQR) 20.0 (17.0–22.5) 20.5 (17.0–27.0) 0.63 ALT, U/L, median (IQR) 16.0 (11.5–21.5) 17.0 (11.8–23.0) 0.63 Creatinine, µmol/L, median (IQR) 70.0 (64.0–84.0) 69.0 (60.5–75.3) 0.38 Albumin, g/L, median (IQR) 39.8 (36.7–42.3) 40.4 (37.3–43.6) 0.47 Abbreviations: IQR, interquartile range; SD: standard deviation; ASA, American Society of Anesthesiologists; Hb, hemoglobin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; TBIL, total bilirubin; ACEI/ARB, angiotensin converting enzyme inhibitor/angiotensin receptor antagonist. Table 2 Procedure and pathology characteristics Variables Stimulation group (n = 39) Sham stimulation group (n = 40) p- value Duration of surgery, min, median (IQR) 145.0 (115.0–182.5) 152.5 (125.8–181.3) 0.28 Procedural approach, n (%) > 0.99 Laparoscopic 35 (89.7%) 35 (87.5%) Robotic 4 (10.3%) 5 (12.5%) Procedure, n (%) 0.43 Anterior resection 9 (23.1%) 11 (27.5%) Sigmoid colectomy 20 (51.3%) 12 (30.0%) Right hemicolectomy 7 (17.9%) 10 (25.0%) Left hemicolectomy 1 (2.6%) 4 (10.0%) Transverse colectomy 1 (2.6%) 2 (5.0%) Extended right hemicolectomy 1 (2.6%) 1 (2.5%) Conversion to open surgery, n (%) 0 (0%) 1 (2.5%) > 0.99 Unplanned stoma formation, n (%) 1 (2.6%) 1 (2.5%) > 0.99 Length of the lesion, cm, mean ± SD 3.7 ± 2.0 4.0 ± 1.9 0.47 Tumor T stage, n (%) 0.31 T0 (premalignant) 2 (5.7%) 1 (2.6%) T1 8 (22.9%) 5 (12.8%) T2 6 (17.1%) 5 (12.8%) T3 16 (45.7%) 18 (46.2%) T4 3 (8.6%) 10 (25.6%) Tumor N stage, n (%) 0.61 N0 20 (57.1%) 18 (46.2%) N1 13 (37.1%) 17 (43.6%) N2 2 (5.7%) 4 (10.3%) Tumor M stage, n (%) > 0.99 M0 34 (97.1%) 37 (94.9%) M1 1 (2.9%) 2 (5.1%) Intraoperative volume of crystalloid and colloid, mL, median (IQR) 1500.0 (1000.0–1500.0) 1500.0 (1475.0–1500.0) 0.25 Intraoperative urine output, mL, median (IQR) 300.0 (200.0–450.0) 300.0 (200.0–525.0) 0.22 Intraoperative blood loss, mL, median (IQR) 50.0 (20.0–50.0) 50.0 (20.0–50.0) 0.84 Abbreviations: IQR: interquartile range; SD, standard deviation. Primary outcome The TFD was significantly shorter in the stimulation group compared with the sham stimulation group (71.5 [62.0-89.8] vs. 90.0 [63.5-114.5] hours). The unadjusted Cox analysis showed hazard ratio (HR) = 1.84 (95% confidence interval [CI], 1.13–2.98; p = 0.01), and after adjustment for operative duration, total fluid input, and intraoperative urine output, the effect remained significant (adjusted HR = 2.04, 95% CI, 1.22–3.40; p = 0.01) (Fig. 2 A, Table 3 ). Table 3 Primary outcome Primary outcome Stimulation group (n = 39) Sham stimulation group (n = 40) Effect estimate (95% CI) p- value Unadjusted Adjusted Unadjusted Adjusted Time to first defecation, hours, median (IQR) 71.5 (62.0-89.8) 90.0 (63.5-114.5) 1.84 (1.13–2.98) 2.04 (1.22–3.40) 0.01 0.01 Effect estimates are expressed as hazard ratios with 95% confidence intervals. Both unadjusted and adjusted analyses are shown. Adjustment was performed for operative duration, total fluid input, and intraoperative urine output using a Cox proportional hazards model. Abbreviations: CI, confidence interval; IQR, interquartile range. Secondary outcomes For the TFF, the median duration was shorter in the stimulation group (45.0 [26.0–60.5] hours) compared with the sham group (51.5 [41.8–67.0] hours). The unadjusted model suggested a trend toward faster recovery (HR = 1.52, 95% CI, 0.96–2.40; p = 0.07), but this association was not significant, and the adjusted model yielded consistent results (adjusted HR = 1.35, 95% CI, 0.85–2.15; p = 0.21). In contrast, the TOF was significantly shorter in the stimulation group (116.0 [108.0–135.0] hours) compared with the sham group (133.5 [114.0–161.5] hours). This effect was significant both before and after covariate adjustment (unadjusted HR = 2.03, 95% CI, 1.26–3.29; p < 0.01; adjusted HR = 1.85, 95% CI, 1.12–3.07; p = 0.02) (Fig. 2 B–C, Table 4 ). Table 4 Secondary outcomes Outcome Stimulation group(n = 39) Sham stimulation group(n = 40) Effect estimate (95% CI) p -value Time to first flatus, hours, median (IQR) 45.0 (26.0–60.5) 51.5 (41.8–67.0) 1.35 (0.85–2.15) 0.21 a Time to tolerance of semisolid diet, hours, median (IQR) 116.0 (108.0–135.0) 133.5 (114.0–161.5) 1.85 (1.12–3.07) 0.02 a VAS, scores, median (IQR) POD1 2 (2–3) 2 (2–2) -0.07 (-0.20, 0.07) 0.34 b POD2 1 (1–2) 1 (1–2) -0.09 (-0.23, 0.04) 0.18 b POD3 1 (1–1.5) 1 (1–2) 0.02 (-0.12, 0.16) 0.76 b Cumulative PCA usage, µg, mean ± SD 95.5 ± 48.7 98.3 ± 34.2 -2.76 (-21.70, 16.18) 0.77 c Length of hospital stay, days, median (IQR) 11.0 (10.0–13.5) 12.0 (9.8–15.0) -0.00 (-2.00, 1.00) 0.50 d Postoperative complications, n (%) 3 (7.7%) 5 (12.5%) 0.62 (0.16–2.40) 0.71 e Hospital readmission, n (%) 1 (2.6%) 3 (7.5%) 0.34 (0.04, 3.15) 0.62 e Effect estimates are presented as hazard ratios for time-to-event outcomes, mean differences for normally distributed continuous outcomes, median differences for non-normally distributed continuous outcomes, and relative risks for categorical outcomes, each with 95% confidence intervals. Abbreviations: CI, confidence interval; IQR, interquartile range; VAS, visual analogue scale; POD, postoperative day; PCA, patient-controlled analgesia; SD, standard deviation. The following statistical methods were applied according to data type and distribution: a, Cox proportional hazards model with log-rank test, adjusted for operative duration, total fluid input, and intraoperative urine output. b, Linear mixed-effects model on log-transformed values, adjusted for operative duration, total fluid input, and intraoperative urine output. Because the treatment-by-time interaction did not exceed the pre-specified threshold of P ≥ 0.20, group differences were examined at each postoperative time point. c, Independent samples t-test. d, Wilcoxon rank-sum test. e, Fisher’s exact test. Pain scores measured by VAS significantly declined over time in both groups (time effect, p < 0.001). The treatment-by-time interaction was below the pre-specified threshold ( p = 0.14 < 0.20), and therefore group differences were examined at each time point. Adjusted analyses revealed no significant differences between stimulation and sham groups at POD 1–3. Descriptive statistics (median [IQR]) are summarized in Table 4 . No significant differences were observed between the groups in cumulative PCA usage, postoperative complications, LOS, or 30-day readmission rates. Postoperative complications occurred in three patients (7.7%) in the stimulation group—two with hepatic insufficiency and one with hypoalbuminemia—and in five patients (12.5%) in the sham stimulation group—two with hepatic insufficiency, one with hypoalbuminemia, one with poor wound healing, and one with postoperative infection. Readmissions occurred in one patient in the stimulation group (due to anastomotic leakage) and three patients in the sham stimulation group (due to intestinal obstruction, pseudomembranous colitis, and ureteral stricture, respectively) (Table 4 ). Postoperative laboratory findings All inflammatory markers increased significantly after surgery (time effect, p < 0.001 for all outcomes). For CRP, the treatment-by-time interaction did not exceed the pre-specified threshold. Therefore, the interaction term was excluded, and overall group comparisons across all time points showed no significant difference between stimulation and sham groups (adjusted β = -0.06, 95% CI -0.35 to 0.23, p = 0.69). For neutrophils, the treatment-by-time interaction also did not exceed the threshold. The overall analysis indicated no significant group difference (adjusted β = 0.05, 95% CI -0.08 to 0.18, p = 0.46). For WBC, the treatment-by-time interaction was below the threshold, and thus post hoc comparisons were conducted. At POD 1, the stimulation group exhibited a significantly smaller increase in WBC compared with the sham group (adjusted β = -0.14, 95% CI -0.27 to -0.01, p = 0.04), whereas no differences were observed at the preoperative or POD 3 time points. Detailed results are presented in Table 5. The temporal patterns of CRP, WBC, and neutrophil counts, expressed as log-transformed estimated means with 95% CI, are illustrated in Fig. 3 . Table 5. Inflammatory outcomes Outcome Stimulation group (n=39) Sham stimulation group (n=40) Effect estimate (95% CI) P-value Unadjusted Adjusted Unadjusted Adjusted CRP, mg/L, median (IQR) 0.09 (-0.19, 0.37) -0.06 (-0.35, 0.23) 0.53 0.69 a Preoperative 1.4 (0.7–5.0) 1.3 (0.6–3.5) POD1 30.1 (20.8–40.7) 38.5 (25.8–59.5) POD3 27.7 (17.2–66.8) 34.4 (21.8–54.9) WBC, ×10^9/L, median (IQR) Preoperative 4.9 (4.3–7.3) 5.8 (4.6–6.8) 0.02 (-0.13, 0.17) -0.04 (-0.20, 0.11) 0.83 0.59 b POD1 8.3 (4.4–10.0) 7.9 (6.5–10.3) 0.16 (0.01, 0.31) -0.14 (-0.27, -0.01) 0.04 0.04 b POD3 6.0 (4.1–7.2) 6.0 (4.9–7.1) 0.04 (-0.11, 0.19) -0.03 (-0.16, 0.10) 0.58 0.69 b Neutrophils, ×10^9/L, median (IQR) -0.07 (-0.20, 0.06) 0.05 (-0.08, 0.18) 0.29 0.46 a Preoperative 3.9 (2.8–5.7) 3.5 (2.9–4.7) POD1 7.2 (5.7–8.5) 6.1 (5.1–8.9) POD3 4.4 (3.5–5.8) 4.4 (3.6–5.4) Values are presented as median (interquartile range) of the raw data. Between-group differences (sham−stimulation) were estimated using linear mixed-effects models fitted on log-transformed outcomes. Both unadjusted and adjusted estimates are reported; adjusted models included intraoperative urine output, operative duration, and total fluid input as covariates. Abbreviations: CI, confidence interval; CRP, C-reactive protein; IQR, interquartile range; POD, postoperative; WBC, white blood cell. a, Overall group differences were calculated across all time points by collapsing the data over time and excluding the interaction term, as the treatment-by-time interaction exceeded the pre-specified significance threshold of 0.20. b, Group differences were examined at each postoperative time point, as the treatment-by-time interaction did not exceed the pre-specified threshold of 0.20. Discussion In our study, perioperative taVNS improved postoperative gastrointestinal recovery, as evidenced by shorter TFD and TOF. In addition, although taVNS did not reduce postoperative CRP or neutrophil levels, it attenuated the increase in WBC count on POD 1. Preclinical studies have consistently demonstrated that vagus nerve stimulation (VNS) promotes gastrointestinal recovery [ 9 – 15 ] . Yana Wang et al. [ 16 ] reported that minimally invasive left cervical VNS inhibited colon shortening, thereby ameliorating gastrointestinal dysfunction in rats with acute cerebral ischemia–reperfusion injury. Hong Gun-Soo et al. [ 11 ] demonstrated that taVNS could attenuate POI in mice. In recent years, clinical studies investigating taVNS for improving gastrointestinal function have also increased. Jie Liu et al. [ 17 ] reported that taVNS could alleviate constipation and abdominal pain symptoms in patients with constipation-predominant irritable bowel syndrome. Consistent with previous findings, studies by Huang et al. [ 5 ] and Ru O et al. [ 6 ] demonstrated that taVNS can accelerate postoperative bowel recovery by reducing TFF in patients undergoing gastrointestinal surgery. However, a multicenter study involving patients with diabetes and autonomic neuropathy reported that cervical taVNS did not improve gastrointestinal symptoms in this population [ 18 ] . Interestingly, although our data suggested a trend toward shorter TFF, this difference did not reach statistical significance. This discrepancy may be attributed to our relatively small sample size or to differences in stimulation parameters (such as frequency, intensity, and duration), which warrant further investigation. Preclinical models have demonstrated that VNS can suppress intestinal inflammation and shorten the duration of POI [ 9 , 11 , 15 ] . Several clinical studies have also shown that VNS attenuates inflammatory responses in intestinal disorders. For instance, Sinniger et al. [ 19 ] reported that left cervical VNS significantly decreased CRP levels in patients with Crohn’s disease. Similarly, Stakenborg et al. [ 20 ] observed that intra-abdominal VNS during pancreaticoduodenectomy reduced interleukin-6 (IL-6) concentrations in the duodenal mucosa two hours postoperatively, although serum IL-6, IL-8, and tumor necrosis factor-α levels remained unchanged. In contrast, a clinical study involving patients undergoing laparoscopic rectal resection demonstrated that taVNS significantly lowered serum IL-6 concentrations [ 6 ] . Consistent with these findings, our study showed that taVNS attenuated the postoperative rise in WBC count among patients with colorectal cancer, suggesting a potential systemic anti-inflammatory effect. Further investigations are warranted to determine whether this modulation also extends to intestinal inflammation and contributes to improved local immune regulation. Another important consideration is the potential impact of VNS on postoperative pain. Both preclinical and clinical studies have suggested that VNS may alleviate pain by modulating central nociceptive pathways and suppressing peripheral inflammatory responses [ 21 – 23 ] . However, in our trial, no significant differences were observed in postoperative pain scores between the active and sham stimulation groups. Several factors may account for this finding. First, intraoperative opioid administration was not standardized among patients. Second, all the patients received additional analgesic interventions, such as transversus abdominis plane blocks or local wound infiltration before the end of surgery. As a result, postoperative VAS from day 1 to day 3 were generally low in both groups. Although cumulative opioid consumption tended to be lower in the active group, the difference did not reach statistical significance. Further studies with standardized analgesic protocols are warranted to better elucidate the effect of taVNS on postoperative pain in patients undergoing colorectal cancer surgery. This study has several notable strengths. First, it is among the few randomized controlled trials to investigate the effects of taVNS on postoperative gastrointestinal recovery in patients undergoing minimally invasive colorectal surgery, providing valuable clinical evidence in a field largely supported by preclinical data. Second, standardized perioperative management protocols minimized confounding effects from surgical technique and anesthesia, allowing for a clearer interpretation of the taVNS intervention. Third, the study incorporated both clinical outcomes and inflammatory markers, offering a comprehensive evaluation of efficacy. Finally, the rigorous statistical adjustment for relevant covariates enhanced the robustness and credibility of the findings. However, several limitations of this study should be acknowledged. First, this was a single center trial with a relatively small sample size, which may limit the generalizability of the findings. Second, autonomic nervous system activity (e.g., heart rate variability) was not monitored; therefore, the physiological mechanisms underlying the effects of taVNS on bowel recovery could not be directly verified. Third, long-term outcomes were not assessed, leaving the durability of taVNS effects on postoperative bowel function uncertain. Finally, with respect to safety, although only one patient discontinued postoperative stimulation due to ear discomfort, this indicates that device tolerability could still be improved. Future studies should aim to enhance device comfort, establish standardized criteria for taVNS-related adverse event reporting, and confirm these findings in larger multicenter populations. Conclusions In summary, this randomized controlled trial demonstrated that perioperative taVNS promoted postoperative gastrointestinal recovery in patients undergoing minimally invasive colorectal surgery, as evidenced by shorter TFD and TOF. Additionally, taVNS attenuated the postoperative increase in WBC count, suggesting a potential anti-inflammatory benefit. The procedure was well tolerated, with only mild, transient ear discomfort reported. These findings indicate that taVNS is a safe and feasible adjunctive therapy for enhancing postoperative bowel function. Abbreviations POI postoperative intestinal obstruction taVNS transcutaneous auricular vagus nerve stimulation PCA patient-controlled analgesia POD postoperative day CRP C-reactive protein WBC white blood cell TFD time to first postoperative defecation TFF time to first flatus TOF: time to oral tolerance of semisolid food VAS visual analogue scale LOS length of hospital stay SD standard deviation IQR interquartile range LMM linear mixed-effects model CI confidence interval HR hazard ratio VNS vagus nerve stimulation. Declarations Conflict of Interest: The authors declare that they have no conflict of interest. Human Ethics and Consent to Participate declarations This study was approved by the Ethics Committee of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University. All procedures were conducted in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments. Written informed consent was obtained from all individual participants included in the study. Funding: None. Author Contribution TT Wei conceived and designed the study, supervised clinical implementation, contributed to data analysis and interpretation, and drafted the manuscript.J Liu, BQ Di, Y Lei, SR Cheng, G Fei, D Zheng, YS Jin, and CHY Xu, coordinated patient enrollment and data collection, assisted with data interpretation, and revised the manuscript for important intellectual content.G Chen contributed to study design and ethics preparation and performed data quality control.TT Wei and G Ch serve as the guarantors of this study and take full responsibility for the integrity of the work, from study conception to the decision to publish.All authors reviewed and approved the final manuscript. Data Availability The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. 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2","display":"","copyAsset":false,"role":"figure","size":235469,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan–Meier curves for postoperative gastrointestinal recovery outcomes.\u003c/strong\u003e\u003cbr\u003e\nCumulative incidence curves are shown for (A) time to first defecation, (B) time to first flatus, and (C) time to tolerance of semisolid diet in patients receiving transcutaneous auricular vagus nerve stimulation (stimulation group) versus sham stimulation (sham group). The y-axis represents the cumulative proportion of patients who experienced the respective outcome (1 − survival probability). Solid lines indicate group-specific estimates and shaded areas denote 95% confidence intervals. Log-rank \u003cem\u003ep\u003c/em\u003e-values are displayed within each panel.\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8241477/v1/a3f7a349a446fde9ccb5be4e.jpeg"},{"id":100014566,"identity":"71276df9-3a14-49d1-ab30-8ff63d366fc5","added_by":"auto","created_at":"2026-01-12 06:24:49","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":78499,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTemporal changes in log-transformed inflammatory markers after surgery.\u003cbr\u003e\n \u003c/strong\u003e(A) Log-transformed C-reactive protein (CRP), (B) white blood cell (WBC), and (C) neutrophil in the stimulation and sham groups at preoperative baseline, postoperative day (POD) 1 and 3. Values are presented as estimated means with 95% confidence intervals derived from linear mixed-effects models adjusted for intraoperative urine output, operative duration, and total fluid infusion. Asterisks indicate statistically significant between-group differences at the corresponding time points (*\u003cem\u003ep \u003c/em\u003e\u0026lt; 0.05).\u003c/p\u003e","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8241477/v1/64db1cd7d439e5fa88181bf2.jpeg"},{"id":107705105,"identity":"0b21be68-7b86-4860-99df-96f1ecf3e0dc","added_by":"auto","created_at":"2026-04-24 09:08:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1366409,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8241477/v1/68d08321-9768-43b7-808a-4181459351e8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Postoperative Ileus Following Minimally Invasive Colorectal Resection: A Single-Center Randomized Controlled Trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSurgery remains the preferred treatment for colorectal cancer; however, 36%\u0026ndash;78% of patients experience postoperative gastrointestinal dysfunction, including abdominal distension, irritation, constipation, and postoperative intestinal obstruction (POI). POI has a multifactorial etiology and is associated with prolonged hospital stay, increased risk of complications, and higher healthcare costs\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Although various strategies have been investigated to prevent POI and its clinical sequelae\u0026mdash;such as early feeding or sham feeding (chewing gum), intravenous lidocaine, neostigmine, erythromycin, and cholecystokinin\u0026mdash;none have demonstrated consistent or clinically significant efficacy\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn recent years, increasing attention has been given to the role of the autonomic nervous system in modulating gastrointestinal function and inflammation. Activation of the vagus nerve has been shown to promote gastrointestinal motility and exert anti-inflammatory effects through the cholinergic anti-inflammatory pathway\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) provides a feasible method to activate vagal pathways and has been tested in several perioperative and gastrointestinal settings with promising results\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. However, evidence regarding its efficacy in preventing POI following colorectal surgery remains limited.\u003c/p\u003e \u003cp\u003eTherefore, we conducted a randomized controlled trial to evaluate whether perioperative taVNS could accelerate gastrointestinal recovery and reduce inflammatory response in patients undergoing minimally invasive colorectal resection.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eEthics and governance\u003c/h2\u003e \u003cp\u003eThis prospective, single-center, randomized, single-blind pilot trial was conducted between July 2024 and April 2025 at Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University. The study was registered at ClinicalTrials.gov (ChiCTR2400083015, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.chictr.org.cn/showproj.html?proj=219458\u003c/span\u003e\u003cspan address=\"https://www.chictr.org.cn/showproj.html?proj=219458\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) on April 13, 2024, and received approval from the hospital\u0026rsquo;s Ethics Committee. Written informed consent was obtained from all participants prior to enrollment. The trial was conducted and reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) 2025 guidelines.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eParticipants\u003c/h3\u003e\n\u003cp\u003eAll patients who were able to independently provide informed consent and were scheduled to undergo elective minimally invasive colorectal resection (either laparoscopic or robotic, without a planned stoma) were eligible for inclusion. Exclusion criteria included active opioid abuse; major cardiovascular conditions such as myocardial infarction within the past six months, NYHA class\u0026thinsp;\u0026ge;\u0026thinsp;3, second- or third-degree atrioventricular block, permanent atrial fibrillation/flutter, or a history of ventricular tachycardia/fibrillation; epilepsy; confirmed chronic gastrointestinal inflammatory diseases. Patients were also excluded if they had a history of abdominal surgery or intestinal obstruction, underwent total colectomy, or needed prolonged intensive care (\u0026gt;\u0026thinsp;1 day) due to intraoperative or postoperative complications. Specific exclusions included skin rash or ear infection and severe adhesive tape allergy.\u003c/p\u003e\n\u003ch3\u003eRandomization and Blinding\u003c/h3\u003e\n\u003cp\u003e After obtaining written informed consent, patients were randomly assigned in a 1:1 ratio to receive either active or sham stimulation. Randomization was conducted using computer-generated random sequence numbers, 1 hour prior to the first preoperative intervention. During the study, only the personnel responsible for randomization and those administering the intervention were aware of the group assignments. Participants, postoperative care providers, and data analysts remained blinded to the allocation throughout the study period.\u003c/p\u003e \u003cp\u003eAll patients were informed that they might or might not perceive any sensation during stimulation, regardless of group assignment.\u003c/p\u003e\n\u003ch3\u003eStudy protocol\u003c/h3\u003e\n \u003cp\u003eIn this study, a standardized perioperative management pathway based on the Enhanced Recovery After Surgery protocol was applied to all participants.\u003c/p\u003e \u003cp\u003eAll patients underwent general anesthesia with endotracheal intubation. Balanced crystalloids were administered as the primary infusion fluid to prevent both excessive fluid overload and inadequate perfusion. Nasogastric tubes were not routinely placed.\u003c/p\u003e \u003cp\u003eMultimodal analgesia was employed in all cases. All patients underwent bilateral transversus abdominis membrane nerve block or local incision infiltration before the end of surgery. Postoperatively, patient-controlled analgesia (PCA) with a standardized sufentanil regimen was provided. Patients were encouraged to resume oral fluids as early as possible and to gradually progress to a regular diet, along with early mobilization.\u003c/p\u003e\n\u003ch3\u003eInterventions\u003c/h3\u003e\n\u003cp\u003ePatients were fitted with an auricular vagus nerve stimulator (tVNS501, Ruishen An Medical Devices Co., Ltd., Changzhou, Jiangsu Province, China), positioned on the right cymba conchae\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Patients in the stimulation group received low intensity taVNS with the following parameters: a frequency of 25 Hz, pulse width of 250 \u0026micro;s, and alternating cycles of 30 seconds on and 30 seconds off. Stimulation began at an initial current of 10 mA and was gradually increased. Once the patient reported a tingling sensation within 20 seconds of stimulation onset, the current was adjusted to a level just below the sensory threshold (typically 20\u0026ndash;60 mA).\u003c/p\u003e \u003cp\u003eIn the sham group, the electrode placement and stimulation parameters were identical to those in the stimulation group; however, the stimulator was turned off after the patient reported a tingling sensation, ensuring blinding.\u003c/p\u003e \u003cp\u003eStimulation was administered for 1 hour in the morning before surgery and was continued intraoperatively and for 30 minutes postoperatively. On postoperative day (POD) 1 and 2, patients received 1 hour of stimulation each morning.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes and measures\u003c/h2\u003e \u003cp\u003ePatient characteristics were collected, including age, sex, height, weight, and American Society of Anesthesiologists classification, as well as histories of hypertension, diabetes mellitus, ischemic heart disease, valvular heart disease, stroke, infectious diseases, and cancer. Information on preoperative medication use was obtained, covering statins, β-blockers, anticoagulants, antiplatelet agents, calcium channel blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, other antihypertensive drugs, corticosteroids, metformin, insulin, other antidiabetic agents, opioids, and probiotics. Preoperative laboratory variables included C-reactive protein (CRP), absolute white blood cell (WBC) count, absolute neutrophil count, hemoglobin, aspartate aminotransferase, alanine aminotransferase, creatinine, and albumin levels. Surgical variables were also recorded, including duration of surgery, surgical approach, specific procedure performed, conversion to open surgery, unplanned stoma formation, lesion length, TNM stage, intraoperative fluid volume, urine output, and blood loss.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePrimary outcome\u003c/h3\u003e\n\u003cp\u003eTime to first postoperative defecation (TFD) (in hours): the interval between the end of surgery and the first observed stool passage\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\n\u003ch3\u003eSecondary outcome\u003c/h3\u003e\n\u003cp\u003eSecondary outcomes included time to first flatus (TFF), defined as the interval from the end of surgery to the first passage of flatus, and time to oral tolerance of semisolid food (TOF), defined as the absence of significant nausea or vomiting within 4 hours after ingestion of semisolid food. Additional outcomes comprised postoperative pain scores on days 1 to 3, assessed using a 10-point visual analogue scale (VAS; 0\u0026thinsp;=\u0026thinsp;no pain, 10\u0026thinsp;=\u0026thinsp;worst pain imaginable), cumulative opioid consumption via PCA, length of hospital stay (LOS), and postoperative complications, including poor wound healing, intestinal obstruction, infection, bleeding, intestinal fistula, hepatic insufficiency, hypoproteinemia, and readmission within 30 days after surgery. Postoperative laboratory markers\u0026mdash;CRP, absolute WBC count, and absolute neutrophil count\u0026mdash;were recorded on POD 1 and 3.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSample size and statistics\u003c/h2\u003e \u003cp\u003eThe sample size was estimated based on data from a pilot study, in which the mean TFD after laparoscopic or robotic colorectal surgery was 70.2 hours. taVNS was found to reduce the mean time to 69.0 hours, with a standard deviation (SD) of 2.0 in both groups. Using G*Power software (version 3.1.9.7) for a two-sided test with a significance level of α\u0026thinsp;=\u0026thinsp;0.05 and a power (1\u0026thinsp;\u0026minus;\u0026thinsp;β) of 0.80, the calculated sample size was 35 patients per group. To account for an anticipated 10% dropout rate in clinical studies, the total sample size was increased to 80 patients, with 40 patients allocated to each group.\u003c/p\u003e \u003cp\u003eAll analyses were performed on an intention-to-treat basis. Continuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or median [interquartile range (IQR)], depending on data distribution assessed by the Shapiro\u0026ndash;Wilk test. Categorical variables were summarized as counts (percentages). Between-group comparisons were conducted using the Chi-squared or Fisher\u0026rsquo;s exact test for categorical variables, and either the Student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e-test or Mann\u0026ndash;Whitney \u003cem\u003eU\u003c/em\u003e test for continuous variables, as appropriate.\u003c/p\u003e \u003cp\u003eKaplan\u0026ndash;Meier curves were generated for the primary outcome and for the secondary outcomes (TFF and TOF). Postoperative changes in inflammatory markers (CRP, WBC, and neutrophil count) and VAS were analyzed using linear mixed-effects models (LMMs). Because of non-normal distributions, inflammatory and VAS data were log-transformed prior to analysis. Each model included Group, Time, and their interaction (Group \u0026times; Time) as fixed effects, with patient ID as a random intercept. A compound symmetry covariance structure was chosen, as it provided comparable model fit to an autoregressive AR (1) structure (ΔAIC\u0026thinsp;\u0026lt;\u0026thinsp;2). If the treatment-by-time interaction did not meet the pre-specified significance threshold (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026ge;\u0026thinsp;0.20), the interaction term was removed, and overall group effects were reported across all time points. When significant, treatment effects were reported separately for each time point, with Bonferroni-adjusted pairwise comparisons. A two-sided \u003cem\u003ep\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. All analyses were performed using R Studio (version 2024.09.0\u0026thinsp;+\u0026thinsp;375).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePatient recruitment、baseline characteristics and surgical variables\u003c/h2\u003e \u003cp\u003ePatient recruitment is summarized in the flow chart (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Between July 2024 and April 2025, a total of 217 patients were screened, of whom 79 met the inclusion criteria and were randomized to the stimulation group (n\u0026thinsp;=\u0026thinsp;39) and the sham stimulation group (n\u0026thinsp;=\u0026thinsp;40).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOnly one patient in the stimulation group refused postoperative stimulation due to ear discomfort. All 79 patients completed the study with no loss to follow-up, and all were included in the intention-to-treat analysis.\u003c/p\u003e \u003cp\u003eBaseline characteristics were well balanced between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Surgical and intraoperative variables are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The median operation time was 145.0 (115.0\u0026ndash;182.5) minutes in the stimulation group and 152.5 (125.8\u0026ndash;181.3) minutes in the sham stimulation group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.28). The intraoperative volumes of crystalloid and colloid were 1500.0 (1000.0\u0026ndash;1500.0) mL in the stimulation group and 1500.0 (1475.0\u0026ndash;1500.0) mL in the sham stimulation group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.25). Intraoperative urine output was 300.0 (200.0\u0026ndash;450.0) mL in the stimulation group and 300.0 (200.0\u0026ndash;525.0) mL in the sham stimulation group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.22). The proportions of patients according to surgical approach, procedures performed, conversion to open surgery, unplanned stoma formation, and pathological TNM stage were similar between the two groups. No significant differences were observed in lesion length or estimated blood loss.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and clinical features of treated patients at entry\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStimulation group (n\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSham stimulation group (n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, year, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64.0 (55.5\u0026ndash;71.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.0 (54.0\u0026ndash;72.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (69.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (30.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (40.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight, cm, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e165.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e163.9\u0026thinsp;\u0026plusmn;\u0026thinsp;7.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight, kg, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62.9\u0026thinsp;\u0026plusmn;\u0026thinsp;9.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.3\u0026thinsp;\u0026plusmn;\u0026thinsp;13.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASA classification, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (92.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37 (92.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of hypertension, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (30.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (35.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of diabetes mellitus, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of ischemic heart disease, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of valvopathy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of stoke, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of infectious diseases, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of cancer, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStatins, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBeta blockers, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnticoagulant, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntiplatelet, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (5.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (5.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCalcium channel blocker, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (20.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (25.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.84\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eACEI/ARB, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther antihypertensive agents, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorticosteroids, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMetformin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInsulin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther antidiabetic agents, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (5.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative opioid use, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProbiotics, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHb, g/L, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e126.3\u0026thinsp;\u0026plusmn;\u0026thinsp;22.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e127.2\u0026thinsp;\u0026plusmn;\u0026thinsp;24.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST, U/L, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.0 (17.0\u0026ndash;22.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.5 (17.0\u0026ndash;27.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT, U/L, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.0 (11.5\u0026ndash;21.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.0 (11.8\u0026ndash;23.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine, \u0026micro;mol/L, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70.0 (64.0\u0026ndash;84.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69.0 (60.5\u0026ndash;75.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin, g/L, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39.8 (36.7\u0026ndash;42.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.4 (37.3\u0026ndash;43.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: IQR, interquartile range; SD: standard deviation; ASA, American Society of Anesthesiologists; Hb, hemoglobin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; TBIL, total bilirubin; ACEI/ARB, angiotensin converting enzyme inhibitor/angiotensin receptor antagonist.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eProcedure and pathology characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStimulation group (n\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSham stimulation group (n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep-\u003c/em\u003evalue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of surgery, min, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e145.0 (115.0\u0026ndash;182.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e152.5 (125.8\u0026ndash;181.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProcedural approach, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaparoscopic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (89.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e35 (87.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRobotic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProcedure, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnterior resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (23.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11 (27.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSigmoid colectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (51.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (30.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRight hemicolectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (17.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (25.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft hemicolectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTransverse colectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (5.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtended right hemicolectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConversion to open surgery, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnplanned stoma formation, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of the lesion, cm, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor T stage, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT0 (premalignant)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (5.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (22.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (12.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (17.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (12.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (45.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18 (46.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (8.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (25.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor N stage, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (57.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18 (46.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (37.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17 (43.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (5.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor M stage, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eM0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (97.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e37 (94.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eM1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (5.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraoperative volume of crystalloid and colloid, mL, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1500.0 (1000.0\u0026ndash;1500.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1500.0 (1475.0\u0026ndash;1500.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraoperative urine output, mL, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e300.0 (200.0\u0026ndash;450.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e300.0 (200.0\u0026ndash;525.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraoperative blood loss, mL, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50.0 (20.0\u0026ndash;50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50.0 (20.0\u0026ndash;50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.84\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: IQR: interquartile range; SD, standard deviation.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003ePrimary outcome\u003c/h2\u003e \u003cp\u003eThe TFD was significantly shorter in the stimulation group compared with the sham stimulation group (71.5 [62.0-89.8] vs. 90.0 [63.5-114.5] hours). The unadjusted Cox analysis showed hazard ratio (HR)\u0026thinsp;=\u0026thinsp;1.84 (95% confidence interval [CI], 1.13\u0026ndash;2.98; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01), and after adjustment for operative duration, total fluid input, and intraoperative urine output, the effect remained significant (adjusted HR\u0026thinsp;=\u0026thinsp;2.04, 95% CI, 1.22\u0026ndash;3.40; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA, Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePrimary outcome\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePrimary outcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eStimulation group (n\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSham stimulation group (n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eEffect estimate (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep-\u003c/em\u003evalue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eUnadjusted\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eAdjusted\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eUnadjusted\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eAdjusted\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime to first defecation, hours, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c2\"\u003e \u003cp\u003e71.5 (62.0-89.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c3\"\u003e \u003cp\u003e90.0 (63.5-114.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.84 (1.13\u0026ndash;2.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.04 (1.22\u0026ndash;3.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eEffect estimates are expressed as hazard ratios with 95% confidence intervals. Both unadjusted and adjusted analyses are shown. Adjustment was performed for operative duration, total fluid input, and intraoperative urine output using a Cox proportional hazards model.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eAbbreviations: CI, confidence interval; IQR, interquartile range.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eSecondary outcomes\u003c/h2\u003e \u003cp\u003eFor the TFF, the median duration was shorter in the stimulation group (45.0 [26.0\u0026ndash;60.5] hours) compared with the sham group (51.5 [41.8\u0026ndash;67.0] hours). The unadjusted model suggested a trend toward faster recovery (HR\u0026thinsp;=\u0026thinsp;1.52, 95% CI, 0.96\u0026ndash;2.40; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.07), but this association was not significant, and the adjusted model yielded consistent results (adjusted HR\u0026thinsp;=\u0026thinsp;1.35, 95% CI, 0.85\u0026ndash;2.15; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.21). In contrast, the TOF was significantly shorter in the stimulation group (116.0 [108.0\u0026ndash;135.0] hours) compared with the sham group (133.5 [114.0\u0026ndash;161.5] hours). This effect was significant both before and after covariate adjustment (unadjusted HR\u0026thinsp;=\u0026thinsp;2.03, 95% CI, 1.26\u0026ndash;3.29; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01; adjusted HR\u0026thinsp;=\u0026thinsp;1.85, 95% CI, 1.12\u0026ndash;3.07; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB\u0026ndash;C, Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSecondary outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStimulation group(n\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSham stimulation group(n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEffect estimate (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime to first flatus, hours, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45.0 (26.0\u0026ndash;60.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.5 (41.8\u0026ndash;67.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.35 (0.85\u0026ndash;2.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.21\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime to tolerance of semisolid diet, hours, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e116.0 (108.0\u0026ndash;135.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e133.5 (114.0\u0026ndash;161.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.85 (1.12\u0026ndash;3.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.02\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVAS, scores, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePOD1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.07 (-0.20, 0.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.34\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePOD2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.09 (-0.23, 0.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.18\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePOD3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1\u0026ndash;1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.02 (-0.12, 0.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.76\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCumulative PCA usage, \u0026micro;g, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95.5\u0026thinsp;\u0026plusmn;\u0026thinsp;48.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98.3\u0026thinsp;\u0026plusmn;\u0026thinsp;34.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-2.76 (-21.70, 16.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.77\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of hospital stay, days, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.0 (10.0\u0026ndash;13.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.0 (9.8\u0026ndash;15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.00 (-2.00, 1.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.50\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative complications, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.62 (0.16\u0026ndash;2.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.71\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital readmission, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.34 (0.04, 3.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.62\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eEffect estimates are presented as hazard ratios for time-to-event outcomes, mean differences for normally distributed continuous outcomes, median differences for non-normally distributed continuous outcomes, and relative risks for categorical outcomes, each with 95% confidence intervals.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations: CI, confidence interval; IQR, interquartile range; VAS, visual analogue scale; POD, postoperative day; PCA, patient-controlled analgesia; SD, standard deviation.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eThe following statistical methods were applied according to data type and distribution:\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003ea, Cox proportional hazards model with log-rank test, adjusted for operative duration, total fluid input, and intraoperative urine output.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eb, Linear mixed-effects model on log-transformed values, adjusted for operative duration, total fluid input, and intraoperative urine output. Because the treatment-by-time interaction did not exceed the pre-specified threshold of P\u0026thinsp;\u0026ge;\u0026thinsp;0.20, group differences were examined at each postoperative time point.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003ec, Independent samples t-test.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003ed, Wilcoxon rank-sum test.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003ee, Fisher\u0026rsquo;s exact test.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePain scores measured by VAS significantly declined over time in both groups (time effect, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The treatment-by-time interaction was below the pre-specified threshold (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.14\u0026thinsp;\u0026lt;\u0026thinsp;0.20), and therefore group differences were examined at each time point. Adjusted analyses revealed no significant differences between stimulation and sham groups at POD 1\u0026ndash;3. Descriptive statistics (median [IQR]) are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. No significant differences were observed between the groups in cumulative PCA usage, postoperative complications, LOS, or 30-day readmission rates. Postoperative complications occurred in three patients (7.7%) in the stimulation group\u0026mdash;two with hepatic insufficiency and one with hypoalbuminemia\u0026mdash;and in five patients (12.5%) in the sham stimulation group\u0026mdash;two with hepatic insufficiency, one with hypoalbuminemia, one with poor wound healing, and one with postoperative infection. Readmissions occurred in one patient in the stimulation group (due to anastomotic leakage) and three patients in the sham stimulation group (due to intestinal obstruction, pseudomembranous colitis, and ureteral stricture, respectively) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003ePostoperative laboratory findings\u003c/h2\u003e \u003cp\u003eAll inflammatory markers increased significantly after surgery (time effect, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for all outcomes). For CRP, the treatment-by-time interaction did not exceed the pre-specified threshold. Therefore, the interaction term was excluded, and overall group comparisons across all time points showed no significant difference between stimulation and sham groups (adjusted β = -0.06, 95% CI -0.35 to 0.23, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.69). For neutrophils, the treatment-by-time interaction also did not exceed the threshold. The overall analysis indicated no significant group difference (adjusted β\u0026thinsp;=\u0026thinsp;0.05, 95% CI -0.08 to 0.18, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.46). For WBC, the treatment-by-time interaction was below the threshold, and thus post hoc comparisons were conducted. At POD 1, the stimulation group exhibited a significantly smaller increase in WBC compared with the sham group (adjusted β = -0.14, 95% CI -0.27 to -0.01, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04), whereas no differences were observed at the preoperative or POD 3 time points. Detailed results are presented in Table\u0026nbsp;5. The temporal patterns of CRP, WBC, and neutrophil counts, expressed as log-transformed estimated means with 95% CI, are illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eTable 5. Inflammatory outcomes\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"916\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStimulation group (n=39)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSham stimulation group (n=40)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 254px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEffect estimate (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnadjusted\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnadjusted\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCRP, mg/L, median (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.09 (-0.19, 0.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-0.06 (-0.35, 0.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.69\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003ePreoperative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1.4 (0.7\u0026ndash;5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1.3 (0.6\u0026ndash;3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003ePOD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e30.1 (20.8\u0026ndash;40.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e38.5 (25.8\u0026ndash;59.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003ePOD3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e27.7 (17.2\u0026ndash;66.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e34.4 (21.8\u0026ndash;54.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWBC, \u0026times;10^9/L, median (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003ePreoperative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e4.9 (4.3\u0026ndash;7.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e5.8 (4.6\u0026ndash;6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.02 (-0.13, 0.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-0.04 (-0.20, 0.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.59\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003ePOD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e8.3 (4.4\u0026ndash;10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e7.9 (6.5\u0026ndash;10.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.16 (0.01, 0.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-0.14 (-0.27, -0.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.04\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003ePOD3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e6.0 (4.1\u0026ndash;7.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e6.0 (4.9\u0026ndash;7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.04 (-0.11, 0.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-0.03 (-0.16, 0.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.69\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNeutrophils, \u0026times;10^9/L, median (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e-0.07 (-0.20, 0.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e0.05 (-0.08, 0.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.46\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003ePreoperative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e3.9 (2.8\u0026ndash;5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e3.5 (2.9\u0026ndash;4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003ePOD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e7.2 (5.7\u0026ndash;8.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e6.1 (5.1\u0026ndash;8.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003ePOD3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e4.4 (3.5\u0026ndash;5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e4.4 (3.6\u0026ndash;5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\u003c/div\u003e\u003cp\u003eValues are presented as median (interquartile range) of the raw data. Between-group differences (sham\u0026minus;stimulation) were estimated using linear mixed-effects models fitted on log-transformed outcomes. Both unadjusted and adjusted estimates are reported; adjusted models included intraoperative urine output, operative duration, and total fluid input as covariates.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAbbreviations: CI, confidence interval; CRP, C-reactive protein; IQR, interquartile range;\u0026nbsp;POD, postoperative; WBC, white blood cell.\u003c/p\u003e\n\u003cp\u003ea, Overall group differences were calculated across all time points by collapsing the data over time and excluding the interaction term, as the treatment-by-time interaction exceeded the pre-specified significance threshold of 0.20.\u003c/p\u003e\n\u003cp\u003eb, Group differences were examined at each postoperative time point, as the treatment-by-time interaction did not exceed the pre-specified threshold of 0.20.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn our study, perioperative taVNS improved postoperative gastrointestinal recovery, as evidenced by shorter TFD and TOF. In addition, although taVNS did not reduce postoperative CRP or neutrophil levels, it attenuated the increase in WBC count on POD 1.\u003c/p\u003e \u003cp\u003ePreclinical studies have consistently demonstrated that vagus nerve stimulation (VNS) promotes gastrointestinal recovery\u003csup\u003e[\u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13 CR14\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. Yana Wang et al.\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e reported that minimally invasive left cervical VNS inhibited colon shortening, thereby ameliorating gastrointestinal dysfunction in rats with acute cerebral ischemia\u0026ndash;reperfusion injury. Hong Gun-Soo et al. \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003edemonstrated that taVNS could attenuate POI in mice. In recent years, clinical studies investigating taVNS for improving gastrointestinal function have also increased. Jie Liu et al.\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e reported that taVNS could alleviate constipation and abdominal pain symptoms in patients with constipation-predominant irritable bowel syndrome. Consistent with previous findings, studies by Huang et al.\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e and Ru O et al.\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e demonstrated that taVNS can accelerate postoperative bowel recovery by reducing TFF in patients undergoing gastrointestinal surgery. However, a multicenter study involving patients with diabetes and autonomic neuropathy reported that cervical taVNS did not improve gastrointestinal symptoms in this population\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. Interestingly, although our data suggested a trend toward shorter TFF, this difference did not reach statistical significance. This discrepancy may be attributed to our relatively small sample size or to differences in stimulation parameters (such as frequency, intensity, and duration), which warrant further investigation.\u003c/p\u003e \u003cp\u003ePreclinical models have demonstrated that VNS can suppress intestinal inflammation and shorten the duration of POI\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. Several clinical studies have also shown that VNS attenuates inflammatory responses in intestinal disorders. For instance, Sinniger et al.\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e reported that left cervical VNS significantly decreased CRP levels in patients with Crohn\u0026rsquo;s disease. Similarly, Stakenborg et al.\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e observed that intra-abdominal VNS during pancreaticoduodenectomy reduced interleukin-6 (IL-6) concentrations in the duodenal mucosa two hours postoperatively, although serum IL-6, IL-8, and tumor necrosis factor-α levels remained unchanged. In contrast, a clinical study involving patients undergoing laparoscopic rectal resection demonstrated that taVNS significantly lowered serum IL-6 concentrations\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Consistent with these findings, our study showed that taVNS attenuated the postoperative rise in WBC count among patients with colorectal cancer, suggesting a potential systemic anti-inflammatory effect. Further investigations are warranted to determine whether this modulation also extends to intestinal inflammation and contributes to improved local immune regulation.\u003c/p\u003e \u003cp\u003eAnother important consideration is the potential impact of VNS on postoperative pain. Both preclinical and clinical studies have suggested that VNS may alleviate pain by modulating central nociceptive pathways and suppressing peripheral inflammatory responses\u003csup\u003e[\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. However, in our trial, no significant differences were observed in postoperative pain scores between the active and sham stimulation groups. Several factors may account for this finding. First, intraoperative opioid administration was not standardized among patients. Second, all the patients received additional analgesic interventions, such as transversus abdominis plane blocks or local wound infiltration before the end of surgery. As a result, postoperative VAS from day 1 to day 3 were generally low in both groups. Although cumulative opioid consumption tended to be lower in the active group, the difference did not reach statistical significance. Further studies with standardized analgesic protocols are warranted to better elucidate the effect of taVNS on postoperative pain in patients undergoing colorectal cancer surgery.\u003c/p\u003e \u003cp\u003eThis study has several notable strengths. First, it is among the few randomized controlled trials to investigate the effects of taVNS on postoperative gastrointestinal recovery in patients undergoing minimally invasive colorectal surgery, providing valuable clinical evidence in a field largely supported by preclinical data. Second, standardized perioperative management protocols minimized confounding effects from surgical technique and anesthesia, allowing for a clearer interpretation of the taVNS intervention. Third, the study incorporated both clinical outcomes and inflammatory markers, offering a comprehensive evaluation of efficacy. Finally, the rigorous statistical adjustment for relevant covariates enhanced the robustness and credibility of the findings.\u003c/p\u003e \u003cp\u003eHowever, several limitations of this study should be acknowledged. First, this was a single center trial with a relatively small sample size, which may limit the generalizability of the findings. Second, autonomic nervous system activity (e.g., heart rate variability) was not monitored; therefore, the physiological mechanisms underlying the effects of taVNS on bowel recovery could not be directly verified. Third, long-term outcomes were not assessed, leaving the durability of taVNS effects on postoperative bowel function uncertain. Finally, with respect to safety, although only one patient discontinued postoperative stimulation due to ear discomfort, this indicates that device tolerability could still be improved. Future studies should aim to enhance device comfort, establish standardized criteria for taVNS-related adverse event reporting, and confirm these findings in larger multicenter populations.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn summary, this randomized controlled trial demonstrated that perioperative taVNS promoted postoperative gastrointestinal recovery in patients undergoing minimally invasive colorectal surgery, as evidenced by shorter TFD and TOF. Additionally, taVNS attenuated the postoperative increase in WBC count, suggesting a potential anti-inflammatory benefit. The procedure was well tolerated, with only mild, transient ear discomfort reported. These findings indicate that taVNS is a safe and feasible adjunctive therapy for enhancing postoperative bowel function.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePOI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epostoperative intestinal obstruction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003etaVNS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etranscutaneous auricular vagus nerve stimulation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePCA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epatient-controlled analgesia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePOD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epostoperative day\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eC-reactive protein\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWBC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ewhite blood cell\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTFD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etime to first postoperative defecation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTFF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etime to first flatus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTOF: time to oral tolerance of semisolid food\u003c/div\u003e \u003cdiv class=\"Description\"\u003e\u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVAS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003evisual analogue scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLOS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003elength of hospital stay\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003estandard deviation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIQR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einterquartile range\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLMM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003elinear mixed-effects model\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003econfidence interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehazard ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVNS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003evagus nerve stimulation.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConflict of Interest:\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eHuman Ethics and Consent to Participate declarations\u003c/strong\u003e \u003cp\u003e This study was approved by the Ethics Committee of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University. All procedures were conducted in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments. Written informed consent was obtained from all individual participants included in the study.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eNone.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eTT Wei conceived and designed the study, supervised clinical implementation, contributed to data analysis and interpretation, and drafted the manuscript.J Liu, BQ Di, Y Lei, SR Cheng, G Fei, D Zheng, YS Jin, and CHY Xu, coordinated patient enrollment and data collection, assisted with data interpretation, and revised the manuscript for important intellectual content.G Chen contributed to study design and ethics preparation and performed data quality control.TT Wei and G Ch serve as the guarantors of this study and take full responsibility for the integrity of the work, from study conception to the decision to publish.All authors reviewed and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMYLES P S, BELLOMO R, CORCORAN T, et al. 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[doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/annrheumdis-2020-217872]\u003c/span\u003e\u003cspan address=\"10.1136/annrheumdis-2020-217872]\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Transcutaneous auricular vagus nerve stimulation, Postoperative ileus, Colorectal surgery, Gastrointestinal recovery, Neuromodulation, Randomized controlled trial","lastPublishedDoi":"10.21203/rs.3.rs-8241477/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8241477/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePostoperative ileus (POI) is a common complication after colorectal surgery, leading to delayed recovery and prolonged hospitalization. Although vagus nerve stimulation has shown promise in enhancing gastrointestinal motility in preclinical and early clinical studies, evidence in the perioperative setting remains limited. This study evaluated whether perioperative transauricular vagus nerve stimulation (taVNS) could improve postoperative bowel recovery in patients undergoing minimally invasive colorectal resection.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn this randomized, sham-controlled trial, 79 patients scheduled for elective minimally invasive colorectal resection were assigned to receive either taVNS or sham stimulation. The primary outcome was time to first defecation (TFD). Secondary outcomes included time to first flatus (TFF), time to tolerance of semisolid food (TOF), postoperative pain scores, opioid consumption, postoperative complications, length of stay, 30-day readmission, and perioperative inflammatory markers. Analyses followed the intention-to-treat principle.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eCompared with the sham group, the taVNS group demonstrated significantly shorter TFD (71.5 [62.0\u0026ndash;89.8] vs. 90.0 [63.5\u0026ndash;114.5] hours; adjusted hazard ratio [HR] 2.04, 95% CI 1.22\u0026ndash;3.40; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01) and TOF (116.0 [108.0\u0026ndash;135.0] vs. 133.5 [114.0\u0026ndash;161.5] hours; adjusted HR 1.85, 95% CI 1.12\u0026ndash;3.07; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02). The taVNS group exhibited a smaller postoperative day-1 increase in white blood cell count (β = \u0026minus;0.14, 95% CI \u0026minus;\u0026thinsp;0.27 to \u0026minus;\u0026thinsp;0.01; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003ePerioperative taVNS accelerated gastrointestinal recovery and attenuated early postoperative inflammation following minimally invasive colorectal surgery. These findings support taVNS as a promising noninvasive strategy to reduce POI, meriting confirmation in larger multicenter studies.\u003c/p\u003e\u003ch2\u003eTrial registration\u003c/h2\u003e \u003cp\u003eChiCTR2400083015, registered April 13, 2024.\u003c/p\u003e","manuscriptTitle":"Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Postoperative Ileus Following Minimally Invasive Colorectal Resection: A Single-Center Randomized Controlled Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-12 06:23:33","doi":"10.21203/rs.3.rs-8241477/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"16d44f48-d1a1-4216-b8e5-4c267e6b6bec","owner":[],"postedDate":"January 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-16T20:54:00+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-12 06:23:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8241477","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8241477","identity":"rs-8241477","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}