Prucalopride succinate accelerates postoperative intestinal recovery following gastrectomy in a randomized clinical trial

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This double-blind, randomized controlled trial enrolled patients scheduled for minimally invasive gastrectomy for gastric cancer. Patients were randomly assigned to receive either mosapride citrate (control) or prucalopride succinate (experimental) from postoperative days 1 to 4. Bowel motility was assessed by tracking radiopaque marker migration on serial abdominal radiographs, along with first-flatus time, food intake, and inflammatory markers. Baseline characteristics were comparable between groups. On postoperative day 5, the percentage of radiopaque markers passed to the colon was significantly higher in the experimental group. (96.90 ± 10.15% vs 90.20 ± 15.29%, p = 0.012) The neutrophil–lymphocyte ratio was also lower on postoperative day 3 in the experimental group (4.85 ± 2.49 vs 6.02 ± 3.06, p = 0.035). Prucalopride succinate enhances bowel motility after gastrectomy and may reduce early postoperative inflammation. It may be considered as an adjunct to ERAS protocols in gastric cancer surgery. Biological sciences/Cancer Health sciences/Gastroenterology Health sciences/Medical research Health sciences/Oncology Figures Figure 1 Figure 2 Figure 3 Introduction Enhanced recovery after surgery (ERAS) protocols have been widely adopted in gastrointestinal surgery to promote early recovery, reduce hospital length of stay, and minimize postoperative complications 1 – 3 . However, postoperative ileus (POI) remains a common problem after major abdominal surgeries such as gastrectomy, often leading to prolonged hospitalization and increased risk of complications such as atelectasis and infection 4 . POI is commonly managed or prevented through the use of prokinetic agents targeting serotonin type 4 (5-HT 4 ) receptors 5 , 6 . Nevertheless, recent evidence has demonstrated that mosapride fails to enhance postoperative bowel function after gastrectomy 7 . In contrast to mosapride, prucalopride succinate, a highly selective 5-HT 4 receptor agonist has a primary effect on promoting colonic motility and has been shown to exert anti-inflammatory effects by modulating cholinergic signaling 8 , 9 . It has demonstrated efficacy in accelerating colonic transit in patients following various gastrointestinal surgeries 10 . These pharmacologic properties make it a suitable agent for addressing POI in the setting of gastric surgery. This randomized controlled trial was conducted to evaluate whether prucalopride improves bowel motility and reduces postoperative inflammation in patients undergoing minimally invasive gastrectomy within an ERAS framework 11 , 12 . Methods Study design and ethics This prospective, double-blind, randomized controlled trial was conducted at Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. The study protocol was approved by the Gangnam Severance Institutional Review Board (IRB No. 2021-0418-006) and complied with the Declaration of Helsinki. All participants provided written informed consent prior to enrollment. The study was registered at ClinicalTrials.gov (NCT05966246) on July 21, 2023. The clinical trial registration was completed post hoc due to an administrative oversight, although all ethical approvals and monitoring were in place. Patients Inclusion criteria included age between 20 and 80 years, histologically confirmed gastric adenocarcinoma prior to surgery, scheduled minimally invasive gastrectomy (laparoscopic or robotic) with curative intent, and American Society of Anesthesiologists (ASA) physical status classification of 3 or lower 13 . Exclusion criteria included distant metastases, evidence of preoperative intestinal obstruction, history of prior chemotherapy, or concurrent malignancy other than gastric cancer. Additional exclusions included history of major abdominal surgery likely to result in extensive adhesions, prior abdominal radiotherapy, hepatic or renal failure due to underlying comorbidities, uncontrolled diabetes mellitus, or known malabsorption syndromes such as inflammatory bowel disease or congenital metabolic disorders 14 . Study withdrawal criteria included requirement for additional bowel resection or extensive adhesiolysis during surgery, conversion to open gastrectomy, inability to resume oral intake postoperatively, or allergic reactions to either prucalopride or mosapride. Treatment and assessments Patients were randomly assigned in a 1:1 ratio to receive either prucalopride succinate (experimental group) or mosapride citrate (control group). Mosapride was selected as the control treatment based on findings from a prior randomized study, which showed no significant difference in bowel recovery between mosapride and placebo following minimally invasive gastrectomy 7 . A clinical research coordinator not involved in patient care performed randomization on the day of surgery. Both patients and healthcare providers were blinded to the group allocation. Control group patients received mosapride citrate (Gasmotin SR®; DaeWoong) 15 mg once daily from postoperative day (POD) 1 to POD 4, while experimental group patients received prucalopride succinate (Resolor®; Janssen Korea) once daily during the same period. Prucalopride dosing was 2 mg for patients under 65 years of age, and 1 mg for those aged 65 or older. During surgery, a capsule containing 20 radiopaque ring markers (Kolomark™; Intropharm, Korea) was placed at the anastomosis site 15 . Bowel transit time was assessed by counting radiopaque markers visible in the stomach, small intestine, or colon on plain abdominal radiographs obtained on postoperative days 1, 3, and 5 (Fig. 1 ). Markers passed in stool were considered to have reached the colon. All patients received perioperative care in accordance with ERAS guidelines, which included standardized anesthetic protocols, goal-directed fluid therapy to maintain near-zero balance, restricted opioid use, avoidance of nasogastric decompression, early initiation of enteral nutrition, and early postoperative mobilization 11 . Epidural anesthesia was not employed. Patients followed a standardized postoperative dietary protocol consisting of sips of water or carbohydrate fluids on day 1, liquid diet on day 2, and soft diet on day 3, unless limited by patient tolerance. The primary outcome was bowel transit time, assessed by the percentage of radiopaque markers that had passed into the colon on postoperative day 3. Secondary outcomes included time to first flatus, abdominal discomfort assessed using a 5-point numerical scale, proportion of food intake (ratio of food consumed to food provided), and inflammatory markers including C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) 16 , 17 . Additionally, postoperative complications were evaluated within 30 days using the Clavien–Dindo classification 18 . Statistical analysis Based on prior data indicating that prucalopride accelerated time to first flatus by approximately 1.37-fold following gastrointestinal surgery 10 , we hypothesized a 1.3-fold increase in bowel motility after gastrectomy. To achieve 90% power at a two-sided significance level of 5% while accounting for a 10% dropout rate with 1:1 randomization, a minimum of 53 patients per group was required. Normality of continuous variables was assessed using the Kolmogorov–Smirnov test. Normally distributed data are presented as mean ± standard deviation, and non-normally distributed data as median (interquartile range). Categorical variables are summarized as counts and percentages. Continuous variables were compared using the Student’s t-test or Mann-Whitney U test, while categorical variables were analyzed using the chi-square test or Fisher’s exact test. For outcomes measured repeatedly over time, a repeated measures analysis of variance (RM-ANOVA) was employed to evaluate group-by-time interactions. The sphericity assumption was assessed; when violated, Greenhouse–Geisser correction was applied. RM-ANOVA tests whether group differences change over time and accounts for the correlation of repeated measurements within subjects. A p -value < 0.05 was considered statistically significant. All analyses were conducted using SPSS version 27.0 (IBM Corp., Armonk, NY, USA). Results Patient characteristics In total, the planned 106 patients were enrolled between January 2022 and June 2023. Patients were randomly assigned, with 53 patients allocated to each group. There were no dropouts from the control group, while two patients dropped out of the prucalopride group. One patient withdrew consent, and another was excluded following reoperation. (Fig. 2 ) A total of 104 patients were included in the statistical analysis. Baseline characteristics, including age, sex, medical history, type of operation, and estimated blood loss, were comparable between the two groups. (Table 1 ) Table 1 Patient characteristics Characteristics Control (n = 53) Experimental (n = 51) p -value Age (years)* 61.0 (53.0–69.5) 58.0 (46.0–69.0) 0.539 Sex > 0.999 Male 28 (52.8%) 27 (52.9%) Female 25 (47.2%) 24 (47.1%) ASA score 0.615 I 3 (5.8%) 2 (3.9%) II 35 (66.0%) 38 (74.5%) III 15 (28.3%) 11 (21.6%) BMI (kg/m2) 23.46 ± 3.47 23.95 ± 3.39 0.464 Prior abdominal surgery (%) 13 (24.5%) 11 (21.6%) 0.817 Estimated blood loss (cc) 55.64 ± 48.62 43.69 ± 43.91 0.192 Operation time (min) 178.30 ± 35.67 173.37 ± 31.18 0.663 Operation method > 0.999 Laparoscopic 44 (83.0%) 42 (82.4%) Robotic 9 (17.0%) 9 (17.6%) Type of resection 0.787 Subtotal gastrectomy 44 (83.0%) 44 (86.3%) Total gastrectomy 9 (17.0%) 7 (13.7%) Anastomosis type 0.874 B-I 18 (34.0%) 19 (37.3%) B-II 16 (30.2%) 13 (25.5%) STG R-Y 10 (18.9%) 12 (23.5%) TG R-Y 9 (17.0%) 7 (13.7%) *Age is presented as median (interquartile range) because the distribution was non-normal; p -value was calculated with the Mann-Whitney U test. ASA American Society of Anesthesiologists physical status score; BMI Body mass index; B-I Billroth I; B-II Billroth II; STG R-Y Subtotal gastrectomy Roux-en Y; TG R-Y Total gastrectomy Roux-en Y Motility evaluation Bowel motility was assessed in 100 patients (50 control, 50 experimental) after excluding four patients with missed radiopaque marker insertion during surgery. In cases where five or more of the 20 radiopaque marker rings remained impacted at the stomach or anastomosis site, those rings were excluded from the denominator. Significant differences in bowel motility between the two groups were observed on postoperative day 5. On POD 3, the mean percentage of markers that migrated to the colon was 58.25 ± 38.25% in the control group and 67.53 ± 37.47% in the experimental group ( p = 0.223). On POD 5, the corresponding values were 90.20 ± 15.29% and 96.90 ± 10.15%, respectively ( p = 0.012). (Table 2 , Fig. 3 ) Table 2 Clinical outcome associated with the gastrointestinal motility. POD postoperative day Control group (n = 53) Experimental group (n = 51) p -value Percentage of markers in colon (%) POD1 0.10 ± 0.71 1.20 ± 8.49 0.363 POD3 58.25 ± 38.25 67.53 ± 37.47 0.223 POD5 90.20 ± 15.29 96.90 ± 10.15 0.012 Proportion of food intake (%) POD2 62.45 ± 24.25 56.67 ± 23.47 0.219 POD3 61.89 ± 16.30 62.25 ± 21.01 0.921 POD4 62.74 ± 18.41 66.47 ± 17.42 0.291 POD5 61.42 ± 19.30 67.94 ± 20.79 0.100 Abdominal discomfort scale (NRS 1–5) POD1 2.94 ± 1.31 2.76 ± 1.19 0.469 POD2 3.55 ± 1.37 3.41 ± 1.47 0.628 POD3 3.53 ± 1.15 3.52 ± 1.29 0.996 POD4 3.26 ± 1.09 3.14 ± 1.02 0.543 POD5 2.79 ± 1.04 2.69 ± 0.84 0.569 First flatus time (hour) 74.97 ± 20.58 68.30 ± 13.46 0.053 POD postoperative day Food intake proportions showed no significant differences between the two groups on POD 3 and POD 5. On POD 3, the control group consumed 61.89 ± 16.30% of provided food, while the experimental group consumed 62.25 ± 21.01% ( p = 0.921). On POD 5, food intake was 61.42 ± 19.30% in the control group and 67.94 ± 20.79% in the experimental group ( p = 0.100). The abdominal discomfort scores (NRS 1–5) showed no significant differences between the groups throughout the postoperative period. On POD 3, the abdominal discomfort score was 3.53 ± 1.15 in the control group and 3.52 ± 1.29 in the experimental group ( p = 0.996). Time to first flatus was slightly shorter in the experimental group (68.30 ± 13.46 hours) compared with the control group (74.97 ± 20.58 hours), with borderline statistical significance ( p = 0.053). For time-course analyses, repeated measures ANOVA revealed no significant group-by-time interactions for radiopaque marker transit ( p = 0.343) or abdominal discomfort scores ( p = 0.973). However, a significant group-by-time interaction was observed for food intake ( p = 0.049), with the experimental group showing progressive increases over time compared to consistent levels in the control group (Fig. 3 ). Postoperative outcomes We observed no significant differences in the incidence or severity of postoperative complications between the two groups (Table 3 ). Among the 104 patients, 24 (23.1%) experienced Clavien-Dindo grade I complications, and 49 (47.1%) experienced grade II complications, with similar distributions across groups. No adverse events related to prucalopride administration, including headache, allergic reactions, or hepatic dysfunction, were observed 19 . No major complications such as anastomotic leakage, intra-abdominal abscess, or sepsis occurred in any patient. Table 3 Laboratory Findings and Postoperative Course. Control group (n = 53) Experimental group (n = 51) p -value Postoperative complication (n) Grade I 10 (18.9%) 14 (27.5%) 0.143 Grade II 22 (41.5%) 27 (52.9%) Grade IIIa 1 (1.9%) 1 (2.0%) CRP level (mg/dL) POD1 28.49 ± 27.10 26.57 ± 17.68 0.671 POD3 122.73 ± 67.71 105.97 ± 61.70 0.191 POD5 79.60 ± 56.22 66.28 ± 52.03 0.213 Neutrophil-to-lymphocyte ratio POD1 6.93 ± 2.77 6.34 ± 3.28 0.33 POD3 6.02 ± 3.06 4.85 ± 2.49 0.035 POD5 3.91 ± 1.62 3.33 ± 1.47 0.059 Opioid injection (n) 3.25 ± 2.93 2.51 ± 2.27 0.156 Hospital stays day (n) 5.45 ± 1.10 5.33 ± 0.59 0.494 POD postoperative day, CRP C-reactive Protein CRP levels showed a similar trend with no significant differences on POD 1, 3 and 5. In contrast, the neutrophil-to-lymphocyte ratio (NLR) demonstrated a greater postoperative decrease in the experimental group. Although NLR values on POD 1 were comparable between groups (6.93 ± 2.77 vs. 6.34 ± 3.28, p = 0.330), the experimental group showed significantly lower NLR on POD 3 (4.85 ± 2.49 vs. 6.02 ± 3.06, p = 0.035), with a marginal difference remaining on POD 5 (3.33 ± 1.47 vs. 3.91 ± 1.62, p = 0.059). The number of opioid injections and the length of postoperative hospital stay were similar between the two groups (3.25 ± 2.93 vs 2.51 ± 2.27, p = 0.156; 5.45 ± 1.10 vs. 5.33 ± 0.59 days, p = 0.494). Discussion In our study, prucalopride led to faster recovery of bowel motility and reduced systemic inflammation compared to mosapride in patients undergoing minimally invasive gastrectomy within an ERAS framework. Although ERAS protocols recommend the use of prokinetic agents, the strength of recommendation has been weak due to limited evidence from randomized trials. Our findings provide robust clinical data supporting the use of prucalopride as an effective adjunct to ERAS protocols for improving postoperative gastrointestinal function. The improvement of bowel transit observed with prucalopride may be attributed to its distinct pharmacological profile. Unlike mosapride, which enhances gastrointestinal motility mainly through vagal stimulation of the pylorus, which is resected during gastrectomy, prucalopride exhibits high selectivity for 5-HT 4 receptors and enhances colonic motility, which is particularly relevant in the setting of gastrectomy 20 – 24 . 5-HT 4 receptor activation by prucalopride can stimulate cholinergic anti-inflammatory pathways through α7 nicotinic acetylcholine receptors on muscularis macrophages, potentially reducing early inflammatory responses 25 , 26 . This mechanism may explain the significantly lower NLR observed in the prucalopride group on POD 3, as NLR reflects early neutrophilic inflammation, while CRP levels—which peak later in the inflammatory cascade—showed no significant differences between groups 27 . A previous randomized controlled trial also investigated the effects of prucalopride on postoperative gastrointestinal recovery in patients undergoing various types of gastrointestinal surgery, including ileocecal resection, colectomy, and gastroduodenal surgeries 11 . In the prior study, the experimental group receiving prucalopride showed significantly faster recovery of bowel motility, compared to the placebo group, which is consistent with the results of our study. However, the majority of patients (79 out of 110, 71.8%) underwent surgery via laparotomy rather than a minimally invasive approach. Therefore, while the findings support the efficacy of prucalopride, the clinical setting differed from our study, which was conducted entirely within the framework of an ERAS protocol incorporating minimally invasive gastrectomy. Our findings suggest that prokinetic agents may be more effective when targeting gastrointestinal segments that remain intact after surgery. For instance, mosapride, which enhances gastric and duodenal motility, has shown efficacy in patients undergoing colectomy, where the upper gastrointestinal tract remains intact 28 . Conversely, in this study with gastrectomy patients where the pylorus and gastric antrum are removed, prucalopride—a colonic prokinetic—demonstrated superior outcomes. This highlights the importance of comprehensive motility recovery, not only small bowel function, in the management of postoperative ileus. Several limitations warrant mention. First, this single-center study was conducted in an ethnically homogeneous population, limiting generalizability to other institutions or diverse populations. Second, although improvements were observed in objective markers such as time to first flatus, radiopaque marker transit, and neutrophil-to-lymphocyte ratio, no significant differences were found in hospital length of stay or complication rates between groups. Notably, however, the experimental group demonstrated progressive increases in food intake over time ( p = 0.049), suggesting potential practical benefits in functional recovery. Finally, the different appearances of mosapride and prucalopride compromised complete blinding, potentially allowing patients to identify their assigned treatment. Despite these limitations, this prospective, randomized controlled trial provides meaningful evidence for the use of prucalopride in postoperative recovery after minimally invasive gastrectomy. The findings strongly support incorporating prucalopride into ERAS protocols, particularly as an evidence-based strategy for enhancing gastrointestinal motility after gastrectomy. In conclusion, prucalopride improves the recovery of intestinal motility and reduces inflammatory markers following minimally invasive gastrectomy in patients with gastric cancer. Therefore, prucalopride may play a promising role in ERAS protocols for gastrectomy patients. Declarations Additional information The authors have no conflicts of interest to declare. Funding This study was supported by the new faculty research seed money grant of Yonsei University College of Medicine for 2019 (2019-32-0021). Author Contribution S.J. and S.O. contributed equally to this work as co-first authors. S.J. conducted data collection and statistical analysis, edited the manuscript, and managed manuscript submission. S.O. contributed to conceptualization and methodology, conducted investigation and data collection, and wrote the original draft. J.E.J. performed data collection and statistical analysis. S.H.N. provided supervision and project administration. I.G.K. contributed to conceptualization and supervision, acquired funding, provided project administration, conducted surgical procedures for enrolled patients, reviewed and edited the manuscript, and served as corresponding author. All authors reviewed and approved the final version of the manuscript. Acknowledgement We would like to thank Editage (www.editage.co.kr) for English language editing. Data Availability Datasets used and/or analyzed are available from the corresponding author on reasonable request. References Kehlet, H. & Wilmore, D. W. Evidence-based surgical care and the evolution of fast-track surgery. Ann. Surg. 248 , 189–198. http://doi.org/10.1097/SLA.0b013e31817f2c1a (2008). Mortensen, K. et al. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7477532","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":534670274,"identity":"28c07fd5-e6ca-48d0-a11c-f22f48cc9c6f","order_by":0,"name":"Shiyeol Jun","email":"","orcid":"","institution":"Gangnam Severance Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shiyeol","middleName":"","lastName":"Jun","suffix":""},{"id":534670275,"identity":"79974dc9-e1e8-4d66-b900-ffba9845fb6e","order_by":1,"name":"Seyeol Oh","email":"","orcid":"","institution":"Danwon 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07:30:13","extension":"png","order_by":22,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":935,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7477532/v1/b0ae502e2342954b121dced9.png"},{"id":94638646,"identity":"5c6a327d-ddb3-4f3a-97f6-9bcbed9ca8a2","added_by":"auto","created_at":"2025-10-29 07:30:13","extension":"xml","order_by":23,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":94725,"visible":true,"origin":"","legend":"","description":"","filename":"49b2efe43caa4251b222a5c7f225c01e1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7477532/v1/4b11360148bfb05d150da09e.xml"},{"id":94638647,"identity":"d0ada8e7-672b-49cb-878a-875a16fa13c0","added_by":"auto","created_at":"2025-10-29 07:30:13","extension":"html","order_by":24,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":107799,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7477532/v1/892ad69e5e613885b4a68d62.html"},{"id":94638631,"identity":"38967a03-4e2b-4328-ad96-d8214285a8d0","added_by":"auto","created_at":"2025-10-29 07:30:13","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":319829,"visible":true,"origin":"","legend":"\u003cp\u003eRadiographic image of radiopaque markers observed in the colon. (Yellow arrow)\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7477532/v1/0697dfcdf2b9ba7ca70797ac.png"},{"id":94638619,"identity":"0cf471b4-d1a6-470b-b8f3-b4d4610afb19","added_by":"auto","created_at":"2025-10-29 07:30:12","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":58259,"visible":true,"origin":"","legend":"\u003cp\u003eCONSORT flow diagram of patient enrollment, randomization, analysis\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7477532/v1/281b0bda86113c33eedccd5a.png"},{"id":94640678,"identity":"eb516ebc-1789-4af1-8c4b-a42ef07ff6c1","added_by":"auto","created_at":"2025-10-29 07:50:04","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":69723,"visible":true,"origin":"","legend":"\u003cp\u003ePostoperative clinical outcomes in the control and experimental groups\u003c/p\u003e\n\u003cp\u003e(a) Proportion of radiopaque markers that had reached the colon\u003c/p\u003e\n\u003cp\u003e(b) Abdominal discomfort on a 5-point numerical rating scale (1 = no discomfort, 5 = worst possible discomfort).\u003c/p\u003e\n\u003cp\u003e(c) Oral food intake, expressed as the percentage of the food provided.\u003c/p\u003e\n\u003cp\u003e(d) Serum C-reactive protein (CRP, mg/L).\u003c/p\u003e\n\u003cp\u003e(e) Neutrophil–lymphocyte ratio (NLR).\u003c/p\u003e\n\u003cp\u003eData are presented as mean ± 2 × standard error of the mean (SEM), which approximates the 95% confidence interval for each time-point.\u003c/p\u003e\n\u003cp\u003e*\u003cem\u003ep\u003c/em\u003e-values reflect the group-by-time interaction as determined by repeated-measures ANOVA .\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCRP,\u003c/em\u003eC-reactive Protein; \u003cem\u003eNLR,\u003c/em\u003e Neutrophil-lymphocyte ratio; \u003cem\u003eNRS,\u003c/em\u003enumerical rating scale; \u003cem\u003ePOD,\u003c/em\u003e postoperative day;\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7477532/v1/7b235cae19c8ccbdd4e6acc6.png"},{"id":107928774,"identity":"2babbc38-69fa-4846-b0fc-bfcc7bfa7b15","added_by":"auto","created_at":"2026-04-27 16:12:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":830326,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7477532/v1/3ffcc1b9-00f6-41c7-92d5-c6559386e028.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prucalopride succinate accelerates postoperative intestinal recovery following gastrectomy in a randomized clinical trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEnhanced recovery after surgery (ERAS) protocols have been widely adopted in gastrointestinal surgery to promote early recovery, reduce hospital length of stay, and minimize postoperative complications\u003csup\u003e\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. However, postoperative ileus (POI) remains a common problem after major abdominal surgeries such as gastrectomy, often leading to prolonged hospitalization and increased risk of complications such as atelectasis and infection\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003ePOI is commonly managed or prevented through the use of prokinetic agents targeting serotonin type 4 (5-HT\u003csub\u003e4\u003c/sub\u003e) receptors \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Nevertheless, recent evidence has demonstrated that mosapride fails to enhance postoperative bowel function after gastrectomy\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. In contrast to mosapride, prucalopride succinate, a highly selective 5-HT\u003csub\u003e4\u003c/sub\u003e receptor agonist has a primary effect on promoting colonic motility and has been shown to exert anti-inflammatory effects by modulating cholinergic signaling\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. It has demonstrated efficacy in accelerating colonic transit in patients following various gastrointestinal surgeries\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThese pharmacologic properties make it a suitable agent for addressing POI in the setting of gastric surgery. This randomized controlled trial was conducted to evaluate whether prucalopride improves bowel motility and reduces postoperative inflammation in patients undergoing minimally invasive gastrectomy within an ERAS framework\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design and ethics\u003c/h2\u003e\u003cp\u003eThis prospective, double-blind, randomized controlled trial was conducted at Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. The study protocol was approved by the Gangnam Severance Institutional Review Board (IRB No. 2021-0418-006) and complied with the Declaration of Helsinki. All participants provided written informed consent prior to enrollment. The study was registered at ClinicalTrials.gov (NCT05966246) on July 21, 2023. The clinical trial registration was completed post hoc due to an administrative oversight, although all ethical approvals and monitoring were in place.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003ePatients\u003c/h3\u003e\n\u003cp\u003eInclusion criteria included age between 20 and 80 years, histologically confirmed gastric adenocarcinoma prior to surgery, scheduled minimally invasive gastrectomy (laparoscopic or robotic) with curative intent, and American Society of Anesthesiologists (ASA) physical status classification of 3 or lower\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eExclusion criteria included distant metastases, evidence of preoperative intestinal obstruction, history of prior chemotherapy, or concurrent malignancy other than gastric cancer. Additional exclusions included history of major abdominal surgery likely to result in extensive adhesions, prior abdominal radiotherapy, hepatic or renal failure due to underlying comorbidities, uncontrolled diabetes mellitus, or known malabsorption syndromes such as inflammatory bowel disease or congenital metabolic disorders\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eStudy withdrawal criteria included requirement for additional bowel resection or extensive adhesiolysis during surgery, conversion to open gastrectomy, inability to resume oral intake postoperatively, or allergic reactions to either prucalopride or mosapride.\u003c/p\u003e\n\u003ch3\u003eTreatment and assessments\u003c/h3\u003e\n\u003cp\u003ePatients were randomly assigned in a 1:1 ratio to receive either prucalopride succinate (experimental group) or mosapride citrate (control group). Mosapride was selected as the control treatment based on findings from a prior randomized study, which showed no significant difference in bowel recovery between mosapride and placebo following minimally invasive gastrectomy\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. A clinical research coordinator not involved in patient care performed randomization on the day of surgery. Both patients and healthcare providers were blinded to the group allocation.\u003c/p\u003e\u003cp\u003eControl group patients received mosapride citrate (Gasmotin SR\u0026reg;; DaeWoong) 15 mg once daily from postoperative day (POD) 1 to POD 4, while experimental group patients received prucalopride succinate (Resolor\u0026reg;; Janssen Korea) once daily during the same period. Prucalopride dosing was 2 mg for patients under 65 years of age, and 1 mg for those aged 65 or older.\u003c/p\u003e\u003cp\u003eDuring surgery, a capsule containing 20 radiopaque ring markers (Kolomark\u0026trade;; Intropharm, Korea) was placed at the anastomosis site\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Bowel transit time was assessed by counting radiopaque markers visible in the stomach, small intestine, or colon on plain abdominal radiographs obtained on postoperative days 1, 3, and 5 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Markers passed in stool were considered to have reached the colon.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAll patients received perioperative care in accordance with ERAS guidelines, which included standardized anesthetic protocols, goal-directed fluid therapy to maintain near-zero balance, restricted opioid use, avoidance of nasogastric decompression, early initiation of enteral nutrition, and early postoperative mobilization\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Epidural anesthesia was not employed.\u003c/p\u003e\u003cp\u003ePatients followed a standardized postoperative dietary protocol consisting of sips of water or carbohydrate fluids on day 1, liquid diet on day 2, and soft diet on day 3, unless limited by patient tolerance.\u003c/p\u003e\u003cp\u003eThe primary outcome was bowel transit time, assessed by the percentage of radiopaque markers that had passed into the colon on postoperative day 3.\u003c/p\u003e\u003cp\u003eSecondary outcomes included time to first flatus, abdominal discomfort assessed using a 5-point numerical scale, proportion of food intake (ratio of food consumed to food provided), and inflammatory markers including C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Additionally, postoperative complications were evaluated within 30 days using the Clavien\u0026ndash;Dindo classification\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eBased on prior data indicating that prucalopride accelerated time to first flatus by approximately 1.37-fold following gastrointestinal surgery\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e, we hypothesized a 1.3-fold increase in bowel motility after gastrectomy. To achieve 90% power at a two-sided significance level of 5% while accounting for a 10% dropout rate with 1:1 randomization, a minimum of 53 patients per group was required.\u003c/p\u003e\u003cp\u003eNormality of continuous variables was assessed using the Kolmogorov\u0026ndash;Smirnov test. Normally distributed data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, and non-normally distributed data as median (interquartile range). Categorical variables are summarized as counts and percentages. Continuous variables were compared using the Student\u0026rsquo;s t-test or Mann-Whitney U test, while categorical variables were analyzed using the chi-square test or Fisher\u0026rsquo;s exact test.\u003c/p\u003e\u003cp\u003eFor outcomes measured repeatedly over time, a repeated measures analysis of variance (RM-ANOVA) was employed to evaluate group-by-time interactions. The sphericity assumption was assessed; when violated, Greenhouse\u0026ndash;Geisser correction was applied. RM-ANOVA tests whether group differences change over time and accounts for the correlation of repeated measurements within subjects.\u003c/p\u003e\u003cp\u003eA \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. All analyses were conducted using SPSS version 27.0 (IBM Corp., Armonk, NY, USA).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003ePatient characteristics\u003c/h2\u003e\u003cp\u003eIn total, the planned 106 patients were enrolled between January 2022 and June 2023. Patients were randomly assigned, with 53 patients allocated to each group. There were no dropouts from the control group, while two patients dropped out of the prucalopride group. One patient withdrew consent, and another was excluded following reoperation. (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eA total of 104 patients were included in the statistical analysis. Baseline characteristics, including age, sex, medical history, type of operation, and estimated blood loss, were comparable between the two groups. (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\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\u003ePatient 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=\"char\" char=\".\" 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\u003eCharacteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControl (n\u0026thinsp;=\u0026thinsp;53)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eExperimental (n\u0026thinsp;=\u0026thinsp;51)\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 (years)*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e61.0 (53.0\u0026ndash;69.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e58.0 (46.0\u0026ndash;69.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.539\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex\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;0.999\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=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e28 (52.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e27 (52.9%)\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\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e25 (47.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e24 (47.1%)\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\u003eASA score\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\u003e0.615\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3 (5.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (3.9%)\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\u003eII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e35 (66.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e38 (74.5%)\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=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e15 (28.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e11 (21.6%)\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\u003eBMI (kg/m2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e23.46\u0026thinsp;\u0026plusmn;\u0026thinsp;3.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e23.95\u0026thinsp;\u0026plusmn;\u0026thinsp;3.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.464\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrior abdominal surgery (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e13 (24.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e11 (21.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.817\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEstimated blood loss (cc)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e55.64\u0026thinsp;\u0026plusmn;\u0026thinsp;48.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e43.69\u0026thinsp;\u0026plusmn;\u0026thinsp;43.91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.192\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOperation time (min)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e178.30\u0026thinsp;\u0026plusmn;\u0026thinsp;35.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e173.37\u0026thinsp;\u0026plusmn;\u0026thinsp;31.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.663\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOperation method\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;0.999\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=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e44 (83.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e42 (82.4%)\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=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9 (17.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9 (17.6%)\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\u003eType of resection\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\u003e0.787\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSubtotal gastrectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e44 (83.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e44 (86.3%)\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\u003eTotal gastrectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9 (17.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7 (13.7%)\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\u003eAnastomosis type\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\u003e0.874\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eB-I\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e18 (34.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e19 (37.3%)\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\u003eB-II\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e16 (30.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13 (25.5%)\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\u003eSTG R-Y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e10 (18.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e12 (23.5%)\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\u003eTG R-Y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9 (17.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7 (13.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e*Age is presented as median (interquartile range) because the distribution was non-normal; \u003cem\u003ep\u003c/em\u003e-value was calculated with the Mann-Whitney U test.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eASA\u003c/em\u003e American Society of Anesthesiologists physical status score; \u003cem\u003eBMI\u003c/em\u003e Body mass index; \u003cem\u003eB-I\u003c/em\u003e Billroth I; \u003cem\u003eB-II\u003c/em\u003e Billroth II; \u003cem\u003eSTG R-Y\u003c/em\u003e Subtotal gastrectomy Roux-en Y; \u003cem\u003eTG R-Y\u003c/em\u003e Total gastrectomy Roux-en Y\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eMotility evaluation\u003c/h3\u003e\n\u003cp\u003eBowel motility was assessed in 100 patients (50 control, 50 experimental) after excluding four patients with missed radiopaque marker insertion during surgery. In cases where five or more of the 20 radiopaque marker rings remained impacted at the stomach or anastomosis site, those rings were excluded from the denominator. Significant differences in bowel motility between the two groups were observed on postoperative day 5. On POD 3, the mean percentage of markers that migrated to the colon was 58.25\u0026thinsp;\u0026plusmn;\u0026thinsp;38.25% in the control group and 67.53\u0026thinsp;\u0026plusmn;\u0026thinsp;37.47% in the experimental group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.223). On POD 5, the corresponding values were 90.20\u0026thinsp;\u0026plusmn;\u0026thinsp;15.29% and 96.90\u0026thinsp;\u0026plusmn;\u0026thinsp;10.15%, respectively (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012). (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\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\u003eClinical outcome associated with the gastrointestinal motility. \u003cem\u003ePOD\u003c/em\u003e postoperative day\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=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControl group (n\u0026thinsp;=\u0026thinsp;53)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eExperimental group (n\u0026thinsp;=\u0026thinsp;51)\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\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003ePercentage of markers in colon (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\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\u003ePOD1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e0.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e1.20\u0026thinsp;\u0026plusmn;\u0026thinsp;8.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.363\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=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e58.25\u0026thinsp;\u0026plusmn;\u0026thinsp;38.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e67.53\u0026thinsp;\u0026plusmn;\u0026thinsp;37.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.223\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePOD5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e90.20\u0026thinsp;\u0026plusmn;\u0026thinsp;15.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e96.90\u0026thinsp;\u0026plusmn;\u0026thinsp;10.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.012\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eProportion of food intake (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\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\u003ePOD2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e62.45\u0026thinsp;\u0026plusmn;\u0026thinsp;24.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e56.67\u0026thinsp;\u0026plusmn;\u0026thinsp;23.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.219\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=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e61.89\u0026thinsp;\u0026plusmn;\u0026thinsp;16.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e62.25\u0026thinsp;\u0026plusmn;\u0026thinsp;21.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.921\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePOD4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e62.74\u0026thinsp;\u0026plusmn;\u0026thinsp;18.41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e66.47\u0026thinsp;\u0026plusmn;\u0026thinsp;17.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.291\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePOD5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e61.42\u0026thinsp;\u0026plusmn;\u0026thinsp;19.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e67.94\u0026thinsp;\u0026plusmn;\u0026thinsp;20.79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.100\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eAbdominal discomfort scale (NRS 1\u0026ndash;5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\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\u003ePOD1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e2.94\u0026thinsp;\u0026plusmn;\u0026thinsp;1.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e2.76\u0026thinsp;\u0026plusmn;\u0026thinsp;1.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.469\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=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e3.55\u0026thinsp;\u0026plusmn;\u0026thinsp;1.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e3.41\u0026thinsp;\u0026plusmn;\u0026thinsp;1.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.628\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=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e3.53\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e3.52\u0026thinsp;\u0026plusmn;\u0026thinsp;1.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.996\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePOD4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e3.26\u0026thinsp;\u0026plusmn;\u0026thinsp;1.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e3.14\u0026thinsp;\u0026plusmn;\u0026thinsp;1.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.543\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePOD5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e2.79\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e2.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.569\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFirst flatus time (hour)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e74.97\u0026thinsp;\u0026plusmn;\u0026thinsp;20.58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e68.30\u0026thinsp;\u0026plusmn;\u0026thinsp;13.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.053\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003ePOD\u003c/em\u003e postoperative day\u003c/p\u003e\u003cp\u003eFood intake proportions showed no significant differences between the two groups on POD 3 and POD 5. On POD 3, the control group consumed 61.89\u0026thinsp;\u0026plusmn;\u0026thinsp;16.30% of provided food, while the experimental group consumed 62.25\u0026thinsp;\u0026plusmn;\u0026thinsp;21.01% (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.921). On POD 5, food intake was 61.42\u0026thinsp;\u0026plusmn;\u0026thinsp;19.30% in the control group and 67.94\u0026thinsp;\u0026plusmn;\u0026thinsp;20.79% in the experimental group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.100).\u003c/p\u003e\u003cp\u003eThe abdominal discomfort scores (NRS 1\u0026ndash;5) showed no significant differences between the groups throughout the postoperative period. On POD 3, the abdominal discomfort score was 3.53\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15 in the control group and 3.52\u0026thinsp;\u0026plusmn;\u0026thinsp;1.29 in the experimental group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.996).\u003c/p\u003e\u003cp\u003eTime to first flatus was slightly shorter in the experimental group (68.30\u0026thinsp;\u0026plusmn;\u0026thinsp;13.46 hours) compared with the control group (74.97\u0026thinsp;\u0026plusmn;\u0026thinsp;20.58 hours), with borderline statistical significance (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.053).\u003c/p\u003e\u003cp\u003eFor time-course analyses, repeated measures ANOVA revealed no significant group-by-time interactions for radiopaque marker transit (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.343) or abdominal discomfort scores (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.973). However, a significant group-by-time interaction was observed for food intake (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.049), with the experimental group showing progressive increases over time compared to consistent levels in the control group (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003ePostoperative outcomes\u003c/h3\u003e\n\u003cp\u003eWe observed no significant differences in the incidence or severity of postoperative complications between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Among the 104 patients, 24 (23.1%) experienced Clavien-Dindo grade I complications, and 49 (47.1%) experienced grade II complications, with similar distributions across groups. No adverse events related to prucalopride administration, including headache, allergic reactions, or hepatic dysfunction, were observed\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. No major complications such as anastomotic leakage, intra-abdominal abscess, or sepsis occurred in any patient.\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\u003eLaboratory Findings and Postoperative Course.\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=\"char\" char=\".\" 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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControl group (n\u0026thinsp;=\u0026thinsp;53)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eExperimental group (n\u0026thinsp;=\u0026thinsp;51)\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\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003ePostoperative complication (n)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\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\u003eGrade I\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e10 (18.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14 (27.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.143\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade II\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e22 (41.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e27 (52.9%)\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\u003eGrade IIIa\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1 (1.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (2.0%)\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\u003eCRP level (mg/dL)\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\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePOD1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e28.49\u0026thinsp;\u0026plusmn;\u0026thinsp;27.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e26.57\u0026thinsp;\u0026plusmn;\u0026thinsp;17.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.671\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=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e122.73\u0026thinsp;\u0026plusmn;\u0026thinsp;67.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e105.97\u0026thinsp;\u0026plusmn;\u0026thinsp;61.70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.191\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePOD5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e79.60\u0026thinsp;\u0026plusmn;\u0026thinsp;56.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e66.28\u0026thinsp;\u0026plusmn;\u0026thinsp;52.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.213\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eNeutrophil-to-lymphocyte ratio\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\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\u003ePOD1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6.93\u0026thinsp;\u0026plusmn;\u0026thinsp;2.77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6.34\u0026thinsp;\u0026plusmn;\u0026thinsp;3.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.33\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=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6.02\u0026thinsp;\u0026plusmn;\u0026thinsp;3.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.85\u0026thinsp;\u0026plusmn;\u0026thinsp;2.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.035\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePOD5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.91\u0026thinsp;\u0026plusmn;\u0026thinsp;1.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.059\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOpioid injection (n)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.25\u0026thinsp;\u0026plusmn;\u0026thinsp;2.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.51\u0026thinsp;\u0026plusmn;\u0026thinsp;2.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.156\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHospital stays day (n)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5.45\u0026thinsp;\u0026plusmn;\u0026thinsp;1.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.494\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003ePOD\u003c/em\u003e postoperative day, \u003cem\u003eCRP\u003c/em\u003e C-reactive Protein\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eCRP levels showed a similar trend with no significant differences on POD 1, 3 and 5. In contrast, the neutrophil-to-lymphocyte ratio (NLR) demonstrated a greater postoperative decrease in the experimental group. Although NLR values on POD 1 were comparable between groups (6.93\u0026thinsp;\u0026plusmn;\u0026thinsp;2.77 vs. 6.34\u0026thinsp;\u0026plusmn;\u0026thinsp;3.28, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.330), the experimental group showed significantly lower NLR on POD 3 (4.85\u0026thinsp;\u0026plusmn;\u0026thinsp;2.49 vs. 6.02\u0026thinsp;\u0026plusmn;\u0026thinsp;3.06, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.035), with a marginal difference remaining on POD 5 (3.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.47 vs. 3.91\u0026thinsp;\u0026plusmn;\u0026thinsp;1.62, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.059).\u003c/p\u003e\u003cp\u003eThe number of opioid injections and the length of postoperative hospital stay were similar between the two groups (3.25\u0026thinsp;\u0026plusmn;\u0026thinsp;2.93 vs 2.51\u0026thinsp;\u0026plusmn;\u0026thinsp;2.27, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.156; 5.45\u0026thinsp;\u0026plusmn;\u0026thinsp;1.10 vs. 5.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59 days, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.494).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn our study, prucalopride led to faster recovery of bowel motility and reduced systemic inflammation compared to mosapride in patients undergoing minimally invasive gastrectomy within an ERAS framework.\u003c/p\u003e\n\u003cp\u003eAlthough ERAS protocols recommend the use of prokinetic agents, the strength of recommendation has been weak due to limited evidence from randomized trials. Our findings provide robust clinical data supporting the use of prucalopride as an effective adjunct to ERAS protocols for improving postoperative gastrointestinal function.\u003c/p\u003e\n\u003cp\u003eThe improvement of bowel transit observed with prucalopride may be attributed to its distinct pharmacological profile. Unlike mosapride, which enhances gastrointestinal motility mainly through vagal stimulation of the pylorus, which is resected during gastrectomy, prucalopride exhibits high selectivity for 5-HT\u003csub\u003e4\u003c/sub\u003e receptors and enhances colonic motility, which is particularly relevant in the setting of gastrectomy\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e5-HT\u003csub\u003e4\u003c/sub\u003e receptor activation by prucalopride can stimulate cholinergic anti-inflammatory pathways through \u0026alpha;7 nicotinic acetylcholine receptors on muscularis macrophages, potentially reducing early inflammatory responses\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. This mechanism may explain the significantly lower NLR observed in the prucalopride group on POD 3, as NLR reflects early neutrophilic inflammation, while CRP levels\u0026mdash;which peak later in the inflammatory cascade\u0026mdash;showed no significant differences between groups\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eA previous randomized controlled trial also investigated the effects of prucalopride on postoperative gastrointestinal recovery in patients undergoing various types of gastrointestinal surgery, including ileocecal resection, colectomy, and gastroduodenal surgeries\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. In the prior study, the experimental group receiving prucalopride showed significantly faster recovery of bowel motility, compared to the placebo group, which is consistent with the results of our study. However, the majority of patients (79 out of 110, 71.8%) underwent surgery via laparotomy rather than a minimally invasive approach. Therefore, while the findings support the efficacy of prucalopride, the clinical setting differed from our study, which was conducted entirely within the framework of an ERAS protocol incorporating minimally invasive gastrectomy.\u003c/p\u003e\n\u003cp\u003eOur findings suggest that prokinetic agents may be more effective when targeting gastrointestinal segments that remain intact after surgery. For instance, mosapride, which enhances gastric and duodenal motility, has shown efficacy in patients undergoing colectomy, where the upper gastrointestinal tract remains intact\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Conversely, in this study with gastrectomy patients where the pylorus and gastric antrum are removed, prucalopride\u0026mdash;a colonic prokinetic\u0026mdash;demonstrated superior outcomes. This highlights the importance of comprehensive motility recovery, not only small bowel function, in the management of postoperative ileus.\u003c/p\u003e\n\u003cp\u003eSeveral limitations warrant mention. First, this single-center study was conducted in an ethnically homogeneous population, limiting generalizability to other institutions or diverse populations. Second, although improvements were observed in objective markers such as time to first flatus, radiopaque marker transit, and neutrophil-to-lymphocyte ratio, no significant differences were found in hospital length of stay or complication rates between groups. Notably, however, the experimental group demonstrated progressive increases in food intake over time (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.049), suggesting potential practical benefits in functional recovery. Finally, the different appearances of mosapride and prucalopride compromised complete blinding, potentially allowing patients to identify their assigned treatment.\u003c/p\u003e\n\u003cp\u003eDespite these limitations, this prospective, randomized controlled trial provides meaningful evidence for the use of prucalopride in postoperative recovery after minimally invasive gastrectomy. The findings strongly support incorporating prucalopride into ERAS protocols, particularly as an evidence-based strategy for enhancing gastrointestinal motility after gastrectomy.\u003c/p\u003e\n\u003cp\u003eIn conclusion, prucalopride improves the recovery of intestinal motility and reduces inflammatory markers following minimally invasive gastrectomy in patients with gastric cancer. Therefore, prucalopride may play a promising role in ERAS protocols for gastrectomy patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eAdditional information\u003c/h2\u003e\u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis study was supported by the new faculty research seed money grant of Yonsei University College of Medicine for 2019 (2019-32-0021).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eS.J. and S.O. contributed equally to this work as co-first authors. S.J. conducted data collection and statistical analysis, edited the manuscript, and managed manuscript submission. S.O. contributed to conceptualization and methodology, conducted investigation and data collection, and wrote the original draft. J.E.J. performed data collection and statistical analysis. S.H.N. provided supervision and project administration. I.G.K. contributed to conceptualization and supervision, acquired funding, provided project administration, conducted surgical procedures for enrolled patients, reviewed and edited the manuscript, and served as corresponding author. All authors reviewed and approved the final version of the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe would like to thank Editage (www.editage.co.kr) for English language editing.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eDatasets used and/or analyzed are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKehlet, H. \u0026amp; Wilmore, D. W. Evidence-based surgical care and the evolution of fast-track surgery. \u003cem\u003eAnn. 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Surg.\u003c/em\u003e \u003cb\u003e15\u003c/b\u003e, 1361\u0026ndash;1367. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11605-011-1567-x\u003c/span\u003e\u003cspan address=\"10.1007/s11605-011-1567-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2011).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7477532/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7477532/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe enhanced recovery after surgery (ERAS) protocol includes prokinetic agents to reduce postoperative ileus. This double-blind, randomized controlled trial enrolled patients scheduled for minimally invasive gastrectomy for gastric cancer. Patients were randomly assigned to receive either mosapride citrate (control) or prucalopride succinate (experimental) from postoperative days 1 to 4. Bowel motility was assessed by tracking radiopaque marker migration on serial abdominal radiographs, along with first-flatus time, food intake, and inflammatory markers. Baseline characteristics were comparable between groups. On postoperative day 5, the percentage of radiopaque markers passed to the colon was significantly higher in the experimental group. (96.90\u0026thinsp;\u0026plusmn;\u0026thinsp;10.15% vs 90.20\u0026thinsp;\u0026plusmn;\u0026thinsp;15.29%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012) The neutrophil\u0026ndash;lymphocyte ratio was also lower on postoperative day 3 in the experimental group (4.85\u0026thinsp;\u0026plusmn;\u0026thinsp;2.49 vs 6.02\u0026thinsp;\u0026plusmn;\u0026thinsp;3.06, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.035). Prucalopride succinate enhances bowel motility after gastrectomy and may reduce early postoperative inflammation. It may be considered as an adjunct to ERAS protocols in gastric cancer surgery.\u003c/p\u003e","manuscriptTitle":"Prucalopride succinate accelerates postoperative intestinal recovery following gastrectomy in a randomized clinical trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-29 07:30:08","doi":"10.21203/rs.3.rs-7477532/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-02T11:09:06+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-23T13:42:56+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-13T03:58:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"184555041999760347914881952708451867418","date":"2025-11-29T23:49:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"157507328150762004658369078768920601647","date":"2025-11-28T10:45:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-16T18:36:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"82217612594298288582780559555584416289","date":"2025-10-23T10:21:48+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-14T22:24:02+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-13T05:41:06+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-08T02:53:58+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-04T06:12:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-09-04T06:10:10+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b1d8a5a8-7b92-4ead-a4be-026708ebb0f8","owner":[],"postedDate":"October 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":56849571,"name":"Biological sciences/Cancer"},{"id":56849572,"name":"Health sciences/Gastroenterology"},{"id":56849573,"name":"Health sciences/Medical research"},{"id":56849574,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2026-04-27T16:09:47+00:00","versionOfRecord":{"articleIdentity":"rs-7477532","link":"https://doi.org/10.1038/s41598-026-45110-2","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2026-04-20 15:57:52","publishedOnDateReadable":"April 20th, 2026"},"versionCreatedAt":"2025-10-29 07:30:08","video":"","vorDoi":"10.1038/s41598-026-45110-2","vorDoiUrl":"https://doi.org/10.1038/s41598-026-45110-2","workflowStages":[]},"version":"v1","identity":"rs-7477532","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7477532","identity":"rs-7477532","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}