Predicting Major Low Anterior Resection Syndrome After Stoma Reversal Using Pre-reversal High-Resolution Anorectal Manometry: A Prospective Study

Predicting Major Low Anterior Resection Syndrome After Stoma Reversal Using Pre-reversal High-Resolution Anorectal Manometry: A Prospective Study | 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 Predicting Major Low Anterior Resection Syndrome After Stoma Reversal Using Pre-reversal High-Resolution Anorectal Manometry: A Prospective Study Xinchun Wu, Xi Zheng, Yuchen Yao, Yuhang Tian, Yingjiang Ye, Changkun Zhong, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9442558/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background Low anterior resection syndrome frequently complicates sphincter-preserving rectal cancer surgery. This study aimed to evaluate the capacity of pre-reversal high-resolution anorectal manometry and clinical factors to predict major low anterior resection syndrome at three months post-stoma reversal. Methods This prospective cohort study enrolled 46 patients with low rectal cancer undergoing protective stoma reversal. Prior to reversal, clinical data, colonoscopy (for diversion colitis), and high-resolution anorectal manometry parameters were assessed. Bowel function was evaluated using the low anterior resection syndrome score at one and three months. Multivariable logistic regression identified independent predictors of major low anterior resection syndrome at three months, followed by the construction and internal validation of a predictive nomogram. Results The incidence of major LARS decreased from 80.4% at one month to 47.8% at three months. Pre-reversal first sensation volume negatively correlated with 3-month low anterior resection syndrome scores (ρ = -0.32, p = 0.030). Multivariable analysis identified diversion colitis (adjusted OR = 6.95, 95% CI: 1.47 to 44.30, p = 0.023) and lower first sensation volume (adjusted OR = 0.90, 95% CI: 0.81 to 0.98, p = 0.031) as independent predictors. Causal mediation analysis confirmed these factors operated independently (p = 0.904). The composite predictive model demonstrated reliable discrimination (AUC = 0.736) and maintained stability (optimism-corrected C-index = 0.712) during internal validation. Conclusions Reduced first sensation volume and diversion colitis independently predict mid-term major low anterior resection syndrome. The developed pre-reversal nomogram facilitates individualized risk stratification, highlighting a potential window for targeted preemptive interventions. Low anterior resection syndrome High-resolution anorectal manometry Stoma reversal Diversion colitis First sensation volume Figures Figure 1 Figure 2 Figure 3 Figure 4 1.Introduction Colorectal cancer remains one of the most prevalent malignancies globally, with rectal cancer accounting for approximately one-third of all cases [ 1 ]. Advancements in surgical techniques and neoadjuvant therapies have significantly improved sphincter preservation rates in patients with low rectal cancer [ 2 ]. However, Low Anterior Resection Syndrome (LARS), characterized by fecal urgency, frequency, and incontinence, remains a prevalent complication, affecting up to 80% of patients postoperatively [ 3 – 4 ]. These symptoms profoundly impair quality of life and social reintegration [ 5 ]. The etiology of LARS is multifactorial, involving anatomical and physiological disruptions. Recognized risk factors include neoadjuvant radiotherapy, low anastomotic height, and the duration of fecal diversion [ 3 ]. During the period of defunctioning ileostomy, the distal bowel may undergo "disuse" changes, such as mucosal atrophy and diversion colitis, which can impact neorectal function following intestinal restoration [ 6 – 7 ]. High-resolution anorectal manometry (HRAM) provides an objective assessment of anorectal physiological integrity [ 8 ]. While HRAM is typically used for the retrospective diagnosis of existing defecation disorders, manometric parameters, such as rectal sensory thresholds and compliance, may indicate the functional reserve of the neorectum [ 9 ]. Consequently, pre-reversal manometric evaluation may offer predictive value regarding functional outcomes after stoma closure [ 5 ]. In this prospective study, we aimed to evaluate the predictive capacity of pre-reversal HRAM parameters, combined with clinicopathological characteristics, for the occurrence of major LARS at three months post-stoma reversal. By identifying physiological and clinical determinants based on HRAM, we sought to develop a risk-stratification model. This framework is intended to provide clinicians with an objective tool to identify high-risk individuals prior to stoma closure, thereby assisting in clinical counseling and the planning of rehabilitative interventions for patients with low rectal cancer. 2.Methods 2.1 Patients and study design This prospective cohort study was conducted at Peking University People’s Hospital. We initially enrolled 50 patients diagnosed with low rectal cancer who underwent sphincter-preserving surgery (low anterior resection) combined with a protective ileostomy from October 2022 to April 2025. Through the screening and follow-up process, 46 patients were finally enrolled for analysis. The inclusion criteria were as follows: (1) histologically confirmed rectal adenocarcinoma; (2) tumor lower margin ≤ 10 cm from the anal verge; (3) underwent radical proctectomy with protective ileostomy and subsequent stoma reversal at our center. The exclusion criteria were: (1) age 80 years; (2) multiple primary malignancies or distant metastasis; (3) concomitant inflammatory bowel disease; (4) severe postoperative complications such as anastomotic leakage or pelvic infection; (5) tumor recurrence or death during the follow-up period; (6) incomplete clinicopathological data or refusal to participate in follow-up. During the follow-up period, 4 patients were excluded: 2 due to refusal of subsequent treatment, 1 due to tumor recurrence, and 1 due to the development of a pelvic abscess ( Fig. 1 ). This study was approved by the Ethics Committee of Peking University People’s Hospital and was conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from all participants. 2.2 Clinical data and follow-up Demographic and clinicopathological data, including age, sex, body mass index (BMI), tumor distance from the anal verge, clinical TNM stage, tumor pathology type, surgical procedure and details of neoadjuvant/adjuvant chemotherapy or radiotherapy, were retrieved from electronic medical records. Diversion colitis was assessed by colonoscopy prior to stoma reversal. Postoperative bowel function was evaluated at 1 month and 3 months following stoma reversal using the LARS score and the Wexner anal incontinence score. The LARS score categorized patients into "no LARS" (0–20), "minor LARS" (21–29), and "major LARS" (30–42). For binary analysis, patients were grouped into Major LARS versus No/Minor LARS. 2.3 Anorectal functional assessment All patients underwent HRAM 1–2 days prior to the stoma reversal surgery. The procedure was performed by an experienced technician using a solid-state manometry system (ZGJ-D3, AOYUAN). The HRAM parameters measured included: mean anal resting pressure (MARP), maximum squeeze pressure (MSP), duration of sustained squeeze (DSS), anal residual pressure (ARP), and rectal resting pressure (RRP). Rectal sensory function was assessed by incremental balloon inflation to determine the first sensation volume (FSV) and maximum tolerated volume (MTV). 2.4 Statistical analysis Statistical analyses used R version 4.3.2, with figures refined in Adobe Illustrator version 28.5.0. For baseline characteristics (Table 1 ), categorical and continuous variables were compared via χ2 and Wilcoxon rank-sum tests, respectively. Spearman’s analysis evaluated correlations between HRAM parameters and functional scores (LARS/Wexner). Variables with p < 0.20 in univariate analysis entered a multivariable logistic regression to identify independent predictors of major LARS at 3 months, yielding odds ratios (OR) and 95% confidence intervals (CI) presented in forest plots. Causal mediation analysis utilizing 1,000 bootstrap resamples investigated the diversion colitis-FSV interaction. A predictive model, visualized via nomogram and 3D response surface plot, was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves (mean absolute error), and decision curve analysis. Internal validation utilized 1,000 bootstrap resamples to calculate the optimism-corrected C-index and calibration slope. Post-hoc power analysis assessed correlation strength. All statistical tests were two-sided, and p < 0.05 was considered statistically significant. Table 1 Population characteristic and correlation with LARS score. Characteristics Level The 1-month Postoperative LARS Score The 3-month Postoperative LARS Score Major No or Minor p Major No or Minor p Sum 37 9 22 24 Age (mean(SD)) 63.76(10.23) 68.67(8.90) 0.194 65.27(8.53) 64.21(11.49) 0.725 BMI (median[IQR]) 23.42[21.45,25.06] 24.47[23.67,25.78] 0.124 23.40[21.70,25.20] 24.01[21.70,25.23] 0.583 Distance from Anal Verge (%) ≤ 5cm 21(56.76) 7(77.78) 0.437 13(59.09) 15(62.50) 1.000 > 5cm 16(43.24) 2(22.22) 9(40.91) 9(37.50) Sex (%) Female 9(24.32) 4(44.44) 0.430 4(18.18) 9(37.50) 0.260 Male 28(75.68) 5(55.56) 18(81.82) 15(62.50) cT (%) T1 2(5.41) 1(11.11) 0.614 1(4.55) 2(8.33) 0.817 T2 5(13.51) 0(0.00) 2(9.09) 3(12.50) T3 21(56.76) 5(55.56) 14(63.64) 12(50.00) T4 9(24.32) 3(33.33) 5(22.73) 7(29.17) cN (%) N0 12(32.43) 2(22.22) 0.835 6(27.27) 8(33.33) 0.905 N1 14(37.84) 4(44.44) 9(40.91) 9(37.50) N2 11(29.73) 3(33.33) 7(31.82) 7(29.17) Preoperative Chemotherapy (%) No 23(62.16) 6(66.67) 1.000 13(59.09) 16(66.67) 0.821 Yes 14(37.84) 3(33.33) 9(40.91) 8(33.33) Preoperative Radiotherapy (%) No 22(59.46) 6(66.67) 0.987 11(50.00) 17(70.83) 0.253 Yes 15(40.54) 3(33.33) 11(50.00) 7(29.17) Anastomosis (%) ETE 30(81.08) 8(88.89) 0.949 19(86.36) 19(79.17) 0.800 ETS 7(18.92) 1(11.11) 3(13.64) 5(20.83) Dilation Time (median[IQR]) 146.00[114.00,219.00] 133.000[115.00,176.00] 0.455 139.00[116.25,165.75] 146.50[114.00,222.00] 0.684 Diversion Colitis (%) No 19(51.35) 7(77.78) 0.289 9(40.91) 17(70.83) 0.081 Yes 18(48.65) 2(22.22) 13(59.09) 7(29.17) Pathology Type (%) Polypoid 8(21.62) 4(44.44) 0.330 5(22.73) 7(29.17) 0.872 Ulcerating 29(78.38) 5(55.56) 17(77.27) 17(70.83) Postoperative Chemotherapy (%) No 21(56.76) 5(55.56) 1.000 13(59.09) 13(54.17) 0.969 Yes 16(43.24) 4(44.44) 9(40.91) 11(45.83) ARP (median[IQR]) 3.80[2.20,5.70] 3.60[2.70,4.70] 0.901 2.80[1.45,5.35] 3.95[2.63,5.80] 0.384 MSP (median[IQR]) 16.00[11.00,22.00] 10.80[7.50,18.30] 0.128 18.15[10.73,22.15] 15.30[9.48,18.35] 0.291 DSS (median[IQR]) 21.00[19.00,29.00] 19.00[10.00,23.00] 0.121 24.50[16.25,29.75] 21.00[19.00,23.25] 0.481 MARP (median[IQR]) 9.60[4.00,12.90] 10.60[7.30,11.30] 0.561 8.50[3.88,12.35] 10.35[6.85,13.20] 0.397 RRP (median[IQR]) 0.10[0.10,0.30] 0.500[0.00,0.60] 0.299 0.10[0.00,0.1] 0.30[0.10,0.60] 0.004 FSV (median[IQR]) 20.00[15.00,30.00] 30.00[20.00,30.00] 0.099 20.00[15.00,28.75] 27.50[20.00,30.00] 0.052 MTV (median[IQR]) 50.00[45.00,60.00] 50.00[45.00,55.00] 0.823 52.50[45.00,60.00] 50.00[45.00,55.00] 0.756 LARS, low anterior resection syndrome; SD, standard deviation; IQR, interquartile range; BMI, body mass index; ETE, end−to−end anastomosis; ETS, end−to−side anastomosis; ARP, anal residual pressure; MSP, maximum squeeze pressure; DSS, duration of sustained squeeze; MARP, mean anal resting pressure; RRP, rectal resting pressure; FSV, first sensation volume; MTV, maximum tolerated volume. 3.Results 3.1 Patients’ characteristics A total of 46 patients undergoing sphincter-preserving surgery and stoma reversal for low rectal cancer completed the follow-up protocol. Baseline characteristics, stratified by LARS severity at one and three months, are summarized in Table 1 . The predominantly male cohort had a mean age of approximately 65 years. Most tumors (60.9%) were within 5 cm of the anal verge, with patients frequently receiving preoperative chemotherapy (37.0%) or radiotherapy (39.1%). Postoperatively, patients exhibited a high initial burden of defecation dysfunction, with major LARS incidence reaching 80.4% (37/46) at one month. However, functional recovery was observed over time; by three months, major LARS prevalence decreased to 47.8% (22/46), while the proportion of patients with no or minor LARS increased from 19.6% to 52.2%. Univariate comparisons revealed no significant differences between the major and no/minor LARS groups at one or three months regarding age, BMI, sex, tumor distance, TNM stage, or neoadjuvant/adjuvant therapies (all p > 0.05). Surgical factors, including anastomosis type and dilation time, also lacked significant correlation with LARS severity. While diversion colitis was more frequent in patients with major LARS at three months (59.09% vs. 29.17%), this baseline difference did not reach statistical significance (p = 0.081). 3.2 Correlation between pre-reversal HRAM parameters and postoperative functional outcomes To further explore the relationship between anorectal physiological profiles and postoperative defecation function, Spearman correlation analysis was performed between pre-reversal HRAM parameters and functional scores (LARS and Wexner) at both follow-up time points ( Fig. 2a ). While several manometric metrics exhibited negative trends with respect to functional scores, the most significant associations were observed between rectal physiological parameters and the 3-month LARS scores. Specifically, the first sensation volume, representing the rectal sensory threshold, demonstrated a significant negative correlation with the LARS score at three months (ρ = −0.32, p = 0.030; Fig. 2b ). A post-hoc power analysis based on this observed effect size (r = − 0.32,n = 46) indicated a statistical power of 0.594 ( Supplementary Fig. S1 a ). This inverse relationship indicates that patients with a lower sensory threshold (rectal hypersensitivity) prior to stoma reversal were more likely to experience higher LARS scores and more severe defecation dysfunction. Similarly, RRP was also significantly and negatively correlated with the 3-month LARS score (ρ = −0.29, p = 0.040; Fig. 2c ). These findings are consistent with the inter-group differences observed in Table 1 , where lower RRP (median 0.10 vs. 0.30; p = 0.004) and a trend toward lower FSV (median 20.00 mL vs. 27.50 mL; p = 0.052) were characteristic of the major LARS cohort, suggesting an association between preoperative rectal hypersensitivity and poor long-term functional outcomes. In contrast, the correlations between HRAM parameters and functional outcomes at one month postoperatively, as well as with the Wexner incontinence scores at both time points, did not reach statistical significance (all p > 0.05). Although certain trends were noted, such as the negative correlation between ARP and the 3-month Wexner score (ρ = −0.24), the overall results suggest that pre-reversal rectal sensory and pressure metrics, particularly FSV and RRP, are more specifically predictive of the severity of LARS during the mid-term recovery phase than of early-stage dysfunction or isolated anal incontinence. 3.3 FSV and diversion colitis as independent predictors of major LARS at 3 months postoperatively To identify the key determinants of significant defecation dysfunction, univariate and multivariable logistic regression analyses were performed targeting major LARS at three months post-stoma reversal (Table 2 ). Factors with a p < 0.200 in the univariate analysis, including sex, preoperative radiotherapy, diversion colitis, and HRAM parameters such as MSP, RRP, and FSV, were incorporated into the multivariable model. The results, visualized in a forest plot ( Fig. 3a ), identified diversion colitis and FSV as the only independent predictors of major LARS. Specifically, the presence of diversion colitis was associated with a nearly seven-fold increase in the risk of major LARS (adjusted OR = 6.95, 95% CI: 1.47 to 44.30, p = 0.023). Conversely, FSV served as a protective factor, with each 1-mL increase in the sensory threshold reducing the odds of major LARS by 10% (adjusted OR = 0.90, 95% CI: 0.81 to 0.98, p = 0.031). Subsequent causal mediation analysis was employed to investigate the potential interaction between diversion colitis and FSV. The results confirmed that the impacts of diversion colitis and FSV on LARS were mutually independent, with no significant indirect effects observed (average causal mediation effect (ACME) = -0.101, 95% CI: -2.74 to 2.79, p = 0.904, Fig. 3b ). To ensure the robustness of this finding, we performed 1,000 non-parametric bootstrap resamples; the resulting density plot demonstrated that the ACME distribution was symmetrically centered around zero, visually corroborating the lack of a significant mediatory pathway ( Fig. 3c ). These findings collectively suggest that diversion colitis and rectal hypersensitivity operate through distinct and independent biological pathways in the development of postoperative LARS. Table 2 Univariate and multivariable logistic regression analysis of factors associated with major LARS at 3 months postoperatively. Characteristics Factors Univariate Regression Multivariable Regression OR(95% CI) p OR(95% CI) p Age 1.01(0.95,1.07) 0.718 BMI 0.95(0.79,1.14) 0.587 Distance from Anal Verge 0.813 5cm 1.15(0.35,3.82) Sex 0.142 0.072 Female — Male 2.70(0.72,11.6) 5.73(0.96, 47.0) cT 0.815 T1 — T2 1.33(0.07,41.6) T3 2.33(0.20,54.0) T4 1.43(0.11,35.9) cN 0.905 N0 — N1 1.33(0.33,5.61) N2 1.33(0.30,6.10) Preoperative Chemotherapy 0.595 No — Yes 1.38(0.42,4.70) Preoperative Radiotherapy 0.147 0.436 No — — Yes 2.43(0.73,8.51) 1.86(0.39, 9.32) Anastomosis 0.518 ETE — ETS 0.60(0.11,2.80) Dilation Time 1.00(0.99,1.01) 0.534 Diversion Colitis 0.039 0.023 No — — Yes 3.51(1.06,12.5) 6.95(1.47, 44.3) Pathology Type 0.619 Polypoid — Ulcerating 1.40(0.37,5.57) Postoperative Chemotherapy 0.736 No — Yes 0.82(0.25,2.64) ARP 0.93(0.75,1.13) 0.444 MSP 1.06(0.98,1.15) 0.177 1.09(0.99, 1.23) 0.111 DSS 1.04(0.96,1.12) 0.351 MARP 0.99(0.91,1.08) 0.846 RRP 0.41(0.09,1.32) 0.144 0.34(0.07, 1.20) 0.108 FSV 0.93(0.86,1.00) 0.035 0.90(0.81, 0.98) 0.031 MTV 0.99(0.95,1.03) 0.587 LARS, low anterior resection syndrome; OR, odds ratio; CI, confidence interval; BMI, body mass index; ETE, end−to−end anastomosis; ETS, end−to−side anastomosis; ARP, anal residual pressure; MSP, maximum squeeze pressure; DSS, duration of sustained squeeze; MARP, mean anal resting pressure; RRP, rectal resting pressure; FSV, first sensation volume; MTV, maximum tolerated volume. The clinical impact of these predictors was further characterized using raincloud plots for phenotypic stratification ( Fig. 3d-k ). Patients were categorized into FSV-High and FSV-Low groups based on the median FSV value. While neither diversion colitis nor FSV significantly affected LARS or Wexner scores at the early 1-month follow-up ( Fig. 3d-g ), their influence became pronounced by the 3-month time point. At three months, LARS scores were significantly higher in patients with diversion colitis compared to those without (p = 0.024; Fig. 3h ) and in the FSV-Low group compared to the FSV-High group (p = 0.032; Fig. 3i ). Notably, these factors specifically predicted the severity of LARS but showed no significant correlation with Wexner incontinence scores at either follow-up interval ( Fig. 3j-k ), underscoring their specific role in the pathophysiology of low anterior resection syndrome rather than isolated anal sphincter insufficiency. 3.4 Construction and validation of the predictive model for major LARS To provide a clinically applicable tool for risk stratification, a multivariable logistic regression model was constructed using the identified independent predictors: FSV and the presence of diversion colitis. The final predictive model was established as follows: logit(P) = 1.2810−(0.0899×FSV)+(1.5105×Diversion Colitis) The model demonstrated a significant goodness-of-fit (Likelihood Ratio χ 2 = 9.72, df = 2, p = 0.008) and a Nagelkerke R 2 of 0.254. The synergistic effect of these two variables on the probability of developing major LARS is illustrated in a 3D response surface plot ( Fig. 4a ), which visually depicts how the risk escalates sharply as FSV decreases in the presence of diversion colitis. The discriminative ability of the composite model was evaluated using ROC curve analysis, which revealed that the composite model achieved an AUC of 0.736 (95% CI: 0.59 to 0.88), significantly outperforming the predictive value of FSV alone ( Fig. 4c ). To facilitate clinical application, these findings were translated into a nomogram ( Fig. 4b ), enabling individualized risk estimation for major LARS. Beyond discriminative performance, the model’s reliability was assessed through calibration and clinical utility analyses. The calibration curve ( Fig. 4d ) demonstrated strong agreement between predicted and observed probabilities, characterized by a mean absolute error of 0.059 and a 0.9 quantile error of 0.14, indicating minimal systematic bias. Subsequent decision curve analysis ( Fig. 4e ) yielded a superior net benefit over "intervention-for-all" or "intervention-for-none" strategies across a broad range of threshold probabilities, which corroborated the model’s potential value. Such results suggest that the model may serve as a supportive tool for risk stratification, potentially assisting surgeons in identifying high-risk individuals and facilitating more informed clinical counseling prior to stoma reversal. Finally, internal validation via 1,000 bootstrap resamples was performed to address potential overfitting. After accounting for over-optimism, the model retained high stability with a corrected C-index of 0.712 and a calibration slope of 0.921 ( Supplementary Fig. S1 b ), reinforcing its reliability for clinical risk prediction. 4.Discussion The most significant finding of this study is the integration of pre-reversal anorectal physiological parameters and clinical inflammatory status to predict major LARS. We identified FSV and diversion colitis as independent determinants, and the established predictive model demonstrated potential performance in risk-stratifying patients at three months post-reversal. A primary highlight of this research is its prospective focus on the pre-reversal window, shifting the clinical paradigm from retrospective symptom management toward proactive identification and early intervention for patients with low rectal cancer. HRAM provides a standardized physiological framework for decoding the complex pathophysiology of LARS, moving beyond basic pressure metrics to quantify neorectal sensitivity and compliance [ 9 ]. In our cohort, the predictive value of FSV highlights rectal hypersensitivity as a primary driver of postoperative dysfunction. A reduced FSV indicates that the neorectum triggers the defecation reflex at lower fecal volumes, a phenomenon fundamentally resulting from the surgical replacement of the compliant rectal ampulla with a less distensible colonic reservoir [ 10 ]. Chen [ 15 ] demonstrated that the urge volume is drastically reduced in patients with major LARS (averaging 11.8 ml) compared to both healthy subjects and those with primary fecal incontinence. This hypersensitivity is further modulated by the inflammatory status of the diverted bowel segment. Diversion colitis, resulting from short-chain fatty acid deficiency, induces mucosal inflammation and disuse atrophy, which sensitizes local visceral afferent nerves and lowers sensory thresholds [ 11 , 12 ]. The clinical relevance of this inflammatory mechanism is underscored by Koifman [ 13 ], who identified a prolonged interval from primary surgery to stoma closure as a primary risk factor for long-term LARS, a duration strongly associated with the progression of diversion colitis and neorectal atrophy. While neorectal hypersensitivity plays a central role, LARS etiology also encompasses structural anal sphincter damage. Ekkarat [ 16 ] and Chen [ 15 ] highlight low anastomotic height, adjuvant radiotherapy, and compromised anal pressures as major LARS risk factors. Similarly, Kakodkar [ 14 ] identified absent rectoanal inhibitory reflexes and subnormal MTV as independent long-term predictors. Although these studies emphasize anatomical disruption and isolated sphincter insufficiency, our research identifies FSV as a more sensitive, early marker of neorectal hypersensitivity and a superior predictor for mid-term LARS. Unlike the traditional focus on sphincter mechanics, our findings suggest mid-term functional impairment is primarily driven by the interplay of heightened sensory thresholds and diversion colitis, which readily overwhelms marginally competent sphincters. Integrating these markers provides a nuanced baseline for pre-reversal risk stratification, enabling proactive identification of high-risk patients. Meanwhile, the temporal evolution of functional recovery warrants discussion. Neither HRAM parameters nor diversion colitis predicted major LARS at one month post-reversal, yet both became highly significant at three months. This delay likely reflects an "acute adaptation phase" where early defecatory patterns are overwhelmed by transient factors like anastomotic edema, surgical stress, and microbiome alterations [ 17 ]. As these acute disturbances subside by the third month, the true functional impact of baseline neorectal hypersensitivity and chronic mucosal inflammation dictates mid-term bowel function [ 18 ]. Furthermore, causal mediation analysis confirmed that diversion colitis and FSV operate independently (ACME = -0.101, p = 0.904), suggesting dual, parallel mechanisms. Diversion colitis induces superficial, chemically driven mucosal sensitization via short-chain fatty acid starvation [ 12 ], whereas reduced FSV reflects deeper structural or neurogenic alterations, including the loss of the compliant rectal ampulla and impaired pelvic nerve signaling [ 19 ]. Understanding these independent pathways supports targeted prehabilitation using our proposed nomogram. For severe diversion colitis, preoperative topical short-chain fatty acid enemas or probiotic irrigations may restore the mucosal barrier and reduce inflammatory sensitization [ 20 – 21 ]. Concurrently, patients with markedly reduced FSV may benefit from early biofeedback therapy, utilizing volumetric balloon desensitization to elevate sensory thresholds [ 22 ]. Ultimately, shifting from postoperative symptom management to preoperative physiological optimization holds the potential to significantly mitigate the burden of major LARS. Several limitations of this study must be acknowledged when interpreting our findings. First, this was a single-center study with a relatively small sample size of 46 patients. As indicated by our post-hoc power analysis, the statistical power for the correlation between FSV and the 3-month LARS score was 0.594, increasing the risk of Type II errors and potentially obscuring the predictive significance of other HRAM parameters. Second, the follow-up period was limited to three months post-stoma reversal. While this timeframe effectively captures early-to-mid-term functional recovery, postoperative bowel function continuously adapts for up to 12 to 24 months. Consequently, the long-term trajectory of major LARS and the durability of FSV as a predictive marker remain to be elucidated. Third, although our multivariable model demonstrated favorable discrimination and was internally validated using 1,000 bootstrap resamples, it lacks external validation. The generalizability of the proposed nomogram must be confirmed in independent, multi-center cohorts. Finally, while we rigorously accounted for key clinicopathological variables, other potential confounders, such as detailed dietary habits, psychological status, and postoperative biofeedback therapy, were not explicitly evaluated. Despite these limitations, our prospective design and the novel integration of manometric metrics with mucosal inflammatory status provide a robust framework for early LARS risk stratification. 5.Conclusion In conclusion, a reduced FSV and diversion colitis independently predict major LARS at three months post-reversal. Integrating these markers, our pre-reversal nomogram offers a valuable tool for individualized risk stratification and guiding preemptive interventions. Further validation in larger, multi-center cohorts is necessary to confirm its broader clinical applicability. Declarations Ethics approval This study was approved by the Ethics Committee of Peking University People’s Hospital. This study conforms to the provisions of the Declaration of Helsinki. Consent to participate Informed consent was obtained from all individual participants included in the study. Consent to publish The participant has consented to the submission of the case report to the journal. Conflicts of interest The authors declare that they have no competing interests. Funding This work was supported by “Research and development funding of Peking university people's hospital (2147001284)” and “Beijing Natural Science Foundation (L252188)”. Author Contribution All authors contributed to the study conception and design. X.W. wrote the first draft. X.Z. performed the analysis of data, Yu.Y. & Y.T. performed the collection of data. Yi.Y. & C.Z. provided the resources for this project. S.H. & Zhidong Gao reviewed this manuscript. All authors reviewed the manuscript. Acknowledgements Not applicable. Data availability The datasets analysed during the current study are available from the corresponding author on reasonable request. References Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin. 2024;74(3):229–63. https://doi.org/10.3322/caac.21834 . Eng C, Yoshino T, Ruíz-García E, Mostafa N, Cann CG, O'Brian B, Benny A, Perez RO, Cremolini C. Colorectal cancer. Lancet (London England). 2024;404(10449):294–310. https://doi.org/10.1016/S0140-6736(24)00360-X . Ryoo SB. Low anterior resection syndrome. Annals gastroenterological Surg. 2023;7(5):719–24. https://doi.org/10.1002/ags3.12695 . Keane C, Fearnhead NS, Bordeianou L, Christensen P, Espin Basany E, Laurberg S, Mellgren A, Messick C, Orangio GR, Verjee A, Wing K, Bissett I, LARS International Collaborative Group. International consensus definition of low anterior resection syndrome. Colorectal disease: official J Association Coloproctology Great Br Irel. 2020;22(3):331–41. https://doi.org/10.1111/codi.14957 . Juul T, Ahlberg M, Biondo S, Espin E, Jimenez LM, Matzel KE, Palmer GJ, Sauermann A, Trenti L, Zhang W, Laurberg S, Christensen P. Low anterior resection syndrome and quality of life: an international multicenter study. Dis Colon Rectum. 2014;57(5):585–91. https://doi.org/10.1097/DCR.0000000000000116 . Matthiessen P, Hallböök O, Rutegård J, Simert G, Sjödahl R. Defunctioning stoma reduces symptomatic anastomotic leakage after low anterior resection of the rectum for cancer: a randomized multicenter trial. Ann Surg. 2007;246(2):207–14. https://doi.org/10.1097/SLA.0b013e3180603024 . Pieniowski EHA, Nordenvall C, Johar A, Palmer G, Tumlin Ekelund S, Lagergren P, Abraham-Nordling M. Defunctioning stoma in rectal cancer surgery - A risk factor for Low Anterior Resection Syndrome? Eur J Surg oncology: J Eur Soc Surg Oncol Br Association Surg Oncol. 2022;48(12):2518–24. https://doi.org/10.1016/j.ejso.2022.06.025 . Son DN, Choi DJ, Woo SU, Kim J, Keom BR, Kim CH, Baek SJ, Kim SH. Relationship between diversion colitis and quality of life in rectal cancer. World J Gastroenterol. 2013;19(4):542–9. https://doi.org/10.3748/wjg.v19.i4.542 . Carrington EV, Heinrich H, Knowles CH, Fox M, Rao S, Altomare DF, Bharucha AE, Burgell R, Chey WD, Chiarioni G, Dinning P, Emmanuel A, Farouk R, Felt-Bersma RJF, Jung KW, Lembo A, Malcolm A, Mittal RK, Mion F, Myung SJ, et al. The international anorectal physiology working group (IAPWG) recommendations: Standardized testing protocol and the London classification for disorders of anorectal function. Neurogastroenterol Motil. 2020;32(1):e13679. https://doi.org/10.1111/nmo.13679 . All members of the International Anorectal Physiology Working Group. Bhattacharyya S, Bhattacharya A, Das P, Choraria A. Low Anterior Resection Syndrome: Current Understanding and Management. Cureus. 2025;17(5):e83942. https://doi.org/10.7759/cureus.83942 . Brierley SM, Linden DR. Neuroplasticity and dysfunction after gastrointestinal inflammation. Nat Rev Gastroenterol Hepatol. 2014;11(10):611–27. https://doi.org/10.1038/nrgastro.2014.103 . Harig JM, Soergel KH, Komorowski RA, Wood CM. Treatment of diversion colitis with short-chain-fatty acid irrigation. N Engl J Med. 1989;320(1):23–8. https://doi.org/10.1056/NEJM198901053200105 . Koifman E, Armoni M, Gorelik Y, Harbi A, Streltsin Y, Duek SD, Brun R, Mazor Y. Long term persistence and risk factors for anorectal symptoms following low anterior resection for rectal cancer. BMC Gastroenterol. 2024;24(1):31. https://doi.org/10.1186/s12876-023-03112-8 . Kakodkar R, Gupta S, Nundy S. Low anterior resection with total mesorectal excision for rectal cancer: functional assessment and factors affecting outcome. Colorectal disease: official J Association Coloproctology Great Br Irel. 2006;8(8):650–6. https://doi.org/10.1111/j.1463-1318.2006.00992.x . Chen SC, Futaba K, Leung WW, Wong C, Mak T, Ng S, Gregersen H. Functional anorectal studies in patients with low anterior resection syndrome. Neurogastroenterol Motil. 2022;34(3):e14208. https://doi.org/10.1111/nmo.14208 . Ekkarat P, Boonpipattanapong T, Tantiphlachiva K, Sangkhathat S. Factors determining low anterior resection syndrome after rectal cancer resection: A study in Thai patients. Asian J Surg. 2016;39(4):225–31. https://doi.org/10.1016/j.asjsur.2015.07.003 . Pieniowski EHA, Palmer GJ, Juul T, Lagergren P, Johar A, Emmertsen KJ, Nordenvall C, Abraham-Nordling M. Low Anterior Resection Syndrome and Quality of Life After Sphincter-Sparing Rectal Cancer Surgery: A Long-term Longitudinal Follow-up. Dis Colon Rectum. 2019;62(1):14–20. https://doi.org/10.1097/DCR.0000000000001228 . Eftaiha SM, Balachandran B, Marecik SJ, Mellgren A, Nordenstam J, Melich G, Prasad LM, Park JJ. Sacral nerve stimulation can be an effective treatment for low anterior resection syndrome. Colorectal disease: official J Association Coloproctology Great Br Irel. 2017;19(10):927–33. https://doi.org/10.1111/codi.13701 . Martellucci J, Falletto E, Ascanelli S, Chimisso L, Rossitti P, Zucchi E, Lauretta A, Mirafiori M, Bondurri A, Zaffaroni G, Clementi I, Cornaglia S, Tonello P, Di Candido F, Zattoni D, Ripetti V, Luffarelli P, d'Alba L, Cestaro G, Bottini C et al. (2025). Transanal irrigation in patients affected by low anterior resection syndrome (LARS): Long-term results from an Italian national study. Digestive and liver disease: official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 57(10), 1913–9. https://doi.org/10.1016/j.dld.2025.07.002 Rodríguez-Padilla Á, Morales-Martín G, Pérez-Quintero R, Rada-Morgades R, Gómez-Salgado J, Ruiz-Frutos C. Diversion Colitis and Probiotic Stimulation: Effects of Bowel Stimulation Prior to Ileostomy Closure. Front Med. 2021;8:654573. https://doi.org/10.3389/fmed.2021.654573 . Sam SW, Hafeez B, Ong HI, Gill S, Smibert O, Lavelle A, Burgess A, Proud D, Mohan H. The impact of faecal diversion on the gut microbiome: a systematic review. Gut microbiome (Cambridge England). 2024;5:e4. https://doi.org/10.1017/gmb.2024.1 . Visser WS, Riele T, Boerma WW, van Ramshorst D, B., van Westreenen HL. Pelvic floor rehabilitation to improve functional outcome after a low anterior resection: a systematic review. Annals coloproctology. 2014;30(3):109–14. https://doi.org/10.3393/ac.2014.30.3.109 . Additional Declarations No competing interests reported. Supplementary Files SupplementaryFig1.eps Supplementary Fig. S1: Post-hoc power analysis and internal validation of the predictive model. (A) Post-hoc power analysis.The curve illustrates the statistical strength of the observed correlation between FSV and the 3-month LARS score. Based on the cohort size (n = 46) and the effect size (r = -0.32), the calculated statistical power is 0.594. (B) Internal validation via bootstrap resampling. The plot assesses the stability of the multivariable predictive model using 1,000 non-parametric bootstrap resamples. After accounting for over-optimism, the model demonstrates high reliability, retaining a corrected C-index of 0.712 and a calibration slope of 0.9205. MDE, Minimum Detectable Effect; AUC, area under the curve. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 13 May, 2026 Reviewers agreed at journal 11 May, 2026 Reviewers agreed at journal 08 May, 2026 Reviewers invited by journal 07 May, 2026 Editor invited by journal 20 Apr, 2026 Editor assigned by journal 17 Apr, 2026 Submission checks completed at journal 17 Apr, 2026 First submitted to journal 16 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-9442558","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":641502855,"identity":"9b760090-d158-4651-aa8b-8880e384953b","order_by":0,"name":"Xinchun Wu","email":"","orcid":"","institution":"Peking University People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xinchun","middleName":"","lastName":"Wu","suffix":""},{"id":641502856,"identity":"fc30771b-c2ff-457b-8e81-4a9ec6563491","order_by":1,"name":"Xi Zheng","email":"","orcid":"","institution":"Peking University People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xi","middleName":"","lastName":"Zheng","suffix":""},{"id":641502857,"identity":"7ee87b2e-e94b-46ec-b4d0-6309eb9fa3cb","order_by":2,"name":"Yuchen Yao","email":"","orcid":"","institution":"Peking University People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuchen","middleName":"","lastName":"Yao","suffix":""},{"id":641502858,"identity":"a7d3d4ef-d487-4689-88d8-ddef146b11f8","order_by":3,"name":"Yuhang Tian","email":"","orcid":"","institution":"Peking University People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuhang","middleName":"","lastName":"Tian","suffix":""},{"id":641502859,"identity":"6f071409-58d3-4ac4-839f-711e435ebed4","order_by":4,"name":"Yingjiang Ye","email":"","orcid":"","institution":"Peking University People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yingjiang","middleName":"","lastName":"Ye","suffix":""},{"id":641502860,"identity":"40254698-9035-4a72-9e97-86cdedf2799a","order_by":5,"name":"Changkun Zhong","email":"","orcid":"","institution":"Peking University People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Changkun","middleName":"","lastName":"Zhong","suffix":""},{"id":641502861,"identity":"1979946e-ba03-4f5a-9c31-992daf862231","order_by":6,"name":"Sen Hou","email":"","orcid":"","institution":"Peking University People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sen","middleName":"","lastName":"Hou","suffix":""},{"id":641502862,"identity":"94ead9ba-0ceb-4e55-a371-e1758d245a36","order_by":7,"name":"Zhidong Gao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+0lEQVRIiWNgGAWjYJACZgYDZhB1gLGBgSEByDIgVgtbAilaQIiBx4A4LfLuhw9/LiiwljPnX/Pt4cy2O3kM7M3bJBhq7uDUYngmLcF4hkG6seWMt9sNN7Y9K2bgOVYmwXDsGW4tDTkGyTwGhxM33Di7TfJh2+HEBokcMwnGhsO4tfS/MTgM0XLmGUSL/Bv8WuQlcgybwVrO97BJbgTbwoNfi4HEs2RmHqBfDG6wmRvOOPcssY0nrdgi4RgeW/qTD3/m+WMtZ3D+8LOHPWV3EvvZD2+88aEGjy0HYCyJBDYgeYABRIJjB6ctDTAW/wGIllEwCkbBKBgF6AAApS5cQtBaq3MAAAAASUVORK5CYII=","orcid":"","institution":"Peking University People's Hospital","correspondingAuthor":true,"prefix":"","firstName":"Zhidong","middleName":"","lastName":"Gao","suffix":""}],"badges":[],"createdAt":"2026-04-17 00:23:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9442558/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9442558/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109435285,"identity":"db20c9f7-146e-45ce-af69-c6bab1fbb9ac","added_by":"auto","created_at":"2026-05-18 06:01:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":393369,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow chart of the study.\u003c/strong\u003e LARS, low anterior resection syndrome; IBD, inflammatory bowel disease; HRAM, high-resolution anorectal manometry.\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-9442558/v1/b8111a39e20d22086c4befa4.png"},{"id":109759878,"identity":"9df611a1-a9f4-429e-8218-bcc903d46a3c","added_by":"auto","created_at":"2026-05-22 07:27:52","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":55753,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCorrelation between pre-reversal HRAM parameters and postoperative functional scores.\u003c/strong\u003e \u003cstrong\u003e(a) Spearman correlation matrix.\u003c/strong\u003e The heatmap illustrates the relationships between baseline anorectal manometric metrics and functional outcomes (LARS and Wexner scores) at 1 and 3 months postoperatively. \u003cstrong\u003e(b) Correlation between FSV and 3-month LARS score.\u003c/strong\u003e A scatter plot demonstrates a significant negative correlation (ρ = -0.32, $p$ = 0.030). \u003cstrong\u003e(c) Correlation between RRP and 3-month LARS score.\u003c/strong\u003e The scatter plot shows a significant negative correlation (ρ = -0.29, $p$ = 0.040) between baseline rectal resting pressure and mid-term LARS severity. HRAM, high-resolution anorectal manometry; LARS, low anterior resection syndrome; MARP, mean anal resting pressure; MSP, maximum squeeze pressure; DSS, duration of sustained squeeze; ARP, anal residual pressure; RRP, rectal resting pressure; FSV, first sensation volume; MTV, maximum tolerated volume.\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-9442558/v1/5453ee940acacabc1adc01a1.png"},{"id":109799560,"identity":"1e5e6e6e-6974-4ef9-840f-58e85c910ad4","added_by":"auto","created_at":"2026-05-22 15:31:23","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":123263,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFSV and diversion colitis are the key predictive factors for major LARS at 3 months post-stoma reversal. (a) Forest plot.\u003c/strong\u003eMultivariable logistic regression analysis identifies diversion colitis and FSV as independent predictors of major LARS at 3 months. \u003cstrong\u003e(b) Causal mediation analysis.\u003c/strong\u003e The results demonstrate mutually independent effects of diversion colitis and FSV on LARS (ACME = -0.101, p = 0.904). \u003cstrong\u003e(c) Density plot of average causal mediation effect\u003c/strong\u003e. Distribution from 1,000 bootstrap resamples visually confirms the lack of a significant mediatory pathway. \u003cstrong\u003e(d-k) Phenotypic stratification by diversion colitis and FSV-High/Low groups\u003c/strong\u003e. (d-g) Functional scores at 1 month show no significant differences. (h-i) At 3 months, LARS scores are significantly higher in patients with diversion colitis (p = 0.024) and in the FSV-Low group (p = 0.032). (j-k) Wexner scores show no significant associations at either follow-up. LARS, low anterior resection syndrome; FSV, first sensation volume; ACME, average causal mediation effect; ADE, average direct effect.\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-9442558/v1/feb785375eda667072310f78.png"},{"id":109435289,"identity":"735383b3-1c10-4356-9e29-90374063902a","added_by":"auto","created_at":"2026-05-18 06:01:18","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":95871,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eConstruction and validation of the predictive model for major LARS. (a) 3D response surface plot\u003c/strong\u003e. The surface visualizes the synergistic effect of FSV and diversion colitis, demonstrating how the predicted probability of major LARS escalates sharply as FSV decreases in the presence of mucosal inflammation. \u003cstrong\u003e(b) Predictive nomogram.\u003c/strong\u003e A clinically applicable tool developed to estimate the individualized risk of major LARS at 3 months post-reversal based on baseline physiological and inflammatory markers. \u003cstrong\u003e(c) ROC curves of the module.\u003c/strong\u003e The plot evaluates the discriminative performance of the composite model (AUC = 0.736), which significantly outperforms the predictive value of FSV alone. \u003cstrong\u003e(d) Calibration curve of the module\u003c/strong\u003e. The curve assesses the model's reliability, showing strong agreement between predicted and observed probabilities with minimal systematic bias (mean absolute error = 0.059). \u003cstrong\u003e(e) Decision curve analysis of the module\u003c/strong\u003e. The analysis highlights the clinical utility of the nomogram, yielding a superior net benefit over \"intervention-for-all\" or \"intervention-for-none\" strategies across a broad range of threshold probabilities. LARS, low anterior resection syndrome; FSV, first sensation volume; AUC, area under the curve; ROC, receiver operating characteristic.\u003c/p\u003e","description":"","filename":"Fig4.png","url":"https://assets-eu.researchsquare.com/files/rs-9442558/v1/ff26160d9ff1f33ed949fde3.png"},{"id":109906408,"identity":"a4b7bb7c-78d5-4c9f-b614-b95d65e990d9","added_by":"auto","created_at":"2026-05-25 06:40:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":910985,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9442558/v1/1e998be1-5977-4c01-814a-2bc09a677f10.pdf"},{"id":109435287,"identity":"4b8cd257-7965-46a3-b4a2-70c0aa47cc31","added_by":"auto","created_at":"2026-05-18 06:01:18","extension":"eps","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1613374,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Fig. S1: Post-hoc power analysis and internal validation of the predictive model. (A) Post-hoc power analysis.\u003c/strong\u003eThe curve illustrates the statistical strength of the observed correlation between FSV and the 3-month LARS score. Based on the cohort size (n = 46) and the effect size (r = -0.32), the calculated statistical power is 0.594. \u003cstrong\u003e(B) Internal validation via bootstrap resampling.\u003c/strong\u003e The plot assesses the stability of the multivariable predictive model using 1,000 non-parametric bootstrap resamples. After accounting for over-optimism, the model demonstrates high reliability, retaining a corrected C-index of 0.712 and a calibration slope of 0.9205. MDE, Minimum Detectable Effect; AUC, area under the curve.\u003c/p\u003e","description":"","filename":"SupplementaryFig1.eps","url":"https://assets-eu.researchsquare.com/files/rs-9442558/v1/cea74eda9a0ba919a07aeced.eps"}],"financialInterests":"No competing interests reported.","formattedTitle":"Predicting Major Low Anterior Resection Syndrome After Stoma Reversal Using Pre-reversal High-Resolution Anorectal Manometry: A Prospective Study","fulltext":[{"header":"1.Introduction","content":"\u003cp\u003eColorectal cancer remains one of the most prevalent malignancies globally, with rectal cancer accounting for approximately one-third of all cases [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Advancements in surgical techniques and neoadjuvant therapies have significantly improved sphincter preservation rates in patients with low rectal cancer [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, Low Anterior Resection Syndrome (LARS), characterized by fecal urgency, frequency, and incontinence, remains a prevalent complication, affecting up to 80% of patients postoperatively [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. These symptoms profoundly impair quality of life and social reintegration [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe etiology of LARS is multifactorial, involving anatomical and physiological disruptions. Recognized risk factors include neoadjuvant radiotherapy, low anastomotic height, and the duration of fecal diversion [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. During the period of defunctioning ileostomy, the distal bowel may undergo \"disuse\" changes, such as mucosal atrophy and diversion colitis, which can impact neorectal function following intestinal restoration [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. High-resolution anorectal manometry (HRAM) provides an objective assessment of anorectal physiological integrity [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. While HRAM is typically used for the retrospective diagnosis of existing defecation disorders, manometric parameters, such as rectal sensory thresholds and compliance, may indicate the functional reserve of the neorectum [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Consequently, pre-reversal manometric evaluation may offer predictive value regarding functional outcomes after stoma closure [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this prospective study, we aimed to evaluate the predictive capacity of pre-reversal HRAM parameters, combined with clinicopathological characteristics, for the occurrence of major LARS at three months post-stoma reversal. By identifying physiological and clinical determinants based on HRAM, we sought to develop a risk-stratification model. This framework is intended to provide clinicians with an objective tool to identify high-risk individuals prior to stoma closure, thereby assisting in clinical counseling and the planning of rehabilitative interventions for patients with low rectal cancer.\u003c/p\u003e"},{"header":"2.Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Patients and study design\u003c/h2\u003e \u003cp\u003eThis prospective cohort study was conducted at Peking University People\u0026rsquo;s Hospital. We initially enrolled 50 patients diagnosed with low rectal cancer who underwent sphincter-preserving surgery (low anterior resection) combined with a protective ileostomy from October 2022 to April 2025. Through the screening and follow-up process, 46 patients were finally enrolled for analysis. The inclusion criteria were as follows: (1) histologically confirmed rectal adenocarcinoma; (2) tumor lower margin\u0026thinsp;\u0026le;\u0026thinsp;10 cm from the anal verge; (3) underwent radical proctectomy with protective ileostomy and subsequent stoma reversal at our center. The exclusion criteria were: (1) age\u0026thinsp;\u0026lt;\u0026thinsp;18 or \u0026gt;\u0026thinsp;80 years; (2) multiple primary malignancies or distant metastasis; (3) concomitant inflammatory bowel disease; (4) severe postoperative complications such as anastomotic leakage or pelvic infection; (5) tumor recurrence or death during the follow-up period; (6) incomplete clinicopathological data or refusal to participate in follow-up. During the follow-up period, 4 patients were excluded: 2 due to refusal of subsequent treatment, 1 due to tumor recurrence, and 1 due to the development of a pelvic abscess (\u003cb\u003eFig.\u0026nbsp;1\u003c/b\u003e).\u003c/p\u003e \u003cp\u003e This study was approved by the Ethics Committee of Peking University People\u0026rsquo;s Hospital and was conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from all participants.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Clinical data and follow-up\u003c/h2\u003e \u003cp\u003eDemographic and clinicopathological data, including age, sex, body mass index (BMI), tumor distance from the anal verge, clinical TNM stage, tumor pathology type, surgical procedure and details of neoadjuvant/adjuvant chemotherapy or radiotherapy, were retrieved from electronic medical records. Diversion colitis was assessed by colonoscopy prior to stoma reversal. Postoperative bowel function was evaluated at 1 month and 3 months following stoma reversal using the LARS score and the Wexner anal incontinence score. The LARS score categorized patients into \"no LARS\" (0\u0026ndash;20), \"minor LARS\" (21\u0026ndash;29), and \"major LARS\" (30\u0026ndash;42). For binary analysis, patients were grouped into Major LARS versus No/Minor LARS.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Anorectal functional assessment\u003c/h2\u003e \u003cp\u003eAll patients underwent HRAM 1\u0026ndash;2 days prior to the stoma reversal surgery. The procedure was performed by an experienced technician using a solid-state manometry system (ZGJ-D3, AOYUAN). The HRAM parameters measured included: mean anal resting pressure (MARP), maximum squeeze pressure (MSP), duration of sustained squeeze (DSS), anal residual pressure (ARP), and rectal resting pressure (RRP). Rectal sensory function was assessed by incremental balloon inflation to determine the first sensation volume (FSV) and maximum tolerated volume (MTV).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Statistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses used R version 4.3.2, with figures refined in Adobe Illustrator version 28.5.0. For baseline characteristics (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), categorical and continuous variables were compared via χ2 and Wilcoxon rank-sum tests, respectively. Spearman\u0026rsquo;s analysis evaluated correlations between HRAM parameters and functional scores (LARS/Wexner). Variables with p\u0026thinsp;\u0026lt;\u0026thinsp;0.20 in univariate analysis entered a multivariable logistic regression to identify independent predictors of major LARS at 3 months, yielding odds ratios (OR) and 95% confidence intervals (CI) presented in forest plots. Causal mediation analysis utilizing 1,000 bootstrap resamples investigated the diversion colitis-FSV interaction. A predictive model, visualized via nomogram and 3D response surface plot, was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves (mean absolute error), and decision curve analysis. Internal validation utilized 1,000 bootstrap resamples to calculate the optimism-corrected C-index and calibration slope. Post-hoc power analysis assessed correlation strength. All statistical tests were two-sided, and p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\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\u003ePopulation characteristic and correlation with LARS score.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\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=\"char\" char=\".\" 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 \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLevel\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eThe 1-month Postoperative LARS Score\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eThe 3-month Postoperative LARS Score\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMajor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo or Minor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMajor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo or Minor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (mean(SD))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63.76(10.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68.67(8.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.194\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e65.27(8.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e64.21(11.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.725\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (median[IQR])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.42[21.45,25.06]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.47[23.67,25.78]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.124\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23.40[21.70,25.20]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e24.01[21.70,25.23]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.583\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDistance from Anal Verge (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;5cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(56.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(77.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.437\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13(59.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15(62.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;5cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16(43.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(22.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9(40.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9(37.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSex (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(24.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(44.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.430\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4(18.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9(37.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.260\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28(75.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(55.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18(81.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15(62.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003ecT (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(5.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(11.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.614\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1(4.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2(8.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.817\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(13.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2(9.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3(12.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(56.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(55.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14(63.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12(50.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(24.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(33.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5(22.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7(29.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ecN (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(32.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(22.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.835\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6(27.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8(33.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.905\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(37.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(44.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9(40.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9(37.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(29.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(33.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7(31.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7(29.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePreoperative Chemotherapy (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23(62.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6(66.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13(59.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e16(66.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.821\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(37.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(33.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9(40.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8(33.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePreoperative Radiotherapy (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22(59.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6(66.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.987\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11(50.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e17(70.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.253\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15(40.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(33.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11(50.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7(29.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAnastomosis (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eETE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30(81.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8(88.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.949\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19(86.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e19(79.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.800\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eETS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(18.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(11.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3(13.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5(20.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDilation Time (median[IQR])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e146.00[114.00,219.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e133.000[115.00,176.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.455\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e139.00[116.25,165.75]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e146.50[114.00,222.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.684\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDiversion Colitis (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19(51.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(77.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.289\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9(40.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e17(70.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.081\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18(48.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(22.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13(59.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7(29.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePathology Type (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePolypoid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(21.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(44.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.330\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5(22.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7(29.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.872\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUlcerating\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29(78.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(55.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17(77.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e17(70.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePostoperative Chemotherapy (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(56.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(55.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13(59.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e13(54.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.969\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16(43.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(44.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9(40.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11(45.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eARP (median[IQR])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.80[2.20,5.70]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.60[2.70,4.70]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.901\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.80[1.45,5.35]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.95[2.63,5.80]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.384\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMSP (median[IQR])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.00[11.00,22.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.80[7.50,18.30]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18.15[10.73,22.15]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15.30[9.48,18.35]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.291\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDSS (median[IQR])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.00[19.00,29.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.00[10.00,23.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e24.50[16.25,29.75]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e21.00[19.00,23.25]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.481\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMARP (median[IQR])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.60[4.00,12.90]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.60[7.30,11.30]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.561\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.50[3.88,12.35]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10.35[6.85,13.20]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.397\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRRP (median[IQR])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.10[0.10,0.30]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.500[0.00,0.60]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.299\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.10[0.00,0.1]\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.30[0.10,0.60]\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFSV (median[IQR])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.00[15.00,30.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30.00[20.00,30.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.099\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20.00[15.00,28.75]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e27.50[20.00,30.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.052\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMTV (median[IQR])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.00[45.00,60.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50.00[45.00,55.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.823\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e52.50[45.00,60.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e50.00[45.00,55.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.756\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003csup\u003e\u003cb\u003eLARS, low anterior resection syndrome; SD, standard deviation; IQR, interquartile range; BMI, body mass index; ETE, end\u0026minus;to\u0026minus;end anastomosis; ETS, end\u0026minus;to\u0026minus;side anastomosis; ARP, anal residual pressure; MSP, maximum squeeze pressure; DSS, duration of sustained squeeze; MARP, mean anal resting pressure; RRP, rectal resting pressure; FSV, first sensation volume; MTV, maximum tolerated volume.\u003c/b\u003e\u003c/sup\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"3.Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Patients\u0026rsquo; characteristics\u003c/h2\u003e \u003cp\u003eA total of 46 patients undergoing sphincter-preserving surgery and stoma reversal for low rectal cancer completed the follow-up protocol. Baseline characteristics, stratified by LARS severity at one and three months, are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The predominantly male cohort had a mean age of approximately 65 years. Most tumors (60.9%) were within 5 cm of the anal verge, with patients frequently receiving preoperative chemotherapy (37.0%) or radiotherapy (39.1%). Postoperatively, patients exhibited a high initial burden of defecation dysfunction, with major LARS incidence reaching 80.4% (37/46) at one month. However, functional recovery was observed over time; by three months, major LARS prevalence decreased to 47.8% (22/46), while the proportion of patients with no or minor LARS increased from 19.6% to 52.2%.\u003c/p\u003e \u003cp\u003eUnivariate comparisons revealed no significant differences between the major and no/minor LARS groups at one or three months regarding age, BMI, sex, tumor distance, TNM stage, or neoadjuvant/adjuvant therapies (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Surgical factors, including anastomosis type and dilation time, also lacked significant correlation with LARS severity. While diversion colitis was more frequent in patients with major LARS at three months (59.09% vs. 29.17%), this baseline difference did not reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.081).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Correlation between pre-reversal HRAM parameters and postoperative functional outcomes\u003c/h2\u003e \u003cp\u003eTo further explore the relationship between anorectal physiological profiles and postoperative defecation function, Spearman correlation analysis was performed between pre-reversal HRAM parameters and functional scores (LARS and Wexner) at both follow-up time points (\u003cb\u003eFig.\u0026nbsp;2a\u003c/b\u003e). While several manometric metrics exhibited negative trends with respect to functional scores, the most significant associations were observed between rectal physiological parameters and the 3-month LARS scores. Specifically, the first sensation volume, representing the rectal sensory threshold, demonstrated a significant negative correlation with the LARS score at three months (ρ = \u0026minus;0.32, p\u0026thinsp;=\u0026thinsp;0.030; \u003cb\u003eFig.\u0026nbsp;2b\u003c/b\u003e). A post-hoc power analysis based on this observed effect size (r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.32,n\u0026thinsp;=\u0026thinsp;46) indicated a statistical power of 0.594 (\u003cb\u003eSupplementary Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003ea\u003c/b\u003e). This inverse relationship indicates that patients with a lower sensory threshold (rectal hypersensitivity) prior to stoma reversal were more likely to experience higher LARS scores and more severe defecation dysfunction. Similarly, RRP was also significantly and negatively correlated with the 3-month LARS score (ρ = \u0026minus;0.29, p\u0026thinsp;=\u0026thinsp;0.040; \u003cb\u003eFig.\u0026nbsp;2c\u003c/b\u003e). These findings are consistent with the inter-group differences observed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, where lower RRP (median 0.10 vs. 0.30; p\u0026thinsp;=\u0026thinsp;0.004) and a trend toward lower FSV (median 20.00 mL vs. 27.50 mL; p\u0026thinsp;=\u0026thinsp;0.052) were characteristic of the major LARS cohort, suggesting an association between preoperative rectal hypersensitivity and poor long-term functional outcomes.\u003c/p\u003e \u003cp\u003eIn contrast, the correlations between HRAM parameters and functional outcomes at one month postoperatively, as well as with the Wexner incontinence scores at both time points, did not reach statistical significance (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Although certain trends were noted, such as the negative correlation between ARP and the 3-month Wexner score (ρ = \u0026minus;0.24), the overall results suggest that pre-reversal rectal sensory and pressure metrics, particularly FSV and RRP, are more specifically predictive of the severity of LARS during the mid-term recovery phase than of early-stage dysfunction or isolated anal incontinence.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3 FSV and diversion colitis as independent predictors of major LARS at 3 months postoperatively\u003c/h2\u003e \u003cp\u003eTo identify the key determinants of significant defecation dysfunction, univariate and multivariable logistic regression analyses were performed targeting major LARS at three months post-stoma reversal (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Factors with a p\u0026thinsp;\u0026lt;\u0026thinsp;0.200 in the univariate analysis, including sex, preoperative radiotherapy, diversion colitis, and HRAM parameters such as MSP, RRP, and FSV, were incorporated into the multivariable model. The results, visualized in a forest plot (\u003cb\u003eFig.\u0026nbsp;3a\u003c/b\u003e), identified diversion colitis and FSV as the only independent predictors of major LARS. Specifically, the presence of diversion colitis was associated with a nearly seven-fold increase in the risk of major LARS (adjusted OR\u0026thinsp;=\u0026thinsp;6.95, 95% CI: 1.47 to 44.30, p\u0026thinsp;=\u0026thinsp;0.023). Conversely, FSV served as a protective factor, with each 1-mL increase in the sensory threshold reducing the odds of major LARS by 10% (adjusted OR\u0026thinsp;=\u0026thinsp;0.90, 95% CI: 0.81 to 0.98, p\u0026thinsp;=\u0026thinsp;0.031). Subsequent causal mediation analysis was employed to investigate the potential interaction between diversion colitis and FSV. The results confirmed that the impacts of diversion colitis and FSV on LARS were mutually independent, with no significant indirect effects observed (average causal mediation effect (ACME) = -0.101, 95% CI: -2.74 to 2.79, p\u0026thinsp;=\u0026thinsp;0.904, \u003cb\u003eFig.\u0026nbsp;3b\u003c/b\u003e). To ensure the robustness of this finding, we performed 1,000 non-parametric bootstrap resamples; the resulting density plot demonstrated that the ACME distribution was symmetrically centered around zero, visually corroborating the lack of a significant mediatory pathway (\u003cb\u003eFig.\u0026nbsp;3c\u003c/b\u003e). These findings collectively suggest that diversion colitis and rectal hypersensitivity operate through distinct and independent biological pathways in the development of postoperative LARS.\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\u003eUnivariate and multivariable logistic regression analysis of factors associated with major LARS at 3 months postoperatively.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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 \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFactors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eUnivariate Regression\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eMultivariable Regression\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOR(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOR(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.01(0.95,1.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.718\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.95(0.79,1.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.587\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistance from Anal Verge\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\u003e0.813\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;=5cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;5cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.15(0.35,3.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\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\u003e0.142\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.072\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\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 \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.70(0.72,11.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.73(0.96, 47.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecT\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\u003e0.815\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.33(0.07,41.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.33(0.20,54.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.43(0.11,35.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecN\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\u003e0.905\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.33(0.33,5.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.33(0.30,6.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative Chemotherapy\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\u003e0.595\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.38(0.42,4.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative Radiotherapy\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\u003e0.147\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.436\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.43(0.73,8.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.86(0.39, 9.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnastomosis\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\u003e0.518\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eETE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eETS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.60(0.11,2.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDilation Time\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00(0.99,1.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.534\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiversion Colitis\u003c/b\u003e\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\u003cb\u003e0.039\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.023\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e\u0026mdash;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026mdash;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e3.51(1.06,12.5)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e6.95(1.47, 44.3)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathology 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\u003e0.619\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePolypoid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUlcerating\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.40(0.37,5.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative Chemotherapy\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\u003e0.736\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.82(0.25,2.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eARP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.93(0.75,1.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.444\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMSP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.06(0.98,1.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.177\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.09(0.99, 1.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.111\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.04(0.96,1.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.351\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMARP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.99(0.91,1.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.846\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRRP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.41(0.09,1.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.34(0.07, 1.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.108\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFSV\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.93(0.86,1.00)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.035\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.90(0.81, 0.98)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.031\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMTV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.99(0.95,1.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.587\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003e\u003cb\u003eLARS, low anterior resection syndrome; OR, odds ratio; CI, confidence interval; BMI, body mass index; ETE, end\u0026minus;to\u0026minus;end anastomosis; ETS, end\u0026minus;to\u0026minus;side anastomosis; ARP, anal residual pressure; MSP, maximum squeeze pressure; DSS, duration of sustained squeeze; MARP, mean anal resting pressure; RRP, rectal resting pressure; FSV, first sensation volume; MTV, maximum tolerated volume.\u003c/b\u003e\u003c/sup\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe clinical impact of these predictors was further characterized using raincloud plots for phenotypic stratification (\u003cb\u003eFig.\u0026nbsp;3d-k\u003c/b\u003e). Patients were categorized into FSV-High and FSV-Low groups based on the median FSV value. While neither diversion colitis nor FSV significantly affected LARS or Wexner scores at the early 1-month follow-up (\u003cb\u003eFig.\u0026nbsp;3d-g\u003c/b\u003e), their influence became pronounced by the 3-month time point. At three months, LARS scores were significantly higher in patients with diversion colitis compared to those without (p\u0026thinsp;=\u0026thinsp;0.024; \u003cb\u003eFig.\u0026nbsp;3h\u003c/b\u003e) and in the FSV-Low group compared to the FSV-High group (p\u0026thinsp;=\u0026thinsp;0.032; \u003cb\u003eFig.\u0026nbsp;3i\u003c/b\u003e). Notably, these factors specifically predicted the severity of LARS but showed no significant correlation with Wexner incontinence scores at either follow-up interval (\u003cb\u003eFig.\u0026nbsp;3j-k\u003c/b\u003e), underscoring their specific role in the pathophysiology of low anterior resection syndrome rather than isolated anal sphincter insufficiency.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Construction and validation of the predictive model for major LARS\u003c/h2\u003e \u003cp\u003eTo provide a clinically applicable tool for risk stratification, a multivariable logistic regression model was constructed using the identified independent predictors: FSV and the presence of diversion colitis. The final predictive model was established as follows:\u003c/p\u003e \u003cp\u003e \u003cb\u003elogit(P)\u0026thinsp;=\u0026thinsp;1.2810\u0026minus;(0.0899\u0026times;FSV)+(1.5105\u0026times;Diversion Colitis)\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe model demonstrated a significant goodness-of-fit (Likelihood Ratio χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;9.72, df\u0026thinsp;=\u0026thinsp;2, p\u0026thinsp;=\u0026thinsp;0.008) and a Nagelkerke R\u003csup\u003e2\u003c/sup\u003e of 0.254. The synergistic effect of these two variables on the probability of developing major LARS is illustrated in a 3D response surface plot (\u003cb\u003eFig.\u0026nbsp;4a\u003c/b\u003e), which visually depicts how the risk escalates sharply as FSV decreases in the presence of diversion colitis.\u003c/p\u003e \u003cp\u003eThe discriminative ability of the composite model was evaluated using ROC curve analysis, which revealed that the composite model achieved an AUC of 0.736 (95% CI: 0.59 to 0.88), significantly outperforming the predictive value of FSV alone (\u003cb\u003eFig.\u0026nbsp;4c\u003c/b\u003e). To facilitate clinical application, these findings were translated into a nomogram (\u003cb\u003eFig.\u0026nbsp;4b\u003c/b\u003e), enabling individualized risk estimation for major LARS. Beyond discriminative performance, the model\u0026rsquo;s reliability was assessed through calibration and clinical utility analyses. The calibration curve (\u003cb\u003eFig.\u0026nbsp;4d\u003c/b\u003e) demonstrated strong agreement between predicted and observed probabilities, characterized by a mean absolute error of 0.059 and a 0.9 quantile error of 0.14, indicating minimal systematic bias. Subsequent decision curve analysis (\u003cb\u003eFig.\u0026nbsp;4e\u003c/b\u003e) yielded a superior net benefit over \"intervention-for-all\" or \"intervention-for-none\" strategies across a broad range of threshold probabilities, which corroborated the model\u0026rsquo;s potential value. Such results suggest that the model may serve as a supportive tool for risk stratification, potentially assisting surgeons in identifying high-risk individuals and facilitating more informed clinical counseling prior to stoma reversal. Finally, internal validation via 1,000 bootstrap resamples was performed to address potential overfitting. After accounting for over-optimism, the model retained high stability with a corrected C-index of 0.712 and a calibration slope of 0.921 (\u003cb\u003eSupplementary Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003eb\u003c/b\u003e), reinforcing its reliability for clinical risk prediction.\u003c/p\u003e \u003c/div\u003e"},{"header":"4.Discussion","content":"\u003cp\u003eThe most significant finding of this study is the integration of pre-reversal anorectal physiological parameters and clinical inflammatory status to predict major LARS. We identified FSV and diversion colitis as independent determinants, and the established predictive model demonstrated potential performance in risk-stratifying patients at three months post-reversal. A primary highlight of this research is its prospective focus on the pre-reversal window, shifting the clinical paradigm from retrospective symptom management toward proactive identification and early intervention for patients with low rectal cancer.\u003c/p\u003e \u003cp\u003eHRAM provides a standardized physiological framework for decoding the complex pathophysiology of LARS, moving beyond basic pressure metrics to quantify neorectal sensitivity and compliance [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In our cohort, the predictive value of FSV highlights rectal hypersensitivity as a primary driver of postoperative dysfunction. A reduced FSV indicates that the neorectum triggers the defecation reflex at lower fecal volumes, a phenomenon fundamentally resulting from the surgical replacement of the compliant rectal ampulla with a less distensible colonic reservoir [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Chen [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] demonstrated that the urge volume is drastically reduced in patients with major LARS (averaging 11.8 ml) compared to both healthy subjects and those with primary fecal incontinence. This hypersensitivity is further modulated by the inflammatory status of the diverted bowel segment. Diversion colitis, resulting from short-chain fatty acid deficiency, induces mucosal inflammation and disuse atrophy, which sensitizes local visceral afferent nerves and lowers sensory thresholds [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The clinical relevance of this inflammatory mechanism is underscored by Koifman [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], who identified a prolonged interval from primary surgery to stoma closure as a primary risk factor for long-term LARS, a duration strongly associated with the progression of diversion colitis and neorectal atrophy.\u003c/p\u003e \u003cp\u003eWhile neorectal hypersensitivity plays a central role, LARS etiology also encompasses structural anal sphincter damage. Ekkarat [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] and Chen [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] highlight low anastomotic height, adjuvant radiotherapy, and compromised anal pressures as major LARS risk factors. Similarly, Kakodkar [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] identified absent rectoanal inhibitory reflexes and subnormal MTV as independent long-term predictors. Although these studies emphasize anatomical disruption and isolated sphincter insufficiency, our research identifies FSV as a more sensitive, early marker of neorectal hypersensitivity and a superior predictor for mid-term LARS. Unlike the traditional focus on sphincter mechanics, our findings suggest mid-term functional impairment is primarily driven by the interplay of heightened sensory thresholds and diversion colitis, which readily overwhelms marginally competent sphincters. Integrating these markers provides a nuanced baseline for pre-reversal risk stratification, enabling proactive identification of high-risk patients.\u003c/p\u003e \u003cp\u003eMeanwhile, the temporal evolution of functional recovery warrants discussion. Neither HRAM parameters nor diversion colitis predicted major LARS at one month post-reversal, yet both became highly significant at three months. This delay likely reflects an \"acute adaptation phase\" where early defecatory patterns are overwhelmed by transient factors like anastomotic edema, surgical stress, and microbiome alterations [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. As these acute disturbances subside by the third month, the true functional impact of baseline neorectal hypersensitivity and chronic mucosal inflammation dictates mid-term bowel function [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Furthermore, causal mediation analysis confirmed that diversion colitis and FSV operate independently (ACME = -0.101, p\u0026thinsp;=\u0026thinsp;0.904), suggesting dual, parallel mechanisms. Diversion colitis induces superficial, chemically driven mucosal sensitization via short-chain fatty acid starvation [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], whereas reduced FSV reflects deeper structural or neurogenic alterations, including the loss of the compliant rectal ampulla and impaired pelvic nerve signaling [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Understanding these independent pathways supports targeted prehabilitation using our proposed nomogram. For severe diversion colitis, preoperative topical short-chain fatty acid enemas or probiotic irrigations may restore the mucosal barrier and reduce inflammatory sensitization [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Concurrently, patients with markedly reduced FSV may benefit from early biofeedback therapy, utilizing volumetric balloon desensitization to elevate sensory thresholds [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Ultimately, shifting from postoperative symptom management to preoperative physiological optimization holds the potential to significantly mitigate the burden of major LARS.\u003c/p\u003e \u003cp\u003eSeveral limitations of this study must be acknowledged when interpreting our findings. First, this was a single-center study with a relatively small sample size of 46 patients. As indicated by our post-hoc power analysis, the statistical power for the correlation between FSV and the 3-month LARS score was 0.594, increasing the risk of Type II errors and potentially obscuring the predictive significance of other HRAM parameters. Second, the follow-up period was limited to three months post-stoma reversal. While this timeframe effectively captures early-to-mid-term functional recovery, postoperative bowel function continuously adapts for up to 12 to 24 months. Consequently, the long-term trajectory of major LARS and the durability of FSV as a predictive marker remain to be elucidated. Third, although our multivariable model demonstrated favorable discrimination and was internally validated using 1,000 bootstrap resamples, it lacks external validation. The generalizability of the proposed nomogram must be confirmed in independent, multi-center cohorts. Finally, while we rigorously accounted for key clinicopathological variables, other potential confounders, such as detailed dietary habits, psychological status, and postoperative biofeedback therapy, were not explicitly evaluated. Despite these limitations, our prospective design and the novel integration of manometric metrics with mucosal inflammatory status provide a robust framework for early LARS risk stratification.\u003c/p\u003e"},{"header":"5.Conclusion","content":"\u003cp\u003eIn conclusion, a reduced FSV and diversion colitis independently predict major LARS at three months post-reversal. Integrating these markers, our pre-reversal nomogram offers a valuable tool for individualized risk stratification and guiding preemptive interventions. Further validation in larger, multi-center cohorts is necessary to confirm its broader clinical applicability.\u003c/p\u003e "},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval\u003c/strong\u003e \u003cp\u003eThis study was approved by the Ethics Committee of Peking University People\u0026rsquo;s Hospital. This study conforms to the provisions of the Declaration of Helsinki.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent to participate\u003c/strong\u003e \u003cp\u003e Informed consent was obtained from all individual participants included in the study.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent to publish\u003c/strong\u003e \u003cp\u003e The participant has consented to the submission of the case report to the journal.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConflicts of interest\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis work was supported by \u0026ldquo;Research and development funding of Peking university people's hospital (2147001284)\u0026rdquo; and \u0026ldquo;Beijing Natural Science Foundation (L252188)\u0026rdquo;.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed to the study conception and design. X.W. wrote the first draft. X.Z. performed the analysis of data, Yu.Y. \u0026amp; Y.T. performed the collection of data. Yi.Y. \u0026amp; C.Z. provided the resources for this project. S.H. \u0026amp; Zhidong Gao reviewed this manuscript. All authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eData availability\u003c/h2\u003e \u003cp\u003eThe datasets 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\u003eBray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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Pelvic floor rehabilitation to improve functional outcome after a low anterior resection: a systematic review. Annals coloproctology. 2014;30(3):109\u0026ndash;14. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3393/ac.2014.30.3.109\u003c/span\u003e\u003cspan address=\"10.3393/ac.2014.30.3.109\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Low anterior resection syndrome, High-resolution anorectal manometry, Stoma reversal, Diversion colitis, First sensation volume","lastPublishedDoi":"10.21203/rs.3.rs-9442558/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9442558/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eLow anterior resection syndrome frequently complicates sphincter-preserving rectal cancer surgery. This study aimed to evaluate the capacity of pre-reversal high-resolution anorectal manometry and clinical factors to predict major low anterior resection syndrome at three months post-stoma reversal.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis prospective cohort study enrolled 46 patients with low rectal cancer undergoing protective stoma reversal. Prior to reversal, clinical data, colonoscopy (for diversion colitis), and high-resolution anorectal manometry parameters were assessed. Bowel function was evaluated using the low anterior resection syndrome score at one and three months. Multivariable logistic regression identified independent predictors of major low anterior resection syndrome at three months, followed by the construction and internal validation of a predictive nomogram.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe incidence of major LARS decreased from 80.4% at one month to 47.8% at three months. Pre-reversal first sensation volume negatively correlated with 3-month low anterior resection syndrome scores (ρ = -0.32, p\u0026thinsp;=\u0026thinsp;0.030). Multivariable analysis identified diversion colitis (adjusted OR\u0026thinsp;=\u0026thinsp;6.95, 95% CI: 1.47 to 44.30, p\u0026thinsp;=\u0026thinsp;0.023) and lower first sensation volume (adjusted OR\u0026thinsp;=\u0026thinsp;0.90, 95% CI: 0.81 to 0.98, p\u0026thinsp;=\u0026thinsp;0.031) as independent predictors. Causal mediation analysis confirmed these factors operated independently (p\u0026thinsp;=\u0026thinsp;0.904). The composite predictive model demonstrated reliable discrimination (AUC\u0026thinsp;=\u0026thinsp;0.736) and maintained stability (optimism-corrected C-index\u0026thinsp;=\u0026thinsp;0.712) during internal validation.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eReduced first sensation volume and diversion colitis independently predict mid-term major low anterior resection syndrome. The developed pre-reversal nomogram facilitates individualized risk stratification, highlighting a potential window for targeted preemptive interventions.\u003c/p\u003e","manuscriptTitle":"Predicting Major Low Anterior Resection Syndrome After Stoma Reversal Using Pre-reversal High-Resolution Anorectal Manometry: A Prospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-18 06:01:14","doi":"10.21203/rs.3.rs-9442558/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-13T17:46:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"3425596553014959425163141417847884350","date":"2026-05-11T22:09:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"174867292856095680417547842884250224266","date":"2026-05-08T20:22:43+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-05-07T10:58:38+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-20T11:54:50+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-17T06:37:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-17T06:37:15+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2026-04-17T00:12:57+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f1e704c1-0bf4-41c5-9af7-341bdad58053","owner":[],"postedDate":"May 18th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-13T17:46:58+00:00","index":43,"fulltext":""},{"type":"reviewerAgreed","content":"3425596553014959425163141417847884350","date":"2026-05-11T22:09:50+00:00","index":41,"fulltext":""},{"type":"reviewerAgreed","content":"174867292856095680417547842884250224266","date":"2026-05-08T20:22:43+00:00","index":37,"fulltext":""},{"type":"reviewersInvited","content":"18","date":"2026-05-07T10:58:38+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-18T06:01:14+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-18 06:01:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9442558","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9442558","identity":"rs-9442558","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}