Predictors for Temporary Stomas Non-Closure among Non-Metastatic Rectal Cancer Patients Undergoing Curative Resection: a Retrospective Analysis

Predictors for Temporary Stomas Non-Closure among Non-Metastatic Rectal Cancer Patients Undergoing Curative Resection: a Retrospective Analysis | 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 Predictors for Temporary Stomas Non-Closure among Non-Metastatic Rectal Cancer Patients Undergoing Curative Resection: a Retrospective Analysis Chia-Chien Hsu, Wen-Sy Tsai, Tzong-yun Tsai, Jeng-Fu You, Chien-Yuh Yeh, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3965721/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 May, 2024 Read the published version in World Journal of Surgical Oncology → Version 1 posted 8 You are reading this latest preprint version Abstract Background: The primary treatment for non-metastatic rectal cancer is curative resection. However, sphincter-preserving surgery may lead to complications. This study aims to develop a predictive model for stoma non-closure in rectal cancer patients who underwent curative-intent restorative proctectomy surgery. Methods: Consecutive patients diagnosed with non-metastatic rectal cancer between January 2005 and December 2017, who underwent proctectomy, were retrospectively included in the Chang Gung Memorial Foundation Institutional Review Board. A comprehensive evaluation and analysis of potential risk factors linked to stoma non-closure were performed. Results: Out of 956 patients with temporary stomas, 10.3% (n = 103) experienced non-closure primarily due to cancer recurrence and anastomosis-related issues. Through multivariate analysis, several preoperative risk factors significantly associated with stoma non-closure were identified, including advanced age, anastomotic leakage, positive nodal status, high preoperative CEA levels, lower rectal cancer presence, margin involvement, and an eGFR below 30 mL/min/1.73m2. A risk assessment model achieved an AUC of 0.724, with a cutoff of 2.5, 84.5% sensitivity, and 51.4% specificity. Importantly, the non-closure rate could rise to 16.6% when more than two risk factors were present, starkly contrasting the 3.7% non-closure rate observed in cases with a risk score of 2 or below (p < 0.001). Conclusion: Prognostic risk factors associated with the non-closure of a temporary stoma include advanced age, symptomatic anastomotic leakage, nodal status, high CEA levels, margin involvement, and an eGFR below 30 mL/min/1.73m2. Hence, it is crucial for surgeons to evaluate these factors and provide patients with a comprehensive prognosis before undergoing surgical intervention. Figures Figure 1 Figure 2 Figure 3 Background Curative resection was considered the primary treatment approach for non-metastatic rectal cancer. Advances in surgical techniques, such as the introduction of neoadjuvant therapy [ 1 ], and the desire of patients to preserve anal function have shifted the preference towards sphincter-sparing surgery over abdominoperineal resection for rectal cancer patients [ 2 , 3 ]. However, sphincter-preserving surgery can be accompanied by complications such as bowel dysfunction or anastomosis leakage [ 4 ]. Therefore, temporary fecal diversion is often necessary following sphincter-sparing surgery [ 5 , 6 ]. The Clinical Practice Guidelines for Ostomy Surgery recommended fecal diversion as an effective method that can reduce the severity of anastomotic dehiscence [ 7 ]. Previous research found that 3–23.2% of patients who underwent sphincter-preserving surgery still required permanent stomas. [ 8 – 12 ] Several predisposing factors may lead to irreversible stomas, including local recurrence and distant metastasis [ 9 , 11 , 13 , 14 ]. Other correlated factors included anastomosis leakage [ 12 , 15 ], advanced age [ 16 ], male gender [ 9 , 17 ], renal dysfunction [ 18 ], and elevated preoperative serum carcinoembryonic antigen (CEA) level [ 19 ]. Additionally, whether neoadjuvant chemoradiation therapy is a risk factor for permanent stoma in rectal cancer patients remains controversial [ 20 ]. This study aims to identify the presented risk factors associated with initially intended temporary stomas that ultimately did not undergo closure in non-metastatic rectal cancer patients who underwent curative-intent restorative proctectomy surgery. This information can be utilized to inform the patients about the potentially unfavorable outcomes before the operation. Methods Approval number 202001577B0 was obtained from the Chang Gung Medical Foundation Institutional Review Board to conduct this study. From January 1, 2005, to December 31, 2017, consecutive patients with rectal cancer were recruited from the Division of Colorectal Surgery at Chang Gung Memorial Hospital in Linkou (Fig. 1 ). This study enrolled 4039 rectal cancer patients who received proctectomy from 2005–2017. The mean follow-up time was 62.3 months, with a maximum of 134 months. The study included non-metastatic rectal cancer patients and those who achieved a pathological complete response (ypT0) following neoadjuvant treatments and underwent curative-intent resection with a stoma. Patients with stage IV rectal cancer, non-curative resection, emergency surgery, non-CRC pathology (squamous carcinoma, melanoma, or gastrointestinal stromal tumor ), and recurrent or synchronous cancer were all excluded. For patients who received abdominal perineal resection and Hartmann's procedure were also excluded due to the challenges and limitations of stoma reversal. Before the surgery, patients underwent preoperative evaluations such as computed tomography of the chest, abdomen, and pelvis, magnetic resonance imaging of the pelvis, preoperative serum carcinoembryonic antigen (CEA), and complete colonoscopy. Postoperative follow-up evaluations were conducted based on a standardized protocol, which included physical examination, serum CEA level, colonoscopy, and computed tomography. Additional positron emission tomography was arranged if imaging reports were equivocal. Adjuvant chemotherapy was primarily based on 5-fluoropyrimidine (5-fluorouracil, capecitabine, or tegafur), and oxaliplatin was administered at the surgeon's discretion. The digital rectal examination was routinely performed to evaluate the anastomosis condition. An additional colonoscopy or lower gastrointestinal series would be conducted if the anastomotic integrity was uncertain. Patients with locally advanced mid-to-low rectal cancer with cT3, cT4, or positive cN stage were treated with neoadjuvant concurrent chemoradiation (CCRT) or short-course radiotherapy at the discretion of the surgeon. Long-course neoadjuvant CCRT patients were administered a 5-fluoropyrimidine-based regimen (intravenous 5-fluorouracil or oral capecitabine, tegafur) and 50.4 Gy in total 28 fractions of radiotherapy, followed by surgery 6–8 weeks after the completion of treatment. Short-course radiotherapy patients received a dose of 25 Gy to the pelvis and tumor in total 5 fractions, and surgery was settled 8–10 days after the end of radiotherapy. A primary stoma was defined as a stoma made during primary surgery, and the decision to create one was at the surgeon's discretion. Factors influencing the decision to create a preventive stoma included a narrow pelvic cavity, malnutrition status, lower rectal cancer, adverse events during surgery, or the patient's inability to tolerate anastomotic leakage. Patients who received neoadjuvant radiotherapy alone or combined chemoradiation were more likely to receive a preventive stoma at the surgeon's discretion. On the other hand, a secondary stoma was defined as a stoma created after the primary surgery due to complications such as diffuse peritonitis, medically uncontrolled pelvic sepsis, purulent discharge from the anus, fecal discharge from drainage tubes, or rectovaginal fistula. A stoma non-closure was defined as failing to perform stoma reversal surgery by the end of the follow-up period. In this study, local recurrence was defined as recurrence within the pelvis. In contrast, distal metastasis was defined as recurrence outside the pelvis, in other organs such as the liver, lung, or bone, or non-regional lymph nodes like the para-aortic lymph nodes. The statistical analysis was conducted using SPSS software (Version 24.0. Armonk, NY: IBM Corp). Continuous variables were compared using independent sample t-tests, while categorical variables were compared using chi-square or Fisher's exact tests, as appropriate. Multivariate logistic regression analysis, using the Allen-Cady modified backward selection procedure, was used to identify independent predictors of non-closure of the stoma. Variables with a p-value < 0.1 in the initial analysis were included in the multivariate model. A p-value < 0.05 was considered statistically significant. Receiver operating characteristic (ROC) curves were constructed to identify risk factors for the stoma's non-closure and determine the optimal cut-off points. The Kaplan-Meier method analyzed stoma-free survival in temporary stoma patients with different risk factors. The log-rank test was used to determine if there were significant differences in survival between groups (p < 0.05). Results A total of 4039 rectal cancer patients were included in this study. After exclusion, 2486 rectal cancer patients who underwent curative-intent restorative proctectomy were analyzed (Fig. 1 ). Out of these, 889 received a primary stoma. Among the 1597 patients who did not initially receive a stoma, 67 later had a secondary stoma due to symptomatic leakage. Table 1 represents the characteristics between patients with a primary stoma and those without, the former was significantly more likely male, had a higher incidence of T3 stage cancers, lower rectal cancer with less than 5 cm from the anal verge, hypoalbuminemia with serum albumin levels below 3.5 g/dL, and tend to receive Neoadjuvant radiotherapy (RT) (p < 0.001). Table 2 describes the pattern of the 103 patients who did not reserve their stoma out of the 956 patients with a temporary stoma. Cancer recurrence (35%) and anastomosis-related complications (22.3%) made up the majority. Table 3 revealed that patients with their stoma unreversed processed a higher proportion of renal dysfunction which was reflected by eGFR ≤ 30 mL/min/1.73m² (1.8% vs. 8.7%, p < 0.001). This group also showed a greater incidence of anastomotic leakage (21.4% vs. 8.9%, p < 0.001). Additionally, T3 and T4 stages patients were less likely to have their stomas reversed (p = 0.014), and a significantly higher proportion of patients with N1 and N2 stages were in the stoma non-closure group (29.1% vs. 27.3% and 30.1% vs. 16.2%, p = 0.001). Tumors involving circumferential margins and preoperative serum CEA levels above 5 ng/mL were also risks for stoma reversing (49.5% vs. 30.3%, 38.8% vs. 21.5%, p < 0.001). In the multivariate survival analysis for stoma non-closure (Table 4), age above 80, anastomotic leakage and the N2 stage emerged as risk factors for stoma non-closure (OR:3.53, 4.09, 5.35 respectively, p < 0.001). Instead, adjuvant chemotherapy was identified as a protective factor with an odds ratio of 0.258 (p < 0.001) after backward selection. The ROC curve analysis for variables associated with stoma non-closure indicated a risk cutoff value of 2.5, with a sensitivity of 84.5% and specificity of 51.4% (Fig. 2 ). The area under the curve (AUC) stood at 0.724 (95% CI: 0.677–0.772). Based on these insights, advanced age, anastomotic leakage, N stage, lower rectal cancer presence, serum CEA > 5 ng/mL, tumors involving circumferential margins, and eGFR ≤ 30 mL/min/1.73m² were highlighted for risk stratification (Table 5). Furthermore, 16.6% of the non-closure group had a risk score above 2, a significantly higher rate than those with a risk score of 2 or below (3.7% vs. 16.6%, p < 0.001) (Fig. 3 ). Discussion This study aimed to investigate the risk factors associated with the non-closure of initially intended temporary stomas, which could not undergo stoma reversal surgery. While previous studies primarily discussed preoperative or post-operative risks of permanent stomas, our focus was on identifying factors that contribute to the non-closure of stomas. In this study, the rate of stoma non-closure was 10.7%. Existing research has indicated that the rate of permanent stomas, including re-do stomas and stoma non-closures, ranged from 3–23.2% [ 21 – 24 ], and the rate of non-closure for temporary stomas ranged from 3–25% [ 21 – 25 ]. We identified seven independent risk factors for stoma non-closure, namely advanced age, anastomotic leakage, N stages, tumor distance from the anal verge 5, and involved circumferential margin, and eGFR ≤ 30 mL/min/1.73 m². These factors can be assessed and communicated to patients by surgeons before the operation. Cancer progression involving local recurrence and distant metastasis has been identified as the primary cause of permanent stomas [ 21 , 23 , 26 , 27 ]. In our study, cancer recurrence accounted for most stoma non-closures (35%), followed by complications related to anastomosis (22.3%). Den Dulk et al. identified advanced age, creation of a secondary stoma, diverting ostomy, surgical difficulties, and cancer recurrence as factors limiting stoma reversal [ 22 ]. Lindgren et al. reported that 56% of patients with symptomatic anastomotic leakage ended up with a permanent stoma [ 24 ]. Our analysis revealed that stenosis and leakage accounted for more than half of the cases with anastomosis-related complications. The inflammatory response triggered by postoperative infection, leading to increased production of IL-6 and VEGF, is considered one of the mechanisms contributing to anastomotic leakage [ 28 ]. Thus, the management of postoperative anastomotic complications remains a significant challenge for surgeons to address. Due to the lower BMI of our patient population, colostomy was primarily chosen as the type of diverting procedure. Although ileostomy is considered a less invasive and more comfortable procedure compared to colostomy, the digestive enzymes present in the output can irritate the mucosa and skin after undergoing ileostomy. The high volume of stoma output may cause dehydration and electrolyte imbalance. In contrast, colostomies produce stool without digestive enzymes. Colostomy patients can be reassured that there are no strict dietary restrictions. Recent studies have demonstrated the comparable diverting function and post-ostomy mortality rates between colostomies and ileostomies [ 29 , 30 ]. In our study, the proportion of stoma non-closure did not show statistical significance between colostomies and ileostomies (81.6% vs. 18.4%, p = 0.494). Therefore, the selection of colostomy or ileostomy should still be individually considered based on the patient's specific condition. Preoperative serum CEA levels have been found to influence the reversal of stomas. Our previous study reported that the preoperative CEA level was an independent prognostic factor for stages I-III CRC after curative resection, particularly when the CEA level > 10 ng/ml [ 31 ]. Another study demonstrated that elevated preoperative serum CEA levels in patients with stage 0-III mid-to-low rectal cancer who underwent curative low anterior resection were related to a higher rate of permanent stomas and poor oncological prognosis [ 32 ]. Our current study found that a CEA level above 5 ng/ml was associated with a higher rate of stoma non-closure (38.8%). Even after neoadjuvant chemoradiation therapy, persistently elevated CEA levels can lead to cancer progression with increased perianal invasion, resulting in reduced overall and disease-free survival. In conclusion, monitoring the pre-treatment CEA level is essential and serves as a predictive factor for stoma non-closure. Circumferential margins have been identified as an independent prognostic factor in rectal cancer surgery. Liu et al. demonstrated that a circumferential margin less than 1mm was associated with an increased cancer-specific mortality rate [ 33 ]. Involvement of the circumferential margin raises the risk of local recurrence and increases the need for permanent stomas [ 34 ]. In our study, patients with non-closure of stomas had a higher rate of involved circumferential margins (49.5%). Consequently, surgeons must strive to achieve maximum circumferential resection margins to improve outcomes and reverse stoma. Impaired renal function is often observed after ileostomy due to dehydration and electrolyte imbalance. A retrospective study demonstrated that a decreased eGFR of ≤ 45 mL/min/1.73 m² was an independent predictor of non-closure in patients who underwent acute resection of left-sided obstructive colon cancer [ 35 ]. Our study revealed that eGFR ≤ 30 mL/min/1.73 m² was a negative predicting factor of reversal of stoma. Khaldi et al found that patients with colostomy may also experience renal dysfunction, which can lead to permanent stoma along with comorbidities such as hypertension and diabetes mellitus, contributing to renal impairment [ 36 ]. Hence, it is crucial to monitor renal function regularly during post-operative follow-up management for patients with a stoma. Neoadjuvant concurrent therapy and radiotherapy in advanced rectal cancer patients remains a controversial issue. Zhou et al. demonstrated that radiotherapy and chemotherapy were not correlated with the non-closure of dysfunctional stomas and could reduce the local recurrence rate in lower rectal cancer [ 27 , 37 , 38 ]. Nevertheless, while neoadjuvant chemoradiation therapy and adjuvant radiotherapy can downstage colorectal cancer by reducing tumor size, preoperative radiotherapy may increase the risk of complications such as anastomotic leakage, leading to the need for a permanent stoma [ 39 , 40 ]. A multivariate analysis reported that preoperative radiotherapy can cause an irreversible secondary stoma [ 22 ]. Our study, however, showed no significant relationship between neoadjuvant radiotherapy and stoma non-closure. Additionally, adjuvant chemotherapy was identified as a protective factor against stoma non-closure (OR: 0.26, p < 0.001). Striking a balance between the advantages of neoadjuvant and adjuvant chemoradiation therapy, considering the risk of complications, and aiming for stoma reversal should be a key consideration. Furthermore, proton beam therapy is less invasive for rectal cancer compared to photon-based radiotherapy [ 41 ]. The future treatment plan can also consider proton therapy to achieve preferable outcomes. This research has several limitations that should be acknowledged. Firstly, the study's retrospective design and single-center introduce the possibility of selection bias. The sample size was limited and consisted of patients from a single ethnic group, which may affect the generalizability of the findings to other populations. Secondly, the neoadjuvant radiotherapy course and surgical procedures varied due to surgeon discretion and patient preferences, leading to unavoidable differences. Additionally, the use of diverse regimens, including radiotherapy or combined chemoradiotherapy, contributed to the heterogeneous treatment approaches. Thirdly, the accuracy of restaging by MRI examination may be compromised, particularly after neoadjuvant therapy, potentially leading to misdiagnosis [ 32 ]. To mitigate this, we relied on the pathological staging method as an alternative to evaluate the extent of the cancer more precisely. Lastly, deviations from standardized treatment protocols may introduce variability and confounding factors. These limitations should be considered when interpreting findings for clinical practice. Future research with larger, multicenter cohorts and more comprehensive evaluations is warranted to overcome these limitations and provide more robust evidence. Conclusions Advanced age, symptomatic anastomotic leakage, positive nodal status, preoperative serum CEA levels > 5 ng/ml, circumferential margins involvement, and eGFR ≤ 30 mL/min/1.73m 2 are independent prognostic factors for temporary stoma non-closure in rectal cancer patients. The non-closure rate may increase to 16.6% when more than 2 factors are presented. Surgeons should thoroughly evaluate and inform the patients before surgery. Abbreviations CEA carcinoembryonic antigen CCRT concurrent chemoradiation ROC Receiver operating characteristic RT radiotherapy AUC area under the curve Declarations Consent to Participate Declaration All participants involved in this research have been provided with sufficient information regarding the purpose of our study. Additionally, the risks and benefits associated with the research were thoroughly explained by the author, and informed consent was obtained. Funding Declaration This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Human Ethics and Consent to Participate Declarations This study has been granted approval by the Chang Gung Medical Foundation Institutional Review Board under approval number 202001577B0. Data availability statement The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author. Competing Interest declaration The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Author Contribution Chia-Chien Hsu and Shu-Huan Huang wrote the main manuscript text. Wen-Sy Tsai, Tzong-yun Tsai, Jeng-Fu You, and Shu-Huan Huang contributed to the design and implementation of the research. Chien-Yuh Yeh, Pao-Shiu Hsieh, Reiping Tang, and Shu-Huan Huang contributed to the analysis of the results. All authors reviewed the manuscript. References Ahmed S, Eng C. Neoadjuvant strategies: Locally advanced rectal cancer. Clin Colon Rectal Surg. 2017;30(05):383–6. Bordeianou L, Maguire LH, Alavi K, Sudan R, Wise PE, Kaiser AM. Sphincter-sparing surgery in patients with low-lying rectal cancer: techniques, oncologic outcomes, and functional results. J Gastrointest Surg. 2014;18:1358–72. Kang S-B, Cho JR, Jeong S-Y, et al. 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Fok M, Toh S, Easow J, et al. Proton beam therapy in rectal cancer: A systematic review and meta-analysis. Surg Oncol. 2021;38:101638. Tables Tables 1 to 5 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files table1.png table2.png table3.png table4.png table5.png Cite Share Download PDF Status: Published Journal Publication published 06 May, 2024 Read the published version in World Journal of Surgical Oncology → Version 1 posted Editorial decision: Revision requested 23 Mar, 2024 Reviews received at journal 21 Mar, 2024 Reviewers agreed at journal 17 Mar, 2024 Reviewers agreed at journal 11 Mar, 2024 Reviewers invited by journal 10 Mar, 2024 Editor assigned by journal 08 Mar, 2024 Submission checks completed at journal 27 Feb, 2024 First submitted to journal 17 Feb, 2024 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3965721","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":275117003,"identity":"2b5b1515-d1a4-47d5-b066-db9cba5c101e","order_by":0,"name":"Chia-Chien Hsu","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chia-Chien","middleName":"","lastName":"Hsu","suffix":""},{"id":275117004,"identity":"50746f83-c473-45ea-911e-b8558a2147d2","order_by":1,"name":"Wen-Sy Tsai","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wen-Sy","middleName":"","lastName":"Tsai","suffix":""},{"id":275117005,"identity":"30eb595d-af29-43f4-a812-448908fa50ee","order_by":2,"name":"Tzong-yun Tsai","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tzong-yun","middleName":"","lastName":"Tsai","suffix":""},{"id":275117006,"identity":"0be784ab-bdbf-437a-8b08-78812c79b75b","order_by":3,"name":"Jeng-Fu You","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jeng-Fu","middleName":"","lastName":"You","suffix":""},{"id":275117007,"identity":"ac943fb2-61ac-4326-92dc-edd3000a48b6","order_by":4,"name":"Chien-Yuh Yeh","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chien-Yuh","middleName":"","lastName":"Yeh","suffix":""},{"id":275117008,"identity":"d4af7d5c-3644-4909-9ebd-6e92205d9a08","order_by":5,"name":"Pao-Shiu Hsieh","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Pao-Shiu","middleName":"","lastName":"Hsieh","suffix":""},{"id":275117009,"identity":"9558493d-c59d-42bb-9e64-851425afa920","order_by":6,"name":"Reiping Tang","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Reiping","middleName":"","lastName":"Tang","suffix":""},{"id":275117010,"identity":"fd0e4109-a910-42c1-86fd-f3647c9250da","order_by":7,"name":"Shu-Huan Huang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3klEQVRIiWNgGAWjYDACCR4wVW/f3gCkDCyI15JgwHMApEWCFC0SCWAuYR3ys3uPSfzcUZtnLvn86oYfBRIM/O3dCXi1GNw5lybZe+Z4seXsnLKbPUCHSZw5uwG/FokcMwnetmOMDbdz0m7wALUYSOTi1yI/I8dM8i9Iy80zaTf/EKOF4UaOmTRvW03ihhvsx24TZYvBjRxja9m2A8aSPTlst2UMJHgI+gXoMMObb9vq5PjZjz+7+eaPjRx/ey8Bh0HAYSDmMQCxeIhRDgJ1QMz+gFjVo2AUjIJRMMIAAAzaSPUihE4MAAAAAElFTkSuQmCC","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":true,"prefix":"","firstName":"Shu-Huan","middleName":"","lastName":"Huang","suffix":""}],"badges":[],"createdAt":"2024-02-18 03:16:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3965721/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3965721/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12957-024-03403-8","type":"published","date":"2024-05-07T03:58:25+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":51820537,"identity":"efa80764-828c-488e-90ec-2b4ca8186168","added_by":"auto","created_at":"2024-02-29 16:01:17","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":167672,"visible":true,"origin":"","legend":"\u003cp\u003eStudy Population\u003c/p\u003e\n\u003cp\u003eThis figure analyzes a total of 956 rectal cancer patients who underwent curative-intent restorative proctectomy and temporary stoma. This includes 889 patients with a primary stoma and 67 with a stoma secondary to symptomatic leakage, analyzed after exclusions.\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3965721/v1/fc9dc8c77e6e6bc5f7942612.png"},{"id":51820538,"identity":"25c973af-f5dd-493d-90c8-f720e8baaec3","added_by":"auto","created_at":"2024-02-29 16:01:17","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":355744,"visible":true,"origin":"","legend":"\u003cp\u003eROC Curve for Temporary Stoma Non-Closure Risk\u003c/p\u003e\n\u003cp\u003eThe Receiver Operating Characteristic (ROC) curve analysis for the risk of non-closure of temporary stomas indicates a cutoff value of 2.5. This is associated with a sensitivity of 84.5% and a specificity of 51.4%. The area under the curve (AUC) stands at 0.724.\u003c/p\u003e","description":"","filename":"figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-3965721/v1/81509fe5d95827dd31de90fd.png"},{"id":51820540,"identity":"dbdad8a5-7fbe-41b9-8e11-cce74013ef4d","added_by":"auto","created_at":"2024-02-29 16:01:17","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":82174,"visible":true,"origin":"","legend":"\u003cp\u003eTemporary Stoma Non-Closure Rate After Risk Stratification\u003c/p\u003e\n\u003cp\u003eThe blue line represents patients with risk factors less than or equal to 2, while the green line represents those with risk factors greater than 2. There is a significantly higher rate of stoma non-closure in patients with a risk score greater than 2 compared to those with a risk score less than or equal to 2 (16.6% vs 3.7%, p\u0026lt;0.001).\u003c/p\u003e","description":"","filename":"figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3965721/v1/e2f65c5fae75503ac26a3307.jpg"},{"id":56140412,"identity":"ba87edfa-ff57-4150-9ec2-e1b7608db597","added_by":"auto","created_at":"2024-05-09 04:23:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":801590,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3965721/v1/38ff1761-cabf-4b47-a60e-e452f0b5b669.pdf"},{"id":51821243,"identity":"75a97216-9273-4e87-afca-c8be503a79e0","added_by":"auto","created_at":"2024-02-29 16:09:18","extension":"png","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":164477,"visible":true,"origin":"","legend":"","description":"","filename":"table1.png","url":"https://assets-eu.researchsquare.com/files/rs-3965721/v1/608ddc1ea144740c8f33c1f0.png"},{"id":51820534,"identity":"1c359db8-f166-4854-8f0d-60652c62ba78","added_by":"auto","created_at":"2024-02-29 16:01:16","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":93245,"visible":true,"origin":"","legend":"","description":"","filename":"table2.png","url":"https://assets-eu.researchsquare.com/files/rs-3965721/v1/3c69233644cb5e14f0108963.png"},{"id":51820539,"identity":"972894ca-aee7-413e-8dff-1b3dd00bdef1","added_by":"auto","created_at":"2024-02-29 16:01:17","extension":"png","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":149927,"visible":true,"origin":"","legend":"","description":"","filename":"table3.png","url":"https://assets-eu.researchsquare.com/files/rs-3965721/v1/2fd028d369fc9d312208e96c.png"},{"id":51820536,"identity":"0e8578cc-4c8a-4328-af20-97f53e8d69bb","added_by":"auto","created_at":"2024-02-29 16:01:17","extension":"png","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":120903,"visible":true,"origin":"","legend":"","description":"","filename":"table4.png","url":"https://assets-eu.researchsquare.com/files/rs-3965721/v1/fd74a6aff6443e851a409a3e.png"},{"id":51820541,"identity":"ebc3e8e7-be39-4b64-b4cd-b8844b197b39","added_by":"auto","created_at":"2024-02-29 16:01:17","extension":"png","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":68117,"visible":true,"origin":"","legend":"","description":"","filename":"table5.png","url":"https://assets-eu.researchsquare.com/files/rs-3965721/v1/404b4616b05d45126d175028.png"}],"financialInterests":"No competing interests reported.","formattedTitle":"Predictors for Temporary Stomas Non-Closure among Non-Metastatic Rectal Cancer Patients Undergoing Curative Resection: a Retrospective Analysis","fulltext":[{"header":"Background","content":"\u003cp\u003eCurative resection was considered the primary treatment approach for non-metastatic rectal cancer. Advances in surgical techniques, such as the introduction of neoadjuvant therapy [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], and the desire of patients to preserve anal function have shifted the preference towards sphincter-sparing surgery over abdominoperineal resection for rectal cancer patients [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, sphincter-preserving surgery can be accompanied by complications such as bowel dysfunction or anastomosis leakage [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Therefore, temporary fecal diversion is often necessary following sphincter-sparing surgery [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The Clinical Practice Guidelines for Ostomy Surgery recommended fecal diversion as an effective method that can reduce the severity of anastomotic dehiscence [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePrevious research found that 3\u0026ndash;23.2% of patients who underwent sphincter-preserving surgery still required permanent stomas. [\u003cspan additionalcitationids=\"CR9 CR10 CR11\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] Several predisposing factors may lead to irreversible stomas, including local recurrence and distant metastasis [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Other correlated factors included anastomosis leakage [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], advanced age [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], male gender [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], renal dysfunction [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], and elevated preoperative serum carcinoembryonic antigen (CEA) level [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Additionally, whether neoadjuvant chemoradiation therapy is a risk factor for permanent stoma in rectal cancer patients remains controversial [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study aims to identify the presented risk factors associated with initially intended temporary stomas that ultimately did not undergo closure in non-metastatic rectal cancer patients who underwent curative-intent restorative proctectomy surgery. This information can be utilized to inform the patients about the potentially unfavorable outcomes before the operation.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e Approval number 202001577B0 was obtained from the Chang Gung Medical Foundation Institutional Review Board to conduct this study. From January 1, 2005, to December 31, 2017, consecutive patients with rectal cancer were recruited from the Division of Colorectal Surgery at Chang Gung Memorial Hospital in Linkou (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis study enrolled 4039 rectal cancer patients who received proctectomy from 2005\u0026ndash;2017. The mean follow-up time was 62.3 months, with a maximum of 134 months. The study included non-metastatic rectal cancer patients and those who achieved a pathological complete response (ypT0) following neoadjuvant treatments and underwent curative-intent resection with a stoma. Patients with stage IV rectal cancer, non-curative resection, emergency surgery, non-CRC pathology (squamous carcinoma, melanoma, or \u003cem\u003egastrointestinal stromal tumor\u003c/em\u003e), and recurrent or synchronous cancer were all excluded. For patients who received abdominal perineal resection and Hartmann's procedure were also excluded due to the challenges and limitations of stoma reversal.\u003c/p\u003e \u003cp\u003eBefore the surgery, patients underwent preoperative evaluations such as computed tomography of the chest, abdomen, and pelvis, magnetic resonance imaging of the pelvis, preoperative serum carcinoembryonic antigen (CEA), and complete colonoscopy. Postoperative follow-up evaluations were conducted based on a standardized protocol, which included physical examination, serum CEA level, colonoscopy, and computed tomography. Additional positron emission tomography was arranged if imaging reports were equivocal. Adjuvant chemotherapy was primarily based on 5-fluoropyrimidine (5-fluorouracil, capecitabine, or tegafur), and oxaliplatin was administered at the surgeon's discretion. The digital rectal examination was routinely performed to evaluate the anastomosis condition. An additional colonoscopy or lower gastrointestinal series would be conducted if the anastomotic integrity was uncertain.\u003c/p\u003e \u003cp\u003ePatients with locally advanced mid-to-low rectal cancer with cT3, cT4, or positive cN stage were treated with neoadjuvant concurrent chemoradiation (CCRT) or short-course radiotherapy at the discretion of the surgeon. Long-course neoadjuvant CCRT patients were administered a 5-fluoropyrimidine-based regimen (intravenous 5-fluorouracil or oral capecitabine, tegafur) and 50.4 Gy in total 28 fractions of radiotherapy, followed by surgery 6\u0026ndash;8 weeks after the completion of treatment. Short-course radiotherapy patients received a dose of 25 Gy to the pelvis and tumor in total 5 fractions, and surgery was settled 8\u0026ndash;10 days after the end of radiotherapy.\u003c/p\u003e \u003cp\u003eA primary stoma was defined as a stoma made during primary surgery, and the decision to create one was at the surgeon's discretion. Factors influencing the decision to create a preventive stoma included a narrow pelvic cavity, malnutrition status, lower rectal cancer, adverse events during surgery, or the patient's inability to tolerate anastomotic leakage. Patients who received neoadjuvant radiotherapy alone or combined chemoradiation were more likely to receive a preventive stoma at the surgeon's discretion. On the other hand, a secondary stoma was defined as a stoma created after the primary surgery due to complications such as diffuse peritonitis, medically uncontrolled pelvic sepsis, purulent discharge from the anus, fecal discharge from drainage tubes, or rectovaginal fistula. A stoma non-closure was defined as failing to perform stoma reversal surgery by the end of the follow-up period.\u003c/p\u003e \u003cp\u003eIn this study, local recurrence was defined as recurrence within the pelvis. In contrast, distal metastasis was defined as recurrence outside the pelvis, in other organs such as the liver, lung, or bone, or non-regional lymph nodes like the para-aortic lymph nodes.\u003c/p\u003e \u003cp\u003eThe statistical analysis was conducted using SPSS software (Version 24.0. Armonk, NY: IBM Corp). Continuous variables were compared using independent sample t-tests, while categorical variables were compared using chi-square or Fisher's exact tests, as appropriate. Multivariate logistic regression analysis, using the Allen-Cady modified backward selection procedure, was used to identify independent predictors of non-closure of the stoma. Variables with a p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.1 in the initial analysis were included in the multivariate model. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Receiver operating characteristic (ROC) curves were constructed to identify risk factors for the stoma's non-closure and determine the optimal cut-off points. The Kaplan-Meier method analyzed stoma-free survival in temporary stoma patients with different risk factors. The log-rank test was used to determine if there were significant differences in survival between groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 4039 rectal cancer patients were included in this study. After exclusion, 2486 rectal cancer patients who underwent curative-intent restorative proctectomy were analyzed (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Out of these, 889 received a primary stoma. Among the 1597 patients who did not initially receive a stoma, 67 later had a secondary stoma due to symptomatic leakage. Table\u0026nbsp;1 represents the characteristics between patients with a primary stoma and those without, the former was significantly more likely male, had a higher incidence of T3 stage cancers, lower rectal cancer with less than 5 cm from the anal verge, hypoalbuminemia with serum albumin levels below 3.5 g/dL, and tend to receive Neoadjuvant radiotherapy (RT) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;2 describes the pattern of the 103 patients who did not reserve their stoma out of the 956 patients with a temporary stoma. Cancer recurrence (35%) and anastomosis-related complications (22.3%) made up the majority. Table\u0026nbsp;3 revealed that patients with their stoma unreversed processed a higher proportion of renal dysfunction which was reflected by eGFR\u0026thinsp;\u0026le;\u0026thinsp;30 mL/min/1.73m\u0026sup2; (1.8% vs. 8.7%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). This group also showed a greater incidence of anastomotic leakage (21.4% vs. 8.9%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Additionally, T3 and T4 stages patients were less likely to have their stomas reversed (p\u0026thinsp;=\u0026thinsp;0.014), and a significantly higher proportion of patients with N1 and N2 stages were in the stoma non-closure group (29.1% vs. 27.3% and 30.1% vs. 16.2%, p\u0026thinsp;=\u0026thinsp;0.001). Tumors involving circumferential margins and preoperative serum CEA levels above 5 ng/mL were also risks for stoma reversing (49.5% vs. 30.3%, 38.8% vs. 21.5%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eIn the multivariate survival analysis for stoma non-closure (Table\u0026nbsp;4), age above 80, anastomotic leakage and the N2 stage emerged as risk factors for stoma non-closure (OR:3.53, 4.09, 5.35 respectively, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Instead, adjuvant chemotherapy was identified as a protective factor with an odds ratio of 0.258 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) after backward selection.\u003c/p\u003e \u003cp\u003eThe ROC curve analysis for variables associated with stoma non-closure indicated a risk cutoff value of 2.5, with a sensitivity of 84.5% and specificity of 51.4% (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The area under the curve (AUC) stood at 0.724 (95% CI: 0.677\u0026ndash;0.772). Based on these insights, advanced age, anastomotic leakage, N stage, lower rectal cancer presence, serum CEA\u0026thinsp;\u0026gt;\u0026thinsp;5 ng/mL, tumors involving circumferential margins, and eGFR\u0026thinsp;\u0026le;\u0026thinsp;30 mL/min/1.73m\u0026sup2; were highlighted for risk stratification (Table\u0026nbsp;5). Furthermore, 16.6% of the non-closure group had a risk score above 2, a significantly higher rate than those with a risk score of 2 or below (3.7% vs. 16.6%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study aimed to investigate the risk factors associated with the non-closure of initially intended temporary stomas, which could not undergo stoma reversal surgery. While previous studies primarily discussed preoperative or post-operative risks of permanent stomas, our focus was on identifying factors that contribute to the non-closure of stomas. In this study, the rate of stoma non-closure was 10.7%. Existing research has indicated that the rate of permanent stomas, including re-do stomas and stoma non-closures, ranged from 3\u0026ndash;23.2% [\u003cspan additionalcitationids=\"CR22 CR23\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], and the rate of non-closure for temporary stomas ranged from 3\u0026ndash;25% [\u003cspan additionalcitationids=\"CR22 CR23 CR24\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. We identified seven independent risk factors for stoma non-closure, namely advanced age, anastomotic leakage, N stages, tumor distance from the anal verge\u0026thinsp;\u0026lt;\u0026thinsp;5 cm, preoperative CEA level\u0026thinsp;\u0026gt;\u0026thinsp;5, and involved circumferential margin, and eGFR\u0026thinsp;\u0026le;\u0026thinsp;30 mL/min/1.73 m\u0026sup2;. These factors can be assessed and communicated to patients by surgeons before the operation.\u003c/p\u003e \u003cp\u003eCancer progression involving local recurrence and distant metastasis has been identified as the primary cause of permanent stomas [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In our study, cancer recurrence accounted for most stoma non-closures (35%), followed by complications related to anastomosis (22.3%). Den Dulk et al. identified advanced age, creation of a secondary stoma, diverting ostomy, surgical difficulties, and cancer recurrence as factors limiting stoma reversal [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Lindgren et al. reported that 56% of patients with symptomatic anastomotic leakage ended up with a permanent stoma [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Our analysis revealed that stenosis and leakage accounted for more than half of the cases with anastomosis-related complications. The inflammatory response triggered by postoperative infection, leading to increased production of IL-6 and VEGF, is considered one of the mechanisms contributing to anastomotic leakage [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Thus, the management of postoperative anastomotic complications remains a significant challenge for surgeons to address.\u003c/p\u003e \u003cp\u003eDue to the lower BMI of our patient population, colostomy was primarily chosen as the type of diverting procedure. Although ileostomy is considered a less invasive and more comfortable procedure compared to colostomy, the digestive enzymes present in the output can irritate the mucosa and skin after undergoing ileostomy. The high volume of stoma output may cause dehydration and electrolyte imbalance. In contrast, colostomies produce stool without digestive enzymes. Colostomy patients can be reassured that there are no strict dietary restrictions. Recent studies have demonstrated the comparable diverting function and post-ostomy mortality rates between colostomies and ileostomies [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In our study, the proportion of stoma non-closure did not show statistical significance between colostomies and ileostomies (81.6% vs. 18.4%, p\u0026thinsp;=\u0026thinsp;0.494). Therefore, the selection of colostomy or ileostomy should still be individually considered based on the patient's specific condition.\u003c/p\u003e \u003cp\u003ePreoperative serum CEA levels have been found to influence the reversal of stomas. Our previous study reported that the preoperative CEA level was an independent prognostic factor for stages I-III CRC after curative resection, particularly when the CEA level\u0026thinsp;\u0026gt;\u0026thinsp;10 ng/ml [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Another study demonstrated that elevated preoperative serum CEA levels in patients with stage 0-III mid-to-low rectal cancer who underwent curative low anterior resection were related to a higher rate of permanent stomas and poor oncological prognosis [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Our current study found that a CEA level above 5 ng/ml was associated with a higher rate of stoma non-closure (38.8%). Even after neoadjuvant chemoradiation therapy, persistently elevated CEA levels can lead to cancer progression with increased perianal invasion, resulting in reduced overall and disease-free survival. In conclusion, monitoring the pre-treatment CEA level is essential and serves as a predictive factor for stoma non-closure.\u003c/p\u003e \u003cp\u003eCircumferential margins have been identified as an independent prognostic factor in rectal cancer surgery. Liu et al. demonstrated that a circumferential margin less than 1mm was associated with an increased cancer-specific mortality rate [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Involvement of the circumferential margin raises the risk of local recurrence and increases the need for permanent stomas [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. In our study, patients with non-closure of stomas had a higher rate of involved circumferential margins (49.5%). Consequently, surgeons must strive to achieve maximum circumferential resection margins to improve outcomes and reverse stoma.\u003c/p\u003e \u003cp\u003eImpaired renal function is often observed after ileostomy due to dehydration and electrolyte imbalance. A retrospective study demonstrated that a decreased eGFR of \u0026le;\u0026thinsp;45 mL/min/1.73 m\u0026sup2; was an independent predictor of non-closure in patients who underwent acute resection of left-sided obstructive colon cancer [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Our study revealed that eGFR\u0026thinsp;\u0026le;\u0026thinsp;30 mL/min/1.73 m\u0026sup2; was a negative predicting factor of reversal of stoma. Khaldi et al found that patients with colostomy may also experience renal dysfunction, which can lead to permanent stoma along with comorbidities such as hypertension and diabetes mellitus, contributing to renal impairment [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Hence, it is crucial to monitor renal function regularly during post-operative follow-up management for patients with a stoma.\u003c/p\u003e \u003cp\u003eNeoadjuvant concurrent therapy and radiotherapy in advanced rectal cancer patients remains a controversial issue. Zhou et al. demonstrated that radiotherapy and chemotherapy were not correlated with the non-closure of dysfunctional stomas and could reduce the local recurrence rate in lower rectal cancer [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Nevertheless, while neoadjuvant chemoradiation therapy and adjuvant radiotherapy can downstage colorectal cancer by reducing tumor size, preoperative radiotherapy may increase the risk of complications such as anastomotic leakage, leading to the need for a permanent stoma [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. A multivariate analysis reported that preoperative radiotherapy can cause an irreversible secondary stoma [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Our study, however, showed no significant relationship between neoadjuvant radiotherapy and stoma non-closure. Additionally, adjuvant chemotherapy was identified as a protective factor against stoma non-closure (OR: 0.26, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Striking a balance between the advantages of neoadjuvant and adjuvant chemoradiation therapy, considering the risk of complications, and aiming for stoma reversal should be a key consideration. Furthermore, proton beam therapy is less invasive for rectal cancer compared to photon-based radiotherapy [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. The future treatment plan can also consider proton therapy to achieve preferable outcomes.\u003c/p\u003e \u003cp\u003eThis research has several limitations that should be acknowledged. Firstly, the study's retrospective design and single-center introduce the possibility of selection bias. The sample size was limited and consisted of patients from a single ethnic group, which may affect the generalizability of the findings to other populations. Secondly, the neoadjuvant radiotherapy course and surgical procedures varied due to surgeon discretion and patient preferences, leading to unavoidable differences. Additionally, the use of diverse regimens, including radiotherapy or combined chemoradiotherapy, contributed to the heterogeneous treatment approaches. Thirdly, the accuracy of restaging by MRI examination may be compromised, particularly after neoadjuvant therapy, potentially leading to misdiagnosis [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. To mitigate this, we relied on the pathological staging method as an alternative to evaluate the extent of the cancer more precisely. Lastly, deviations from standardized treatment protocols may introduce variability and confounding factors. These limitations should be considered when interpreting findings for clinical practice. Future research with larger, multicenter cohorts and more comprehensive evaluations is warranted to overcome these limitations and provide more robust evidence.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eAdvanced age, symptomatic anastomotic leakage, positive nodal status, preoperative serum CEA levels\u0026thinsp;\u0026gt;\u0026thinsp;5 ng/ml, circumferential margins involvement, and eGFR\u0026thinsp;\u0026le;\u0026thinsp;30 mL/min/1.73m\u003csup\u003e2\u003c/sup\u003e are independent prognostic factors for temporary stoma non-closure in rectal cancer patients. The non-closure rate may increase to 16.6% when more than 2 factors are presented. Surgeons should thoroughly evaluate and inform the patients before surgery.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCEA \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; carcinoembryonic antigen\u003c/p\u003e\n\u003cp\u003eCCRT \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; concurrent chemoradiation\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eROC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Receiver operating characteristic \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRT \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;radiotherapy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAUC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;area under the curve\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eConsent to Participate Declaration\u003c/p\u003e\n\u003cp\u003eAll participants involved in this research have been provided with sufficient information regarding the purpose of our study. Additionally, the risks and benefits associated with the research were thoroughly explained by the author, and informed consent was obtained.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFunding Declaration\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003eHuman Ethics and Consent to Participate Declarations\u003c/p\u003e\n\u003cp\u003eThis study has been granted approval by the Chang Gung Medical Foundation Institutional Review Board under approval number 202001577B0.\u003c/p\u003e\n\u003cp\u003eData availability statement\u003c/p\u003e\n\u003cp\u003eThe original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author.\u003c/p\u003e\n\u003cp\u003eCompeting Interest declaration\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eChia-Chien Hsu and Shu-Huan Huang wrote the main manuscript text. Wen-Sy Tsai, Tzong-yun Tsai, Jeng-Fu You, and Shu-Huan Huang contributed to the design and implementation of the research. Chien-Yuh Yeh, Pao-Shiu Hsieh, Reiping Tang, and Shu-Huan Huang contributed to the analysis of the results. All authors reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAhmed S, Eng C. Neoadjuvant strategies: Locally advanced rectal cancer. Clin Colon Rectal Surg. 2017;30(05):383\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBordeianou L, Maguire LH, Alavi K, Sudan R, Wise PE, Kaiser AM. Sphincter-sparing surgery in patients with low-lying rectal cancer: techniques, oncologic outcomes, and functional results. J Gastrointest Surg. 2014;18:1358\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKang S-B, Cho JR, Jeong S-Y, et al. Quality of life after sphincter preservation surgery or abdominoperineal resection for low rectal cancer (ASPIRE): a long-term prospective, multicentre, cohort study. The Lancet Regional Health\u0026ndash;Western Pacific; 2021. p. 6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShin US, Kim CW, Yu CS, Kim JC. Delayed anastomotic leakage following sphincter-preserving surgery for rectal cancer. Int J Colorectal Dis. 2010;25:843\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eH\u0026uuml;ser N, Michalski CW, Erkan M, et al. Systematic review and meta-analysis of the role of defunctioning stoma in low rectal cancer surgery. Ann Surg. 2008;248(1):52\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTan W, Tang C, Shi L, Eu K. Meta-analysis of defunctioning stomas in low anterior resection for rectal cancer. J Br Surg. 2009;96(5):462\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHendren S, Hammond K, Glasgow SC, et al. Clinical practice guidelines for ostomy surgery. Dis Colon Rectum. 2015;58(4):375\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoo RN, Kim G, Kye B-H, Cho H-M, Kim H. The fate of preserved sphincter in rectal cancer patients. Int J Colorectal Dis. 2018;33:745\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSeo SI, Yu CS, Kim GS, et al. Characteristics and risk factors associated with permanent stomas after sphincter-saving resection for rectal cancer. World J Surg. 2013;37:2490\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eden Dulk M, Smit M, Peeters KC, et al. A multivariate analysis of limiting factors for stoma reversal in patients with rectal cancer entered into the total mesorectal excision (TME) trial: a retrospective study. Lancet Oncol. 2007;8(4):297\u0026ndash;303.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLim SW, Kim HJ, Kim CH, Huh JW, Kim YJ, Kim HR. Risk factors for permanent stoma after low anterior resection for rectal cancer. Langenbeck's archives Surg. 2013;398:259\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLindgren R, Hallb\u0026ouml;\u0026ouml;k O, Ruteg\u0026aring;rd J, Sj\u0026ouml;dahl R, Matthiessen P. What is the risk for a permanent stoma after low anterior resection of the rectum for cancer? A six-year follow-up of a multicenter trial. Dis colon rectum. 2011;54(1):41\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJunginger T, G\u0026ouml;nner U, Trinh TT, Lollert A, Oberholzer K, Berres M. Permanent stoma after low anterior resection for rectal cancer. Dis colon rectum. 2010;53(12):1632\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou X, Wang B, Li F, Wang J, Fu W. Risk factors associated with nonclosure of defunctioning stomas after sphincter-preserving low anterior resection of rectal cancer: a meta-analysis. Dis Colon Rectum. 2017;60(5):544\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDinnewitzer A, J\u0026auml;ger T, Nawara C, Buchner S, Wolfgang H, \u0026Ouml;fner D. Cumulative incidence of permanent stoma after sphincter preserving low anterior resection of mid and low rectal cancer. Volume 56. Diseases of the colon \u0026amp; rectum; 2013. pp. 1134\u0026ndash;42. 10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDavid G, Slavin J, Willmott S, Corless D, Khan A, Selvasekar C. Loop ileostomy following anterior resection: is it really temporary? Colorectal Dis. 2010;12(5):428\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim MJ, Kim YS, Park SC, et al. Risk factors for permanent stoma after rectal cancer surgery with temporary ileostomy. Surgery. 2016;159(3):721\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Ommeren\u0026ndash;Olijve S, Burbach J, Furn\u0026eacute;e E. Risk factors for non-closure of an intended temporary defunctioning stoma after emergency resection of left-sided obstructive colon cancer. Int J Colorectal Dis. 2020;35:1087\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang S-H, Tsai K-Y, Tsai T-y, et al. Preoperative risk stratification of permanent stoma in patients with non-metastatic mid and low rectal cancer undergoing curative resection and a temporary stoma. Langenbeck's Archives Surg. 2022;407(5):1991\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaker B, Salameh H, Al-Salman M, Daoud F. How does preoperative radiotherapy affect the rate of sphincter-sparing surgery in rectal cancer? Surg Oncol. 2012;21(3):e103\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSeo SI, Yu CS, Kim GS, et al. Characteristics and risk factors associated with permanent stomas after sphincter-saving resection for rectal cancer. World J Surg. 2013;37(10):2490\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eden Dulk M, Smit M, Peeters KC, et al. A multivariate analysis of limiting factors for stoma reversal in patients with rectal cancer entered into the total mesorectal excision (TME) trial: a retrospective study. Lancet Oncol. 2007;8(4):297\u0026ndash;303.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLim SW, Kim HJ, Kim CH, Huh JW, Kim YJ, Kim HR. Risk factors for permanent stoma after low anterior resection for rectal cancer. Langenbecks Arch Surg. 2013;398(2):259\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLindgren R, Hallbook O, Rutegard J, Sjodahl R, Matthiessen P. What is the risk for a permanent stoma after low anterior resection of the rectum for cancer? A six-year follow-up of a multicenter trial. Dis Colon Rectum. 2011;54(1):41\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDavid GG, Slavin JP, Willmott S, Corless DJ, Khan AU, Selvasekar CR. Loop ileostomy following anterior resection: is it really temporary? Colorectal Dis. 2010;12(5):428\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJunginger T, Gonner U, Trinh TT, Lollert A, Oberholzer K, Berres M. Permanent stoma after low anterior resection for rectal cancer. Dis Colon Rectum. 2010;53(12):1632\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou X, Wang B, Li F, Wang J, Fu W. Risk Factors Associated With Nonclosure of Defunctioning Stomas After Sphincter-Preserving Low Anterior Resection of Rectal Cancer: A Meta-Analysis. Dis Colon Rectum. 2017;60(5):544\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlonso S, Pascual M, Salvans S, et al. Postoperative intra-abdominal infection and colorectal cancer recurrence: a prospective matched cohort study of inflammatory and angiogenic responses as mechanisms involved in this association. Eur J Surg Oncol. 2015;41(2):208\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKlink CD, Lioupis K, Binnebosel M, et al. Diversion stoma after colorectal surgery: loop colostomy or ileostomy? Int J Colorectal Dis. 2011;26(4):431\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChudner A, Gachabayov M, Dyatlov A, Lee H, Essani R, Bergamaschi R. The influence of diverting loop ileostomy vs. colostomy on postoperative morbidity in restorative anterior resection for rectal cancer: a systematic review and meta-analysis. Langenbecks Arch Surg. 2019;404(2):129\u0026ndash;39.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang SH, Tsai WS, You JF, et al. Preoperative Carcinoembryonic Antigen as a Poor Prognostic Factor in Stage I-III Colorectal Cancer After Curative-Intent Resection: A Propensity Score Matching Analysis. Ann Surg Oncol. 2019;26(6):1685\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang SH, Tsai KY, Tsai TY, et al. Preoperative risk stratification of permanent stoma in patients with non-metastatic mid and low rectal cancer undergoing curative resection and a temporary stoma. Langenbecks Arch Surg. 2022;407(5):1991\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu Q, Luo D, Cai S, Li Q, Li X. Circumferential resection margin as a prognostic factor after rectal cancer surgery: A large population-based retrospective study. Cancer Med. 2018;7(8):3673\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim MJ, Kim YS, Park SC, et al. Risk factors for permanent stoma after rectal cancer surgery with temporary ileostomy. Surgery. 2016;159(3):721\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Ommeren-Olijve SJ, Burbach JPM, Furnee EJB. Dutch Snapshot Research, \u003cem\u003eRisk factors for non-closure of an intended temporary defunctioning stoma after emergency resection of left-sided obstructive colon cancer\u003c/em\u003e. Int J Colorectal Dis. 2020;35(6):1087\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAl Khaldi SS, Al Harbi R, Albastaki S, et al. Deterioration in renal function after stoma creation: a retrospective review from a Middle Eastern tertiary care center. Ann Saudi Med. 2023;43(2):76\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Gijn W, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 2011;12(6):575\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRolf Sauer MD, Heinz Becker MD, Werner Hohenberger MD, Claus R\u0026ouml;del MD, Wittekind C, Fietkau MDR, Martus MDP, J\u0026ouml;rg PD, Tschmelitsch MD, Hager E, Clemens MD, Hess F, Karstens MDJ-H, Liersch MDT, Heinz Schmidberger MD, M.D., and, Raab R. M.D., \u003cem\u003ePreoperative versus Postoperative Chemoradiotherapy for Rectal Cancer.\u003c/em\u003e 2004.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNesbakken A, Lunde KNOC. \u003cem\u003eOutcome and late functional results after anastomotic leakage following mesorectal excision for rectal cancer.\u003c/em\u003e 2001.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhu H, Bai B, Shan L, et al. Preoperative radiotherapy for patients with rectal cancer: a risk factor for non-reversal of ileostomy caused by stenosis or stiffness proximal to colorectal anastomosis. Oncotarget. 2017;8(59):100746\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFok M, Toh S, Easow J, et al. Proton beam therapy in rectal cancer: A systematic review and meta-analysis. Surg Oncol. 2021;38:101638.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 5 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"world-journal-of-surgical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjso","sideBox":"Learn more about [World Journal of Surgical Oncology](http://wjso.biomedcentral.com)","snPcode":"12957","submissionUrl":"https://submission.nature.com/new-submission/12957/3","title":"World Journal of Surgical Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3965721/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3965721/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003eThe primary treatment for non-metastatic rectal cancer is curative resection. However, sphincter-preserving surgery may lead to complications. This study aims to develop a predictive model for stoma non-closure in rectal cancer patients who underwent curative-intent restorative proctectomy surgery.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003e Consecutive patients diagnosed with non-metastatic rectal cancer between January 2005 and December 2017, who underwent proctectomy, were retrospectively included in the Chang Gung Memorial Foundation Institutional Review Board. A comprehensive evaluation and analysis of potential risk factors linked to stoma non-closure were performed.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eOut of 956 patients with temporary stomas, 10.3% (n\u0026thinsp;=\u0026thinsp;103) experienced non-closure primarily due to cancer recurrence and anastomosis-related issues. Through multivariate analysis, several preoperative risk factors significantly associated with stoma non-closure were identified, including advanced age, anastomotic leakage, positive nodal status, high preoperative CEA levels, lower rectal cancer presence, margin involvement, and an eGFR below 30 mL/min/1.73m2. A risk assessment model achieved an AUC of 0.724, with a cutoff of 2.5, 84.5% sensitivity, and 51.4% specificity. Importantly, the non-closure rate could rise to 16.6% when more than two risk factors were present, starkly contrasting the 3.7% non-closure rate observed in cases with a risk score of 2 or below (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003ePrognostic risk factors associated with the non-closure of a temporary stoma include advanced age, symptomatic anastomotic leakage, nodal status, high CEA levels, margin involvement, and an eGFR below 30 mL/min/1.73m2. Hence, it is crucial for surgeons to evaluate these factors and provide patients with a comprehensive prognosis before undergoing surgical intervention.\u003c/p\u003e","manuscriptTitle":"Predictors for Temporary Stomas Non-Closure among Non-Metastatic Rectal Cancer Patients Undergoing Curative Resection: a Retrospective Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-29 16:01:12","doi":"10.21203/rs.3.rs-3965721/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-03-23T08:02:33+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-03-21T18:47:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"3914f71e-de5a-4bb3-b5e0-d42c7ae5b3e3","date":"2024-03-17T08:36:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"f5bf629f-a0c2-4656-a630-5443bd83e7ea","date":"2024-03-11T06:15:09+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-03-11T02:38:27+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-03-08T05:10:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-02-27T06:51:53+00:00","index":"","fulltext":""},{"type":"submitted","content":"World Journal of Surgical Oncology","date":"2024-02-18T03:13:12+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"world-journal-of-surgical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjso","sideBox":"Learn more about [World Journal of Surgical Oncology](http://wjso.biomedcentral.com)","snPcode":"12957","submissionUrl":"https://submission.nature.com/new-submission/12957/3","title":"World Journal of Surgical Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"af87733d-3bf8-4ef9-94d7-c021e581bc78","owner":[],"postedDate":"February 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-05-09T03:58:25+00:00","versionOfRecord":{"articleIdentity":"rs-3965721","link":"https://doi.org/10.1186/s12957-024-03403-8","journal":{"identity":"world-journal-of-surgical-oncology","isVorOnly":false,"title":"World Journal of Surgical Oncology"},"publishedOn":"2024-05-07 03:58:25","publishedOnDateReadable":"May 7th, 2024"},"versionCreatedAt":"2024-02-29 16:01:12","video":"","vorDoi":"10.1186/s12957-024-03403-8","vorDoiUrl":"https://doi.org/10.1186/s12957-024-03403-8","workflowStages":[]},"version":"v1","identity":"rs-3965721","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3965721","identity":"rs-3965721","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}