Laparoscopic Surgery is Associated with Increased Risk of Postoperative Peritoneal Metastases in T4 Colon Cancer: A Propensity Score Analysis

Laparoscopic Surgery is Associated with Increased Risk of Postoperative Peritoneal Metastases in T4 Colon Cancer: A Propensity Score 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 Laparoscopic Surgery is Associated with Increased Risk of Postoperative Peritoneal Metastases in T4 Colon Cancer: A Propensity Score Analysis Shuyuan Li, Ye Wang, Cheng Xin, Shihao Li, Wen Di Jiang, Chen Ming Zhang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5098253/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Jan, 2025 Read the published version in International Journal of Colorectal Disease → Version 1 posted 17 You are reading this latest preprint version Abstract Background This study aims to evaluate the postoperative safety, long-term survival, and postoperative peritoneal metastases (PPM) rate associated with laparoscopic surgery (LS) for T4 colon cancer. Materials and methods After propensity score matching, there were 85 patients in each of the LS and Open surgery groups. The primary outcomes were the 2-year OS, DFS, and PPM rates. Results After matching, 85 patients in each of the groups. The LS group had a higher cumulative 2-year peritoneal metastasis rate (13.9% vs. 3.9%, P = .029), while the 2-year OS (83.0% vs. 84.2%, P = .860) and 2-year DFS (70.9% vs. 74.4%, P = .540) showed no significant difference, compared to the open surgery group. The time to resume diet and the postoperative hospitalization in the LS group were shorter. There were no significant difference harvested lymph nodes, time to remove the drainage and gastric tube, and postoperative complications. The multivariate analysis revealed that LS (HR = 10.783, P = .002), postoperative complications (HR = 17.181, P < .001), and pN stage (N1: HR = 5.786, P = .045; N2: HR = 8.579, P = .027, respectively) were all independent risk factors for PPM. Conclusion For non-metastatic T4 colon cancer, the LS does not affect postoperative safety and long-term survival. Therefore, it should not be considered an contraindication for locally advanced T4 colon cancer. However, it is crucial to fully recognize the potential risk of increased PPM associated with LS. laparoscopic surgery propensity score matching non-metastatic pT4 colon cancer Figures Figure 1 Figure 2 Introduction Colorectal cancer is among the most common cancers globally[ 1 ], with about 10–15% of patients diagnosed at stage T4[ 2 , 3 ]. Currently, radical surgery plus postoperative adjuvant chemotherapy is the standard treatment for T4 colon cancer without metastases. In some cases, more extensive multivisceral surgery may be required[ 4 ]. Laparoscopic surgery (LS) offers several advantages, including reduced surgical trauma, improved postoperative recovery, and comparable survival compared to the open surgery[ 5 , 6 ]. Therefore, an increasing number of surgeons tend to choose LS when dealing with T4 colon cancer[ 7 ]. T4 stage colon cancer has completely invaded the bowel wall, even after radical surgery, approximately 20–40% of patients experience metastasis or recurrence[ 8 – 10 ]. Meta-analyses have shown a positive association between T4 and metachronous peritoneal metastases[ 11 ]. Once peritoneal metastases occur postoperatively, symptoms such as bowel obstruction and ascites often develop, rapidly leading to death[ 12 – 15 ]. Some clinical studies suggest that LS for stage T4 colon cancer may increase the risk of postoperative peritoneal metastases (PPM)[ 16 , 17 ]. Especially at the port site[ 18 , 19 ]. However, this potential risk has not been thoroughly evaluated and remains controversial[ 20 ]. This study aims to evaluate the postoperative safety, long-term survival, and postoperative peritoneal metastases (PPM) rate associated with LS for non-metastatic T4 colon cancer. Materials and methods Patient selection Between January 2015 and December 2021, we collected clinical and pathological data from patients with non-metastatic pT4 stage colon cancer who underwent surgery at the Department of Anorectal Surgery, First Affiliated Hospital of the Naval Military Medical University. The data were collected from electronic medical records. Inclusion criteria were as follows: (1) age ≥ 18 years; (2) postoperative pathological examination indicating T4 stage colon adenocarcinoma (including cecum and rectosigmoid junction); (3) preoperative examination revealed no metastasis to distant organs; (4) surgical approach was either laparoscopic or open; (5) complete data were available. Exclusion criteria were as follows: (1) patients with other malignant tumors; (2) distant organ metastases discovered during surgery; (3) hereditary cancer (e.g. familial adenomatous polyposis); (4) combination of other serious diseases requiring palliative treatment; (5) emergency surgery (e.g. acute obstruction, perforation); and (6) recurrent or multiple primary colon cancers. This work has been reported according to the STROCSS criteria[ 21 ]. Assessment parameters Demographic variables including age, gender, American Society of Anesthesiologists (ASA) grade, BMI, preoperative CEA and CA199 levels, tumor location, preoperative neoadjuvant chemotherapy, and adjuvant postoperative chemotherapy were collected. Additionally, we assessed intraoperative and postoperative data, including operative time, complications (using the Clavien–Dindo classification), surgical approach, estimated blood loss, removal of the drainage tube, time to resume diet, removal of the gastric tube, and length of postoperative hospital stay. Histopathological data were also extracted, including tumor maximum diameter, pT stage, pN stage, harvested lymph nodes, surgical surgery margin, tumor differentiation, lymphovascular invasion, nerve invasion, and KRAS/NRAS/BRAF status. Outcome measurement and follow-up The main outcomes of the study were the 2-year OS rate, DFS rate, and incidence of PPM. PPM were defined as the presence of any tumor lesion at the peritoneal level after surgery, whether radiologically suspected or pathologically confirmed[ 22 ]. The follow-up protocol included clinical examinations, tumor marker evaluations, colonoscopy, CT of the chest and abdomen. Survival data were collected through chart reviews and telephone follow-ups. The last date of follow-up was December 31, 2023. Statistical analysis For continuous variables, the Mann-Whitney U test or Student's t-test was used. Categorical variables were compared using Fisher’s exact test. Due to the imbalance of patient characteristics between the two groups, propensity score matching (PSM) was performed. The surgical approach was set as the dependent variable. Patients were then matched with the nearest neighbor method. Covariates included age, gender, ASA grade, BMI, preoperative CEA, preoperative CA199, pT stage, pN stage, tumor maximum diameter, and surgical surgery margin[ 23 ]. Survival analyses were conducted with Kaplan–Meier analysis. Significant variables in the univariate analysis were further evaluated using multivariate Cox regression analysis. A P-value of less than 0.05 was considered significant. All of the statistical analyses were performed using R (version 4.3.2). Result Baseline characteristics A total of 292 patients were enrolled, including 97 patients in the LS group and 195 patients in the open group (Fig. 1). Before matching, the LS group had a higher proportion of obesity and overweight patients ( P = .033) and a smaller tumor maximum diameter compared to the open group ( P = .024). After matching, each group consisted of 85 patients. No significant differences were found in the baseline characteristics or histopathological outcomes between the two groups. (Tables 1 and 2). Intraoperative and postoperative outcomes The LS group had a significantly longer operation time (198 ± 80.7 min vs. 165 ± 61.9 min, P = .004) but less estimated blood loss ( P = .008). Additionally, patients in the LS group resumed their diet more quickly (3.54 ± 1.21 days vs. 4.18 ± 1.90 days, P = .012) and had shorter postoperative hospital stays (7.31 ± 3.50 days vs. 8.01 ± 3.75 days, P = .012). In contrast, there was no significant difference in number of harvested lymph nodes, time to remove the drainage and gastric tube, and postoperative complications between the two groups (Table 3). Long-term outcomes The 2-year cumulative peritoneal metastasis rate in the LS group was 13.9%, which was significantly higher ( P = .029). However, no statistically significant difference was observed in the 2-year OS rate (83.0% vs. 84.2%, P = .860) or DFS rate (70.9% vs. 74.4%, P = .540) between the two groups (Fig. 2). The results of the multivariate Cox analysis revealed that LS (HR = 10.783, 95% CI = 2.326–49.978, P = .002), pN stage (N1: HR = 5.786, 95% CI = 1.037–32.283, P = .045; N2: HR = 8.579, 95% CI = 1.277–57.625, P = .027, respectively), and postoperative complications (HR = 17.181, 95% CI = 3.973–74.297, P < .001) were all independent risk factors for PPM. Furthermore, although it did not reach statistical significance in the multivariate analysis, lymphovascular invasion was identified as a potential risk factor for PPM in the univariate analysis (Table 4). Discussion LS has been favored by a growing number of surgeons due to its faster recovery, shorter hospital stays, and long-term outcomes comparable to those of open surgery[ 20 , 24 , 25 ]. However, studies have suggested that LS may be associated with the increased risk of peritoneal metastasis[ 17 , 26 ]. These studies were all retrospective and exhibited an imbalance in baseline characteristics. Currently, there are no randomized controlled trials addressing this issue[ 15 ]. Moreover, clinical trials for metastatic colon cancer have systematically excluded patients with peritoneal metastases, potentially due to challenges in imaging and assessment[ 27 , 28 ]. Since larger tumors and local tissue invasion can significantly increase surgical difficulty, the decision between open or LS is made by the surgeon based on the individual characteristics of each patient. Consequently, in our study, the tumor diameter was smaller and the proportion of overweight and obese patients was higher in the LS group. In contrast to some previous studies addressing this issue [ 17 , 26 , 29 ], we used PSM to balance baseline characteristics and minimize bias. Through multivariate analysis, we found that the LS was a risk factor for PPM. The use of cold, dry carbon dioxide for pneumoperitoneum during LS may damage peritoneal mesothelial cells[ 30 – 32 ], leading to the release of proinflammatory and proangiogenic mediators, including COX-2 and VEGF-A. This process could build a microenvironment conducive to tumor cell proliferation, enhance the adhesion of disseminated cells, and ultimately increase the risk of metastasis[ 33 , 34 ]. Although laparoscopy offers a magnified view, it may result in the omission of small peritoneal metastases hidden behind organs or situated in blind spots of the camera's field of vision[ 35 ]. In contrast, during open surgery, the surgeon can palpate and explore areas beyond visual reach, potentially detecting peritoneal metastases that might otherwise go unnoticed[ 36 ]. Additionally, since the intraoperative lavage area is more restricted in LS, there may be a higher chance of residual free cancer cells remaining in the abdominal cavity postoperatively, which also increases the risk of PPM[ 37 , 38 ]. Notably, we found pN stage and postoperative complications to be independent risk factors for PPM, which is consistent with previous studies[ 39 , 40 ]. Since postoperative complications may trigger an inflammatory response[ 41 , 42 ], the inflammation may promote tumor metastasis and recurrence through mechanisms such as damage to the intestinal vascular barrier[ 43 ]. When locally advanced tumors require multivisceral surgery, LS presents a significantly greater challenge[ 44 , 45 ]. In this study, 5 patients were converted to open surgery. The reasons were as follows: in 2 cases, tumor invasion into adjacent organs made LS difficult; in 2 cases, severe intra-abdominal adhesions obstructed the view; and in 1 case, the tumor was too large to be safely resected. Conversion of laparoscopic colon cancer surgery introduces additional trauma and increased costs, and it may also elevate the risk of long-term recurrence and metastasis[ 46 ]. Before selecting LS for T4 colon cancer surgery, surgeons must thoroughly assess the surgical difficulty using imaging and colonoscopy findings to minimize the risk of conversion. Our study has some limitations. Despite performing PSM to balance baseline characteristics, the retrospective, single-center design limits the generalizability of the results. A larger cohort could enhance the statistical power of our findings. Conclusions Compared to open surgery, LS offers faster postoperative recovery and comparable long-term survival outcomes. Therefore, it should not be considered an contraindication for T4 colon cancer. However, it is crucial to fully recognize the potential risk of increased PPM associated with LS and to prioritize early detection of peritoneal metastasis to facilitate further treatment. Multi-center prospective studies are necessary to provide insights into treatment effects across different patient populations, aiding in the determination of which subgroups might benefit from this. Declarations Ethical approval The study was approved by the Ethics Committee of the First Affiliated Hospital of the Naval Military Medical University (Ethics Approval No. CHEC2023-067). 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Surg. Oncol. 47 (2021) 2405–2413. https://doi.org/10.1016/j.ejso.2021.05.009. M. Enblad, W. Graf, H. Birgisson, Risk factors for appendiceal and colorectal peritoneal metastases, Eur. J. Surg. Oncol. J. Eur. Soc. Surg. Oncol. Br. Assoc. Surg. Oncol. 44 (2018) 997–1005. https://doi.org/10.1016/j.ejso.2018.02.245. J.A. Krall, F. Reinhardt, O.A. Mercury, D.R. Pattabiraman, M.W. Brooks, M. Dougan, A.W. Lambert, B. Bierie, H.L. Ploegh, S.K. Dougan, R.A. Weinberg, The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy, Sci. Transl. Med. 10 (2018) eaan3464. https://doi.org/10.1126/scitranslmed.aan3464. H. Dillekås, R. Demicheli, I. Ardoino, S.A.H. Jensen, E. Biganzoli, O. Straume, The recurrence pattern following delayed breast reconstruction after mastectomy for breast cancer suggests a systemic effect of surgery on occult dormant micrometastases, Breast Cancer Res. Treat. 158 (2016) 169–178. https://doi.org/10.1007/s10549-016-3857-1. A. Bertocchi, S. Carloni, P.S. Ravenda, G. Bertalot, I. Spadoni, A. Lo Cascio, S. Gandini, M. Lizier, D. Braga, F. Asnicar, N. Segata, C. Klaver, P. Brescia, E. Rossi, A. Anselmo, S. Guglietta, A. Maroli, P. Spaggiari, N. Tarazona, A. Cervantes, S. Marsoni, L. Lazzari, M.G. Jodice, C. Luise, M. Erreni, S. Pece, P.P. Di Fiore, G. Viale, A. Spinelli, C. Pozzi, G. Penna, M. Rescigno, Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver, Cancer Cell 39 (2021) 708-724.e11. https://doi.org/10.1016/j.ccell.2021.03.004. S. Zaman, P. Bhattacharya, A.Y.Y. Mohamedahmed, F.Y. Cheung, K. Rakhimova, S. Di Saverio, R. Peravali, A. Akingboye, Outcomes following open versus laparoscopic multi-visceral resection for locally advanced colorectal cancer: A systematic review and meta-analysis, Langenbecks Arch. Surg. 408 (2023) 98. https://doi.org/10.1007/s00423-023-02835-2. Y. Ishiyama, Y. Tachimori, T. Harada, I. Mochizuki, Y. Tomizawa, S. Ito, M. Oneyama, M. Amiki, Y. Hara, K. Narita, M. Goto, K. Sekikawa, Y. Hirano, Oncologic outcomes after laparoscopic versus open multivisceral resection for local advanced colorectal cancer: A meta-analysis, Asian J. Surg. 46 (2023) 6–12. https://doi.org/10.1016/j.asjsur.2022.02.047. H. Ptok, R. Kube, U. Schmidt, F. Köckerling, I. Gastinger, H. Lippert, “Colon/Rectum Carcinoma (Primary Tumor)” Study Group, Conversion from laparoscopic to open colonic cancer resection - associated factors and their influence on long-term oncological outcome, Eur. J. Surg. Oncol. J. Eur. Soc. Surg. Oncol. Br. Assoc. Surg. Oncol. 35 (2009) 1273–1279. https://doi.org/10.1016/j.ejso.2009.06.006. Tables Tables are available in the Supplementary Files section. Additional Declarations No competing interests reported. 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Lou","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIiWNgGAWjYDACCQY2IGnBwMDe2PjwAwlaJBgYeA43G0uQpkUivU2Ahxgd8rObnz3mbZOwN7j5sA2o005Ot4GAFoM7x8yNgVoSN9xObHtQwJBsbHaAkBaJHDZpoJYEg9uJ7QYSDAcStxHSIj8DogXosINtEjzEaGG4AdHCuOEGI5FaDG6kmUnOOSeROPNMIjCQDYjwi/yM5GcSb8ps7PmOH3/48EOFnRxBLSDAxAuMGgWwSgMilIMA448/QOsaiFQ9CkbBKBgFIw8AAP1HQO4iVoWwAAAAAElFTkSuQmCC","orcid":"","institution":"Changhai Hospital","correspondingAuthor":true,"prefix":"","firstName":"Zheng","middleName":"","lastName":"Lou","suffix":""}],"badges":[],"createdAt":"2024-09-16 14:57:56","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5098253/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5098253/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00384-024-04773-x","type":"published","date":"2025-01-02T15:57:45+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":68001583,"identity":"d59185fb-4822-405c-b17e-7716c6b67c20","added_by":"auto","created_at":"2024-11-01 08:05:24","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":207585,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5098253/v1/df5aaa99a4bb4a5477d41ecf.png"},{"id":68000933,"identity":"ce1b373d-5c41-4281-b102-8c724f11b9f5","added_by":"auto","created_at":"2024-11-01 07:57:24","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":346036,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5098253/v1/9885de1d4a5bfb81c34354da.png"},{"id":73093437,"identity":"e4bbde46-09de-40db-a837-8a0efa4868cb","added_by":"auto","created_at":"2025-01-06 16:18:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":822491,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5098253/v1/0224d527-b82c-4c85-865e-ac1d6bc55f2b.pdf"},{"id":68000931,"identity":"97625e92-dadd-4f36-bfec-6f51936e52e5","added_by":"auto","created_at":"2024-11-01 07:57:24","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1491133,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-5098253/v1/f2019d705ab1a78195d6ea77.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Laparoscopic Surgery is Associated with Increased Risk of Postoperative Peritoneal Metastases in T4 Colon Cancer: A Propensity Score Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eColorectal cancer is among the most common cancers globally[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], with about 10\u0026ndash;15% of patients diagnosed at stage T4[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Currently, radical surgery plus postoperative adjuvant chemotherapy is the standard treatment for T4 colon cancer without metastases. In some cases, more extensive multivisceral surgery may be required[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Laparoscopic surgery (LS) offers several advantages, including reduced surgical trauma, improved postoperative recovery, and comparable survival compared to the open surgery[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Therefore, an increasing number of surgeons tend to choose LS when dealing with T4 colon cancer[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eT4 stage colon cancer has completely invaded the bowel wall, even after radical surgery, approximately 20\u0026ndash;40% of patients experience metastasis or recurrence[\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Meta-analyses have shown a positive association between T4 and metachronous peritoneal metastases[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Once peritoneal metastases occur postoperatively, symptoms such as bowel obstruction and ascites often develop, rapidly leading to death[\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Some clinical studies suggest that LS for stage T4 colon cancer may increase the risk of postoperative peritoneal metastases (PPM)[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Especially at the port site[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, this potential risk has not been thoroughly evaluated and remains controversial[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study aims to evaluate the postoperative safety, long-term survival, and postoperative peritoneal metastases (PPM) rate associated with LS for non-metastatic T4 colon cancer.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient selection\u003c/h2\u003e \u003cp\u003eBetween January 2015 and December 2021, we collected clinical and pathological data from patients with non-metastatic pT4 stage colon cancer who underwent surgery at the Department of Anorectal Surgery, First Affiliated Hospital of the Naval Military Medical University. The data were collected from electronic medical records.\u003c/p\u003e \u003cp\u003eInclusion criteria were as follows: (1) age\u0026thinsp;\u0026ge;\u0026thinsp;18 years; (2) postoperative pathological examination indicating T4 stage colon adenocarcinoma (including cecum and rectosigmoid junction); (3) preoperative examination revealed no metastasis to distant organs; (4) surgical approach was either laparoscopic or open; (5) complete data were available.\u003c/p\u003e \u003cp\u003eExclusion criteria were as follows: (1) patients with other malignant tumors; (2) distant organ metastases discovered during surgery; (3) hereditary cancer (e.g. familial adenomatous polyposis); (4) combination of other serious diseases requiring palliative treatment; (5) emergency surgery (e.g. acute obstruction, perforation); and (6) recurrent or multiple primary colon cancers.\u003c/p\u003e \u003cp\u003eThis work has been reported according to the STROCSS criteria[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eAssessment parameters\u003c/h2\u003e \u003cp\u003eDemographic variables including age, gender, American Society of Anesthesiologists (ASA) grade, BMI, preoperative CEA and CA199 levels, tumor location, preoperative neoadjuvant chemotherapy, and adjuvant postoperative chemotherapy were collected. Additionally, we assessed intraoperative and postoperative data, including operative time, complications (using the Clavien\u0026ndash;Dindo classification), surgical approach, estimated blood loss, removal of the drainage tube, time to resume diet, removal of the gastric tube, and length of postoperative hospital stay. Histopathological data were also extracted, including tumor maximum diameter, pT stage, pN stage, harvested lymph nodes, surgical surgery margin, tumor differentiation, lymphovascular invasion, nerve invasion, and KRAS/NRAS/BRAF status.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eOutcome measurement and follow-up\u003c/h2\u003e \u003cp\u003eThe main outcomes of the study were the 2-year OS rate, DFS rate, and incidence of PPM. PPM were defined as the presence of any tumor lesion at the peritoneal level after surgery, whether radiologically suspected or pathologically confirmed[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe follow-up protocol included clinical examinations, tumor marker evaluations, colonoscopy, CT of the chest and abdomen. Survival data were collected through chart reviews and telephone follow-ups. The last date of follow-up was December 31, 2023.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eFor continuous variables, the Mann-Whitney U test or Student's t-test was used. Categorical variables were compared using Fisher\u0026rsquo;s exact test. Due to the imbalance of patient characteristics between the two groups, propensity score matching (PSM) was performed. The surgical approach was set as the dependent variable. Patients were then matched with the nearest neighbor method. Covariates included age, gender, ASA grade, BMI, preoperative CEA, preoperative CA199, pT stage, pN stage, tumor maximum diameter, and surgical surgery margin[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Survival analyses were conducted with Kaplan\u0026ndash;Meier analysis. Significant variables in the univariate analysis were further evaluated using multivariate Cox regression analysis. A P-value of less than 0.05 was considered significant. All of the statistical analyses were performed using R (version 4.3.2).\u003c/p\u003e \u003c/div\u003e"},{"header":"Result","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eBaseline characteristics\u003c/h2\u003e \u003cp\u003eA total of 292 patients were enrolled, including 97 patients in the LS group and 195 patients in the open group (Fig.\u0026nbsp;1). Before matching, the LS group had a higher proportion of obesity and overweight patients (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.033) and a smaller tumor maximum diameter compared to the open group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.024).\u003c/p\u003e \u003cp\u003eAfter matching, each group consisted of 85 patients. No significant differences were found in the baseline characteristics or histopathological outcomes between the two groups. (Tables\u0026nbsp;1 and 2).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eIntraoperative and postoperative outcomes\u003c/h2\u003e \u003cp\u003eThe LS group had a significantly longer operation time (198\u0026thinsp;\u0026plusmn;\u0026thinsp;80.7 min vs. 165\u0026thinsp;\u0026plusmn;\u0026thinsp;61.9 min, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.004) but less estimated blood loss (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.008). Additionally, patients in the LS group resumed their diet more quickly (3.54\u0026thinsp;\u0026plusmn;\u0026thinsp;1.21 days vs. 4.18\u0026thinsp;\u0026plusmn;\u0026thinsp;1.90 days, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.012) and had shorter postoperative hospital stays (7.31\u0026thinsp;\u0026plusmn;\u0026thinsp;3.50 days vs. 8.01\u0026thinsp;\u0026plusmn;\u0026thinsp;3.75 days, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.012). In contrast, there was no significant difference in number of harvested lymph nodes, time to remove the drainage and gastric tube, and postoperative complications between the two groups (Table\u0026nbsp;3).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eLong-term outcomes\u003c/h2\u003e \u003cp\u003eThe 2-year cumulative peritoneal metastasis rate in the LS group was 13.9%, which was significantly higher (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.029). However, no statistically significant difference was observed in the 2-year OS rate (83.0% vs. 84.2%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.860) or DFS rate (70.9% vs. 74.4%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.540) between the two groups (Fig.\u0026nbsp;2).\u003c/p\u003e \u003cp\u003eThe results of the multivariate Cox analysis revealed that LS (HR\u0026thinsp;=\u0026thinsp;10.783, 95% CI\u0026thinsp;=\u0026thinsp;2.326\u0026ndash;49.978, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.002), pN stage (N1: HR\u0026thinsp;=\u0026thinsp;5.786, 95% CI\u0026thinsp;=\u0026thinsp;1.037\u0026ndash;32.283, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.045; N2: HR\u0026thinsp;=\u0026thinsp;8.579, 95% CI\u0026thinsp;=\u0026thinsp;1.277\u0026ndash;57.625, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.027, respectively), and postoperative complications (HR\u0026thinsp;=\u0026thinsp;17.181, 95% CI\u0026thinsp;=\u0026thinsp;3.973\u0026ndash;74.297, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.001) were all independent risk factors for PPM. Furthermore, although it did not reach statistical significance in the multivariate analysis, lymphovascular invasion was identified as a potential risk factor for PPM in the univariate analysis (Table\u0026nbsp;4).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eLS has been favored by a growing number of surgeons due to its faster recovery, shorter hospital stays, and long-term outcomes comparable to those of open surgery[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. However, studies have suggested that LS may be associated with the increased risk of peritoneal metastasis[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. These studies were all retrospective and exhibited an imbalance in baseline characteristics. Currently, there are no randomized controlled trials addressing this issue[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Moreover, clinical trials for metastatic colon cancer have systematically excluded patients with peritoneal metastases, potentially due to challenges in imaging and assessment[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSince larger tumors and local tissue invasion can significantly increase surgical difficulty, the decision between open or LS is made by the surgeon based on the individual characteristics of each patient. Consequently, in our study, the tumor diameter was smaller and the proportion of overweight and obese patients was higher in the LS group. In contrast to some previous studies addressing this issue [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], we used PSM to balance baseline characteristics and minimize bias.\u003c/p\u003e \u003cp\u003eThrough multivariate analysis, we found that the LS was a risk factor for PPM. The use of cold, dry carbon dioxide for pneumoperitoneum during LS may damage peritoneal mesothelial cells[\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], leading to the release of proinflammatory and proangiogenic mediators, including COX-2 and VEGF-A. This process could build a microenvironment conducive to tumor cell proliferation, enhance the adhesion of disseminated cells, and ultimately increase the risk of metastasis[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Although laparoscopy offers a magnified view, it may result in the omission of small peritoneal metastases hidden behind organs or situated in blind spots of the camera's field of vision[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. In contrast, during open surgery, the surgeon can palpate and explore areas beyond visual reach, potentially detecting peritoneal metastases that might otherwise go unnoticed[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Additionally, since the intraoperative lavage area is more restricted in LS, there may be a higher chance of residual free cancer cells remaining in the abdominal cavity postoperatively, which also increases the risk of PPM[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNotably, we found pN stage and postoperative complications to be independent risk factors for PPM, which is consistent with previous studies[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Since postoperative complications may trigger an inflammatory response[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e], the inflammation may promote tumor metastasis and recurrence through mechanisms such as damage to the intestinal vascular barrier[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhen locally advanced tumors require multivisceral surgery, LS presents a significantly greater challenge[\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. In this study, 5 patients were converted to open surgery. The reasons were as follows: in 2 cases, tumor invasion into adjacent organs made LS difficult; in 2 cases, severe intra-abdominal adhesions obstructed the view; and in 1 case, the tumor was too large to be safely resected. Conversion of laparoscopic colon cancer surgery introduces additional trauma and increased costs, and it may also elevate the risk of long-term recurrence and metastasis[\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. Before selecting LS for T4 colon cancer surgery, surgeons must thoroughly assess the surgical difficulty using imaging and colonoscopy findings to minimize the risk of conversion.\u003c/p\u003e \u003cp\u003eOur study has some limitations. Despite performing PSM to balance baseline characteristics, the retrospective, single-center design limits the generalizability of the results. A larger cohort could enhance the statistical power of our findings.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eCompared to open surgery, LS offers faster postoperative recovery and comparable long-term survival outcomes. Therefore, it should not be considered an contraindication for T4 colon cancer. However, it is crucial to fully recognize the potential risk of increased PPM associated with LS and to prioritize early detection of peritoneal metastasis to facilitate further treatment. Multi-center prospective studies are necessary to provide insights into treatment effects across different patient populations, aiding in the determination of which subgroups might benefit from this.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval \u003c/strong\u003e \u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of the First Affiliated Hospital of the Naval Military Medical University (Ethics Approval No. CHEC2023-067).\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eSource of funding \u003c/strong\u003e \u003c/p\u003e\n\u003cp\u003eThis work was supported by Science and Technology Innovation Plan Of Shanghai Science and Technology Commission (No.23DZ2202000)\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eConflicts of interest disclosure \u003c/strong\u003e \u003c/p\u003e\n\u003cp\u003eThe authors have no competing interests for this manuscript.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAcknowledgements \u003c/strong\u003e \u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGBD 2016 Disease and Injury Incidence and Prevalence Collaborators, Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016, Lancet Lond. 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Surg. Oncol. J. Eur. Soc. Surg. Oncol. Br. Assoc. Surg. Oncol. 35 (2009) 1273\u0026ndash;1279. https://doi.org/10.1016/j.ejso.2009.06.006.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 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":"international-journal-of-colorectal-disease","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijcd","sideBox":"Learn more about [International Journal of Colorectal Disease](http://link.springer.com/journal/384)","snPcode":"384","submissionUrl":"https://submission.nature.com/new-submission/384/3","title":"International Journal of Colorectal Disease","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"laparoscopic surgery, propensity score matching, non-metastatic pT4 colon cancer","lastPublishedDoi":"10.21203/rs.3.rs-5098253/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5098253/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThis study aims to evaluate the postoperative safety, long-term survival, and postoperative peritoneal metastases (PPM) rate associated with laparoscopic surgery (LS) for T4 colon cancer.\u003c/p\u003e\u003ch2\u003eMaterials and methods\u003c/h2\u003e \u003cp\u003eAfter propensity score matching, there were 85 patients in each of the LS and Open surgery groups. The primary outcomes were the 2-year OS, DFS, and PPM rates.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAfter matching, 85 patients in each of the groups. The LS group had a higher cumulative 2-year peritoneal metastasis rate (13.9% vs. 3.9%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.029), while the 2-year OS (83.0% vs. 84.2%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.860) and 2-year DFS (70.9% vs. 74.4%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.540) showed no significant difference, compared to the open surgery group. The time to resume diet and the postoperative hospitalization in the LS group were shorter. There were no significant difference harvested lymph nodes, time to remove the drainage and gastric tube, and postoperative complications. The multivariate analysis revealed that LS (HR\u0026thinsp;=\u0026thinsp;10.783, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.002), postoperative complications (HR\u0026thinsp;=\u0026thinsp;17.181, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.001), and pN stage (N1: HR\u0026thinsp;=\u0026thinsp;5.786, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.045; N2: HR\u0026thinsp;=\u0026thinsp;8.579, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.027, respectively) were all independent risk factors for PPM.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eFor non-metastatic T4 colon cancer, the LS does not affect postoperative safety and long-term survival. Therefore, it should not be considered an contraindication for locally advanced T4 colon cancer. However, it is crucial to fully recognize the potential risk of increased PPM associated with LS.\u003c/p\u003e","manuscriptTitle":"Laparoscopic Surgery is Associated with Increased Risk of Postoperative Peritoneal Metastases in T4 Colon Cancer: A Propensity Score Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-01 07:57:19","doi":"10.21203/rs.3.rs-5098253/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-10-16T06:19:01+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-15T23:20:19+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-15T16:33:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"8267147002171766838065978500201674063","date":"2024-10-15T16:06:30+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-15T03:16:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-14T00:39:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"139412035502639156121030914888461620805","date":"2024-10-12T17:32:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"45792969605417027953169820009406831348","date":"2024-10-12T08:59:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"293169436052897131731788445101770631952","date":"2024-10-12T07:37:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"148296743001183235130087435685527388303","date":"2024-10-09T23:07:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"56541548126657691099278908749163087341","date":"2024-10-09T08:22:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"301655215288710627727375006554263742540","date":"2024-10-07T23:59:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"278471866117648869621196628667350340624","date":"2024-10-07T07:33:09+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-10-07T07:25:12+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-09-17T01:07:56+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-09-17T01:07:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Colorectal Disease","date":"2024-09-16T14:56:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-colorectal-disease","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijcd","sideBox":"Learn more about [International Journal of Colorectal Disease](http://link.springer.com/journal/384)","snPcode":"384","submissionUrl":"https://submission.nature.com/new-submission/384/3","title":"International Journal of Colorectal Disease","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"043102be-3b04-4e54-b70a-24c0e5d76f8f","owner":[],"postedDate":"November 1st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-01-06T16:03:19+00:00","versionOfRecord":{"articleIdentity":"rs-5098253","link":"https://doi.org/10.1007/s00384-024-04773-x","journal":{"identity":"international-journal-of-colorectal-disease","isVorOnly":false,"title":"International Journal of Colorectal Disease"},"publishedOn":"2025-01-02 15:57:45","publishedOnDateReadable":"January 2nd, 2025"},"versionCreatedAt":"2024-11-01 07:57:19","video":"","vorDoi":"10.1007/s00384-024-04773-x","vorDoiUrl":"https://doi.org/10.1007/s00384-024-04773-x","workflowStages":[]},"version":"v1","identity":"rs-5098253","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5098253","identity":"rs-5098253","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}