Peritoneal reflection involvement as a prognostic factor in rectal cancer. Long-term oncological outcomes from a prospective study.

Peritoneal reflection involvement as a prognostic factor in rectal cancer. 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Long-term oncological outcomes from a prospective study. Eduardo Alvarez-Sarrado, Matteo Frasson, Jorge Sancho-Muriel, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6297876/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 10 May, 2025 Read the published version in International Journal of Colorectal Disease → Version 1 posted 8 You are reading this latest preprint version Abstract Purpose: To assess the relevance of peritoneal reflection involvement in long-term oncological outcomes in patients with rectal cancer. Methods: prospective observational study from a specialized colorectal unit, that included a consecutive series of patients undergoing mesorectal excision for rectal cancer. PR involvement was evaluated on pathological examination using Shepherd’s classification. Overall survival (OS), disease-free survival (DFS) and local recurrence (LR) were assessed. Results: 160 patients were included in the present analysis. Peritoneal involvement was present in 28.2% of the 85 tumours above or at the level of PR. There were no differences in OS, DFS or LR according to tumour’s height location. The 5-year OS, DFS and LR for tumours involving PR were 58.3%, 61.7% and 30.3%, respectively. Patients with peritoneal involvement had a higher LR rate (p=0.02) and shorter OS (p=0.04). Shepherd’s grade 4 peritoneal involvement was an independent risk factor for OS (HR 2.9; 95% IC 1.1-9.5, p=0.04) and LR (HR 4.2; 95% IC 1.2-16.9, p=0.04). Conclusion: After rectal cancer resection, peritoneal involvement is an independent risk factor for local recurrence and poor survival. rectal cancer peritoneal reflection peritoneal involvement local recurrence carcinomatosis Figures Figure 1 Figure 2 INTRODUCTION Circumferential resection margin (CRM) involvement after surgical resection is widely known to be a risk factor for both local recurrence (LR) and poor survival [ 1 – 5 ]. However, for anterior tumours above the peritoneal reflection (PR), peritoneal involvement should be carefully assessed and independently reported from CRM involvement [ 6 , 7 ]. Moreover, most publications do not take this aspect into account and data concerning CRM involvement for anterior tumours may be misunderstood [ 8 – 10 ]. Previous publications about oncological outcomes in rectal cancer have mainly focused on pathological CRM (pCRM) status as it has been proved to be one of the most important LR-related factors. Patients with pCRM involvement have a 5-year LR rate around 23.7–26.7% [ 10 , 11 ]. However, up to 25% of anterior rectal surface is covered by peritoneum, even if this fact is frequently ignored [ 12 , 13 ]. In upper and middle rectal tumours involving the serosal surface, the concept of CRM is not applicable and they must be classified as pT4a as they are intraperitoneal tumours[ 6 – 7 , 14 ]. Additionally, tumours above or at the level of PR may have peritoneal spread in addition to the classical lymphatic and hematologic patterns of dissemination developed by lower rectal tumours [ 15 ]. High-resolution magnetic resonance imaging (MRI) is the gold standard for rectal cancer local staging as it can determine the depth of invasion, distance to anal margin and predict the involvement of mesorrectal fascia with high accuracy[ 5 , 16 – 21 ]. This information is crucial to select patients for neoadjuvant treatment and to determine the appropriate surgical technique[ 8 , 10 , 22 , 23 ]. Nonetheless, peritoneal involvement is not always detected by preoperative MRI, as shown in our previous publication, reaching an overall accuracy of 80.5–95.9% [ 19 , 24 ]. In 1995, Shepherd established four degrees of peritoneal involvement according to the depth of invasion[ 25 ]. They later demonstrated that serosal invasion is a relevant risk factor for LR and poor OS, however, this association did not reach statistical significance in the multivariate analysis[ 26 ]. Consequently, certain authors have advocated for neoadjuvant systemic chemotherapy protocols in the management of upper rectal tumors with serosal involvement, mirroring most recent strategies employed for locally advanced colon cancer. This recommendation is supported by studies such as the FOXTROT trial, aiming to induce tumor downstaging and mitigate the potential for peritoneal dissemination[ 27 ]. Despite CRM involvement relevance has been widely investigated, very few publications have focused on peritoneal reflection involvement. Recently, several authors have highlighted the importance of MRI accuracy for identification and determination of the level of PR[ 12 , 28 – 31 ]. Nonetheless, the prognostic importance of peritoneal involvement on oncological outcomes remains to be determined. The primary objective of this prospective study is to PR involvement as a relevant factor determining local recurrence (LR), disease-free survival (DFS), and overall survival (OS) after rectal resection for adenocarcinoma. METHODS This is a prospective, observational study conducted by a specialized multidisciplinary colorectal unit at a tertiary hospital. This manuscript has been written following the STROBE guidelines. Ethical statements The study was approved by the institution’s ethics committee and written informed consent was obtained from each patient. Registry number: 2016/0373. Description of participants All patients with histopathologically confirmed rectal adenocarcinoma undergoing surgical resection with total or subtotal mesorrectal excision were enrolled from June 2016 to May 2019. Some of the patients of the present analysis were already included in a previous publication focused on overall MRI accuracy for PR location and involvement [24]. Radiologic assessment High-resolution MRI was performed in a 1.5 tesla MRI scanner (General Electric Medical System, Milwaukee, Wisconsin, USA) with pelvic phased-array coil. MRI protocol details are explained in our previous publication[24]. MRI images were evaluated and discussed at the multidisciplinary board. Peritoneal reflection involvement was defined as direct contact or nodular extension of the tumour into peritoneal surface. CRM involvement was defined as direct contact or tumour within 1 millimeter (mm) to mesorectal fascia. Pathological assessment A double-ink technique was applied, indian ink on mesorrectal extraperitoneal surface and orange ink for the peritoneal surface. Detailed pathological protocol and dying technique are explained in our previous paper[24]. Tumours located within 5 mm of the peritoneal reflection were considered at the level of PR for the purpose of analysis. Peritoneal involvement was assessed according to Shepherd’s classification into 4 degrees, as shown in Table 1 [25]. Grades 1-2 were considered free of serosal involvement and grades 3-4 as involved serosa. Figure 1 shows microscopy photographies of pathological findings according to Shepherd’s peritoneal involvement degrees. CRM involvement was defined as a tumour within 1 mm to mesorectal fascia. Both pathological data, PR and pCRM involvement, were considered for survival analysis. Follow-up and oncological outcomes Recommendations for neoadjuvant treatment were discussed by the multidisciplinary board for all patients. Preoperative chemoradiotherapy was considered for cT3 and cT4 low and middle rectal cancer with high-risk factors such as involved mesorectal fascia. None of the patients received a total neoadjuvant regime during the period study. Oxaliplatin-based adjuvant regimes were given to selected patients after surgery. None of the patients received postoperative radiotherapy. Patients were followed by serial clinical examination and carcinoembryonic antigen assessment every 3 months during the first year, every 6 months during the second year, and annually thereafter. Thoracoabdominal computed tomography scanning was performed every 6 months for the first 2 years and annually thereafter for 5 years. Colonoscopy was performed after 1 year and 3 to 5 years thereafter, depending on individual patient risk. If recurrence was suspected, then further diagnostic methods were used as required. OS was defined as the time from surgery to death for any cause. DFS was defined as the time from surgery to date of local recurrence or distant metastases diagnosis. LR was defined as the presence of tumour at anastomosis, pelvic mass, peritoneal carcinomatosis, or locoregional lymphatic recurrence. Local recurrence-free survival (LRFS) was defined as the time from surgery to date of LR. Statistical analysis SPSS software (IBM SPSS Statistics for Macintosh, version 24.0, IBM Corp, Armonk, NY) was used for statistical analysis. Categorical variables were compared among groups using χ2 and Fisher exact tests. Continuous variables were compared by ANOVA or Kruskal-Wallis test. All time-to-event variables were calculated from the date of surgery. The univariate influence of prognostic factors on LR, DFS and OS was analyzed for all of the groups with the Kaplan-Meier method and the log-rank (Mantel-Cox) test. A Cox multivariate regression model was constructed including variables with p<0.10 at univariate analysis. Proportional hazards assumption of the Cox model was assessed. Statistical significance for all the results was defined as p<0.05. RESULTS Patient’s baseline A total of 160 patients were enrolled in the study. The median age was 65 years (interquartile range (IQR): 57-73 years) and 56.3% were males. 27.5% of tumours were located in the upper third (11-15cm from anal verge), 39.4% in the middle third (7-10cm) and 33.1% in the lower rectum (0-6cm). Sixty-four patients (40%) received neoadjuvant chemoradiotherapy. After surgical resection, good quality mesorectal excision plane was achieved in 126 (78.8%) specimens. CRM was involved in 11 cases (6.9%). When extended resections for locally advanced pT4b-tumours are excluded, CRM was involved in 6/146 (4.1%). After pathological examination, 22 (13.8%) tumours were located above the PR, 63 (39.4%) at the level of PR and 75 (46.9%) below the PR. For tumours located at or above the PR (n=85), peritoneal involvement was confirmed in 24 out of 85 (28.2%) patients, with 14 classified as grade 3 and 10 as grade 4 according to Shepherd’s classification. Demographic, preoperative and pathological data for the whole group are shown in table 2. Oncological outcomes The median follow-up time was 67 months. 5-year OS, 5-year DFS and 5-year LRFS were 75% (95% CI, 68.3-81.6), 72.1% (95% CI, 65-79.1) and 84.4% (95% CI, 78.5-90.2), respectively. Isolated LR occurred in 5 patients (3.1%) whereas 18 (11.2%) patients had both LR and distant metastasis, and 21 patients (13.1%) developed distant metastasis only. The median time to LR after surgery was 24 months (IQR: 12-39). Patterns of local recurrence included carcinomatosis in 11 patients, pelvic mass and carcinomatosis in 2 patients and pelvic recurrence alone in 9 patients. Three patients showed locoregional lymph node involvement, one as the sole LR site. In our series, pT4 tumours represent 21.9% of cases, with LR occurring in 28.6% of these cases: 9 patients as carcinomatosis, while 1 patient developed pelvic recurrence. 4 patients underwent pelvic exenteration after local recurrence. The median OS after LR diagnosis was 14 months (IQR: 4-22 months). The median time to diagnosis of distant metastasis after surgery was 15 months (IQR: 6-22). Metastasis patterns were observed as follows: 7 cases presented with hepatic metastases only, 13 cases hepatic and pulmonary metastases, 13 cases pulmonary metastasis only and 6 cases showed multiple-organ metastases. The median OS following metastatic progression was 22 months (IQR: 8-47). - Location of the tumour in relation with the peritoneal reflection. According to tumour’s location no statistical difference was found in 5-y OS (90% vs. 77.3% vs. 79.5%, p=0.603), 5-y DFS (76.2% vs. 62.1% vs. 72.6%, p=0.58) and LRFS (90.5% vs. 81% vs 84.1%, p=0.639) for tumours above, at or below the PR, respectively. - Involvement of peritoneal reflection Table 3 shows the baseline characteristics in patients with or without peritoneal involvement. More frequently, patients with peritoneal involvement required an extended resection and had more advanced tumours at pathological staging with higher proportion of lympho-vascular invasion, pT4 stages and lymph nodes involvement. For patients with peritoneal involvement, 5-y OS (58.3% vs. 73.8%, p=0.043) and 5-y LRFS (69.7% vs. 87.1%, p=0.02) were significantly shorter. Patients with Shepherd’s grade 4 peritoneal involvement compared to the rest of the patients had the worse long-term outcomes with 5-y OS (50% vs. 76.7%, p=0.05), 5-y DFS (50% vs. 73.7%, p=0.027) and 5-y LRFS (50% vs. 86.8%, p<0.001). Kaplan-Meier curves for OS, DFS and LRFS are shown in figure 2. - Risk factor for OS, DFS and LR On multivariate Cox regression analysis, Shepherd’s grade 4 peritoneal involvement was confirmed as independent prognostic factor for higher LR (HR 4.2, 95% CI 1.2-16.9) and worse OS (HR 2.9, 95% CI 1.1-9.5). Table 4 summarizes the results of univariate and multivariate analysis for OS, DFS and LRFS. DISCUSSION This study assesses the prognostic relevance of peritoneal involvement at PR in rectal cancer and evidences that is a strong predictor of LR, with an adjusted-HR 4.2 (95% CI 1.2-16.9) for grade 4 Shepherd’s involvement. Peritoneal involvement at that location was present in 24 out of 85 (28.2%) tumours above or at the level of PR and 29.1% (7/24) of these patients developed LR, all presenting with carcinomatosis. Notably, while serosal ulceration with tumour cells free in the peritoneum (grade-4 involvement) was found in only 6.25% of all patients, this subgroup developed LR in 50% of cases. This data is in concordance with previous publications by Shepherd and colleagues and highlights the importance of the peritoneal involvement in the oncological outcomes[25,26]. Anterior rectal tumours at the level of peritoneal reflection can, potentially, reach the peritoneal surface or/and the anterior mesorrectal fascia as the mesorrectal fat becomes very thin at this level[12,30,32]. In this regard, The European Society of Gastrointestinal and Abdominal Radiology (ESGAR) recommends to describe the relationship of rectal tumours with the anterior peritoneal reflection, as tumour’s invasion above the level of PR at the anterior side should be considered at risk for peritoneal involvement rather than anterior CRM involvement[17,33]. However, although MRI has demonstrated a high accuracy for determination of tumour’s location according to PR, preoperative evaluation of PR involvement can be challenging[24], and may not have been adequately considered in the analysis of the prognostic implications of the circumferential location of distal cancer [2]. Estimated rectal cancer carcinomatosis rate is 3-4.2% but pT4 tumours present up to 10 times higher risk of carcinomatosis[11,13,36,37]. Patients with rectal cancer and resected local carcinomatosis at the primary surgery present worse median OS (48 vs. 97 months, p<0.001) and a 5-year LR of 15.7%[36]. In our series, pT4 tumours accounted for 21.9% of cases, with LR developing in 28.6% of these cases: 9 patients as carcinomatosis, while 1 patient developed pelvic recurrence. To date, guidelines recommend upfront surgery for rectal tumour above the PR but peritoneal involvement is not taken into account[22]. Marinello et al reviewed 1145 patients comparing oncological outcomes of sigmoid and rectal tumours and concluded that upper rectal tumours can be managed as sigmoid cancer without neoadjuvant chemoradiotherapy and subtotal mesorrectal excision with similar outcomes (LR 4.9% vs. 7%, p>0,05) [8]. However, due to the high incidence of local recurrence as carcinomatosis when peritoneal involvement is present, existing strategies are being reevaluated to improve oncological outcomes. These have mainly focused on two strategies: neoadjuvant treatment aimed to achieve tumor’s regression and intensive follow-up for early detection and treatment of local recurrence. Recent publications advocate for neoadjuvant systemic chemotherapy (NAC) in the management of locally advanced colon cancer. The finding of the FOxTROT trial suggest that NAC improves tumour control by reducing incomplete resections and promoting higher regression rates. The primary end point of achieving improved 2-year disease control for cT3-4 colon cancer seems to be achieved, with a HR 0.72, 95% CI 0.54-0.98; p=0.037[36]. Additionally, the more recent OPTICAL trial also compares NAC regime for cT3-4 colon cancer with upfront surgery. While this trial did not revealed superior 3-year DFS in the NAC group, it showed a potentially improved OS (HR 0.44, 95% CI 0.25-0.77)[37]. Ongoing trials, such as the ELECLA trial[38], aim to provide further evidence on NAC strategies for locally advanced colorectal tumours. Therefore, most recent studies advocate for neoadjuvant strategies for the management of locally advanced colorectal tumours, NAC for colonic and TNT including radiotherapy for lower rectal tumors. Given this new trend, it seems logical to consider neoadjuvant treatment strategies for tumors above the PR when preoperative suspected serosal involvement is present, which have traditionally undergone direct surgical resection. It remains to be determined what the optimal neoadjuvant regimen might be considering the limitations of MRI in accurately assessing PR involvement[24,39,40]. On the other hand, several authors have evaluated different intensive follow-up strategies for patients at high risk of developing peritoneal carcinomatosis following surgery for colorectal tumors. A meta-analysis of 17 trials evaluating intensive follow-up demonstrated that patients were twice as likely to undergo salvage surgery after interval recurrence, however, this approach failed to demonstrate improved cancer-related OS [41]. The COLOPEC trial evaluated the role of adjuvant oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) for pT4 or perforated colon cancer[42]. The results showed no improved peritoneal metastasis-free survival at 18 months (80.9% vs. 76.2%). Similarly, the PHROPHYLOCHIP-PRODIGE 15 trial aimed to investigate the role of prophylactic oxaliplatin-based HIPEC following primary colonic resection with synchronic local carcinomatosis removal, excision of ovarian metastases or treatment for tumour perforation[35]. After a 5-year follow-up, they failed to demonstrate improved DFS compared to standard surveillance alone. The more recent HIPECT4 trial, assesses the efficacy of concomitant mitomycin C-based HIPEC for cT4 colon and rectal tumours above PR during primary surgery[43]. The 3-year local control (LC) rate was higher in the HIPEC group (97.6% vs. 87.6%, p=0.03) but there were no differences in DFS and OS. Within the subgroup with pT4 disease (67.9% of enrolled patients), there was a pronounced benefit in 3-year LC in the HIPEC group (98.3% vs. 82.1%, p=0.003; HR 0.09, 95% CI 0.01-0.70). In view of this results, NAC strategies for intraperitoneal rectal tumours involving the peritoneal reflection could be extrapolated from NAC regimens used in trials for locally advanced colon tumours. In addition, the role of prophylactic HIPEC in T4 intraperitoneal colorectal tumours remains uncertain. Randomized control trials are needed to determine the optimal neoadjuvant and adjuvant therapies for upper rectal tumours with PR involvement as it may have major implications in oncological outcomes. This study presents several limitations. Firstly, due to the study being conducted in a single institution with restricted patient enrollment, the sample size is limited. Furthermore, patients undergoing neoadjuvant chemoradiotherapy with PR involvement on preoperative MRI may not demonstrate serosal involvement in the pathological examination due to tumour regression. However, microscopic peritoneal spread may already exist within the abdominal cavity, potentially leading to early recurrence. Moreover, computed tomography scanners have inherent limitations in detecting peritoneal nodules smaller than 1 centimeter, with published accuracy ranging from 44 to 93.8% [44]. Consequently, the actual incidence of LR may be underestimated during follow-up. This study demonstrates that peritoneal reflection involvement is a strong predictor of both local recurrence and poor overall survival in rectal cancer. These findings highlight the importance for multidisciplinary colorectal teams to consider peritoneal reflection involvement when discussing treatment strategies for rectal tumours. Declarations No funding was received to assist with the preparation of this manuscript. The authors have no relevant financial or non-financial interests to disclose. 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J Clin Oncol 41:1541–1552. 10.1200/JCO.22.00046 Hu H, Zhang J, Li Y, Wang X, Wang Z, Wang H, Kang L, Liu P, Lan P, Wu X, Zhen Y, Pei H, Huang Z, Zhang H, Chen W, Zeng Y, Lai J, Wei H, Huang X, Chen J, Chen J, Tao K, Xu Q, Peng X, Liang J, Cai G, Ding K, Ding Z, Hu M, Zhang W, Tang B, Hong C, Cao J, Huang Z, Cao W, Li F, Wang X, Wang C, Huang Y, Zhao Y, Cai Y, Ling J, Xie X, Wu Z, Shi L, Ling L, Liu H, Wang J, Huang M, Deng Y, OPTICAL study group (2024) Neoadjuvant Chemotherapy With Oxaliplatin and Fluoropyrimidine Versus Upfront Surgery for Locally Advanced Colon Cancer: The Randomized, Phase III OPTICAL Trial. J Clin Oncol 2:JCO2301889. 10.1200/JCO.23.01889 Arredondo J, Almeida A, Castañón C, Sánchez C, Villafañe A, Tejedor P, Simó V, Baixauli J, Rodríguez J, Pastor C (2024) The ELECLA trial: A multicentre randomised control trial on outcomes of neoadjuvant treatment on locally advanced colon cancer. Colorectal Dis 26:745–753. 10.1111/codi.16908 Nougaret S, Jhaveri K, Kassam Z, Lall C, Kim DH Rectal cancer MR staging: pearls and pitfalls at baseline examination. Abdom Radiol (NY) 44:3536–3548 Gollub MJ, Maas M, Weiser M, Beets GL, Goodman K, Berkers L, Beets-Tan RG (2013) Recognition of the anterior peritoneal reflection at rectal MRI. AJR Am J Roentgenol 200:97–101. 10.2214/AJR.11.7602 Zhao Y, Yi C, Zhang Y, Fang F, Faramand A (2019) Intensive follow-up strategies after radical surgery for non-metastatic colorectal cancer: A systematic review and meta-analysis of randomized controlled trials. PLoS ONE 14:e0220533. 10.1371/journal.pone.0220533 Klaver CEL, Wisselink DD, Punt CJA, Snaebjornsson P, Crezee J, Aalbers AGJ, Brandt A, Bremers AJA, Burger JWA, Fabry HFJ, Ferenschild F, Festen S, van Grevenstein WMU, Hemmer PHJ, de Hingh IHJT, Kok NFM, Musters GD, Schoonderwoerd L, Tuynman JB, van de Ven AWH, van Westreenen HL, Wiezer MJ, Zimmerman DDE, van Zweeden AA, Dijkgraaf MGW, Tanis PJ, COLOPEC collaborators group (2019) Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial. Lancet Gastroenterol Hepatol 4:761–770. 10.1016/S2468-1253(19)30239-0 Arjona-Sánchez A, Espinosa-Redondo E, Gutiérrez-Calvo A, Segura-Sampedro JJ, Pérez-Viejo E, Concepción-Martín V, Sánchez-García S, García-Fadrique A, Prieto-Nieto I, Barrios-Sanchez P, Torres-Melero J, Ramírez Faraco M, Prada-Villaverde A, Carrasco-Campos J, Artiles-Armas M, Villarejo-Campos P, Ortega-Pérez G, Boldo-Roda E, Sánchez-Hidalgo JM, Casado-Adam A, Rodríguez-Ortiz L, Aranda E, Cano-Osuna MT, Díaz-López C, Romero-Ruiz A, Briceño-Delgado J, Rufián-Peña S, Grupo Español de Carcinomatosis Peritoneal (2023) Efficacy and Safety of Intraoperative Hyperthermic Intraperitoneal Chemotherapy for Locally Advanced Colon Cancer: A Phase 3 Randomized Clinical Trial. JAMA Surg 158:683–691. 10.1001/jamasurg.2023.0662 Ahmed SA, Abou-Taleb H, Yehia A, El Malek NAA, Siefeldein GS, Badary DM, Jabir MA (2019) The accuracy of multi-detector computed tomography and laparoscopy in the prediction of peritoneal carcinomatosis index score in primary ovarian cancer. Acad Radiol 26:1650–1658. 10.1016/j.acra.2019.04.005 Tables Table 1. Pathological characteristics of different peritoneal involvement grades defined by Shepherd Table 1. Shepherd’s degrees of peritoneal involvement [25] Grade 1 Free of peritoneal involvement. Grade 2 Mesothelial inflammation or hyperplastic with tumour close but not actually present at the peritoneal surface. Grade 3 Microscopic involvement of peritoneal surface Grade 4 Peritoneal ulceration with free tumour cells in peritoneum. Table 2. Demographic, preoperative and pathological characteristics of patients. Table 2. Data for the whole group (n=160) N % Patient’s variables Sex (male/female) 90/70 56.3/43.7 Median age (IQR) 65 (57-73) Rectal Tumour height Upper (11-15cm) Middle (7-10cm) Lower (0-6cm) 44 63 53 27.5 39.4 33.1 rmN+ 87 54.4 rmCRM+/threatened 55 34.4 Neoadjuvant chemoradiation 64 40 Surgery Procedure: Low anterior resection Hartmann’s procedure Abdominoperineal resection Pelvic Exenteration Other 100 8 35 7 10 62.5 5 21.9 4.4 6.2 Extended resection 32 20 Laparoscopic 102 63.7 Focal carcinomatosis 9 5,6 Obstruction 5 23.1 Tumour’s perforation 2 1.2 RBC transfusion 5 3.1 Pathological exam Quality of mesorectum Complete Nearly complete Non-complete 126 18 16 78.8 11.2 10 Poor tumoral differentiation 15 9.4 Tumoral budding 103 64.4 Lympho-vascular invasion 53 33.1 Neural invasion 28 17.5 T stage: pT1-2 pT3 pT4a pT4b 67 58 19 16 41.9 36.2 11.9 10 pN+ 62 38.7 Relationship with peritoneal reflection Above At the level Below 22 63 75 13.8 39.4 46.9 Shepherd’s degree Not applicable 1 2 3 4 75 51 10 14 10 46.9 31.9 6.2 8.8 6.2 pCRM+ 11 6.9 Abbreviations: IQR: interquartile range; rm: refers to magnetic resonance-preoperative staging; N+: positive adenophaties; CRM+: circumferential resection margin involvement; RBC: red blood cell; p: refers to final pathological staging. Table 3 . Preoperative and pathological characteristics in both groups, based on the presence or absence of peritoneal involvement. Table 3. Demographic’s variables No peritoneal involvement (n=136) N (%) Peritoneal involvement (n=24) N (%) p Patient’s variables Male sex 76 (55.8) 14 (58.3) 0.82 rmN+ 72 (52.9) 15 (62.5) 0.42 Neoadjuvant chemoradiation 57 (41.9) 7 (29.1) 0.24 Laparoscopic approach 91 (66.2) 11 (45.8) 0.07 Extended resection 23 (16.9) 9 (37.5) 0.02* Obstruction 2 1.5) 3 (12.5) 0.004* Tumour’s perforation 3 (2.2) 3 (12.5) 0.04* Pathological data Complete mesorectum 109 (80.1) 17 (70.8) 0.3 Poor tumoral differentiation 12 (14.7) 3 (12.5) 0.57 Tumoral budding 86 (63.2) 17 (70.8) 0.72 Lympho-vascular invasion 40 (29.4) 13 (54.2) 0.018* Neural invasion 21 (15.4) 7 (29.2) 0.1 pT4 11 (8.1) 24 (100) <0.001* pN+ 46 (33.8) 16 (66.7) 0.002* pCRM+ 9 (6.6) 2 (8.3) 0.76 * Statistically significant p-value (p<0.05) Abbreviations: rm: refers to magnetic resonance-preoperative staging; N+: positive adenophaties; p: refers to final pathological staging; T4: refers to T4 staging on TNM classification; CRM+: circumferential resection margin involvement. Table 4 . Univariate and multivariate Cox analysis for OS, DFS and LRFS in patients with resected rectal cancer Table 4. Univariate and multivariate survival analysis for LR, OS and DFS Overall survival Disease-free Survival Local recurrence-free Survival Univariate analysis Multivariate analysis Univariate analysis Multivariate analysis Univariate analysis Multivariate analysis Hazard Ratio P Adjusted-HR p Hazard Ratio p Adjusted-HR p Hazard Ratio P Adjusted-HR p Variables Preoperative Male sex 1.1 (0.5-2.6) 0.73 1.2 (0.6-2.5) 0.55 1.2 (0.5-3) 0.62 Lower vs. Upper-middle third 0.9 (0.4-2.3) 0.98 1.1 (0.5-2.3) 0.73 0.9 (0.4-2.3) 0.85 Below vs. At/above PR 0.9 (0.4-2.1) 0.88 1.3 (0.6-2.6) 0.46 1.2 (0.5-2.8) 0.72 rmT4 1.2 (0.5-3.1) 0.56 1.5 (0.7-3.2) 0.23 2.1 (0.9-2.3) 0.09 1.1 (0.5-2.2) 0.72 rmCRM+ 2 (0.8-4.6) 0.09 1.1 (0.4-2.8) 0.43 2.3 (1.2-4.8) 0.01* 1.4 (0.7-2.7) 0.39 1.9 (0.8-4.7) 0.14 rmN+ 2.2 (0.9-5.3) 0.07 1.2 (0.5-2.6) 0.67 2.3 (1.1-4.9) 0.02* 1.1 (0.5-2.5) 0.91 1.6 (0.7-4.1) 0.29 Neoadjuvant CRT 3.7 (1.5-9) 0.002* 2.9 (1.2-6.6) 0.01* 2.4 (1.2-4.9) 0.01* 1.9 (1.1-3.7) 0.03* 2.2 (0.9-5.3) 0.08 1.1 (0.5-2.4) 0.83 Intraoperative Extended resection 0.9 (0.3-2.5) 0.83 1 (0.4-2.4) 0.59 2 (0.7-5.2) 0.17 Laparoscopic approach 0.8 (0.3-1.8) 0.59 1 (0.5-2.1) 0.91 0.9 (0.4-2.1) 0.75 RBC transfusion 3.4 (0.5-21) 0.16 1.7 (0.3-10.7) 0.54 4.2 (0.7-27) 0.09 1.1 (0.5-2.2) 0.78 Tumoral obstruction 0.8 (0.7-1.1) 0.39 1.3 (0.3-7.3) 0.54 1.2 (0.2-10.7) 0.87 1 (0.5-2) 0.89 Rectal perforation 2.5 (0.4-14.8) 0.26 0.7 (0.6-1.1) 0.18 0.9 (0.8-1.1) 0.35 Focal carcinomatosis 16.5 (1.6-165) 0.002* 4.7 (1.1-21) 0.04* 25 (1.4-475) 0.03* 15.8 (2.2-115) 0.006* 20.4 (2-205) <0.001* 6.2 (1.3-29.3) 0.02* Postoperative TME quality (incomplete) 0.9 (0.3-2.5) 0.89 0.7 (0.3-1.7) 0.53 0.7 (0.3-2) 0.54 Poor tumoral differentiation 2.8 (0.9-8.9) 0.07 1.2 (0.4-2.9) 0.45 6.2 (2-19.6) <0,001* 1.6 (0.7-3.7) 0.31 3.5 (1.1-11.5) 0.02* 1.1 (0.3-4.1) 0.83 Tumoral budding 2.1 (0.7-6) 0.15 2.2 (0.9-5.2) 0.06 1.1 (0.4-2.3) 0.66 1.8 (0.6-5.3) 0.24 Lympho-vascular invasion 2.6 (1.1-6) 0.02* 1.1 (0.4-3.4) 0.78 3.4 (1.6-6.9) 0.001* 1.2 (0.5-3.1) 0.74 3.2 (1.3-7.7) 0.01* 2.7 (0.7-10.7) 0.16 Neural invasion 2.3 (0.9-6.1) 0.06 1 (0.5-2.2) 0.86 4.7 (2-11.1) <0,001* 1.9 (0.8-4.6) 0.13 3.4 (1.5-10.5) 0.003* 2.6 (0.7-8.9) 0.13 pT4 1.6 (0.6-4.1) 0.28 2.4 (1.1-5.2) 0.02* 1.2 (0.5-2.5) 0.73 3.5 (1.4-8.7) 0.007* 2.3 (0.5-10.4) 0.29 pN+ 4 (1.6-9.7) 0.001* 2.5 (1.1-6.3) 0.03* 3.9 (1.9-8.1) 0,001* 2.2 (1.1-4.3) 0.02* 2.9 (1.2-7.2) 0.02* 1.4 (0.5-3.7) 0.52 Peritoneal involvement 1.4 (0.5-4) 0.57 1.6 (0.7-4.1) 0.26 3.1 (1.1-8.6) 0.02* 1.2 (0.4-3.2) 0.85 Shepherd’s 4 grade 3.6 (1-14) 0.04* 2.9 (1.1-9.5) 0.04* 2.7 (1.1-10) 0.05* 2.1 (0.7-6.7) 0.21 7.3 (1.9-27.8) 0.001* 4.2 (1.2-16.9) 0.04* pCRM+ 4.8 (1.3-17) 0.009* 3.1 (1.1-8.8) 0.03* 8.1 (2-32) 0.001* 3.3 (1.4-8.1) 0.007* 6.1 (1.7-21.9) 0.002* 4.1 (1.1-15.5) 0.03* Hazard ratio (95% CI) * Statistically significant p-value (p<0.05) Abbreviations: PR: peritoneal reflection; rm: refers to magnetic resonance-preoperative staging; T4: refers to T4 staging on TNM classification; CRM: circumferential resection margin; N+: positive adenophaties; CRT: hemoradiotherapy; RBC: red blood cell; TME: total mesorrectal excision; p: refers to final pathological staging. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 10 May, 2025 Read the published version in International Journal of Colorectal Disease → Version 1 posted Editorial decision: Revision requested 14 Apr, 2025 Reviews received at journal 13 Apr, 2025 Reviewers agreed at journal 05 Apr, 2025 Reviewers agreed at journal 29 Mar, 2025 Reviewers invited by journal 27 Mar, 2025 Editor assigned by journal 26 Mar, 2025 Submission checks completed at journal 26 Mar, 2025 First submitted to journal 24 Mar, 2025 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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18:53:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6297876/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6297876/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00384-025-04909-7","type":"published","date":"2025-05-10T15:57:02+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":80710967,"identity":"ba1d770a-64ec-41df-9ade-f9a126d74a37","added_by":"auto","created_at":"2025-04-16 09:03:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":14600751,"visible":true,"origin":"","legend":"\u003cp\u003eMicroscopy photography of formalin fixed and paraffin-embedded rectal cancer specimens showing peritoneal involvement according to Shepherd’s classification: A) Shepherd’s grade 1 (HE stain; 2.8x, bar=800μm); B) Shepherd’s grade 2 (HE stain; 4.6x, bar=500μm); C) Shepherd’s grade 3 (HE stain; 5.8x, bar=400μm); D) Shepherd’s grade 4 (HE stain; 4x,). Asterisk (*) show tumour cells at invasion front. Arrow shows peritoneal surface with orange dye. HE: hematoxylin-eosin.\u003c/p\u003e","description":"","filename":"4.Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6297876/v1/5185426f4cd925b70c202995.png"},{"id":80710964,"identity":"b7768c76-a4f3-46e2-8ff4-edb23713f9d7","added_by":"auto","created_at":"2025-04-16 09:03:49","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1101646,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curves for OS, DFS and LRFS for patients with and without peritoneal involvement.\u003c/p\u003e","description":"","filename":"5.Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6297876/v1/5d41588ac5841907f4357efe.png"},{"id":82537439,"identity":"2be7b9fc-963c-4d5a-8e35-476a906cc0d3","added_by":"auto","created_at":"2025-05-12 16:06:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":15141866,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6297876/v1/ac4f61f3-1509-4e22-b6b1-be97c3707dc7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Peritoneal reflection involvement as a prognostic factor in rectal cancer. Long-term oncological outcomes from a prospective study.","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eCircumferential resection margin (CRM) involvement after surgical resection is widely known to be a risk factor for both local recurrence (LR) and poor survival [\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, for anterior tumours above the peritoneal reflection (PR), peritoneal involvement should be carefully assessed and independently reported from CRM involvement [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Moreover, most publications do not take this aspect into account and data concerning CRM involvement for anterior tumours may be misunderstood [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePrevious publications about oncological outcomes in rectal cancer have mainly focused on pathological CRM (pCRM) status as it has been proved to be one of the most important LR-related factors. Patients with pCRM involvement have a 5-year LR rate around 23.7\u0026ndash;26.7% [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, up to 25% of anterior rectal surface is covered by peritoneum, even if this fact is frequently ignored [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In upper and middle rectal tumours involving the serosal surface, the concept of CRM is not applicable and they must be classified as pT4a as they are intraperitoneal tumours[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Additionally, tumours above or at the level of PR may have peritoneal spread in addition to the classical lymphatic and hematologic patterns of dissemination developed by lower rectal tumours [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHigh-resolution magnetic resonance imaging (MRI) is the gold standard for rectal cancer local staging as it can determine the depth of invasion, distance to anal margin and predict the involvement of mesorrectal fascia with high accuracy[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17 CR18 CR19 CR20\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. This information is crucial to select patients for neoadjuvant treatment and to determine the appropriate surgical technique[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Nonetheless, peritoneal involvement is not always detected by preoperative MRI, as shown in our previous publication, reaching an overall accuracy of 80.5\u0026ndash;95.9% [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In 1995, Shepherd established four degrees of peritoneal involvement according to the depth of invasion[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. They later demonstrated that serosal invasion is a relevant risk factor for LR and poor OS, however, this association did not reach statistical significance in the multivariate analysis[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Consequently, certain authors have advocated for neoadjuvant systemic chemotherapy protocols in the management of upper rectal tumors with serosal involvement, mirroring most recent strategies employed for locally advanced colon cancer. This recommendation is supported by studies such as the FOXTROT trial, aiming to induce tumor downstaging and mitigate the potential for peritoneal dissemination[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite CRM involvement relevance has been widely investigated, very few publications have focused on peritoneal reflection involvement. Recently, several authors have highlighted the importance of MRI accuracy for identification and determination of the level of PR[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan additionalcitationids=\"CR29 CR30\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Nonetheless, the prognostic importance of peritoneal involvement on oncological outcomes remains to be determined.\u003c/p\u003e \u003cp\u003eThe primary objective of this prospective study is to PR involvement as a relevant factor determining local recurrence (LR), disease-free survival (DFS), and overall survival (OS) after rectal resection for adenocarcinoma.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eThis is a prospective, observational study conducted by a specialized multidisciplinary colorectal unit at a tertiary hospital. This manuscript has been written following the STROBE guidelines.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical statements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the institution\u0026rsquo;s ethics committee and written informed consent was obtained from each patient. Registry number: 2016/0373.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDescription of participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients with histopathologically confirmed rectal adenocarcinoma undergoing surgical resection with total or subtotal mesorrectal excision were enrolled from June 2016 to May 2019. Some of the patients of the present analysis were already included in a previous publication focused on overall MRI accuracy for PR location and involvement [24].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRadiologic assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHigh-resolution MRI was performed in a 1.5 tesla MRI scanner (General Electric Medical System, Milwaukee, Wisconsin, USA) with pelvic phased-array coil. MRI protocol details are explained in our previous publication[24].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMRI images were evaluated and discussed at the multidisciplinary board. Peritoneal reflection involvement was defined as direct contact or nodular extension of the tumour into peritoneal surface. CRM involvement was defined as direct contact or tumour within 1 millimeter (mm) to mesorectal fascia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePathological assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA double-ink technique was applied, indian ink on mesorrectal extraperitoneal surface and orange ink for the peritoneal surface. Detailed pathological protocol and dying technique are explained in our previous paper[24].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTumours located within 5 mm of the peritoneal reflection were considered at the level of PR for the purpose of analysis. Peritoneal involvement was assessed according to Shepherd\u0026rsquo;s classification into 4 degrees, as shown in Table 1 [25]. Grades 1-2 were considered free of serosal involvement and grades 3-4 as involved serosa. Figure 1 shows microscopy photographies of pathological findings according to Shepherd\u0026rsquo;s peritoneal involvement degrees. CRM involvement was defined as a tumour within 1 mm to mesorectal fascia. Both pathological data, PR and pCRM involvement, were considered for survival analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFollow-up and oncological outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRecommendations for neoadjuvant treatment were discussed by the multidisciplinary board for all patients. Preoperative chemoradiotherapy was considered for cT3 and cT4 low and middle rectal cancer with high-risk factors such as involved mesorectal fascia. None of the patients received a total neoadjuvant regime during the period study. Oxaliplatin-based adjuvant regimes were given to selected patients after surgery. None of the patients received postoperative radiotherapy.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients were followed by serial clinical examination and carcinoembryonic antigen assessment every 3 months during the first year, every 6 months during the second year, and annually thereafter. Thoracoabdominal computed tomography scanning was performed every 6 months for the first 2 years and annually thereafter for 5 years. Colonoscopy was performed after 1 year and 3 to 5 years thereafter, depending on individual patient risk. If recurrence was suspected, then further diagnostic methods were used as required.\u003c/p\u003e\n\u003cp\u003eOS was defined as the time from surgery to death for any cause. DFS was defined as the time from surgery to date of local recurrence or distant metastases diagnosis. LR was defined as the presence of tumour at anastomosis, pelvic mass, peritoneal carcinomatosis, or locoregional lymphatic recurrence. Local recurrence-free survival (LRFS) was defined as the time from surgery to date of LR.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSPSS software (IBM SPSS Statistics for Macintosh, version 24.0, IBM Corp, Armonk, NY) was used for statistical analysis. Categorical variables were compared among groups using \u0026chi;2 and Fisher exact tests. Continuous variables were compared by ANOVA or Kruskal-Wallis test. All time-to-event variables were calculated from the date of surgery. The univariate influence of prognostic factors on LR, DFS and OS was analyzed for all of the groups with the Kaplan-Meier method and the log-rank (Mantel-Cox) test. A Cox multivariate regression model was constructed including variables with p\u0026lt;0.10 at univariate analysis. Proportional hazards assumption of the Cox model was assessed. Statistical significance for all the results was defined as p\u0026lt;0.05.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003ePatient\u0026rsquo;s baseline\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 160 patients were enrolled in the study. The median age was 65 years (interquartile range (IQR): 57-73 years) and 56.3% were males. 27.5% of tumours were located in the upper third (11-15cm from anal verge), 39.4% in the middle third (7-10cm) and 33.1% in the lower rectum (0-6cm). Sixty-four patients (40%) received neoadjuvant chemoradiotherapy.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter surgical resection, good quality mesorectal excision plane was achieved in 126 (78.8%) specimens. CRM was involved in 11 cases (6.9%). When extended resections for locally advanced pT4b-tumours are excluded, CRM was involved in 6/146 (4.1%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter pathological examination, 22 (13.8%) tumours were located above the PR, 63 (39.4%) at the level of PR and 75 (46.9%) below the PR. For tumours located at or above the PR (n=85), peritoneal involvement was confirmed in 24 out of 85 (28.2%) patients, with 14 classified as grade 3 and 10 as grade 4 according to Shepherd\u0026rsquo;s classification. Demographic, preoperative and pathological data for the whole group are shown in table 2.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOncological outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median follow-up time was 67 months. 5-year OS, 5-year DFS and 5-year LRFS were 75% (95% CI, 68.3-81.6), 72.1% (95% CI, 65-79.1) and 84.4% (95% CI, 78.5-90.2), respectively. Isolated LR occurred in 5 patients (3.1%) whereas 18 (11.2%) patients had both LR and distant metastasis, and 21 patients (13.1%) developed distant metastasis only.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe median time to LR after surgery was 24 months (IQR: 12-39). Patterns of local recurrence included carcinomatosis in 11 patients, pelvic mass and carcinomatosis in 2 patients and pelvic recurrence alone in 9 patients. Three patients showed locoregional lymph node involvement, one as the sole LR site. In our series, pT4 tumours represent 21.9% of cases, with LR occurring in 28.6% of these cases: 9 patients as carcinomatosis, while 1 patient developed pelvic recurrence. 4 patients underwent pelvic exenteration after local recurrence. The median OS after LR diagnosis was 14 months (IQR: 4-22 months). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe median time to diagnosis of distant metastasis after surgery was 15 months (IQR: 6-22). Metastasis patterns were observed as follows: 7 cases presented with hepatic metastases only, 13 cases hepatic and pulmonary metastases, 13 cases pulmonary metastasis only and 6 cases showed multiple-organ metastases. The median OS following metastatic progression was 22 months (IQR: 8-47).\u003c/p\u003e\n\u003cp\u003e- \u003cstrong\u003eLocation of the tumour in relation with the peritoneal reflection.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAccording to tumour\u0026rsquo;s location no statistical difference was found in 5-y OS (90% vs. 77.3% vs. 79.5%, p=0.603), 5-y DFS (76.2% vs. 62.1% vs. 72.6%, p=0.58) and LRFS (90.5% vs. 81% vs 84.1%, p=0.639) for tumours above, at or below the PR, respectively.\u003c/p\u003e\n\u003cp\u003e- \u003cstrong\u003eInvolvement of peritoneal reflection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 3 shows the baseline characteristics in patients with or without peritoneal involvement. More frequently, patients with peritoneal involvement required an extended resection and had more advanced tumours at pathological staging with higher proportion of lympho-vascular invasion, pT4 stages and lymph nodes involvement.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor patients with peritoneal involvement, 5-y OS (58.3% vs. 73.8%, p=0.043) and 5-y LRFS (69.7% vs. 87.1%, p=0.02) were significantly shorter. Patients with Shepherd\u0026rsquo;s grade 4 peritoneal involvement compared to the rest of the patients had the worse long-term outcomes with 5-y OS (50% vs. 76.7%, p=0.05), 5-y DFS (50% vs. 73.7%, p=0.027) and 5-y LRFS (50% vs. 86.8%, p\u0026lt;0.001). Kaplan-Meier curves for OS, DFS and LRFS are shown in figure 2.\u003c/p\u003e\n\u003cp\u003e- \u003cstrong\u003eRisk factor for OS, DFS and LR\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOn multivariate Cox regression analysis, Shepherd\u0026rsquo;s grade 4 peritoneal involvement was confirmed as independent prognostic factor for higher LR (HR 4.2, 95% CI 1.2-16.9) and worse OS (HR 2.9, 95% CI 1.1-9.5). Table 4 summarizes the results of univariate and multivariate analysis for OS, DFS and LRFS.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study assesses the prognostic relevance of peritoneal involvement at PR in rectal cancer and evidences that is a strong predictor of LR, with an adjusted-HR 4.2 (95% CI 1.2-16.9) for grade 4 Shepherd\u0026rsquo;s involvement. Peritoneal involvement at that location was present in 24 out of 85 (28.2%) tumours above or at the level of PR and 29.1% (7/24) of these patients developed LR, all presenting with carcinomatosis. Notably, while serosal ulceration with tumour cells free in the peritoneum (grade-4 involvement) was found in only 6.25% of all patients, this subgroup developed LR in 50% of cases. This data is in concordance with previous publications by Shepherd and colleagues and highlights the importance of the peritoneal involvement in the oncological outcomes[25,26].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAnterior rectal tumours at the level of peritoneal reflection can, potentially, reach the peritoneal surface or/and the anterior mesorrectal fascia as the mesorrectal fat becomes very thin at this level[12,30,32]. In this regard, The European Society of Gastrointestinal and Abdominal Radiology (ESGAR) recommends to describe the relationship of rectal tumours with the anterior peritoneal reflection, as tumour\u0026rsquo;s invasion above the level of PR at the anterior side should be considered at risk for peritoneal involvement rather than anterior CRM involvement[17,33]. However, although MRI has demonstrated a high accuracy for determination of tumour\u0026rsquo;s location according to PR, preoperative evaluation of PR involvement can be challenging[24], and may not have been adequately considered in the analysis of the prognostic implications of the circumferential location of distal cancer [2].\u003c/p\u003e\n\u003cp\u003eEstimated rectal cancer carcinomatosis rate is 3-4.2% but pT4 tumours present up to 10 times higher risk of carcinomatosis[11,13,36,37]. Patients with rectal cancer and resected local carcinomatosis at the primary surgery present worse median OS (48 vs. 97 months, p\u0026lt;0.001) and a 5-year LR of 15.7%[36]. In our series, pT4 tumours accounted for 21.9% of cases, with LR developing in 28.6% of these cases: 9 patients as carcinomatosis, while 1 patient developed pelvic recurrence.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo date, guidelines recommend upfront surgery for rectal tumour above the PR but peritoneal involvement is not taken into account[22]. Marinello et al reviewed 1145 patients comparing oncological outcomes of sigmoid and rectal tumours and concluded that upper rectal tumours can be managed as sigmoid cancer without neoadjuvant chemoradiotherapy and subtotal mesorrectal excision with similar outcomes (LR 4.9% vs. 7%, p\u0026gt;0,05) [8]. However, due to the high incidence of local recurrence as carcinomatosis when peritoneal involvement is present, existing strategies are being reevaluated to improve oncological outcomes. These have mainly focused on two strategies: neoadjuvant treatment aimed to achieve tumor\u0026rsquo;s regression and intensive follow-up for early detection and treatment of local recurrence.\u003c/p\u003e\n\u003cp\u003eRecent publications advocate for neoadjuvant systemic chemotherapy (NAC) in the management of locally advanced colon cancer. The finding of the FOxTROT trial suggest that NAC improves tumour control by reducing incomplete resections and promoting higher regression rates. The primary end point of achieving improved 2-year disease control for cT3-4 colon cancer seems to be achieved, with a HR 0.72, 95% CI 0.54-0.98; p=0.037[36]. Additionally, the more recent OPTICAL trial also compares NAC regime for cT3-4 colon cancer with upfront surgery. While this trial did not revealed superior 3-year DFS in the NAC group, it showed a potentially improved OS (HR 0.44, 95% CI 0.25-0.77)[37]. Ongoing trials, such as the ELECLA trial[38], aim to provide further evidence on NAC strategies for locally advanced colorectal tumours.\u003c/p\u003e\n\u003cp\u003eTherefore, most recent studies advocate for neoadjuvant strategies for the management of locally advanced colorectal tumours, NAC for colonic and TNT including radiotherapy for lower rectal tumors. Given this new trend, it seems logical to consider neoadjuvant treatment strategies for tumors above the PR when preoperative suspected serosal involvement is present, which have traditionally undergone direct surgical resection. It remains to be determined what the optimal neoadjuvant regimen might be considering the limitations of MRI in accurately assessing PR involvement[24,39,40].\u003c/p\u003e\n\u003cp\u003eOn the other hand, several authors have evaluated different intensive follow-up strategies for patients at high risk of developing peritoneal carcinomatosis following surgery for colorectal tumors. A meta-analysis of 17 trials evaluating intensive follow-up demonstrated that patients were twice as likely to undergo salvage surgery after interval recurrence, however, this approach failed to demonstrate improved cancer-related OS [41]. The COLOPEC trial evaluated the role of adjuvant oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) for pT4 or perforated colon cancer[42]. The results showed no improved peritoneal metastasis-free survival at 18 months (80.9% vs. 76.2%). Similarly, the PHROPHYLOCHIP-PRODIGE 15 trial aimed to investigate the role of prophylactic oxaliplatin-based HIPEC following primary colonic resection with synchronic local carcinomatosis removal, excision of ovarian metastases or treatment for tumour perforation[35]. After a 5-year follow-up, they failed to demonstrate improved DFS compared to standard surveillance alone. The more recent HIPECT4 trial, assesses the efficacy of concomitant mitomycin C-based HIPEC for cT4 colon and rectal tumours above PR during primary surgery[43]. The 3-year local control (LC) rate was higher in the HIPEC group (97.6% vs. 87.6%, p=0.03) but there were no differences in DFS and OS. Within the subgroup with pT4 disease (67.9% of enrolled patients), there was a pronounced benefit in 3-year LC in the HIPEC group (98.3% vs. 82.1%, p=0.003; HR 0.09, 95% CI 0.01-0.70).\u003c/p\u003e\n\u003cp\u003eIn view of this results, NAC strategies for intraperitoneal rectal tumours involving the peritoneal reflection could be extrapolated from NAC regimens used in trials for locally advanced colon tumours. In addition, the role of prophylactic HIPEC in T4 intraperitoneal colorectal tumours remains uncertain. Randomized control trials are needed to determine the optimal neoadjuvant and adjuvant therapies for upper rectal tumours with PR involvement as it may have major implications in oncological outcomes.\u003c/p\u003e\n\u003cp\u003eThis study presents several limitations. Firstly, due to the study being conducted in a single institution with restricted patient enrollment, the sample size is limited. Furthermore, patients undergoing neoadjuvant chemoradiotherapy with PR involvement on preoperative MRI may not demonstrate serosal involvement in the pathological examination due to tumour regression. However, microscopic peritoneal spread may already exist within the abdominal cavity, potentially leading to early recurrence. Moreover, computed tomography scanners have inherent limitations in detecting peritoneal nodules smaller than 1 centimeter, with published accuracy ranging from 44 to 93.8% [44]. Consequently, the actual incidence of LR may be underestimated during follow-up.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study demonstrates that peritoneal reflection involvement is a strong predictor of both local recurrence and poor overall survival in rectal cancer. These findings highlight the importance for multidisciplinary colorectal teams to consider peritoneal reflection involvement when discussing treatment strategies for rectal tumours.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eNo funding was received to assist with the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDebove C, Maggiori L, Chau A, Kanso F, Ferron M, Panis Y (2015) What happens after R1 resection in patients undergoing laparoscopic total mesorectal excision for rectal cancer? A study in 333 consecutive patients. 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JAMA Surg 158:683\u0026ndash;691. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamasurg.2023.0662\u003c/span\u003e\u003cspan address=\"10.1001/jamasurg.2023.0662\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAhmed SA, Abou-Taleb H, Yehia A, El Malek NAA, Siefeldein GS, Badary DM, Jabir MA (2019) The accuracy of multi-detector computed tomography and laparoscopy in the prediction of peritoneal carcinomatosis index score in primary ovarian cancer. Acad Radiol 26:1650\u0026ndash;1658. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.acra.2019.04.005\u003c/span\u003e\u003cspan address=\"10.1016/j.acra.2019.04.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Pathological characteristics of different peritoneal involvement grades defined by Shepherd\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 566px;\"\u003e\n \u003cp\u003eTable 1. Shepherd\u0026rsquo;s degrees of peritoneal involvement [25]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eGrade 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 472px;\"\u003e\n \u003cp\u003eFree of peritoneal involvement.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eGrade 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 472px;\"\u003e\n \u003cp\u003eMesothelial inflammation or hyperplastic with tumour close but not actually present at the peritoneal surface.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eGrade 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 472px;\"\u003e\n \u003cp\u003eMicroscopic involvement of peritoneal surface\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eGrade 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 472px;\"\u003e\n \u003cp\u003ePeritoneal ulceration with free tumour cells in peritoneum.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eDemographic, preoperative and pathological characteristics of patients.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"621\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 621px;\"\u003e\n \u003cp\u003eTable 2. Data for the whole group (n=160)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003ePatient\u0026rsquo;s variables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eSex (male/female)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e90/70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e56.3/43.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eMedian age (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e65 (57-73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eRectal Tumour height\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eUpper (11-15cm)\u003c/li\u003e\n \u003cli\u003eMiddle (7-10cm)\u003c/li\u003e\n \u003cli\u003eLower (0-6cm)\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27.5\u003c/p\u003e\n \u003cp\u003e39.4\u003c/p\u003e\n \u003cp\u003e33.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003ermN+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e54.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003ermCRM+/threatened\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e34.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eNeoadjuvant chemoradiation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003eSurgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eProcedure:\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eLow anterior resection\u003c/li\u003e\n \u003cli\u003eHartmann\u0026rsquo;s procedure\u003c/li\u003e\n \u003cli\u003eAbdominoperineal resection\u003c/li\u003e\n \u003cli\u003ePelvic Exenteration\u003c/li\u003e\n \u003cli\u003eOther\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e62.5\u003c/p\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003cp\u003e21.9\u003c/p\u003e\n \u003cp\u003e4.4\u003c/p\u003e\n \u003cp\u003e6.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eExtended resection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eLaparoscopic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e63.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eFocal carcinomatosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e5,6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eObstruction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e23.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eTumour\u0026rsquo;s perforation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eRBC transfusion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003ePathological exam\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp;Quality of mesorectum\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eComplete\u003c/li\u003e\n \u003cli\u003eNearly complete\u003c/li\u003e\n \u003cli\u003eNon-complete\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e126\u003c/p\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e78.8\u003c/p\u003e\n \u003cp\u003e11.2\u003c/p\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003ePoor tumoral differentiation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e9.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eTumoral budding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e103\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e64.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eLympho-vascular invasion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e33.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eNeural invasion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e17.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eT stage:\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003epT1-2\u003c/li\u003e\n \u003cli\u003epT3\u003c/li\u003e\n \u003cli\u003epT4a\u003c/li\u003e\n \u003cli\u003epT4b\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e41.9\u003c/p\u003e\n \u003cp\u003e36.2\u003c/p\u003e\n \u003cp\u003e11.9\u003c/p\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003epN+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e38.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eRelationship with peritoneal reflection\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eAbove\u003c/li\u003e\n \u003cli\u003eAt the level\u003c/li\u003e\n \u003cli\u003eBelow\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13.8\u003c/p\u003e\n \u003cp\u003e39.4\u003c/p\u003e\n \u003cp\u003e46.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eShepherd\u0026rsquo;s degree\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eNot applicable\u003c/li\u003e\n \u003cli\u003e1\u003c/li\u003e\n \u003cli\u003e2\u003c/li\u003e\n \u003cli\u003e3\u003c/li\u003e\n \u003cli\u003e4\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e46.9\u003c/p\u003e\n \u003cp\u003e31.9\u003c/p\u003e\n \u003cp\u003e6.2\u003c/p\u003e\n \u003cp\u003e8.8\u003c/p\u003e\n \u003cp\u003e6.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003epCRM+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e6.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: IQR: interquartile range; rm: refers to magnetic resonance-preoperative staging; N+: positive adenophaties; CRM+: circumferential resection margin involvement; RBC: red blood cell; p: refers to final pathological staging.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e. Preoperative and pathological characteristics in both groups, based on the presence or absence of peritoneal involvement.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"586\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 519px;\"\u003e\n \u003cp\u003eTable 3. Demographic\u0026rsquo;s variables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 193px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003eNo peritoneal involvement (n=136)\u003c/p\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003ePeritoneal involvement\u003c/p\u003e\n \u003cp\u003e(n=24)\u003c/p\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003ePatient\u0026rsquo;s variables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 193px;\"\u003e\n \u003cp\u003eMale sex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e76 (55.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e14 (58.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 193px;\"\u003e\n \u003cp\u003ermN+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e72 (52.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e15 (62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 193px;\"\u003e\n \u003cp\u003eNeoadjuvant chemoradiation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e57 (41.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e7 (29.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 193px;\"\u003e\n \u003cp\u003eLaparoscopic approach\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e91 (66.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e11 (45.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 193px;\"\u003e\n \u003cp\u003eExtended resection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e23 (16.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e9 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.02*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 193px;\"\u003e\n \u003cp\u003eObstruction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e2 1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e3 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.004*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 193px;\"\u003e\n \u003cp\u003eTumour\u0026rsquo;s perforation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e3 (2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e3 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.04*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003ePathological data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 193px;\"\u003e\n \u003cp\u003eComplete mesorectum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e109 (80.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e17 (70.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 193px;\"\u003e\n \u003cp\u003ePoor tumoral differentiation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e12 (14.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e3 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 193px;\"\u003e\n \u003cp\u003eTumoral budding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e86 (63.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e17 (70.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 193px;\"\u003e\n \u003cp\u003eLympho-vascular invasion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e40 (29.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e13 (54.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.018*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 193px;\"\u003e\n \u003cp\u003eNeural invasion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e21 (15.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e7 (29.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 193px;\"\u003e\n \u003cp\u003epT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e11 (8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e24 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 193px;\"\u003e\n \u003cp\u003epN+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e46 (33.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e16 (66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.002*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 193px;\"\u003e\n \u003cp\u003epCRM+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e9 (6.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e2 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e* Statistically significant p-value (p\u0026lt;0.05)\u003c/p\u003e\n\u003cp\u003eAbbreviations: rm: refers to magnetic resonance-preoperative staging; N+: positive adenophaties; p: refers to final pathological staging; T4: refers to T4 staging on TNM classification; CRM+: circumferential resection margin involvement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u003c/strong\u003e. Univariate and multivariate Cox analysis for OS, DFS and LRFS in patients with resected rectal cancer\u003c/p\u003e\n\u003ctable cellpadding=\"0\" cellspacing=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"1005\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"14\" style=\"width: 1005px;\"\u003e\n \u003cp\u003eTable 4. Univariate and multivariate survival analysis for LR, OS and DFS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 261px;\"\u003e\n \u003cp\u003eOverall survival\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 276px;\"\u003e\n \u003cp\u003eDisease-free Survival\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 249px;\"\u003e\n \u003cp\u003eLocal recurrence-free Survival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 138px;\"\u003e\n \u003cp\u003eUnivariate analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 122px;\"\u003e\n \u003cp\u003eMultivariate analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 143px;\"\u003e\n \u003cp\u003eUnivariate analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 133px;\"\u003e\n \u003cp\u003eMultivariate analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 133px;\"\u003e\n \u003cp\u003eUnivariate analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 116px;\"\u003e\n \u003cp\u003eMultivariate analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eHazard Ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eAdjusted-HR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003eHazard Ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eAdjusted-HR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eHazard Ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eAdjusted-HR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003ePreoperative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003eMale sex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.1 (0.5-2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e1.2 (0.6-2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1.2 (0.5-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003eLower vs. Upper-middle third\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.9 (0.4-2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e1.1 (0.5-2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e0.9 (0.4-2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003eBelow vs. At/above PR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.9 (0.4-2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e1.3 (0.6-2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1.2 (0.5-2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003ermT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.2 (0.5-3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e1.5 (0.7-3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e2.1 (0.9-2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1.1 (0.5-2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003ermCRM+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e2 (0.8-4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1.1 (0.4-2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e2.3 (1.2-4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.4 (0.7-2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1.9 (0.8-4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003ermN+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e2.2 (0.9-5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1.2 (0.5-2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e2.3 (1.1-4.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.02*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.1 (0.5-2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1.6 (0.7-4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003eNeoadjuvant CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e3.7 (1.5-9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.002*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e2.9 (1.2-6.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e2.4 (1.2-4.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.9 (1.1-3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e0.03*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e2.2 (0.9-5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1.1 (0.5-2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003eIntraoperative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003eExtended resection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.9 (0.3-2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e1 (0.4-2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e2 (0.7-5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003eLaparoscopic approach\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.8 (0.3-1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e1 (0.5-2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e0.9 (0.4-2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003eRBC transfusion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e3.4 (0.5-21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e1.7 (0.3-10.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e4.2 (0.7-27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1.1 (0.5-2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003eTumoral obstruction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.8 (0.7-1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e1.3 (0.3-7.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1.2 (0.2-10.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1 (0.5-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003eRectal perforation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e2.5 (0.4-14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e0.7 (0.6-1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e0.9 (0.8-1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003eFocal carcinomatosis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e16.5 (1.6-165)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.002*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e4.7 (1.1-21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.04*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e25 (1.4-475)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.03*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e15.8 (2.2-115)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e0.006*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e20.4 (2-205)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e6.2 (1.3-29.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e0.02*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003ePostoperative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003eTME quality (incomplete)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.9 (0.3-2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e0.7 (0.3-1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e0.7 (0.3-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003ePoor tumoral differentiation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e2.8 (0.9-8.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1.2 (0.4-2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e6.2 (2-19.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026lt;0,001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.6 (0.7-3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e3.5 (1.1-11.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.02*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1.1 (0.3-4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003eTumoral budding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e2.1 (0.7-6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e2.2 (0.9-5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.1 (0.4-2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1.8 (0.6-5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003eLympho-vascular invasion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e2.6 (1.1-6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.02*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1.1 (0.4-3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e3.4 (1.6-6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.2 (0.5-3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e3.2 (1.3-7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e2.7 (0.7-10.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003eNeural invasion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e2.3 (0.9-6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1 (0.5-2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e4.7 (2-11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026lt;0,001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.9 (0.8-4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e3.4 (1.5-10.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.003*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e2.6 (0.7-8.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003epT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.6 (0.6-4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e2.4 (1.1-5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.02*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.2 (0.5-2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e3.5 (1.4-8.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.007*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e2.3 (0.5-10.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003epN+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e4 (1.6-9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e2.5 (1.1-6.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.03*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e3.9 (1.9-8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0,001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e2.2 (1.1-4.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e0.02*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e2.9 (1.2-7.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.02*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1.4 (0.5-3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003ePeritoneal involvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.4 (0.5-4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e1.6 (0.7-4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e3.1 (1.1-8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.02*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1.2 (0.4-3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003eShepherd\u0026rsquo;s 4 grade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e3.6 (1-14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.04*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e2.9 (1.1-9.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.04*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e2.7 (1.1-10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.05*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e2.1 (0.7-6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e7.3 (1.9-27.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e4.2 (1.2-16.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e0.04*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003epCRM+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e4.8 (1.3-17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.009*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e3.1 (1.1-8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.03*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e8.1 (2-32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e3.3 (1.4-8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e0.007*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e6.1 (1.7-21.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0.002*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e4.1 (1.1-15.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003e0.03*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eHazard ratio (95% CI)\u003c/p\u003e\n\u003cp\u003e* Statistically significant p-value (p\u0026lt;0.05)\u003c/p\u003e\n\u003cp\u003eAbbreviations: PR: peritoneal reflection; rm: refers to magnetic resonance-preoperative staging; T4: refers to T4 staging on TNM classification; CRM: circumferential resection margin; N+: positive adenophaties; CRT: \u0026nbsp;hemoradiotherapy; RBC: red blood cell; TME: total mesorrectal excision; p: refers to final pathological staging.\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":"rectal cancer, peritoneal reflection, peritoneal involvement, local recurrence, carcinomatosis","lastPublishedDoi":"10.21203/rs.3.rs-6297876/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6297876/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eTo assess the relevance of peritoneal reflection involvement in long-term oncological outcomes in patients with rectal cancer.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eprospective observational study from a specialized colorectal unit, that included a consecutive series of patients undergoing mesorectal excision for rectal cancer. PR involvement was evaluated on pathological examination using Shepherd’s classification. Overall survival (OS), disease-free survival (DFS) and local recurrence (LR) were assessed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003e160 patients were included in the present analysis. Peritoneal involvement was present in 28.2% of the 85 tumours above or at the level of PR. There were no differences in OS, DFS or LR according to tumour’s height location. The 5-year OS, DFS and LR for tumours involving PR were 58.3%, 61.7% and 30.3%, respectively. Patients with peritoneal involvement had a higher LR rate (p=0.02) and shorter OS (p=0.04). Shepherd’s grade 4 peritoneal involvement was an independent risk factor for OS (HR 2.9; 95% IC 1.1-9.5, p=0.04) and LR (HR 4.2; 95% IC 1.2-16.9, p=0.04).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eAfter rectal cancer resection, peritoneal involvement is an independent risk factor for local recurrence and poor survival.\u003c/p\u003e","manuscriptTitle":"Peritoneal reflection involvement as a prognostic factor in rectal cancer. Long-term oncological outcomes from a prospective study.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-16 08:55:44","doi":"10.21203/rs.3.rs-6297876/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-14T08:32:45+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-13T10:02:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"289042780235742900994140135615987326811","date":"2025-04-05T17:34:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"295233458138570507360244870133232984994","date":"2025-03-29T18:16:11+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-27T07:52:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-27T00:52:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-27T00:52:27+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Colorectal Disease","date":"2025-03-24T18:47:20+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":"7eb37ab6-08fc-4c51-b0da-7415f1f43b25","owner":[],"postedDate":"April 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-05-12T15:59:06+00:00","versionOfRecord":{"articleIdentity":"rs-6297876","link":"https://doi.org/10.1007/s00384-025-04909-7","journal":{"identity":"international-journal-of-colorectal-disease","isVorOnly":false,"title":"International Journal of Colorectal Disease"},"publishedOn":"2025-05-10 15:57:02","publishedOnDateReadable":"May 10th, 2025"},"versionCreatedAt":"2025-04-16 08:55:44","video":"","vorDoi":"10.1007/s00384-025-04909-7","vorDoiUrl":"https://doi.org/10.1007/s00384-025-04909-7","workflowStages":[]},"version":"v1","identity":"rs-6297876","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6297876","identity":"rs-6297876","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}