Prognostic value of peritoneal scar-like tissue in patients with peritoneal metastases of ovarian origin presenting for curative-intent cytoreductive surgery

Prognostic value of peritoneal scar-like tissue in patients with peritoneal metastases of ovarian origin presenting for curative-intent cytoreductive surgery | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prognostic value of peritoneal scar-like tissue in patients with peritoneal metastases of ovarian origin presenting for curative-intent cytoreductive surgery Antoine El Asmar, Florin Pop, Etienne El Helou, Pieter Demetter, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3110480/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Aug, 2023 Read the published version in World Journal of Surgical Oncology → Version 1 posted 7 You are reading this latest preprint version Abstract Background Complete cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC), remain the gold standard in the treatment of peritoneal metastases of ovarian cancer (PMOC). Given the increasing rate of neoadjuvant chemotherapy in patients with high PCI, prior abdominal surgeries, inflammation and fibrotic changes, the benefit of removing any “peritoneal scar-like tissues” (PST) during CRS, hasn’t been thoroughly investigated. Our objective in this retrospective cohort was to identify the proportion of malignant cells positivity in PST of patients with PMOC, undergoing curative-intent CRS ± HIPEC. Methods This is a retrospective study, conducted at our comprehensive cancer center, including patients with PMOC, presenting for curative-intent CRS. During CRS, benign-looking peritoneal lesions, lacking the typical hard nodular, aggressive, and invasive morphology, were systematically resected or electro fulgurated. PSTs were analyzed for the presence of tumoral cells by our pathologist. Correlations between the presence of PST and their positivity, and the different patients’ variables, were studied. Results In 51% of patients, PST harbored malignant cells. Those were associated with poorly differentiated serous tumors, a high PCI (> 8) and a worse DFS: 17 months in the positive PST group versus 29 months in the negative PST group ( p = 0.05 ), on univariate analysis. Multivariate analysis revealed that PCI > 8 and poorly differentiated primary tumor histology were correlated with a worse DFS, and that higher PCI and advanced FIGO were correlated with a worse OS. Conclusion Benign-looking PST harbors malignancy in 51% of cases. The benefit of their systematic resection and their prognostic value should be further investigated in larger cohorts. Ovarian cancer Peritoneal Carcinomatosis Peritoneal Fibroses Cytoreductive Surgery Prognostic Factors Figures Figure 1 Introduction Ovarian cancer (OC) is the most common cause of cancer-associated death in women, and is responsible for approximately 150,000 annual deaths worldwide ( 1 , 2 ). Around 75% present with advanced stages and a 5-year survival rate less than 50% ( 3 ). The peritoneal carcinomatosis index (PCI) and complete cytoreductive surgery (CRS) remain the most important prognostic factors in determining the survival of these patients ( 4 ). Attempts to downstage patients with a very high peritoneal disease burden prior to surgery, using neoadjuvant chemotherapy (NACT), revealed successful in decreasing surgery-related morbidities, by decreasing the extent of resections required to achieve complete cytoreduction (CCR-0) and achieving similar results to upfront surgery ( 5 ). Macroscopic complete cytoreduction (CCR-0) remains the pillar on which surgeons should rely in order to achieve the best patients’ outcome ( 6 ). Currently, intraoperative detection of tumor lesions involves palpation and visual inspection. Palpation limits the surgeon’s ability to identify non-palpable flat lesions, while visual inspection difficulty lies in poor tissue contrast and spatial resolution ( 7 ). Multiple studies attempted quantifying residual tumors in patients with PMOC, however, with the use of NACT, especially in cases with a high PCI, microscopically carcinomatous areas can present with a benign visual appearance. This leads to an underestimation of the tumoral spread, and hence potential incomplete resections ( 2 , 8 ). This has been reported as an argument by upfront protagonists as it allows resecting all visible disease before neoadjuvant treatment. However, the counter part is the lower rate of CCR-0 resection ( 9 ). A major concern in patients treated by NACT for peritoneal metastases of OC origin (PMOC) is the management of residual scar-like lesions. Moreover, many PMOC patients, who did not receive NACT, can present with scar-like lesions on their peritoneum, either due to previous surgeries, local inflammatory reactions, granulomas or fibrosis, or benign lesions. These peritoneal patches usually lack the typical nodular, granular, invasive morphology that PM have, and thus are usually considered benign and not subject to resection. At present, no clear rules exist concerning the intraoperative management of these lesions. Very few study have focused on the pathology of peritoneal scars and their prognostic role remains undetermined ( 2 , 7 , 9 , 10 ). More recently, intraoperative fluorescence imaging (FI) techniques have been used trying to increase residual tumor detection in ovarian cancer ( 10 ). van Dam et al. has reported encouraging results in a pilot study on folate-receptor-α positive ovarian cancer patients, using specific FI technique ( 11 ). Moreover, Veys et al. have reported the role of ICG-FI in detecting residual peritoneal disease. They were able to detect malignant cells in 68% of resected peritoneal scar tissue in patients with PMOC. ICG-FI revealed to be an accurate tool in identifying PM, however, given its relatively low positive predictive value of 57%, it was not able to discriminate between benign and malignant lesions post-NACT ( 10 ). The objective of this study was to identify the proportion of malignant cells positivity in peritoneal scar-like tissue (PST), in patients with PMOC, who underwent or not NACT, to evaluate if there are predictive factors for the presence of tumoral scars, and analyze the potential prognostic value of positive PST. Patients and methods Study design and population This is a retrospective study, conducted at our comprehensive cancer center, Institut Jules Bordet (Université Libre de Bruxelles – part of the “Hopitaux Universitaires de Bruxelles”, H.U.B.) including patients with PMOC, presenting for curative-intent CRS ± HIPEC, from 2012 until 2018. The study was approved by the ethical committee at Institut Jules Bordet (CE3375). Peritoneal scar-like tissue During CRS, benign-looking peritoneal lesions are systematically resected or electro fulgurated in all patients with PMOC. Visual and tactile inspection was undergone by the surgeon in order to categorize these lesions as “scar-like tissue” rather than “peritoneal metastases”, lacking the typical hard nodular, aggressive, and invasive morphology. Peritoneal scar-like tissue (PST) was defined using the following visual and tactile characteristics: Flat demarcated zone of the visceral or parietal peritoneum, Whitish discoloration, Absence of nodules or nodular formation, Soft, non-granular on palpation Flaccid, loose, non-rigid upon resection. These areas consisted mainly of residual scar tissue post-NACT, exhibiting partial or complete pathological response, or areas of postoperative adhesions, or fibrosis, or granulomas, in patients who did not undergo NACT prior to the CRS (Fig. 1 ). Typical lymphatic serosal discoloration on the small bowel or on the Glisson capsule were not included in this definition. Histopathological analysis All resected PSTs were sent to histopathological analysis. Upon inspection, the pathologist reported the presence or absence of malignant cells within each PST. Statistical analysis A descriptive analysis of the whole population was conducted. Pre-, intra-, and post-operative clinical, demographical and histopathological patients’ characteristics were included. The proportion of PST presence and PST positivity for malignant cells was calculated. Values are expressed as medians (interquartile range, IQR), means (standard deviations, SD), or the number of patients with percentages. Medians and means were compared using the Mann-Whitney U test and the Student’s t-test, respectively. Differences in proportions were evaluated using the chi-square test. We performed univariate and multivariate analyses to evaluate the correlations, first between the presence of PST and the different variables, and second between the positivity of PST and the different variables. Risk factors with a p < 0.1 were entered into the multivariate model. Disease-free survival (DFS) and overall survival (OS) were calculated for the whole population and for each group of patients separately (PST positive vs PST negative patients’ categories) using the Kaplan Meier method and the statistical significance was calculated using the log-rank test. The factors affecting survival were evaluated using a univariate and multivariate cox regression analysis. Proportional hazard regression results are reported using hazard ratios (HR) and corresponding 95% confidence intervals (Cis). Factors with a p value of < 0.05 in univariate analysis were entered to a multivariate cox regression model. A p < 0.05 was considered statistically significant. Statistical analyses were performed using SPSS VERSION 28. Results During the study period, 193 patients with PMOC underwent curative-intent CRS at our institution. The mean population age was 61 years, 69% had NACT for locally advanced disease, 12% were subject to HIPEC and the median preoperative PCI was 8. The majority presented with high grade serous ovarian cancer. An CCR-0 resection was achieved in 176 patients (91.2%), while 17 patients (8.8%) were subject to an R2a resection. On final pathology reports, 80% of patients were classified in the FIGO III category, versus 14% FIGO IVa and 6% FIGO II. The median DFS and OS for the whole population were 22 and 66 months respectively. The median follow-up time was 82 months (70.9–93.1). Patients characteristics are reported in Table 1 . Table 1 Patients’ pre-, intra-, and post-operative demographic, clinical and histopathological characteristics Variables N = 193 (%) Absence of PST N = 114 (59.1%)*** Presence of PST N = 79 (40.9%)*** p Negative PST N = 39 (49.3%)*** Positive PST N = 40 (50.7%)*** p Mean Age (± SD) in years 61 (± 12) 58.8 (± 11.9) 63.7 (± 11.7) 0.005 62.5 (12) 64.8 (11.4) 0.39 Median BMI [IQR] kg/m 2 23.8 [6] 23.8 [7] 23.8 [6] 0.91 24 [5] 23.6 [7] 0.91 ASA score I II III IV 11 (5.7) 138 (71.5) 44 (22.8) - 7 (6.1) 85 (74.6) 22 (19.3) - 4 (5.1) 53 (67.1) 22 (27.8) - 0.37 2 (5.2) 27 (69.2) 10 (25.6) - 2 (5) 26 (65) 12 (30) - 0.91 Median CA125 pre-NAC [IQR] u/ml 321 [820] 367 [877.5] 257 [803] 0.26 522 [1118] 210 [256.7] 0.58 Median CA125 post-NAC [IQR] u/ml 38 [139.5] 42.5 [210.7] 30 [87] 0.59 31 [142] 29 [60] 0.91 NAC Yes No 133 (69) 60 (31) 76 (66.7) 38 (33.3) 57 (72.2) 22 (27.8) 0.41 29 (74.4) 10 (25.6) 28 (70) 12 (30) 0.66 Median number of NAC cycles 3 [4] 3 [4] 3 [4] 0.94 3 [4] 3 [4] 0.75 FIGO stage* II III IVa** 12 (6.2) 153 (79.3) 28 (14.5) 9 (7.9) 88 (77.2) 17 (14.9) 3 (3.8) 65 (82.3) 11 (13.9) 0.48 3 (7.7) 31 (79.5) 5 (12.8) 0 34 (85) 6 (15) 0.20 Primary tumor histology Serous Other or mixed 169 (87.5) 24 (12.5) 100 (87.7) 14 (12.3) 69 (87.3) 10 (12.7) 0.93 31 (79.5) 8 (20.5) 38 (95) 2 (5) 0.038 Degree of differentiation Well Moderate Poor 27 (14) 27 (14) 139 (72) 15 (13.2) 18 (15.8) 81 (71) 12 (15.2) 9 (11.4) 58 (73.4) 0.66 10 (25.7) 5 (12.8) 24 (61.5) 2 (5) 4 (10) 34 (85) 0.028 Lymph nodes status Positive Negative 53 (27.6) 139 (72.4) 83 (72.8) 31 (27.2) 56 (71.8) 22 (28.2) 0.88 13 (34.2) 25 (65.8) 9 (22.5) 31 (77.5) 0.25 Median PCI [IQR] 8 [13] 9 [13] 7 [12] 0.38 5 [11] 9 [14] 0.03 HIPEC No Yes 170 (88.1) 23 (11.9) 107 (93.9) 7 (6.1) 63 (79.7) 16 (20.3) 0.003 30 (76.9) 9 (23.1) 33 (82.5) 7 (17.5) 0.53 Median intraoperative blood loss [IQR] in cc 1300 [1993] 1000 [1800] 1600 [2025] 0.043 1825 (2075) 1500 [1900] 0.39 Median CRS time [IQR] in min 326 [275] 283 [264] 390 [208] 0.001 406 [206] 380 [216] 0.12 CD complications No complications CD-I CD-II CD-IIIA CD-IIIB CD-IV CD-V 191 86 (45) 31 (16.2) 49 (25.7) 7 (3.7) 7 (3.7) 10 (5.2) 1 (0.5) 113 56 (49.5) 19 (16.8) 23 (20.4) 3 (2.7) 4 (3.5) 8 (7.1) 0 78 30 (38.5) 12 (15.4) 26 (33.3) 4 (5.1) 3 (3.8) 2 (2.6) 1 (1.3) 0.21 38 17 (44.7) 5 (13.2) 13 (34.2) 2 (5.3) 1 (2.6) 0 0 40 13 (32.5) 7 (17.5) 13 (32.5) 2 (5) 2 (5) 2 (5) 1 (2.5) 0.65 Median number of scar [IQR] - - 2 [2] - 2 [2] 2 [2] 0.94 Median DFS (95% CI) in months 22 (18.8–25.2) 22 (16.8–27.1) 22 (16.8–27.1) 0.88 29 (20.1–37.9) 17 (14.9–19) 0.05 Median OS (95% CI) in months 66 (58.9–73.1) 64 (49.8–78.1) 66 (56.3–75.6) 0.56 68 (43.2–92.8) 64 (48.4–79.6) 0.63 * FIGO stage reported on final pathology. ** Patients with FIGO IVa were included, with resectable peritoneal disease, and in whom CRS was complete. *** Relative Risk within the concerned category. (PST: Peritoneal Scar-like Tissue; SD: standard deviation; IQR: interquartile range; BMI: body mass index; PCI: peritoneal carcinomatosis index; ASA: American Society of Anesthesiologists; NAC: neoadjuvant chemotherapy, pre-cytoreductive surgery; HIPEC: hyperthermic intraperitoneal chemotherapy; CRS: cytoreductive surgery; CD: Clavien-Dindo) Peritoneal scar-like tissue Peritoneal scar-like tissue was found in 79 patients (40.9%). PSTs were harboring malignant cells in 40 patients (50.7%). Positive PSTs were associated with serous tumors, poorly differentiated, a high PCI (> 8) and a worse DFS: 17 months in the positive PST group versus 29 months in the negative PST group ( p = 0.05 ). However, none of these factors were independent predictors of PST positivity on multivariate analysis (Table 1 ). In the group of patients with PST , 57 (72%) were subject to NACT and 22 (28%) were not. In addition, amongst patients who received NACT, 28 (70%) had PST positive for tumoral cells, versus 12 (30%) patients with positive PST, amongst those who did not receive any neoadjuvant treatment. In terms of prognosis, an advanced FIGO stage, a PCI > 8, and poorly differentiated tumor histology were also associated with a worse DFS (HR = 2.62, 95% CI: 1.15–5.97, p = 0.02; HR = 1.97, 95% CI: 1.41–2.76, p 8, and poorly differentiated primary tumor histology, were significant independent variables correlated with an unfavorable DFS. Furthermore, only higher PCI (HR = 1.87, 95% CI: 1.2–2.9), and an advanced FIGO stage (HR = 3.4, 95% CI: 0.9–12.2) were predictors of worse OS on multivariate analysis (Table 2 ). Table 2 Univariate and Multivariate analyses of prognostic factors in patients with PMOC presenting for curative-intent CRS Variables DFS OS Univariate Mutlivariate Univariate Mutlivariate HR (95%CI) p HR (95%CI) p HR (95%CI) p HR (95%CI) p Age (cont) 1.01 (0.99–1.02) 0.35 1.01 (0.99–1.03) 0.19 BMI (cont) 1.00 (0.97–1.03) 0.91 1.01 (0.97–1.05) 0.76 CA125 pre-Tx > 321 u/ml 1.27 (0.91–1.77) 0.16 1.25 (0.85–1.85) 0.25 CA 125 post-Tx > 38 u/ml 1.11 (0.80–1.55) 0.51 1.39 (0.94–2.07) 0.09 1.13 (0.74–1.74) 0.57 NAC 0.88 (0.62–1.25) 0.47 0.93 (0.62–1.39) 0.73 FIGO III vs II IVa vs II 2.62 (1.15–5.97) 3.01 (1.21–7.44) 0.02 0.17 1.81 (0.78–4.24) 1.88 (0.73–4.82) 0.17 0.19 3.73 (1.17–11.8) 5.35 (1.56–18.3) 0.025 0.008 2.52 (0.76–8.31) 3.43 (0.96–12.27) 0.13 0.05 PCI > 8 1.97 (1.41–2.76) < 0.001 1.78 (1.25–2.53) 0.001 2.16 (1.45–3.24) < 0.001 1.87 (1.20–2.91) 0.005 Primary tumor histology: Serous vs Other or mixed 0.76 (0.44–1.31) 0.32 0.92 (0.50–1.69) 0.79 Degree of differentiation: Moderate vs well Poor vs well 2.04 (0.96–4.32) 2.20 (1.15–4.22) 0.06 0.01 2.04 (0.96–4.32) 2.03 (1.06–3.89) 0.06 0.03 2.51 (1.11–5.68) 1.84 (0.89–3.83) 0.027 0.099 2.19 (0.95–5.04) 1.53 (0.73–2.21) 0.06 0.26 Positive LN status 0.96 (0.67–1.38) 0.86 0.99 (0.65–1.50) 0.97 HIPEC 0.83 (0.47–1.46) 0.52 0.86 (0.44–1.65) 0.65 CD complication: CD 0-I-II vs CD III-IV 1.14 (0.71–1.83) 0.59 1.19 (0.69–2.03) 0.52 Positive PST 1.35 (0.92–1.99) 0.12 1.15 (0.77–1.70) 0.49 1.01 (0.62–1.61) 0.97 (BMI: body mass index; PCI: peritoneal carcinomatosis index; NAC: neoadjuvant chemotherapy, pre-cytoreductive surgery; LN: Lymph nodes; HIPEC: hyperthermic intraperitoneal chemotherapy; CRS: cytoreductive surgery; CD: Clavien-Dindo, PST: Peritoneal scar tissue). Discussion We hereby offer one of the first studies evaluating residual disease in peritoneal scars in patients treated by CRS ± HIPEC for ovarian cancer peritoneal metastases. We observed that around 51% of patients had microscopic residual disease in resected peritoneal scar-like lesions. The presence of positive peritoneal scar-like lesions were significantly associated with worse DFS on univariate analysis, 17 months for positive versus 29 months for negative PST. Given the need for new prognostic factors to optimize PMOC patients’ selection and management, every clinical, histopathological and anatomical aspect, capable of enhancing the outcome of curative-intent CRS, should to be further explored. PM from OC origin have a less aggressive behavior compared to those from colorectal or gastric origin, reason why patients with a relatively higher PCI are still eligible for surgery ( 12 , 13 ). This warrants a higher rate of gastrointestinal resections, splenectomies and peritonectomies in PMOC patients compared to others. Platine-based chemotherapy and complete cytoreductive surgery, upfront or interval, remain the pillars of treatment in patients with PMOC ( 4 , 14 ). Major prognostic factors remain the radicality of the CRS, PCI score, tumor histology and platinum-sensitivity, along with ascites and certain molecular expressions in ongoing investigations ( 15 – 17 ). This is corroborated by our study, reporting poorly differentiated tumors, advanced FIGO stage and high PCI score as independent prognostic factors in patients with PMOC. Very few studies focused on the possible role of residual tumoral cells in peritoneal scar-like tissue ( 2 , 10 , 18 ). Recently, we have reported the potential role of ICG-FI in detecting residual tumoral disease in peritoneal scars ( 10 ). Despite the fact that ICG-FI was able to detect tumoral cells with a sensitivity of 73%, the reported specificity was low (57%). The present study was aiming to analyze the rate and positivity of residual peritoneal scar-like tissue at pathology. It shows that benign-looking positive PST predict a worse median DFS (17 versus 29 months) on univariate analysis. However, it was not significant on multivariate analysis. Furthermore, we were not able to determine predictive factors for these PST positivity, especially when considering the group of patients with NACT versus those who did not take any neoadjuvant treatment. PST presence and positivity was not related to whether the patients received or not any type of NACT. This raises the question on whether PST should be systematically resected during CRS. At this stage, we still are unable to answer this question, and further studies on the effect of removing these PST are warranted. Our study has numerous weaknesses and biases, starting with its retrospective design. In practice, the results of this study are based on our surgical attitude tending towards systematic resection or electrofulguration of all PST. However, some patients in the early stages of the study period were not operated while following this strategy. Therefore, it is possible that the rate of PST is still underestimated. This could also explain the absence of significant results for positive PST at multivariate analysis, given that a subgroup of patients is still harboring positive scar-like tissue. In addition, an operator-dependent bias is also present, given that visual and tactile evaluations were performed by the surgeon and his fellow. However, we tended to categorize lesions as “PST” using a set of morphological characteristics devised by the oncologic surgeons. Still the results reported hereby, could constitute a modest foundation for further investigations in prospective studies. Moreover, the use of specific FI guided surgery in the future, should help the surgeons in detecting residual disease on a molecular level. Conclusion Benign-looking PST harbor cancerous cells in 51% of cases, and could represent a prognostic factor in patients with PMOC. A large prospective study on the role of PST in patients with PMOC, presenting for curative-intent cytoreductive surgery, to evaluate their exact prognostic value and the benefit of their resection, could respond to these questions. Declarations Funding: We disclose that we have not received any funding for this work from any of the following organizations: National Institutes of Health (NIH); Welcome Trust; Howard Hughes Medical Institute (HHMI); and other(s). Authors' contributions: Antoine El Asmar: Conceptualization; Data curation; Formal analysis; Methodology; Project administration; Investigation; Roles/Writing - original draft; Writing - review & editing. 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Available from: https://www.karger.com/Article/FullText/313823 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 28 Aug, 2023 Read the published version in World Journal of Surgical Oncology → Version 1 posted Editorial decision: Major revision 01 Jul, 2023 Reviews received at journal 27 Jun, 2023 Reviewers agreed at journal 27 Jun, 2023 Reviewers invited by journal 27 Jun, 2023 Editor assigned by journal 27 Jun, 2023 Submission checks completed at journal 27 Jun, 2023 First submitted to journal 26 Jun, 2023 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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Asmar","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFUlEQVRIie2Pv0rEQBCHJyyczYXtZI7A5RXmCIjicb5KloCVoKVg4cFBrORa5R7BRggslpEtbAy2e2hxeQDB624rNX8aJYnYCe5XzO4sv4/ZAbBY/iphUbbqhpcvJ115Vius7gfTQqEflC8npWVtF/hifr/K78bAGThrczQ5Dp5uxNuKwOfbaaOCL4qReDyEwQyY58poT+rXBD8/NrpehM1jdNRDESsgBeA5ktGOzm4LJaTnZsWvlHc4UMCMkecUXGXJpkuhSkmBGPTQlYqIX8rOKSMdBSTiqI/Kifdd+UCoXbkbErbuMtQiz008GfKLmVoaeUZ8niXLzenY517L+jV9AGdaXbFMYmf8Gzz9TdpisVj+AR9sTFiQHIB61QAAAABJRU5ErkJggg==","orcid":"","institution":"Institut Jules Bordet","correspondingAuthor":true,"prefix":"","firstName":"Antoine","middleName":"El","lastName":"Asmar","suffix":""},{"id":213531848,"identity":"8f9297e0-bae2-46d2-a23f-62bf7c959b12","order_by":1,"name":"Florin Pop","email":"","orcid":"","institution":"Institut Jules Bordet","correspondingAuthor":false,"prefix":"","firstName":"Florin","middleName":"","lastName":"Pop","suffix":""},{"id":213531849,"identity":"c74de6d2-26fe-4690-acec-29c6a4a473bc","order_by":2,"name":"Etienne El Helou","email":"","orcid":"","institution":"Institut Jules Bordet","correspondingAuthor":false,"prefix":"","firstName":"Etienne","middleName":"El","lastName":"Helou","suffix":""},{"id":213531850,"identity":"1f2a53e4-00ef-40e3-87d3-ebb579470a52","order_by":3,"name":"Pieter Demetter","email":"","orcid":"","institution":"Institut Jules Bordet","correspondingAuthor":false,"prefix":"","firstName":"Pieter","middleName":"","lastName":"Demetter","suffix":""},{"id":213531851,"identity":"5aecc4f8-7962-4e0a-83c9-0af4fba512bb","order_by":4,"name":"Isabelle Veys","email":"","orcid":"","institution":"Institut Jules Bordet","correspondingAuthor":false,"prefix":"","firstName":"Isabelle","middleName":"","lastName":"Veys","suffix":""},{"id":213531852,"identity":"3e22fea9-b9ca-4eaf-b627-ae959b66b820","order_by":5,"name":"Laura Polastro","email":"","orcid":"","institution":"Institut Jules Bordet","correspondingAuthor":false,"prefix":"","firstName":"Laura","middleName":"","lastName":"Polastro","suffix":""},{"id":213531853,"identity":"9aa4c03b-86f9-4daa-8905-7eab105708af","order_by":6,"name":"Ali Bohlok","email":"","orcid":"","institution":"Institut Jules Bordet","correspondingAuthor":false,"prefix":"","firstName":"Ali","middleName":"","lastName":"Bohlok","suffix":""},{"id":213531854,"identity":"e4729510-60db-4717-b8e2-3bca25df648e","order_by":7,"name":"Gabriel Liberale","email":"","orcid":"","institution":"Institut Jules Bordet","correspondingAuthor":false,"prefix":"","firstName":"Gabriel","middleName":"","lastName":"Liberale","suffix":""}],"badges":[],"createdAt":"2023-06-26 11:29:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3110480/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3110480/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12957-023-03153-z","type":"published","date":"2023-08-28T15:08:29+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":39331974,"identity":"7c341220-291e-4179-adf7-99379168afda","added_by":"auto","created_at":"2023-06-29 21:42:08","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1900397,"visible":true,"origin":"","legend":"\u003cp\u003eBenign peritoneal scar-like tissue (A) versus malignant peritoneal scar-like tissue (B), as confirmed by pathology examination, on the mesocolon of a patient presenting with PMOC.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3110480/v1/388d04ace6fef25307a34dd3.png"},{"id":42781888,"identity":"d45e76a5-4caf-45c4-9caf-e4cc5ad4c2bd","added_by":"auto","created_at":"2023-09-07 15:14:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1904076,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3110480/v1/a2a8beda-ef59-47b3-96b1-1ab7c8b9b710.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prognostic value of peritoneal scar-like tissue in patients with peritoneal metastases of ovarian origin presenting for curative-intent cytoreductive surgery","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOvarian cancer (OC) is the most common cause of cancer-associated death in women, and is responsible for approximately 150,000 annual deaths worldwide (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Around 75% present with advanced stages and a 5-year survival rate less than 50% (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). The peritoneal carcinomatosis index (PCI) and complete cytoreductive surgery (CRS) remain the most important prognostic factors in determining the survival of these patients (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Attempts to downstage patients with a very high peritoneal disease burden prior to surgery, using neoadjuvant chemotherapy (NACT), revealed successful in decreasing surgery-related morbidities, by decreasing the extent of resections required to achieve complete cytoreduction (CCR-0) and achieving similar results to upfront surgery (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Macroscopic complete cytoreduction (CCR-0) remains the pillar on which surgeons should rely in order to achieve the best patients\u0026rsquo; outcome (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCurrently, intraoperative detection of tumor lesions involves palpation and visual inspection. Palpation limits the surgeon\u0026rsquo;s ability to identify non-palpable flat lesions, while visual inspection difficulty lies in poor tissue contrast and spatial resolution (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Multiple studies attempted quantifying residual tumors in patients with PMOC, however, with the use of NACT, especially in cases with a high PCI, microscopically carcinomatous areas can present with a benign visual appearance. This leads to an underestimation of the tumoral spread, and hence potential incomplete resections (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). This has been reported as an argument by upfront protagonists as it allows resecting all visible disease before neoadjuvant treatment. However, the counter part is the lower rate of CCR-0 resection (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA major concern in patients treated by NACT for peritoneal metastases of OC origin (PMOC) is the management of residual scar-like lesions. Moreover, many PMOC patients, who did not receive NACT, can present with scar-like lesions on their peritoneum, either due to previous surgeries, local inflammatory reactions, granulomas or fibrosis, or benign lesions. These peritoneal patches usually lack the typical nodular, granular, invasive morphology that PM have, and thus are usually considered benign and not subject to resection. At present, no clear rules exist concerning the intraoperative management of these lesions. Very few study have focused on the pathology of peritoneal scars and their prognostic role remains undetermined (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMore recently, intraoperative fluorescence imaging (FI) techniques have been used trying to increase residual tumor detection in ovarian cancer (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). van Dam et al. has reported encouraging results in a pilot study on folate-receptor-α positive ovarian cancer patients, using specific FI technique (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Moreover, Veys et al. have reported the role of ICG-FI in detecting residual peritoneal disease. They were able to detect malignant cells in 68% of resected peritoneal scar tissue in patients with PMOC. ICG-FI revealed to be an accurate tool in identifying PM, however, given its relatively low positive predictive value of 57%, it was not able to discriminate between benign and malignant lesions post-NACT (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe objective of this study was to identify the proportion of malignant cells positivity in peritoneal scar-like tissue (PST), in patients with PMOC, who underwent or not NACT, to evaluate if there are predictive factors for the presence of tumoral scars, and analyze the potential prognostic value of positive PST.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and population\u003c/h2\u003e \u003cp\u003eThis is a retrospective study, conducted at our comprehensive cancer center, Institut Jules Bordet (Universit\u0026eacute; Libre de Bruxelles \u0026ndash; part of the \u0026ldquo;Hopitaux Universitaires de Bruxelles\u0026rdquo;, H.U.B.) including patients with PMOC, presenting for curative-intent CRS\u0026thinsp;\u0026plusmn;\u0026thinsp;HIPEC, from 2012 until 2018. The study was approved by the ethical committee at Institut Jules Bordet (CE3375).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePeritoneal scar-like tissue\u003c/h2\u003e \u003cp\u003eDuring CRS, benign-looking peritoneal lesions are systematically resected or electro fulgurated in all patients with PMOC. Visual and tactile inspection was undergone by the surgeon in order to categorize these lesions as \u0026ldquo;scar-like tissue\u0026rdquo; rather than \u0026ldquo;peritoneal metastases\u0026rdquo;, lacking the typical hard nodular, aggressive, and invasive morphology.\u003c/p\u003e \u003cp\u003ePeritoneal scar-like tissue (PST) was defined using the following visual and tactile characteristics:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eFlat demarcated zone of the visceral or parietal peritoneum,\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eWhitish discoloration,\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAbsence of nodules or nodular formation,\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eSoft, non-granular on palpation\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eFlaccid, loose, non-rigid upon resection.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eThese areas consisted mainly of residual scar tissue post-NACT, exhibiting partial or complete pathological response, or areas of postoperative adhesions, or fibrosis, or granulomas, in patients who did not undergo NACT prior to the CRS (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Typical lymphatic serosal discoloration on the small bowel or on the Glisson capsule were not included in this definition.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eHistopathological analysis\u003c/h2\u003e \u003cp\u003eAll resected PSTs were sent to histopathological analysis. Upon inspection, the pathologist reported the presence or absence of malignant cells within each PST.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eA descriptive analysis of the whole population was conducted. Pre-, intra-, and post-operative clinical, demographical and histopathological patients\u0026rsquo; characteristics were included. The proportion of \u003cem\u003ePST presence\u003c/em\u003e and \u003cem\u003ePST positivity\u003c/em\u003e for malignant cells was calculated. Values are expressed as medians (interquartile range, IQR), means (standard deviations, SD), or the number of patients with percentages. Medians and means were compared using the Mann-Whitney U test and the Student\u0026rsquo;s t-test, respectively. Differences in proportions were evaluated using the chi-square test. We performed univariate and multivariate analyses to evaluate the correlations, first between the presence of PST and the different variables, and second between the positivity of PST and the different variables. Risk factors with a \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.1\u003c/em\u003e were entered into the multivariate model. Disease-free survival (DFS) and overall survival (OS) were calculated for the whole population and for each group of patients separately (PST positive vs PST negative patients\u0026rsquo; categories) using the Kaplan Meier method and the statistical significance was calculated using the log-rank test. The factors affecting survival were evaluated using a univariate and multivariate cox regression analysis. Proportional hazard regression results are reported using hazard ratios (HR) and corresponding 95% confidence intervals (Cis). Factors with a \u003cem\u003ep\u003c/em\u003e value of \u0026lt;\u0026thinsp;0.05 in univariate analysis were entered to a multivariate cox regression model. A \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/em\u003e was considered statistically significant. Statistical analyses were performed using SPSS VERSION 28.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eDuring the study period, 193 patients with PMOC underwent curative-intent CRS at our institution. The mean population age was 61 years, 69% had NACT for locally advanced disease, 12% were subject to HIPEC and the median preoperative PCI was 8. The majority presented with high grade serous ovarian cancer. An CCR-0 resection was achieved in 176 patients (91.2%), while 17 patients (8.8%) were subject to an R2a resection. On final pathology reports, 80% of patients were classified in the FIGO III category, versus 14% FIGO IVa and 6% FIGO II. The median DFS and OS for the whole population were 22 and 66 months respectively. The median follow-up time was 82 months (70.9\u0026ndash;93.1). Patients characteristics are reported in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatients\u0026rsquo; pre-, intra-, and post-operative demographic, clinical and histopathological characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eVariables\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eN\u0026thinsp;=\u0026thinsp;193 (%)\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAbsence of PST\u003c/span\u003e\u003c/p\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eN\u0026thinsp;=\u0026thinsp;114 (59.1%)***\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePresence of PST\u003c/span\u003e\u003c/p\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eN\u0026thinsp;=\u0026thinsp;79 (40.9%)***\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNegative PST\u003c/span\u003e\u003c/p\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eN\u0026thinsp;=\u0026thinsp;39 (49.3%)***\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePositive PST\u003c/span\u003e\u003c/p\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eN\u0026thinsp;=\u0026thinsp;40 (50.7%)***\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean Age (\u0026plusmn;\u0026thinsp;SD) in years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (\u0026plusmn;\u0026thinsp;12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58.8 (\u0026plusmn;\u0026thinsp;11.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63.7 (\u0026plusmn;\u0026thinsp;11.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e62.5 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e64.8 (11.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e0.39\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian BMI [IQR] kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.8 [6]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.8 [7]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.8 [6]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.91\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e24 [5]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e23.6 [7]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e0.91\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASA score\u003c/p\u003e \u003cp\u003eI\u003c/p\u003e \u003cp\u003eII\u003c/p\u003e \u003cp\u003eIII\u003c/p\u003e \u003cp\u003eIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (5.7)\u003c/p\u003e \u003cp\u003e138 (71.5)\u003c/p\u003e \u003cp\u003e44 (22.8)\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (6.1)\u003c/p\u003e \u003cp\u003e85 (74.6)\u003c/p\u003e \u003cp\u003e22 (19.3)\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (5.1)\u003c/p\u003e \u003cp\u003e53 (67.1)\u003c/p\u003e \u003cp\u003e22 (27.8)\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.37\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (5.2)\u003c/p\u003e \u003cp\u003e27 (69.2)\u003c/p\u003e \u003cp\u003e10 (25.6)\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 (5)\u003c/p\u003e \u003cp\u003e26 (65)\u003c/p\u003e \u003cp\u003e12 (30)\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e0.91\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian CA125 pre-NAC [IQR] u/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e321 [820]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e367 [877.5]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e257 [803]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.26\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e522 [1118]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e210 [256.7]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e0.58\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian CA125 post-NAC [IQR] u/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 [139.5]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.5 [210.7]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 [87]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.59\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31 [142]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e29 [60]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e0.91\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNAC\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e133 (69)\u003c/p\u003e \u003cp\u003e60 (31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76 (66.7)\u003c/p\u003e \u003cp\u003e38 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57 (72.2)\u003c/p\u003e \u003cp\u003e22 (27.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.41\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e29 (74.4)\u003c/p\u003e \u003cp\u003e10 (25.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e28 (70)\u003c/p\u003e \u003cp\u003e12 (30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e0.66\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian number of NAC cycles\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 [4]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 [4]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 [4]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.94\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 [4]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3 [4]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e0.75\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFIGO stage*\u003c/p\u003e \u003cp\u003eII\u003c/p\u003e \u003cp\u003eIII\u003c/p\u003e \u003cp\u003eIVa**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (6.2)\u003c/p\u003e \u003cp\u003e153 (79.3)\u003c/p\u003e \u003cp\u003e28 (14.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (7.9)\u003c/p\u003e \u003cp\u003e88 (77.2)\u003c/p\u003e \u003cp\u003e17 (14.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (3.8)\u003c/p\u003e \u003cp\u003e65 (82.3)\u003c/p\u003e \u003cp\u003e11 (13.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.48\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 (7.7)\u003c/p\u003e \u003cp\u003e31 (79.5)\u003c/p\u003e \u003cp\u003e5 (12.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e34 (85)\u003c/p\u003e \u003cp\u003e6 (15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e0.20\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary tumor histology\u003c/p\u003e \u003cp\u003eSerous\u003c/p\u003e \u003cp\u003eOther or mixed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e169 (87.5)\u003c/p\u003e \u003cp\u003e24 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (87.7)\u003c/p\u003e \u003cp\u003e14 (12.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e69 (87.3)\u003c/p\u003e \u003cp\u003e10 (12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.93\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31 (79.5)\u003c/p\u003e \u003cp\u003e8 (20.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e38 (95)\u003c/p\u003e \u003cp\u003e2 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.038\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDegree of differentiation\u003c/p\u003e \u003cp\u003eWell\u003c/p\u003e \u003cp\u003eModerate\u003c/p\u003e \u003cp\u003ePoor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (14)\u003c/p\u003e \u003cp\u003e27 (14)\u003c/p\u003e \u003cp\u003e139 (72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (13.2)\u003c/p\u003e \u003cp\u003e18 (15.8)\u003c/p\u003e \u003cp\u003e81 (71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (15.2)\u003c/p\u003e \u003cp\u003e9 (11.4)\u003c/p\u003e \u003cp\u003e58 (73.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.66\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10 (25.7)\u003c/p\u003e \u003cp\u003e5 (12.8)\u003c/p\u003e \u003cp\u003e24 (61.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 (5)\u003c/p\u003e \u003cp\u003e4 (10)\u003c/p\u003e \u003cp\u003e34 (85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.028\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymph nodes status\u003c/p\u003e \u003cp\u003ePositive\u003c/p\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (27.6)\u003c/p\u003e \u003cp\u003e139 (72.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83 (72.8)\u003c/p\u003e \u003cp\u003e31 (27.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56 (71.8)\u003c/p\u003e \u003cp\u003e22 (28.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.88\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13 (34.2)\u003c/p\u003e \u003cp\u003e25 (65.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9 (22.5)\u003c/p\u003e \u003cp\u003e31 (77.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e0.25\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian PCI [IQR]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 [13]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 [13]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 [12]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.38\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5 [11]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9 [14]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.03\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHIPEC\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e170 (88.1)\u003c/p\u003e \u003cp\u003e23 (11.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e107 (93.9)\u003c/p\u003e \u003cp\u003e7 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63 (79.7)\u003c/p\u003e \u003cp\u003e16 (20.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30 (76.9)\u003c/p\u003e \u003cp\u003e9 (23.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e33 (82.5)\u003c/p\u003e \u003cp\u003e7 (17.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e0.53\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian intraoperative blood loss [IQR] in cc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1300 [1993]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1000 [1800]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1600 [2025]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.043\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1825 (2075)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1500 [1900]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e0.39\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian CRS time [IQR] in min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e326 [275]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e283 [264]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e390 [208]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e406 [206]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e380 [216]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e0.12\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD complications\u003c/p\u003e \u003cp\u003eNo complications\u003c/p\u003e \u003cp\u003eCD-I\u003c/p\u003e \u003cp\u003eCD-II\u003c/p\u003e \u003cp\u003eCD-IIIA\u003c/p\u003e \u003cp\u003eCD-IIIB\u003c/p\u003e \u003cp\u003eCD-IV\u003c/p\u003e \u003cp\u003eCD-V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e191\u003c/p\u003e \u003cp\u003e86 (45)\u003c/p\u003e \u003cp\u003e31 (16.2)\u003c/p\u003e \u003cp\u003e49 (25.7)\u003c/p\u003e \u003cp\u003e7 (3.7)\u003c/p\u003e \u003cp\u003e7 (3.7)\u003c/p\u003e \u003cp\u003e10 (5.2)\u003c/p\u003e \u003cp\u003e1 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e113\u003c/p\u003e \u003cp\u003e56 (49.5)\u003c/p\u003e \u003cp\u003e19 (16.8)\u003c/p\u003e \u003cp\u003e23 (20.4)\u003c/p\u003e \u003cp\u003e3 (2.7)\u003c/p\u003e \u003cp\u003e4 (3.5)\u003c/p\u003e \u003cp\u003e8 (7.1)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78\u003c/p\u003e \u003cp\u003e30 (38.5)\u003c/p\u003e \u003cp\u003e12 (15.4)\u003c/p\u003e \u003cp\u003e26 (33.3)\u003c/p\u003e \u003cp\u003e4 (5.1)\u003c/p\u003e \u003cp\u003e3 (3.8)\u003c/p\u003e \u003cp\u003e2 (2.6)\u003c/p\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.21\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e38\u003c/p\u003e \u003cp\u003e17 (44.7)\u003c/p\u003e \u003cp\u003e5 (13.2)\u003c/p\u003e \u003cp\u003e13 (34.2)\u003c/p\u003e \u003cp\u003e2 (5.3)\u003c/p\u003e \u003cp\u003e1 (2.6)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e40\u003c/p\u003e \u003cp\u003e13 (32.5)\u003c/p\u003e \u003cp\u003e7 (17.5)\u003c/p\u003e \u003cp\u003e13 (32.5)\u003c/p\u003e \u003cp\u003e2 (5)\u003c/p\u003e \u003cp\u003e2 (5)\u003c/p\u003e \u003cp\u003e2 (5)\u003c/p\u003e \u003cp\u003e1 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e0.65\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian number of scar [IQR]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 [2]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 [2]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 [2]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e0.94\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian DFS (95% CI) in months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (18.8\u0026ndash;25.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (16.8\u0026ndash;27.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (16.8\u0026ndash;27.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.88\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e29 (20.1\u0026ndash;37.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e17 (14.9\u0026ndash;19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian OS (95% CI) in months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66 (58.9\u0026ndash;73.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64 (49.8\u0026ndash;78.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66 (56.3\u0026ndash;75.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.56\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e68 (43.2\u0026ndash;92.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e64 (48.4\u0026ndash;79.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e0.63\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003cem\u003e* FIGO stage reported on final pathology.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003cem\u003e** Patients with FIGO IVa were included, with resectable peritoneal disease, and in whom CRS was complete.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003cem\u003e*** Relative Risk within the concerned category.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003cem\u003e(PST: Peritoneal Scar-like Tissue; SD: standard deviation; IQR: interquartile range; BMI: body mass index; PCI: peritoneal carcinomatosis index; ASA: American Society of Anesthesiologists; NAC: neoadjuvant chemotherapy, pre-cytoreductive surgery; HIPEC: hyperthermic intraperitoneal chemotherapy; CRS: cytoreductive surgery; CD: Clavien-Dindo)\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePeritoneal scar-like tissue\u003c/h2\u003e \u003cp\u003ePeritoneal scar-like tissue was found in 79 patients (40.9%). PSTs were harboring malignant cells in 40 patients (50.7%). Positive PSTs were associated with serous tumors, poorly differentiated, a high PCI (\u0026gt;\u0026thinsp;8) and a worse DFS: 17 months in the \u003cem\u003epositive PST group\u003c/em\u003e versus 29 months in the \u003cem\u003enegative PST group\u003c/em\u003e (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.05\u003c/em\u003e). However, none of these factors were independent predictors of PST positivity on multivariate analysis (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In the group of patients \u003cem\u003ewith PST\u003c/em\u003e, 57 (72%) were subject to NACT and 22 (28%) were not. In addition, amongst patients who received NACT, 28 (70%) had PST positive for tumoral cells, versus 12 (30%) patients with positive PST, amongst those who did not receive any neoadjuvant treatment.\u003c/p\u003e \u003cp\u003eIn terms of prognosis, an advanced FIGO stage, a PCI\u0026thinsp;\u0026gt;\u0026thinsp;8, and poorly differentiated tumor histology were also associated with a worse DFS (HR\u0026thinsp;=\u0026thinsp;2.62, 95% CI: 1.15\u0026ndash;5.97, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.02;\u003c/em\u003e HR\u0026thinsp;=\u0026thinsp;1.97, 95% CI: 1.41\u0026ndash;2.76, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e; HR\u0026thinsp;=\u0026thinsp;2.2, 95% CI: 1.15\u0026ndash;4.22, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.01\u003c/em\u003e, respectively) on univariate analysis. Multivariate analysis revealed that PCI\u0026thinsp;\u0026gt;\u0026thinsp;8, and poorly differentiated primary tumor histology, were significant independent variables correlated with an unfavorable DFS. Furthermore, only higher PCI (HR\u0026thinsp;=\u0026thinsp;1.87, 95% CI: 1.2\u0026ndash;2.9), and an advanced FIGO stage (HR\u0026thinsp;=\u0026thinsp;3.4, 95% CI: 0.9\u0026ndash;12.2) were predictors of worse OS on multivariate analysis (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate and Multivariate analyses of prognostic factors in patients with PMOC presenting for curative-intent CRS\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eDFS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnivariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMutlivariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eUnivariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eMutlivariate\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR (95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHR (95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHR (95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHR (95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (cont)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.01 (0.99\u0026ndash;1.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e0.35\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.01 (0.99\u0026ndash;1.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003e0.19\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (cont)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.00 (0.97\u0026ndash;1.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e0.91\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.01 (0.97\u0026ndash;1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003e0.76\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCA125 pre-Tx\u0026thinsp;\u0026gt;\u0026thinsp;321 u/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.27 (0.91\u0026ndash;1.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e0.16\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.25 (0.85\u0026ndash;1.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003e0.25\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCA 125 post-Tx\u0026thinsp;\u0026gt;\u0026thinsp;38 u/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.11 (0.80\u0026ndash;1.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e0.51\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.39 (0.94\u0026ndash;2.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003e0.09\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1.13 (0.74\u0026ndash;1.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cem\u003e0.57\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNAC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.88 (0.62\u0026ndash;1.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e0.47\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.93 (0.62\u0026ndash;1.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003e0.73\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFIGO\u003c/p\u003e \u003cp\u003eIII vs II\u003c/p\u003e \u003cp\u003eIVa vs II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.62 (1.15\u0026ndash;5.97)\u003c/p\u003e \u003cp\u003e3.01 (1.21\u0026ndash;7.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e0.17\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.81 (0.78\u0026ndash;4.24)\u003c/p\u003e \u003cp\u003e1.88 (0.73\u0026ndash;4.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.17\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e0.19\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.73 (1.17\u0026ndash;11.8)\u003c/p\u003e \u003cp\u003e5.35 (1.56\u0026ndash;18.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.025\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e0.008\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.52 (0.76\u0026ndash;8.31)\u003c/p\u003e \u003cp\u003e3.43 (0.96\u0026ndash;12.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cem\u003e0.13\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e0.05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePCI\u0026thinsp;\u0026gt;\u0026thinsp;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.97 (1.41\u0026ndash;2.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.78 (1.25\u0026ndash;2.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.16 (1.45\u0026ndash;3.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1.87 (1.20\u0026ndash;2.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary tumor histology:\u003c/p\u003e \u003cp\u003eSerous vs Other or mixed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.76 (0.44\u0026ndash;1.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e0.32\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.92 (0.50\u0026ndash;1.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003e0.79\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDegree of differentiation:\u003c/p\u003e \u003cp\u003eModerate vs well\u003c/p\u003e \u003cp\u003ePoor vs well\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.04 (0.96\u0026ndash;4.32)\u003c/p\u003e \u003cp\u003e2.20 (1.15\u0026ndash;4.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e0.06\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.04 (0.96\u0026ndash;4.32)\u003c/p\u003e \u003cp\u003e2.03 (1.06\u0026ndash;3.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.06\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e0.03\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.51 (1.11\u0026ndash;5.68)\u003c/p\u003e \u003cp\u003e1.84 (0.89\u0026ndash;3.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.027\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e0.099\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.19 (0.95\u0026ndash;5.04)\u003c/p\u003e \u003cp\u003e1.53 (0.73\u0026ndash;2.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cem\u003e0.06\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e0.26\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive LN status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.96 (0.67\u0026ndash;1.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e0.86\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.99 (0.65\u0026ndash;1.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003e0.97\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHIPEC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.83 (0.47\u0026ndash;1.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e0.52\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.86 (0.44\u0026ndash;1.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003e0.65\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD complication:\u003c/p\u003e \u003cp\u003eCD 0-I-II vs CD III-IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.14 (0.71\u0026ndash;1.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e0.59\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.19 (0.69\u0026ndash;2.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003e0.52\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive PST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.35 (0.92\u0026ndash;1.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e0.12\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.15 (0.77\u0026ndash;1.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.49\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.01 (0.62\u0026ndash;1.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003e0.97\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u003cem\u003e(BMI: body mass index; PCI: peritoneal carcinomatosis index; NAC: neoadjuvant chemotherapy, pre-cytoreductive surgery; LN: Lymph nodes; HIPEC: hyperthermic intraperitoneal chemotherapy; CRS: cytoreductive surgery; CD: Clavien-Dindo, PST: Peritoneal scar tissue).\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe hereby offer one of the first studies evaluating residual disease in peritoneal scars in patients treated by CRS\u0026thinsp;\u0026plusmn;\u0026thinsp;HIPEC for ovarian cancer peritoneal metastases. We observed that around 51% of patients had microscopic residual disease in resected peritoneal scar-like lesions. The presence of positive peritoneal scar-like lesions were significantly associated with worse DFS on univariate analysis, 17 months for positive versus 29 months for negative PST.\u003c/p\u003e \u003cp\u003eGiven the need for new prognostic factors to optimize PMOC patients\u0026rsquo; selection and management, every clinical, histopathological and anatomical aspect, capable of enhancing the outcome of curative-intent CRS, should to be further explored.\u003c/p\u003e \u003cp\u003ePM from OC origin have a less aggressive behavior compared to those from colorectal or gastric origin, reason why patients with a relatively higher PCI are still eligible for surgery (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). This warrants a higher rate of gastrointestinal resections, splenectomies and peritonectomies in PMOC patients compared to others. Platine-based chemotherapy and complete cytoreductive surgery, upfront or interval, remain the pillars of treatment in patients with PMOC (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Major prognostic factors remain the radicality of the CRS, PCI score, tumor histology and platinum-sensitivity, along with ascites and certain molecular expressions in ongoing investigations (\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). This is corroborated by our study, reporting poorly differentiated tumors, advanced FIGO stage and high PCI score as independent prognostic factors in patients with PMOC.\u003c/p\u003e \u003cp\u003eVery few studies focused on the possible role of residual tumoral cells in peritoneal scar-like tissue (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Recently, we have reported the potential role of ICG-FI in detecting residual tumoral disease in peritoneal scars (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Despite the fact that ICG-FI was able to detect tumoral cells with a sensitivity of 73%, the reported specificity was low (57%).\u003c/p\u003e \u003cp\u003eThe present study was aiming to analyze the rate and positivity of residual peritoneal scar-like tissue at pathology. It shows that benign-looking positive PST predict a worse median DFS (17 versus 29 months) on univariate analysis. However, it was not significant on multivariate analysis. Furthermore, we were not able to determine predictive factors for these PST positivity, especially when considering the group of patients with NACT versus those who did not take any neoadjuvant treatment. PST presence and positivity was not related to whether the patients received or not any type of NACT. This raises the question on whether PST should be systematically resected during CRS. At this stage, we still are unable to answer this question, and further studies on the effect of removing these PST are warranted.\u003c/p\u003e \u003cp\u003eOur study has numerous weaknesses and biases, starting with its retrospective design. In practice, the results of this study are based on our surgical attitude tending towards systematic resection or electrofulguration of all PST. However, some patients in the early stages of the study period were not operated while following this strategy. Therefore, it is possible that the rate of PST is still underestimated. This could also explain the absence of significant results for positive PST at multivariate analysis, given that a subgroup of patients is still harboring positive scar-like tissue. In addition, an operator-dependent bias is also present, given that visual and tactile evaluations were performed by the surgeon and his fellow. However, we tended to categorize lesions as \u0026ldquo;PST\u0026rdquo; using a set of morphological characteristics devised by the oncologic surgeons.\u003c/p\u003e \u003cp\u003eStill the results reported hereby, could constitute a modest foundation for further investigations in prospective studies. Moreover, the use of specific FI guided surgery in the future, should help the surgeons in detecting residual disease on a molecular level.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eBenign-looking PST harbor cancerous cells in 51% of cases, and could represent a prognostic factor in patients with PMOC. A large prospective study on the role of PST in patients with PMOC, presenting for curative-intent cytoreductive surgery, to evaluate their exact prognostic value and the benefit of their resection, could respond to these questions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eWe disclose that we have not received any funding for this work from any of the following organizations: National Institutes of Health (NIH); Welcome Trust; Howard Hughes Medical Institute (HHMI); and other(s).\u003c/p\u003e\u003ch2\u003eAuthors' contributions:\u003c/h2\u003e \u003cp\u003eAntoine El Asmar: Conceptualization; Data curation; Formal analysis; Methodology; Project administration; Investigation; Roles/Writing - original draft; Writing - review \u0026amp; editing.\u003c/p\u003e\u003ch2\u003eAvailability of data and materials:\u003c/h2\u003e \u003cp\u003eResearch data supporting this publication is available upon Editor\u0026rsquo;s request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003evan Baal JOAM, van Noorden CJF, Nieuwland R, Van de Vijver KK, Sturk A, van Driel WJ, et al. 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Oncol Res Treat [Internet]. 2010 [cited 2022 Jun 13];33(6):324\u0026ndash;30. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.karger.com/Article/FullText/313823\u003c/span\u003e\u003cspan address=\"https://www.karger.com/Article/FullText/313823\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"world-journal-of-surgical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjso","sideBox":"Learn more about [World Journal of Surgical Oncology](http://wjso.biomedcentral.com)","snPcode":"12957","submissionUrl":"https://submission.nature.com/new-submission/12957/3","title":"World Journal of Surgical Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Ovarian cancer, Peritoneal Carcinomatosis, Peritoneal Fibroses, Cytoreductive Surgery, Prognostic Factors","lastPublishedDoi":"10.21203/rs.3.rs-3110480/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3110480/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eComplete cytoreductive surgery (CRS)\u0026thinsp;\u0026plusmn;\u0026thinsp;hyperthermic intraperitoneal chemotherapy (HIPEC), remain the gold standard in the treatment of peritoneal metastases of ovarian cancer (PMOC). Given the increasing rate of neoadjuvant chemotherapy in patients with high PCI, prior abdominal surgeries, inflammation and fibrotic changes, the benefit of removing any \u0026ldquo;peritoneal scar-like tissues\u0026rdquo; (PST) during CRS, hasn\u0026rsquo;t been thoroughly investigated. Our objective in this retrospective cohort was to identify the proportion of malignant cells positivity in PST of patients with PMOC, undergoing curative-intent CRS\u0026thinsp;\u0026plusmn;\u0026thinsp;HIPEC.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis is a retrospective study, conducted at our comprehensive cancer center, including patients with PMOC, presenting for curative-intent CRS. During CRS, benign-looking peritoneal lesions, lacking the typical hard nodular, aggressive, and invasive morphology, were systematically resected or electro fulgurated. PSTs were analyzed for the presence of tumoral cells by our pathologist. Correlations between the presence of PST and their positivity, and the different patients\u0026rsquo; variables, were studied.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eIn 51% of patients, PST harbored malignant cells. Those were associated with poorly differentiated serous tumors, a high PCI (\u0026gt;\u0026thinsp;8) and a worse DFS: 17 months in the \u003cem\u003epositive PST group\u003c/em\u003e versus 29 months in the \u003cem\u003enegative PST group\u003c/em\u003e (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.05\u003c/em\u003e), on univariate analysis. Multivariate analysis revealed that PCI\u0026thinsp;\u0026gt;\u0026thinsp;8 and poorly differentiated primary tumor histology were correlated with a worse DFS, and that higher PCI and advanced FIGO were correlated with a worse OS.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eBenign-looking PST harbors malignancy in 51% of cases. The benefit of their systematic resection and their prognostic value should be further investigated in larger cohorts.\u003c/p\u003e","manuscriptTitle":"Prognostic value of peritoneal scar-like tissue in patients with peritoneal metastases of ovarian origin presenting for curative-intent cytoreductive surgery","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-06-29 21:42:03","doi":"10.21203/rs.3.rs-3110480/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2023-07-02T03:16:16+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-06-28T00:55:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"d0a33ca9-0f40-405f-b5ec-c697f2adafe6","date":"2023-06-28T00:02:11+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-06-27T21:08:04+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-06-27T13:01:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-06-27T06:30:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"World Journal of Surgical Oncology","date":"2023-06-26T11:22:13+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"world-journal-of-surgical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjso","sideBox":"Learn more about [World Journal of Surgical Oncology](http://wjso.biomedcentral.com)","snPcode":"12957","submissionUrl":"https://submission.nature.com/new-submission/12957/3","title":"World Journal of Surgical Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"90d8312f-8289-4b86-9a9e-95ec128ef304","owner":[],"postedDate":"June 29th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-09-07T15:11:23+00:00","versionOfRecord":{"articleIdentity":"rs-3110480","link":"https://doi.org/10.1186/s12957-023-03153-z","journal":{"identity":"world-journal-of-surgical-oncology","isVorOnly":false,"title":"World Journal of Surgical Oncology"},"publishedOn":"2023-08-28 15:08:29","publishedOnDateReadable":"August 28th, 2023"},"versionCreatedAt":"2023-06-29 21:42:03","video":"","vorDoi":"10.1186/s12957-023-03153-z","vorDoiUrl":"https://doi.org/10.1186/s12957-023-03153-z","workflowStages":[]},"version":"v1","identity":"rs-3110480","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3110480","identity":"rs-3110480","version":["v1"]},"buildId":"J0_U0BvcaRcwD8yVFaRlm","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}