Myxoid stroma is associated with postoperative relapse in patients with stage II colon cancer

Myxoid stroma is associated with postoperative relapse in patients with stage II colon cancer | 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 Myxoid stroma is associated with postoperative relapse in patients with stage II colon cancer Takashi Okuyama, Shinichi Sameshima, Emiko Takeshita, Takashi Mitsui, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.2.20269/v3 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Sep, 2020 Read the published version in BMC Cancer → Version 3 posted 4 You are reading this latest preprint version Show more versions Abstract Background: Fibrosis surrounding cancer cells has been shown to affect cancer cell metastatic behavior. The present study aimed to explore the utility of myxoid stroma as a predictive factor for postoperative relapse in patients with stage II colon cancer. Methods: The present study retrospectively investigated 169 patients who underwent curative surgical resection of stage II colon cancer. The fibrotic stroma was classified according to Ueno’s criteria, and the patients were divided into the myxoid (MY) group and the non-MY (NMY) group. We also recorded tumor budding (TB) and investigated the combination of MY and TB for postoperative relapse. Postoperative survival was also explored. Results: Thirty-two (18.9%) patients had MY. MY was significantly associated with tumor budding (TB) and postoperative relapse (p<0.001 and p<0.001, respectively). The 5-year RFS rates in MY group and NMY group were 52.1% and 94.6% (p<0.0001), and the 5-year OS rates in MY group and NMY group were 74.6% and 93.3% (p=0.001). Multivariate analysis showed that both MY and TB were significant risk factors for postoperative relapse (p<0.001 and p=0.02, respectively), and that only TB was a significant risk factor for OS (p=0.043). Furthermore, compared with patients with either one of MY or TB, patients with both MY and TB had postoperative relapse more frequently (11.4% vs. 53.8%). Conclusions: The present study suggests that MY is a predictive marker for postoperative relapse in patients with stage II colon cancer. Oncology Myxoid stroma Desmoplastic reaction stage II colon cancer Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background The actual role of adjuvant chemotherapy (AC) in patients with stage II colon cancer remains unclear despite several clinical trials and meta-analyses [ 1-4 ]. However, surveillance, epidemiology, and end results analyses have shown that there are groups of patients having a higher risk of relapse than others [5]. International guidelines therefore recommend that patients with stage II colon cancer should be divided into a high-risk group and a low-risk group for postoperative relapse, and that AC should be considered in patients with high-risk features, but high-level evidence including molecular and genetic factors is still lacking [ 6-12 ]. Current molecular and genetic studies have indicated that tumor progression, growth, and spread are determined by the interaction between a cancer and its surrounding stromal cells [13, 14]. The tumor stroma contains many different cells, including lymphocytes, macrophages, leukocytes, Rouget cells, vascular endothelial cells, and fibroblasts. Of these stromal cells, it is increasingly clear that active fibroblasts (cancer-associated fibroblasts, CAFs) are an important regulator of cancer progression, invasion, and metastasis [15, 16 ]. CAFs or myofibroblasts induce peritumoral fibrosis that may promote tumoral progression by regulating the interaction between cancer and stromal cells [17, 18 ]. The fibrotic stroma (i.e. desmoplastic reaction, DR) refers to the state of extracellular matrix (ECM) remodeling generated by CAFs in cancer stroma [19, 20]. Recent reports have indicated a close relationship between the form of DR and the prognosis of patients with several solid cancers [21-23]. In the present study, the aim was to explore the relationship between myxoid stroma (one of the forms of DR) and postoperative relapse in patients with stage II colon cancer. Methods Resected specimens from 169 consecutive patients with stage II colon cancer at Saitama Medical Center, Dokkyo Medical University between April 2010 and March 2016 were included in this study. Patients who received neoadjuvant chemotherapy and patients with synchronous or metachronous, multiple advanced cancers were excluded. Pathological findings were classified according to the TNM classification of Malignant Tumors (8 th edition) [24]. The lymph node dissection was considered sufficient when 12 or more lymph nodes had been examined pathologically [24]. This study was approved by the Ethics Committee of Saitama Medical Center, Dokkyo Medical University (No. 1762). Desmoplastic reaction and tumor budding DR was assessed at the advancing edge of a primary tumor with hematoxylin and eosin (H&E) staining, and the specimens were divided according to Ueno’s criteria: the myxoid stroma (MY) group and the non-myxoid stroma (NMY) group [25] (Fig. 1). Immature stroma in Ueno’s criteria was defined as MY, and mature fibrosis and keloid-like stroma was defined as NMY in this study. When tumors involved the areas of myxoid changes (an amorphous stromal substance with basophilic extracellular material), the DR was recorded as MY regardless of the existence of mature stroma or keloid-like collagens. Small areas of myxoid fibrotic change were assessed according to whether these features were observed with a 40× objective lens in areas without microscopic abscesses. DR was evaluated by two independent observers. One of them was an experienced pathologist (YO), with no knowledge of outcomes and other clinical information, and the other was a surgeon (TO). Their inter-observer agreement was calculated using k -statistics. The inter-observer agreement coefficient k was 0.72. Tumor budding (TB) was evaluated with H&E staining and defined as single cells or clusters of up to four cells at the advancing edge of colorectal cancer [26]. The evaluation of TB was performed under a 20× objective lens in the areas where TB was observed most frequently (hotspot method) [27]. TB was classified as low-grade (0-4 buds), intermediate-grade (5-9 buds), and high-grade (10 or more buds) [27, 28]. Follow-up and adjuvant chemotherapy Postoperative surveillance including medical examinations and laboratory tests was performed every 3 months, and computed tomography (CT) of the chest, abdomen, and pelvis was performed every 6 months until 5 years after surgery. Surveillance colonoscopy was performed within 1 year after surgery and annually thereafter until no neoplastic lesions were observed. If no neoplastic lesions were detected on surveillance colonoscopy, the subsequent colonoscopy was performed 3 years later. Adjuvant chemotherapy (AC) was usually recommended to patients with high-risk features, such as T4 lesions, poor differentiation, lymphovascular or perineural invasion, <12 lymph nodes harvested, positive margin, or bowel obstruction or perforation, for a total of 6 months using a regimen including 5-fluorouracil (5-FU)-leucovorin or capecitabine (FOLFOX or CAPOX). The use and selection of the PAC regimen depended on the primary surgeon. Statistical analysis Associations between MY and clinicopathological findings were assessed using the two-tailed chi-squared test or Fisher’s exact test. Continuous variables were assessed using the Mann-Whitney U test. RFS rate was calculated from the date of surgery to the date of diagnosis of tumor relapse. OS rate was calculated from the date of surgery to the date of death by any cause or the last follow-up visit. RFS and OS rates were calculated using the Kaplan-Meier method, and differences were evaluated using the log-rank test. Multivariate analysis was performed using the Cox proportional hazard regression model with data that trended toward significance (P<.10) on univariate analysis. A two-sided P value of <.05 was considered significant. All analyses were performed using the SPSS statistical software package, version 24 (IBM Japan Ltd., Tokyo, Japan). Results Patients’ clinical and pathological characteristics More than half of the patients were men (55.6%), and the patients’ average age at the time of surgery was 70.5 years (range 29 - 92 years). The median follow-up period of the entire patient group was 60 months. The baseline clinicopathological characteristics of the 169 patients are shown in Table 1. In this study, 32 patients (18.9%) had MY (MY group), and 137 (71.1%) patients did not (NMY group). The regimens of adjuvant chemotherapy in MY group and NMY group are shown in Table 2. Patients who received completely AC was 22 (13.6%) cases (MY; 6 patients, NMY; 16 patients). Three of 22 patients who were withdrawal due to have a drug allergy, were excluded from AC group. These patients received 2-4 cycles intravenous or oral AC. Twenty-three of 169 patients developed postoperative relapses, including lung metastasis (6 patients), liver metastasis (8 patients), peritoneal dissemination (5 patients), metastasis to the para-aortic lymph nodes (3 patients), and local relapse (1 patient). Seventeen patients (17/169, 10.1%) died of any causes within the follow-up period, and seven of these patients (7/17, 41.2%) died of causes other than primary colon cancer. Relationships between myxoid stroma and clinicopathological characteristics The relationships between MY and clinicopathological characteristics are shown in Table 3. TB and postoperative relapse were significantly more frequent in the MY group than in the NMY group (p<0.001 and p<0.001, respectively). None of the other clinicopathological characteristics was associated with the presence of MY. Survival analyses of relapse-free survival and overall survival The 5-year RFS and OS rates were 87% and 89.6%, respectively, for the entire group of patients in this study. The MY group had significantly lower RFS and OS rate than the NMY group ( p<0.0001 and p=0.001, respectively, Figs. 2, 3 ). The 5-year RFS rates in MY group and NMY group were 52.1% and 94.6% (p<0.0001), and the 5-year OS rates in MY group and NMY group were 74.6% and 93.3% (p=0.001). Regarding patients who did not receive AC, the MY group had significantly lower RFS and OS rates than the NMY group (p<0.001 and p=0.028, respectively, Figs. 4 and 5 ). Univariate- and multivariate analyses to identify characteristics related to relapse-free survival and overall survival Univariate and multivariate analyses to identify characteristics significantly related to RFS and OS rates were performed using Cox proportional hazard models (Table 4). On univariate analyses for RFS rate, TB, surgical margin, and the presence of MY were significantly associated with lower RFS rate (p<0.001, p=0.038 and p=<0.001, respectively). Regarding the OS rate, the serum CA19-9 level, deep tumor penetration, TB, positive surgical margin, and the presence of MY were significantly associated with lower OS rate in univariate analysis (p=0.026, p=0.011, p=0.001, p=0.014 and p=0.003). On multivariate analysis for RFS and OS rates, the presence of MY and TB were significant risk factors for RFS rate (MY: HR, 6.80; 95% CI, 2.579-17.911; p<0.001, TB: HR, 4.11; 95% CI, 1.301-13.002; p=0.02), and only TB was a significant risk factor for OS rate (HR, 1.94; 95% CI, 1.020-3.668; p=0.043). Combination of myxoid stroma and tumor budding for postoperative relapse and survival The relationships of the combination of MY and TB with 5-year RFS and OS rates are shown in Table 5. The relapse rate in patients with both MY and TB was nearly five-fold higher than with either one of MY or TB (53.8% vs. 11.4%). Patients with both MY and TB had a much worse 5-year RFS rate than those with either one of MY or TB (44.2% vs. 87.7%, p<0.001) . Furthermore, Cox regression analysis showed that there was a significant difference in RFS rate between patients with both MY and TB and those with either one of MY or TB (HR, 5.801; 95% CI, 2.0884-16.146; p=0.001). Regarding the OS rate, there was no significant difference between patients with both MY and TB and those with either one of MY or TB on Cox regression analysis. Discussion The aim of the present study was to explore the utility of MY as a predictor of postoperative relapse and survival in patients with stage II colon cancer, respectively. In addition, the utility of the combination of MY and TB was similarly explored. In this study, patients with MY had more frequent postoperative relapse than those without MY. Furthermore, Kaplan-Meier analyses showed that patients with MY had significantly worse RFS and OS rates than those without MY, and multivariate analysis demonstrated that MY was an independent predictor of postoperative relapse in patients with stage II colon cancer. On the analysis for the combination of MY and TB, patients with both MY and TB had a significant worse 5-year RFS rate than those with either one of MY or TB. These results suggest a close relationship between MY and cancer cell metastatic behavior. DR classified by the type of fibrotic stroma is simply detected by routine H&E staining. This inexpensive pathological feature has been reported as a useful predictor for metastasis and survival in several solid cancers, including cutaneous cancer, breast cancer, lung cancer, pancreatic cancer, and colorectal cancer [21, 29-32]. In colorectal cancer, although the amount of fibrosis was evaluated as an index of the stromal reaction first, Ueno et al. recently have proposed categorizing it into three types by the fibrotic responses of cancer stroma, and they reported that their classification was useful for predicting the prognosis of patients with colorectal cancer [32-34]. Recent approaches using molecular and genetic methods may offer predictive information for relapse and survival in patients with stage II colon cancer in addition to the routine pathological examination [9, 10]. Microsatellite instability (MSI) due to mutation or modification of mismatch repair (MMR) is mainly detected in Lynch syndrome, which is an autosomal dominant cancer syndrome associated with an increased risk of colorectal cancer and other extracolonic malignancies, including endometrial cancer, stomach, small bowel, and ovarian cancers [35, 36]. In stages II/III colorectal cancer, it is generally recognized the biological difference in tumors with MMR states [9, 10, 37]. Hutchins et al. demonstrated that patients with dMMR had significantly lower relapse than that with pMMR [38]. On the other hand, Ribic et al. and Sargent et al. reported that there was no benefit from FU based AC in stage II/III patients with dMMR [37, 39]. In addition, Gavin et al. showed MMR states were not predictive for oxaliplatin benefit [10]. Although MSI or the MMR test need immunohistochemistry or expensive gene analyses, clinical evidence supporting their use is still insufficient. Among cells of the stromal component, fibroblasts have been termed cancer-associated fibroblasts (CAFs) and are important promotors of tumor progression and metastasis [40]. CAFs can induce dedifferentiation by extracellular matrix (ECM) remodeling and desmoplasia by increasing the deposition of ECM [41, 42 ]. In several reports, single or small clusters of cancer cells (TB) have been frequently observed at MY areas [25, 29], and TB was associated with DR in the present study. These results suggest that CAFs may have a critical role in regulating DR and TB. Recently, Ueno et al. reported that a tumor grading system based on DR and TB provides more precise prediction of individual patients than the conventional staging [43]. In the present study, compared with patients with either one of MY or TB, those with both MY and TB developed postoperative relapse much more frequently. The presence of both MY and TB might have a synergistic effect rather than an additive effect for postoperative relapse. Circulating CAFs (cCAFs) have recently been identified in the circulation, and metastasis-associated fibroblasts at the metastatic site promote the proliferation of cancer cells [44, 45] . Cornil et al. reported that fibroblasts affected the proliferation of melanoma cells, and that only metastasized melanoma cells were influenced by fibroblasts [46]. Since MY has been closely associated with metastasis in previous reports [21, 29-32], specific stimuli released by MY may move cCAFs to metastatic sites. In fact, 65% of patients with MY developed tumor relapse, whereas only 12% of patients without MY did. The present study has several limitations, such as its retrospective design and small sample size in a single institution. A difference in the relapse rate between patients with mature stroma and those with intermediate stroma might have been found if the sample size had been larger. In the present study, multivariate analysis did not show that MY was an independent risk factor for OS in patients with stage II colon cancer. This might have been due to the short follow-up and the effects of AC and treatment for relapse, such as surgical intervention and intensive chemotherapy. In addition, neither MSI nor MMR, which are considered to be predictive in the NCCN guideline, was examined, and the effect of AC according to the NCCN guideline was not examined. In conclusion, the present results suggest that MY is a useful predictive feature for postoperative relapse in patients with stage II colon cancer. Although the additional larger trials should be added, if both MY and TB are identified in the lesion, the risk of tumor relapse may be a high. Since MY may become a useful information for deciding whether to add AC in patients with stage II colon cancer, it should be confirmed in multi-institutional trials for a large number of patients. Declarations Ethics approval and consent to participate: This study was approved by the Ethics Committee of Saitama Medical Center, Dokkyo Medical University (No. 1762). All participants were provided written informed consent in the study. Consent for publication: Not applicable. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interest: The authors declare that they have no competing interests. Funding: Not applicable. Authors Contributions: TO participate in the design of this study, the surgical procedures, and the data analysis. SS, ET, TM, TN, NT, and MO participated in the surgical procedures. YO, SB, TO participated in the pathological diagnosis. All authors read and approved the final manuscript. Acknowledgements: Not applicable. Abbreviations AC: Adjuvant chemotherapy; CAF: Cancer-associated fibroblast; CAPE: Capecitabin; CAPEOX: CAPE plus oxaliplatin; DR: Desmoplastic reaction; FOLFOX: Fluorouracil, leucovorin plus oxaliplatin; MA: Mature stroma; ECM: Extracellular matrix; IN: Intermediate stroma; MSI: Microsatellite instability; MMR: Mismatch repair; MY: Myxoid stroma; NCCN: National Comprehensive Cancer Network; NMY: Non-myxoid stroma; UFT/LV: Fluorouracil plus leucovorin; OS: Overall survival; RFS: Relapse-free survival; TB: Tumor budding References O’Connor ES, Greenblatt DY, LoConte NK, et al. Adjuvant chemotherapy for stage II colon cancer with poor prognostic features J Clin Oncol 2011; 29: 3381-3388. Si Q, Andre T, Grother A, et al. Comparison of outcomes after fluorouracil-based adjuvant therapy for stage II and III colon cancer between 1978 to 1995 and 1996 to 2007: Evidence of stage migration from the ACCENT database. J Clin Oncol 2013: 31; 3656-3663. Weiss JM, Schumacher J, Allen GO, et al. 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Tables Table 1 Demographic and clinical characteristics, postoperative treatment, and outcome at baseline of participants in this study Characteristics Number (%) Characteristics Number (%) Gender Surgical margin Male 94 (55.6) Negative 163 (96.4) Female 75 (44.4) Positive 6 (3.6) Age (yr, average, range) 70.5 (29-92) Glucose tolerance Preoperative serum CEA value Normal 120 (71.0) < 5 106 (62.7) Abnormal 49 (29.0) ≥ 5 63 (37.3) Obstruction / perforation Preoperative serum CA19-9 value Absence 157 (92.9) < 37 143 (84.6) Presence 12 (7.1) ≥ 37 26 (15.4) Surgical approach Tumor location Laparotomy 101 (59.8) Right 88 (52.1) Laparoscopic surgery 68 (40.2) Left 81 (47.9) Examined lymph node Tumor size (cm, average, range) 5.0 (1-17) ≥ 12 115 (68.0) Differentiation <12 54 (32.0) Well, Mod, pap 150 (88.8) Postoperative adjuvant chemotherapy Por, Muc, Sig 19 (11.2) No 147 (86.1) pT category Yes 22 (13.9) pT3 144 (85.2) Postoperative relapse n=23 pT4a 13 (7.7) Lung 6 pT4b 12 (7.1) Liver 8 Lymphatic invasion Peritoneum 5 Absent 104 (61.5) Paraaortic lymph node 3 Present 65 (38.5) Local relapse 1 Vessel invasion Desmoplastic reaction Absent 71 (42.0) Mature stroma 76 (45.0) Present 98 (58.0) Intermediate stroma 62 (36.1) Tumor budding Myxoid (i.e. immature) stroma 32 (18.9) Grade 1 106 (62.7) Grade 2 43 (25.4) Grade 3 20 (11.9) Table 2 The regimens of adjuvant chemotherapy used in patients with or without myxoid stroma Adjuvant Chemotherapy No UFT/LV CAPE FOLFOX XELOX Withdrawal NMY 118 6 5 3 2 3 MY 26 3 1 2 0 0 UFT/LV: Fluorouracil plus leucovorin; CAPE: Capecitabin; CAPEOX: CAPE plus oxaliplatin; FOLFOX: Fluorouracil, leucovorin plus oxaliplatin Table 3 The relationships between the myxoid stroma and clinicopathological characteristics analyzed using χ 2 and Fisher’s exact tests Myxoid Myxoid Absent (%) Present (%) p value Absent (%) Present (%) p value Gender) Lymphatic invasion Female 62 (45) 13 (41) 0.7 Absent 87 (64) 17 (53) 0.36 Male 75 (55) 19 (59) Present 50 (36) 15 (47) Age Vessel invasion < 70 53 (39) 16 (50) 0.32 Absent 61 (45) 10 (31) 0.23 ≥ 70 84 (61) 16 (50) Present 76 (55) 22 (69) Serum CEA value Tumor budding < 5 85 (62) 21 (66) 0.84 Grade 1 100 (73) 6 (19) <0.001 ≥ 5 52 (38) 11 (34) Grade 2, 3 37 (27) 26 (81) Serum CA19-9 value Surgical margin < 37 116 (85) 27 (84) 0.26 Negative 133 (97) 31 (97) 1* ≥ 37 21 (15) 5 (16) Positive 4 (3) 1 (3) Tumor location Examined lymph node Right 72 (53) 16 (50) 0.85 < 12 42 (31) 12 (38) 0.53 Left 65 (47) 16 (50) ≥ 12 95 (69) 20 (62) Tumor size (cm) Obstruction/perforation < 5 63 (46) 18 (56) 0.33 Absent 128 (93) 29 (91) 0.7* ≥ 5 74 (54) 14 (44) Present 9 (7) 3 (9) Differentiation Glucose tolerance Well, moderately, pap 121 (88) 29 (91) 1* Normal 95 (69) 25 (78) 0.39 Por, Muc, Sig 16 (12) 3 (9) Abnormality 42 (31) 7 (22) Tumor depth Tumor relapse pT3 118 (86) 26 (81) 0.58 Absent 129 (94) 17 (53) <0.001 pT4 19 (14) 6 (19) Present 8 (6) 15 (47) *Fisher’s exact tests Table 4 Uni- and multi-variate analyses using Cox proportional hazard regression models to identify to Clinicopathological characteristics related to relapse free survival and overall survival RFS OS Predictor Univariate analysis Multivariate analysis Univariate analysis Multivariate analysis HR 95%CI p value HR 95%CI p value HR 95%CI p value HR 95%CI p value Gender Male 1 1.00 Female 0.71 0.298-1.697 0.44 0.67 0.247-1.808 0.43 Age < 70 yr 1 1.00 ≥ 70 yr 1.05 0.446-2.445 0.92 2.43 0.792-7.465 0.12 Serum CEA level < 5 1 1.00 ≥ 5 1.41 0.609-3.264 0.42 0.91 0.337-2.465 0.86 Serum CA19-9 level < 37.5 1 1.00 1 ≥ 37.5 1.73 0.638-4.693 0.28 3.11 1.149-8.428 0.026 0.62 0.355-1.096 0.10 Tumor location Right 1 1.00 Left 1.10 0.478-2.541 0.82 0.58 0.214-1.565 0.28 Differentiation Well, moderately, pap 1 1.00 por, muc 0.36 0.049-2.698 0.32 1.18 0.268-5.198 0.83 Tumor size ≤ 5 1 1.00 > 5 1.22 0.536-2.789 0.63 0.80 0.310-2.080 0.65 Tumor depth pT3 1 1 1.00 1 pT4 2.52 0.986-6.452 0.054 1.75 0.594-5.153 0.31 3.66 1.352-9.922 0.011 0.84 0.429-1.651 0.62 Lymphatic invasion Absent 1 1.00 1 Present 1.03 0.398-2.264 0.91 2.48 0.941-6.515 0.07 0.91 0.519-1.596 0.74 Vessel invasion Absent 1 1.00 Present 1.65 0.674-4.056 0.27 1.09 0.416-2.875 0.86 Tumor budding Grade 1 1 1 1.00 1 Grade 2,3 9.00 3.042-26.624 <0.001 4.11 1.301-13.002 0.02 6.18 2.015-18.977 0.001 1.94 1.020-3.668 0.043 Surgical margin Absent 1 1 1.00 1 Present 4.69 1.088-20.207 0.038 4.33 0.769-24.343 0.10 6.52 1.465-28.999 0.014 0.56 0.219-1.411 0.22 Lymph node yield 12 or more 1 1.00 Less than 12 1.03 0.420-2.524 0.95 1.10 3.87-3.131 0.86 Obstruction/perforation Absent 1 1.00 Present 1.39 0.325-5.945 0.66 1.85 0.423-8.110 0.41 Operation Laparotomy 1 1.00 Laparoscopic surgery 1.26 0.542-2.906 0.60 1.13 0.427-2.972 0.81 Glucose tolerance Normal 1 1 Abnormality 1.88 0.636-5.556 0.25 1.92 0.550-6.677 0.31 Adjuvant chemotherapy No 1 1 Yes 1.07 0.317-3.622 0.91 2.18 0.710-6.683 0.17 Myxoid stroma Absent 1 1 1 1 Present 11.24 4.572-27.613 <0.001 6.80 2.579-17.911 <0.001 4.14 1.596-10.742 0.003 0.66 0.371-1.157 0.15 Table 5 Analyses using Cox proportional hazard model for the combination myxoid stroma and tumor budding on relapse free survival and overall survival rates Combinations Number of relapse (%) 5-year RFS rate (%) HR 95% CI p value 5-year OS rate (%) HR 95% CI p value MY- / TB - 4/99 (4) 96.7 1 97.9 1 MY - / TB + 4/37 (10.8) 88.1 4.003 0.896-17.896 0.069 85.2 8.75 1.766-43.360 0.008 MY+ / TB - 1/7 (14.3) 85.7 4.798 0.499-46.134 0.174 71.4 12.95 1.815-92.432 0.011 MY+ / TB + 14/26 (53.8) 44.2 24.42 6.992-85.255 < 0.001 72.5 15.64 3.245-75.337 0.001 MY+ / TB- or MY- / TB+ 5/44 (11.4) 87.7 1 82.1 1 MY+ / TB + 14/26 (53.8) 44.2 5.801 2.084-16.146 0.001 72.5 1.619 0.596-4.562 0.335 MY: Myxoid stroma TB: Tumor budding Cite Share Download PDF Status: Published Journal Publication published 03 Sep, 2020 Read the published version in BMC Cancer → Version 3 posted Editorial decision: Accept 22 Aug, 2020 Editor assigned by journal 12 Aug, 2020 Submission checks completed at journal 11 Aug, 2020 Editor invited by journal 11 Aug, 2020 You are reading this latest preprint version Show more versions 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-10881","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":1431296,"identity":"c4810e8c-0409-4a8d-923e-3e7a792442ed","order_by":0,"name":"Takashi Okuyama","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYDACHgglxyZ/+ACQlpAhWosxnwRbAkgLD9FaEuUkeAyQ+HgAP88ZM4mfOXYJbNI9n1/dqLHgYWA/fHQDPi2SvT1mkr3bkvPYZM5us845BnQYT1raDXxaDM7zmEnwbmMuZmPI3WacwwbUIsFjRlCL5N9t9YltDDnPjHP+EaPlbI+ZNO+2w4ltEjnMj3PbiNAi2XOs2Fp223FjNp5jZsy5fRI8bIT8ws+TvPHm223VcvLtzY8/53yrk+NnP3wMrxYgYJGAMtjADDYCykGA+QM6YxSMglEwCkYBCgAAHFNCB7ejI6IAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-5985-4754","institution":"Saitama Medical Center, Dokkyo Medical University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Takashi","middleName":"","lastName":"Okuyama","suffix":""},{"id":1431297,"identity":"049b6fe8-0660-4c03-8f77-7e2069bf6aa9","order_by":1,"name":"Shinichi Sameshima","email":"","orcid":"","institution":"Saitama Medical Center, Dokkyo Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shinichi","middleName":"","lastName":"Sameshima","suffix":""},{"id":1431298,"identity":"01345760-dbe5-49ad-8612-b4e20f6d60ac","order_by":2,"name":"Emiko Takeshita","email":"","orcid":"","institution":"Saitama Medical Center, Dokkyo Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Emiko","middleName":"","lastName":"Takeshita","suffix":""},{"id":1431299,"identity":"a4392af2-98fe-4c0b-8158-45f5f1cebb09","order_by":3,"name":"Takashi Mitsui","email":"","orcid":"","institution":"Saitama Medical Center, Dokkyo Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Takashi","middleName":"","lastName":"Mitsui","suffix":""},{"id":1431300,"identity":"fb25370f-649d-49a0-a2f6-b1b41e09aac5","order_by":4,"name":"Takuji Noro","email":"","orcid":"","institution":"Saitama Medical Center, Dokkyo Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Takuji","middleName":"","lastName":"Noro","suffix":""},{"id":1431301,"identity":"6e653e25-705d-4ac1-88c5-9bb610f27b7d","order_by":5,"name":"Yuko Ono","email":"","orcid":"","institution":"Saitama Medical Center, Dokkyo Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yuko","middleName":"","lastName":"Ono","suffix":""},{"id":1431302,"identity":"a2937850-aea3-42a5-bca1-fd8d04bb420f","order_by":6,"name":"Tamaki Noie","email":"","orcid":"","institution":"Saitama Medical Center, Dokkyo Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tamaki","middleName":"","lastName":"Noie","suffix":""},{"id":1431303,"identity":"2e234cbe-8e3e-4a63-a880-ce6754119978","order_by":7,"name":"Shinichi Ban","email":"","orcid":"","institution":"Saitama Medical Center, Dokkyo Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shinichi","middleName":"","lastName":"Ban","suffix":""},{"id":1431304,"identity":"5a494e0a-70ef-49c4-9934-470d2d9eb8bb","order_by":8,"name":"Masatoshi Oya","email":"","orcid":"","institution":"Saitama Medical Center, Dokkyo Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Masatoshi","middleName":"","lastName":"Oya","suffix":""}],"badges":[],"createdAt":"2020-01-05 14:23:38","currentVersionCode":3,"declarations":"","doi":"10.21203/rs.2.20269/v3","doiUrl":"https://doi.org/10.21203/rs.2.20269/v3","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12885-020-07335-w","type":"published","date":"2020-09-03T12:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":1970134,"identity":"7e3ab2bb-998d-4dc8-a343-a06fb31c2c9d","added_by":"auto","created_at":"2020-08-18 14:23:12","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":327211,"visible":true,"origin":"","legend":"A, Immature type DR: amorphous and myxomatous stroma with slightly basophilic matrix. B, Intermediate type DR: keloid-like, thick bundles of hypocellular collagen with bright eosinophilic hyalinization around the tumor nests. C, Mature type DR: fine mature collagen fibers stratified into multiple layers. Fibrotic stroma contains neither myxomatous stroma nor keloid-like collagen (A, B, C, hematoxylin and eosin, Magnifications x100).\nDR, desmoplastic reaction.","description":"","filename":"Figure1resubmit.jpg","url":"https://assets-eu.researchsquare.com/files/rs-10881/v3/Figure1resubmit.jpg"},{"id":1970135,"identity":"f588e7e6-d405-4eb3-9be9-093b10686f5d","added_by":"auto","created_at":"2020-08-18 14:23:12","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":48294,"visible":true,"origin":"","legend":"Relapse-free survival rates in NMY group and MY group.","description":"","filename":"fig2.PNG","url":"https://assets-eu.researchsquare.com/files/rs-10881/v3/fig2.PNG"},{"id":1970136,"identity":"9ea61226-b59a-4b7e-be5f-c7a77ceadae4","added_by":"auto","created_at":"2020-08-18 14:23:12","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":47688,"visible":true,"origin":"","legend":"Overall survival rates in NMY group and MY group.","description":"","filename":"fig3.PNG","url":"https://assets-eu.researchsquare.com/files/rs-10881/v3/fig3.PNG"},{"id":1970137,"identity":"fa4aed66-648f-4f5d-97ac-6c136734a6c5","added_by":"auto","created_at":"2020-08-18 14:23:12","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":47435,"visible":true,"origin":"","legend":"Relapse-free survival rates in NMY group and MY group without adjuvant chemotherapy.","description":"","filename":"fig4.PNG","url":"https://assets-eu.researchsquare.com/files/rs-10881/v3/fig4.PNG"},{"id":1970138,"identity":"8a4c09a4-a707-4a76-a3b2-5b71f8caf157","added_by":"auto","created_at":"2020-08-18 14:23:13","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":47481,"visible":true,"origin":"","legend":"Overall survival rates in NMY group and MY group without adjuvant chemotherapy.","description":"","filename":"fig5.PNG","url":"https://assets-eu.researchsquare.com/files/rs-10881/v3/fig5.PNG"},{"id":13580936,"identity":"11e1a12a-ee54-4b93-923a-4c245e869797","added_by":"auto","created_at":"2021-09-17 04:25:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":766262,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-10881/v3/91c03e7f-e9ff-486f-b00c-b7456079afb2.pdf"}],"financialInterests":"","formattedTitle":"Myxoid stroma is associated with postoperative relapse in patients with stage II colon cancer","fulltext":[{"header":"Background","content":"\u003cp\u003eThe actual role of adjuvant chemotherapy (AC) in patients with stage II colon cancer remains unclear despite several clinical trials and meta-analyses [\u003cu\u003e1-4\u003c/u\u003e]. However, surveillance, epidemiology, and end results analyses have shown that there are groups of patients having a higher risk of relapse than others [5]. International guidelines therefore recommend that patients with stage II colon cancer should be divided into a high-risk group and a low-risk group for postoperative relapse, and that AC should be considered in patients with high-risk features, but high-level evidence including molecular and genetic factors is still lacking [\u003cu\u003e6-12\u003c/u\u003e].\u003c/p\u003e\n\u003cp\u003eCurrent molecular and genetic studies have indicated that tumor progression, growth, and spread are determined by the interaction between a cancer and its surrounding stromal cells [13, 14]. The tumor stroma contains many different cells, including lymphocytes, macrophages, leukocytes, Rouget cells, vascular endothelial cells, and fibroblasts. Of these stromal cells, it is increasingly clear that active fibroblasts (cancer-associated fibroblasts, CAFs) are an important regulator of cancer progression, invasion, and metastasis [15, \u003cu\u003e16\u003c/u\u003e].\u003c/p\u003e\n\u003cp\u003eCAFs or myofibroblasts induce peritumoral fibrosis that may promote tumoral progression by regulating the interaction between cancer and stromal cells [17, \u003cu\u003e18\u003c/u\u003e]. The fibrotic stroma (i.e. desmoplastic reaction, DR) refers to the state of extracellular matrix (ECM) remodeling generated by CAFs in cancer stroma [19, 20]. Recent reports have indicated a close relationship between the form of DR and the prognosis of patients with several solid cancers [21-23]. In the present study, the aim was to explore the relationship between myxoid stroma (one of the forms of DR) and postoperative relapse in patients with stage II colon cancer.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eResected specimens from 169 consecutive patients with stage II colon cancer at Saitama Medical Center, Dokkyo Medical University between April 2010 and March 2016 were included in this study. Patients who received neoadjuvant chemotherapy and patients with synchronous or metachronous, multiple advanced cancers were excluded. Pathological findings were classified according to the TNM classification of Malignant Tumors (8\u003csup\u003eth\u003c/sup\u003e edition) [24]. The lymph node dissection was considered sufficient when 12 or more lymph nodes had been examined pathologically [24]. This study was approved by the Ethics Committee of Saitama Medical Center, Dokkyo Medical University (No. 1762).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDesmoplastic reaction and tumor budding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDR was assessed at the advancing edge of a primary tumor with hematoxylin and eosin (H\u0026amp;E) staining, and the specimens were divided according to Ueno\u0026rsquo;s criteria: the myxoid stroma (MY) group and the non-myxoid stroma (NMY) group [25] (Fig. 1). Immature stroma in Ueno\u0026rsquo;s criteria was defined as MY, and mature fibrosis and keloid-like stroma was defined as NMY in this study. When tumors involved the areas of myxoid changes (an amorphous stromal substance with basophilic extracellular material), the DR was recorded as MY regardless of the existence of mature stroma or keloid-like collagens. Small areas of myxoid fibrotic change were assessed according to whether these features were observed with a 40\u0026times; objective lens in areas without microscopic abscesses.\u003c/p\u003e\n\u003cp\u003eDR was evaluated by two independent observers. One of them was an experienced pathologist (YO), with no knowledge of outcomes and other clinical information, and the other was a surgeon (TO). Their inter-observer agreement was calculated using \u003cem\u003ek\u003c/em\u003e-statistics. The inter-observer agreement coefficient \u003cem\u003ek\u003c/em\u003e was 0.72.\u003c/p\u003e\n\u003cp\u003eTumor budding (TB) was evaluated with H\u0026amp;E staining and defined as single cells or clusters of up to four cells at the advancing edge of colorectal cancer [26]. The evaluation of TB was performed under a 20\u0026times; objective lens in the areas where TB was observed most frequently (hotspot method) [27]. TB was classified as low-grade (0-4 buds), intermediate-grade (5-9 buds), and high-grade (10 or more buds) [27, 28].\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFollow-up and adjuvant chemotherapy\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePostoperative surveillance including medical examinations and laboratory tests was performed every 3 months, and computed tomography (CT) of the chest, abdomen, and pelvis was performed every 6 months until 5 years after surgery. Surveillance colonoscopy was performed within 1 year after surgery and annually thereafter until no neoplastic lesions were observed. If no neoplastic lesions were detected on surveillance colonoscopy, the subsequent colonoscopy was performed 3 years later. Adjuvant chemotherapy (AC) was usually recommended to patients with high-risk features, such as T4 lesions, poor differentiation, lymphovascular or perineural invasion, \u0026lt;12 lymph nodes harvested, positive margin, or bowel obstruction or perforation, for a total of 6 months using a regimen including 5-fluorouracil (5-FU)-leucovorin or capecitabine (FOLFOX or CAPOX). The use and selection of the PAC regimen depended on the primary surgeon.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAssociations between MY and clinicopathological findings were assessed using the two-tailed chi-squared test or Fisher\u0026rsquo;s exact test. Continuous variables were assessed using the Mann-Whitney U test. RFS rate was calculated from the date of surgery to the date of diagnosis of tumor relapse. OS rate was calculated from the date of surgery to the date of death by any cause or the last follow-up visit. RFS and OS rates were calculated using the Kaplan-Meier method, and differences were evaluated using the log-rank test. Multivariate analysis was performed using the Cox proportional hazard regression model with data that trended toward significance (P\u0026lt;.10) on univariate analysis. A two-sided P value of \u0026lt;.05 was considered significant. All analyses were performed using the SPSS statistical software package, version 24 (IBM Japan Ltd., Tokyo, Japan).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cem\u003ePatients\u0026rsquo; clinical and pathological characteristics\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eMore than half of the patients were men (55.6%), and the patients\u0026rsquo; average age at the time of surgery was 70.5 years (range 29 - 92 years). The median follow-up period of the entire patient group was 60 months. The baseline clinicopathological characteristics of the 169 patients are shown in Table 1. In this study, 32 patients (18.9%) had MY (MY group), and 137 (71.1%) patients did not (NMY group). The regimens of adjuvant chemotherapy in MY group and NMY group are shown in Table 2. Patients who received completely AC was 22 (13.6%) cases (MY; 6 patients, NMY; 16 patients). Three of 22 patients who were withdrawal due to have a drug allergy, were excluded from AC group. These patients received 2-4 cycles intravenous or oral AC. Twenty-three of 169 patients developed postoperative relapses, including lung metastasis (6 patients), liver metastasis (8 patients), peritoneal dissemination (5 patients), metastasis to the para-aortic lymph nodes (3 patients), and local relapse (1 patient). Seventeen patients (17/169, 10.1%) died of any causes within the follow-up period, and seven of these patients (7/17, 41.2%) died of causes other than primary colon cancer.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eRelationships between myxoid stroma and clinicopathological characteristics\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe relationships between MY and clinicopathological characteristics are shown in Table 3. TB and postoperative relapse were significantly more frequent in the MY group than in the NMY group (p\u0026lt;0.001 and p\u0026lt;0.001, respectively). None of the other clinicopathological characteristics was associated with the presence of MY.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSurvival analyses of relapse-free survival and overall survival\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe 5-year RFS and OS rates were 87% and 89.6%, respectively, for the entire group of patients in this study. The MY group had significantly lower RFS and OS rate than the NMY group (\u003cu\u003ep\u0026lt;0.0001 and p=0.001, respectively, Figs. 2, 3\u003c/u\u003e). The 5-year RFS rates in MY group and NMY group were 52.1% and 94.6% (p\u0026lt;0.0001), and the 5-year OS rates in MY group and NMY group were 74.6% and 93.3% (p=0.001). Regarding patients who did not receive AC, the MY group had significantly lower RFS and OS rates than the NMY group (p\u0026lt;0.001 and p=0.028, respectively, \u003cu\u003eFigs. 4 and 5\u003c/u\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eUnivariate- and multivariate analyses to identify characteristics related to relapse-free survival and overall survival\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eUnivariate and multivariate analyses to identify characteristics significantly related to RFS and OS rates were performed using Cox proportional hazard models (Table 4). On univariate analyses for RFS rate, TB, surgical margin, and the presence of MY were significantly associated with lower RFS rate (p\u0026lt;0.001, p=0.038 and p=\u0026lt;0.001, respectively). Regarding the OS rate, the serum CA19-9 level, deep tumor penetration, TB, positive surgical margin, and the presence of MY were significantly associated with lower OS rate in univariate analysis (p=0.026, p=0.011, p=0.001, p=0.014 and p=0.003).\u003c/p\u003e\n\u003cp\u003eOn multivariate analysis for RFS and OS rates, the presence of MY and TB were significant risk factors for RFS rate (MY: HR, 6.80; 95% CI, 2.579-17.911; p\u0026lt;0.001, TB: HR, 4.11; 95% CI, 1.301-13.002; p=0.02), and only TB was a significant risk factor for OS rate (HR, 1.94; 95% CI, 1.020-3.668; p=0.043).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCombination of myxoid stroma and tumor budding for postoperative relapse and survival\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe relationships of the combination of MY and TB with 5-year RFS and OS rates are shown in Table 5. The relapse rate in patients with both MY and TB was nearly five-fold higher than with either one of MY or TB (53.8% vs. 11.4%). Patients with both MY and TB had a much worse 5-year RFS rate than those with either one of MY or TB (44.2% vs. 87.7%, \u003cu\u003ep\u0026lt;0.001)\u003c/u\u003e. Furthermore, Cox regression analysis showed that there was a significant difference in RFS rate between patients with both MY and TB and those with either one of MY or TB (HR, 5.801; 95% CI, 2.0884-16.146; p=0.001). Regarding the OS rate, there was no significant difference between patients with both MY and TB and those with either one of MY or TB on Cox regression analysis.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe aim of the present study was to explore the utility of MY as a predictor of postoperative relapse and survival in patients with stage II colon cancer, respectively. In addition, the utility of the combination of MY and TB was similarly explored. In this study, patients with MY had more frequent postoperative relapse than those without MY. Furthermore, Kaplan-Meier analyses showed that patients with MY had significantly worse RFS and OS rates than those without MY, and multivariate analysis demonstrated that MY was an independent predictor of postoperative relapse in patients with stage II colon cancer. On the analysis for the combination of MY and TB, patients with both MY and TB had a significant worse 5-year RFS rate than those with either one of MY or TB. These results suggest a close relationship between MY and cancer cell metastatic behavior.\u003c/p\u003e\n\u003cp\u003eDR classified by the type of fibrotic stroma is simply detected by routine H\u0026amp;E staining. This inexpensive pathological feature has been reported as a useful predictor for metastasis and survival in several solid cancers, including cutaneous cancer, breast cancer, lung cancer, pancreatic cancer, and colorectal cancer [21, 29-32]. In colorectal cancer, although the amount of fibrosis was evaluated as an index of the stromal reaction first, Ueno et al. recently have proposed categorizing it into three types by the fibrotic responses of cancer stroma, and they reported that their classification was useful for predicting the prognosis of patients with colorectal cancer [32-34].\u003c/p\u003e\n\u003cp\u003eRecent approaches using molecular and genetic methods may offer predictive information for relapse and survival in patients with stage II colon cancer in addition to the routine pathological examination [9, 10]. Microsatellite instability (MSI) due to mutation or modification of mismatch repair (MMR) is mainly detected in Lynch syndrome, which is an autosomal dominant cancer syndrome associated with an increased risk of colorectal cancer and other extracolonic malignancies, including endometrial cancer, stomach, small bowel, and ovarian cancers [35, 36]. In stages II/III colorectal cancer, it is generally recognized the biological difference in tumors with MMR states [9, 10, 37]. Hutchins et al. demonstrated that patients with dMMR had significantly lower relapse than that with pMMR [38]. On the other hand, Ribic et al. and Sargent et al. reported that there was no benefit from FU based AC in stage II/III patients with dMMR [37, 39]. In addition, Gavin et al. showed MMR states were not predictive for oxaliplatin benefit [10]. Although MSI or the MMR test need immunohistochemistry or expensive gene analyses, clinical evidence supporting their use is still insufficient.\u003c/p\u003e\n\u003cp\u003eAmong cells of the stromal component, fibroblasts have been termed cancer-associated fibroblasts (CAFs) and are important promotors of tumor progression and metastasis [40]. CAFs can induce dedifferentiation by extracellular matrix (ECM) remodeling and desmoplasia by increasing the deposition of ECM [41, \u003cu\u003e42\u003c/u\u003e]. In several reports, single or small clusters of cancer cells (TB) have been frequently observed at MY areas [25, 29], and TB was associated with DR in the present study. These results suggest that CAFs may have a critical role in regulating DR and TB. Recently, Ueno et al. reported that a tumor grading system based on DR and TB provides more precise prediction of individual patients than the conventional staging [43]. In the present study, compared with patients with either one of MY or TB, those with both MY and TB developed postoperative relapse much more frequently. The presence of both MY and TB might have a synergistic effect rather than an additive effect for postoperative relapse.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eCirculating CAFs (cCAFs) have recently been identified in the circulation, and metastasis-associated fibroblasts at the metastatic site promote the proliferation of cancer cells [44, 45]\u003c/u\u003e. Cornil et al. reported that fibroblasts affected the proliferation of melanoma cells, and that only metastasized melanoma cells were influenced by fibroblasts [46]. Since MY has been closely associated with metastasis in previous reports [21, 29-32], specific stimuli released by MY may move cCAFs to metastatic sites. In fact, 65% of patients with MY developed tumor relapse, whereas only 12% of patients without MY did.\u003c/p\u003e\n\u003cp\u003eThe present study has several limitations, such as its retrospective design and small sample size in a single institution. A difference in the relapse rate between patients with mature stroma and those with intermediate stroma might have been found if the sample size had been larger. In the present study, multivariate analysis did not show that MY was an independent risk factor for OS in patients with stage II colon cancer. This might have been due to the short follow-up and the effects of AC and treatment for relapse, such as surgical intervention and intensive chemotherapy. In addition, neither MSI nor MMR, which are considered to be predictive in the NCCN guideline, was examined, and the effect of AC according to the NCCN guideline was not examined.\u003c/p\u003e\n\u003cp\u003eIn conclusion, the present results suggest that MY is a useful predictive feature for postoperative relapse in patients with stage II colon cancer. Although the additional larger trials should be added, if both MY and TB are identified in the lesion, the risk of tumor relapse may be a high. Since MY may become a useful information for deciding whether to add AC in patients with stage II colon cancer, it should be confirmed in multi-institutional trials for a large number of patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Saitama Medical Center, Dokkyo Medical University (No. 1762). All participants were provided written informed consent in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding: \u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u003c/strong\u003e\u003cstrong\u003e Contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTO participate in the design of this study, the surgical procedures, and the data analysis. SS, ET, TM, TN, NT, and MO participated in the surgical procedures. YO, SB, TO participated in the pathological diagnosis. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e Not applicable.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAC: Adjuvant chemotherapy; CAF: Cancer-associated fibroblast; CAPE: Capecitabin; CAPEOX: CAPE plus oxaliplatin; DR: Desmoplastic reaction; FOLFOX: Fluorouracil, leucovorin plus oxaliplatin; MA: Mature stroma; ECM: Extracellular matrix; IN: Intermediate stroma; MSI: Microsatellite instability; MMR: Mismatch repair; MY: Myxoid stroma; NCCN: National Comprehensive Cancer Network; NMY: Non-myxoid stroma; UFT/LV: Fluorouracil plus leucovorin; OS: Overall survival; RFS: Relapse-free survival; TB: Tumor budding\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003e\u003cu\u003eO\u0026rsquo;Connor ES, Greenblatt DY, LoConte NK, et al. 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J Clin Oncol 2010 28 3219-26.\u003c/li\u003e\n\u003cli\u003eHutchins G, Southward K, Handley K, et al: Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer. J Clin Oncol 2011; 29: 1261-1270.\u003c/li\u003e\n\u003cli\u003eRibic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 2003; 349: 247-57.\u003c/li\u003e\n\u003cli\u003eMueller MM, Fusenig NE. Friends of foes - bipolar effects of the tumor stroma in cancer. Nature Rev Cancer 2004 4 839-49.\u003c/li\u003e\n\u003cli\u003evan Kempen LC, Ruiter DJ, van Muijen GN, Coussens LM. The tumor microenvironment: a critical determinant of neoplastic evolution. Eur J Cell 2003; 82: 539-48.\u003c/li\u003e\n\u003cli\u003e\u003cu\u003ePaolillo M, Schinelli S. 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Fibroblast cell interactions with human melanoma cells affect tumor cell growth as a function of tumor progression. Proc Natl Acad Sci USA 1991; 88: 6028-32.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003eTable 1\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border: none;width:379.0pt;border-collapse:collapse;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width:379.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.25pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cu\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003eDemographic and clinical characteristics, postoperative treatment, and outcome at baseline of participants in this study\u003c/span\u003e\u003c/u\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003eCharacteristics\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003eNumber (%)\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003eCharacteristics\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003eNumber (%)\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003eGender\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003eSurgical margin\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Male\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;94 (55.6)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Negative\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e163 (96.4)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Female\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;75 (44.4)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Positive\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;6 (3.6)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003eAge (yr, average, range)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e70.5 (29-92)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003eGlucose tolerance\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003ePreoperative serum CEA value\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Normal\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;120 (71.0)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt; 5\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;106 (62.7)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Abnormal\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; 49 (29.0)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/span\u003e\u003cspan style='font-size: 12px; font-family: \"Yu Gothic\", sans-serif;'\u003e\u0026ge;\u003c/span\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;5\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; 63 (37.3)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003eObstruction / perforation\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003ePreoperative serum CA19-9 value \u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Absence\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;157 (92.9)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt; 37\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;143 (84.6)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", 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style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003eSurgical approach\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003eTumor location\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Laparotomy\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;101 (59.8)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Right\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;88 (52.1)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Laparoscopic surgery\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan 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(47.9)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003eExamined lymph node\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003eTumor size (cm, average, range)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e5.0 (1-17)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/span\u003e\u003cspan style='font-size: 12px; font-family: \"MS PMincho\", serif;'\u003e\u0026ge;\u003c/span\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e12\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;115 (68.0)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003eDifferentiation\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt;12\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;54 (32.0)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Well, Mod, pap\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; 150 (88.8)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003ePostoperative adjuvant chemotherapy\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Por, Muc, Sig\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; 19 (11.2)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;No\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;147 (86.1)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003epT category\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Yes\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; 22 (13.9)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;pT3\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;144 (85.2)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003ePostoperative relapse\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;n=23\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;pT4a\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;13 (7.7)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Lung\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e6\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;pT4b\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;12 (7.1)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Liver\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e8\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003eLymphatic invasion\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Peritoneum\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e5\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Absent\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;104 (61.5)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Paraaortic lymph node\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e3\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Present\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; 65 (38.5)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Local relapse\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e1\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003eVessel invasion\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003eDesmoplastic reaction\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Absent\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;71 (42.0)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; Mature stroma\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e76 (45.0)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Present\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;98 (58.0)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; Intermediate stroma\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;62 (36.1)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003eTumor budding\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; Myxoid (i.e. immature) stroma\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;32 (18.9)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; Grade 1\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e106 (62.7)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; Grade 2\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;43 (25.4)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:127.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; Grade 3\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 12px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;20 (11.9)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.05pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:138.85pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:53.7pt;padding:0in 4.95pt 0in 4.95pt;height:10.5pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cu\u003eTable 2\u003c/u\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border: none;width:350.0pt;border-collapse:collapse;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width:350.0pt;padding:0in 4.95pt 0in 4.95pt;height:14.25pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eThe regimens of adjuvant chemotherapy used in patients with or without myxoid stroma\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width:350.0pt;border:none;border-bottom: solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eAdjuvant Chemotherapy\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:37.9pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Yu Gothic\", sans-serif;'\u003e \u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:25.15pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eNo\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:55.65pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eUFT/LV\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.35pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eCAPE\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.6pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eFOLFOX\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:.75in;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eXELOX\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:74.35pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eWithdrawal\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:37.9pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eNMY\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:25.15pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e118\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:55.65pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e6\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.35pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e5\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.6pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e3\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:.75in;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e2\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:74.35pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e3\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:37.9pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eMY\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:25.15pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e26\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:55.65pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e3\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.35pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e1\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.6pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e2\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:.75in;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:74.35pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:37.9pt;padding:0in 4.95pt 0in 4.95pt;height:6.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:25.15pt;padding:0in 4.95pt 0in 4.95pt;height:6.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:55.65pt;padding:0in 4.95pt 0in 4.95pt;height:6.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:41.35pt;padding:0in 4.95pt 0in 4.95pt;height:6.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:61.6pt;padding:0in 4.95pt 0in 4.95pt;height:6.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:.75in;padding:0in 4.95pt 0in 4.95pt;height:6.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:74.35pt;padding:0in 4.95pt 0in 4.95pt;height:6.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:37.9pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd colspan=\"6\" rowspan=\"2\" style=\"width:312.1pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eUFT/LV: Fluorouracil plus leucovorin; CAPE: Capecitabin; CAPEOX: CAPE plus oxaliplatin; FOLFOX: Fluorouracil, leucovorin plus oxaliplatin\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:37.9pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003eTable 3\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border: none;width:389.0pt;border-collapse:collapse;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\" style=\"width:389.0pt;padding:0in 4.95pt 0in 4.95pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cu\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003eThe relationships between the myxoid stroma and clinicopathological characteristics analyzed using \u0026chi;\u003csup\u003e2\u003c/sup\u003e and Fisher\u0026rsquo;s exact tests\u003c/span\u003e\u003c/u\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:95.45pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:86.1pt;border:none;border-bottom: solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003eMyxoid\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:27.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:67.35pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:86.1pt;border:none;border-bottom: solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003eMyxoid\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:27.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:95.45pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Yu Gothic\", sans-serif;'\u003e \u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003eAbsent (%)\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003ePresent (%)\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:27.0pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003ep value\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:67.35pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Yu Gothic\", sans-serif;'\u003e \u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003eAbsent (%)\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003ePresent (%)\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:27.0pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003ep value\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:95.45pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003eGender)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 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style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:11px;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;62 (45)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:11px;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;13 (41)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width:27.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e0.7\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:67.35pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Absent\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;87 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4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Male\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:11px;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;75 (55)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu 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serif;'\u003e50 (36)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;15 (47)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:95.45pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003eAge\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 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style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:27.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:95.45pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt; 70\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:11px;font-family:\"Times New Roman\",serif;'\u003e53 (39)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:11px;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;16 (50)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width:27.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e0.32\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:67.35pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Absent\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e61 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style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Negative\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e133 (97)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e31 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sans-serif;'\u003e\u0026ge;\u003c/span\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;37\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:11px;font-family:\"Times New Roman\",serif;'\u003e21 (15)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:11px;font-family:\"Times New Roman\",serif;'\u003e5 (16)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n 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style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e1 (3)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:95.45pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003eTumor location\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:27.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:109.5pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;Examined lymph node\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:27.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:95.45pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Right\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:11px;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;72 (53)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:11px;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;16 (50)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width:27.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e0.85\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:67.35pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt; 12\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e42 (31)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e12 (38)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width:27.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e0.53\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:95.45pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Left\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:11px;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;65 (47)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:11px;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;16 (50)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:67.35pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/span\u003e\u003cspan style='font-size: 11px; font-family: \"Yu Gothic\", sans-serif;'\u003e\u0026ge;\u003c/span\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;12\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e95 (69)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e20 (62)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:95.45pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003eTumor size (cm)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:27.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:109.5pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003eObstruction/perforation\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:27.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:95.45pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt; 5\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:11px;font-family:\"Times New Roman\",serif;'\u003e63 (46)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:11px;font-family:\"Times New Roman\",serif;'\u003e18 (56)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width:27.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:11px;font-family:\"Times New Roman\",serif;'\u003e0.33\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:67.35pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Absent\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e128 (93)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp 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style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;42 (31)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e7 (22)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:95.45pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: 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font-family: \"Times New Roman\", serif;'\u003eTumor relapse\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:27.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:95.45pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: 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style=\"width:27.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e0.58\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:67.35pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Absent\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e129 (94)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e17 (53)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width:27.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:95.45pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;pT4\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:11px;font-family:\"Times New Roman\",serif;'\u003e19 (14)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:11px;font-family:\"Times New Roman\",serif;'\u003e6 (19)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:67.35pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Present\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e8 (6)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e15 (47)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:95.45pt;padding:0in 4.95pt 0in 4.95pt;height:5.25pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:5.25pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:5.25pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:27.0pt;padding:0in 4.95pt 0in 4.95pt;height:5.25pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:67.35pt;padding:0in 4.95pt 0in 4.95pt;height:5.25pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:5.25pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:5.25pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:27.0pt;padding:0in 4.95pt 0in 4.95pt;height:5.25pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:95.45pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:43.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:27.0pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:67.35pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:42.15pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:70.95pt;padding:0in 4.95pt 0in 4.95pt;height:9.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 11px; font-family: \"Times New Roman\", serif;'\u003e*Fisher\u0026rsquo;s exact tests\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003eTable 4\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border: none;width:427.0pt;border-collapse:collapse;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"13\" style=\"width:427.0pt;padding:0in 4.95pt 0in 4.95pt;height:24.75pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cu\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003eUni- and multi-variate analyses using Cox proportional hazard regression models to identify to Clinicopathological characteristics related to relapse free survival and overall survival\u003c/span\u003e\u003c/u\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:84.9pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd colspan=\"6\" style=\"width:175.0pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003eRFS\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"6\" style=\"width:167.1pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003eOS\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:84.9pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003ePredictor\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width:89.5pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003eUnivariate analysis\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width:85.5pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003eMultivariate analysis\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width:85.5pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003eUnivariate analysis\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width:81.6pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003eMultivariate analysis\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:84.9pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:19.65pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003eHR\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.7pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e95%CI\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:26.15pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003ep value\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:15.65pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003eHR\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.7pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e95%CI\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n 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style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e0.83\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:15.65pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:39.8pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:26.15pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:84.9pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003eTumor size\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:19.65pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:43.7pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:26.15pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:15.65pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 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style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e1\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:39.8pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:26.15pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:84.9pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan 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style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp; \u0026nbsp;12 or more\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:19.65pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e1\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.7pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:26.15pt;padding:0in 4.95pt 0in 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style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e0.420-2.524\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:26.15pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e0.95\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:15.65pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:43.7pt;padding:0in 4.95pt 0in 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style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e4.14\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.7pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e1.596-10.742\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:26.15pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e0.003\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:15.65pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e0.66\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:39.8pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e0.371-1.157\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:26.15pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e0.15\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003eTable 5\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border: none;width:435.0pt;border-collapse:collapse;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\" style=\"width:435.0pt;padding:0in 4.95pt 0in 4.95pt;height:29.25pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cu\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eAnalyses using Cox proportional hazard model for the combination myxoid stroma and tumor budding on relapse free survival and overall survival\u003c/span\u003e\u003c/u\u003e\u003cu\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/u\u003e\u003cu\u003e\u003cspan style='font-size:13px;font-family:\"Times New Roman\",serif;'\u003erates\u003c/span\u003e\u003c/u\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:58.1pt;padding:0in 4.95pt 0in 4.95pt;height:39.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eCombinations\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:59.45pt;padding:0in 4.95pt 0in 4.95pt;height:39.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eNumber of relapse (%)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:40.3pt;padding:0in 4.95pt 0in 4.95pt;height:39.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e5-year \u003cu\u003eRFS\u003c/u\u003e rate (%)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:24.2pt;padding:0in 4.95pt 0in 4.95pt;height:39.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eHR\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:55.25pt;padding:0in 4.95pt 0in 4.95pt;height:39.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e95% CI\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:35.95pt;padding:0in 4.95pt 0in 4.95pt;height:39.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;p value\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:46.35pt;padding:0in 4.95pt 0in 4.95pt;height:39.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e5-year OS rate (%)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:24.2pt;padding:0in 4.95pt 0in 4.95pt;height:39.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eHR\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:55.25pt;padding:0in 4.95pt 0in 4.95pt;height:39.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e95% CI\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:35.95pt;padding:0in 4.95pt 0in 4.95pt;height:39.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;p value\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:58.1pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eMY- / TB -\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:59.45pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e4/99 \u003cu\u003e(4)\u003c/u\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:40.3pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e96.7\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:24.2pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e1\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:55.25pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:35.95pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:46.35pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e97.9\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:24.2pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e1\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:55.25pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:35.95pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:58.1pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eMY - / TB +\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:59.45pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e4/37 \u003cu\u003e(10.8)\u003c/u\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:40.3pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e88.1\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:24.2pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e4.003\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:55.25pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003e0.896-17.896\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:35.95pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", 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style=\"width:55.25pt;padding:0in 4.95pt 0in 4.95pt;height:8.25pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:35.95pt;padding:0in 4.95pt 0in 4.95pt;height:8.25pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:46.35pt;padding:0in 4.95pt 0in 4.95pt;height:8.25pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:24.2pt;padding:0in 4.95pt 0in 4.95pt;height:8.25pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:55.25pt;padding:0in 4.95pt 0in 4.95pt;height:8.25pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:35.95pt;padding:0in 4.95pt 0in 4.95pt;height:8.25pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width:117.55pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eMY: Myxoid stroma\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:40.3pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:24.2pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:55.25pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width:197.7pt;padding:0in 4.95pt 0in 4.95pt;height:12.0pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width:117.55pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; font-family: \"Times New Roman\", serif;'\u003eTB: Tumor budding\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:40.3pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:24.2pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:55.25pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:35.95pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:46.35pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:24.2pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:55.25pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"width:35.95pt;padding:0in 4.95pt 0in 4.95pt;height:12.75pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Myxoid stroma, Desmoplastic reaction, stage II colon cancer","lastPublishedDoi":"10.21203/rs.2.20269/v3","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.2.20269/v3","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Fibrosis surrounding cancer cells has been shown to affect cancer cell metastatic behavior. The present study aimed to explore the utility of myxoid stroma as a predictive factor for postoperative relapse in patients with stage II colon cancer.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e The present study retrospectively investigated 169 patients who underwent curative surgical resection of stage II colon cancer. The fibrotic stroma was classified according to Ueno’s criteria, and the patients were divided into the myxoid (MY) group and the non-MY (NMY) group. We also recorded tumor budding (TB) and investigated the combination of MY and TB for postoperative relapse. Postoperative survival was also explored.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Thirty-two (18.9%) patients had MY. MY was significantly associated with tumor budding (TB) and postoperative relapse (p\u0026lt;0.001 and p\u0026lt;0.001, respectively). The 5-year RFS rates in MY group and NMY group were 52.1% and 94.6% (p\u0026lt;0.0001), and the 5-year OS rates in MY group and NMY group were 74.6% and 93.3% (p=0.001). Multivariate analysis showed that both MY and TB were significant risk factors for postoperative relapse (p\u0026lt;0.001 and p=0.02, respectively), \u003cu\u003eand that only TB was a significant risk factor for OS (p=0.043).\u003c/u\u003e Furthermore, compared with patients with either one of MY or TB, patients with both MY and TB had postoperative relapse more frequently (11.4% vs. 53.8%).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e The present study suggests that MY is a predictive marker for postoperative relapse in patients with stage II colon cancer.\u003c/p\u003e","manuscriptTitle":"Myxoid stroma is associated with postoperative relapse in patients with stage II colon cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":3,"date":"2020-08-18 14:22:47","doi":"10.21203/rs.2.20269/v3","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accept","date":"2020-08-22T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-08-12T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-08-11T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-08-11T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":2,"date":"2020-07-16 15:19:23","doi":"10.21203/rs.2.20269/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2020-07-30T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-07-24T12:00:00+00:00","index":1,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nThe thema of this paper is very important and interesting for predicting the surgical outcome of stage II colon cancer. I think this new classification is very useful according to the data. This new paper is completely corrected by the reviews' comments.\nI have another request. It is necessary to describe \" number at risk for each survival curve (Figure 2,3,4,5).\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"reviewerAgreed","content":"","date":"2020-07-17T12:00:00+00:00","index":2,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-07-17T12:00:00+00:00","index":2,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nYou have made the corrections as I required. No I have still some recommendations or new findings, which need to be corrected, if you agree:\n\nResults section, \"survival analysis of relapse free survival and overall survival: When I compare your numbers in the text and look at the figures, there is no coincidence between the nr.´s reported and the Kaplan-Meier-Curves at the check point of 60 months (=5-y- RFS (Fig.1) and 5-y-OS (Fig.2)!!! This must be corrected!!!\n\nResults section: Please write the corresponding p-values also in the text!\n\nResults section: \"multivariate analysis\": You should mention the result according to TB-OS p=0.043 as the only independent risk factor for OS in the abstract!! Dto. concerning the \"combinations MY+TB vs. MY or TB.\n\nDiscusison section: Are references 25, 26 also from the Ueno group (as you indicated in line 48)? -\n In the passage \"Metastasis-associated fibroblasts.... you are citing [37]. The title of this paper is giving no evidence for circulating tumor cells, but refernce [39] does. Do you have to correct this reference 39 vs. 37?* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **No**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n"},{"type":"reviewerAgreed","content":"","date":"2020-07-15T12:00:00+00:00","index":1,"fulltext":""},{"type":"editorAssigned","content":"","date":"2020-07-14T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-07-14T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-07-13T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-07-13T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2020-01-08 15:48:45","doi":"10.21203/rs.2.20269/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-06-16T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-05-20T12:00:00+00:00","index":2,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nGeneral. The study tries to demonstrate the prognostic impact of the characteristics of the stroma of the tumor front in a series of 169 cases of stage II colon cancer. The authors clearly demonstrate the prognostic role of myxoid matrix and budding tumor in the prognosis of these patients. The manuscript is well written, easy to read and easy to follow, however I have a few suggestions that will improve its presentation before it is even published.\n\nIntroduction\n- In the sentence \"Recent reports have indicated a close relationship\nbetween the form of DR and the prognosis of patients with several solid cancers \"a reference is missing.\n- In the main objective, it is established that we seek to explore the relationship of myxoid stroma with recurrence. Why then was a survival analysis performed?\n\nMethodology:\n- The sentence: \"they were classified according to the TNM classification\", it is necessary to specify here that it is part of the 8th edition (later it is indicated that this is, however, to increase clarity it must be here.\n- The sentence: \"In the present study, since there was no association between the DR classification, except MY (data not shown) and the postoperative results, DR explored in the MY group and the NMY group was explored ... · and others Parts of the manuscript (such as establishing that the objective is to determine the association with recurrence and the methodology and results show that a survival analysis was made) suggest that the results presented are post hoc analyzes where it seems that the authors originally intended to demonstrate the association of tumor stoma characteristics with prognosis in terms of recurrence and survival I think these parts of the manuscript are confusing, so I suggest deleting the sentence quoted at the beginning of this paragraph and modifying the purpose of the study, I suggest: The objective is to determine the association of myxoid stroma with recurrence and survival.\nDiscussion\n- I recommend rewriting this paragraph: \"The QUASAR trial and several studies showed that patients with MMR deficiency (dMMR) had a higher risk of relapse than those who were competent in MMR (pMMR), but other studies showed the ineffectiveness of 5-FU chemotherapy in patients with dMMR compared to patients with pMMR [29-31]. \"In the present form, it is understood that patients with dMMR have a worse prognosis, which is wrong, since patients with dMMMR they have a better stage-by-stage prognosis than patients with pMMR tumors. In the QUASAR study, it was observed that patients who had dMMR showed a lower survival, but this is due to the harmful effect of 5-FU, since all the cases in that series were taken to QT since they had risk factors for recurrence.\n- Page 3 of discussion, sentence: \"Therefore, we recommend the evaluation of DR in metastatic sites for patients who undergo surgical resection of metastatic lesions.\" Recommendations should be based on the results of this study, we cannot make recommendations for other studies.* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests' below.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please publish my name with my report.**\n"},{"type":"editorInvitedReview","content":"","date":"2020-05-20T12:00:00+00:00","index":3,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nThis is very interesting and informative paper. I agree that the desmoplastic reaction as immature type is one of the good indicators for colorectal cancer prognosis. But in this paper there are several problems.\n\n1)It is unclear to define MY group and NMY group. Ueno's criteria is 3 groups. Which do you record \"the intermediate\" as MY or NMY? Which do you record aws MY or NMY when both \"immature\" and \" mature\" exist in a tumor?\n\n2)Is it possible to record the exact state of DR for T4 cases at the tumor invasive front? Tumor front is often modified by inflammation or ulceration.\n\n3)The exact evaluation of tumor budding is easy for T1 or T2 cancer, but is difficult for T3 or T4 cancer because of the similarity of the true tumor budding and true tumor invasion. How do you evaluate tumor budding?\n\n4)Adjuvant chemotherapy was carried out by the primary surgeons' selection. There is a big selection bias. It is necessary at least to show the distribution of adjuvant chemotherapy (the regimen and the duration) between MY group and NMY group.\n\n5)It is necessary to mention about RFS and OS for MY group and NMY group without adjuvant chemotherapy if possible.\n\nI think major revision is necessary.\n\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I declare that I have no competing interests' below.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n"},{"type":"reviewerAgreed","content":"","date":"2020-05-18T12:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-05-18T12:00:00+00:00","index":3,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-05-09T12:00:00+00:00","index":1,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nPlease include all comments for the authors in this box rather than uploading your report as an attachment. Please only upload as attachments annotated versions of manuscripts, graphs, supporting materials or other aspects of your report which cannot be included in a text format.\nPlease overwrite this text when adding your comments to the authors.\n\nBasically, the work is interesting and could contribute to a better selection of colon cancer UICC IIa patients for postoperative adjuvant chemotherapy. Please note, that AC for UICCII with FOLFOX or CAPOX is not unanimously recommended. To my knowledge, at least in the German AWMF Guide Lines, 5-FU+FA is recommended (in UICC IIB)/high risk patients.\n\nI have several comments/critical points concerning the text and Tables that should be corrected/improved:\n\nConcerning the introduction many older papers are cited; some new reports would improve the knowledge about the actual status. No papers about molecular biologic prognostic factors are cited. Please note, that in your specific patient cohort only colon cancer patients are examined. It is important that no referals to the literature examining \"colorectal cancer\" patients are made for specific conclusions/comparisons of your date. Colon cancer is different from rectal cancer (there are excellent actual papers available on that issue).\n\nYou are using the abbriviation PAC and AC, PAC is not explained in \"abbreviations\". You are using DFS and RFS rates and times (?); DFS is not included in \"abbreviations\". In the text and tables/figures it must be totally clear, whether you mean DFS or RFS time (!). The DFS and OS usually are expressed in rates; please make this clear to understand.\n\nConcerning AC/PAC: Please indicate in the text, what kind of patients received this treatment. Furtheron, in your text, tables and figures the Impact of adjuvant chemotherapy is not extensively adressed - although in the conclusion you reccommend, that MY+TB should be used as prognostic factors for the decision on AC (in UICC IIA+B)? In the text you write that \"Twenty-two (23/169, 13.6%\"... : 22 or 23?. Could you tell us in the results section, whether AC had an effect in any patient-subgroup (e.g. in My+/TB+).\n\nYou are making the statemnt in the results section, that 10/169 Patiens died due to relapses; this should be acknowledged in the discussion concerning OS-rates.\n\nConcerning In the results section \"Survival analyses...\" you make the Statement, that that the MY Group has \"shorter RFS and OS\": The statement of relapse free survival time may be correct but: you certainly lower 5-year Disease Free Survival Rates?! Now: Concerning 5-year OS-Rates, int he text they are 94.6% in the MY Group and 93.3% in the NMY Group, which obviously are not at all differing. In your Fig.3 the 5-year OS-rates are differing from your text statements! Please give in this text section your Statement on the effect of AC in MY vs. NMY.\n\nIn the section \"Univariate- and multivariate....\" in the last chapter you Switch to results of univariate Analysis, while before you reported also on univariate/multivarate. This sequence of reporting could be more clear: Report first \"univariate\", then \"multivariate\".\n\nConcerning the results of Table 4 and the corresponding text: \"RFS/DFS or Relapse Rates... (!): In the Text you use RFS, in the Table you Show 5-year-Disease Free Survival Rates: Confusing!\n\nIn the Discussion you begin with the Statement, that you looked at MY - but you examined both, TB and MY.\n\nPlease be cautious to recommend MY/TB instead of immunochemistry or expensive gene Analysis; your paper is based on (only) 169 pts. and a single Institution Analysis! Please make sure to Show, that you examined \"only\" UICC II colon cancer patients. In the conclusion, you must reccommend affirmative Trials before you make recommendations to use MY/TB routinely.\n\nThe tables must be better outlined: Shorter/more comprehensive. \n\nNow one important notice to Table 2: It definitely would be clear to note the numbers below \"Myxoid Absent and Myxoid present. The % you Show should be calculated from the Relations to the number of \"absent\" or \"present. E.g. Tumor relapse no/yes in \"MY absent\" 129/137 (94%) and \"MY present\" (17/32 (53%) / 8/137 (6%) and 15/32 (47%)!!!! and so on, in the whole table. Than your reader can evaluate your data with the biometric/statistical results.\n\nAs questionen above, in Figure 3 with OS you Show p= 0.001, but in the text you say and Show different numbers and no difference = no way to be included in this paper.\n\nSo, it is clear, that you have to make major corrections before your paper with interesting results can be published. * Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please publish my name with my report.**\n"},{"type":"reviewersInvited","content":"","date":"2020-01-16T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-01-16T12:00:00+00:00","index":1,"fulltext":""},{"type":"editorAssigned","content":"","date":"2019-12-30T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2019-12-29T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2019-12-29T12:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2019-12-28T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d4a7561e-d610-4afc-b3aa-3ffa849e234e","owner":[],"postedDate":"August 18th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":317666,"name":"Oncology"}],"tags":[],"updatedAt":"2020-09-06T15:01:57+00:00","versionOfRecord":{"articleIdentity":"rs-10881","link":"https://doi.org/10.1186/s12885-020-07335-w","journal":{"identity":"bmc-cancer","isVorOnly":false,"title":"BMC Cancer"},"publishedOn":"2020-09-03 12:00:00","publishedOnDateReadable":"September 3rd, 2020"},"versionCreatedAt":"2020-08-18 14:22:47","video":"","vorDoi":"10.1186/s12885-020-07335-w","vorDoiUrl":"https://doi.org/10.1186/s12885-020-07335-w","workflowStages":[]},"version":"v3","identity":"rs-10881","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"identity":"rs-10881","version":["v3"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}