Vertical margin distance in T1 colorectal carcinoma resected by endoscopic submucosal dissection affects prognosis after additional surgery

Vertical margin distance in T1 colorectal carcinoma resected by endoscopic submucosal dissection affects prognosis after additional surgery | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Vertical margin distance in T1 colorectal carcinoma resected by endoscopic submucosal dissection affects prognosis after additional surgery Fumiaki Tanino, Ken Yamashita, Shinji Nagata, Toshio Kuwai, Yuki Kamigaichi, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3893476/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Aug, 2024 Read the published version in International Journal of Colorectal Disease → Version 1 posted 7 You are reading this latest preprint version Abstract Purpose A vertical margin (VM) distance of < 500 µm is a risk factor for recurrence in patients with T1 colorectal carcinoma (CRC) resected by endoscopy. We aimed to determine the effects of the VM distance on the recurrence and prognosis of T1 CRC Methods We enrolled 154 patients with T1 CRC who underwent additional surgery after endoscopic submucosal dissection (ESD) at multiple centers between 2008 and 2016. None of the patients had lymph node metastasis (pStage I) and were followed up for > 5 years. A total of 154 patients were classified into patients with VM distance of < 500 µm including positive VM (n = 62, VM distance < 500 µm group) and patients with VM distance of ≥ 500 µm (n = 92, VM distance ≥ 500 µm group). The clinicopathological features, recurrence rates, and prognoses were compared between the groups using propensity-score matching (PSM). Results Tumor size and the rate of budding grade 2/3 in the VM distance < 500 µm group was significantly smaller and higher, respectively, than those in the VM distance ≥ 500 µm group. Tumors recurred in six of the 154 patients with VM distance < 500 µm. The 5-year recurrence-free survival rate was significantly higher in the VM distance ≥ 500 µm group than that in VM distance < 500 µm group after PSM (100% vs. 90%, p < 0.012). Conclusions Complete en bloc resection of T1 CRC via ESD must include a sufficient amount of submucosa to reduce the risk of metastasis and recurrence after additional surgery. colorectal cancer metastasis recurrence vertical margin endoscopic submucosal dissection Figures Figure 1 Figure 2 Figure 3 Introduction Colorectal carcinoma (CRC) is one of the most common malignancies of the gastrointestinal tract worldwide [ 1 ]. Intramucosal carcinoma does not metastasize to the lymph nodes (LN) and is a good indication for endoscopic resection (ER) [ 2 ]. However, surgery with LN dissection is recommended in principle when T1 CRC is suspected [ 3 ]. Preoperative diagnosis of submucosal (SM) invasion depth is important for treatment selection. According to the Japan Society of Cancer for Colon and Rectum (JSCCR) guidelines 2022, risk factors for lymph node metastasis (LNM) include the depth of SM invasion, histological grade, lymphatic and venous invasion, and tumor budding [ 3 – 6 ]. Additional surgery after ER is recommended when at least one risk factor for LNM is identified [ 3 ]. However, the rate of LNM in T1 CRC is 10% [ 3 , 7 , 8 ]. Therefore, additional surgeries after ER for approximately 90% of patients with T1 CRC who do not have LNM might result in overtreatment. The reported rate of LNM is 1.2% in patients with T1 CRC whose only high-risk histological characteristic is an SM invasion depth of ≥ 1,000 µm [ 9 ]. The number of T1 CRC resected by ER has increased due to society’s advancing age and patient’s comorbidities [ 10 ]. Under these circumstances, endoscopic submucosal dissection (ESD) is considered useful for en bloc resection as a total excisional biopsy in patients with clinical T1 CRC [ 11 – 13 ]. The 9th edition of the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma describes that local recurrence after ER in patients with distance from the site of cancer invasion to the vertical margin (VM) of < 500 µm [ 3 ]. However, the distance that should be maintained from the site of cancer invasion to the VM to reduce the risk of local recurrence in T1 CRC has not been established. We previously evaluated the effects of the distance from the vertical tumor margin to the edge of resected specimen (VM distance) in ER for T1b CRC on the prognosis of patients who underwent surgery after ER [ 14 ]. For the purpose of generalization, we aimed to evaluate the effects of the VM distance in ESD for T1b CRC on metastatic recurrence and the prognosis of patients who underwent additional surgery after ESD at multiple centers. Methods Patients Figure 1 shows the flow of patients through the study. Among 277 patients with T1 CRC who underwent ESD between January 2008 and June 2016 (at Hiroshima University Hospital, Hiroshima City North Medical Center Asa Citizens Hospital, and National Organization Kure Medical Center and Chugoku Cancer Center), we excluded 123 based on the following: SM invasion < 1,000 µm, treated only by ESD, positive LNM at additional surgery after ESD (pStage Ⅲ), and < 5 years of follow-up. We finally analyzed data from 154 patients. We did not include patients with pedunculated-type CRC because they might be easier to treat by endoscopic mucosal resection than by ESD. Moreover, to assess risk factors for the pathological features of LNM, evaluating an accurate pathological specimen was necessary. Therefore, only patients who underwent resection using ESD were included. The patients were classified into two groups based on the VM distance of ESD specimens: patients with VM distance < 500 µm including positive VM, (VM distance < 500 µm group, n = 62) and patients with VM distance of ≥ 500 µm (VM distance ≥ 500 µm group, n = 92). Finally, to align the background factors for each group, we performed one-to-one propensity-score matching (PSM), using the covariates of age, sex, tumor size, location, and macroscopic type. Thereafter, we identified 53 patients in each group. All cases were performed ESD by the experienced experts. The study proceeded according to ethical standards of Declaration of Helsinki (2014). The Ethics Committees at Hiroshima University and its affiliated hospital approved the study protocol (Approval No. E-0334) and each affiliated hospital and was in accordance with the guidelines of the Ministry of Health Labour and Welfare. All patients provided informed consent prior to the procedures. Indications for ESD The indications for ER in early-stage CRC followed the JSCCR guidelines [ 3 ]. Intramucosal carcinoma and T1 CRC with SM depth invasion < 1,000 µm are at low risk for LNM and a good indication for en bloc resection by ER. By contrast, clinically obvious T1b CRC is usually surgically treated. However, we sometimes attempted ER for T1b CRC as a total excisional biopsy depending on patient preference, comorbidities, and general physical condition. The indications for ESD were as follows: lesions difficult to resect en bloc (non-granular, laterally spreading tumors, particularly those of the pseudo-depressed type), lesions with a type V I pit pattern, carcinoma with shallow SM invasion, large elevated lesions of suspected carcinoma, mucosal lesions with SM fibrosis caused by biopsy or severe peristalsis, local residual early carcinoma after ER, and sporadically localized lesions in chronic inflammation such as ulcerative colitis. Indications for additional surgery after ESD According to the JSCCR guidelines, patients with VM positivity require additional surgery after ESD. Patients with VM negativity are considered for additional surgery if any of the following pathological features are found in resected specimens: SM invasion depth ≥ 1,000 µm, main histology of poorly differentiated adenocarcinoma or mucinous carcinoma or signet-cell carcinoma, positive lymphatic and/or venous invasion, and budding grade 2/3 at the site of deepest invasion [ 3 ]. In principle, additional surgery should proceed within 3 months of ESD. D2 LN dissection (middle LN) was performed according to the JSCCR guidelines. Pathological evaluation Resected specimens were fixed in 10% buffered formalin for 12–48 h. Surgical and endoscopic specimens were cut into parallel sections 3–4- and 2-mm-thick, respectively. A single gastrointestinal pathologist diagnosed all histopathological findings, and the patients were blinded to the clinical information. Pathological features, including the depth of SM invasion, histological grade, tumor budding grade, and lymphatic and venous invasion, were evaluated by hematoxylin–eosin (HE) and specific staining (Victoria blue, Elastica van Gieson, D2-40, Desmin) as needed. The depth of SM invasion was measured from the lower border of the muscularis mucosae when possible. If the muscularis mucosae could not be identified or located, the depth of SM invasion was measured from the surface layer of the mucosa [ 3 , 15 ]. The histological grade was classified as favorable (tubular or papillary adenocarcinoma) and unfavorable (poorly differentiated adenocarcinoma, mucinous carcinoma, or signet-ring cell carcinoma). The histological type of the invasive front was classified as well, moderately well, moderately poorly, and poorly differentiated adenocarcinoma. Tumor budding grade was graded per microscopic field at 200× magnification: low grade: grade 1, 0–4 buds; high grade: grade 2, 5–9, buds; and grade 3, 10 or more buds [ 16 ]. VM positivity was defined as the presence of tumors and mucinous components at the VM. VM distance was defined as the distance from the site of the deepest invasion of the cancer to the VM. Surveillance after additional surgery The follow-up was extended to > 5 years after the initial treatment. The patients were postoperatively interviewed and physically examined, underwent blood tests, and were assessed by chest and abdominal computed tomography (CT) every 6 months for the first 3 years, then annually for the next 2 years. In principle, the patients were postoperatively assessed by total colonoscopy annually for 5 years. Recurrence was confirmed by endoscopy, CT, and other findings. Recurrence at CRC sites and pelvic recurrence in patients with rectal CRC were defined as local. Metastases outside the intestinal tract were defined as distant. Investigated variables We compared the clinicopathological variables of age, sex, tumor size, tumor location, macroscopic type, treatment, metastasis/recurrence, main histology, SM invasive depth, VM distance, lymphatic and venous invasion, budding grade, and LNM after additional surgery for T1 CRC between VM distance < 500 and ≥ 500 µm groups before and after PSM. We compared the incidences of recurrence, overall survival (OS; to the day of death from any cause), and recurrence-free survival (RFS; elapsed time from the day of ESD until local and/or distant recurrence was identified) between the groups after PSM. Statistical analysis Data are presented as means ± standard deviation. Between-group differences were analyzed using chi-square or Fisher exact tests. Values with p < 0.05 were considered statistically significant. The OS and the RFS were calculated using the Kaplan–Meier method. Significant differences in the baseline clinical characteristics of the patients and the influence of possible confounding factors were adjusted using PSM. Propensity scores were estimated using a logistic regression model that included age, sex, tumor location, tumor size, and macroscopic type as variables. Thereafter, the closest eligible control unit to be paired with each treated unit was selected by one-to-one nearest neighbor matching using a caliper set at 0.25. All data were statistically analyzed using JMP statistical software v. 16.2.0 (SAS Institute, Cary, NC, USA). Results Baseline characteristics of patients Table 1 shows the baseline characteristics of the 277 patients (mean age, 68.9 y; male, n = 161 [58%]). The mean tumor size was 31 mm, and 173 (62%) of 277 lesions were located in the colon. Among macroscopic type, 95 (34%) of 277 patients had protruded lesions. Among 194 (70%) of 277 patients who underwent additional surgery, LNM were found in 17 (9%). Local recurrence and distant metastasis were found in 6 (2%) and 7 (3%) of the 277 patients. Table 2 shows the clinicopathological features of patients with T1b CRC without LNM who underwent additional surgery (pStage I) before and after PSM. Before PSM, the VM distance < 500 µm group consisted of 62 patients, and the VM distance ≥ 500 µm group consisted of 92 patients. Age, sex, tumor location, macroscopic type, main histology, and lymphatic or venous invasion did not significantly differ between the groups. Tumors were significantly smaller in the VM distance < 500 group than that in the ≥ 500 µm group (26 ± 15 vs. 33 ± 19 mm; p = 0.012). The rate of budding grade 2/3 was significantly higher in the VM distance < 500 µm group than that in the VM distance ≥ 500 µm group (22 [35%] of 62 vs. 15 [16%] of 92; p = 0.007). The clinicopathological backgrounds did not significantly differ between the groups were found after PSM. Table 1 Clinicopathological features of enrolled patients (n = 277) Variables Age (years old, mean ± SD) 68.9 ± 9.9 Sex Male 161 (58) Female 116 (42) Tumor location Colon 173 (62) Rectum 104 (38) Tumor size (mm) Mean ± SD 31.0 ± 18.4 Median (range) 27 (4-100) Macroscopic type Protruded 0-Is 67 (24) 3 (1) 8 (3) 0-Is + IIa 0-Is + IIc 0-Isp 15 (5) 0-Isp + IIc 2 (1) Superficial 0-IIa 125 (45) 54 (19) 3 (1) 0-IIa + IIc 0-IIc Treatment ESD alone 83 (30) Additional surgery after ESD 194 (70) Metastasis/Recurrence Local 6 (2) Distant 7 (3) Histology tub/pap 274 (99) por/muc/sig 3 (1) SM depth (µm) <1000 97 (35) ≧1000 180 (65) VM distance (µm) <500 (including VM positive) 140 (51) ≧500 137 (49) Lymphatic invasion positive 68 (25) Venous invasion positive 67 (24) Budding grade 2/3 48 (17) LNM after additional surgery 17/194 (9) (%) SD: standard deviation; ESD: endoscopic submucosal dissection; tub: tubular adenocarcinoma; pap: papillary adenocarcinoma; por: poorly differentiated adenocarcinoma; muc: mucinous adenocarcinoma; sig: signet-ring adenocarcinoma; SM: submucosal; VM: vertical margin; LNM: lymph node metastasis Table 2 Clinicopathological features of T1 CRC patients without LNM after additional surgery before and after propensity-score matching Variables All patients (n = 154) Propensity-matched patients (n = 106) VM distance P-value VM distance P-value <500 µm, (n = 62) ≧ 500 µm, (n = 92) <500 µm, (n = 53) ≧ 500 µm, (n = 53) Age (years old, mean ± SD) 68 ± 9 70 ± 11 0.581 68 ± 9 69 ± 10 0.959 Sex Male 36 (58) 48 (52) 0.471 31 (58) 27 (51) 0.435 Female 26 (42) 44 (48) 22 (42) 26 (49) Tumor size (mm, mean ± SD) 26 ± 15 33 ± 19 0.012 27.0 ± 15.8 26.9 ± 14.3 0.866 Tumor location Colon 42 (68) 52 (57) 0.161 37 (70) 31 (58) 0.224 Rectum 20 (32) 40 (43) 16 (30) 22 (42) Macroscopic type Protruded 0-Is 16 (26) 31 (34) 0.068 16 (30) 22 (41) 0.548 0-Is + IIa 1 (2) 2 (2) 1 (2) 0 (0) 0-Is + IIc 5 (8) 2 (2) 4 (8) 2 (4) 0-Isp 3 (5) 7 (8) 3 (6) 3 (6) 0-Isp + IIc 0 (0) 2 (2) 0 (0) 1 (2) Superficial 0-IIa 17 (27) 35 (38) 15 (28) 17 (32) 0-IIa + IIc 19 (31) 13 (14) 13 (24) 8 (15) 0-IIc 1 (2) 0 (0) 1 (2) 0 (0) Main histology tub/pap 61 (98) 91 (99) 0.778 52 (98) 52 (98) 1.000 por/sig/muc 1 (2) 1 (1) 1 (2) 1 (2) Lymphatic invasion Negative 40 (65) 70 (76) 0.121 35 (66) 43 (81) 0.078 Positive 22 (35) 22 (24) 18 (34) 10 (19) Venous invasion Negative 23 (37) 24 (24) 0.147 33 (62) 40 (75) 0.142 Positive 39 (63) 68 (76) 20 (38) 13 (25) Budding grade Grade 1 40 (65) 77 (84) 0.007 40 (75) 41 (77) 0.819 Grade 2/3 22 (35) 15 (16) 13 (25) 12 (23) Metastasis/ recurrence 6 (10) 0 (0) 0.002 6 (11) 0 (0) 0.011 Average follow-up period (months, mean ± SD) 79 ± 22 74 ± 23 0.178 79 ± 21 77 ± 26 0.372 CRC: colorectal carcinoma; LNM: lymph node metastasis; VM: vertical margin; SD: standard deviation; tub: tubular adenocarcinoma; pap: papillary adenocarcinoma; (%) por: poorly differentiated adenocarcinoma; sig: signet-ring adenocarcinoma; muc: mucinous adenocarcinoma Prognosis after additional surgery The average follow-up periods in the VM distance < 500 µm group and VM distance ≥ 500 µm group were 79 ± 22 and 74 ± 23 months, respectively. The rates of recurrence in the VM distance < 500 and ≥ 500 µm groups after PSM were 6 (11%) and 0 (0%) of 53, respectively. The recurrence rate was also significantly higher in the VM distance < 500 than that in the ≥ 500 µm group after PSM (Table 2 ). Table 3 shows the characteristics of six patients with recurrence within 5 years of ESD in within the intrapelvis (n = 1), lungs (n = 3), lung and lymph node (n = 1) and liver (n = 1). Five recurrences were located in rectum and had tumor budding grade 2 or 3. Four recurrences of 6 were positive for lymphatic invasion. All patients with recurrence had VM distance < 500 µm, and one had a positive VM. The 5-year OS rates in the VM distance ≥ 500 µm group and VM distance < 500 µm group were 100% and 98.1%, respectively (Fig. 2 ), whereas that of RFS significantly differed at 88.6% and 100%, respectively (p = 0.012; Fig. 3 ). Table 3 Characteristics of 6 patients with recurrence Case Age (years) Sex Tumor location Tumorsize (mm) Macroscopic type SM depth (µm) Ly/V Main histology Histology in invasive front BD VM distance (µm) Recurrence site Interval of recurrence (month) Prognosis 1 76 M Ra 65 0-IIa 6000 -/+ Well Well 1 290 Liver 19 Death (from other disease) 2 73 F Ra 60 0-Is 5700 -/+ Pap Mode 2 210 Lung 29 Death (from other disease) 3 60 M Rb 40 0-IIa + IIc 2000 +/+ Mode Por 3 380 Lung, LN 46 Alive 4 73 F Rb 25 0-Is 2800 +/+ Well Mode 2 130 Lung 22 Alive 5 62 M A/C 30 0-IIa 3300 +/+ Well Mode 2 VM positive Lung 53 Alive 6 64 M Rb 20 0-Is + IIc 2800 +/- Well Mode 2 450 Intrapelvis 32 Alive SM: submucosal; Ly: lymphatic invasion; V: venous invasion; BD: budding grade; VM: vertical margin; Ra: rectum above the peritoneal reflection; Rb: rectum below the peritoneal reflection; A/C: ascending colon; Well: well differentiated adenocarcinoma; Pap: papillary adenocarcinoma; Mode: moderately differentiated adenocarcinoma; Por: poorly differentiated adenocarcinoma; LN: lymph node Discussion This multicenter study found that ESD for T1 CRC required complete en bloc resection, including sufficient submucosa, to reduce the risk of metastasis and/or recurrence after additional surgery. The pathological risk factors for LNM include SM depth invasion ≥ 1,000 µm, an unfavorable histological grade (poorly differentiated adenocarcinoma or mucinous carcinoma or signet-ring cell carcinoma), positive lymphatic and/or venous invasion, and tumor budding grade 2/3 according to the JSCCR guidelines [ 3 , 5 , 9 , 17 ]. Furthermore, others have found that female sex, left-sided colorectal lesions, rectal lesions, and completely disrupted muscularis mucosae are risk factors for LNM [ 5 , 14 , 17 – 19 ]. The LNM rate of T1 CRC range is 9%‒15.8% [ 3 , 4 , 7 , 8 , 18 , 21 – 26 ]. In other words, additional surgery for all cases with risk factors for LNM might result in unnecessary or excessive treatment, which is a concern. To select patients with low risk factors for LNM, a specimen that can be properly evaluated is needed. We previously reported that en bloc ESD, as a total excisional biopsy for clinical T1b CRC, is effective and establishes a precise histological diagnosis [ 11 ]. However, ESD for T1b tumors is technically difficult, and some lesions cannot be resected en bloc. We previously reported that SM fibrosis or poor differentiation at the deepest invasive front of the tumor is associated with a high risk of positive VM in ESD for CRC with SM deep invasion [ 12 ]. In addition, Yasue et al. reported that pathological T1b CRC with obvious depression and severe fibrosis have a high risk of incomplete VM ESD [ 27 ]. Patients with VM positive require additional surgery because the likelihood of recurrence is high due to local remnants of cancer [ 3 ]. Moreover, residual tumors and incomplete ER are associated with high risk for local recurrence [ 20 , 21 ]. Growth of residual tumors after ER is reportedly more rapid [ 28 ]. Therefore, very careful ESD is needed for T1b CRC with preoperative suspicions of obvious depression, mucus components at the deepest point on endoscopic ultrasonography (EUS), or the expectation of severe SM fibrosis. Several studies have reported whether ER before surgery affects the subsequent prognosis in patients with T1 CRC. The local recurrence rate of pathologically high-risk T1 CRC after ER is 2.7–20.1% [ 7 , 23 , 25 , 26 , 29 ], while that for additional surgery after ER is 0–2.5% [ 23 , 25 , 29 – 32 ]. Additional surgery deters local recurrence of T1 CRC with high-risk factors for LNM. Moreover, prior ER does not affect the recurrence or prognosis of T1 CRC after additional surgery [ 29 , 32 , 33 ]. We previously found no significant differences in 5-year OS (96.9% vs. 92.0%) and 5-year disease-free survival rates (96.7% vs. 98.6%) after treatment between the additional surgery after ESD and surgery alone groups, respectively [ 29 ]. Therefore, prior ESD for T1 CRC had no adverse oncological effects on en bloc histological resection. However, whether additional surgery would be effective in patients with VM-positive cases is unclear because these reports included and evaluated both VM-positive and VM-negative cases [ 29 , 32 , 33 ]. Kono et al. reported remnant cancer in the intestinal tract resected by additional surgery in one case with VM distance of < 500 µm and in one case with positive VM [ 34 ]. In addition, Belderbos et al. reported that a positive resection margin was an independent risk factor for recurrence [ 20 ]. Thus, a positive VM in ESD might also be a risk factor for recurrence. We previously evaluated associations between the VM distance and recurrence or metastasis and the prognosis of patients with T1b CRC. We found that the 5-year OS and disease-specific survival rates were significantly lower in the VM distance < 500 µm group compared with the VM distance ≥ 500 µm group [ 14 ]. This study had similar results, although ER was limited to cases resected by ESD. Why metastasis or recurrence was more prevalent in the VM distance < 500 µm group was higher was under discussion. Several opinions have been offered to explain this phenomenon. During colorectal ESD, tumor cells are exfoliated into the intestinal lumen [ 35 ]. Colorectal cancer cells might become implanted into artificial ulcers after ER [ 36 ]. Neoplastic cells might shed from the tumor surface and become implanted on the exposed SM layer or directly into the damaged lymphatics of an artificial ulcer because ESD for primary lesions is a lengthy process [ 36 ]. Moreover, for stage I CRC, the cause of recurrence is either undetectable local residual tumors or the presence of micrometastasis [ 37 ]. Several studies reported that lymphatic invasion is an independent risk factor for metastatic recurrence in patients with surgically treated pT1 CRC [ 38 – 41 ]. Complete en bloc resection with a sufficient SM layer (VM distance ≥ 500 µm) by ESD for T1 CRC is essential to reduce the risk of recurrence. Predicting whether T1 CRC is sufficiently distant from the VM to be resected by ESD is important. Preoperative EUS is useful for predicting the VM distance [ 12 , 42 ]. We defined the distance from the tumor invasive front to the muscle layer on EUS as being tumor-free and found that classifying tumor-free distance as < 1 or ≥ 1 mm was useful for preoperative prediction of VM distance ≥ 500 µm [ 42 ]. In the near future, preoperative EUS will become increasingly important for evaluating whether pT1b CRC can be treated by ESD as a total excisional biopsy. This study has several limitations. First, this was a retrospective cohort study based on clinical records. Second, we reevaluated the pathological diagnosis and features, including tumor budding; however, we did not reevaluate lymphovascular invasion using immunohistochemical staining in all cases. Third, we could not collect data about parameters such as performance status and comorbidities. At least 12 LNs should be dissected to accurately diagnose advanced colon cancer according to the National Comprehensive Cancer Network, some patients with 12 LNs were dissected and evaluated for LNM; thus, LNM might have been underestimated. Large multicenter studies are needed to overcome these limitations. Conclusions The recurrence rate was significantly higher in the VM distance < 500 µm group compared with the VM distance ≥ 500 µm group, and the 5-year OS and RFS rates were significantly lower in the VM distance < 500 µm group than in the VM distance ≥ 500 µm group after PSM. Therefore, ensuring a sufficient VM distance during ESD is important to reduce the risk of recurrence after additional surgery. Declarations Author contributions Study design: Shiro Oka, Ken Yamashita and Fumiaki Tanino. Sample collection: Fumiaki Tanino, Shinji Ngata, Toshio Kuwai, Yuki Kamigaichi, Hidenori Tanaka, Yuzuru Tamaru, Hidehiko Takigawa, Naoki Asayama, Yuji Urabe. Sample evaluation: Fumio Shimamoto. Data collection: Fumiaki Tanino. Data analysis: Fumiaki Tanino. Manuscript writing: Fumiaki Tanino and Ken Yamashita. All authors have read and approved the final version of the manuscript. Funding No funding was obtained for this study. Data availability The data that support the findings of this study are not openly available due to the privacy of patients and are available from the corresponding author upon reasonable request. Data are in controlled access data storage at Hiroshima University Hospital. 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Gastrointest Endosc 79:951–960. https://doi.org/10.1016/j.gie.2013.11.014 Asayama N, Oka S, Tanaka S et al (2016) Long-term outcomes after treatment for T1 colorectal carcinoma. Int J Colorectal Dis 31:571–578. https://doi.org/10.1007/s00384-015-2473-6 Choi DH, Sohn DK, Chang HJ et al (2009) Indications for subsequent surgery after endoscopic resection of submucosally invasive colorectal carcinomas: a prospective cohort study. Dis Colon Rectum 52:438–445. https://doi.org/10.1007/DCR.0b013e318197e37f Tamaru Y, Oka S, Tanaka S et al (2017) Long-term outcomes after treatment for T1 colorectal carcinoma: a multicenter retrospective cohort study of Hiroshima GI Endoscopy Research Group. J Gastroenterol 52:1169–1179. https://doi.org/10.1007/s00535-017-1318-1 Yoshii S, Nojima M, Nosho K et al (2014) Factors associated with risk for colorectal cancer recurrence after endoscopic resection of T1 tumors. Clin Gastroenterol Hepatol 12:292–302e3. https://doi.org/10.1016/j.cgh.2013.08.008 Yasue C, Chino A, Ishioka M et al (2022) Risk factors for vertical incomplete resection in endoscopic submucosal dissection of deep invasive submucosal colorectal cancer. Scand J Gastroenterol 57:1011–1017. https://doi.org/10.1080/00365521.2022.2053738 Kunihiro M, Tanaka S, Haruma K et al (2000) Electrocautery snare resection stimulates cellular proliferation of residual colorectal tumor: an increasing gene expression related to tumor growth. Dis Colon Rectum 43:1107–1115. https://doi.org/10.1007/BF02236558 Yamashita K, Oka S, Tanaka S et al (2019) Preceding endoscopic submucosal dissection for T1 colorectal carcinoma does not affect the prognosis of patients who underwent additional surgery: a large multicenter propensity score-matched analysis. J Gastroenterol 54:897–906. https://doi.org/10.1007/s00535-019-01590-w Yamashita K, Oka S, Tanaka S et al (2019) Long-term prognosis after treatment for T1 carcinoma of laterally spreading tumors: a multicenter retrospective study. Int J Colorectal Dis 34:481–490. https://doi.org/10.1007/s00384-018-3203-7 Nishimura T, Oka S, Tanaka S et al (2021) Clinical significance of immunohistochemical lymphovascular evaluation to determine additional surgery after endoscopic submucosal dissection for colorectal T1 carcinoma. Int J Colorectal Dis 36:949–958. https://doi.org/10.1007/s00384-020-03795-5 Yamaoka Y, Imai K, Shiomi A et al (2020) Endoscopic resection of T1 colorectal cancer prior to surgery does not affect surgical adverse events and recurrence. Surg Endosc 34:5006–5016. https://doi.org/10.1007/s00464-019-07295-8 Takamaru H, Saito Y, Sekiguchi M et al (2021) Endoscopic Resection before Surgery Does Not Affect the Recurrence Rate in Patients with high-risk T1 Colorectal Cancer. Clin Transl Gastroenterol 12:e00336. https://doi.org/10.14309/ctg.0000000000000336 Kouno H, Tsuruta O, Hasegawa S (2009) Pathological diagnostic issue concerning the vertical margin of submucosal cancer in the colon and rectum. Stomach Intestine 44:1255–1262 Inoue T, Fujii H, Koyama F et al (2016) Intraluminal lavage to remove exfoliated tumor cells after colorectal endoscopic submucosal dissection. Surg Endosc 30:2773–2778. https://doi.org/10.1007/s00464-015-4550-x Tajika M, Niwa Y, Bhatia V et al (2012) A first report of tumor cell implantation after EMR in a patient with rectosigmoid cancer. Gastrointest Endosc 75:1117–1118. https://doi.org/10.1016/j.gie.2011.05.028 Leijssen LGJ, Dinaux AM, Kinutake H, Bordeianou LG, Berger DL (2019) Do Stage I colorectal cancers with lymphatic invasion require a different postoperative approach? J Gastrointest Surg 23:1884–1892. https://doi.org/10.1007/s11605-018-4054-9 Iida S, Hasegawa H, Okabayashi K et al (2012) Risk factors for postoperative recurrence in patients with pathologically T1 colorectal cancer. World J Surg 36:424–430. https://doi.org/10.1007/s00268-011-1378-y Lee JH, Lee JL, Park IJ et al (2017) Identification of recurrence-predictive indicators in Stage I colorectal cancer. World J Surg 41:1126–1133. https://doi.org/10.1007/s00268-016-3833-2 Fukui Y, Hida K, Hoshino N et al (2022) Identification of high-risk stage I colon and rectal cancer patients: a retrospective analysis of a large Japanese cohort. Int J Colorectal Dis 37:1403–1410. https://doi.org/10.1007/s00384-022-04161-3 Teloken PE, Ransom D, Faragher I et al (2016) Recurrence in patients with stage I colorectal cancer. ANZ J Surg 86:49–53. https://doi.org/10.1111/ans.13254 Kamigaichi Y, Oka S, Tanino F et al (2022) Novel endoscopic ultrasonography classification for assured vertical resection margin (≥ 500 µm) in colorectal endoscopic submucosal dissection. J Gastroenterol Hepatol 37:2289–2296. https://doi.org/10.1111/jgh.16008 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 16 Aug, 2024 Read the published version in International Journal of Colorectal Disease → Version 1 posted Editorial decision: Revision requested 29 Feb, 2024 Reviews received at journal 09 Feb, 2024 Reviewers agreed at journal 27 Jan, 2024 Reviewers invited by journal 25 Jan, 2024 Editor assigned by journal 25 Jan, 2024 Submission checks completed at journal 25 Jan, 2024 First submitted to journal 24 Jan, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-3893476","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":269618842,"identity":"82ee736b-77f3-4f0f-9869-e48a2c168f0f","order_by":0,"name":"Fumiaki Tanino","email":"","orcid":"","institution":"Department of Gastroenterology, Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Fumiaki","middleName":"","lastName":"Tanino","suffix":""},{"id":269618843,"identity":"2e8c51aa-6d16-41c4-86ed-2a99cfc1768c","order_by":1,"name":"Ken Yamashita","email":"data:image/png;base64,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","orcid":"","institution":"Department of Gastroenterology, Hiroshima University","correspondingAuthor":true,"prefix":"","firstName":"Ken","middleName":"","lastName":"Yamashita","suffix":""},{"id":269618844,"identity":"1441e1e7-61bd-411e-b211-3b22084f6077","order_by":2,"name":"Shinji Nagata","email":"","orcid":"","institution":"Department of Gastroenterology, Hiroshima City North Medical Center Asa Citizens 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Citizens Hospital","correspondingAuthor":false,"prefix":"","firstName":"Naoki","middleName":"","lastName":"Asayama","suffix":""},{"id":269618851,"identity":"7d2bbc8a-c3e8-4a5c-b84b-92512b448d77","order_by":9,"name":"Yuji Urabe","email":"","orcid":"","institution":"Department of Gastrointestinal Endoscopy and Medicine, Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Yuji","middleName":"","lastName":"Urabe","suffix":""},{"id":269618852,"identity":"8e08cb33-f819-49f4-8912-46b08dfbe943","order_by":10,"name":"Fumio Shimamoto","email":"","orcid":"","institution":"Department of Health Sciences, Hiroshima Cosmopolitan University","correspondingAuthor":false,"prefix":"","firstName":"Fumio","middleName":"","lastName":"Shimamoto","suffix":""},{"id":269618853,"identity":"3052a5bc-6c28-4400-903c-0d83b7e720a3","order_by":11,"name":"Shiro Oka","email":"","orcid":"","institution":"Department of Gastroenterology, Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Shiro","middleName":"","lastName":"Oka","suffix":""}],"badges":[],"createdAt":"2024-01-24 08:33:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3893476/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3893476/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00384-024-04700-0","type":"published","date":"2024-08-16T15:56:59+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":50386683,"identity":"8d620a69-2128-4197-8c64-4122a0ea00d9","added_by":"auto","created_at":"2024-01-30 17:47:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":17154,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of enrolled patients\u003c/p\u003e","description":"","filename":"Figure14.png","url":"https://assets-eu.researchsquare.com/files/rs-3893476/v1/c4ef8f51534dec681de5631c.png"},{"id":50385870,"identity":"ca4f8e4d-ea90-4637-92f7-4da4dc152cb2","added_by":"auto","created_at":"2024-01-30 17:39:02","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":29384,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curve for overall survival rate of patients with T1 CRC underwent additional surgery after propensity-score matching (n=106)\u003c/p\u003e","description":"","filename":"Slide2.png","url":"https://assets-eu.researchsquare.com/files/rs-3893476/v1/285ef9c185da088efe8ab334.png"},{"id":50385868,"identity":"c90c6bb5-7ec5-4d01-b549-0b1c6fe5665f","added_by":"auto","created_at":"2024-01-30 17:39:02","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":27973,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curve for recurrence-free survival rate of patients with T1 CRC underwent additional surgery after propensity-score matching (n=106)\u003c/p\u003e","description":"","filename":"Slide3.png","url":"https://assets-eu.researchsquare.com/files/rs-3893476/v1/e1ef77d106dfab20036c9f92.png"},{"id":63071146,"identity":"9704f035-add8-4427-a5dc-2d73631a9ba8","added_by":"auto","created_at":"2024-08-22 20:04:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":808668,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3893476/v1/563a9903-837c-443f-8390-119055b28593.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Vertical margin distance in T1 colorectal carcinoma resected by endoscopic submucosal dissection affects prognosis after additional surgery","fulltext":[{"header":"Introduction","content":"\u003cp\u003eColorectal carcinoma (CRC) is one of the most common malignancies of the gastrointestinal tract worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Intramucosal carcinoma does not metastasize to the lymph nodes (LN) and is a good indication for endoscopic resection (ER) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, surgery with LN dissection is recommended in principle when T1 CRC is suspected [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePreoperative diagnosis of submucosal (SM) invasion depth is important for treatment selection. According to the Japan Society of Cancer for Colon and Rectum (JSCCR) guidelines 2022, risk factors for lymph node metastasis (LNM) include the depth of SM invasion, histological grade, lymphatic and venous invasion, and tumor budding [\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Additional surgery after ER is recommended when at least one risk factor for LNM is identified [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, the rate of LNM in T1 CRC is 10% [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Therefore, additional surgeries after ER for approximately 90% of patients with T1 CRC who do not have LNM might result in overtreatment. The reported rate of LNM is 1.2% in patients with T1 CRC whose only high-risk histological characteristic is an SM invasion depth of \u0026ge;\u0026thinsp;1,000 \u0026micro;m [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The number of T1 CRC resected by ER has increased due to society\u0026rsquo;s advancing age and patient\u0026rsquo;s comorbidities [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Under these circumstances, endoscopic submucosal dissection (ESD) is considered useful for en bloc resection as a total excisional biopsy in patients with clinical T1 CRC [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe 9th edition of the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma describes that local recurrence after ER in patients with distance from the site of cancer invasion to the vertical margin (VM) of \u0026lt;\u0026thinsp;500 \u0026micro;m [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, the distance that should be maintained from the site of cancer invasion to the VM to reduce the risk of local recurrence in T1 CRC has not been established. We previously evaluated the effects of the distance from the vertical tumor margin to the edge of resected specimen (VM distance) in ER for T1b CRC on the prognosis of patients who underwent surgery after ER [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. For the purpose of generalization, we aimed to evaluate the effects of the VM distance in ESD for T1b CRC on metastatic recurrence and the prognosis of patients who underwent additional surgery after ESD at multiple centers.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the flow of patients through the study. Among 277 patients with T1 CRC who underwent ESD between January 2008 and June 2016 (at Hiroshima University Hospital, Hiroshima City North Medical Center Asa Citizens Hospital, and National Organization Kure Medical Center and Chugoku Cancer Center), we excluded 123 based on the following: SM invasion\u0026thinsp;\u0026lt;\u0026thinsp;1,000 \u0026micro;m, treated only by ESD, positive LNM at additional surgery after ESD (pStage Ⅲ), and \u0026lt;\u0026thinsp;5 years of follow-up. We finally analyzed data from 154 patients. We did not include patients with pedunculated-type CRC because they might be easier to treat by endoscopic mucosal resection than by ESD. Moreover, to assess risk factors for the pathological features of LNM, evaluating an accurate pathological specimen was necessary. Therefore, only patients who underwent resection using ESD were included. The patients were classified into two groups based on the VM distance of ESD specimens: patients with VM distance\u0026thinsp;\u0026lt;\u0026thinsp;500 \u0026micro;m including positive VM, (VM distance\u0026thinsp;\u0026lt;\u0026thinsp;500 \u0026micro;m group, n\u0026thinsp;=\u0026thinsp;62) and patients with VM distance of \u0026ge;\u0026thinsp;500 \u0026micro;m (VM distance\u0026thinsp;\u0026ge;\u0026thinsp;500 \u0026micro;m group, n\u0026thinsp;=\u0026thinsp;92). Finally, to align the background factors for each group, we performed one-to-one propensity-score matching (PSM), using the covariates of age, sex, tumor size, location, and macroscopic type. Thereafter, we identified 53 patients in each group. All cases were performed ESD by the experienced experts. The study proceeded according to ethical standards of Declaration of Helsinki (2014). The Ethics Committees at Hiroshima University and its affiliated hospital approved the study protocol (Approval No. E-0334) and each affiliated hospital and was in accordance with the guidelines of the Ministry of Health Labour and Welfare. All patients provided informed consent prior to the procedures.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eIndications for ESD\u003c/h2\u003e \u003cp\u003eThe indications for ER in early-stage CRC followed the JSCCR guidelines [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Intramucosal carcinoma and T1 CRC with SM depth invasion\u0026thinsp;\u0026lt;\u0026thinsp;1,000 \u0026micro;m are at low risk for LNM and a good indication for en bloc resection by ER. By contrast, clinically obvious T1b CRC is usually surgically treated. However, we sometimes attempted ER for T1b CRC as a total excisional biopsy depending on patient preference, comorbidities, and general physical condition. The indications for ESD were as follows: lesions difficult to resect en bloc (non-granular, laterally spreading tumors, particularly those of the pseudo-depressed type), lesions with a type V\u003csub\u003eI\u003c/sub\u003e pit pattern, carcinoma with shallow SM invasion, large elevated lesions of suspected carcinoma, mucosal lesions with SM fibrosis caused by biopsy or severe peristalsis, local residual early carcinoma after ER, and sporadically localized lesions in chronic inflammation such as ulcerative colitis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eIndications for additional surgery after ESD\u003c/h2\u003e \u003cp\u003e According to the JSCCR guidelines, patients with VM positivity require additional surgery after ESD. Patients with VM negativity are considered for additional surgery if any of the following pathological features are found in resected specimens: SM invasion depth\u0026thinsp;\u0026ge;\u0026thinsp;1,000 \u0026micro;m, main histology of poorly differentiated adenocarcinoma or mucinous carcinoma or signet-cell carcinoma, positive lymphatic and/or venous invasion, and budding grade 2/3 at the site of deepest invasion [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In principle, additional surgery should proceed within 3 months of ESD. D2 LN dissection (middle LN) was performed according to the JSCCR guidelines.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003ePathological evaluation\u003c/h2\u003e \u003cp\u003eResected specimens were fixed in 10% buffered formalin for 12\u0026ndash;48 h. Surgical and endoscopic specimens were cut into parallel sections 3\u0026ndash;4- and 2-mm-thick, respectively. A single gastrointestinal pathologist diagnosed all histopathological findings, and the patients were blinded to the clinical information. Pathological features, including the depth of SM invasion, histological grade, tumor budding grade, and lymphatic and venous invasion, were evaluated by hematoxylin\u0026ndash;eosin (HE) and specific staining (Victoria blue, Elastica van Gieson, D2-40, Desmin) as needed. The depth of SM invasion was measured from the lower border of the muscularis mucosae when possible. If the muscularis mucosae could not be identified or located, the depth of SM invasion was measured from the surface layer of the mucosa [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The histological grade was classified as favorable (tubular or papillary adenocarcinoma) and unfavorable (poorly differentiated adenocarcinoma, mucinous carcinoma, or signet-ring cell carcinoma). The histological type of the invasive front was classified as well, moderately well, moderately poorly, and poorly differentiated adenocarcinoma. Tumor budding grade was graded per microscopic field at 200\u0026times; magnification: low grade: grade 1, 0\u0026ndash;4 buds; high grade: grade 2, 5\u0026ndash;9, buds; and grade 3, 10 or more buds [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. VM positivity was defined as the presence of tumors and mucinous components at the VM. VM distance was defined as the distance from the site of the deepest invasion of the cancer to the VM.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eSurveillance after additional surgery\u003c/h2\u003e \u003cp\u003eThe follow-up was extended to \u0026gt;\u0026thinsp;5 years after the initial treatment. The patients were postoperatively interviewed and physically examined, underwent blood tests, and were assessed by chest and abdominal computed tomography (CT) every 6 months for the first 3 years, then annually for the next 2 years. In principle, the patients were postoperatively assessed by total colonoscopy annually for 5 years. Recurrence was confirmed by endoscopy, CT, and other findings. Recurrence at CRC sites and pelvic recurrence in patients with rectal CRC were defined as local. Metastases outside the intestinal tract were defined as distant.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eInvestigated variables\u003c/h2\u003e \u003cp\u003eWe compared the clinicopathological variables of age, sex, tumor size, tumor location, macroscopic type, treatment, metastasis/recurrence, main histology, SM invasive depth, VM distance, lymphatic and venous invasion, budding grade, and LNM after additional surgery for T1 CRC between VM distance\u0026thinsp;\u0026lt;\u0026thinsp;500 and \u0026ge;\u0026thinsp;500 \u0026micro;m groups before and after PSM. We compared the incidences of recurrence, overall survival (OS; to the day of death from any cause), and recurrence-free survival (RFS; elapsed time from the day of ESD until local and/or distant recurrence was identified) between the groups after PSM.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData are presented as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Between-group differences were analyzed using chi-square or Fisher exact tests. Values with p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant. The OS and the RFS were calculated using the Kaplan\u0026ndash;Meier method. Significant differences in the baseline clinical characteristics of the patients and the influence of possible confounding factors were adjusted using PSM. Propensity scores were estimated using a logistic regression model that included age, sex, tumor location, tumor size, and macroscopic type as variables. Thereafter, the closest eligible control unit to be paired with each treated unit was selected by one-to-one nearest neighbor matching using a caliper set at 0.25. All data were statistically analyzed using JMP statistical software v. 16.2.0 (SAS Institute, Cary, NC, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eBaseline characteristics of patients\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the baseline characteristics of the 277 patients (mean age, 68.9 y; male, n\u0026thinsp;=\u0026thinsp;161 [58%]). The mean tumor size was 31 mm, and 173 (62%) of 277 lesions were located in the colon. Among macroscopic type, 95 (34%) of 277 patients had protruded lesions. Among 194 (70%) of 277 patients who underwent additional surgery, LNM were found in 17 (9%). Local recurrence and distant metastasis were found in 6 (2%) and 7 (3%) of the 277 patients. Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the clinicopathological features of patients with T1b CRC without LNM who underwent additional surgery (pStage I) before and after PSM. Before PSM, the VM distance\u0026thinsp;\u0026lt;\u0026thinsp;500 \u0026micro;m group consisted of 62 patients, and the VM distance\u0026thinsp;\u0026ge;\u0026thinsp;500 \u0026micro;m group consisted of 92 patients. Age, sex, tumor location, macroscopic type, main histology, and lymphatic or venous invasion did not significantly differ between the groups. Tumors were significantly smaller in the VM distance\u0026thinsp;\u0026lt;\u0026thinsp;500 group than that in the \u0026ge;\u0026thinsp;500 \u0026micro;m group (26\u0026thinsp;\u0026plusmn;\u0026thinsp;15 vs. 33\u0026thinsp;\u0026plusmn;\u0026thinsp;19 mm; p\u0026thinsp;=\u0026thinsp;0.012). The rate of budding grade 2/3 was significantly higher in the VM distance\u0026thinsp;\u0026lt;\u0026thinsp;500 \u0026micro;m group than that in the VM distance\u0026thinsp;\u0026ge;\u0026thinsp;500 \u0026micro;m group (22 [35%] of 62 vs. 15 [16%] of 92; p\u0026thinsp;=\u0026thinsp;0.007). The clinicopathological backgrounds did not significantly differ between the groups were found after PSM.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinicopathological features of enrolled patients (n\u0026thinsp;=\u0026thinsp;277)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge (years old, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68.9\u0026thinsp;\u0026plusmn;\u0026thinsp;9.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e161 (58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e116 (42)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTumor location\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eColon\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e173 (62)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eRectum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e104 (38)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTumor size (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31.0\u0026thinsp;\u0026plusmn;\u0026thinsp;18.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMedian (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (4-100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMacroscopic type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eProtruded\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0-Is\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e67 (24)\u003c/p\u003e \u003cp\u003e3 (1)\u003c/p\u003e \u003cp\u003e8 (3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0-Is +\u0026thinsp;IIa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0-Is +\u0026thinsp;IIc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0-Isp\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0-Isp\u0026thinsp;+\u0026thinsp;IIc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuperficial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0-IIa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"2\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e125 (45)\u003c/p\u003e \u003cp\u003e54 (19)\u003c/p\u003e \u003cp\u003e3 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0-IIa\u0026thinsp;+\u0026thinsp;IIc\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0-IIc\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eESD alone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83 (30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAdditional surgery after ESD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e194 (70)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMetastasis/Recurrence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLocal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDistant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eHistology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003etub/pap\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e274 (99)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003epor/muc/sig\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSM depth (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u0026lt;1000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e97 (35)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e≧1000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e180 (65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVM distance (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u0026lt;500 (including VM positive)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e140 (51)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e≧500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e137 (49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLymphatic invasion positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68 (25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVenous invasion positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67 (24)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eBudding grade 2/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48 (17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLNM after additional surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17/194 (9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e(%)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eSD: standard deviation; ESD: endoscopic submucosal dissection; tub: tubular adenocarcinoma;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003epap: papillary adenocarcinoma; por: poorly differentiated adenocarcinoma; muc: mucinous adenocarcinoma;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003esig: signet-ring adenocarcinoma; SM: submucosal; VM: vertical margin; LNM: lymph node metastasis\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinicopathological features of T1 CRC patients without LNM after additional surgery before and after propensity-score matching\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e \u003cp\u003eAll patients (n\u0026thinsp;=\u0026thinsp;154)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e \u003cp\u003ePropensity-matched patients (n\u0026thinsp;=\u0026thinsp;106)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVM distance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eVM distance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;500 \u0026micro;m, (n\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e≧\u0026thinsp;500 \u0026micro;m, (n\u0026thinsp;=\u0026thinsp;92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;500 \u0026micro;m, (n\u0026thinsp;=\u0026thinsp;53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e≧\u0026thinsp;500 \u0026micro;m, (n\u0026thinsp;=\u0026thinsp;53)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge (years old, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e70\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.581\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e68\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e69\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.959\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36 (58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48 (52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.471\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e31 (58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e27 (51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.435\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e44 (48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e22 (42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e26 (49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTumor size (mm, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33\u0026thinsp;\u0026plusmn;\u0026thinsp;19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e27.0\u0026thinsp;\u0026plusmn;\u0026thinsp;15.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e26.9\u0026thinsp;\u0026plusmn;\u0026thinsp;14.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.866\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTumor location\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eColon\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42 (68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52 (57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.161\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e37 (70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e31 (58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.224\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRectum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40 (43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e16 (30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e22 (42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMacroscopic type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eProtruded\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0-Is\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31 (34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.068\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e16 (30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e22 (41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.548\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"3\" nameend=\"c2\" namest=\"c1\" rowspan=\"4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0-Is +\u0026thinsp;IIa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0-Is +\u0026thinsp;IIc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0-Isp\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0-Isp\u0026thinsp;+\u0026thinsp;IIc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eSuperficial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0-IIa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35 (38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e15 (28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e17 (32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0-IIa\u0026thinsp;+\u0026thinsp;IIc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e13 (24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e8 (15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0-IIc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMain histology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003etub/pap\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61 (98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e91 (99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.778\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e52 (98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e52 (98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epor/sig/muc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLymphatic invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e70 (76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e35 (66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e43 (81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.078\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22 (24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e18 (34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e10 (19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVenous invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24 (24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.147\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e33 (62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e40 (75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.142\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39 (63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e68 (76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e20 (38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e13 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eBudding grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGrade 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e77 (84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e40 (75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e41 (77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.819\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGrade 2/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15 (16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e13 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e12 (23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMetastasis/ recurrence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eAverage follow-up period (months, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79\u0026thinsp;\u0026plusmn;\u0026thinsp;22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e74\u0026thinsp;\u0026plusmn;\u0026thinsp;23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.178\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e79\u0026thinsp;\u0026plusmn;\u0026thinsp;21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e77\u0026thinsp;\u0026plusmn;\u0026thinsp;26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.372\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003eCRC: colorectal carcinoma; LNM: lymph node metastasis; VM: vertical margin; SD: standard deviation; tub: tubular adenocarcinoma; pap: papillary adenocarcinoma; (%)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003epor: poorly differentiated adenocarcinoma; sig: signet-ring adenocarcinoma; muc: mucinous adenocarcinoma\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ePrognosis after additional surgery\u003c/h2\u003e \u003cp\u003eThe average follow-up periods in the VM distance\u0026thinsp;\u0026lt;\u0026thinsp;500 \u0026micro;m group and VM distance\u0026thinsp;\u0026ge;\u0026thinsp;500 \u0026micro;m group were 79\u0026thinsp;\u0026plusmn;\u0026thinsp;22 and 74\u0026thinsp;\u0026plusmn;\u0026thinsp;23 months, respectively. The rates of recurrence in the VM distance\u0026thinsp;\u0026lt;\u0026thinsp;500 and \u0026ge;\u0026thinsp;500 \u0026micro;m groups after PSM were 6 (11%) and 0 (0%) of 53, respectively. The recurrence rate was also significantly higher in the VM distance\u0026thinsp;\u0026lt;\u0026thinsp;500 than that in the \u0026ge;\u0026thinsp;500 \u0026micro;m group after PSM (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the characteristics of six patients with recurrence within 5 years of ESD in within the intrapelvis (n\u0026thinsp;=\u0026thinsp;1), lungs (n\u0026thinsp;=\u0026thinsp;3), lung and lymph node (n\u0026thinsp;=\u0026thinsp;1) and liver (n\u0026thinsp;=\u0026thinsp;1). Five recurrences were located in rectum and had tumor budding grade 2 or 3. Four recurrences of 6 were positive for lymphatic invasion. All patients with recurrence had VM distance\u0026thinsp;\u0026lt;\u0026thinsp;500 \u0026micro;m, and one had a positive VM. The 5-year OS rates in the VM distance\u0026thinsp;\u0026ge;\u0026thinsp;500 \u0026micro;m group and VM distance\u0026thinsp;\u0026lt;\u0026thinsp;500 \u0026micro;m group were 100% and 98.1%, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), whereas that of RFS significantly differed at 88.6% and 100%, respectively (p\u0026thinsp;=\u0026thinsp;0.012; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of 6 patients with recurrence\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"15\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCase\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003cp\u003e(years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTumor\u003c/p\u003e \u003cp\u003elocation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTumorsize\u003c/p\u003e \u003cp\u003e(mm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMacroscopic\u003c/p\u003e \u003cp\u003etype\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSM\u003c/p\u003e \u003cp\u003edepth\u003c/p\u003e \u003cp\u003e(\u0026micro;m)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eLy/V\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMain\u003c/p\u003e \u003cp\u003ehistology\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eHistology in invasive front\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eVM\u003c/p\u003e \u003cp\u003edistance\u003c/p\u003e \u003cp\u003e(\u0026micro;m)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eRecurrence\u003c/p\u003e \u003cp\u003esite\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003eInterval of\u003c/p\u003e \u003cp\u003erecurrence\u003c/p\u003e \u003cp\u003e(month)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c15\"\u003e \u003cp\u003ePrognosis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0-IIa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-/+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eWell\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eWell\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e290\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eLiver\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003cp\u003e(from other disease)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0-Is\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5700\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-/+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePap\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eMode\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e210\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eLung\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003cp\u003e(from other disease)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0-IIa\u0026thinsp;+\u0026thinsp;IIc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+/+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMode\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003ePor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e380\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eLung, LN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0-Is\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2800\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+/+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eWell\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eMode\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eLung\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eA/C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0-IIa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+/+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eWell\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eMode\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eVM positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eLung\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0-Is +\u0026thinsp;IIc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2800\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+/-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eWell\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eMode\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eIntrapelvis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"15\"\u003eSM: submucosal; Ly: lymphatic invasion; V: venous invasion; BD: budding grade; VM: vertical margin; Ra: rectum above the peritoneal reflection; Rb: rectum below the peritoneal\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"15\"\u003ereflection; A/C: ascending colon; Well: well differentiated adenocarcinoma; Pap: papillary adenocarcinoma; Mode: moderately differentiated adenocarcinoma;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"15\"\u003ePor: poorly differentiated adenocarcinoma; LN: lymph node\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis multicenter study found that ESD for T1 CRC required complete en bloc resection, including sufficient submucosa, to reduce the risk of metastasis and/or recurrence after additional surgery.\u003c/p\u003e \u003cp\u003eThe pathological risk factors for LNM include SM depth invasion\u0026thinsp;\u0026ge;\u0026thinsp;1,000 \u0026micro;m, an unfavorable histological grade (poorly differentiated adenocarcinoma or mucinous carcinoma or signet-ring cell carcinoma), positive lymphatic and/or venous invasion, and tumor budding grade 2/3 according to the JSCCR guidelines [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Furthermore, others have found that female sex, left-sided colorectal lesions, rectal lesions, and completely disrupted muscularis mucosae are risk factors for LNM [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The LNM rate of T1 CRC range is 9%‒15.8% [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan additionalcitationids=\"CR22 CR23 CR24 CR25\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In other words, additional surgery for all cases with risk factors for LNM might result in unnecessary or excessive treatment, which is a concern.\u003c/p\u003e \u003cp\u003eTo select patients with low risk factors for LNM, a specimen that can be properly evaluated is needed. We previously reported that en bloc ESD, as a total excisional biopsy for clinical T1b CRC, is effective and establishes a precise histological diagnosis [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, ESD for T1b tumors is technically difficult, and some lesions cannot be resected en bloc. We previously reported that SM fibrosis or poor differentiation at the deepest invasive front of the tumor is associated with a high risk of positive VM in ESD for CRC with SM deep invasion [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In addition, Yasue et al. reported that pathological T1b CRC with obvious depression and severe fibrosis have a high risk of incomplete VM ESD [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Patients with VM positive require additional surgery because the likelihood of recurrence is high due to local remnants of cancer [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Moreover, residual tumors and incomplete ER are associated with high risk for local recurrence [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Growth of residual tumors after ER is reportedly more rapid [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Therefore, very careful ESD is needed for T1b CRC with preoperative suspicions of obvious depression, mucus components at the deepest point on endoscopic ultrasonography (EUS), or the expectation of severe SM fibrosis.\u003c/p\u003e \u003cp\u003eSeveral studies have reported whether ER before surgery affects the subsequent prognosis in patients with T1 CRC. The local recurrence rate of pathologically high-risk T1 CRC after ER is 2.7\u0026ndash;20.1% [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], while that for additional surgery after ER is 0\u0026ndash;2.5% [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan additionalcitationids=\"CR30 CR31\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Additional surgery deters local recurrence of T1 CRC with high-risk factors for LNM. Moreover, prior ER does not affect the recurrence or prognosis of T1 CRC after additional surgery [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. We previously found no significant differences in 5-year OS (96.9% vs. 92.0%) and 5-year disease-free survival rates (96.7% vs. 98.6%) after treatment between the additional surgery after ESD and surgery alone groups, respectively [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Therefore, prior ESD for T1 CRC had no adverse oncological effects on en bloc histological resection. However, whether additional surgery would be effective in patients with VM-positive cases is unclear because these reports included and evaluated both VM-positive and VM-negative cases [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Kono et al. reported remnant cancer in the intestinal tract resected by additional surgery in one case with VM distance of \u0026lt;\u0026thinsp;500 \u0026micro;m and in one case with positive VM [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. In addition, Belderbos et al. reported that a positive resection margin was an independent risk factor for recurrence [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Thus, a positive VM in ESD might also be a risk factor for recurrence. We previously evaluated associations between the VM distance and recurrence or metastasis and the prognosis of patients with T1b CRC. We found that the 5-year OS and disease-specific survival rates were significantly lower in the VM distance\u0026thinsp;\u0026lt;\u0026thinsp;500 \u0026micro;m group compared with the VM distance\u0026thinsp;\u0026ge;\u0026thinsp;500 \u0026micro;m group [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. This study had similar results, although ER was limited to cases resected by ESD. Why metastasis or recurrence was more prevalent in the VM distance\u0026thinsp;\u0026lt;\u0026thinsp;500 \u0026micro;m group was higher was under discussion. Several opinions have been offered to explain this phenomenon. During colorectal ESD, tumor cells are exfoliated into the intestinal lumen [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Colorectal cancer cells might become implanted into artificial ulcers after ER [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Neoplastic cells might shed from the tumor surface and become implanted on the exposed SM layer or directly into the damaged lymphatics of an artificial ulcer because ESD for primary lesions is a lengthy process [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Moreover, for stage I CRC, the cause of recurrence is either undetectable local residual tumors or the presence of micrometastasis [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Several studies reported that lymphatic invasion is an independent risk factor for metastatic recurrence in patients with surgically treated pT1 CRC [\u003cspan additionalcitationids=\"CR39 CR40\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Complete en bloc resection with a sufficient SM layer (VM distance\u0026thinsp;\u0026ge;\u0026thinsp;500 \u0026micro;m) by ESD for T1 CRC is essential to reduce the risk of recurrence.\u003c/p\u003e \u003cp\u003ePredicting whether T1 CRC is sufficiently distant from the VM to be resected by ESD is important. Preoperative EUS is useful for predicting the VM distance [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. We defined the distance from the tumor invasive front to the muscle layer on EUS as being tumor-free and found that classifying tumor-free distance as \u0026lt;\u0026thinsp;1 or \u0026ge;\u0026thinsp;1 mm was useful for preoperative prediction of VM distance\u0026thinsp;\u0026ge;\u0026thinsp;500 \u0026micro;m [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. In the near future, preoperative EUS will become increasingly important for evaluating whether pT1b CRC can be treated by ESD as a total excisional biopsy.\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, this was a retrospective cohort study based on clinical records. Second, we reevaluated the pathological diagnosis and features, including tumor budding; however, we did not reevaluate lymphovascular invasion using immunohistochemical staining in all cases. Third, we could not collect data about parameters such as performance status and comorbidities. At least 12 LNs should be dissected to accurately diagnose advanced colon cancer according to the National Comprehensive Cancer Network, some patients with 12 LNs were dissected and evaluated for LNM; thus, LNM might have been underestimated. Large multicenter studies are needed to overcome these limitations.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe recurrence rate was significantly higher in the VM distance\u0026thinsp;\u0026lt;\u0026thinsp;500 \u0026micro;m group compared with the VM distance\u0026thinsp;\u0026ge;\u0026thinsp;500 \u0026micro;m group, and the 5-year OS and RFS rates were significantly lower in the VM distance\u0026thinsp;\u0026lt;\u0026thinsp;500 \u0026micro;m group than in the VM distance\u0026thinsp;\u0026ge;\u0026thinsp;500 \u0026micro;m group after PSM. Therefore, ensuring a sufficient VM distance during ESD is important to reduce the risk of recurrence after additional surgery.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy design: Shiro Oka, Ken Yamashita and Fumiaki Tanino. Sample collection: Fumiaki Tanino, Shinji Ngata, Toshio Kuwai, Yuki Kamigaichi, Hidenori Tanaka, Yuzuru Tamaru, Hidehiko Takigawa, Naoki Asayama, Yuji Urabe. Sample evaluation: Fumio Shimamoto. Data collection: Fumiaki Tanino. Data analysis: Fumiaki Tanino. Manuscript writing: Fumiaki Tanino and Ken Yamashita. All authors have read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was obtained for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are not openly available due to the privacy of patients and are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003eData are in controlled access data storage at Hiroshima University Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone of the authors has any competing interests to disclose.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHori M, Matsuda T, Shibata A et al (2015) Cancer incidence and incidence rates in Japan in 2009: a study of 32 population-based cancer registries for the Monitoring of Cancer Incidence in Japan (MCIJ) project. 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J Gastroenterol Hepatol 37:2289\u0026ndash;2296. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/jgh.16008\u003c/span\u003e\u003cspan address=\"10.1111/jgh.16008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-colorectal-disease","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijcd","sideBox":"Learn more about [International Journal of Colorectal Disease](http://link.springer.com/journal/384)","snPcode":"384","submissionUrl":"https://submission.nature.com/new-submission/384/3","title":"International Journal of Colorectal Disease","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"colorectal cancer, metastasis, recurrence, vertical margin, endoscopic submucosal dissection","lastPublishedDoi":"10.21203/rs.3.rs-3893476/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3893476/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eA vertical margin (VM) distance of \u0026lt;\u0026thinsp;500 \u0026micro;m is a risk factor for recurrence in patients with T1 colorectal carcinoma (CRC) resected by endoscopy. We aimed to determine the effects of the VM distance on the recurrence and prognosis of T1 CRC\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe enrolled 154 patients with T1 CRC who underwent additional surgery after endoscopic submucosal dissection (ESD) at multiple centers between 2008 and 2016. None of the patients had lymph node metastasis (pStage I) and were followed up for \u0026gt;\u0026thinsp;5 years. A total of 154 patients were classified into patients with VM distance of \u0026lt;\u0026thinsp;500 \u0026micro;m including positive VM (n\u0026thinsp;=\u0026thinsp;62, VM distance\u0026thinsp;\u0026lt;\u0026thinsp;500 \u0026micro;m group) and patients with VM distance of \u0026ge;\u0026thinsp;500 \u0026micro;m (n\u0026thinsp;=\u0026thinsp;92, VM distance\u0026thinsp;\u0026ge;\u0026thinsp;500 \u0026micro;m group). The clinicopathological features, recurrence rates, and prognoses were compared between the groups using propensity-score matching (PSM).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTumor size and the rate of budding grade 2/3 in the VM distance\u0026thinsp;\u0026lt;\u0026thinsp;500 \u0026micro;m group was significantly smaller and higher, respectively, than those in the VM distance\u0026thinsp;\u0026ge;\u0026thinsp;500 \u0026micro;m group. Tumors recurred in six of the 154 patients with VM distance\u0026thinsp;\u0026lt;\u0026thinsp;500 \u0026micro;m. The 5-year recurrence-free survival rate was significantly higher in the VM distance\u0026thinsp;\u0026ge;\u0026thinsp;500 \u0026micro;m group than that in VM distance\u0026thinsp;\u0026lt;\u0026thinsp;500 \u0026micro;m group after PSM (100% vs. 90%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.012).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eComplete en bloc resection of T1 CRC \u003cem\u003evia\u003c/em\u003e ESD must include a sufficient amount of submucosa to reduce the risk of metastasis and recurrence after additional surgery.\u003c/p\u003e","manuscriptTitle":"Vertical margin distance in T1 colorectal carcinoma resected by endoscopic submucosal dissection affects prognosis after additional surgery","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-30 17:38:57","doi":"10.21203/rs.3.rs-3893476/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-02-29T11:24:28+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-02-09T23:10:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"2acf489d-e188-4014-aad0-b5e102463ffd","date":"2024-01-27T14:52:25+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-01-25T14:25:31+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-01-25T07:00:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-01-25T07:00:59+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Colorectal Disease","date":"2024-01-24T08:32:02+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-colorectal-disease","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijcd","sideBox":"Learn more about [International Journal of Colorectal Disease](http://link.springer.com/journal/384)","snPcode":"384","submissionUrl":"https://submission.nature.com/new-submission/384/3","title":"International Journal of Colorectal Disease","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"c2d79ff6-852f-40fc-960a-13f4f7ba4333","owner":[],"postedDate":"January 30th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-08-22T19:33:07+00:00","versionOfRecord":{"articleIdentity":"rs-3893476","link":"https://doi.org/10.1007/s00384-024-04700-0","journal":{"identity":"international-journal-of-colorectal-disease","isVorOnly":false,"title":"International Journal of Colorectal Disease"},"publishedOn":"2024-08-16 15:56:59","publishedOnDateReadable":"August 16th, 2024"},"versionCreatedAt":"2024-01-30 17:38:57","video":"","vorDoi":"10.1007/s00384-024-04700-0","vorDoiUrl":"https://doi.org/10.1007/s00384-024-04700-0","workflowStages":[]},"version":"v1","identity":"rs-3893476","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3893476","identity":"rs-3893476","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}