Comparative Study on Efficacy and Risk of Pathological Upgrading between Endoscopic and Surgical Resection for Colorectal High-Grade Intraepithelial Neoplasia: A Retrospective Analysis

Comparative Study on Efficacy and Risk of Pathological Upgrading between Endoscopic and Surgical Resection for Colorectal High-Grade Intraepithelial Neoplasia: A Retrospective Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparative Study on Efficacy and Risk of Pathological Upgrading between Endoscopic and Surgical Resection for Colorectal High-Grade Intraepithelial Neoplasia: A Retrospective Analysis Yang Yang, Kexin Shen, Zhongshi Xie This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8279345/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background Accurate management of colorectal high-grade intraepithelial neoplasia (HGIN) is challenging due to the limited accuracy of diagnostic endoscopic biopsy and the difficulty in choosing between endoscopic therapy and radical surgery. Methods We retrospectively analyzed 69 patients with preoperative biopsy-diagnosed colorectal HGIN (2019–2023). Data included demographics, lesion features, and treatments, focusing on preoperative-postoperative pathological concordance. Results Fifty-six and thirteen patients underwent endoscopic resection (ER) and additional surgery resection (ASR), respectively. The baseline characteristics were balanced between the two groups, with no statistically significant differences observed in age, sex, clinical presentation, or lesion number (P > 0.05). Complication rates were similar (16.1% vs. 15.4%, P = 0.723). The biopsy accuracy was 81.2%; 18.8% of lesions were upgraded to T1 colorectal cancer (CRC). Lesions in the ASR group were larger than in the ER group (2.2 ± 0.51 cm vs. 1.9 ± 0.43 cm, P = 0.015). T1 lesions were larger than HGIN lesions (P = 0.002). Rectosigmoid location (P = 0.032) and solitary lesions (carcinoma rate: ASR 62.5% vs. ER 4.76%; OR = 33.33, P < 0.001) conferred higher cancer risk. For solitary lesions, the carcinoma rate was significantly higher in the ASR group than in the ER group (62.5% vs. 4.76%, OR = 33.33, P < 0.001). Although sessile morphology was associated with the decision for surgical intervention (P = 0.003), its efficacy in discriminating between HGIN and T1 carcinoma was limited (P = 0.057). Lymph node metastasis (LNM) occurred only in T1 patients (27.3%; 28.6% in the ASR). High-grade tumor budding (Bd > 1) and lymph vascular invasion (LVI) were enriched in the ASR group (OR = 43.33, P < 0.001) and strongly associated with T1 cancer (P < 0.001). The R0 resection rate was comparable between HGIN and T1 lesions (P = 0.264). Conclusion Improving endoscopic biopsy accuracy is essential. ER is safe and feasible, providing effective local control for HGIN and low-risk T1 CRC without LNM. Colorectal high-grade intraepithelial neoplasia Endoscopic resection Surgical resection Colorectal cancer Diagnostic accuracy Risk factors Introduction In 2000, the World Health Organization (WHO) recommended the term "intraepithelial neoplasia" (IN) to replace previous designations such as "dysplasia" and "carcinoma in situ," aiming to more accurately reflect the biological nature of lesions and guide clinical management. When neoplastic tissue is confined within the muscularis mucosae, the lack of lymphatic vessels in the mucosal epithelium and lamina propria renders the probability of metastasis extremely low. Lacking the defining metastatic characteristics of cancer, such lesions are classified as HGIN. However, some scholars note that a minor lymphatic plexus and a well-developed capillary network do exist within the colorectal mucosa, potentially explaining why LNM can still occur in some patients even when the lesion is superficial[ 1 , 2 ].In recent years, pathologists have emphasized the new definition of tumor budding (TB) and recommended its inclusion in pathological diagnoses due to its strong association with LNM, disease prognosis, and mortality risk. The International Tumor Budding Consensus Conference (ITBCC) recommends a three-tier grading system: low-grade (Bd1, 0–4 buds), intermediate-grade (Bd2, 5–9 buds), and high-grade (Bd3, ≥ 10 buds), which should be specified in pathology reports[ 3 ]. Colorectal HGIN, as a precancerous lesion, often lacks obvious clinical symptoms such as hematochezia or constipation and is not limited to the lower rectum. Consequently, endoscopic examination serves as the primary method for its screening. The accuracy of endoscopic biopsy is crucial in selecting treatment, as it can be used for both diagnosis and therapy, offering advantages such as minimal invasiveness, a short procedure time, and a low cost. However, because only a small, localized area of the lesion is sampled, foci of carcinoma may be missed. Inaccurate sampling due to inexperience can also lead to misdiagnosis or underdiagnosis. Generally, superficial submucosal invasion (depth ≤ 1000 µm) is considered an indication for endoscopic treatment, while deep submucosal invasion (> 1000 µm) carries a risk of LNM and vascular invasion, warranting ASR. Common clinical endoscopic techniques include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). EMR is typically suitable for lesions less than 2.0 cm in diameter with a relatively flat morphology. ESD is indicated for lesions that are not amenable to EMR, those larger than 2.0 cm, or those with slight submucosal infiltration but without evidence of LNM or vascular/neural invasion. Although ER offers benefits like shorter hospital stays, lower cost, and minimal trauma, it is not without risks, including delayed postoperative hemorrhage, perforation, and tumor recurrence or metastasis. Delayed bleeding often presents acutely with significant blood loss, requiring surgical intervention. Additionally, overly aggressive resection damaging the muscular layer can lead to perforation, potentially resulting in peritonitis, abdominal infection, or septic shock. Surgical treatment has evolved from open surgery to laparoscopic and robotic-assisted techniques. These advancements have significantly reduced bodily trauma, shortened hospital stays, and lowered the risks of postoperative complications such as intra-abdominal and wound infections compared to open surgery. Surgery allows for the complete removal of the tumor along with any infiltrated or metastatic lymphatics and nerves, thereby reducing the risk of recurrence and metastasis. However, the postoperative period, requiring fasting and bed rest, is associated with higher incidences of hypostatic pneumonia and hypoproteinemia. Furthermore, the hospital stay is typically longer, and the cost is higher compared to endoscopic treatment. Based on the preoperative and postoperative pathological findings from patients with colorectal HGIN treated endoscopically or surgically, this study aims to analyze the accuracy of endoscopic diagnosis, identify high-risk factors for pathological upgrading in HGIN, and evaluate the complete therapeutic efficacy of endoscopic treatment. The goal is to provide evidence for optimizing treatment strategies for patients. Methods Patients This study was approved by the Ethics Committee of the China-Japan Union Hospital, Jilin University. Clinical data were retrospectively collected from 69 patients with a preoperative diagnosis of colorectal HGIN at our institution between January 2019 and January 2023. Among them, 56 patients underwent endoscopic therapy alone, and 13 patients underwent surgical treatment. The cohort consisted of 47 males and 22 females, aged 30–84 years (mean, 60.4 ± 9.0 years). Tumor staging was performed according to the Tumor, Node, Metastasis (TNM) classification system of the American Joint Committee on Cancer (AJCC, 8th edition). The inclusion criteria were: (1) Preoperative pathological diagnosis of colorectal HGIN before endoscopic or surgical therapy; (2) No prior neoadjuvant chemoradiotherapy or other anti-tumor treatments before endoscopic or surgical intervention; (3) Availability of complete clinical, pathological, and imaging data. The exclusion criteria were: (1) Preoperative pathology confirming carcinoma (e.g., intramucosal carcinoma); (2) Preoperative diagnosis of colorectal LGIN or benign tumors; (3) History of neoadjuvant chemoradiotherapy or other anti-tumor treatments; (4) Lack of pathological confirmation of HGIN by endoscopic biopsy; (5) Incomplete case data. Histopathological evaluation Biopsy specimens were fixed in formaldehyde, embedded in paraffin, and serially sectioned. Sections were stained with hematoxylin and eosin (H&E). According to WHO criteria, colorectal HGIN was defined by the presence of dysplastic epithelial cells with significant cytological and architectural abnormalities, confined above the basement membrane without evidence of invasive carcinoma. Lesions were classified as T1CRC when neoplastic cells breached the basement membrane and invaded the submucosa but did not reach the muscularis propria. Grouping Patients were divided into two groups: The ER group comprised 56 patients who underwent endoscopic therapy (EMR or ESD) without subsequent surgical intervention. The ASR group consisted of 13 patients who underwent radical surgery following initial ER due to the presence of one or more high-risk pathological features: (1) positive resection margins; (2) submucosal invasion depth > 1000 µm (SM2/3); (3) LVI; (4) poorly differentiated adenocarcinoma, signet-ring cell carcinoma, or mucinous adenocarcinoma; (5) tumor budding grade Bd2 or Bd3. Data collection Collected data included: (1) Demographic characteristics: age and sex; (2) Lesion characteristics: size, location (rectum/sigmoid colon/other colon), morphology (pedunculated/sessile), number (solitary/multiple), depth of invasion, LNM status, LVI, and histological type; (3) Clinical presentation: presence or absence of symptoms (e.g., hematochezia, abdominal pain, altered bowel habits); (4) Pathological results: preoperative biopsy pathology and final postoperative pathology (TNM staging according to AJCC 8th edition); (5) Treatment-related details: surgical approach and postoperative complications. Statistical analysis Statistical analysis was performed using SPSS software (version 25.0). Continuous variables are presented as mean ± standard deviation and were compared using the independent samples t-test. Categorical variables are presented as numbers (percentages) and were compared using the Chi-square test or Fisher's exact test, as appropriate. Variables with a P value < 0.1 in univariate analysis were entered into a multivariate logistic regression model to identify independent risk factors for pathological upgrading. A two-sided P value < 0.05 was considered statistically significant. Results Baseline characteristics This study ultimately included 69 patients, with 56 in the ER group and 13 in the ASR group. No statistically significant differences were observed between the two groups regarding age (P = 0.789), sex distribution (P = 0.591), clinical presentation (P = 0.432), or lesion number (solitary/multiple, P = 0.756). This indicates that HGIN cannot be distinguished from carcinogenesis based solely on age, sex, or clinical symptoms, and confirms that the baseline characteristics of the two groups were comparable (Table 1 ). Table 1 Baseline characteristics Variable Total ER(n = 56) ASR(n = 13) p value p value (n = 69) HGIN(52) T1(n = 4) HGIN(n = 6) T1(n = 7) (ER VS ASR) (HGIN VS T1 ) Age <65 50 38 3 4 5 0.789 1 ≥ 65 19 14 1 2 2 Sex Male 47 38 1 3 5 0.519 0.325 Female 22 14 3 3 2 Size <2.0cm 34 31 1 2 0 0.015 0.0002 ≥ 2.0cm 35 21 3 4 7 peduncle Yes 29 18 1 5 5 0.003 0.057 No 40 34 3 1 2 Location Rectum 23 13 2 4 4 0.032 0.0002 Ascending colon 5 5 0 0 0 Transverse colon 6 4 0 1 1 Descending colon 7 6 0 0 1 Sigmoid colon 28 24 2 1 1 Resection margin Positive 6 1 1 3 1 Negative 63 51 3 3 6 Budding Bd1 55 50 2 2 1 <0.001 Bd1 14 2 2 4 6 LNM Positive 4 0 2 0 2 Negative 65 52 2 6 5 LVI Positive 7 0 3 1 3 0.002 <0.001 Negative 62 52 1 5 4 Clinical features Asymptomatic 23 17 1 3 2 0.432 0.586 hematochezia 7 5 0 1 1 stomachache 11 8 1 1 1 uncomfortable 11 9 0 1 1 Altered bowel habit 7 5 1 0 1 Vomiting 4 3 1 0 0 loss of weight 6 5 0 0 1 Number Solitary lesion 50 40 2 3 5 0.756 0.723 Multiple lesions 19 12 2 3 2 ER, Endoscopic resection; HGIN, High-grade intraepithelial neoplasia; ASR, Additional surgical resection; Bd, budding. Comparison of complications between ER and ASR groups in treating colorectal HGIN and T1CRC Treatment-related complications occurred in 9 patients (16.1%) in the ER group, including hematemesis, hematochezia, and abdominal pain. Among these, one case involved delayed bleeding, and another patient suffered an intracranial hemorrhage during the procedure, requiring transfer for specialized care. In the ASR group, 2 patients (15.4%) experienced complications such as minor ascites and wound infection, which resolved with supportive care without impacting subsequent treatment. The overall complication rate showed no statistically significant difference between the two groups (P = 0.723). Both treatment strategies demonstrated comparable overall safety profiles. Although the types of complications differed, the majority were effectively managed with conservative or interventional measures, further reinforcing the advantageous position of endoscopic techniques as a minimally invasive treatment option. Analysis of endoscopic biopsy accuracy All 69 patients in this study were diagnosed with colorectal HGIN by preoperative endoscopic biopsy. Following definitive treatment, postoperative pathology revealed that 13 lesions (18.8%) were upgraded to T1CRC, while the remaining 56 (81.2%) were consistent with the initial biopsy diagnosis. Our data indicate a biopsy accuracy of 81.2%, aligning with previously reported figures. This highlights the limitations of relying solely on biopsy for HGIN diagnosis, as some early carcinomas may be missed. Relationship between lesion size, location, number, morphology, and the diagnosis of colorectal HGIN Analysis of lesion size revealed a significantly larger diameter in the ASR group compared to the ER group (2.2 ± 0.51 cm vs. 1.9 ± 0.43 cm, P = 0.015). A significant difference in diameter was also found between HGIN and T1 lesions (P = 0.002), with T1 lesions tending to be larger. Larger lesions (> 2.0 cm) should be viewed with high suspicion for malignant transformation (Table 2 ). Stratified analysis based on anatomical location showed a significant difference in the concordance between preoperative and postoperative diagnoses across sites (P = 0.032). Specifically, lesions located in the rectum and sigmoid colon presented a higher risk of carcinogenesis. In the ER group, the carcinoma rates for rectal and sigmoid lesions were 13.33% and 7.69%, respectively. These rates were substantially higher in the ASR group, reaching 50.00% and 12.0%. This finding suggests that the rectum and sigmoid colon may be specific anatomical regions where HGIN is prone to progression or where biopsy tends to underestimate malignancy, warranting particular attention in therapeutic strategy formulation. Although the overall distribution of lesion number (solitary vs. multiple) showed no difference between the two groups (P = 0.756), further subgroup analysis revealed a crucial finding. Among patients with solitary lesions, the T1 carcinoma rate was significantly higher in the ASR group compared to the ER group (62.5% vs. 4.76%, OR: 33.33, 95% CI: 4.44–250.5, P 0.05). This indicates that the "solitary" feature may be an important factor in predicting the potential malignancy of a lesion, suggesting a need for more aggressive diagnostic and therapeutic approaches for solitary HGIN lesions in clinical practice. Analysis of macroscopic morphology found that for sessile lesions, the T1 carcinoma rate was significantly higher in the ASR group compared to the ER group (P = 0.003), indicating that sessile morphology is a significant consideration in the clinical decision to opt for surgical intervention. However, when directly comparing the distribution of sessile morphology between the HGIN group and the T1 carcinoma group, the difference was of borderline statistical significance (P = 0.057). This suggests that while sessile morphology is significantly associated with the choice of treatment modality, its efficacy as an independent morphological indicator for discriminating between HGIN and T1 carcinoma may be limited. The discrepancies observed between our findings and those of some previous studies may be attributed, in part, to the relatively limited sample size of this study. Therefore, future investigations with larger cohorts are warranted to validate these preliminary findings and draw more robust conclusions. Table 2 Comparative Analysis of Lesion Size in Patients with HGIN and T1 CRC Group Pathologicaltype Number Averagesize(cm) Size(cm) ERonly HGIN 52 1.89 ± 0.42 1.2–3.1 ERonly T1 4 2.4 ± 0.54 1.9-3.0 ASR HGIN 6 2.12 ± 0.44 1.5–2.8 ASR T1 7 2.59 ± 0.49 2.0-3.4 ER, Endoscopic resection; HGIN, High-grade intraepithelial neoplasia; ASR, Additional surgical resection. Efficacy and safety analysis of ER for HGIN and T1CRC Analysis of post-ER resection specimens revealed that the pathological grade (HGIN vs. T1CRC) was not an independent predictor of R0 resection. The rate of incomplete resection did not differ significantly between the two groups (p = 0.264). Although the incomplete resection rate was numerically higher for T1 lesions compared to HGIN lesions (18.2% vs. 6.8%), this difference was not statistically significant (OR = 0.327, 95% CI: 0.052–2.054), indicating that most patients, irrespective of pathological grade, achieved microscopically complete resection via ER. However, from an oncological safety perspective, LNM occurred exclusively in patients with T1CRC, with an overall LNM rate of 27.3% (3/11). Among T1 patients with high-risk features who consequently underwent additional surgery, the LNM rate was as high as 28.6%. These results suggest that while ER is effective in achieving local en bloc resection, the inherent risk of LNM in T1CRC with submucosal invasion cannot be overlooked. Therefore, for patients with a postoperative pathological diagnosis of T1CRC after endoscopic resection, the risk of residual disease and long-term recurrence is significantly elevated if radical surgery is not subsequently performed. High-Grade TB and LVI predict high aggressiveness Analysis of TB grade showed that the proportion of high-grade TB (Bd > 1) was significantly higher in T1 lesions compared to HGIN lesions, both in the ER group (50.0% vs. 3.8%) and the ASR group (85.7% vs. 66.7%). Further intergroup comparison revealed a significantly higher proportion of cases with Bd > 1 in the ASR group compared to the ER group (77.9% vs. 7.1%), with a statistically significant difference (OR = 43.33, 95% CI: 8.39–224.11, p < 0.001), indicating that lesions in the ASR group overall had a higher TB grade, reflecting a more aggressive biological behavior. Concurrently, the incidence of LVI was significantly higher in the ASR group than in the ER group (p = 0.002). Furthermore, across all cases, the LVI positivity rate was significantly lower in the HGIN group compared to the T1 group (p < 0.001). These findings collectively demonstrate that both high-grade TB and LVI are important pathological characteristics indicative of malignant progression and enhanced invasive potential. Their marked enrichment in the ASR group provides key pathological justification for the more aggressive surgical intervention undertaken in these patients. ER, Endoscopic resection; HGIN, High-grade intraepithelial neoplasia; ASR, Additional surgical resection. Discussion CRC ranks as the third most common malignancy and the second leading cause of cancer-related deaths globally, with a trend toward affecting younger individuals. Approximately 25% of CRC patients present with distant metastases at diagnosis[ 4 , 5 ]. Early screening is therefore paramount. With the widespread adoption of endoscopic screening and technological advancements, the detection rate of precancerous lesions has increased. Regular colonoscopies and early treatment of precancerous lesions have been shown to reduce CRC incidence by 46% and mortality by 88%[ 3 ]. The clinical adoption of " HGIN" over terms like "carcinoma in situ" or "intramucosal carcinoma" stems from its recognition as a non-metastasizing entity, thereby mitigating the risk of overtreatment. Improving biopsy accuracy is thus crucial for guiding definitive treatment selection. However, due to the superficial nature of biopsies, which often fail to capture deeper mucosal invasion, misdiagnosis and under-diagnosis can occur. En bloc resection is recommended for definitive pathological assessment[ 6 ]. Studies have demonstrated that endoscopic submucosal dissection (ESD) for colorectal HGIN achieves en bloc resection, histologically complete resection, and major complication rates of 94.3%, 89.4%, and 2.3%, respectively[ 7 ]. Piecemeal resection can fragment the specimen, compromising the assessment of lateral and vertical margins and the accurate evaluation of invasion depth, leading to potential under-staging. Our comparative analysis revealed that nearly one-fifth of lesions initially diagnosed as HGIN by endoscopic biopsy were pathologically upgraded to T1 CRC upon complete resection, a finding consistent with numerous domestic and international reports. The reasons for this underestimation are multifactorial, primarily involving the limitations of endoscopic sampling (depth, location, number), interpretive variability among pathologists, and inherent tumor heterogeneity. A core finding of our study is the identification of lesion diameter > 2.0 cm, location in the rectum or sigmoid colon as independent risk factors for pathological upgrading, with larger lesions correlating with a higher risk of malignancy[ 8 ]. However, some studies suggest that for lesions with a diameter > 2.0 cm but lacking other high-risk features (e.g., poor differentiation, signet-ring cell component, deep submucosal invasion [≥ 1000 µm/SM2-3], LVI, or Bd > 1), the likelihood of deep submucosal invasion and LNM may be relatively low[ 9 ]. The rectum and sigmoid colon, as predominant sites for CRC, possess unique anatomical, immunological, and molecular characteristics. The distribution and functional state of immune cells may vary along the colorectum. Research indicates that an increased number of Foxp3 + T cells (typically immunosuppressive Tregs) and a high Foxp3/CD4 + and Foxp3/CD8 + ratio at the invasive tumor front is positively correlated with LNM. A similarly immunosuppressive microenvironment in the rectum and sigmoid may facilitate immune evasion and early tumor infiltration. Furthermore, the tumor immune microenvironment (TIME) in CRC is heterogeneous. Molecular features such as microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS/BRAF mutation status are significantly associated with prognosis in specific anatomical locations[ 10 , 11 ]. For instance, MSI-H status is a favorable prognostic marker in the proximal colon but is associated with poorer cancer-specific survival in the distal colon (e.g., sigmoid). This "location effect" suggests that the local mucosal environment (including microbiome, metabolites, and bile acid concentration) in the rectum and sigmoid may "select for" or promote the progression of specific molecular subtypes with differing invasive and metastatic potentials. The rich lymphatic network in these regions provides an anatomical basis for local LNM. Beyond immune factors, upregulation of epithelial-mesenchymal transition (EMT)-related proteins is also linked to LNM, potentially enabling early submucosal colonization and spread[ 12 ]. In our study, no significant difference in carcinoma rate was observed between groups for patients with multiple lesions, whereas a significantly higher rate was found for solitary lesions in the ASR group. This suggests that "solitary" status may be an important predictor of malignant potential. Our data indicate that "solitary" is a valuable risk indicator independent of size and morphology. While the traditional view holds that cancer originates from a single cell, studies in familial adenomatous polyposis (FAP) patients reveal that up to 40% of benign polyps and 28% of dysplastic polyps are polyclonal in origin. This implies that a seemingly solitary lesion may result from the fusion and clonal competition of initially independent cell populations under local microenvironmental "pressure," wherein the most aggressive clone becomes dominant, endowing the final lesion with a stronger inherent malignant tendency. These insights could aid in more precise risk stratification[ 13 ]. When clinicians encounter an "HGIN" lesion with the high-risk features, they should be aware of the underlying risk of invasive carcinoma and exercise greater caution in therapeutic planning. Notably, patients' clinical symptoms in our study showed no predictive value for pathological upgrading, aligning with some previous reports and underscoring the inadequacy of relying on symptoms alone to assess lesion severity[ 14 ]. En bloc biopsy is recommended over piecemeal sampling because the latter can induce significant local tissue damage. Studies suggest that within 24 hours of piecemeal resection, levels of malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) increase significantly. MDA, a terminal product of lipid peroxidation, reflects cell membrane damage, while GSH-Px is crucial for maintaining intracellular redox balance and protecting against oxidative damage[ 15 , 16 ]. Their abnormal elevation post-biopsy indicates ischemia-reperfusion injury, metabolic disturbance, and excessive reactive oxygen species generation, which may theoretically accelerate tumor progression[ 17 ]. Therefore, improving the en bloc resection rate is advocated. This can be complemented by serum markers (e.g., Ki-67, telomerase activity, which are often elevated in HGIN compared to adjacent tissue) and imaging modalities[ 18 , 19 ]. CT imaging shows increasing utility in detecting HGIN and can serve as part of a combined diagnostic approach[ 20 ]. Additionally, obesity and a family history of CRC are independent risk factors for adenoma development (p < 0.05) and can serve as diagnostic references[ 21 ]. Regarding treatment safety, our study showed comparable complication rates between the ER and ASR groups. Pathological grade (HGIN vs. T1 CRC) was not an independent predictor of R0 resection, and the incomplete resection rate did not differ significantly, indicating that ER can achieve microscopically complete resection in many patients regardless of grade. This is closely related to advancements in minimally invasive techniques and the accumulating experience of endoscopists, which have effectively controlled risks like bleeding and perforation associated with ESD/EMR, establishing endoscopy as a safe and primary treatment for HGIN.Our study found that LNM occurred exclusively in T1 CRC patients, with an overall rate of 27.3%, rising to 28.6% in the T1 subgroup undergoing additional surgery. This highlights that while ER achieves excellent local resection, the inherent LNM risk in T1 CRC with submucosal invasion cannot be ignored. Reported metastasis/recurrence rates for endoscopically treated T1b-SM1/2 lesions are 10.7% and 6.6%, with overall survival rates of 71.4% and 67.4%, respectively[ 22 ]. These non-negligible rates underscore the need for accurate diagnosis and appropriate treatment selection. Our analysis of TB grade revealed a significantly higher proportion of Bd > 1 in T1 CRC compared to HGIN (ER group: 50.0% vs. 3.8%; ASR group: 85.7% vs. 66.7%, p < 0.001). Regardless of clinical context or tumor type, a higher Bd grade correlates with worse pathological differentiation, warranting its mandatory documentation in pathology reports[ 23 ]. Concurrently, LVI was significantly more frequent in the ASR group (p = 0.002), and studies confirm LVI as a high-risk factor for LNM[ 24 ]. These findings collectively establish high-grade TB and LVI as critical pathological markers of malignant progression and invasive potential. Their marked enrichment in the ASR group provides key pathological justification for the more aggressive surgical intervention undertaken in these patients. Consequently, for patients with a postoperative diagnosis of T1 CRC, the presence of high-risk factors without further treatment significantly increases the likelihood of LNM. This is particularly crucial for low rectal lesions, where recurrence or metastasis may compromise sphincter preservation and quality of life. This study has several limitations. First, as a single-center, retrospective study, it carries inherent selection bias. Second, the small sample size of the ASR group may affect the stability of the multivariate analysis results. Third, long-term follow-up data for the ER group are lacking, precluding assessment of long-term recurrence and survival outcomes. Future multicenter, large-scale prospective studies incorporating molecular biomarkers are needed to develop more accurate predictive models. Conclusion In summary, the clinical management of colorectal HGIN requires individualized and precise strategies. For high-risk patients with lesions > 2.0 cm in diameter, located in the rectum or sigmoid colon, and exhibiting sessile morphology, endoscopic biopsy carries a significant risk of diagnostic underestimation. Clinical decision-making should be based on multidisciplinary team (MDT) discussion, integrating advanced assessment tools such as high-definition chromoendoscopy and endoscopic ultrasound (EUS). Initial treatment should prioritize ESD for its high en bloc resection rate, ensuring comprehensive pathological assessment. Upon identification of high-risk features in the postoperative pathology, timely additional radical surgery should be pursued to maximize oncological cure and improve patient prognosis. Abbreviations HGIN High-grade intraepithelial neoplasia ER Endoscopic resection ASR Additional surgery resection CRC Colorectal cancer LNM Lymph node metastasis LVI Lymph vascular invasion TB Tumor budding EMR Endoscopic mucosal resection ESD Endoscopic submucosal dissection TIME Tumor immune microenvironment MSI Microsatellite instability CIMP CpG island methylator phenotype EMT Epithelial-mesenchymal transition FAP Familial adenomatous polyposis MDA Malondialdehyde GSH-Px Glutathione peroxidase MDT Multidisciplinary team EUS Endoscopic ultrasound Declarations Acknowledgments The authors would like to thank all staff members of the Department of Gastroenterocolorectal Surgery at the China-Japan Union Hospital of Jilin University for their clinical and technical support. We also gratefully acknowledge the hospital administration for their facilitation of this study. Author contributions Yang Yang wrote the main manuscript text,Kexin Shen prepared Table 1 and 2 and Xie Zhongshi supervised the study. All authors reviewed the manuscript. Funding The authors declare no funding for this study. Data Availability The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate This study was performed in accordance with the ethical standards of the Declaration of Helsinki. The study protocol was approved by the Ethics Committee of the China-Japan Union Hospital of Jilin University. Written informed consent was obtained from all individual participants included in the study. Consent for publication Not applicable. Competing of interests The authors declare no conflict of interests. References Choe K, Jang JY, Park I, Kim Y, Ahn S, Park DY, Hong YK, Alitalo K, Koh GY, Kim P. 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Polyclonal origins of human premalignant colorectal lesions. Nature 2025. Burnett-Hartman AN, Lee JK, Demb J, Gupta S. An Update on the Epidemiology, Molecular Characterization, Diagnosis, and Screening Strategies for Early-Onset Colorectal Cancer. Gastroenterology. 2021;160(4):1041–9. Golomb BA, Devaraj S, Messner AK, Koslik HJ, Han JH, Yik B. Lower blood malondialdehyde is associated with past pesticide exposure: findings in Gulf War illness and healthy controls. Mil Med Res. 2021;8(1):46. Zhang Y, Fan W, Li X, Wang WX, Liu S. Enhanced Removal of Free Radicals by Aqueous Hydrogen Nanobubbles and Their Role in Oxidative Stress. Environ Sci Technol. 2022;56(21):15096–107. Pan Y, Wei J, Qin D, Zhou X, Gao F, Yu L, Feng C, Mi J, Wu J, Law BYK, et al. Prosapogenin CP4 exacerbates mitophagy to induce apoptosis via AMPK-mTOR and PINK1/Parkin pathways in A549 cells. Phytomedicine. 2025;148:157333. Kin R, Hoshi D, Fujita H, Kosaka T, Takamura H, Kiyokawa E. Prognostic significance of p16, p21, and Ki67 expression at the invasive front of colorectal cancers. Pathol Int. 2023;73(2):81–90. Nersisyan L, Hopp L, Loeffler-Wirth H, Galle J, Loeffler M, Arakelyan A, Binder H. Telomere Length Maintenance and Its Transcriptional Regulation in Lynch Syndrome and Sporadic Colorectal Carcinoma. Front Oncol. 2019;9:1172. Chen FX, Jiang KK, Zhu JF, Wang MR, Fan XL, Yang JS, He BS. Diagnostic accuracy of dual-layer spectral computed tomography virtual monoenergetic imaging with multiplanar reformation for T-staging of colorectal cancer. World J Gastroenterol. 2025;31(32):110573. Zhou MJ, Lebwohl B, Krigel A. Patient and Physician Factors Associated with Adenoma and Sessile Serrated Lesion Detection Rates. Dig Dis Sci. 2020;65(11):3123–31. Naito S, Yoshio T, Ishiyama A, Tsuchida T, Tokura J, Namikawa K, Tokai Y, Yoshimizu S, Horiuchi Y, Hirasawa T, et al. Long-term outcomes of esophageal squamous cell carcinoma with invasion depth of pathological T1a-muscularis mucosae and T1b-submucosa by endoscopic resection followed by appropriate additional treatment. Dig Endosc. 2022;34(4):793–804. Lugli A, Zlobec I, Berger MD, Kirsch R, Nagtegaal ID. Tumour budding in solid cancers. Nat Rev Clin Oncol. 2021;18(2):101–15. Ebbehøj AL, Smith HG, Jørgensen LN, Krarup PM. Prognostic Factors for Lymph Node Metastases in pT1 Colorectal Cancer Differ According to Tumor Morphology: A Nationwide Cohort Study. Ann Surg. 2023;277(1):127–35. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 06 Mar, 2026 Reviewers agreed at journal 25 Feb, 2026 Reviewers invited by journal 24 Feb, 2026 Editor invited by journal 02 Feb, 2026 Editor assigned by journal 08 Dec, 2025 Submission checks completed at journal 08 Dec, 2025 First submitted to journal 04 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-8279345","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":596866162,"identity":"8d0e91ab-6ad1-4b66-81eb-8a710d0b2be2","order_by":0,"name":"Yang Yang","email":"","orcid":"","institution":"Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Yang","middleName":"","lastName":"Yang","suffix":""},{"id":596866163,"identity":"e8525675-9b74-41c3-a7a4-d89471ce1ebc","order_by":1,"name":"Kexin Shen","email":"","orcid":"","institution":"Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Kexin","middleName":"","lastName":"Shen","suffix":""},{"id":596866164,"identity":"c1055b3a-a603-4a01-bfec-9c037b9f4f9b","order_by":2,"name":"Zhongshi Xie","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuElEQVRIiWNgGAWjYDACZhBRwSYDoiRI0HKGjYcELSDA2MZAghaD48yHP/6cx8djcID54G0eBrs8glokm9kSjHm3sQG1sCVb8zAkFxPUws/MY5DMCNbCYybNw3AgsYGQFjZm/g8Hf84BaeH/RpwWoC2MDbwNYFvYiNMC9IsxM88xNh7Jw2zGlnMMkglrMTh/+PHHHzXH5PiONz+88abCjrAWKDgGjVMDItUDQQ3xSkfBKBgFo2DkAQB3UTA6x+uj0AAAAABJRU5ErkJggg==","orcid":"","institution":"Jilin University","correspondingAuthor":true,"prefix":"","firstName":"Zhongshi","middleName":"","lastName":"Xie","suffix":""}],"badges":[],"createdAt":"2025-12-04 12:38:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8279345/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8279345/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103508206,"identity":"1e9e93e4-1c85-4aad-aeec-147218291d20","added_by":"auto","created_at":"2026-02-26 13:47:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":835792,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8279345/v1/d6b8b17a-a547-4808-bd18-8cacb86aad08.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparative Study on Efficacy and Risk of Pathological Upgrading between Endoscopic and Surgical Resection for Colorectal High-Grade Intraepithelial Neoplasia: A Retrospective Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn 2000, the World Health Organization (WHO) recommended the term \"intraepithelial neoplasia\" (IN) to replace previous designations such as \"dysplasia\" and \"carcinoma in situ,\" aiming to more accurately reflect the biological nature of lesions and guide clinical management. When neoplastic tissue is confined within the muscularis mucosae, the lack of lymphatic vessels in the mucosal epithelium and lamina propria renders the probability of metastasis extremely low. Lacking the defining metastatic characteristics of cancer, such lesions are classified as HGIN. However, some scholars note that a minor lymphatic plexus and a well-developed capillary network do exist within the colorectal mucosa, potentially explaining why LNM can still occur in some patients even when the lesion is superficial[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].In recent years, pathologists have emphasized the new definition of tumor budding (TB) and recommended its inclusion in pathological diagnoses due to its strong association with LNM, disease prognosis, and mortality risk. The International Tumor Budding Consensus Conference (ITBCC) recommends a three-tier grading system: low-grade (Bd1, 0\u0026ndash;4 buds), intermediate-grade (Bd2, 5\u0026ndash;9 buds), and high-grade (Bd3, \u0026ge;\u0026thinsp;10 buds), which should be specified in pathology reports[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eColorectal HGIN, as a precancerous lesion, often lacks obvious clinical symptoms such as hematochezia or constipation and is not limited to the lower rectum. Consequently, endoscopic examination serves as the primary method for its screening. The accuracy of endoscopic biopsy is crucial in selecting treatment, as it can be used for both diagnosis and therapy, offering advantages such as minimal invasiveness, a short procedure time, and a low cost. However, because only a small, localized area of the lesion is sampled, foci of carcinoma may be missed. Inaccurate sampling due to inexperience can also lead to misdiagnosis or underdiagnosis.\u003c/p\u003e \u003cp\u003eGenerally, superficial submucosal invasion (depth\u0026thinsp;\u0026le;\u0026thinsp;1000 \u0026micro;m) is considered an indication for endoscopic treatment, while deep submucosal invasion (\u0026gt;\u0026thinsp;1000 \u0026micro;m) carries a risk of LNM and vascular invasion, warranting ASR. Common clinical endoscopic techniques include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). EMR is typically suitable for lesions less than 2.0 cm in diameter with a relatively flat morphology. ESD is indicated for lesions that are not amenable to EMR, those larger than 2.0 cm, or those with slight submucosal infiltration but without evidence of LNM or vascular/neural invasion. Although ER offers benefits like shorter hospital stays, lower cost, and minimal trauma, it is not without risks, including delayed postoperative hemorrhage, perforation, and tumor recurrence or metastasis. Delayed bleeding often presents acutely with significant blood loss, requiring surgical intervention. Additionally, overly aggressive resection damaging the muscular layer can lead to perforation, potentially resulting in peritonitis, abdominal infection, or septic shock.\u003c/p\u003e \u003cp\u003eSurgical treatment has evolved from open surgery to laparoscopic and robotic-assisted techniques. These advancements have significantly reduced bodily trauma, shortened hospital stays, and lowered the risks of postoperative complications such as intra-abdominal and wound infections compared to open surgery. Surgery allows for the complete removal of the tumor along with any infiltrated or metastatic lymphatics and nerves, thereby reducing the risk of recurrence and metastasis. However, the postoperative period, requiring fasting and bed rest, is associated with higher incidences of hypostatic pneumonia and hypoproteinemia. Furthermore, the hospital stay is typically longer, and the cost is higher compared to endoscopic treatment.\u003c/p\u003e \u003cp\u003eBased on the preoperative and postoperative pathological findings from patients with colorectal HGIN treated endoscopically or surgically, this study aims to analyze the accuracy of endoscopic diagnosis, identify high-risk factors for pathological upgrading in HGIN, and evaluate the complete therapeutic efficacy of endoscopic treatment. The goal is to provide evidence for optimizing treatment strategies for patients.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003e This study was approved by the Ethics Committee of the China-Japan Union Hospital, Jilin University. Clinical data were retrospectively collected from 69 patients with a preoperative diagnosis of colorectal HGIN at our institution between January 2019 and January 2023. Among them, 56 patients underwent endoscopic therapy alone, and 13 patients underwent surgical treatment. The cohort consisted of 47 males and 22 females, aged 30\u0026ndash;84 years (mean, 60.4\u0026thinsp;\u0026plusmn;\u0026thinsp;9.0 years). Tumor staging was performed according to the Tumor, Node, Metastasis (TNM) classification system of the American Joint Committee on Cancer (AJCC, 8th edition). The inclusion criteria were: (1) Preoperative pathological diagnosis of colorectal HGIN before endoscopic or surgical therapy; (2) No prior neoadjuvant chemoradiotherapy or other anti-tumor treatments before endoscopic or surgical intervention; (3) Availability of complete clinical, pathological, and imaging data. The exclusion criteria were: (1) Preoperative pathology confirming carcinoma (e.g., intramucosal carcinoma); (2) Preoperative diagnosis of colorectal LGIN or benign tumors; (3) History of neoadjuvant chemoradiotherapy or other anti-tumor treatments; (4) Lack of pathological confirmation of HGIN by endoscopic biopsy; (5) Incomplete case data.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eHistopathological evaluation\u003c/h3\u003e\n\u003cp\u003eBiopsy specimens were fixed in formaldehyde, embedded in paraffin, and serially sectioned. Sections were stained with hematoxylin and eosin (H\u0026amp;E). According to WHO criteria, colorectal HGIN was defined by the presence of dysplastic epithelial cells with significant cytological and architectural abnormalities, confined above the basement membrane without evidence of invasive carcinoma. Lesions were classified as T1CRC when neoplastic cells breached the basement membrane and invaded the submucosa but did not reach the muscularis propria.\u003c/p\u003e\n\u003ch3\u003eGrouping\u003c/h3\u003e\n\u003cp\u003ePatients were divided into two groups: The ER group comprised 56 patients who underwent endoscopic therapy (EMR or ESD) without subsequent surgical intervention. The ASR group consisted of 13 patients who underwent radical surgery following initial ER due to the presence of one or more high-risk pathological features: (1) positive resection margins; (2) submucosal invasion depth\u0026thinsp;\u0026gt;\u0026thinsp;1000 \u0026micro;m (SM2/3); (3) LVI; (4) poorly differentiated adenocarcinoma, signet-ring cell carcinoma, or mucinous adenocarcinoma; (5) tumor budding grade Bd2 or Bd3.\u003c/p\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eCollected data included: (1) Demographic characteristics: age and sex; (2) Lesion characteristics: size, location (rectum/sigmoid colon/other colon), morphology (pedunculated/sessile), number (solitary/multiple), depth of invasion, LNM status, LVI, and histological type; (3) Clinical presentation: presence or absence of symptoms (e.g., hematochezia, abdominal pain, altered bowel habits); (4) Pathological results: preoperative biopsy pathology and final postoperative pathology (TNM staging according to AJCC 8th edition); (5) Treatment-related details: surgical approach and postoperative complications.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using SPSS software (version 25.0). Continuous variables are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and were compared using the independent samples t-test. Categorical variables are presented as numbers (percentages) and were compared using the Chi-square test or Fisher's exact test, as appropriate. Variables with a P value\u0026thinsp;\u0026lt;\u0026thinsp;0.1 in univariate analysis were entered into a multivariate logistic regression model to identify independent risk factors for pathological upgrading. A two-sided P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eBaseline characteristics\u003c/h2\u003e \u003cp\u003eThis study ultimately included 69 patients, with 56 in the ER group and 13 in the ASR group. No statistically significant differences were observed between the two groups regarding age (P\u0026thinsp;=\u0026thinsp;0.789), sex distribution (P\u0026thinsp;=\u0026thinsp;0.591), clinical presentation (P\u0026thinsp;=\u0026thinsp;0.432), or lesion number (solitary/multiple, P\u0026thinsp;=\u0026thinsp;0.756). This indicates that HGIN cannot be distinguished from carcinogenesis based solely on age, sex, or clinical symptoms, and confirms that the baseline characteristics of the two groups were comparable (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"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 \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eER(n\u0026thinsp;=\u0026thinsp;56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eASR(n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHGIN(52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eT1(n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHGIN(n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eT1(n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(ER VS ASR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e(HGIN VS T1 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.789\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.519\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.325\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSize\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;2.0cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e0.015\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e0.0002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2.0cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003epeduncle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.057\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eLocation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRectum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e\u003cb\u003e0.032\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e\u003cb\u003e0.0002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAscending colon\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTransverse colon\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDescending colon\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSigmoid colon\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eResection margin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBudding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBd1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;Bd1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLNM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLVI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003eClinical features\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAsymptomatic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003e0.432\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003e0.586\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ehematochezia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003estomachache\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003euncomfortable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAltered bowel habit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eloss of weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSolitary lesion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.756\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.723\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMultiple lesions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eER, Endoscopic resection; HGIN, High-grade intraepithelial neoplasia; ASR, Additional surgical resection; Bd, budding.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eComparison of complications between ER and ASR groups in treating colorectal HGIN and T1CRC\u003c/h3\u003e\n\u003cp\u003eTreatment-related complications occurred in 9 patients (16.1%) in the ER group, including hematemesis, hematochezia, and abdominal pain. Among these, one case involved delayed bleeding, and another patient suffered an intracranial hemorrhage during the procedure, requiring transfer for specialized care. In the ASR group, 2 patients (15.4%) experienced complications such as minor ascites and wound infection, which resolved with supportive care without impacting subsequent treatment. The overall complication rate showed no statistically significant difference between the two groups (P\u0026thinsp;=\u0026thinsp;0.723). Both treatment strategies demonstrated comparable overall safety profiles. Although the types of complications differed, the majority were effectively managed with conservative or interventional measures, further reinforcing the advantageous position of endoscopic techniques as a minimally invasive treatment option.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eAnalysis of endoscopic biopsy accuracy\u003c/h2\u003e \u003cp\u003eAll 69 patients in this study were diagnosed with colorectal HGIN by preoperative endoscopic biopsy. Following definitive treatment, postoperative pathology revealed that 13 lesions (18.8%) were upgraded to T1CRC, while the remaining 56 (81.2%) were consistent with the initial biopsy diagnosis. Our data indicate a biopsy accuracy of 81.2%, aligning with previously reported figures. This highlights the limitations of relying solely on biopsy for HGIN diagnosis, as some early carcinomas may be missed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eRelationship between lesion size, location, number, morphology, and the diagnosis of colorectal HGIN\u003c/h2\u003e \u003cp\u003eAnalysis of lesion size revealed a significantly larger diameter in the ASR group compared to the ER group (2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.51 cm vs. 1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.43 cm, P\u0026thinsp;=\u0026thinsp;0.015). A significant difference in diameter was also found between HGIN and T1 lesions (P\u0026thinsp;=\u0026thinsp;0.002), with T1 lesions tending to be larger. Larger lesions (\u0026gt;\u0026thinsp;2.0 cm) should be viewed with high suspicion for malignant transformation (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Stratified analysis based on anatomical location showed a significant difference in the concordance between preoperative and postoperative diagnoses across sites (P\u0026thinsp;=\u0026thinsp;0.032). Specifically, lesions located in the rectum and sigmoid colon presented a higher risk of carcinogenesis. In the ER group, the carcinoma rates for rectal and sigmoid lesions were 13.33% and 7.69%, respectively. These rates were substantially higher in the ASR group, reaching 50.00% and 12.0%. This finding suggests that the rectum and sigmoid colon may be specific anatomical regions where HGIN is prone to progression or where biopsy tends to underestimate malignancy, warranting particular attention in therapeutic strategy formulation. Although the overall distribution of lesion number (solitary vs. multiple) showed no difference between the two groups (P\u0026thinsp;=\u0026thinsp;0.756), further subgroup analysis revealed a crucial finding. Among patients with solitary lesions, the T1 carcinoma rate was significantly higher in the ASR group compared to the ER group (62.5% vs. 4.76%, OR: 33.33, 95% CI: 4.44\u0026ndash;250.5, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In contrast, no statistically significant difference in carcinoma rate was observed between the groups for patients with multiple lesions (40.0% vs. 14.29%, P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). This indicates that the \"solitary\" feature may be an important factor in predicting the potential malignancy of a lesion, suggesting a need for more aggressive diagnostic and therapeutic approaches for solitary HGIN lesions in clinical practice. Analysis of macroscopic morphology found that for sessile lesions, the T1 carcinoma rate was significantly higher in the ASR group compared to the ER group (P\u0026thinsp;=\u0026thinsp;0.003), indicating that sessile morphology is a significant consideration in the clinical decision to opt for surgical intervention. However, when directly comparing the distribution of sessile morphology between the HGIN group and the T1 carcinoma group, the difference was of borderline statistical significance (P\u0026thinsp;=\u0026thinsp;0.057). This suggests that while sessile morphology is significantly associated with the choice of treatment modality, its efficacy as an independent morphological indicator for discriminating between HGIN and T1 carcinoma may be limited. The discrepancies observed between our findings and those of some previous studies may be attributed, in part, to the relatively limited sample size of this study. Therefore, future investigations with larger cohorts are warranted to validate these preliminary findings and draw more robust conclusions.\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\u003eComparative Analysis of Lesion Size in Patients with HGIN and T1 CRC\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePathologicaltype\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAveragesize(cm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSize(cm)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eERonly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHGIN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.2\u0026ndash;3.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eERonly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.9-3.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHGIN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e2.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.5\u0026ndash;2.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e2.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.0-3.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eER, Endoscopic resection; HGIN, High-grade intraepithelial neoplasia; ASR, Additional surgical resection.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eEfficacy and safety analysis of ER for HGIN and T1CRC\u003c/h2\u003e \u003cp\u003eAnalysis of post-ER resection specimens revealed that the pathological grade (HGIN vs. T1CRC) was not an independent predictor of R0 resection. The rate of incomplete resection did not differ significantly between the two groups (p\u0026thinsp;=\u0026thinsp;0.264). Although the incomplete resection rate was numerically higher for T1 lesions compared to HGIN lesions (18.2% vs. 6.8%), this difference was not statistically significant (OR\u0026thinsp;=\u0026thinsp;0.327, 95% CI: 0.052\u0026ndash;2.054), indicating that most patients, irrespective of pathological grade, achieved microscopically complete resection via ER. However, from an oncological safety perspective, LNM occurred exclusively in patients with T1CRC, with an overall LNM rate of 27.3% (3/11). Among T1 patients with high-risk features who consequently underwent additional surgery, the LNM rate was as high as 28.6%. These results suggest that while ER is effective in achieving local en bloc resection, the inherent risk of LNM in T1CRC with submucosal invasion cannot be overlooked. Therefore, for patients with a postoperative pathological diagnosis of T1CRC after endoscopic resection, the risk of residual disease and long-term recurrence is significantly elevated if radical surgery is not subsequently performed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eHigh-Grade TB and LVI predict high aggressiveness\u003c/h2\u003e \u003cp\u003eAnalysis of TB grade showed that the proportion of high-grade TB (Bd\u0026thinsp;\u0026gt;\u0026thinsp;1) was significantly higher in T1 lesions compared to HGIN lesions, both in the ER group (50.0% vs. 3.8%) and the ASR group (85.7% vs. 66.7%). Further intergroup comparison revealed a significantly higher proportion of cases with Bd\u0026thinsp;\u0026gt;\u0026thinsp;1 in the ASR group compared to the ER group (77.9% vs. 7.1%), with a statistically significant difference (OR\u0026thinsp;=\u0026thinsp;43.33, 95% CI: 8.39\u0026ndash;224.11, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), indicating that lesions in the ASR group overall had a higher TB grade, reflecting a more aggressive biological behavior. Concurrently, the incidence of LVI was significantly higher in the ASR group than in the ER group (p\u0026thinsp;=\u0026thinsp;0.002). Furthermore, across all cases, the LVI positivity rate was significantly lower in the HGIN group compared to the T1 group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). These findings collectively demonstrate that both high-grade TB and LVI are important pathological characteristics indicative of malignant progression and enhanced invasive potential. Their marked enrichment in the ASR group provides key pathological justification for the more aggressive surgical intervention undertaken in these patients.\u003c/p\u003e \u003cp\u003eER, Endoscopic resection; HGIN, High-grade intraepithelial neoplasia; ASR, Additional surgical resection.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eCRC ranks as the third most common malignancy and the second leading cause of cancer-related deaths globally, with a trend toward affecting younger individuals. Approximately 25% of CRC patients present with distant metastases at diagnosis[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Early screening is therefore paramount. With the widespread adoption of endoscopic screening and technological advancements, the detection rate of precancerous lesions has increased. Regular colonoscopies and early treatment of precancerous lesions have been shown to reduce CRC incidence by 46% and mortality by 88%[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The clinical adoption of \" HGIN\" over terms like \"carcinoma in situ\" or \"intramucosal carcinoma\" stems from its recognition as a non-metastasizing entity, thereby mitigating the risk of overtreatment. Improving biopsy accuracy is thus crucial for guiding definitive treatment selection. However, due to the superficial nature of biopsies, which often fail to capture deeper mucosal invasion, misdiagnosis and under-diagnosis can occur. En bloc resection is recommended for definitive pathological assessment[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Studies have demonstrated that endoscopic submucosal dissection (ESD) for colorectal HGIN achieves en bloc resection, histologically complete resection, and major complication rates of 94.3%, 89.4%, and 2.3%, respectively[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Piecemeal resection can fragment the specimen, compromising the assessment of lateral and vertical margins and the accurate evaluation of invasion depth, leading to potential under-staging. Our comparative analysis revealed that nearly one-fifth of lesions initially diagnosed as HGIN by endoscopic biopsy were pathologically upgraded to T1 CRC upon complete resection, a finding consistent with numerous domestic and international reports. The reasons for this underestimation are multifactorial, primarily involving the limitations of endoscopic sampling (depth, location, number), interpretive variability among pathologists, and inherent tumor heterogeneity. A core finding of our study is the identification of lesion diameter\u0026thinsp;\u0026gt;\u0026thinsp;2.0 cm, location in the rectum or sigmoid colon as independent risk factors for pathological upgrading, with larger lesions correlating with a higher risk of malignancy[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, some studies suggest that for lesions with a diameter\u0026thinsp;\u0026gt;\u0026thinsp;2.0 cm but lacking other high-risk features (e.g., poor differentiation, signet-ring cell component, deep submucosal invasion [\u0026ge;\u0026thinsp;1000 \u0026micro;m/SM2-3], LVI, or Bd\u0026thinsp;\u0026gt;\u0026thinsp;1), the likelihood of deep submucosal invasion and LNM may be relatively low[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe rectum and sigmoid colon, as predominant sites for CRC, possess unique anatomical, immunological, and molecular characteristics. The distribution and functional state of immune cells may vary along the colorectum. Research indicates that an increased number of Foxp3\u0026thinsp;+\u0026thinsp;T cells (typically immunosuppressive Tregs) and a high Foxp3/CD4\u0026thinsp;+\u0026thinsp;and Foxp3/CD8\u0026thinsp;+\u0026thinsp;ratio at the invasive tumor front is positively correlated with LNM. A similarly immunosuppressive microenvironment in the rectum and sigmoid may facilitate immune evasion and early tumor infiltration. Furthermore, the tumor immune microenvironment (TIME) in CRC is heterogeneous. Molecular features such as microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS/BRAF mutation status are significantly associated with prognosis in specific anatomical locations[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. For instance, MSI-H status is a favorable prognostic marker in the proximal colon but is associated with poorer cancer-specific survival in the distal colon (e.g., sigmoid). This \"location effect\" suggests that the local mucosal environment (including microbiome, metabolites, and bile acid concentration) in the rectum and sigmoid may \"select for\" or promote the progression of specific molecular subtypes with differing invasive and metastatic potentials. The rich lymphatic network in these regions provides an anatomical basis for local LNM. Beyond immune factors, upregulation of epithelial-mesenchymal transition (EMT)-related proteins is also linked to LNM, potentially enabling early submucosal colonization and spread[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study, no significant difference in carcinoma rate was observed between groups for patients with multiple lesions, whereas a significantly higher rate was found for solitary lesions in the ASR group. This suggests that \"solitary\" status may be an important predictor of malignant potential. Our data indicate that \"solitary\" is a valuable risk indicator independent of size and morphology. While the traditional view holds that cancer originates from a single cell, studies in familial adenomatous polyposis (FAP) patients reveal that up to 40% of benign polyps and 28% of dysplastic polyps are polyclonal in origin. This implies that a seemingly solitary lesion may result from the fusion and clonal competition of initially independent cell populations under local microenvironmental \"pressure,\" wherein the most aggressive clone becomes dominant, endowing the final lesion with a stronger inherent malignant tendency. These insights could aid in more precise risk stratification[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhen clinicians encounter an \"HGIN\" lesion with the high-risk features, they should be aware of the underlying risk of invasive carcinoma and exercise greater caution in therapeutic planning. Notably, patients' clinical symptoms in our study showed no predictive value for pathological upgrading, aligning with some previous reports and underscoring the inadequacy of relying on symptoms alone to assess lesion severity[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. En bloc biopsy is recommended over piecemeal sampling because the latter can induce significant local tissue damage. Studies suggest that within 24 hours of piecemeal resection, levels of malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) increase significantly. MDA, a terminal product of lipid peroxidation, reflects cell membrane damage, while GSH-Px is crucial for maintaining intracellular redox balance and protecting against oxidative damage[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Their abnormal elevation post-biopsy indicates ischemia-reperfusion injury, metabolic disturbance, and excessive reactive oxygen species generation, which may theoretically accelerate tumor progression[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Therefore, improving the en bloc resection rate is advocated. This can be complemented by serum markers (e.g., Ki-67, telomerase activity, which are often elevated in HGIN compared to adjacent tissue) and imaging modalities[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. CT imaging shows increasing utility in detecting HGIN and can serve as part of a combined diagnostic approach[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Additionally, obesity and a family history of CRC are independent risk factors for adenoma development (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and can serve as diagnostic references[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRegarding treatment safety, our study showed comparable complication rates between the ER and ASR groups. Pathological grade (HGIN vs. T1 CRC) was not an independent predictor of R0 resection, and the incomplete resection rate did not differ significantly, indicating that ER can achieve microscopically complete resection in many patients regardless of grade. This is closely related to advancements in minimally invasive techniques and the accumulating experience of endoscopists, which have effectively controlled risks like bleeding and perforation associated with ESD/EMR, establishing endoscopy as a safe and primary treatment for HGIN.Our study found that LNM occurred exclusively in T1 CRC patients, with an overall rate of 27.3%, rising to 28.6% in the T1 subgroup undergoing additional surgery. This highlights that while ER achieves excellent local resection, the inherent LNM risk in T1 CRC with submucosal invasion cannot be ignored. Reported metastasis/recurrence rates for endoscopically treated T1b-SM1/2 lesions are 10.7% and 6.6%, with overall survival rates of 71.4% and 67.4%, respectively[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. These non-negligible rates underscore the need for accurate diagnosis and appropriate treatment selection.\u003c/p\u003e \u003cp\u003eOur analysis of TB grade revealed a significantly higher proportion of Bd\u0026thinsp;\u0026gt;\u0026thinsp;1 in T1 CRC compared to HGIN (ER group: 50.0% vs. 3.8%; ASR group: 85.7% vs. 66.7%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Regardless of clinical context or tumor type, a higher Bd grade correlates with worse pathological differentiation, warranting its mandatory documentation in pathology reports[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Concurrently, LVI was significantly more frequent in the ASR group (p\u0026thinsp;=\u0026thinsp;0.002), and studies confirm LVI as a high-risk factor for LNM[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. These findings collectively establish high-grade TB and LVI as critical pathological markers of malignant progression and invasive potential. Their marked enrichment in the ASR group provides key pathological justification for the more aggressive surgical intervention undertaken in these patients. Consequently, for patients with a postoperative diagnosis of T1 CRC, the presence of high-risk factors without further treatment significantly increases the likelihood of LNM. This is particularly crucial for low rectal lesions, where recurrence or metastasis may compromise sphincter preservation and quality of life.\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, as a single-center, retrospective study, it carries inherent selection bias. Second, the small sample size of the ASR group may affect the stability of the multivariate analysis results. Third, long-term follow-up data for the ER group are lacking, precluding assessment of long-term recurrence and survival outcomes. Future multicenter, large-scale prospective studies incorporating molecular biomarkers are needed to develop more accurate predictive models.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, the clinical management of colorectal HGIN requires individualized and precise strategies. For high-risk patients with lesions\u0026thinsp;\u0026gt;\u0026thinsp;2.0 cm in diameter, located in the rectum or sigmoid colon, and exhibiting sessile morphology, endoscopic biopsy carries a significant risk of diagnostic underestimation. Clinical decision-making should be based on multidisciplinary team (MDT) discussion, integrating advanced assessment tools such as high-definition chromoendoscopy and endoscopic ultrasound (EUS). Initial treatment should prioritize ESD for its high en bloc resection rate, ensuring comprehensive pathological assessment. Upon identification of high-risk features in the postoperative pathology, timely additional radical surgery should be pursued to maximize oncological cure and improve patient prognosis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHGIN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHigh-grade intraepithelial neoplasia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eER\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEndoscopic resection\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eASR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAdditional surgery resection\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eColorectal cancer\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLNM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLymph node metastasis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLVI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLymph vascular invasion\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTumor budding\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEMR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEndoscopic mucosal resection\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eESD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEndoscopic submucosal dissection\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTIME\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTumor immune microenvironment\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMSI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMicrosatellite instability\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCIMP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCpG island methylator phenotype\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEMT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEpithelial-mesenchymal transition\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFAP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFamilial adenomatous polyposis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMDA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMalondialdehyde\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGSH-Px\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGlutathione peroxidase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMDT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMultidisciplinary team\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEUS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEndoscopic ultrasound\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all staff members of the Department of Gastroenterocolorectal Surgery at the China-Japan Union Hospital of Jilin University for their clinical and technical support. We also gratefully acknowledge the hospital administration for their facilitation of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYang Yang wrote the main manuscript text,Kexin Shen prepared Table 1 and 2 and Xie Zhongshi supervised the study. \u0026nbsp;All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no funding for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in accordance with the ethical standards of the Declaration of Helsinki. The study protocol was approved by the Ethics Committee of the China-Japan Union Hospital of Jilin University. Written informed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting of interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChoe K, Jang JY, Park I, Kim Y, Ahn S, Park DY, Hong YK, Alitalo K, Koh GY, Kim P. Intravital imaging of intestinal lacteals unveils lipid drainage through contractility. J Clin Invest. 2015;125(11):4042\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMohan BP, Khan SR, Chandan S, Kassab LL, Ponnada S, Asokkumar R, Shen B, Iacucci M, Navaneethan U. Endoscopic resection of colon dysplasia in patients with inflammatory bowel disease: a systematic review and meta-analysis. Gastrointest Endosc. 2021;93(1):59\u0026ndash;e6710.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee JK, Jensen CD, Levin TR, Zauber AG, Schottinger JE, Quinn VP, Udaltsova N, Zhao WK, Fireman BH, Quesenberry CP, et al. Long-term Risk of Colorectal Cancer and Related Deaths After a Colonoscopy With Normal Findings. JAMA Intern Med. 2019;179(2):153\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoda K, Oka S, Tanaka S, Nagata S, Kunihiro M, Kuwai T, Hiraga Y, Furudoi A, Terasaki M, Nakadoi K, et al. Clinical outcomes of endoscopic submucosal dissection for colorectal tumors: a large multicenter retrospective study from the Hiroshima GI Endoscopy Research Group. Gastrointest Endosc. 2018;87(3):714\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSiegel RL, Torre LA, Soerjomataram I, Hayes RB, Bray F, Weber TK, Jemal A. Global patterns and trends in colorectal cancer incidence in young adults. Gut. 2019;68(12):2179\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorita S, Goda K, Yano T, Kaise M, Kato M, Inoue H, Niwa Y, Kodashima S, Miyahara R, Ochiai A, et al. Multicenter prospective in vivo study of an endocytoscope system (ECS) for superficial esophageal cancer. J Gastroenterol. 2021;56(9):808\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen T, Qin WZ, Yao LQ, Zhong YS, Zhang YQ, Chen WF, Hu JW, Ooi M, Chen LL, Hou YY, et al. Long-term outcomes of endoscopic submucosal dissection for high-grade dysplasia and early-stage carcinoma in the colorectum. Cancer Commun (Lond). 2018;38(1):3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTokutake K, Morelos-Gomez A, Hoshi KI, Katouda M, Tejima S, Endo M. Artificial intelligence for the prevention and prediction of colorectal neoplasms. J Transl Med. 2023;21(1):431.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi R, Sun X, Yu Z, Li P, Zhao X. Identification of predictors for lymph node metastasis in T2 colorectal cancer: retrospective cohort study from a high-volume hospital. BMC Cancer. 2025;25(1):700.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTamari H, Kitadai Y, Takigawa H, Yuge R, Urabe Y, Shimamoto F, Oka S. Investigating the Role of Tumor-Infiltrating Lymphocytes as Predictors of Lymph Node Metastasis in Deep Submucosal Invasive Colorectal Cancer: A Retrospective Cross-Sectional Study. \u003cem\u003eCancers (Basel)\u003c/em\u003e 2023, 15(21).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXue Y, Jiang Z, Gu J, Deng S, Cai K, Wu K. Analysis of Immune Cell Infiltration Distribution and Prognostic Value in Obstructive Colorectal Cancer. Biomedicines 2025, 13(11).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSteffen P, Li J, Chandra J, Ahadi MS, Gill AJ, Engel AF, Molloy MP. Molecular Features of Lymph Node Metastasis in T1/2 Colorectal Cancer from Formalin-Fixed Paraffin-Embedded Archival Specimens. J Proteome Res. 2021;20(2):1304\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan Egeren D, Schenck RO, Khan A, Horning AM, Mo S, Wei\u0026szlig; CL, Esplin ED, Becker WR, Wu S, Hanson C et al. Polyclonal origins of human premalignant colorectal lesions. Nature 2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBurnett-Hartman AN, Lee JK, Demb J, Gupta S. An Update on the Epidemiology, Molecular Characterization, Diagnosis, and Screening Strategies for Early-Onset Colorectal Cancer. Gastroenterology. 2021;160(4):1041\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGolomb BA, Devaraj S, Messner AK, Koslik HJ, Han JH, Yik B. Lower blood malondialdehyde is associated with past pesticide exposure: findings in Gulf War illness and healthy controls. Mil Med Res. 2021;8(1):46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang Y, Fan W, Li X, Wang WX, Liu S. Enhanced Removal of Free Radicals by Aqueous Hydrogen Nanobubbles and Their Role in Oxidative Stress. Environ Sci Technol. 2022;56(21):15096\u0026ndash;107.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePan Y, Wei J, Qin D, Zhou X, Gao F, Yu L, Feng C, Mi J, Wu J, Law BYK, et al. Prosapogenin CP4 exacerbates mitophagy to induce apoptosis via AMPK-mTOR and PINK1/Parkin pathways in A549 cells. Phytomedicine. 2025;148:157333.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKin R, Hoshi D, Fujita H, Kosaka T, Takamura H, Kiyokawa E. Prognostic significance of p16, p21, and Ki67 expression at the invasive front of colorectal cancers. Pathol Int. 2023;73(2):81\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNersisyan L, Hopp L, Loeffler-Wirth H, Galle J, Loeffler M, Arakelyan A, Binder H. Telomere Length Maintenance and Its Transcriptional Regulation in Lynch Syndrome and Sporadic Colorectal Carcinoma. Front Oncol. 2019;9:1172.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen FX, Jiang KK, Zhu JF, Wang MR, Fan XL, Yang JS, He BS. Diagnostic accuracy of dual-layer spectral computed tomography virtual monoenergetic imaging with multiplanar reformation for T-staging of colorectal cancer. World J Gastroenterol. 2025;31(32):110573.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou MJ, Lebwohl B, Krigel A. Patient and Physician Factors Associated with Adenoma and Sessile Serrated Lesion Detection Rates. Dig Dis Sci. 2020;65(11):3123\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNaito S, Yoshio T, Ishiyama A, Tsuchida T, Tokura J, Namikawa K, Tokai Y, Yoshimizu S, Horiuchi Y, Hirasawa T, et al. Long-term outcomes of esophageal squamous cell carcinoma with invasion depth of pathological T1a-muscularis mucosae and T1b-submucosa by endoscopic resection followed by appropriate additional treatment. Dig Endosc. 2022;34(4):793\u0026ndash;804.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLugli A, Zlobec I, Berger MD, Kirsch R, Nagtegaal ID. Tumour budding in solid cancers. Nat Rev Clin Oncol. 2021;18(2):101\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEbbeh\u0026oslash;j AL, Smith HG, J\u0026oslash;rgensen LN, Krarup PM. Prognostic Factors for Lymph Node Metastases in pT1 Colorectal Cancer Differ According to Tumor Morphology: A Nationwide Cohort Study. Ann Surg. 2023;277(1):127\u0026ndash;35.\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":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Colorectal high-grade intraepithelial neoplasia, Endoscopic resection, Surgical resection, Colorectal cancer, Diagnostic accuracy, Risk factors","lastPublishedDoi":"10.21203/rs.3.rs-8279345/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8279345/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAccurate management of colorectal high-grade intraepithelial neoplasia (HGIN) is challenging due to the limited accuracy of diagnostic endoscopic biopsy and the difficulty in choosing between endoscopic therapy and radical surgery.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively analyzed 69 patients with preoperative biopsy-diagnosed colorectal HGIN (2019\u0026ndash;2023). Data included demographics, lesion features, and treatments, focusing on preoperative-postoperative pathological concordance.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eFifty-six and thirteen patients underwent endoscopic resection (ER) and additional surgery resection (ASR), respectively. The baseline characteristics were balanced between the two groups, with no statistically significant differences observed in age, sex, clinical presentation, or lesion number (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Complication rates were similar (16.1% vs. 15.4%, P\u0026thinsp;=\u0026thinsp;0.723). The biopsy accuracy was 81.2%; 18.8% of lesions were upgraded to T1 colorectal cancer (CRC). Lesions in the ASR group were larger than in the ER group (2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.51 cm vs. 1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.43 cm, P\u0026thinsp;=\u0026thinsp;0.015). T1 lesions were larger than HGIN lesions (P\u0026thinsp;=\u0026thinsp;0.002). Rectosigmoid location (P\u0026thinsp;=\u0026thinsp;0.032) and solitary lesions (carcinoma rate: ASR 62.5% vs. ER 4.76%; OR\u0026thinsp;=\u0026thinsp;33.33, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) conferred higher cancer risk. For solitary lesions, the carcinoma rate was significantly higher in the ASR group than in the ER group (62.5% vs. 4.76%, OR\u0026thinsp;=\u0026thinsp;33.33, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Although sessile morphology was associated with the decision for surgical intervention (P\u0026thinsp;=\u0026thinsp;0.003), its efficacy in discriminating between HGIN and T1 carcinoma was limited (P\u0026thinsp;=\u0026thinsp;0.057). Lymph node metastasis (LNM) occurred only in T1 patients (27.3%; 28.6% in the ASR). High-grade tumor budding (Bd\u0026thinsp;\u0026gt;\u0026thinsp;1) and lymph vascular invasion (LVI) were enriched in the ASR group (OR\u0026thinsp;=\u0026thinsp;43.33, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and strongly associated with T1 cancer (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The R0 resection rate was comparable between HGIN and T1 lesions (P\u0026thinsp;=\u0026thinsp;0.264).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eImproving endoscopic biopsy accuracy is essential. ER is safe and feasible, providing effective local control for HGIN and low-risk T1 CRC without LNM.\u003c/p\u003e","manuscriptTitle":"Comparative Study on Efficacy and Risk of Pathological Upgrading between Endoscopic and Surgical Resection for Colorectal High-Grade Intraepithelial Neoplasia: A Retrospective Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-26 06:58:47","doi":"10.21203/rs.3.rs-8279345/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-03-06T22:00:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"116654213392019472629900096341127711026","date":"2026-02-26T04:30:16+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-24T10:01:52+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-02T10:14:48+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-08T10:53:35+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-08T10:52:14+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2025-12-04T12:30:09+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dd25fa3a-d514-49ec-8249-70fda35f81d0","owner":[],"postedDate":"February 26th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-26T06:58:48+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-26 06:58:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8279345","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8279345","identity":"rs-8279345","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}