A new clinical model for predicting lymph node metastasis in T1 colorectal cancer.

PURPOSE: Lymph node metastasis (LNM) is a crucial factor that determines the prognosis of T1 colorectal cancer (CRC) patients. We aimed to develop a practical prediction model for LNM in T1 CRC. METHODS: We conducted a retrospective analysis of data from 825 patients with T1 CRC who underwent radical resection at a single center in China. All enrolled patients were randomly divided into a training set and a validation set at a ratio of 7:3 using R software. Risk factors for LNM were identified through multivariate logistic regression analyses. Subsequently, a prediction model was developed using the selected variables. RESULTS: The lymph node metastasis (LNM) rate was 10.1% in the training cohort and 9.3% in the validation cohort. In the training set, risk factors for LNM in T1 CRC were identified, including depressed endoscopic gross appearance, sex, submucosal invasion combined with tumor grade (DSI-TG), lymphovascular invasion (LVI), and tumor budding. LVI emerged as the most potent predictor for LNM. The prediction model based on these factors exhibited good discrimination ability in the validation sets (AUC: 79.3%). Compared to current guidelines, the model could potentially reduce over-surgery by 48.9%. Interestingly, we observed that sex had a differential impact on LNM between early-onset and late-onset CRC patients. CONCLUSIONS: We developed a clinical prediction model for LNM in T1 CRC using five factors that are easily accessible in clinical practice. The model has better predictive performance and practicality than the current guidelines and can assist clinicians in making treatment decisions for T1 CRC patients.

Potential Molecular Markers Related to Lymph Node Metastasis and Stalk Resection Margins in Pedunculated T1 Colorectal Cancers Using Digital Spatial Profiling: A Pilot Study with a Small Case Series.

There is a debate regarding the prediction of lymph node metastasis (LNM) in pedunculated T1 colorectal cancer (CRC). In this study with four cases of pedunculated T1 CRCs, we aimed to investigate gene expression variations based on the distance from the Haggitt line (HL) and identify potential molecular risk factors for LNM. By leveraging the Cancer Transcriptome Atlas and digital spatial profiling technology, we meticulously analyzed discrete regions, including the head, HL, proximal stalk region (300-1000 µm from HL), and distal stalk region (1500-2000 µm from HL) to identify spatially sequential molecular changes. Our findings showed significant overall gene expression variations among the head, proximal stalk, and distal stalk regions of pedunculated T1 CRCs compared to the control adenoma. Compared to LNM-negative T1 CRCs, LNM-positive T1 CRC showed that the expression of genes involved in immune-related pathways such as B2M, HLA-B, and HLA-E were significantly downregulated in the distal stalk region compared to the proximal stalk region. In summary, our results may tentatively suggest considering endoscopic resection of the stalk with a minimum 2000 µm margin from the HL, taking into account the gene expression alterations related to immune-related pathways. However, we acknowledge the limitations of this pilot study, notably the small case series, which may restrict the depth of interpretation. Further validation is imperative to substantiate these findings.

Are the width, length, depth, and area of submucosal invasion predictive of lymph node metastasis in pT1 colorectal cancer?

PURPOSE: Submucosa-limited (pathological T1, pT1) colorectal cancers (CRCs) pose a continuing challenge in the choice of treatment options, which range from local excision to radical surgery. The aim of this study was to evaluate the morphometric and morphologic risk factors associated with regional lymph node metastasis (LNM) in pT1 CRC. METHODS: We performed a histological review of patients who underwent oncological resection between 2016 and 2022. Tumor grade, budding, poorly differentiated clusters (PDCs), cancer gland rupture, lymphovascular invasion (LVI), and presence of deep submucosal invasion (DSI), as well as width, length, total area, and area of DSI, were evaluated as potential risk factors for LNM. RESULTS: A total of 264 cases of colon and rectal carcinomas with invasion into the submucosal layer (pT1) were identified. LNM was found in 46 of the 264 cases (17.4%). All morphometric parameters, as well as DSI (P=0.330), showed no significant association with LNM. High grade adenocarcinoma (P=0.050), budding (P=0.056), and PDCs (P<0.001) were associated with LNM. In the multivariate analysis, LVI presence remained the only significant independent risk factor (odds ratio, 15.7; 95% confidence interval, 8.5-94.9; P<0.001). CONCLUSION: The DSI of T1 CRC, as well as other morphometric parameters of submucosal tumor spread, held no predictive value in terms of LNM. LVI was the only independent risk factor of LNM.

Reduced DEFA5 Expression and STAT3 Activation Underlie the Submucosal Invasion of Early Gastric Cancers.

INTRODUCTION: Submucosal invasion is a core hallmark of early gastric cancer (EGC) with poor prognosis. However, the molecular mechanism of the progression from intramucosal gastric cancer (IMGC) to early submucosal-invasive gastric cancer (SMGC) is not fully understood. The objective of this study was to identify genes and pathways involved in the submucosal invasion in EGC using comprehensive gene expression analysis. METHODS: Gene expression profiling was performed for eight cases of IMGC and eight cases of early SMGC with submucosal invasion ≥500 µm. To validate the findings of gene expression analysis and to examine the gene expression pattern in tissues, immunohistochemical (IHC) staining was performed for 50 cases of IMGC and SMGC each. RESULTS: Gene expression analysis demonstrated that the expression levels of small intestine-specific genes were significantly decreased in SMGC. Among them, defensin alpha 5 (DEFA5) was the most downregulated gene in SMGC, which was further validated in SMGC tissues by IHC staining. Gene set enrichment analysis showed a strong association between SMGC, the JAK-STAT signaling pathway, and the upregulation of STAT3-activating cytokines. The expression of phosphorylated STAT3 was significant in the nucleus of tumor cells in SMGC tissues but not in areas expressing DEFA5. CONCLUSION: The results of this study strongly suggest that the downregulation of DEFA5 and the activation of STAT3 play a significant role in the submucosal invasion of EGC.

Chicken skin mucosa surrounding small colorectal cancer could be an endoscopic predictive marker of submucosal invasion.

BACKGROUND: Chicken skin mucosa (CSM) surrounding colon polyps is a common endoscopic finding with pale yellow-speckled mucosa during a colonoscopy screening. Although reports about CSM surrounding small colorectal cancer are scarce, and its clinical significance in intramucosal and submucosal cancers is unclear, previous studies have suggested it could be an endoscopic predictive marker for colonic neoplastic and advanced polyps. Currently, because of the inaccurate preoperative evaluation by endoscopists, many small colorectal cancers, particularly lesions with a diameter < 2 cm, are improperly treated. Therefore, more effective methods are required to better assess the depth of the lesion before treatment. AIM: To explore potential markers of small colorectal cancer early invasion under white light endoscopy, providing patients with better treatment alternatives. METHODS: This retrospective cross-sectional study included 198 consecutive patients [233 early colorectal cancers (ECCs)] who underwent endoscopy or surgical procedures at the Digestive Endoscopy Center of Chengdu Second People's Hospital between January 2021 and August 2022. The participants had pathologically confirmed colorectal cancer with a lesion diameter < 2 cm and received endoscopic or surgical treatment, including endoscopic mucosal resection and submucosal dissection. Clinical pathology and endoscopy parameters, including tumor size, invasion depth, anatomical position, and morphology, were reviewed. Fisher's exact test, the χ2 test, and Student's t-test were used to analyze the patient's basic characteristics. Logistic regression analysis was used to examine the relationship between morphological characteristics, size, CSM prevalence, and ECC invasion depth under white light endoscopy. Statistical significance was set at P < 0.05. RESULTS: The submucosal carcinoma (SM stage) was larger than the mucosal carcinoma (M stage) with a significant difference (17.2 ± 4.1 vs 13.4 ± 4.6 mm, P < 0.01). M- and SM-stage cancers were common in the left colon; however, no significant differences were found between them (151/196, 77% and 32/37, 86.5%, respectively, P = 0.199). The endoscopic features of colorectal cancer revealed that CSM, depressed areas with clear boundaries, and erosion or ulcer bleeding were more common in the SM-stage cancer group than in the M-stage cancer group (59.5% vs 26.2%, 46% vs 8.7%, and 27.3% vs 4.1%, respectively, P < 0.05). CSM prevalence in this study was 31.3% (73/233). The positive rates of CSM in flat, protruded, and sessile lesions were 18% (11/61), 30.6% (30/98), and 43.2% (32/74), respectively, with significant differences (P = 0.007). CONCLUSION: CSM-related small colorectal cancer was primarily located in the left colon and could be a predictive marker of submucosal invasion in the left colon.

Lesion size, elevated morphology, and non or closed-type atrophy are predictive factors for gastric adenocarcinoma of the fundic gland type rather than oxyntic gland adenoma.

Background: An oxyntic gland neoplasm confined to the mucosal layer (T1a) is classified as an oxyntic gland adenoma, whereas that with submucosal invasion (T1b) is defined as gastric adenocarcinoma of the fundic gland type (GA-FG). Methods: To reveal the differences in clinical features between them, we retrospectively investigated 136 patients with 150 oxyntic gland adenoma and GA-FG lesions. Results: The univariate analysis revealed that the mean size (GA-FG vs. oxyntic gland adenoma, 7.7±5.4 vs. 5.5±3.1 mm), the prevalence of elevated morphology (79.1% vs. 51.8%), black pigmentation within the lesion (23.9% vs. 9.6%), and non or closed-type atrophy (81.2% vs. 65.1%) were different between the two groups. A multivariate logistic regression analysis revealed that ≥5 mm lesion size (odds ratio, 2.96; 95% confidence interval: 1.21-7.23), elevated morphology (odds ratio, 2.40; 95% confidence interval: 1.06-5.45), and no or closed-type atrophy (odds ratio, 2.49; 95% confidence interval: 1.07-5.80) were factors in distinguishing GA-FG from oxyntic gland adenoma. When oxyntic gland neoplasms with no or one feature were judged as oxyntic gland adenomas and those with two or three features were judged as GA-FG, the sensitivity and specificity were 85.1% and 43.4% for GA-FG, respectively. Conclusions: We identified three possible distinctive features of GA-FG compared to oxyntic gland adenoma: lesion size ≥5 mm, elevated morphology, and no or closed-type atrophy.

[Analysis of risk factors for depth of invasion and angiolymphatic invasion for circumferential superficial esophageal squamous cell carcinoma and precancerous lesion].

Objective: To analyze clinicopathological features of circumferential superficial esophageal squamous cell carcinoma and precancerous lesions and investigate the risk factors for deep submucosal invasion and angiolymphatic invasion retrospectively. Methods: A total of 116 cases of esophageal squamous epithelial high-grade intraepithelial neoplasia or squamous cell carcinoma diagnosed by gastroscopy, biopsy pathology and endoscopic resection pathology during November 2013 to October 2021 were collected, and their clinicopathological features were analyzed. The independent risk factors of deep submucosal invasion and angiolymphatic invasion were analyzed by logistic regression model. Results: The multivariate logistic regression analysis showed that drinking history (OR=3.090, 95% CI: 1.165-8.200; P<0.05), The AB type of intrapapillary capillary loop (IPCL) (OR=11.215, 95% CI: 3.955-31.797; P<0.05) were the independent risk factors for the depth of invasion. The smoking history (OR=5.824, 95% CI: 1.704-19.899; P<0.05), the presence of avascular area (AVA) (OR=3.393, 95% CI: 1.285-12.072; P<0.05) were the independent factors for the angiolymphatic invasion. Conclusions: The risk of deep submucosal infiltration is greater for circumferential superficial esophageal squamous cell carcinoma patients with drinking history and IPCL type B2-B3 observed by magnifying endoscopy, while the risk of angiolymphatic invasion should be vigilant for circumferential superficial esophageal squamous cell carcinoma patients with smoking history and the presence of AVA observed by magnifying endoscopy. Ultrasound endoscopy combined with narrowband imagingand magnification endoscopy can improve the accuracy of preoperative assessment of the depth of infiltration of superficial squamous cell carcinoma and precancerous lesions and angiolymphaticinvasion in the whole perimeter of the esophagus, and help endoscopists to reasonably grasp the indications for endoscopic treatment.

The Feasibility and Safety of Endoscopic Submucosal Dissection for Circumferential Superficial Esophageal Squamous Cell Neoplasms.

Background It remains controversial whether endoscopic submucosal dissection (ESD) is still appropriate for circumferential superficial esophageal squamous cell neoplasms (SESCN), and few studies compared the short-term and long-term outcomes of ESD with radical surgery. Methods A total of 140 patients with SESCN who underwent ESD or surgery between February 2014 and October 2021 were retrospectively reviewed. The characteristics of patients, operative time, postoperative complications, overall survival (OS), recurrence-free survival (RFS), and quality of life (QOL) were compared between the ESD and surgery groups. The effect of different methods to prevent esophageal stenosis after ESD were analysed. Results Drinking, family history of cancer, macroscopic type, and intrapapillary capillary loop (IPCL) type were independent risk factors for deep submucosal invasion (SM ≥ 200 µm). Smoking and IPCL type were independent predictive factors for angiolymphatic invasion. The average operative time of ESD was significantly shorter than that of surgery (174.5 ± 51.16 min vs. 255.9 ± 88.18 min, p < 0.001). The incidence of perioperative complications in ESD group was significantly lower than that in surgery group (5.5% vs. 19.4%, p = 0.015). The ESD group had significantly better functional scale scores for emotional functioning, cognitive functioning, and global health status, and lower rates of pain, dyspnoea, insomnia, appetite loss, diarrhoea, reflux, and trouble with taste than the surgery group. No significant difference in OS and RFS between ESD and surgery group. Conclusions ESD can significantly shorten the operative time and reduce perioperative complications. Additionally, on the premise of using appropriate measures to prevent postoperative stenosis, ESD can be the first choice for the treatment of SESCN, which could provide better QOL, and the long-term prognosis of ESD is no less than that of surgery.

Clinicopathological features of endoscopically treated early gastric cancer with lymphovascular infiltration.

PURPOSE: Lymphovascular infiltration (LVI) may play a critical role in radicality and prognostic assessment of early gastric cancer (EGC). However, risk factors for LVI in endoscopically resected EGC remain unknown. This study evaluated the clinicopathological characteristics and prognoses of patients who underwent endoscopic resection of EGC to identify potential risk factors of LVI. METHODS: A cross-sectional study of patients who received gastric endoscopic submucosal dissection between February 1, 2012, and December 31, 2019, at two institutions was conducted. Among 1,462 lesions, 943 met the criteria for radical treatment considering features other than LVI and were included. The lesions were classified based on the presence of LVI. The clinicopathological characteristics of the two groups were compared. RESULTS: LVI was detected in 17 lesions (1.8%). The positivity rates of LVI were 0.7% (7/903) for intramucosal cancer and 25% (10/40) for submucosally invasive cancer. The LVI positivity rate was significantly higher for mixed-type cancer (lesions containing differentiated and undifferentiated-type carcinoma) than for non-mixed-type cancer (35.3 vs. 2.8%; P < 0.001) and for submucosally invasive cancer than for intramucosal cancer (58.8 vs. 3.2%; P < 0.001). In the multivariate logistic regression analysis, independent risk factors for LVI were mixed-type cancer (odds ratio; 95% confidence interval: 23.9; 5.0-115; P < 0.001) and submucosal invasion (58.7; 16.0-215; P < 0.001). CONCLUSIONS: Mixed-type cancer and submucosal invasion were risk factors for LVI in endoscopically resected EGC. These factors may play a critical role in the radicality and prognostic assessment of EGC.

Analysis of risk factors for depth of invasion and angiolymphatic invasion for circumferential superficial esophageal squamous cell carcinoma and precancerous lesion / 中华肿瘤杂志

Objective: To analyze clinicopathological features of circumferential superficial esophageal squamous cell carcinoma and precancerous lesions and investigate the risk factors for deep submucosal invasion and angiolymphatic invasion retrospectively. Methods: A total of 116 cases of esophageal squamous epithelial high-grade intraepithelial neoplasia or squamous cell carcinoma diagnosed by gastroscopy, biopsy pathology and endoscopic resection pathology during November 2013 to October 2021 were collected, and their clinicopathological features were analyzed. The independent risk factors of deep submucosal invasion and angiolymphatic invasion were analyzed by logistic regression model. Results: The multivariate logistic regression analysis showed that drinking history (OR=3.090, 95% CI: 1.165-8.200; P<0.05), The AB type of intrapapillary capillary loop (IPCL) (OR=11.215, 95% CI: 3.955-31.797; P<0.05) were the independent risk factors for the depth of invasion. The smoking history (OR=5.824, 95% CI: 1.704-19.899; P<0.05), the presence of avascular area (AVA) (OR=3.393, 95% CI: 1.285-12.072; P<0.05) were the independent factors for the angiolymphatic invasion. Conclusions: The risk of deep submucosal infiltration is greater for circumferential superficial esophageal squamous cell carcinoma patients with drinking history and IPCL type B2-B3 observed by magnifying endoscopy, while the risk of angiolymphatic invasion should be vigilant for circumferential superficial esophageal squamous cell carcinoma patients with smoking history and the presence of AVA observed by magnifying endoscopy. Ultrasound endoscopy combined with narrowband imagingand magnification endoscopy can improve the accuracy of preoperative assessment of the depth of infiltration of superficial squamous cell carcinoma and precancerous lesions and angiolymphaticinvasion in the whole perimeter of the esophagus, and help endoscopists to reasonably grasp the indications for endoscopic treatment.

Diagnosis of Depth of Submucosal Invasion in Colorectal Cancer with AI Using Deep Learning.

The submucosal invasion depth predicts prognosis in early colorectal cancer. Although colorectal cancer with shallow submucosal invasion can be treated via endoscopic resection, colorectal cancer with deep submucosal invasion requires surgical colectomy. However, accurately diagnosing the depth of submucosal invasion via endoscopy is difficult. We developed a tool to diagnose the depth of submucosal invasion in early colorectal cancer using artificial intelligence. We reviewed data from 196 patients who had undergone a preoperative colonoscopy at the Osaka University Hospital and Osaka International Cancer Institute between 2011 and 2018 and were diagnosed pathologically as having shallow submucosal invasion or deep submucosal invasion colorectal cancer. A convolutional neural network for predicting invasion depth was constructed using 706 images from 91 patients between 2011 and 2015 as the training dataset. The diagnostic accuracy of the constructed convolutional neural network was evaluated using 394 images from 49 patients between 2016 and 2017 as the validation dataset. We also prospectively tested the tool from 56 patients in 2018 with suspected early-stage colorectal cancer. The sensitivity, specificity, accuracy, and area under the curve of the convolutional neural network for diagnosing deep submucosal invasion colorectal cancer were 87.2% (258/296), 35.7% (35/98), 74.4% (293/394), and 0.758, respectively. The positive predictive value was 84.4% (356/422) and the sensitivity was 75.7% (356/470) in the test set. The diagnostic accuracy of the constructed convolutional neural network seemed to be as high as that of a skilled endoscopist. Thus, endoscopic image recognition by deep learning may be able to predict the submucosal invasion depth in early-stage colorectal cancer in clinical practice.

Lymph node metastasis in T1 colorectal cancer with the only high-risk histology of submucosal invasion depth ≥ 1000 µm.

PURPOSE: The number of patients undergoing additional surgery after endoscopic resection (ER) for T1 colorectal cancer (CRC) is increasing. Regarding high-risk histology of lymph node metastasis (LNM) in T1 CRC, a submucosal invasion depth ≥ 1000 µm (T1b) alone may be related to a low incidence of LNM. This study was conducted to clarify the incidence of LNM and to identify factors associated with LNM in T1 CRC with high-risk histology characterized only by T1b. METHODS: We retrospectively investigated patients with pathological T1b CRC who underwent colorectal resection between 2010 and 2020. Patients were divided into two groups with high-risk histology: those in whom the only high-risk feature was T1b (low-risk T1b group, n = 263), and those with T1b as well as lymphovascular invasion, tumor budding, or poorly differentiated or mucinous adenocarcinoma (high-risk T1b group, n = 289). The incidences of LNM and recurrence were compared. Multivariate analysis was performed to identify factors associated with LNM in the low-risk T1b group. RESULTS: The incidences of LNM were 3.8% and 21.6% in the Low- and High-risk T1b groups, respectively (p < 0.01), while the 5-year recurrence rates in the two groups were 0.6% and 3.4%, respectively (p = 0.10). Multivariate analysis revealed that only a predominant histological type of moderately differentiated adenocarcinoma (p = 0.04) was independently associated with LNM in the low-risk T1b group. CONCLUSION: When considering the omission of additional surgery after ER in cases of T1 CRC whose only high-risk histological feature is T1b, attention should be paid to the predominant histological type.

Predictors for malignant potential and deep submucosal invasion in colorectal laterally spreading tumors.

BACKGROUND: Colorectal laterally spreading tumors (LSTs) with malignant potential require en bloc resection by endoscopic submucosal dissection (ESD), but lesions with deep submucosal invasion (SMI) are endoscopically unresectable. AIM: To investigate the factors associated with high-grade dysplasia (HGD)/carcinoma and deep SMI in colorectal LSTs. METHODS: The endoscopic and histological results of consecutive patients who underwent ESD for colorectal LSTs in our hospital from June 2013 to March 2019 were retrospectively analyzed. The characteristics of LST subtypes were compared. Risk factors for HGD/carcinoma and deep SMI (invasion depth ≥ 1000 µm) were determined using multivariate logistic regression. RESULTS: A total of 323 patients with 341 colorectal LSTs were enrolled. Among the four subtypes, non-granular pseudodepressed (NG-PD) LSTs (85.5%) had the highest rate of HGD/carcinoma, followed by the granular nodular mixed (G-NM) (77.0%), granular homogenous (29.5%), and non-granular flat elevated (24.2%) subtypes. Deep SMI occurred commonly in NG-PD LSTs (12.9%). In the adjusted multivariate analysis, NG-PD [odds ratio (OR) = 16.8, P < 0.001) and G-NM (OR = 7.8, P < 0.001) subtypes, size ≥ 2 cm (OR = 2.2, P = 0.005), and positive non-lifting sign (OR = 3.3, P = 0.024) were independently associated with HGD/carcinoma. The NG-PD subtype (OR = 13.3, P < 0.001) and rectosigmoid location (OR = 8.7, P = 0.007) were independent risk factors for deep SMI. CONCLUSION: Because of their increased risk for malignancy, it is highly recommended that NG-PD and G-NM LSTs are removed en bloc through ESD. Given their substantial risk for deep SMI, surgery needs to be considered for NG-PD LSTs located in the rectosigmoid, especially those with positive non-lifting signs.

A rare case of Helicobacter pylori-uninfected foveolar-type gastric cancer with submucosal invasion and lymph node metastasis.

Gastric cancer without Helicobacter pylori infection accounts for less than 1% of all gastric cancers, and is generally considered to be less invasive. This report describes a rare case of H. pylori-uninfected gastric cancer with deep submucosal invasion and lymph node metastasis. Endoscopic submucosal dissection was performed, and pathological examination revealed tubular adenocarcinoma with deep submucosal invasion. We diagnosed foveolar-type gastric adenocarcinoma. While many cases of foveolar-type gastric adenocarcinoma, especially of the white elevated type, are reported as early stage gastric cancer, this case is very rare because it showed submucosal invasion and lymph node metastasis.

Artificial intelligence predicts lymph node metastasis or risk of lymph node metastasis in T1 colorectal cancer.

BACKGROUND: The treatment strategies for colorectal cancer (CRC) must ensure a radical cure of cancer and prevent over/under treatment. Biopsy specimens used for the definitive diagnosis of T1 CRC were analyzed using artificial intelligence (AI) to construct a risk index for lymph node metastasis. METHODS: A total of 146 T1 CRC cases were analyzed. The specimens for analysis were mainly biopsy specimens, and in the absence of biopsy specimens, the mucosal layer of the surgical specimens was analyzed. The pathology slides for each case were digitally imaged, and the morphological features of cancer cell nuclei were extracted from the tissue images. First, statistical methods were used to analyze how well these features could predict lymph node metastasis risk. A lymph node metastasis risk model using AI was created based on these morphological features, and accuracy in test cases was verified. RESULTS: Each developed model could predict lymph node metastasis risk with a > 90% accuracy in each region of interest of the training cases. Lymph node metastasis risk was predicted with 81.8-86.3% accuracy for randomly validated cases, using a learning model with biopsy data. Moreover, no case with lymph node metastasis or lymph node risk was judged to have no risk using the same model. CONCLUSIONS: AI models suggest an association between biopsy specimens and lymph node metastases in T1 CRC and may contribute to increased accuracy of preoperative diagnosis.

Deep Submucosal Invasion Is Not an Independent Risk Factor for Lymph Node Metastasis in T1 Colorectal Cancer: A Meta-Analysis.

BACKGROUND & AIMS: Deep submucosal invasion (DSI) is considered a key risk factor for lymph node metastasis (LNM) and important criterion to recommend surgery in T1 colorectal cancer. However, metastatic risk for DSI is shown to be low in the absence of other histologic risk factors. This meta-analysis determines the independent risk of DSI for LNM. METHODS: Suitable studies were included to establish LNM risk for DSI in univariable analysis. To assess DSI as independent risk factor, studies were eligible if risk factors (eg, DSI, poor differentiation, lymphovascular invasion, and high-grade tumor budding) were simultaneously included in multivariable analysis or LNM rate of DSI was described in absence of poor differentiation, lymphovascular invasion, and high-grade tumor budding. Odds ratios (OR) and 95% CIs were calculated. RESULTS: Sixty-seven studies (21,238 patients) were included. Overall LNM rate was 11.2% and significantly higher for DSI-positive cancers (OR, 2.58; 95% CI, 2.10-3.18). Eight studies (3621 patients) were included in multivariable meta-analysis and did not weigh DSI as a significant predictor for LNM (OR, 1.73; 95% CI, 0.96-3.12). As opposed to a significant association between LNM and poor differentiation (OR, 2.14; 95% CI, 1.39-3.28), high-grade tumor budding (OR, 2.83; 95% CI, 2.06-3.88), and lymphovascular invasion (OR, 3.16; 95% CI, 1.88-5.33). Eight studies (1146 patients) analyzed DSI as solitary risk factor; absolute risk of LNM was 2.6% and pooled incidence rate was 2.83 (95% CI, 1.66-4.78). CONCLUSIONS: DSI is not a strong independent predictor for LNM and should be reconsidered as a sole indicator for oncologic surgery. The expanding armamentarium for local excision as first-line treatment prompts serious consideration in amenable cases to tailor T1 colorectal cancer management.

Minimally Invasive Endoscopic and Surgical Management of Rectal Neoplasia.

Rectal cancer demonstrates a characteristic natural history in which benign rectal neoplasia precedes malignancy. The worldwide burden of rectal cancer is significant, with rectal cancer accounting for one-third of colorectal cancer cases annually. The importance of early detection and successful management is essential in decreasing its clinical burden. Minimally invasive treatment of rectal neoplasia has evolved over the past several decades, which has led to reduced local recurrence rates and improved survival outcomes. The approach to diagnosis, staging, and selection of appropriate treatment modalities is a multidisciplinary effort combining interventional endoscopy, surgery, and radiology tools. This review examines the currently available minimally invasive endoscopic and surgical management options of rectal neoplasia.

The essential problem of over-measuring the depth of submucosal invasion in pT1 colorectal cancer.

A depth of submucosal invasion (DSI) of ≥1000 µm is an important risk factor for lymph node metastasis (LNM) in patients with submucosal invasive (pT1) colorectal cancer (CRC), according to the European Society of Gastrointestinal Endoscopy and the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines. According to the latter, if the location of the muscularis mucosae in the invasive area is not confirmed, the DSI can be measured from the surface. In these cases, a 'remaining intramucosal lesion' (rIL), which is in the invasive area, is sometimes observed. To avoid over-measuring the DSI, we proposed a 'modified DSI' (mDSI), which excludes the rIL from the JSCCR DSI. We investigated the characteristics and effectiveness of the rIL and mDSI by grouping cases with polypoid growth (PG) and non-polypoid growth (NPG) histologically. Three hundred and thirty-nine consecutive patients with pT1 CRC were examined. LNM was detected in 37 cases. The distribution of the DSI and rIL was significantly higher in PG than in NPG cases (P<0.001). There was no difference in the mDSI distribution between the PG-/NPG-type cases. An rIL was observed in 39% (127/301) of cases, in which the location of the muscularis mucosae could not be determined or estimated and the mDIS could be estimated. In 13% (16/127) of cases, the mDSI was effective (JSCCR DSI ≥1000 and mDSI <1000 µm). Among these 16 cases, 11 (69%) did not have risk factors (mDSI, lymphovascular invasion, budding grade, or special histological types) and may have avoided unnecessary surgery.

A diagnostic test: diagnostic value of gastrointestinal endoscopy narrow-band imaging (NBI) for colorectal laterally spreading tumor (LST) and submucosal invasion.

Background: Endoscopic ultrasonography is an effective endoscopic examination method for determining the depth of colorectal cancer invasion. Narrow-band imaging (NBI) techniques increase the contrast of vascular structures and more clearly highlight subtle structures on mucosal surfaces, thereby improving the accuracy of endoscopic assessment. This study investigated the diagnostic efficacy of NBI in colorectal laterally spreading tumor (LST) and its submucosal invasion. Methods: A total of 224 patients with colorectal LST admitted to the Affiliated Hospital of Putian University from January 2015 to December 2021 were enrolled in this study. The patients were divided into NBI and endoscopic ultrasonography groups according to the different examination methods they received. Subsequently, the clinicopathological characteristics of the patients were collected, and the rates of submucosal invasion of the four subtypes (LST-G-H, LST-G-NM, LST-NG-F, LST-NG-PD) were compared between the two groups. Also, the accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of judging the depth of LST lesions of the two examination methods were compared, taking the results of pathological tissue examination as the gold standard. Results: This study enrolled 224 patients with LST (mean onset age: 57.98±6.48 years), including 123 males and 101 females. In terms of tumor location, 21 cases were located in the cecum, 22 cases in the ascending colon, 38 cases in the transverse colon, 11 cases in the descending colon, 12 cases in the descending sigmoid junction, 23 cases in the sigmoid colon, and 97 cases in the rectum. The sizes of the tumors ranged from 18.81 to 52.88 mm. Moreover, there were 21 cases of lesion infiltration into the submucosa, and the infiltration rate was 9.38%. Furthermore, the accuracy of NBI in diagnosing colorectal LST was significantly higher than that of endoscopic ultrasonography (87.05% vs. 57.14%); NBI was more accurate than endoscopic ultrasonography in the preoperative diagnosis of LST lesion depth in the rectal, non-rectal, granular (LST-G), non-granular (LST-NG), <40, and ≥40 mm groups. Conclusions: Gastrointestinal NBI has a superior accuracy rate and value than endoscopic ultrasonography in diagnosing colorectal LST, tumor lesion depth, and submucosal invasion. Therefore, gastrointestinal NBI deserves to be promoted in clinical work.

Activated macrophages promote invasion by early colorectal cancer via an interleukin 1ß-serum amyloid A1 axis.

Submucosal invasion and lymph node metastasis are important issues affecting treatment options for early colorectal cancer (CRC). In this study, we aimed to unravel the molecular mechanism underlying the invasiveness of early CRCs. We performed RNA-sequencing (RNA-seq) with poorly differentiated components (PORs) and their normal counterparts isolated from T1 CRC tissues and detected significant upregulation of serum amyloid A1 (SAA1) in PORs. Immunohistochemical analysis revealed that SAA1 was specifically expressed in PORs at the invasive front of T1b CRCs. Upregulation of SAA1 in CRC cells promoted cell migration and invasion. Coculture experiments using CRC cell lines and THP-1 cells suggested that interleukin 1ß (IL-1ß) produced by macrophages induces SAA1 expression in CRC cells. Induction of SAA1 and promotion of CRC cell migration and invasion by macrophages were inhibited by blocking IL-1ß. These findings were supported by immunohistochemical analysis of primary T1 CRCs showing accumulation of M1-like/M2-like macrophages at SAA1-positive invasive front regions. Moreover, SAA1 produced by CRC cells stimulated upregulation of matrix metalloproteinase-9 in macrophages. Our data suggest that tumor-associated macrophages at the invasive front of early CRCs promote cancer cell migration and invasion through induction of SAA1 and that SAA1 may be a predictive biomarker and a useful therapeutic target.