Submucosal Invasive Cancer Research Articles

Real-Time Artificial Intelligence-Based Histologic Classifications of Colorectal Polyps Using Narrow-Band Imaging.

Background and AimsWith the development of artificial intelligence (AI), we have become capable of applying real-time computer-aided detection (CAD) in clinical practice. Our aim is to develop an AI-based CAD-N and optimize its diagnostic performance with narrow-band imaging (NBI) images.MethodsWe developed the CAD-N model with ResNeSt using NBI images for real-time assessment of the histopathology of colorectal polyps (type 1, hyperplastic or inflammatory polyps; type 2, adenomatous polyps, intramucosal cancer, or superficial submucosal invasive cancer; type 3, deep submucosal invasive cancer; and type 4, normal mucosa). We also collected 116 consecutive polyp videos to validate the accuracy of the CAD-N.ResultsA total of 10,573 images (7,032 images from 650 polyps and 3,541 normal mucous membrane images) from 478 patients were finally chosen for analysis. The sensitivity, specificity, PPV, NPV, and accuracy for each type of the CAD-N in the test set were 89.86%, 97.88%, 93.13%, 96.79%, and 95.93% for type 1; 93.91%, 95.49%, 91.80%, 96.69%, and 94.94% for type 2; 90.21%, 99.29%, 90.21%, 99.29%, and 98.68% for type 3; and 94.86%, 97.28%, 94.73%, 97.35%, and 96.45% for type 4, respectively. The overall accuracy was 93%. We also built models for polyps ≤5 mm, and the sensitivity, specificity, PPV, NPV, and accuracy for them were 96.81%, 94.08%, 95%, 95.97%, and 95.59%, respectively. Video validation results showed that the sensitivity, specificity, and accuracy of the CAD-N were 84.62%, 86.27%, and 85.34%, respectively.ConclusionsWe have developed real-time AI-based histologic classifications of colorectal polyps using NBI images with good accuracy, which may help in clinical management and documentation of optical histology results.

New scoring system to distinguish deep invasive submucosal and muscularis propria colorectal cancer during colonoscopy: a development and global multicenter external validation study (e-T2 Score)

Diagnostics to differentiate deep submucosal invasive (invasion depth≥1000 μm [T1b]) colorectal cancer (CRC) from muscularis propria invasive (T2) CRC are limited. We aimed to establish and validate a scoring system that differentiates T1b from T2. A multicenter retrospective cross-validation study was performed. Four hundred sixty-one consecutive pathologically confirmed T1b or T2 CRCs were divided into the development (T1b, 222; T2, 189) and internal validation (T1b, 31; T2, 19) cohorts. Eight potential endoscopic findings were evaluated using the development cohort: loss of lobulation, deep depression, demarcated depressed area, protuberance within the depression, expanding appearance, fold convergency, erosion or white plaque, and Borrmann type 2 or 3 tumor. A scoring system that differentiates T1b from T2 was developed, and diagnostic performance was tested using the internal validation cohort by 8 endoscopists. External validation was conducted using 50 CRC images by 4 endoscopists from other institutions, including outside of Japan. Multivariate analysis identified the following 5 independent predictive endoscopic findings of T2 CRC: deep depression (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.07-4.04), demarcated depressed area (OR, 4.40; 95% CI, 1.39-13.9), 4-fold convergency or more (OR, 3.41; 95% CI, 1.90-6.11), erosion or white plaque (OR, 8.28; 95% CI, 2.77-24.7), and Borrmann type 2 or 3 tumor (OR, 8.76; 95% CI, 3.58-21.5). The area under the receiver-operating characteristic curve (AUROC) was .90 (95% CI, .87-.93) in the development cohort, .80 (95% CI, .76-.85) in the internal validation, and .76 (95% CI, .69-.83) in the external validation. We established and validated a new scoring system to differentiate T1b from T2 CRC using 5 simple endoscopic findings.

Oncological outcomes after piecemeal endoscopic mucosal resection of large non-pedunculated colorectal polyps with covert submucosal invasive cancer

ObjectiveManagement of covert submucosal invasive cancer (SMIC) discovered after piecemeal endoscopic mucosal resection (pEMR) of large (>20 mm) non-pedunculated colorectal polyps is challenging. The residual cancer risk is largely unknown....

A111 A RECTUM-SPECIFIC SELECTIVE RESECTION ALGORITHM OPTIMIZES ONCOLOGIC OUTCOMES FOR LARGE NON-PEDUNCULATED RECTAL POLYPS

BackgroundEndoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are complementary techniques for large (≥ 20mm) non-pedunculated rectal polyps (LNPRPs). A mechanism for appropriate technique selection has not been described.AimsTo evaluate whether a selective resection algorithm using EMR and ESD, based on real-time optical evaluation, optimizes oncologic outcomes for LNPRPsMethodsWe evaluated the performance of a selective resection algorithm (SRA; 08/2017-04/2021) compared to a universal EMR algorithm (UEA; 07/2008-07/2017) for LNPRPs within a prospective observational study. In the SRA, LNPRPs with features of superficial submucosal invasive cancer (SMIC < 1000μm; S-SMIC; Kudo pit pattern Vi), or with an increased risk of SMIC (Paris 0-Is or 0-IIa+Is non-granular, 0-IIa+Is granular with a dominant nodule ≥ 10mm) underwent ESD. The remaining LNPRPs underwent EMR. Algorithm performance was evaluated by SMIC identified after EMR, curative oncologic resection (R0 resection, S-SMIC, absence of negative histologic features), technical success, adverse events, and recurrence at first surveillance colonoscopy.Results480 LNPRPs were evaluated (290 UEA, 190 SRA). Median lesion size was 40mm (IQR 30-60mm). In the SRA, 103 (54.2%) and 87 (45.8%) LNPRPs underwent EMR and ESD, respectively. SMIC was identified in 56 (11.7%) LNPRPs. Significant differences in SMIC after EMR (SRA 1 (1.0%) vs. UEA 35 (12.1%); p = 0.001), curative oncologic resection (SRA 7 (33.3%) vs. UEA 2 (5.7%); p = 0.010), and recurrence (SRA 2 (1.6%) vs. UEA 40 (17.2%); p < 0.001) were identified. No significant differences in technical success or adverse events were identified (all p > 0.137). Among potentially curable malignant LNPRPs which underwent ESD, 100% (7/7) were cured.ConclusionsA SRA optimizes oncologic outcomes for LNPRPs and mitigates the risk of piecemeal resection of cancers.Oncologic Outcomes for Malignant LNPRPsOverall LNPRPs (N = 56, %)UEA LNPRPs (N = 35, %)SRA LNPRPs (N = 21, %)P-valueSMIC after EMR*36 (9.2)35 (12.1)1 (1.0)0.001En Bloc Resection23 (41.1)4 (11.4)19 (90.5)<0.001R0 Resection20 (35.7)2 (5.7)18 (85.7)<0.001Curative Resection9 (16.1)2 (5.7)7 (33.3)0.010EMR, endoscopic mucosal resection; LNPRP, large non-pedunculated rectal polyp; SMIC, submucosal invasive cancer; SRA, selective resection algorithm; UEA, universal endoscopic mucosal resection algorithm *Denominator: Large non-pedunculated rectal polyps which underwent endoscopic mucosal resectionFunding AgenciesThe Cancer Institute of New South Wales provided funding for a research nurse and data manager to assist with the administration of the study. Neal Shahidi was supported by the University of British Columbia Clinician Investigator Program. There was no influence from either institution regarding study design or conduct, data collection, management, analysis, interpretation, preparation, review, or approval of the manuscript.

The Risk Analyses of Lymph Node Metastasis and Recurrence for Submucosal Invasive Colorectal Cancer: Novel Criteria to Skip Completion Surgery.

Simple SummaryCompletion surgery is recommended for patients with submucosal invasive colorectal cancer (pT1 CRC) with known risk factors for lymph node metastasis (LNM). However, completion surgery would be able to be skipped for more of the population with very low risk for LNM and recurrence. The present study thus analyzed both short- and long-term outcomes for high-risk pT1 CRC patients who underwent surgery, showing that lymphovascular invasion was a potential independent risk factor for LNM, and rectal cancer and undifferentiated histology were independent risk factors for poor relapse-free survival in patients with high-risk pT1 CRC. No LNMs were observed in pT1 CRCs with an SM invasion depth ≤2000 µm that had no other risk factors except for budding. Based on the results, novel criteria to skip completion surgery for high-risk pT1 CRC have been established in the current study, which were also validated in an independent validation cohort.(1) Background: Additional surgical resection after endoscopic resection (ER) is recommended for patients with submucosal invasive colorectal cancer (pT1 CRC) who have risk factors for lymph node metastasis (LNM) (high-risk pT1 CRC). This study aimed to identify risk factors for LNM and metastatic recurrence and to determine the low-risk population for whom additional surgery can be omitted among high-risk pT1 CRCs. (2) Methods: We retrospectively identified 404 patients with pT1 CRC who underwent ER or surgery, and patients were divided into three groups: low-risk (n = 79); high-risk pT1 with ER (n = 40); and high-risk with surgery (n = 285). We also enrolled another 64 patients with high-risk pT1 CRC in an independent validation cohort. (3) Results: In the high-risk with surgery group, LNM was seen in 11.2%, and vascular and lymphatic invasions were significantly independent risk factors for LNM on multivariate analysis. No LNMs were observed in pT1 CRCs with a negative vertical margin and SM invasion depth ≤2000 µm that had no other risk factors except for budding. Five patients developed metastatic recurrence in the high-risk with surgery group, and rectal cancer and undifferentiated histology were significantly independent risk factors for poor relapse-free survival. No LNM or recurrent cases were seen in high-risk pT1 CRCs that met these criteria: differentiated adenocarcinoma, no lymphovascular invasion, colon cancer, SM invasion depth ≤2000 μm, and a negative vertical margin, which were validated in an independent validation cohort. (4) Conclusions: Completion surgery may be skipped for high-risk pT1 CRCs that meet our proposed criteria.

Incremental benefit of dye-based chromoendoscopy to predict the risk of submucosal invasive cancer in large nonpedunculated colorectal polyps

Detailed lesion assessment of large nonpedunculated colorectal polyps (LNPCPs;≥20mm) can help predict the risk of submucosal invasive cancer (SMIC). Traditionally this has required the use of dye-based chromoendoscopy (DBC). We sought to assess the accuracy and incremental benefit of DBC in addition to high-definition white-light imaging (HDWLI) and virtual chromoendoscopy (VCE) for the prediction of SMIC within LNPCPs. A prospective observational study of consecutive LNPCPs at a single tertiary referral center was performed. Before resection all lesions were assessed for the presence of a demarcated area (DA), defined as an area of disordered pit or microvascular pattern, by 2 trained endoscopists before and after DBC. Diagnostic performance characteristics were calculated with histology as the reference criterion standard, and overall agreement was calculated using the κ statistic. Over 39 months to March 2021, 400 consecutive LNPCPs (median lesion size, 35mm; interquartile range, 25-45) were analyzed. The overall rate of SMIC was 6.5%. Presence of a DA had an accuracy of 91% (95% confidence interval, 87.7-93.5) for SMIC, independent of the use of DBC. The rate of interobserver agreement for presence of a DA using HDWLI+ VCE was very high (κ= .96) with no benefit gained by the addition of DBC. The use of HDWLI and VCE is likely to be adequate for lesion assessment for the prediction of SMIC among LNPCPs. Further, the absence of a DA is strongly predictive for the absence of SMIC, independent to the use of DBC. (Clinical trial registration number: NCT03506321.).

Adenocarcinoma occurring from a sigmoid colostomy 20years after Hartmann's procedure for rectal cancer: A case report.

Cancer arising from the stoma is relatively rare. There is no established surgical procedure for stomal cancer. Furthermore, when a subcutaneous lymphovascular invasion occurs, there is no consensus on whether lymph node dissection along the lymph flow is required. We diagnosed colorectal cancer 20years after radical resection of rectal cancer. We encountered a 70-year-old man who had undergone Hartmann's procedure for rectal cancer 20years before consultation. Colonoscopy revealed a 30-mm-sized sub-pedunculated polyp with a base at the stoma, and a well-differentiated adenocarcinoma was detected. Approximately 30mm of the intestinal tract, including the stoma and skin in contact with the tumor, was resected. Pathological examination revealed submucosal invasive cancer with infiltration into the resected skin dermis and invasion of lymphatic vessels under the mucosa. Surgical margins were negative. It is thought that several causes overlap for stomal cancer, although a clear cause of occurrence is yet to be identified. However, as no established surgical procedure exists, the necessity for resection of the lymph nodes without exposure appears indisputable. Although it was reported that skin or subcutaneous metastasis in colorectal cancer is generally regarded as a symptom of systemic metastasis, opinions on the subcutaneous dissection margin of stomal cancer are rarely discussed. Stomal cancer can be observed macroscopically without colonoscopy. Patients and staff engaged in stoma care should be fully aware that continuous observation of the stoma is necessary even after rectal cancer surveillance is complete.

Clinical Updates in Colorectal Endoscopic Submucosal Dissection

Laterally spreading tumors (LSTs) are increasingly encountered with the uptake of colorectal cancer screening programs. The approach to LSTs is determined by the risk of submucosal invasive cancer (SMIC), because this dictates the most appropriate endoscopic or surgical intervention. In the West, endoscopic mucosal resection (EMR) is the first-line treatment for LSTs without SMIC, given its cost-effectiveness, superior safety profile, and patient quality of life when compared with surgery. Conversely, LSTs with SMIC have been traditionally referred for surgery.

Diagnosis and treatment of colorectal tumors: Differences between Japan and the West and future prospects.

Dye‐based chromoendoscopy has long been used routinely for endoscopic diagnosis of gastrointestinal tumors including colorectal tumors in Japan. In the West, on the other hand, dye‐based chromoendoscopy was not so commonly used. However, with the development of narrow band imaging (NBI), image‐enhanced endoscopy diagnosis has rapidly increased in the West.The most critical difference between Japan and the West is the histopathological evaluation of the lesions, which determines a major cause of differences in diagnostic and treatment strategies. In the West, intramucosal adenocarcinoma is not diagnosed until the cancer has invaded submucosal layer. In Japan, on the other hand, cancer is mainly diagnosed based on nuclear and structural atypia, and thus intramucosal adenocarcinoma is diagnosed in lesions that correspond to high‐grade adenoma in the West.In the West, since intramucosal carcinoma is not diagnosed by pathology, all benign adenomas are treated by piecemeal endoscopic resection, and only cancer invading the superficial submucosal layer is indicated for endoscopic submucosal dissection (ESD). Because of the risk of lymph node metastasis in the deep submucosal invasion, the European Society of Gastrointestinal Endoscopy and American Society for Gastrointestinal Endoscopy guidelines state that only superficial submucosal cancer is an indication for ESD. Unfortunately, it is impossible to selectively extract only superficial submucosal invasive cancer even with the use of magnified NBI and pit pattern observation. Therefore, we think that pathologists need to diagnose intramucosal adenocarcinoma with the potential to invade the submucosal layer based on the nuclear and structural atypia. Consequently, intramucosal adenocarcinoma and superficial submucosal cancers should be considered for en‐bloc ESD.

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.

Indications and outcomes of endoscopic resection for non-pedunculated colorectal lesions: A narrative review.

In the last years, endoscopic techniques gained a crucial role in the treatment of colorectal flat lesions. At the same time, the importance of a reliable assessment of such lesions to predict the malignancy and the depth of invasion of the colonic wall emerged. The current unsolved dilemma about the endoscopic excision techniques concerns the necessity of a reliable submucosal invasive cancer assessment system that can stratify the risk of the post-procedural need for surgery. Accordingly, this narrative literature review aims to compare the available diagnostic strategies in predicting malignancy and to give a guide about the best techniques to employ. We performed a literature search using electronic databases (MEDLINE/PubMed, EMBASE, and Cochrane Library). We collected all articles about endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) registering the outcomes. Moreover, we analyzed all meta-analyses comparing EMR vs ESD outcomes for colorectal sessile or non-polypoid lesions of any size, preoperatively estimated as non-invasive. Seven meta-analysis studies, mainly Eastern, were included in the analysis comparing 124 studies and overall 22954 patients who underwent EMR and ESD procedures. Of these, eighty-two were retrospective, twenty-four perspective, nine case-control, and six cohorts, while three were randomized clinical trials. A total of 18118 EMR and 10379 ESD were completed for a whole of 28497 colorectal sessile or non-polypoid lesions > 5-10 mm in size. In conclusion, it is crucial to enhance the preoperative diagnostic workup, especially in deciding the most suitable endoscopic method for radical resection of flat colorectal lesions at risk of underlying malignancy. Additionally, the ESD necessitates further improvement because of the excessively time-consuming as well as the intraprocedural technical hindrances and related complications. We found a higher rate of en bloc resections and R0 for ESD than EMR for non-pedunculated colorectal lesions. Nevertheless, despite the lower local recurrence rates, ESD had greater perforation rates and needed lengthier procedural times. The prevailing risk for additional surgery in ESD rather than EMR for complications or oncologic reasons is still uncertain.

Unified magnifying endoscopic classification for esophageal, gastric and colonic lesions: a feasibility pilot study.

Background and study aims Image-enhanced magnifying endoscopy allows optimization of the detection and diagnosis of lesions found in the gastrointestinal tract. Current organ-specific classifications are well-accepted by specialized endoscopists but may pose confusion for general gastroenterologists. To address this, our group proposed the Unified Magnifying Endoscopic Classification (UMEC) which can be applied either in esophagus, stomach, or colon. The aim of this study was to evaluate the diagnostic performance and clinical applicability of UMEC. Patients and methods A single-center, feasibility pilot study was conducted. Two endoscopists with experience in magnifying narrow band imaging (NBI), blinded to white-light and non-magnifying NBI findings as well as histopathological diagnosis, independently reviewed and diagnosed all images based on UMEC. In brief, UMEC is divided into three categories: non-neoplasia, intramucosal neoplasia, and deep submucosal invasive cancer. The diagnostic performance of UMEC was assessed while using the gold standard histopathology as a reference. Results A total of 303 gastrointestinal lesions (88 esophageal squamous lesions, 90 gastric lesions, 125 colonic lesions) were assessed. The overall accuracy for both endoscopists in the diagnosis of esophageal squamous cell cancer, gastric cancer, and colorectal cancer were 84.7 %, 89.5 %, and 83.2 %, respectively. The interobserver agreement for each organ, Kappa statistics of 0.51, 0.73, and 0.63, was good. Conclusions UMEC appears to be a simple and practically acceptable classification, particularly to general gastroenterologists, due to its good diagnostic accuracy, and deserves further evaluation in future studies.

Microenvironmental markers are correlated with lymph node metastasis in invasive submucosal colorectal cancer.

AimsRecent studies have shown that the microenvironment can include cancer cells and cancer‐associated fibroblasts (CAFs), and that both play important roles in the progression and metastasis of CRC. Here, we aimed to analyse the expression patterns of cancer cell‐ and CAF‐related proteins in submucosal invasive colorectal cancer (SiCRC) and whether such markers are correlated with lymph node metastasis (LNM).Methods and resultsQuantitative analysis was conducted for Ki‐67, p53, β‐catenin and matrix metalloproteinase‐7 (MMP7) to assess cancer cell markers. In addition, we examined CAF markers, including smooth muscle alpha‐actin (α‐SMA), CD10, podoplanin, fibroblast‐specific protein 1 (FSP‐1), platelet‐derived growth factor receptor (PDGFR)‐α, PDGFR‐β, adipocyte enhancer‐binding protein 1 (AEBP1), fibroblast‐associated protein 1 (FAP‐1), zinc finger E‐box binding homeobox 1 (ZEB1) and TWIST‐related protein 1 (TWIST1). In both cases, we conducted digital pathology with Aperio software. We also examined the expression patterns of biomarkers using hierarchical cluster analysis. Two subgroups were established based on the expression patterns of cancer cell‐ and CAF‐ related markers, and the associations of these subgroups with clinicopathological variables. In multivariate analysis, subgroup 2, which was characterised by high expression of Ki‐67, p53, FAP‐1, platelet‐derived growth factor receptor (PDGFR)‐α, PDGFR‐β and TWIST1, was correlated with LNM (P < 0.01). Next, we examined the associations of individual biomarkers with LNM. Multivariate analysis showed that high expression levels of Ki‐67 and FAP‐1 were significantly associated with LNM (P < 0.05).ConclusionsOur findings showed that expression patterns of cancer cell‐ and CAF‐related proteins may allow for stratification of patients into risk categories for LNM in SiCRC. In addition, Ki‐67‐ and FAP‐1‐expressing microenvironmental cells might be helpful for identification of correlations with LNM in SiCRC.

Long-term outcomes of endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma in Taiwan

BackgroundEndoscopic submucosal dissection (ESD) is gradually turning into the standard treatment for superficial esophageal squamous cell carcinoma (SESCC), however, the long-term outcomes have hardly ever been reported outside Japan.MethodWe consecutively recruited patients with SESCC who had received ESD treatment at E-Da Hospital. The demographics, pathological characteristics, and Lugol staining background pattern (type A or B: none or < 10 small Lugol-voiding lesions [LVLs]; type C or D: > 10 small or multiform LVLs) were collected, and then correlated to outcomes and survival.ResultsTotal of 229 lesions were enrolled and the mean lesion size was 3.28 ± 1.69 (range 1–10) cm. 72% of the lesions had a type C-D Lugol staining background pattern. After ESD, the en bloc and R0 resection rates were 93.9% and 83.5%, respectively. Forty-nine subjects developed complications, including six (2.6%) with major bleeding, two (0.9%) with perforation, and 41 (17.9%) with strictures. Pathological staging showed that 19 cases had deep submucosal cancer invasion and subsequently received adjuvant therapies. During a mean follow-up period of 52.6 (range 3–146) months, 41 patients developed metachronous recurrence. The patients with a type C-D Lugol staining background pattern were associated with a higher risk of recurrence than those with few LVLs (log-rank P = 0.019). The 10-year survival rate was more than 90%, and only eight patients died of ESCC.ConclusionESD has excellent long-term outcomes but a high risk of metachronous recurrence. The Lugol staining pattern over the background mucosa could offer the risk stratification of metachronous recurrence.

Is barium enema examination negligible for the management of colorectal cancer? Comparison with conventional colonoscopy and magnifying colonoscopy.

The aim of this investigation was to evaluate the clinical value of barium enema (BE) examination for the management of colorectal epithelial neoplasms. We reviewed the colonoscopy records at our institution from 2014 to 2019 and identified cases of endoscopically or surgically resected colorectal epithelial neoplasms evaluated by BE, conventional colonoscopy, magnifying narrow-band imaging colonoscopy (M-NBI), and magnifying chromoendoscopy (MCE). The yield of each modality for the diagnosis of massively submucosal invasive (mSM) colorectal cancer was evaluated by a receiver-operating characteristic analysis including the area under the curve (AUC). We analyzed the records of 105 patients (17 adenomas, 53 high-grade dysplasias (HGDs), and 35 cancers). Smooth surface, irregularity in depression, and eccentric deformity on the profile view with BE were observed more frequently in mSM cancers than adenomas/HGDs/slightly submucosal invasive cancers (p < 0.01). The AUC of BE was 0.8355, the value of which was not different from the other three modalities (conventional colonoscopy 0.7678; M-NBI 0.7835; MCE 0.8376). Although the specificity, PPV, and accuracy of BE were lower than those of M-NBI and MCE, the sensitivity and NPV of BE were the highest among the four types of examinations. BE is still available and may serve as a supplementary modality for the diagnosis of mSM cancers.

Japan narrow-band imaging Expert Team type 2B colorectal cancer: consistency between endoscopic prediction and pathological diagnosis

To explore the potential factors that affect the accuracy of endoscopic diagnosis for Japan narrow-band imaging (NBI) Expert Team (JNET) type 2B colorectal lesions. The clinical data were collected from 261 patients with JNET type 2B colorectal lesions diagnosed in Nanfang Hospital between July, 2018 and July, 2021. We analyzed the macroscopic type, size, location or pit pattern classification of the lesions for their potential influence of the diagnostic accuracy of JNET type 2B lesions. The 261 lesions included 91 low-grade intramucosal neoplasia lesions (34.9%), 132 high-grade intramucosal neoplasia lesions (50.6%), 13 submucosal invasive cancer lesions (5.0%), and 25 deep submucosal invasive cancer lesions (9.6%). The coincidence rate between endoscopic prediction and pathological diagnosis of these lesions was 55.6% (145/ 261). The macroscopic type and size of the lesions were significantly associated with the diagnostic accuracy of JNET type 2B lesions (P < 0.001). There was a significant difference in the diagnostic accuracy among the lesions with different pit pattern types (P < 0.001). Both the macroscopic type and size affect the accuracy of endoscopic diagnosis of JNET type 2B colorectal lesions. JNET classification combined with pit pattern types can have better accuracy in predicting the pathological diagnosis of these lesions.

Role of tumor-associated macrophages at the invasive front in human colorectal cancer progression.

Macrophages are an essential component of antitumor activity; however, the role of tumor‐associated macrophages (TAMs) in colorectal cancer (CRC) remains controversial. Here, we elucidated the role of TAMs in CRC progression, especially at the early stage. We assessed the TAM number, phenotype, and distribution in 53 patients with colorectal neoplasia, including intramucosal neoplasia, submucosal invasive colorectal cancer (SM‐CRC), and advanced cancer, using double immunofluorescence for CD68 and CD163. Next, we focused on the invasive front in SM‐CRC and association between TAMs and clinicopathological features including lymph node metastasis, which were evaluated in 87 SM‐CRC clinical specimens. The number of M2 macrophages increased with tumor progression and dynamic changes were observed with respect to the number and phenotype of TAMs at the invasive front, especially at the stage of submucosal invasion. A high M2 macrophage count at the invasive front was correlated with lymphovascular invasion, low histological differentiation, and lymph node metastasis; a low M1 macrophage count at the invasive front was correlated with lymph node metastasis. Furthermore, receiver operating characteristic curve analysis revealed that the M2/M1 ratio was a better predictor of the risk of lymph node metastasis than the pan‐, M1, or M2 macrophage counts at the invasive front. These results suggested that TAMs at the invasive front might play a role in CRC progression, especially at the early stages. Therefore, evaluating the TAM phenotype, number, and distribution may be a potential predictor of metastasis, including lymph node metastasis, and TAMs may be a potential CRC therapeutic target.

Optical Evaluation for Predicting Cancer in Large Nonpedunculated Colorectal Polyps Is Accurate for Flat Lesions

The ability of optical evaluation to diagnose submucosal invasive cancer (SMIC) prior to endoscopic resection of large (≥20 mm) nonpedunculated colorectal polyps (LNPCPs) is critical to inform therapeutic decisions. Prior studies suggest that it is insufficiently accurate to detect SMIC. It is unknown whether lesion morphology influences optical evaluation performance. LNPCPs ≥20 mm referred for endoscopic resection within a prospective, multicenter, observational cohort were evaluated. Optical evaluation was performed prior to endoscopic resection with the optical prediction of SMIC based on established features (Kudo V pit pattern, depressed morphology, rigidity/fixation, ulceration). Optical evaluation performance outcomes were calculated. Outcomes were reported by dominant morphology: nodular (Paris 0-Is/0-IIa+Is) vs flat (Paris 0-IIa/0-IIb) morphology. From July 2013 to July 2019, 1583 LNPCPs (median size 35 [interquartile range, 25-50] mm; 855 flat, 728 nodular) were assessed. SMIC was identified in 146 (9.2%; 95% confidence interval [CI], 7.9%-10.8%). Overall sensitivity and specificity were 67.1% (95% CI, 59.2%-74.2%) and 95.1% (95% CI, 93.9%-96.1%), respectively. The overall SMIC miss rate was 3.0% (95% CI, 2.3%-4.0%). Significant differences in sensitivity (90.9% vs 52.7%), specificity (96.3% vs 93.7%), and SMIC miss rate (0.6% vs 5.9%) between flat and nodular LNPCPs were identified (all P < .027). Multiple logistic regression identified size ≥40 mm (odds ratio [OR], 2.0; 95% CI, 1.0-3.8), rectosigmoid location (OR, 2.0; 95% CI, 1.1-3.7), and nodular morphology (OR, 7.2; 95% CI, 2.8-18.9) as predictors of missed SMIC (all P < .039). Optical evaluation performance is dependent on lesion morphology. In the absence of features suggestive of SMIC, flat lesions can be presumed benign and be managed accordingly.

How to Manage the Large Nonpedunculated Colorectal Polyp

How to Manage the Large Nonpedunculated Colorectal Polyp

Nuclear Factor Erythroid 2-related Factor 2 Knockout Suppresses the Development of Aggressive Colorectal Cancer Formation Induced by Azoxymethane/Dextran Sulfate Sodium-Treatment in Female Mice.

Colon tumors develop more frequently in male than in female. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays differential roles in the stage of tumorigenesis. The purpose of this study was to investigate the role of Nrf2 on colitis-associated tumorigenesis using Nrf2 knockout (KO) female mice. Azoxymethane (AOM) and dextran sulfate sodium (DSS)-treated wild-type (WT) and Nrf2 KO female mice were sacrificed at week 2 and 16 after AOM injection. Severity of colitis, tumor incidence, and levels of inflammatory mediators were evaluated in AOM/DSS-treated WT and Nrf2 KO mice. Furthermore, qRT-PCR, Western blot abnalysis, and ELISA were performed in colon tissues. At week 2, AOM/DSS-induced colon tissue damages were significantly greater in Nrf2 KO than in WT mice. At week 16, tumor numbers (> 2 mm size) were significantly lower in both the proximal and distal colon in Nrf2 KO compared to WT. The overall incidences of adenoma/cancer of the proximal colon and submucosal invasive cancer of the distal colon were reduced by Nrf2 KO. The mRNA and protein expression levels of NF-κB-related mediators (i.e., iNOS and COX-2) and Nrf2-related antioxidants (i.e., heme oxygenase-1 and glutamate-cysteine ligase catalytic subunit) were significantly lower in the Nrf2 KO than in WT mice. Interestingly, the protein level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) was higher in AOM/DSS-treated Nrf2 KO than in WT mice. Our results support the oncogenic effect of Nrf2 in the later stage of carcinogenesis and upregulation of tumor suppressor 15-PGDH might contribute to the repression of colitis-associated tumorigenesis in Nrf2 KO female mice.