Depth Of Submucosal Invasion Research Articles

Novel endoscopic ultrasonography classification for assured vertical resection margin (≥500μm) in colorectal endoscopic submucosal dissection.

The risk of local recurrence might be low in pT1 colorectal carcinoma with a tumor vertical margin (VM)≥500μm. We investigated the relationship between endoscopic ultrasonography (EUS) findings and VM in cases with colorectal endoscopic submucosal dissection (ESD) categorized as Type 2B according to the Japan NBI Expert Team (JNET) classification. We analyzed 179 JNET Type 2B colorectal tumors resected by ESD at Hiroshima University Hospital from January 2010 to May 2021. The distance from the tumor invasive front to the muscle layer on EUS was defined as the tumor-free distance (EUS-TFD) and classified as Type I (EUS-TFD≥1mm) and II (<1mm). We investigated the relationship between EUS-TFD and VM and analyzed the predictive factors for VM≥500μm. EUS-TFD Type I was diagnosed in 133 (74.3%) lesions: VM≥500μm (114, 85.7%); VM<500μm (19, 14.3%); and VM positive (VM1) (0, 0%). Type II was diagnosed in 46 (25.7%) lesions: VM≥500μm (14, 30.5%); VM<500μm (22, 47.8%); and VM1 (10, 21.7%). In the EUS-TFD Type I cases, 84.5% and 87.8% were protruded and superficial types; whereas for Type II cases, these were 38.9% and 25%, respectively. EUS-TFD classification (Type I), scope operability (good), submucosal invasion depth (<2000μm), histology at the deepest invasive portion (favorable), and degree of fibrosis (F0/F1) were significant predictors of VM≥500μm. In JNET Type 2B lesions, EUS-TFD classification is a novel diagnostic indicator to predict VM≥500μm in ESD preoperatively.

Multidisciplinary treatment strategy for early colon cancer

Background: Treatment for early colon cancer has progressed rapidly with endoscopic resection and minimally invasive surgery. Selection of patients without risk of lymph node metastasis is necessary before deciding on endoscopic resection for early colon cancer treatment. We aimed to review the optimal multidisciplinary treatment strategies for early colon cancer, including endoscopy and surgery.Current Concepts: Pathological risk factors include histologic grade of cancer cell differentiation, lymphovascular invasion, perineural invasion, tumor budding, and deep submucosal invasion. These risk factors for predicting lymph node metastasis are crucial for determining the treatment strategy of endoscopic excision and radical resection for early colon cancer. Prediction of the depth of invasion in early colon cancer using endoscopic optical assessments is vital to determine the appropriate treatment method for endoscopic or surgical resection. Furthermore, optical assessment of pit and vascular patterns is useful for estimating the depth of submucosal invasion using magnifying chromoendoscopy and narrow-band imaging endoscopy. Performing an endoscopic and pathologic evaluation of the risk factors for lymph node metastasis is imperative when selecting endoscopic or surgical resection. Endoscopic treatments include cold snare polypectomy, endoscopic mucosal resection, and endoscopic submucosal dissection. In addition, appropriate surgical treatment should be recommended for patients with early colon cancer with a high risk of lymph node metastasis.Discussion and Conclusion: A multidisciplinary approach should be recommended to establish an optimized treatment strategy, minimize the risk of complications, and obtain excellent oncologic outcomes via patienttailored treatment in patients with early colon cancer.

A 5-Year Follow-Up of a Submucosal Tumor in the Stomach

Question: An asymptomatic 51-year-old man underwent esophagogastroduodenoscopy (EGD) at a health examination in August 2015, which revealed a gastric submucosal tumor at the lesser curvature of the lower gastric body (Figures A and B). The biopsy of the lesion showed chronic inflammation of the mucosa, with no evidence of gastric carcinoma; the patient was Helicobacter pylori–negative (Figure C). No significant abnormality was found during the physical examination or using laboratory tests such as blood biochemistry index and tumor makers. One year later (2016), the patient underwent endoscopic ultrasound that revealed a mixed-echoic spindle-shaped mass that originated from the submucosal layer and deep mucosal layer, measuring 1.3 × 0.9 cm, and that was sharply demarcated (Figures D, E, and F). The surfaces of the lesion were smooth, showing no ulcers or erosion. Heterotopic pancreas was diagnosed. In the next year of subsequent follow-up (2017), EGD showed there was no significant change of the submucosal tumor (SMT) (Figures G and H), and the pathologic section of the center of the lesion revealed chronic atrophic gastritis with moderate intestinal metaplasia; the patient was H pylori–negative (Figure I). Two years later in 2019, EGD showed a submucosal tumor of about 1.4 × 0.9 cm with a congestion surface (Figures J and K). The biopsy revealed active inflammation with lymphatic tissue hyperplasia; the patient was now H pylori–positive (Figure L). After H pylori eradication, 14 C-urea breath test was negative. Following it up 2 years later (March 2021), the EGD revealed a slightly depressed center of the SMT, which measured approximately 2.0 × 1.0 cm in size, covered with a normally appearing mucosa (Figure M). Magnifying narrow-band imaging showed regular microvascular structure similar to the corpus normal mucosa, and the depressed area was covered with white exudates. The microvascular structure was invisible (Figure N). The biopsy specimen obtained from the depressed area showed chronic gastritis with lymphoid follicle, with a few atypical cells in lymphocytic infiltration (Figure O). Abdominal contrast-enhanced computed tomography demonstrated a clearly enhanced mass in the lower gastric body near the notch, measuring 1.9 × 1.0 cm. No enlarged lymph nodes were found (Figure P). The patient underwent endoscopic submucosal dissection (ESD). What is the most likely diagnosis? See the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. The ESD specimen size is 4.0 × 3.5 cm (Figure Q), and the tumor size is 2.0 × 1.0 cm. Histologic examination showed adenocarcinoma invading the submucosal layer mixed with rich lymphoid stroma (Figures R and S). CK(AE1/AE3) highlighted irregular sheets and trabeculae of tumor cells embedded within a prominent lymphocytic infiltrate (Figure T). The diagnosis is medullary carcinoma with lymphoid infiltration (MCLI). The in situ hybridization of Epstein-Barr encoding region was positive. The macroscopic type is type 0-Is. The lymphovascular invasion is negative. There is no ulcer. Both vertical and horizontal margins are negative. The depth of submucosal invasion is 1,000 μm (pT1b). Distal gastrectomy and D2 lymph node dissection were performed. Postoperative pathology showed no tumor residue or lymph node metastasis. The stage was pT1bN0M0. No recurrence or metastasis was found in the 1-year follow-up. Gastric MCLI is a rare subtype of gastric cancer, accounting for about 9%. It is also related to Epstein-Barr virus infection at an early stage of the disease.1Takano Y. Kato Y. Sugano H. Epstein-Barr-virus-associated medullary carcinomas with lymphoid infiltration of the stomach.J Cancer Res Clin Oncol. 1994; 120: 303-308Crossref PubMed Scopus (25) Google Scholar MCLI is characterized by poorly differentiated carcinoma cells with dense, diffuse, and uniform lymphoid infiltration. Most gross appearances of MCLI show a clear boundary with a central depression.2Watanabe H. Enjoji M. Imai T. Gastric carcinoma with lymphoid stroma. Its morphologic characteristics and prognostic correlations.Cancer. 1976; 38: 232-243Crossref PubMed Scopus (297) Google Scholar,3Minamoto T. Mai M. Watanabe K. et al.Medullary carcinoma with lymphocytic infiltration of the stomach. Clinicopathologic study of 27 cases and immunohistochemical analysis of the subpopulations of infiltrating lymphocytes in the tumor.Cancer. 1990; 66: 945-952Crossref PubMed Scopus (74) Google Scholar Sometimes it is difficult to diagnose MCLI with standard biopsy because of the dense lymphoid infiltration, which makes it difficult to find carcinoma cells in such a small number of tissues acquired by biopsy. Therefore, we report an unusual case of MCLI mimicking SMT with a smooth surface. Although the patient was followed up for 5 years, 3 times biopsy showed no evidence of carcinoma. The patient was diagnosed using ESD. We suggest that MCLI should be taken into account in the differential diagnosis of SMTs. Diagnostic ESD should also be applied when clinical diagnosis is suspected but biopsy cannot confirm the diagnosis.

Risk Factors for Predicting Lymph Node Metastasis in Submucosal Colorectal Cancer.

Objectives: The cornerstone of treating colorectal cancer (CRC) is generally a surgical resection with lymph node (LN) dissection. The tools for predicting lymph node metastasis (LNM) in submucosal (SM) CRC are useful to avoid unnecessary surgical resection. Methods: Retrospectively, we analyzed 526 consecutive patients with SM CRC who underwent surgical resection at the Osaka International Cancer Institute, Osaka University Hospital, and Minoh City Hospital, Japan, between 1984 and 2012. The Osaka International Cancer Institute group and the Osaka University Hospital group were randomly divided into a training set and a test set of 2:1. The prediction model was validated in Minoh City Hospital. Results: We partitioned patients using three risk factors involved in the presence or absence of LNM in SM CRC: lymphatic invasion (Ly), budding grade (BD) and the depth of submucosal invasion (DSI) (cut-off value 2789 μm) that were significantly different in the multivariate analysis. As a result, a predictive model of “LNM <5%” when “Ly negative and DSI <2789 μm” was evaluated. We similarly partitioned by DSI 3000 μm as easy-to-evaluate values in clinical use. We developed the additional model for predicting LNM is 1.05%, that is, LNM <5%, when there are “Ly negative and DSI <3000 μm.” Conclusions: As a limitation, only patients who underwent surgical resection were included in this study. This predictive model could help clinicians and CRC patients decide on the additional surgery required after endoscopic resection.

Utility of artificial intelligence with deep learning of hematoxylin and eosin-stained whole slide images to predict lymph node metastasis in T1 colorectal cancer using endoscopically resected specimens; prediction of lymph node metastasis in T1 colorectal cancer.

When endoscopically resected specimens of early colorectal cancer(CRC) show high-risk features, surgery should be performed based on current guidelines because of the high-risk of lymph node metastasis (LNM). The aim of this study was to determine the utility of an artificial intelligence (AI) with deep learning(DL) of hematoxylin and eosin (H&E)-stained endoscopic resection specimens without manual-pixel-level annotation for predicting LNM in T1 CRC. In addition, we assessed AI performance for patients with only submucosal (SM) invasion depth of 1000 to 2000μm known to be difficult to predict LNM in clinical practice. H&E-stained whole slide images (WSIs) were scanned for endoscopic resection specimens of 400 patients who underwent endoscopic treatment for newly diagnosed T1 CRC with additional surgery. The area under the curve(AUC) of the receiver operating characteristic curve was used to determine the accuracy of AI for predicting LNM with a fivefold cross-validation in the training set and in a held-out test set. We developed an AI model using a two-step attention-based DL approach without clinical features (AUC, 0.764). Incorporating clinical features into the model did not improve its prediction accuracy for LNM. Our model reduced unnecessary additional surgery by 15.1% more than using the current guidelines (67.4% vs. 82.5%). In patients with SM invasion depth of 1000 to 2000μm, the AI avoided 16.1% of unnecessary additional surgery than using the JSCCR guidelines. Our study is the first to show that AI trained with DL of H&E-stained WSIs has the potential to predict LNM in T1 CRC using only endoscopically resected specimens with conventional histologic risk factors.

Differences in Factors Predicting Lymph Node Metastasis Between pT1 Rectal Cancer and pT1 Colon Cancer: A Retrospective Study.

Studies have demonstrated conflicting results regarding factors that predict lymph node metastasis (LNM) in pT1 colorectal cancers. We hypothesized that these discrepancies could be related to different factors predicting LNM between rectal and colon cancer. This study aimed to compare predicting factors for LNM between pT1 rectal and colon cancer. This retrospective study evaluated a prospectively maintained database that included 380 patients with pT1 colorectal cancer from January 2010 to December 2020. Patients were grouped according to whether they had rectal or colon cancer, with or without LNM, and factors predicting LNM were analyzed. In pT1 rectal cancer, LNM was associated with deeper submucosal (SM) invasion (P = .024) and a higher proportion of poorly differentiated tumors (P = .006). In pT1 colon cancer, LNM was associated with a higher proportion of moderately/poorly differentiated tumors (P = .002) and lymphatic invasion (P = .004). In the multivariate analysis for rectal cancer, depth of SM invasion (≥3000μm) was an independent predictive factor for LNM (95% confidence interval [CI], 1.48-27.94; P = .013), whereas for colon cancer, moderately/poorly differentiated tumors (95% CI, 1.38-8.13; P = .008) and lymphatic invasion (95% CI, 1.44-11.78; P = .008) were independent predictive factors for LNM. There were distinct differences in the factors predicting LNM between pT1 rectal cancer and colon cancer. These results suggest the necessity in differentiating between rectal and colon cancer when performing studies on LNM in pT1 colorectal cancer.

Endoscopic Submucosal Dissection of Deeply Invasive Colorectal Cancers Using the Pocket-Creation Method: Analysis of Vertical Margins

Background and aimsThe standard treatment for stage T1b colorectal cancers with 1,000µm or greater submucosal invasion is surgical resection. However, the risk of lymph node metastases is only 1-2% when excluding risk factors for metastases other than depth of submucosal invasion. The number of elderly patients with significant comorbidities is increasing with societal aging in Japan. Therefore, local endoscopic resection of T1b colorectal cancers needs more consideration in the future. We previously showed that the pocket-creation method (PCM) for endoscopic submucosal dissection (ESD) is useful regardless of the morphology, including large sessile tumors with submucosal fibrosis, or location of the colorectal tumor. However, some T1b colorectal cancers have pathologically positive margins even when using the PCM. We retrospectively investigated the causes of failure to achieve negative vertical margins.MethodsWe retrospectively analyzed 953 colorectal tumors in 886 patients resected with the PCM. Finally, 65 pathological T1b colorectal cancers after en bloc resection were included in this study. ESD specimens and recorded procedure videos of T1b cancer resections with pathologically positive vertical margins were reviewed.ResultsThe 65 cancers were divided into positive vertical margin (VM+ group) and negative vertical margin (VM- group) groups with 10 [10/65 (15%)] and 55 [55/65 (85%)] patients in each group, respectively. There was a significant difference in the rate of submucosal fibrosis (P=0.012) and dissection speed (P=0.044). There were no significant differences between the two groups in other regards. When verifying 8/10 available videos in the VM+ group, endoscopic technical factors led to positive vertical margins in five patients, and essential pathological factors of ESD led to positive vertical margins in the other three. Six of these eight patients underwent additional surgical resection. No residual tumor was identified in six T1b cancers. None of these six resected specimens contained lymph node metastases on pathological examination.ConclusionThe PCM resulted in a high rate of negative-vertical-margin resections. The PCM resulted in complete resection of T1b cancers when examining additional surgical specimens. ESD using the PCM is a viable option for the endoscopic treatment of T1b colorectal cancers.

Interobserver Variability in Assessment of Depth of Submucosal Invasion for Colonic Endoscopic Resections Among Subspecialized Gastrointestinal Pathologists.

Recent data support that low-risk submucosally invasive (pT1) colonic adenocarcinomas (ie, completely resected tumors that lack high-grade morphology, tumor budding, and lymphovascular invasion) are considered cured via endoscopic resection, provided that the submucosal invasion is less than 1000 μm. Hence, the pathologists' assessment of depth of submucosal invasion may guide further management (ie, surveillance versus colectomy). To assess interobserver concordance among gastrointestinal pathologists in measuring submucosal depth of invasion in colonic endoscopic resections. Six gastrointestinal pathologists from 5 academic centers independently measured the greatest depth of submucosal invasion in micrometers on 52 hematoxylin-eosin-stained slides from colonic endoscopic specimens with pT1 adenocarcinomas, per published guidelines (round 1 scoring). Two separate measurements (round 2 scoring) were subsequently performed by each pathologist following a consensus meeting, (1) from surface of lesion and (2) from muscularis mucosae, and pathologists were asked to choose their (3) "real-life (best)" assessment between the first 2 measurements. Interobserver agreement was assessed by the intraclass correlation coefficient (ICC) and Cohen κ statistics. Round 1 had poor ICC (0.43; 95% CI, 0.31-0.56). Round 2 agreement was good when measuring from surface (ICC = 0.83; 95% CI, 0.76-0.88) but moderate (ICC = 0.59; 95% CI, 0.47- 0.70) when measuring from muscularis mucosae and became poor (ICC = 0.49; 95% CI, 0.36-0.61) for the best-assessment measurement. Our findings indicate that clearer and reproducible guidelines are needed if clinical colleagues are to base important management decisions on pathologists' estimate of depth of submucosal invasion in the colonic endoscopic resections.

Establishment of a Dynamic Nomogram for Predicting the Risk of Lymph Node Metastasis in T1 Stage Colorectal Cancer.

BackgroundAccurate prediction of the risk of lymph node metastasis in patients with stage T1 colorectal cancer is crucial for the formulation of treatment plans for additional surgery and lymph node dissection after endoscopic resection. The purpose of this study was to establish a predictive model for evaluating the risk of LNM in patients with stage T1 colorectal cancer.MethodsThe clinicopathological and imaging data of 179 patients with T1 stage colorectal cancer who underwent radical resection of colorectal cancer were collected. LASSO regression and a random forest algorithm were used to screen the important risk factors for LNM, and a multivariate logistic regression equation and dynamic nomogram were constructed. The C index, Calibration curve, and area under the ROC curve were used to evaluate the discriminant and prediction ability of the nomogram. The net reclassification index (NRI), comprehensive discriminant improvement index (IDI), and clinical decision curve (DCA) were compared with traditional ESMO criteria to evaluate the accuracy, net benefit, and clinical practicability of the model.ResultsThe probability of lymph node metastasis in patients with T1 colorectal cancer was 11.17% (20/179). Multivariate analysis showed that the independent risk factors for LNM in T1 colorectal cancer were submucosal invasion depth, histological grade, CEA, lymphovascular invasion, and imaging results. The dynamic nomogram model constructed with independent risk factors has good discrimination and prediction capabilities. The C index was 0.914, the corrected C index was 0.890, the area under the ROC curve was 0.914, and the accuracy, sensitivity, and specificity were 93.3, 80.0, and 91.8%, respectively. The NRI, IDI, and DCA show that this model is superior to the ESMO standard.ConclusionThis study establishes a dynamic nomogram that can effectively predict the risk of lymph node metastasis in patients with stage T1 colorectal cancer, which will provide certain help for the formulation of subsequent treatment plans for patients with stage T1 CRC after endoscopic resection.

Vertical tumor margin of endoscopic resection for T1 colorectal carcinoma affects the prognosis of patients undergoing additional surgery.

Vertical tumor margin-negative T1 colorectal carcinoma (CRC) is an absolute curative condition following complete endoscopic resection (ER). However, the influence on prognosis in relation to vertical tumor margin is unclear. Therefore, we evaluated the influence of the distance from vertical tumor margin to resected specimen edge (vertical margin distance) of ER for T1b (submucosal invasion depth > 1000μm) CRC on the prognosis of patients undergoing additional surgery after ER. In total, 215 consecutive patients with T1b CRC who underwent additional surgery after ER at Hiroshima University Hospital between February 1992 and June 2019 were enrolled. We assessed 191 patients without lymph node metastases at the additional surgery. The specimens resected by ER were classified into three groups based on the vertical margin distance: patients with a vertical margin distance of ≥ 500μm (Group A); patients with a vertical margin distance of < 500μm (Group B); and patients with a positive vertical tumor margin (Group C). Subsequently, we evaluated the prognosis of the patients in relation to the clinicopathological characteristics among the three groups. There were no significant differences in clinicopathological characteristics among the three groups. Group A had a significantly higher recurrence-free 5-year survival rate than Groups B and C (100%, 84.5%, and 81.8%, respectively). Similarly, Group A had a significantly higher disease-specific 5-year survival rate than Group C (100% vs. 95.5%). Complete en bloc resection with sufficient submucosal layer from the invasive front (vertical margin distance > 500μm) by ER for T1 CRC reduces the risk of metastatic recurrence after additional surgery.

Current problems and perspectives of pathological risk factors for lymph node metastasis in T1 colorectal cancer: Systematic review.

With the prevalence of endoscopic submucosal dissection and endoscopic full thickness resection, which enable complete resection of T1 colorectal cancer with a negative margin, the treatment strategy following endoscopic resection has become more important. The necessity of secondary surgical resection is determined on the basis of the risk of lymph node metastasis according to the histopathological findings of resected specimens because ~10% of T1 colorectal cancer cases have lymph node metastasis. The current Japanese treatment guidelines state four risk factors for lymph node metastasis: lymphovascular invasion, histological differentiation, depth of submucosal invasion, and tumor budding. These guidelines have succeeded in stratifying the low-risk group for lymph node metastasis, in which endoscopic resection alone is acceptable for cure. On the other hand, there are some problems: there is variation in diagnosis methods and low interobserver agreement for each pathological factor and 90% of surgical resections are unnecessary, with lymph node metastasis negativity. To ensure patients with T1 colorectal cancer receive more appropriate treatment, these problems should be addressed. In this systematic review, we gave some suggestions to these practical issues of four pathological factors as predictors.

Short- and long-term outcomes of local excision with adjuvant radiotherapy in high-risk T1 rectal cancer patients.

PurposeThe standard of care for early rectal cancer is radical surgery; however, it carries high postoperative morbidity. This study aimed to assess the short-term and oncological outcomes of local excision and adjuvant radiotherapy in patients with high-risk pathological stage (p) T1 rectal cancer.MethodsFifty-five patients underwent local excision with adjuvant radiotherapy or radical resection for high-risk T1 rectal cancer. Patients with adenocarcinoma within 10 cm from the anal verge; pT1 with high-risk features (grade 3–4); a tumor size of ≥3 cm; a positive margin; a lymphovascular or perineural invasion; or a submucosal invasion depth of ≥SM2 were included.ResultsThe rates of postoperative complications and stoma formation were higher in the radical surgery group (P = 0.021 and P = 0.003, respectively). No significant differences were observed in the overall survival and disease-free survival (DFS) between the 2 groups (P = 0.301 and P = 0.076, respectively). Vascular invasion was a significantly poor prognostic factor for DFS (P = 0.033). The presence of 3 or more high-risk features was associated with a poor DFS (P = 0.002).ConclusionLocal excision with adjuvant radiotherapy significantly reduces the risk of complications and stoma formation. It is also an alternative option for patients with fewer than 3 high-risk features.

New morphological risk factors for metastasis to regional lymph nodes in rectal cancer with invasion into the submucosa

AIM to assess prognostic significance of pathologic features of T1 rectal carcinoma in relation to regional lymph nodes involvement (N+).MATERIAL AND METHODS: surgical specimens (n = 66) from rectal resection for carcinoma pT1 were investigated. Following prognosticators were evaluated: depth of submucosal invasion, grade of differentiation, lymphovascular invasion (LVI), tumor budding (Bd), poorly differentiated clusters (PDC) of tumor and rupture of cancer glands (CGR).RESULTS: lymph nodes metastases were found in 13 (19.7%) specimens. LVI was associated lymphatic spread in great possibility OR 38.0 95% CI 2.1-670 (p &lt; 0.0001). Tumor budding of high grade (Bd3) OR 6.2 95% CI 1.2-31 (p &lt; 0.0001) and poorly differentiated clusters (p = 0,03) also increased risk of lymph node metastases. Depth of submucosal invasion, grade of differentiation, and rupture of cancer glands failed to demonstrate significant association with N+. Logistic regression analysis allowed to determine LVI as independent prognostic factor of lymph node tumor involvement.CONCLUSION: lymphovascular invasion, tumor budding and poorly differentiated clusters of tumor are risk factors of T1 rectal carcinoma lymph node metastases.

Not So Smart? Artificial Intelligence May Need to Go Deeper to Predict Colorectal Cancer Invasion Depth

Not So Smart? Artificial Intelligence May Need to Go Deeper to Predict Colorectal Cancer Invasion Depth

Role of barium enema examination for the diagnosis of submucosal invasion depth in T1 colorectal cancers

BackgroundThe indication for endoscopic resection for submucosally invasive colorectal cancer (T1-CRC) depends on the preoperative diagnosis of invasion depth. The aim of this investigation was to evaluate the association between barium enema examination (BE) profile views and depth of submucosal (SM) invasion in CRCs.MethodsWe reviewed the radiographic and endoscopic findings of 145 T1-CRCs diagnosed from 2008 to 2019. We measured the widths of horizontal and vertical rigidity under a BE profile view corresponding to CRC and compared the values with SM invasion depth. Horizontal rigidity was defined as the horizontal length and vertical rigidity as the vertical width of the barium defect corresponding to each target lesion. The most appropriate cut-off values for predicting SM invasion ≥1.8 mm were calculated by receiver operating characteristic curve analysis.ResultsValues of horizontal rigidity (r = 0.626, P < 0.05) and vertical rigidity (r = 0.482, P < 0.05) correlated significantly with SM invasion depth. The most appropriate cut-off values for the prediction of SM invasion depth ≥ 1.8 mm were 4.5 mm for horizontal rigidity, with an accuracy of 80.7%; and 0.7 mm for vertical rigidity, with an accuracy of 77.9%. The prevalence of lympho-vascular invasion was significantly different when those cut-off values were applied (43.2% vs. 17.5% for horizontal rigidity, P < 0.005).ConclusionsIn T1-CRC, values of horizontal and vertical rigidities under a BE profile view were correlated with SM invasion depth. While the accuracy of the rigidities for the prediction of SM invasion depth ≥ 1.8 mm was not high, horizontal rigidity may be predictive of lympho-vascular invasion, thus aiding in therapeutic decision-making.

Supervised Learning Based Systemic Inflammatory Markers Enable Accurate Additional Surgery for pT1NxM0 Colorectal Cancer: A Comparative Analysis of Two Practical Prediction Models for Lymph Node Metastasis.

PurposePredicting lymph node metastasis (LNM) after endoscopic resection is crucial in determining whether patients with pT1NxM0 colorectal cancer (CRC) should undergo additional surgery. This study was aimed to develop a predictive model that can be used to reduce the current likelihood of overtreatment.Patients and MethodsWe recruited a total of 1194 consecutive CRC patients with pT1NxM0 who underwent endoscopic or surgical resection at the Gezhouba Central Hospital of Sinopharm between January 1, 2006, and August 31, 2021. The random forest classifier (RFC) and generalized linear algorithm (GLM) were used to screen out the variables that greatly affected the LNM prediction, respectively. The area under the curve (AUC) and decision curve analysis (DCA) were applied to assess the accuracy of predictive models.ResultsAnalysis identified the top 10 candidate factors including depth of submucosal invasion, neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), platelet-to-neutrophil ratio(PNR), venous invasion, poorly differentiated clusters, tumor budding, grade, lymphatic vascular invasion, and background adenoma. The performance of the GLM achieved the highest AUC of 0.79 (95% confidence interval [CI]: 0.30 to 1.28) in the training cohort and robust AUC of 0.80 (95% confidence interval [CI]: 0.36 to 1.24) in the validation cohort. Meanwhile, the RFC exhibited a robust AUC of 0.84 (95% confidence interval [CI]: 0.40 to 1.28) in the training cohort and a high AUC of 0.85 (95% CI: 0.41 to 1.29) in the validation cohort. DCAs also showed that the RFC had superior predictive ability.ConclusionOur supervised learning-based model incorporating histopathologic parameters and inflammatory markers showed a more accurate predictive performance compared to the GLM. This newly supervised learning-based predictive model can be used to determine an individually tailored treatment strategy.

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.

Measuring depth of invasion of submucosa - invasive adenocarcinoma in oesophageal endoscopic specimens: how good are we?

Emerging data support that submucosa-invasive (pT1b) esophageal adenocarcinomas are cured via endoscopic resection, provided that invasion measures ≤500 μm, they lack other histological features predictive of nodal metastasis and have negative margins. Hence, pathologists' measurement of the depth of submucosal invasion in endoscopic resections may dictate further management (i.e. endoscopic follow-up versus oesophagectomy). In this study, we assessed the interobserver agreement in measuring the depth of submucosal invasion in oesophageal endoscopic resections. Six subspecialised gastrointestinal (GI) pathologists from five academic centres independently measured the depth of submucosal invasion in μm from the deepest muscularis mucosae on 37 oesophageal endoscopic resection slides (round 1 scoring). A consensus meeting with a systematic approach for measuring and discussion of pitfalls was undertaken and remeasuring (round 2 scoring) was conducted. Interobserver agreement was assessed by the intraclass correlation coefficient (ICC) and Cohen's kappa statistics. A lack of agreement was seen among the six reviewers with a poor ICC for both rounds: 1 [0.40, 95% confidence interval (CI) = 0.26-0.56] and 2 (0.49, 95% CI = 0.34-0.63). When measurements were categorised as < or >500 μm, the overall agreement among the six reviewers was only fair for both rounds: 1 (kappa = 0.37, 95% CI = 0.22-0.53) and 2 (kappa = 0.29, 95% CI = 0.12-0.46). Our study shows a lack of agreement among gastrointestinal pathologists in measuring the depth of submucosal invasion in oesophageal endoscopic resections despite formulating a consensus approach for scoring. If important management decisions continue to be based upon this parameter, more reproducible and concrete guidelines are needed.

Tolerability and safety of adjuvant chemoradiotherapy with S-1 after limited surgery for T1 or T2 lower rectal cancer.

Chemo-radiotherapy (CRT) after local excision for pT1 with high-risk features or pT2 rectal cancer is recommended as an optional treatment to achieve both curability and maintenance of quality of life. The aim of this study was to evaluate the short-term safety of combining limited surgery with adjuvant CRT for T1 or T2 lower rectal cancer. This was a multicenter, single-arm, prospective phase II trial. Patients diagnosed with lower rectal or anal canal cancer (clinical T1 or T2 with a maximum diameter of 30mm and N0 and M0) underwent local excision or endoscopic resection. Patients received CRT with S-1 (tegafur/gimeracil/oteracil) after confirmation of well- or moderately differentiated adenocarcinoma, and negative margins, and/or depth of submucosal invasion ≥ 1000µm or muscularis propria, and/or positive lymphovascular invasion, and/or tumor budding grade of 2/3. The primary endpoint was relapse-free survival. Secondary endpoints included overall and local relapse-free survival, safety, anal sphincter preservation rate, and anal function. Pathological diagnosis was T1 in 36 patients and T2 in 16 patients. Serious complications after surgery were not reported. The CRT completion rate per protocol was 86.5% (45/52). Thirty-two patients developed 54 events of CRT-related adverse events, including only one patient with a grade 3 event (stomatitis). The most common CRT-related adverse event was diarrhea (n = 14). No patients showed deterioration of anal function at 3years postoperatively. CRT with S-1 after limited surgery for T1 or T2 lower rectal cancer resulted in a low incidence of toxicities and maintenance of anal function.

Histopathological risk factors for lymph node metastases in T1 colorectal cancer: meta-analysis

National screening programmes increase the proportion of T1 colorectal cancers. Local excision may be possible, but the risk of lymph node metastases (LNMs) could jeopardize long-term outcomes. The aim of the present study was to review the association between histopathological findings and LNMs in T1 colorectal cancer. A systematic literature search was conducted using PubMed,Embase, and Cochrane online databases. Studies investigating the association between one or more histopathological factors and LNMs in patients who underwent resection for T1 colorectal cancer were included. Sixteen observational studies were included in the meta-analysis, including a total of 10 181 patients, of whom 1 307 had LNMs. Lymphovascular invasion (odds ratio (OR) 7.42; P < 0.001), tumour budding (OR 4.00; P < 0.001), depth of submucosal invasion, whether measured as at least 1000 µm (OR 3.53; P < 0.001) or Sm2-3 (OR 2.12; P = 0.020), high tumour grade (OR 3.75; P < 0.001), polypoid growth pattern (OR 1.59; P = 0.040), and rectal location of tumour (OR 1.36; P = 0.003) were associated with LNMs. Distinct histopathological factors associated with nodal metastases in T1 colorectal cancer can aid selection of patients for local excision or major excisional surgery.