Although tumor necrosis factor receptor 2 (TNFR2) may serve a protumor role in several types of tumors, the clinical significance of TNFR2, including the diagnostic and prognostic value in tumor (T) stage 2-3 esophageal squamous cell carcinoma (ESCC), remains unclear. Therefore, the present study aimed to explore the clinical significance of TNFR2 in stage T2-3 ESCC. The present study collected the mRNA expression data of TNFR2 from two databases and confirmed the high expression of TNFR2 in ESCC tissue. TNFR2 expression in stage T2-3 ESCC tissue (n=404) was detected using immunohistochemistry and a stratified analysis was performed. For all patients with stage T2-3 ESCC, TNFR2 expression was associated with clinical stage, invasion depth and metastatic lymph nodes. Stage T3 and low differentiation was associated with an increase in the risk of lymph node metastasis, but older age was associated with a decrease. TNFR2 expression was associated with poor overall survival (OS) of all patients with stage T2-3 ESCC and stratified patients with stage T3 ESCC. Moreover, TNFR2 expression and metastatic lymph nodes were independent prognostic factors for these patients. For stratified patients aged ≤60 years, TNFR2 expression was associated with clinical stage and metastatic lymph nodes. In addition, TNFR2 expression was associated with poor OS in stratified patients with stage T2 ESCC. The presence of metastatic lymph nodes was also an independent prognostic factor for these patients. For stratified patients aged >60 years, TNFR2 expression was associated with invasion depth. TNFR2 expression was also associated with poor OS in all patients with stage T2-3 ESCC and stratified patients with stage T3 ESCC. TNFR2 expression and metastatic lymph nodes were identified as independent prognostic factors for these patients. In conclusion, TNFR2 expression is associated with progression and poor prognosis in patients with stage T2-3 ESCC as an independent prognostic factor, except in the subgroup of patients with stage T2-3 ESCC aged ≤60 years.

BACKGROUND: The low positive predictive value for lymph node metastases (LNM) of common practice risk criteria (CPRC) in T1 colorectal carcinoma (CRC) leads to manyunnecessary additional surgeries following local resection. This study aimed to identify criteria that may improve on the CPRC.
METHODS: Logistic regression analysis was performed to determine the association of diverse variables with LNM or \'poor outcome\' (LNM and/or distant metastases and/or recurrence) in a single center T1 CRC cohort. The diagnostic capacity of the set of variables obtained was compared with that of the CPRC.
RESULTS: The study comprised 161 cases. Poorly differentiated clusters (PDC) and tumor budding grade > 1 (TB > 1) were the only independent variables associated with LNM. The area under the curve (AUC) for these criteria was 0.808 (CI 95% 0.717-0.880) compared to 0.582 (CI 95% 0.479-0.680) for CPRC. TB > 1 and lymphovascular invasion (LVI) were independently associated with \'poor outcome\', with an AUC of 0.801 (CI 95% 0.731-0.859), while the AUC for CPRC was 0.691 (CI 95% 0.603-0.752). TB > 1, combined either with PDC or LVI, would reduce false positives between 41.5% and 45% without significantly increasing false negatives.
CONCLUSIONS: Indicating additional surgery in T1 CRC only when either TB > 1, PDC, or LVI are present could reduce unnecessary surgeries significantly.

Conventional endoscopy is widely used in the diagnosis of early gastric cancers (EGCs), but the graphical features were loosely defined and dependent on endoscopists\' experience. We aim to establish a more accurate predictive model for infiltration depth of early gastric cancer including a standardized colorimetric system, which demonstrates promising clinical implication. A retrospective study of 718 EGC cases was performed. Clinical and pathological characteristics were included, and Commission Internationale de l\'Eclariage (CIE) standard colorimetric system was used to evaluate the chromaticity of lesions. The predicting models were established in the derivation set using multivariate backward stepwise logistic regression, decision tree model, and random forest model. Logistic regression shows location, macroscopic type, length, marked margin elevation, WLI color difference and histological type are factors significantly independently associated with infiltration depth. In the decision tree model, margin elevation, lesion located in the lower 1/3 part, WLI a*color value, b*color value, and abnormal thickness in enhanced CT were selected, which achieved an AUROC of 0.810. A random forest model was established presenting the importance of each feature with an accuracy of 0.80, and an AUROC of 0.844. Quantified color metrics can improve the diagnostic precision in the invasion depth of EGC. We have developed a nomogram model using logistic regression and machine learning algorithms were also explored, which turned out to be helpful in decision-making progress.

UNASSIGNED: The microsurface structure reflects the degree of damage to the glands, which is related to the invasion depth of early gastric cancer. To evaluate the diagnostic value of quantitative microsurface structure analysis for estimating the invasion depth of early gastric cancer.
UNASSIGNED: White-light imaging and narrow-band imaging (NBI) endoscopy were used to visualize the lesions of the included patients. The area ratio and depth-predicting score (DPS) of each patient were calculated; meanwhile, each lesion was examined by endoscopic ultrasonography (EUS).
UNASSIGNED: Ninety-three patients were included between 2016 and 2019. Microsurface structure is related to the histological differentiation and progression of early gastric cancer. The receiver operating characteristic curve showed that when an area ratio of 80.3% was used as a cut-off value for distinguishing mucosal (M) and submucosal (SM) type 0-II gastric cancers, the sensitivity, specificity, and accuracy were 82.9%, 80.2%, and 91.6%, respectively. The accuracies for distinguishing M/SM differentiated and undifferentiated early gastric cancers were 87.4% and 84.8%, respectively. The accuracy of EUS for distinguishing M/SM early gastric cancer was 74.9%. DPS can only distinguish M-SM1 (SM infiltration <500 μm)/SM (SM infiltration ≥500 μm) with an accuracy of 83.8%. The accuracy of using area ratio for distinguishing 0-II early gastric cancers was better than those of using DPS and EUS (P < 0.05).
UNASSIGNED: Quantitative analysis of microsurface structure can be performed to assess M/SM type 0-II gastric cancer and is expected to be effective for judging the invasion depth of gastric cancer.

Tumor depth evaluation is essential for pathological tumor staging because it affects clinical management as an independent risk factor for lymph node metastasis in colorectal cancers. However, poor interobserver variability of invasion depth has been reported. This study aimed to clarify the effectiveness of desmin immunostaining in the histological diagnosis of colorectal cancer. Overall, 63 sets of slides of colorectal cancer stained with hematoxylin and eosin (H&E) and desmin were prepared and independently reviewed by four examiners. After reviewing the desmin-stained slides, the interobserver variability of H&E slides alone was significantly improved for all examiners. For the assessment of Tis vs. T1, the sensitivity and accuracy were significantly improved for all examiners by combining H&E and desmin immunostaining. For the diagnosis of T1b vs. Tis or T1a, specificity and accuracy were significantly improved by adding desmin immunostaining. Ancillary desmin staining to assess submucosal invasion in colorectal cancers significantly improved interobserver agreement, led to efficient screening of T1 cancers, and reduced excessive T1b diagnoses. The combination of desmin immunostaining and H&E staining is highly recommended for diagnosing invasive colorectal cancer.

Endoscopic resection (ER) is widely applied to treat early colorectal cancer (CRC). Predicting the invasion depth of early CRC is critical in determining treatment strategies. The use of computer-aided diagnosis (CAD) algorithms could theoretically make accurate and objective predictions regarding the suitability of lesions for ER indication based on invasion depth. This study aimed to assess diagnostic test accuracy of CAD algorithms in predicting the invasion depth of early CRC and to compare the performance between the CAD algorithms and endoscopists.
Multiple databases were searched until June 30, 2022 for studies that evaluated the diagnostic performance of CAD algorithms for invasion depth of CRC. Meta-analysis of diagnostic test accuracy using a bivariate mixed-effects model was performed.
Ten studies consisting of 13 arms (13,918 images from 1472 lesions) were included. Due to significant heterogeneity, studies were stratified into Japan/Korea-based or China-based studies. For the former, the area under the curve (AUC), sensitivity, and specificity of the CAD algorithms were 0.89 (95% CI 0.86-0.91), 62% (95% CI 50-72%), and 96% (95% CI 93-98%), respectively. For the latter, AUC, sensitivity, and specificity were 0.94 (95% CI 0.92-0.96), 88% (95% CI 78-94%), and 88% (95% CI 80-93%), respectively. The performance of the CAD algorithms in Japan/Korea-based studies was not significantly different from that of all endoscopists (0.88 vs. 0.91, P = 0.10) but was inferior to that of expert endoscopists (0.88 vs. 0.92, P = 0.03). The performance of the CAD algorithms in China-based studies was better than that of all endoscopists (0.94 vs. 0.90, P = 0.01).
The CAD algorithms showed comparable accuracy for prediction of invasion depth of early CRC compared to all endoscopists, which was still lower than expert endoscopists in diagnostic accuracy; more improvements should be achieved before it can be extensively applied to clinical practice.

OBJECTIVE: Endoscopic diagnosis of invasion depth of superficial esophageal squamous cell carcinoma (SESCC) by white-light imaging (WLI) modality remains difficult. This study aims to clarify WLI-based features which are predictive for invasion depth of SESCC.
METHODS: A two-phase study was performed by enrolling 1288 patients with 1396 SESCC lesions. Endoscopic appearances, clinical characteristics and post-operative pathological outcomes were collected and reviewed. The association between lesion features and invasion depth were analyzed. A predictive nomogram was constructed for prediction of invasion depth.
RESULTS: Among 1396 lesions in derivation and validation cohort, 1139 (81.6%), 194 (13.9%) and 63 (4.5%) lesions were diagnosed as lesions confined into the intraepithelium or the lamina propria mucosa (T1a-EP/LPM), lesions invading the muscularis mucosa (T1a-MM) or superficial submucosa (T1b-SM1) and tumor with moderate invasion into the submucosa or deeper submucosal invasion (≥ T1b-SM2), respectively. Lesion length > 2 cm (p < 0.001), wider circumferential extension (p < 0.001, 0.002 and 0.048 for > 3/4, 1/2-3/4 and 1/4-1/2 circumferential extension, respectively), surface unevenness (p < 0.001 for both type 0-IIa/0-IIc lesions and mixed type lesions), spontaneous bleeding (p < 0.001), granularity (p < 0.001) and nodules (p < 0.001) were identified as significant factors predictive for lesion depth. A nomogram based on these factors was constructed and the values of area under the Receiver Operating Characteristics curve were 0.89 and 0.90 in the internal and external patient cohort.
CONCLUSIONS: Our study provides six WLI-based morphological features predicting for lesion depth of SESCC. Our findings will make endoscopic evaluation of invasion depth for SESCC more convenient by assessing these profiles.

BACKGROUND: The depth-predicting score (DPS) was proposed based on conventional white-light imaging (C-WLI) endoscopic features of early gastric cancer (EGC) to determine the invasion depth of the neoplasm. However, the effect of DPS on training endoscopists remains unclear. Therefore, we aimed to investigate the effect of short-term DPS training on improving the diagnostic ability of EGC invasion depth and compare the training effect among non-expert endoscopists at different levels.
METHODS: In the training session, the definitions and scoring rules of DPS were instructed, and classic C-WLI endoscopic example graphics were exhibited to the participants. Another C-WLI endoscopic images of 88 cases of histologically proven differentiated EGC were selected as an independent test dataset for evaluating the training effect. Each participant was tested, and the diagnostic accuracy rate of invasion depth was calculated differently one week before the training and after the completion of training.
RESULTS: A total of 16 participants were enrolled and completed the training. Participants were divided into a trainee group and a junior endoscopist group according to the total number of C-WLI endoscopies performed. The total number of C-WLI endoscopies performed showed a significant difference between the trainee group and junior endoscopist group (350 vs. 2500, P = 0.001). No significant difference between the trainee group and junior endoscopist group was observed for pre-training accuracy. The overall diagnostic accuracy of invasion depth was improved significantly after completing DPS training compared with before (68.75 ± 5.71% vs. 61.58 ± 9.61%, P = 0.009). In the subgroup analysis, the post-training accuracy was higher than the pre-training accuracy, but significant improvement was observed only in the trainee group (61.65 ± 7.33% vs. 68.32 ± 5.71%, P = 0.034). In addition, no significant difference in post-training accuracy between the two groups was observed.
CONCLUSIONS: Short-term DPS training can improve the diagnostic ability of the invasion depth of EGC and homogenize the diagnostic ability of non-expert endoscopists at different levels. The depth-predicting score was convenient and effective for endoscopist training.

OBJECTIVE: Endoscopic resection (ER) of gastric gastrointestinal stromal tumors (gGISTs) is a commonly used treatment; however, it is associated with a risk of conversion to laparoscopic resection (LR). This study was performed to identify factors influencing conversion from ER to LR and the effects of conversion on outcomes.
METHODS: The clinicopathological features of patients treated for gGISTs from March 2010 to May 2021 were retrospectively collected. Endpoints included the determination of risk factors associated with LR conversion, with comparisons of surgical outcomes with and without conversion. Propensity score matching was performed to compare the two groups.
RESULTS: In total, 371 gGISTs were analyzed. Sixteen patients required conversion from ER to LR. Propensity score matching demonstrated that invasion depth (muscularis propria with exophytic growth) and gGIST size (≥3 cm) were independent risk factors for conversion to LR. The procedure duration (median, 160.5 vs. 60.0 minutes), postoperative hospitalization duration (median, 8 vs. 6 days), and postoperative fasting duration (median, 5 vs. 3 days) were significantly longer in patients who underwent conversion to LR.
CONCLUSIONS: Accurate preoperative measurements of tumor size and invasion depth may help determine more appropriate surgical approaches for patients with gGISTs.

Although the combination of conventional endoscopy (CE) and endoscopic ultrasonography (EUS) is useful for predicting the depth of early gastric cancer (EGC), the diagnostic value of EUS for submucosal (SM) invasive cancer has not been fully investigated.
We conducted a multicenter prospective study from May 2017 to January 2021 to evaluate the validity of a diagnostic strategy combining CE and EUS and to clarify the additional value of EUS for EGC suspected of SM invasion. In each case, the diagnosis was first made using CE, followed by EUS, and finally confirmed using a combination algorithm.
A total of 180 patients with EGC were enrolled from 10 institutions, of which 175 were analyzed. The histopathological depths were M, SM1, SM2, and ≥ MP in 72, 16, 64, and 23 lesions, respectively. Treatment included 92 endoscopic submucosal dissection cases and 83 surgical cases. The overall diagnostic accuracy classified by M-SM1 or SM2-MP was 58.3% for CE, 75.7% for EUS, and 78.9% for the combination of CE and EUS; the latter two were significantly higher than that of CE alone (P < 0.001). The CE, EUS, and combination accuracy rates in 108 differentiated-type lesions were 51.9%, 77.4%, and 79.6%, respectively; the latter two were significantly higher than CE alone (P < 0.001). A significant additive effect of EUS was observed in CE-SM2 low-confidence lesions but not in CE-M-SM1 lesions or in CE-SM2 high-confidence lesions. Among the nine CE findings, irregular surface, submucosal tumor-like elevation, and non-extension signs were significant independent markers of pSM2-MP. Poorly delineated EUS lesions were misdiagnosed.
EUS provides additional value for differentiated-type and CE-SM2 low-confidence EGCs in diagnosing invasion depth.
UMIN000025862.