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Background Due to negative results in clinical trials of postoperative chemoradiation for gastric cancer, at present, there is a tendency to move chemoradiation therapy forward in gastric and gastroesophageal junction (GEJ) adenocarcinoma. Several randomized controlled trials (RCTs) are currently recruiting subjects to investigate the effect of neo-adjuvant radiotherapy (NRT) in gastric and GEJ cancer. Large retrospective studies may be beneficial in clarifying the potential benefit of NRT, providing implications for RCTs. Methods We retrieved the clinicopathological and treatment data of gastric and GEJ adenocarcinoma patients who underwent surgical resection and chemotherapy between 2004 and 2015 from Surveillance, Epidemiology, and End Results (SEER) database. We compared survival between NRT and non-NRT patients among four clinical subgroups (T1–2N−, T1–2N+, T3–4N−, and T3–4N+). Results Overall, 5272 patients were identified, among which 1984 patients received NRT. After adjusting confounding variables, significantly improved survival between patients with and without NRT was only observed in T3–4N+ subgroup [hazard ratio (HR) 0.79, 95% confidence interval (CI): 0.66–0.95; P = 0.01]. Besides, Kaplan-Meier plots showed significant cause-specific survival advantage of NRT in intestinal type (P P = 0.11) for T3–4N+ patients. In the multivariate competing risk model, NRT still showed survival advantage only in T3–4 N+ patients (subdistribution HR: 0.77; 95% CI: 0.64–0.93; P = 0.006), but not in other subgroups. Conclusions NRT might benefit resectable gastric and GEJ cancer patients of T3–4 stages with positive lymph nodes, particularly for intestinal-type. Nevertheless, these results should be interpreted with caution, and more data from ongoing RCTs are warranted.

Background and study aims The aim of the study was to evaluate short- and long-term outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in China because no study has yet been conducted to confirm its effectiveness in EGC in China. Patients and methods A total of 570 EGC samples from 537 patients were collected for evaluation of en bloc, complete, and curative resection using ESD. Data from 302 patients with at least 3 years of active follow-up were collected for analysis of recurrence of EGC and occurrence of metachronous GC (MGC). Short- and long-outcomes of mixed-type and pure differentiated EGC were also compared. Results En bloc resection rates of 96.0 %, 98.7 %, and 95.2 %, complete resection rates of 91.2 %, 96.6 % and 90.8 %, and curative resection rates of 83.0 %, 96.2 % and 88.2 % were achieved in all EGCs included in the study, those with absolute indication, and those with expanded indication, respectively. As a long-term outcome, recurrence was observed in 1.3 % of patients, 3-year and 5-year recurrence rates being 0.7 % and 1.2 %, respectively. Thirteen patients (4.3 %) exhibited MGCs during follow-up, all of which were resected in a second ESD. Conclusions The effectiveness of ESD for EGC in China was confirmed, with satisfactory short- and long-term outcomes. With scheduled follow-up, the outcomes for mixed-type EGC can be similar to those for pure differentiated EGC after complete resection without development of lymphovascular invasion.

A novel series of quinazoline derivatives were designed, synthesized, and evaluated as multikinase inhibitors. Most of these compounds showed antiproliferation activities of several human cancer cell lines and exhibited inhibition efficacy against the estimated glomerular filtration rate (EGFR) in the nanomolar level. Among those compounds, compound B5 (also named SIPI6473) displayed the maximum effect, and thus was chosen for further study. Our data revealed that B5 inhibited the activity of several kinases (such as EGFR, VEGFR2, and PDGFRα) that contributed to the development of non-small cell lung cancer (NSCLC). Besides, an in vivo study also showed that B5 inhibited tumor growth without signs of adverse effects in the A549 xenograft model. In conclusion, B5 may represent a new and promising drug for the treatment of NSCLC.

Objective The purpose of this study was to explore the role of different undifferentiated components in the lymph node metastasis (LNM) of early mixed gastric cancer. Methods A total of 1596 patients with EGC who underwent gastrectomy were divided into four types: pure differentiated (PD), pure poorly differentiated (Poorly D), pure signet ring cell carcinoma (SRC), and mixed. Mixed type was classified into four subtypes: differentiated-predominant type mixed with poorly differentiated component (MD-P), poorly differentiated-predominant type mixed with differentiated component (MP-D), differentiated-predominant type mixed with SRC component (MD-S), and poorly differentiated-predominant type mixed with SRC component (MP-S). We analyzed the clinicopathological differences between all types and the rates of LNM of patients fulfilling endoscopic submucosal dissection (ESD) criteria. Results LNM was more common in mixed (21.9%) than in PD (7.5%, P P P = 0.003). LNM in MD-S (7.4%, P = 1.000) was not higher than in PD. MP-S (24.5%) showed a higher rate of LNM than SRC (11.3%, P P = 0.681). For lesions satisfying ESD criteria, MD-S (0%, P = 1.000), and MD-P (5.9%, P = 0.12) did not have higher rates of LNM than PD (1.4%). Conclusion The presence of poorly differentiated component but not SRC increases the LNM rate of mixed type. ESD is recommended for the treatment of MD-S and MD-P consistent with ESD criteria.

OBJECTIVE We aimed to investigate whether Chinese endoscopists without narrow-band imaging (NBI) experiences could achieve high accuracy in the real-time diagnosis of colorectal polyps using NBI International Colorectal Endoscopic (NICE) classification after web-based training. METHODS Altogether 15 endoscopists from five centers with no NBI experiences followed a short, web-based training program on the NICE classification and took web-based test. Their performances were compared with 15 matched experienced endoscopists with no NBI experience who received no NBI training. These 15 trained endoscopists then made real-time diagnoses of colorectal neoplasia. A logistic regression was used to assess potential predictors of diagnostic performance. RESULTS Compared with those who received no training, trained endoscopists achieved comparable overall accuracy (85.3% vs 83.1%, P = 0.408) and accuracy at a high-confidence level (87.0% vs 86.0%, P = 0.670), but had a higher confidence rate (86.1% vs 83.7%, P = 0.004) for the diagnosis of neoplasia. Real-time diagnostic accuracy, sensitivity and specificity were 94.3% (95% confidence interval [CI] 91.5%-96.2%), 96.2% (95% CI 93.4%-97.9%) and 85.3% (95% CI 74.8%-92.1%) at high-confidence level. The high-confidence level was the strongest predictor of real-time diagnostic accuracy (odds ratio 12.66, P

AIM: To explore whether the same corneal curvature parameters and anterior chamber depth measured by Pentacam and VX120 have a good consistency and can replace each other. METHODS: This study enrolled 140 eyes of 70 patients ranging in age from 19 to 53y. All eyes underwent a comprehensive ophthalmologic examination including an anterior segment analysis with the VX120 system (Visionix-Luneau Technologies, Chartres, France) and Pentacam (Oculus Optikgerate GmbH) respectively. The comparison on corneal curvature parameters was done between Pentacam and VX120 using clustered signed rank test; the interclass correlation coefficients (ICC) with 95% confidence intervals (CI) was calculated for each parameter between Pentacam and VX120; the Bland-Altman plot of each parameter was supplemented. RESULTS: The anterior corneal curvature measured by VX120 was Ks: 44.00±1.78 D, KsAt: 89.45±22.18, Kf: 42.84±1.58 D, KfAt: 93.91±79.34; which measured by Pentacam was Ks: 43.80±1.82 D, KsAt: 91.17±21.40, Kf: 42.61±1.64 D, KfAt: 91.16±78.69. There was statistical difference between Pentacam and VX120 for anterior corneal curvature parameter (P

Background Tripartite motif 47 (TRIM47), a member of the TRIM family proteins, plays a key role in many types of cancers including colorectal cancer (CRC). We found that levels of TRIM47 mRNA and protein were increased significantly in colorectal tumors compared with nontumor tissues and the increased levels were associated with advanced tumor stage and poor outcome. Methods We used quantitative polymerase chain reaction and western blot to measure levels of TRIM47 mRNA and protein in human colorectal cancer and paired normal tissues. TRIM47 was knocked down and overexpressed in colorectal cancer cells, and the effects on cell proliferation, migration and growth of xenograft tumors in nude mice were assessed. The signaling pathways were examined by western blot and immunoprecipitation assays. Results TRIM47 promoted CRC proliferation and metastasis in vitro and in vivo as an oncogene. Mechanistically, TRIM47 interacted physically with SMAD4, increasing its ubiquitination and degradation. Loss of SMAD4 leaded to up-regulation of CCL15 expression and caused growth and invasion in human CRC cells through the CCL15-CCR1 signaling. Moreover, TRIM47 overexpression played a role in CRC chemoresistance in response to 5-FU therapy. Conclusions Our study demonstrated a functional role of the TRIM47-SMAD4-CCL15 axis in CRC progression and suggested a potential target for CRC therapy. Electronic supplementary material The online version of this article (10.1186/s13046-019-1143-x) contains supplementary material, which is available to authorized users.

Guidelines have differed in their opinion regarding the indications for endoscopic resection of gastric-neuroendocrine neoplasms (g-NENs) and duodenal-NENs (d-NENs). We examined the association between size and lymph node metastasis (LNM) to identify candidates most suitable for endoscopic resection. We identified 706 patients with T1/T2 g-NENs and 621 patients with T1/T2 d-NENs from the SEER database. The prevalence of LNM and risk factors associated with LNM were analyzed. LNM was present in 8.1% of patients with gastroduodenal neuroendocrine tumors (NETs) and 31.6% of patients with neuroendocrine carcinomas (NECs). Multivariate logistic regression indicated that tumor size >10mm, greater invasion depth, and poor differentiation were independently associated with LNM. In addition, the percentage of g-NETs invading submucosa with LNM increased with tumor size (≤10 mm,3.9%;11–20 mm,8.6%;>20 mm,16.1%). However, in contrast to the low LNM risk in patients with small g-NETs (≤10 mm), we found that LNM rate exceeded 5% even for patients with small submucosal-infiltrating d-NETs. Among patients with nodal-negative g-NETs, the cause specific survival (CSS) was similar for those who received surgical resection and endoscopic resection. Among patients with d-NETs, the CSS was better for those who received endoscopic resection. In conclusion, patients with d-NETs had a higher probability of LNM than those with g-NETs. Endoscopic resection can be utilized for curative treatment of submucosa-infiltrating g-NETs and intramucosal d-NETs when the size is 10 mm or less. These results reinforce the need to search for LNM in lesions that are larger than 10 mm.

BACKGROUND Ultrasound guidance has become a standard method for detection of nerve structures in regional anesthesia. During ultrasound-guided blockade, to identify anatomical structures is crucial but can be challenging. In clinical practice, we find a wide difference in the visibility score of the sciatic nerve (SN) through different approaches. This study aimed to compare SNB through the anterior and above-knee lateral approach in terms of identification ease, performance efficacy, and safety. METHODS Patients scheduled for below-knee surgery were randomized to either receive SNB using the above-knee lateral approach (Group L, n=27) or the anterior approach (Group A, n=26). The primary outcome was the visibility score of SN. Secondary outcomes included the time taken to identify the SN, nerve depth, success rate of SN identification, number of needle passes, time to elicit foot flexion, needle depth, and occurrence of SNB complications. Additionally, the sensory block onset and analgesia duration were assessed. RESULTS We included 53 adult patients. Compared with Group A, Group L showed a higher SN visibility score [3.25 (3.17, 3.67) vs. 2.50 (1.86, 2.68), P

This work seeks the development and validation of radiomics signatures from nonenhanced computed tomography (CT, NE‐RS) to preoperatively predict the malignancy degree of gastrointestinal stromal tumors (GISTs) and the comparison of these signatures with those from contrast‐enhanced CT. A dataset for 370 GIST patients was collected from four centers. This dataset was divided into cohorts for training, as well as internal and external validation. The minimum‐redundancy maximum‐relevance algorithm and the least absolute shrinkage and selection operator (LASSO) algorithm were used to filter unstable features. (a) NE‐RS and radiomics signature from contrast‐enhanced CT (CE‐RS) were built and compared for the prediction of malignancy potential of GIST based on the area under the receiver operating characteristic curve (AUC). (b) The radiomics model was also developed with both the tumor size and NE‐RS. The AUC values were comparable between NE‐RS and CE‐RS in the training (.965 vs .936; P = .251), internal validation (.967 vs .960; P = .801), and external validation (.941 vs .899; P = .173) cohorts in diagnosis of high malignancy potential of GISTs. We next focused on the NE‐RS. With 0.185 selected as the cutoff of NE‐RS for diagnosis of the malignancy potential of GISTs, accuracy, sensitivity, and specificity for diagnosis high‐malignancy potential GIST was 90.0%, 88.2%, and 92.3%, respectively, in the training cohort. For the internal validation set, the corresponding metrics are 89.1%, 94.9%, and 80.0%, respectively. The corresponding metrics for the external cohort are 84.6%, 76.1%, and 91.0%, respectively. Compared with only NE‐RS, the radiomics model increased the sensitivity in the diagnosis of GIST with high‐malignancy potential by 5.9% (P = .025), 2.5% (P = .317), 10.5% (P = .008) for the training set, internal validation set, and external validation set, respectively. The NE‐RS had comparable prediction efficiency in the diagnosis of high‐risk GISTs to CE‐RS. The NE‐RS and radiomics model both had excellent accuracy in predicting malignancy potential of GISTs., A dataset for 370 GIST patients was collected from four centers and was divided into cohorts for training, as well as internal and external validation. The minimum‐redundancy maximum‐relevance (mRMR) algorithm, and the least absolute shrinkage and selection operator (LASSO) algorithm were used to filter unstable features. The area under the curve (AUC) values were comparable between radiomics signatures from non‐enhanced CT (NE‐RS) and radiomics signatures from enhanced CT (CE‐RS) in the three cohorts in diagnosis of high malignancy potential of GISTs. With 0.185 selected as the cut‐off of NE‐RS for diagnosis of the malignancy potential of GISTs, accuracy for diagnosis high‐malignancy potential GIST was 89%, 85% for the internal validation and external validation cohort. Compared with only NE‐RS, the radiomics model with combination of radiomic signature and tumor size, had increased accuracy of 91%, 89% for the internal validation and external validation cohort. The NE‐RS and radiomics model both had excellent accuracy in predicting malignancy potential of GISTs.

Objective Sessile serrated adenoma/polyps (SSA/P) are recognized as precancerous lesions in the colon and resemble hyperplastic polyps (HP). Definite endoscopic features under narrow band imaging (NBI) with or without magnification may help differentiate these two lesions. Our study aimed to identify specific endoscopic features of SSA/P by NBI. Methods A total of 199 patients with histopathologically proven colorectal SSA/P or HP after a polypectomy were enrolled. Magnifying and non-magnifying NBI pictures of 206 matching lesions were evaluated by one expert and two non-expert endoscopists using various endoscopic characteristics retrospectively. Results Multivariate analysis indicated that a clouded surface (odds ratio [OR] 6.48, 95% confidence interval [CI] 2.72-15.44, P = 0.000) and dilated and branching vessels (DBV) (OR 7.95, 95% CI 3.71-17.02, P = 0.000) were significant endoscopic features for diagnosing SSA/P compared with HP. The combination of these two features could improve diagnostic specificity to 96%, and the area under the receiver operating characteristic curve was 0.749. However, it seemed that the presence of dark spots (OR 1.93, 95% CI 0.94-4.00, P = 0.075) was not a definite feature in differentiating these two lesions. Neither a mucus cap nor CP-II meshed capillary vessels showed statistical significance in differentiating SSA/P from HP (P = 0.590 and 0.293, respectively). Conclusions A clouded surface and DBV were two indicators for diagnosing SSA/P. Combining these two factors together under NBI with or without magnification achieved better diagnostic performance than when they were used alone.

Background Current methods of lymph node (LN) staging are controversial in predicting the survival of SBA. We aimed to develop an alternative LN-classification-based nomogram to individualize SBA prognosis. Methods Based on the data from the Surveillance, Epidemiology, and End Results (SEER) database of patients diagnosed with SBA between 2004 and 2014, we identified the cut-off points for the number of LNs examined and the number found to be metastatic using the K-adaptive partitioning (KAPS) algorithm. Using metastatic LNs, a nomogram predicting the survival of SBA was derived, internally and externally validated, and measured by calibration curve, C-index, and decision curve analysis (DCA), and compared to the 8th TNM stage. Results A total of 1516 patients were included. The cut-off of 17 was the optimal examined LN number. For metastatic LN numbers, the cut-off points were 0, 2, and 8. The C-index for the nomogram was higher than the 8th TNM staging (internal: 0.734; 95% CI, 0.693 to 0.775 vs. 0.677; 95% CI, 0.652 to 0.702, P 8 metastatic LNs and set the least examined LN number to 17. A nomogram based on this staging showed great clinical usability than TNM staging for predicting the survival of SBA patients., Highlights • The least examined number of lymph nodes was 16 in small bowel adenocarcinoma patients. • A new 4-level metastatic LNs staging was recommended: N0, no metastasis; N1, 1–2 LNs; N2, 3–8 LNs and N3, >8 LNs. • A nomogram with new staging showed great clinical usability than TNM staging for predicting survival of SBA patients. The number of examined and metastatic lymph nodes (LNs) is correlated inversely with survival of patients with small bowel adenocarcinoma (SBA). However, there was no verdict on the number of examined LNs and current staging of metastatic LNs was controversial in predicting survival of SBA. In this study, based on survival data of 6440 adults diagnosed SBA, we modified the examined LN number of 16 and introduced a new 4-level metastatic LN staging. Based on this new staging, we developed and validated a nomogram with greater clinical usability than traditional TNM staging for predicting survival of SBA patients.

A series of arylalkanol and aralkyl piperazine derivatives have been synthesized and evaluated for 5-HT reuptake inhibitory abilities and binding affinities at the 5-HT 1A /5-HT 7 receptors. Antidepressant activities of the compounds in vivo were screened using the forced swimming test (FST). The results indicated that the compound 8j exhibited high affinities for the 5-HT 1A /5-HT 7 receptors (5-HT 1A , k i = 0.84 nM; 5-HT 7 , k i = 12 nM) coupling with moderate 5-HT reuptake inhibitory activity (RUI, IC 50 = 100 nM) and showed a marked antidepressant-like activity in the FST model.

// Qing-Wei Zhang 1, * , Xiao-Lu Lin 1, 5 * , Chi-Hao Zhang 2, * , Chen-Yue Tang 3, * , Xin-Tian Zhang 1, * , La-Mei Teng 1, 4, * , Zhi-Zheng Ge 1 and Xiao-Bo Li 1 1 Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai 200001, China 2 Department of General Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Baoshan 201999, Shanghai, China 3 Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200000, China 4 Division of Gastroenterology and Hepatology, Liqun Clinical Medicine College, The Second Military Medical University, Liqun Hospital, Shanghai 200001, China 5 Department of Digestive Endoscopy, Provincial Clinic Medical College, Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, China * These authors have contributed equally to this work Correspondence to: Zhi-Zheng Ge, email: zhizhengge@aliyun.com Xiao-Bo Li, email: lxb_1969@163.com Keywords: esophageal cancer, marital status, SEER, OS, CSS Received: February 22, 2017 Accepted: April 04, 2017 Published: July 22, 2017 ABSTRACT Background and aims: Multiple studies have shown that marital status is associated with the survival of various types of cancer patients. However, there has not been adequate evidence of the association between marital status and the survival of patients with esophageal cancer (EC). We aimed to investigate the effect of marital status on survival of EC patients. Methods: We identified 15,598 EC patients from the Surveillance, Epidemiology, and End Results (SEER) database. Meanwhile, propensity scores for marital status, which were calculated for each patient using a nonparsimonious multivariable logistic regression model, were used to match 6,319 unmarried patients with 9,279 married patients. We performed Kaplan–Meier analysis and multivariate Cox regression to analyze the association between marital status and the overall survival (OS) and EC cause-specific survival (CSS) of EC patients before matching and after matching. Results: We matched 2,986 unmarried patients with 2,986 married patients. Unmarried patients had poorer OS than married patients before matching (hazard ratio [HR]: 1.22; 95% confidence interval [CI]: 1.18–1.27; P < 0.0001) and after matching (HR: 1.20; 95% CI: 1.13–1.27; P < 0.0001) and poorer CSS than married patients before matching (HR: 1.21; 95% CI: 1.16–1.26; P < 0.0001) and after matching (HR: 1.17; 95% CI: 1.10–1.24; P < 0.0001). Further analysis showed that among different unmarried patients, widowed patients had the poorest OS (HR: 1.46; 95% CI: 1.38–1.55; P < 0.0001) and CSS (HR: 1.43; 95% CI: 1.34–1.52; P < 0.0001) compared with married patients. Conclusions: Unmarried EC patients had poorer survival rates than married EC patients. Meanwhile, widowed patients with EC had the highest risk of death compared with single, married, and divorced patients.

In search of novel neuroprotective agents with higher potency and lower hERG liability, a series of novel Fenazinel derivatives were designed and synthesized, among which compounds 8m–o containing amide moiety exhibited good neuroprotective effects in vitro and in vivo . Especially, the representative compound 8o showed lower activity in a patch clamp hERG K + ion channel screen and could be considered as a lead compound for further development. These findings provided an alternative approach to the development of drugs more potent than Fenazinel for the intervention of ischemic stroke.

Background and aims Magnifying endoscopy with narrow-band imaging (M-NBI) has been widely used in the differential diagnosis of deep submucosal colorectal cancers (dSMCs) from superficial submucosal cancers (sSMCs) and intramucosal neoplasms. We aimed to pool the diagnostic efficacy of M-NBI and compare it with that of magnifying chromoendoscopy (M-CE) in diagnosing colorectal dSMC. Methods PubMed, EMBASE, and the Cochrane Library were searched to identify eligible studies. Meeting abstracts were also searched. A bivariate mixed-effects binary regression model was used in the meta-analysis to calculate the pooled diagnostic efficacy of M-NBI and compare it with that of M-CE in the diagnosis of dSMC. Subgroup analyses and meta-regression were conducted to explore sources of heterogeneity. Results We included 17 studies: 14 full texts and 3 meeting abstracts. The pooled sensitivity, specificity, and area under the summary receiver operating characteristic curve (AUC) with 95 % confidence intervals (CIs) in diagnosing dSMC were 74 % (66 % – 81 %; I2 = 84.6 %), 98 % (94 % – 99 %; I2 = 94.4 %), and 0.91 (0.88 – 0.93), respectively, for M-NBI. The pooled sensitivity, specificity and AUC (95 %CI) were 84 % (76 % – 89 %; I2 = 76.9 %), 97 % (94 % – 99 %; I2 = 90.2 %), and 0.97 (0.95 – 0.98), respectively, for M-CE. M-NBI had lower sensitivity (P Conclusions M-NBI and M-CE had comparable specificities in diagnosing dSMC, but the sensitivity of M-NBI was slightly lower than that of M-CE.

Background: There existed limited evidence about prognosis of young-onset early colorectal cancer (ECRC). In the present study, we aimed to compare prognosis between patients with young-onset ECRCs and patients with conventional ECRCs.Method: Patients with surgically resected, histologically diagnosed ECRCs were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Young-onset ECRC was defined as ECRC occurring in patients aged

Background: Log odds of positive lymph nodes (LODDS) classification showed superiority over 8th edition N staging in predicting survival of small bowel adenocarcinoma (SBA) patients. The aim of this study was to develop and validate the Tumor, LODDS, and Metastasis (TLM) staging of SBA. Methods: Totally 1789 SBA patients from the Surveillance, Epidemiology, and End Results (SEER) database between 1988–2010, 437 patients from SEER database between 2011–2013 and 166 patients from multicenters were categorized into development, validation and test cohort, respectively. The TLM staging was developed in the development cohort using Ensemble Algorithm for Clustering Cancer Data (EACCD) method. C-index was used to assess the performance of the TLM staging in predicting cancer-specific survival (CSS) and was compared with the traditional 8th edition TNM staging. Findings: Four-category TLM staging designed for the development cohort showed higher discriminatory power than TNM staging in predicting CSS in the development cohort (0.682 vs. 0.650, P

Background and aim: To construct proper and externally validate cut-off points for log odds of positive lymph nodes scheme (LODDS) staging scheme in colorectal cancer (CRC). Patients and methods: The X-tile approach was used to find the cut-off points for the novel LODDS staging scheme in 240,898 patients from the Surveillance, Epidemiology and End Results (SEER) database and externally validated in 1,878 from the international multicenter cohort. Kaplan-Meier plot and multivariate Cox proportional hazard models were performed to investigate the role of the novel LODDS classification. Results: The prognostic cut-off values were determined as -2.18, and -0.23 (P< 0.001). Patients had 5-year cancer-specific survival rates of 83.8%, 57.4% and 24.4% with increasing LODDS (P< 0.001) in the SEER database. Five-year overall survival rates were 77.2%, 55.0% and 26.7% with increasing LODDS (P< 0.001) in the external international multicenter cohort. Multivariate survival analysis identified both the LODDS classification, the patient's age, the T category, the M status, and the tumor grade as independent prognostic factors in both two independent databases. The analyses of the subgroup of patients stratified by tumor location (colon or rectum), number of retrieved lymph node (< 12 or ≥ 12), TNM stage III, lymph node-negative also confirmed the LODDS as independent prognostic factors (P< 0.001) in both two independent databases. Conclusions: The novel LODDS classification was an independent prognostic factor for patients with CRCs and should be calculated for additional risk group stratification with pN scheme.

Background and Aim To develop and validate radiomic prediction models using contrast-enhanced computed tomography (CE-CT) to preoperatively predict Ki-67 expression in gastrointestinal stromal tumors (GISTs). Method A total of 339 GIST patients from four centers were categorized into the training, internal validation, and external validation cohort. By filtering unstable features, minimum redundancy, maximum relevance, Least Absolute Shrinkage and Selection Operator (LASSO) algorithm, a radiomic signature was built to predict the malignant potential of GISTs. Individual nomograms of Ki-67 expression incorporating the radiomic signature or clinical factors were developed using the multivariate logistic model and evaluated regarding its calibration, discrimination, and clinical usefulness. Results The radiomic signature, consisting of 6 radiomic features had AUC of 0.787 [95% confidence interval (CI) 0.632–0.801], 0.765 (95% CI 0.683–0.847), and 0.754 (95% CI 0.666–0.842) in the prediction of high Ki-67 expression in the training, internal validation and external validation cohort, respectively. The radiomic nomogram including the radiomic signature and tumor size demonstrated significant calibration, and discrimination with AUC of 0.801 (95% CI 0.726–0.876), 0.828 (95% CI 0.681–0.974), and 0.784 (95% CI 0.701–0.868) in the training, internal validation and external validation cohort respectively. Based on the Decision curve analysis, the radiomics nomogram was found to be clinically significant and useful. Conclusions The radiomic signature from CE-CT was significantly associated with Ki-67 expression in GISTs. A nomogram consisted of radiomic signature, and tumor size had maximum accuracy in the prediction of Ki-67 expression in GISTs. Results from our study provide vital insight to make important preoperative clinical decisions.

Background Superficial colorectal cancer (SCRC) is defined as colorectal cancer (CRC) confined to the mucosa or submucosa. Endoscopic resection (ER) is widely used to resect differentiated SCRC from patients without lymph node metastasis (LNM). However, it is unclear whether ER is suitable for use with patients with differentiated early-onset SCRC because early-onset CRC is more aggressive. Therefore, we aimed to investigate the association between age of CRC onset and LNM. Materials and Methods We retrieved data for patients with surgically resected differentiated-type SCRCs from the Surveillance, Epidemiology, and End Results (SEER) database. Rate of LNM was compared among patients aged 18–39, 40–49, 50–59, 60–69, and ≥70 years. The association between age and LNM was further examined using multivariate logistic regression. Results We retrieved 34,506 records of differentiated SCRCs from the SEER database, including 667 patients aged 18–39 years, 2,385 aged 40–49, 8,075 aged 50–59 years, 9,577 aged 60–69 years, and 13,802 aged ≥70 years. Rates of LNM were 15.74%, 14.13%, 10.67%, 8.07%, and 6.76% for patients aged 18–39, 40–49, 50–59, 60–69, and ≥70 years, respectively. We found an inverse correlation between age at diagnosis and risk of LNM from the univariate analysis (p < .001). Compared with patients aged 18–39, the odds ratios with 95% confidence interval (CI) for patients aged 40–49, 50–59, 60–69, and ≥70 years were 0.90 (0.71–1.15, p = .376), 0.69 (0.56–0.87, p = .001), 0.54 (0.43–0.68, p < .001), and 0.47 (0.38–0.60, p < .001), respectively. Conclusion In differentiated SCRCs, younger age at diagnosis was associated with higher risk of LNM. Implications for Practice Endoscopic resection (ER) is widely used to resect differentiated superficial colorectal cancer (SCRC) without lymph node metastasis (LNM). However, no study has ever investigated risk of LNM of early-onset SCRC compared with average onset SCRC to explore whether ER is suitable for early-onset SCRC. To the authors' knowledge, this population-based study is the first study to find inverse correlation between age at diagnosis and risk of LNM in differentiated SCRCs. This finding indicates that ER may not be suitable for young patients with differentiated SCRC. Because the 30-day operative mortality after surgery is higher but the risk of LNM is lower in older patients compared with younger patients, ER for differentiated SCRCs may be advantageous over surgery for older patients.

Background Marital status proves to be an independent prognostic factor in a variety of cancers. However, its prognostic impact on gastric neuroendocrine neoplasms (G-NEN) has not been investigated. Methods We identified 3947 G-NEN patients from the Surveillance, Epidemiology, and End Results (SEER) database. Meanwhile, propensity scores for marital status were used to match 506 unmarried patients with 506 married patients. We used Kaplan–Meier method and multivariate Cox regression to analyse the association between marital status and the overall survival (OS) and G-NEN cause-specific survival (CSS) before matching and after matching. Results Married patients enjoyed better OS and CSS, compared with divorced/separated, single, and widowed patients. Multivariate Cox regression analysis indicated that unmarried status was associated with higher mortality hazards for both OS and CSS among G-NEN patients. Additionally, widowed individuals had the highest risks of overall (adjusted hazard ratio (HR): 1.56, 95% confidence interval (CI): 1.35–1.81, P P = 0.02) compared to other unmarried groups in both males and females. Furthermore, unmarried status remained an independent prognostic and risk factor for both OS (HR 1.51, 95% CI 1.19–1.90, P = 0.001) and CSS (HR 1.50, 95% CI 1.10–2.05, P = 0.01) in 1:1 propensity score-matched analysis. Conclusion Marital status was an independent prognostic factor for G-NEN. Meanwhile, widowed patients with G-NEN had the highest risk of death compared with single, married, and divorced/separated patients.

Multiple studies have shown that cancer-specific alternative splicing (AS) alterations are associated with clinical outcome. In this study, we aimed to profile prognostic AS signatures for pancreatic ductal adenocarcinoma (PDAC). We integrated the percent-spliced-in (PSI) data of AS in 140 PDAC patients based on the Cancer Genome Atlas (TCGA) dataset. We identified overall survival (OS)-associated AS events using univariate Cox regression analysis. Then, prognostic AS signatures were constructed for OS and chemoresistance prediction using the least absolute shrinkage and selection operator (LASSO) method. We also analyzed splicing factors (SFs) regulatory networks by Pearson's correlation. We detected 677 OS-related AS events in 485 genes by profiling 10,354 AS events obtained from 140 PDAC patients. Gene functional enrichment analysis demonstrated the pathways enriched by survival-associated AS. The AS signatures constructed with significant survival-associated AS events revealed high performance in predicting PDAC survival and gemcitabine chemoresistance. The area under the receiver operator characteristic curve was 0.937 in training cohort and 0.748 in validation cohort at 2000 days of OS. Furthermore, we identified prognostic SFs (e.g., ESRP1 and HNRNPC) to build the AS regulatory network. We constructed AS signatures for OS and gemcitabine chemoresistance in PDAC patients, which may provide clues for further experiment-based mechanism study.

Background: The prognostic roles of three common lymph node staging schemes, number of positive lymph nodes (pN), lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) in small bowel adenocarcinoma (SBA) are unclear. We assessed their prognostic ability in SBA. Methods: A total of 2128 patients diagnosed with SBA between 1988 and 2010 from the Surveillance, Epidemiology, and End Results (SEER) database and 186 patients from 15 hospitals in France and China were identified. We evaluated the prognostic ability of the schemes in both continuous and stratified patterns using R2, Harrell's C, and time-dependent receiver operating characteristic curve analyses. Findings: For continuous pattern, the LODDS had a better capacity of discrimination and higher accuracy of prognosis than pN and LNR. Similarly, the stratified LODDS classification had a better performance of discrimination and higher accuracy of prognosis than the pN and LNR classification. The multivariable model using the LODDS classification also showed superiorly predictive accuracy and discriminatory capacity to those of the 7th and, 8th TNM node and LNR classification. These results were fully validated in an independent international multicentre cohort. Interpretation: The LODDS scheme showed a better prognostic performance than the LNR or pN schemes in patients with SBA regardless of continuous or stratified pattern. The LODDS scheme could serve as an auxiliary to lymph node staging systems in future revisions of the American Joint Committee on Cancer (AJCC) manual. Fund: This work was funded by the Zhejiang Province Natural Science Fund of China. Keywords: Small bowel adenocarcinoma, Log odds of positive lymph nodes, Lymph node ratio, Number of positive lymph nodes, Prognosis, Multicentre cohort

Background and Aims Limited evidence and contradictory results exist regarding the impact of Lauren type, namely diffuse and intestinal types, of lymph node metastasis (LNM) and prognosis for early gastric cancer (EGC). We aimed to compare LNM and prognosis between diffuse and intestinal type EGCs using comprehensive statistical analysis. Methods The Surveillance, Epidemiology, and End Results (SEER) database was used to identify all patients with surgically resected, histologically diagnosed, intestinal or diffuse type EGC. Multivariate logistic regression, multivariate Cox regression, multivariate competing risk model, and propensity score matching were used to analyze association the Lauren type and LNM or prognosis. Results We identified 5593 EGCs from the SEER database, including 4376 intestinal types and 1217 diffuse types. No positive association was found between LNM and Lauren type (odds ratio, .93; 95% confidence interval [CI], .70-1.24; P = .62) after adjustment for other risk factors. Moreover, diffuse-type EGCs showed a similar prognosis to intestinal type EGCs in both multivariate Cox regression (HR [hazard ratio], .95; 95% CI, .77-1.18; P = .66) and the multivariate competing risk model (subdistribution HR [SHR], .99; 95% CI, .80-1.22; P = .926). Propensity score matching was used, and 733 diffuse types were matched with 733 intestinal types. We did not find any association between the Lauren type and LNM (odds ratio, .98; 95% CI, .71-1.37; P = .934) or prognosis in the univariate Cox regression (HR, .98; 95% CI, .76-1.26; P = .893) and univariate competing risk model (SHR, .98; 95% CI, .76-1.26; P = .893). Conclusions Diffuse-type EGC may have a comparable risk of LNM and prognosis to intestinal-type EGC. Nevertheless, these results should be carefully interpreted with caution when choosing endoscopic resection instead of surgery, because the treatment choice for EGC depends on the risk of lymphovascular invasion rather than LNM rate or prognosis.

Epidermal growth factor-like protein 6 (EGFL6) serves as an exocrine protein promoting proliferation and migration during carcinogenesis in ovarian cancer. However, its function and mechanisms in colorectal cancer (CRC) have not been completely explored. To investigate the role of EGFL6 in CRC cell growth, in vitro CCK8, colony formation assays, flow cytometric analysis of the cell cycle and apoptosis, and an in vivo tumor xenograft model were utilized. Additionally, Western blotting and luciferase reporter assays were used to investigate the underlying mechanisms of EGFL6 function on the WNT/β-catenin signaling pathway. Immunohistochemical staining showed that EGFL6 is overexpressed in CRCs and this overexpression was highly correlated with advanced T classification, N classification, distant metastasis, and poor survival. Knocking down EGFL6 in CRC cell lines induced the inhibition of cell growth, cell cycle arrest at the G0/G1 phase, and apoptosis. Further, knockdown of EGFL6 blocked WNT/β-catenin signaling as measured by Western blotting and luciferase reporter assay. Results also showed that recombinant EGFL6 (rEGFL6) induced β-catenin in a concentration- and time-dependent manner. Further experiments showed that administration of rEGFL6 to cell cultures with EGFL6 knocked down or treated with the WNT/β-catenin inhibitor ICG-001 increased β-catenin and its downstream protein CyclinD1. The CCK8 assay showed that EGFL6 promoted CRC cell growth partly by the promotion of TCF7L2 expression. These findings suggest that EGFL6 plays a crucial role in the progression of CRC by regulation of the WNT/β-catenin signaling pathway.

This study was performed to evaluate the prognostic effect of lymphadenectomy on outcomes in patients with resectable metastatic colorectal adenocarcinoma (mCRC). We selected patients with mCRC from 2004 to 2013 from Surveillance, Epidemiology, and End Results Program (SEER) database. Kaplan-Meier analysis, univariate Cox regression and multivariate Cox regression analysis were performed to assess the clinical value of lymphadenectomy on overall survival (OS) and cause-specific survival (CSS) of patients with resectable mCRC. A total 24178 eligible patients were included, 23056 (95.36%) of which received lymphadenectomy. Results showed that lymphadenectomy was an independent protective factor for survival of patients with mCRC overall [OS (HR: 0.86, 95%CI: 0.79-0.93, P=0.002) and CSS (HR: 0.85, 95%CI: 0.78-0.93, P

This study was aimed to determine the effect of the local tumor therapy on patients’ prognosis in the management of metastatic rectal cancer. Patients diagnosed with metastatic rectal cancer from 2004 to 2013 were selected from the SEER (Surveillance, Epidemiology, and End Results) database. Overall survival and cancer-specific survival were compared between the local treatment group and the nonlocal treatment group using Kaplan–Meier methods. Uni- and multivariate analyses were further performed to confirm or deny the results. The statistical approach of propensity score matching was conducted to avoid potential confounding factors. Of 6867 patients included in this analysis, 3971 (57.8%) received local therapy to the primary tumor and 2896 (42.2%) did not receive. Both univariable and multivariable analysis showed local therapy continued to be associated with an improvement in OS (HR 0.532; 95% CI 0.503–0.563, p

A Trend of Preference of Magnifying Chromoendoscopy to Narrow Band Imaging in Diagnosis of T1 Colorectal Cancer With Deep Invasion Could Be Observed

Targeted biopsy under the guidance of magnifying endoscopy with narrow band imaging (ME-NBI) has higher accuracy than endoscopic forceps biopsy (EFB) in the differential diagnosis of cancerous lesions from noncancerous lesions. The aims of this study were to validate diagnostic efficacy of targeted biopsy under the guidance of ME-NBI (MNTB) and further evaluate whether it is necessary to perform MNTB when combined with ME-NBI.This study prospectively analyzed 211 gastric lesions of suspected cancerous tissues. The sensitivity, specificity, positive predictive value, and negative predictive value of EFB, ME-NBI, MNTB, EFB plus ME-NBI, and MNTB plus ME-NBI for the diagnosis of cancerous lesions were determined, respectively. The accuracy, sensitivity, specificity of EFB and MNTB, EFB plus ME-NBI, and MNTB plus ME-NBI were also compared, respectively.The accuracy, sensitivity, and specificity with 95% confidence intervals were 68.2% (61.4-74.4%), 62.3% (54.1-69.9%), 84.2% (71.6-92.1%) for EFB, 75.4% (68.9-80.9%), 72.7% (64.9-79.4%), 82.5% (69.6-90.8%) for MNTB, 76.8% (70.4-82.2%), 73.4% (65.5-80.0%), 86.0% (73.7-93.3%) for ME-NBI, 82.0% (76.0-86.8%), 85.7% (79.0-90.6%), 71.9% (58.3-82.6%) for EFB plus ME-NBI, 84.8% (79.1-89.3%), 89.6% (83.4-93.8%), and 71.9% (58.3-82.6%) for MNTB plus ME-NBI, respectively. The sensitivity of MNTB was significantly higher than that of EFB (P=0.048). There was no significant difference in the sensitivity (P=0.307), specificity (P=1.000), and accuracy (P=0.337) between EFB plus ME-NBI and MNTB plus ME-NBI.Although MNTB has a higher diagnostic efficacy than EFB in the diagnosis of cancerous lesions, it may be not necessary to perform MNTB when combined with ME-NBI.