Development and validation of an online calculator to predict the pathological nature of colorectal tumors.

BACKGROUND: No single endoscopic feature can reliably predict the pathological nature of colorectal tumors (CRTs). AIM: To establish and validate a simple online calculator to predict the pathological nature of CRTs based on white-light endoscopy. METHODS: This was a single-center study. During the identification stage, 530 consecutive patients with CRTs were enrolled from January 2015 to December 2021 as the derivation group. Logistic regression analysis was performed. A novel online calculator to predict the pathological nature of CRTs based on white-light images was established and verified internally. During the validation stage, two series of 110 images obtained using white-light endoscopy were distributed to 10 endoscopists [five highly experienced endoscopists and five less experienced endoscopists (LEEs)] for external validation before and after systematic training. RESULTS: A total of 750 patients were included, with an average age of 63.6 ± 10.4 years. Early colorectal cancer (ECRC) was detected in 351 (46.8%) patients. Tumor size, left semicolon site, rectal site, acanthosis, depression and an uneven surface were independent risk factors for ECRC. The C-index of the ECRC calculator prediction model was 0.906 (P = 0.225, Hosmer-Lemeshow test). For the LEEs, significant improvement was made in the sensitivity, specificity and accuracy (57.6% vs 75.5%; 72.3% vs 82.4%; 64.2% vs 80.2%; P < 0.05), respectively, after training with the ECRC online calculator prediction model. CONCLUSION: A novel online calculator including tumor size, location, acanthosis, depression, and uneven surface can accurately predict the pathological nature of ECRC.

Surveillance Colonoscopies of Synchronous Colorectal Cancer: What Should We Do?

BACKGROUND: The aim of this study is to investigate the occurrence of metachronous neoplasms at 2-year surveillance colonoscopy for synchronous colorectal cancer patients and the relative risk factors. METHODS: Synchronous colorectal cancer patients who underwent surgery or endoscopic resection for colorectal cancer between January 2008 and December 2019 were enrolled. All patients underwent surveillance colonoscopies at least twice within 2 years after operation. Univariate and multivariate analyses were conducted to assess the risk factors for the metachronous neoplasms. RESULTS: Totally 38 patients (male/female: 26/12) were included, with an average age of 64.6 years (±11.5 years) and a mean surveillance interval of 23.47 ± 4.39 months. In 21 of 38 patients (55.3%), metachronous adenoma was detected, including 6 metachronous advanced adenomas. Two patients were detected with metachronous carcinomas. In univariate analysis, male sex, elderly age at diagnosis, and the presence of synchronous adenomas/synchronous advanced adenoma at baseline colonoscopy were associated with the development of metachronous adenoma (P = .037, .047, .013, .039), but not associated with metachronous advanced adenoma (P = 0.455, .746, .503, .269). Patients tends to occur less metachronous advanced adenoma if index colorectal tumors were treated by endoscopic resection (P = .010), but the tendency was not discovered in metachronous adenoma (P = .289). Tumor location (with/ without rectum cancer) was not associated with the development of metachronous lesions (P = .526, .382). On multivariate analysis, the presence of synchronous adenomas at baseline colonoscopy was an independent risk factor for MA during follow-up (odds ratio = 15.0; 95% CI: 1.55-145.22). CONCLUSION: For postoperative synchronous colorectal cancer patients, doctors should design individual surveillance strategies according to sex, baseline colonoscopy, and operative (or endoscopic) approach of resection.

Endoscopic classification and pathological features of primary intestinal lymphangiectasia.

BACKGROUND: The appearance of the intestinal mucosa during endoscopy varies among patients with primary intestinal lymphangiectasia (PIL). AIM: To classify the endoscopic features of the intestinal mucosa in PIL under endoscopy, combine the patients' imaging and pathological characteristics of the patients, and explain their causes. METHODS: We retrospectively analyzed the endoscopic images of 123 patients with PIL who were treated at the hospital between January 1, 2007 and December 31, 2018. We compared and analyzed all endoscopic images, classified them into four types according to the endoscopic features of the intestinal mucosa, and analyzed the post-lymphographic computed tomography (PLCT) and pathological characteristics of each type. RESULTS: According to the endoscopic features of PIL in 123 patients observed during endoscopy, they were classified into four types: nodular-type, granular-type, vesicular-type, and edematous-type. PLCT showed diffuse thickening of the small intestinal wall, and no contrast agent was seen in the small intestinal wall and mesentery in the patients with nodular and granular types. Contrast agent was scattered in the small intestinal wall and mesentery in the patients with vesicular and edematous types. Analysis of the small intestinal mucosal pathology revealed that nodular-type and granular-type lymphangiectasia involved the small intestine mucosa in four layers, whereas ectasia of the vesicular- and edematous-type lymphatic vessels largely involved the lamina propria mucosae, submucosae, and muscular layers. CONCLUSION: Endoscopic classification, combined with the patients' clinical manifestations and pathological examination results, is significant and very useful to clinicians when scoping patients with suspected PIL.

A Network Pharmacology Approach for Uncovering the Antitumor Effects and Potential Mechanisms of the Sijunzi Decoction for the Treatment of Gastric Cancer.

Background: Sijunzi decoction (SJZD), a classic Chinese formula, has been clinically used for the treatment of gastrointestinal disorders. However, few studies have uncovered its antitumor effects and its potential mechanisms against gastric cancer (GC). Therefore, this work aimed to identify the active compounds and putative targets of the SJZD and to further explore the potential mechanisms involved in the treatment of GC. Materials and Methods: The active compounds and potential targets of the SJZD and related genes for GC treatment were collected from a public database. Traditional Chinese medicine (TCM)-compound-target-disease networks, Venn diagrams, protein-protein interactions (PPIs), gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to obtain the bioactive compounds, key targets, and potential pathways. Next, the human gastric adenocarcinoma cell line NUGC-4 was inoculated subcutaneously into the right flank of NCG mice to build a tumor-bearing mouse model to further verify the findings. Results: There were 117 compounds in the SJZD in total. The SJZD and GC had 161 and 3288 potential targets, respectively, among which 123 targets overlapped. The network analysis showed that quercetin, kaempferol formononetin, ginsenoside, atractylenolide III, etc., were bioactive molecules. The tumor necrosis factor (TNF), interleukin-6 (IL-6), cellular tumor antigen p53 (TP53), transcription factor AP-1 (JUN), and vascular endothelial growth factor A (VEGFA) were potential targets. A KEGG pathway enrichment analysis revealed 110 pathways involved in the pathways for cancer, including the PI3K-AKT signaling pathway. Validation experiments showed that the SJZD inhibited tumor growth and induced apoptosis in tumor cells. In addition, the SJZD downregulated expressions of VEGFA, iNOS, COX-2, and Bax/Bcl2 and inhibited the expressions of p-PI3K and p-AKT. Conclusion: The SJZD treats GC by inhibiting blood vessel hyperplasia and inducing cell apoptosis by regulating the PI3K/AKT pathway.

Design and verification of individualized follow-up strategy of colonoscopy for postoperative patients with colorectal cancer.

BACKGROUND: Current guidelines do not establish an individual scheme for surveillance colonoscopy in postoperative colorectal cancer (CRC) patients. AIMS: The purpose of the study was to screen possible risk factors for the development of metachronous adenoma in postoperative CRC patients and to develop a risk prediction model and verify it. METHODS: Consecutive postoperative patients with CRC were enrolled from April 2007 to December 2013 as the derivation group. Baseline data of patients and clinicopathological features of the tumor were collected, logistic regression analysis was performed, and clinical model was established and was verified internally. The model was externally validated in an independent cohort (validation group) from January 2014 to October 2017 in the same hospital. RESULTS: A total of 734 patients were included, with average (64.6 ± 11.5) years old. The overall incidence of metachronous adenoma was 35.4%. There was no significant difference in the incidence of metachronous adenoma between the derivation group and validation group (P > 0.05). Age, diabetes mellitus, right colon cancer, moderately to poorly differentiated adenocarcinoma and synchronous adenoma were independent risk factors for metachronous adenoma. The C-index of the metachronous adenoma line chart model was 0.932, and the index decreased by 0.022 after internal verification. The C-index of external validation was 0.910. The Hosmer-Lemeshow test showed that the P value of metachronous adenoma risk prediction model was 0.247. CONCLUSIONS: Individual surveillance strategies should be designed for postoperative patients with CRC. For high-risk patients, it is appropriate to undergo more than two colonoscopies in 36 months after operation.

Comprehensive Analysis of Differentially Expressed Long Noncoding RNA-mRNA in the Adenoma-Carcinoma Sequence of DNA Mismatch Repair Proficient Colon Cancer.

DNA proficient mismatch repair colon cancer (pMMR CC) is the most common subtype of sporadic CC. We aimed to investigate the role of long noncoding RNAs (lncRNAs) in pMMR CC carcinogenesis. In the present study, we conducted transcriptomic analysis of lncRNAs-mRNAs in five low-grade intraepithelial neoplasia (LGIN), five high-grade intraepithelial neoplasia (HGIN), four pMMR CC, and five normal control (NC) tissues. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway, and coexpression network analyses were performed to elucidate the functions of lncRNAs and mRNAs as well as their interactions. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate five dysregulated lncRNAs in a large set of colon tissues. Receiver-operating characteristic (ROC) curves were employed to evaluate the performance of the candidate lncRNAs. A set of 5783 differentially expressed lncRNAs and 4483 differentially expressed mRNAs were detected among the LGIN, HGIN, pMMR CC, and NC samples. These differentially expressed lncRNAs and mRNAs were assigned to 275 significant GO terms and 179 significant KEGG enriched pathways. qRT-PCR confirmed that the expression of five selected lncRNAs (ENST00000521815, ENST00000603052, ENST00000609220, NR_026543, and ENST00000545920) were consistent with the microarray data. ROC analysis showed that four lncRNAs (ENST00000521815, ENST00000603052, ENST00000609220, and NR_026543) had larger area under the ROC curve (AUC) values compared to serum carcinoembryonic antigens, thereby distinguishing NC from pMMR CC. In conclusion, several lncRNAs play various roles in the adenoma-carcinoma sequence and may serve as potential biomarkers for the early diagnosis of pMMR CC.

The Polymorphisms of Interleukin-12B Gene and Susceptibility to Inflammatory Bowel Diseases: A Meta-analysis and Trial Sequential Analysis.

Objective: Inflammatory bowel disease (IBD) is a heterogeneous complex disease referring to two chronic disorders: Crohn's disease (CD) and ulcerative colitis (UC). To clarify the relationship between IL-12B gene polymorphisms and susceptibility to CD and UC, a meta-analysis was conducted.Methods: A comprehensive search of the PubMed, Web of Science, Embase and Cochrane databases was conducted up to Oct 2019. Studies evaluating the relationship between risk of IBD and variants of IL-12B (rs6887695, rs3212227 and rs10045431) were included. Odds ratio (OR) and 95% confidence interval (CI) were calculated. Trial sequential analysis (TSA) was implemented to estimate the required information size (RIS) and evaluate the credibility of the meta-analysis results.Results: Seventeen studies containing 9827 patients with CD, 7583 patients with UC and 16044 controls were included. The results showed significant association between rs6887695 polymorphism and susceptibility to CD (allele model: OR = 1.17, 95% CI: 1.12-1.22) and UC (allele model: OR = 1.16, 95% CI: 1.09-1.23), and "C" allele carriers had a higher risk, with TSA conclusive. For rs10045431, no significant association with CD susceptibility was identified, while a significantly increased risk in UC was found (allele mode: OR = 1.16, 95% CI: 1.07-1.25), both results were conclusive according to TSA. No significant association between rs3212227 and CD or UC susceptibility was found, and TSA research warranted further investigation to certify the results. No significant heterogeneity was found.Conclusion: IL-12B rs6887695 polymorphism was associated with increased risk of CD and UC, while IL-12B rs10045431 polymorphism might only be correlated with the risk of UC.Abbreviations: IBD: inflammatory bowel disease; CD: Crohn's disease; UC: ulcerative colitis; IL-12B: interleukin-12B; OR: odds ratio; CI: confidence interval; TSA: trial sequential analysis; RIS: required information size; DCs: dendritic cells; NK: nature killer; APCs: antigen-presenting cells; TNF: tumor necrosis factor; SNP: single nucleotide polymorphisms; HWE: Hardy-Weinberg equilibrium; NOS: Newcastle-Ottawa scale; RRR: relative risk reduction.

Personal instruction for patients before colonoscopies could improve bowel preparation quality and increase detection of colorectal adenomas.

BACKGROUND: To analyze whether face-to-face education before colonoscopy improves the quality of bowel preparation and increases the detection of adenomas. METHODS: A retrospective cross-sectional study of adult patients with colorectal polyps identified by colonoscopy as outpatients was performed. The patients underwent an added colonoscopy inpatient for resection of colorectal polyps. As outpatients, we gave the patients written bowel preparation instructions; however, when they were inpatients, we supplied face-to-face education. We analyzed the data from the two colonoscopies of the same group of patients out- and in-patients, including the quality of the intestinal preparation, the time to reach the ileocecal region, and the detection of adenomas. RESULTS: A total of 260 patients {age 63 [56, 68] years old, male/female (169/91)} were retrospectively included in our study. Two hundred fifty-two patients with a total of 685 adenomas were detected, 94 patients with 179 adenomas overlooked in the first colonoscopy. The BBPS Score during inpatient was higher than that during outpatient, {9 [8, 9] vs. 7 [6, 9]}, P<0.05, the Bubble Score during inpatient was lower than that during outpatient [0 (0.00, 0.00) vs. 0 (0.00, 1.00)], P<0.05. The time to reach the ileocecal region during inpatient is shorter than that during outpatient {6 [5, 9] vs. 7.5 [5, 11] min}, P<0.05. Poor bowel preparation, flat adenoma morphology, and adenoma diameter lower than 5mm were related adenoma misdiagnoses, P<0.05. CONCLUSIONS: Face-to-face patient education can improve the quality of bowel preparation, then shorten the time to reach the ileocecal region, and increase detection of colorectal adenomas.

Gastric phytobezoars: the therapeutic experience of 63 patients in Northern China.

INTRODUCTION: Sixty-three patients with gastric phytobezoars were reviewed. METHODS: forty-eight (76.2%) patients received endoscopic combined with chemical therapies and 15 (23.8%) received only chemical therapy initially. Fifty-one (81.0%) patients achieved complete removal (only chemical therapy 14/15), while 12 (19.0%) received further endoscopic therapies. RESULTS: finally, 62 (98.4%) patients achieved a complete removal. Considering only patients with combined treatment as a first approach, treatment success was associated with a softer phytobezoar consistency (p = 0.023). CONCLUSION: in conclusion, most patients achieve a favorable outcome. Chemical therapy is useful in selected cases. Repeated endoscopic therapies may be needed in order to completely remove phytobezoars with a hard consistency.

Long noncoding RNA ENST00000455974 plays an oncogenic role through up-regulating JAG2 in human DNA mismatch repair-proficient colon cancer.

DNA mismatch repair-proficient colon cancer is the most common type of colon cancer, but its initiation and progression are still unknown. Our previous study has revealed that a long noncoding RNA (lncRNA) ENST00000455974 was significantly associated with TNM stage and distant metastasis in patients with DNA mismatch repair-proficient (pMMR) colon cancer (CC). Here, firstly, we observed that ENST00000455974 was gradual increased across colon normal-adenoma-carcinoma-metastasis sequence by quantitative real-time PCR. Secondly, ENST00000455974 showed a better sensitivity and specificity than CEA and CA19-9 in the diagnosis of pMMR CC by drawing the receiver operating characteristic (ROC) curve. Thirdly, a higher level of ENST00000455974 was associated with a poorer patient survival. Furthermore, Knockdown of ENST00000455974 led to reduced proliferation and migration of colon cancer cells. Mechanistically, ENST00000455974 was mainly located in the nucleus of colon cancer cells and it promoted the growth and metastasis of pMMR CC cells through up-regulating JAG2.

Evaluation of the medical economics and safety: two methods for the endoscopic removal of jujube pits.

OBJECTIVE: to evaluate the medical economics and safety of two methods for the endoscopic removal of jujube pits, one with a transparent cap combined with a stone basket and the other with a transparent cap combined with foreign body forceps. METHODS: consecutive patients with a suspected jujube pit ingestion in the esophagus between January 2008 and December 2017 were enrolled into the study. Fifty-three patients who met the criteria were divided into two groups. Group A patients were treated by a transparent cap combined with a stone basket and group B patients were treated by a transparent cap combined with foreign body forceps. The following clinical data were collected: age, sex, location of jujube pits, complications, operation time, extraction success and average hospital costs. RESULTS: a total of 53 patients who met the criteria were enrolled into the study; 29 cases in group A and 24 cases in group B. Endoscopic removal was successful in 98.1% (52/53) of the patients and the remaining 1.9% (1/53) required surgery. Severe complications were less frequent in group A than in group B (p = 0.017). Surgery time was not significantly different between the two groups (p = 0.647). The extraction success in group A was higher than in group B (p = 0.001). The medical costs including the total cost, inspection, treatment, radiation and drug cost were not significantly different between the two groups (p > 0.05 in all cases). CONCLUSION: endoscopic baskets are suitable for cases of jujube pit ingestion and have a higher extraction success and a lower proportion of severe complications. Surgery time was not significantly extended and the medical costs did not increase.

Variable Levels of Long Noncoding RNA Expression in DNA Mismatch Repair-Proficient Early-Stage Colon Cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) have been suggested to be biomarkers for diagnosis and prognosis of sporadic colorectal cancer. AIMS: This study aimed to characterize the expression profile of lncRNAs in DNA mismatch repair-proficient (pMMR) early-stage colon cancer (CC). METHODS: The microsatellite instability (MSI) status was examined by a multiplex PCR. The expression of lncRNA and mRNA was analyzed by microarrays. The differentially expressed lncRNAs and mRNAs were determined by bioinformatic analyses and validated in 44 CC samples and 32 non-tumor colonic specimens by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: We found that 16 out of 67 CC had MSI-L CC and 7 with MSI-H. In comparison with that in five non-tumor colonic samples, microarray indicated that 1492 lncRNAs and 1639 mRNAs were upregulated while 1804 lncRNAs and 1073 mRNAs downregulated in four pMMR early-stage CC. Bioinformatic analyses revealed that the differentially expressed mRNAs were involved in the process of cell division, angiogenesis, apoptotic, differentiation, the PI3K-Akt/p53/TNF pathways and others. The co-expression lncRNA and mRNA networks indicated five hot spots with significantly high co-expression degrees. Further quantitative RT-PCR revealed that 4 out of 6 lncRNAs were significantly upregulated while the other 2 lncRNAs were downregulated in the CC. Stratification analysis demonstrated that 5 out of 6 lncRNAs were significantly associated with TNM stage and/or distant metastasis in this population. CONCLUSION: Differentially expressed lncRNAs were significantly associated with clinical features of patients with pMMR CC and may participate in the tumorigenesis of pMMR CC.

Doxorubicin nanobubble for combining ultrasonography and targeted chemotherapy of rabbit with VX2 liver tumor.

A new class of multifunctional nanobubble using poly(lactic-co-glycolic acid) (PLGA) has been developed as ultrasound imaging contrast agents, doxorubicin carriers, and enhancers of ultrasound-mediated drug delivery. The doxorubicin nanobubble (DOX-NB) wrapping carbon tetrafluoride gas was prepared with double emulsion method. We evaluated the enhanced ultrasonic function of the DOX-NB in vivo; its antitumor function was confirmed. The diameter of the prepared bubble was 500 nm, and the potential was -23 mV. The drug loading and encapsulation efficiency of the bubble were 78.6 and 7.4 %, respectively. Therefore, the DOX-NB greatly enhanced ultrasound imaging in vivo. Ultrasound combined with DOX-NB had significant antitumor effect. Compared with other groups, the tumor growth rate and the proliferation index were the lowest while the survival rate and apoptosis index were the highest.

The mechanisms of 5-FU-PLA-O-CMC-NPS-mediated inhibition of the proliferation of colorectal cancer cell line SW480.

We aimed to investigate how 5-FU-PLA-O-CMC-NP (5-FPOCN) inhibits the proliferation of the SW480 colon cancer cell line. Following the treatment of cell line SW480 with 0.1, 1, 10 or 100 µg/ml 5-FPOCN or 5-fluorouracil (fluorouracil, 5-Fu) for 0, 24, 48, or 72, the rate of cell was tested by the tetrazolium assay (MTT). After the SW480 cells were treated with 5-FPOCN or 5-FU for 72 h, the growth rate and apoptosis were detected. After the SW480 cells were treated with 5-FPOCN or 5-FU for 24, 48, 72, or 120, flow cytometry (FCM) was used to determine the cell cycle distribution. The changes in the expression of P21, CyclinD1 and Rb were detected by Western blotting and real-time PCR. We found that different doses of 5-FPOCN can significantly inhibit the growth rate of SW480 cells, and this effect is dose and time dependent. However, there is no significant difference from 72 to 120 h (P>0.05). After 5-FPOCN treatment for 72 h, there is a negative correlation between the concentration of 5-FPOCN and the activity of SW480 cells and a positive correlation between the concentration of 5-FPOCN and SW480 cell apoptosis. G1 phase was significantly increased, and S phase was significantly decreased in 5-FPOCN-treated SW480 cells at 72 h compared to the control group (P<0.05); there was a positive correlation between the concentration of 5-FPOCN and the above changes. It was suggested that 5-FPOCN can delay G1/S phase and that this is a dose-dependent effect. The expression of P21 protein and messenger RNA (mRNA) and Rb protein and mRNA was significantly increased in 5-FPOCN-treated SW480 cells at 72 h compared to the control group, and this was a dose- and time-dependent effect. CyclinD1 protein and mRNA expression was reduced as the dose increased, and its expression was negatively associated with the increased expression of P21. We concluded that 5-FPOCN can significantly inhibit the growth of colon cancer SW480 cells. 5-FPOCN increased P21 expression and decreased cyclin family and pRb expression to promote cell cycle delay and apoptosis.

{2-[(3-Carboxy-1-oxopropyl) amino]-2-deoxy-D-Glucose} suppresses proliferation and induces apoptosis in the human esophageal cancer cell line.

The aim of this study was to investigate the molecular mechanisms of apoptosis induced by {2-[(3-Carboxy-1-oxopropyl) amino]-2-deoxy-D-Glucose} (COPADG) in the esophageal cancer cell line Eca-109 and to establish a relationship between the rate of apoptosis and Fas and Bcl-2 protein expression. Eca-109 cells were cultured under standard condition. Cell growth was measured by MTT assay. Apoptosis and cell proliferation were determined by flow cytometry. Expressions of apoptosis-regulated genes Fas and Bcl-2 were detected by immunohistochemical methods and image analysis. COPADG dose- and time-dependently inhibited the growth of Eca-109 cells in vitro. Incubation of Eca-109 cells with 40 µmol/l of COPADG for 48 h induced significant apoptosis. After drug treatment, Fas protein expression was increased, while Bcl-2 protein expression was decreased. COPADG is able to induce apoptosis in the esophageal cancer cell line Eca-109. The mechanism of apoptosis in these cells may be related to up-regulation of Fas gene expression and the down-regulation of Bcl-2, which may serve as the experimental evidence for development of new drugs for the non-surgical management of human esophageal cancer.