Colonoscopy plays an important role in detecting colorectal neoplasms in patients with gastric neoplasms

BACKGROUND Gastric cancer(GC)and colorectal cancer(CRC)are the fifth and third most common cancer worldwide,respectively.Nowadays,GC is reported to have a potential predictive value for CRC,especially for advanced CRC.AIM To evaluate the necessity of colonoscopy for gastric neoplasm(GN)patients.METHODS Four databases,including PubMed,EMBASE,the Cochrane Library,and Ovid,were used to perform the search strategy on May 2,2023.The prevalence of colorectal neoplasms(CRN)and baseline characteristics were compared between the neoplasm group and the control group.Continuous variables are expressed as the mean difference and standard deviation.Relationships of categorical variables in the two groups are expressed as odds ratios(OR)and 95%confidence intervals(95%CIs).Subgroup analysis according to different kinds of GNs was conducted for more in-depth analysis.The results of this study are represented by forest plots.Publication bias was evaluated by a funnel plot.All data analyses were performed by STATA SE 16.0 software.RESULTS A total of 3018 patients with GNs and 3905 healthy controls(age and sex matched)were enrolled for analysis.After comparing the prevalence of CRNs between the two groups,CRNs were detected significantly more frequently in GN patients than in controls(OR=1.69,95%CI=1.28 to 2.23,I^(2)=85.12%,P=0.00),especially in patients with GC(OR=1.80,95%CI=1.49 to 2.18,I^(2)=25.55%,P<0.1).Moreover,other risk factors including age(OR=1.08,95%CI=1.00 to 1.17,I^(2)=90.13%,P=0.00)and male sex(OR=2.31,95%CI=1.26 to 4.22,I^(2)=87.35%,P=0.00),were related to the prevalence of CRNs.For patients in the GN group,body mass index(BMI,OR=0.88,95%CI=0.80 to 0.98,I^(2)=0.00%,P=0.92)and smoking(OR=1.03,95%CI=1.01 to 1.05,I^(2)=0.00%,P=0.57)were protective and risk factors for CRNs,respectively.CONCLUSION Patients are recommended to undergo colonoscopy when diagnosed with GNs,especially GC patients with a low BMI and a history of smoking.

Recent advances in endoscopic management of gastric neoplasms

The development and clinical application of new diagnostic endoscopic technologies such as endoscopic ultrasonography with biopsy,magnification endoscopy,and narrow-band imaging,more recently supplemented by artificial intelligence,have enabled wider recognition and detection of various gastric neoplasms including early gastric cancer(EGC)and subepithelial tumors,such as gastrointestinal stromal tumors and neuroendocrine tumors.Over the last decade,the evolution of novel advanced therapeutic endoscopic techniques,such as endoscopic mucosal resection,endoscopic submucosal dissection,endoscopic fullthickness resection,and submucosal tunneling endoscopic resection,along with the advent of a broad array of endoscopic accessories,has provided a promising and yet less invasive strategy for treating gastric neoplasms with the advantage of a reduced need for gastric surgery.Thus,the management algorithms of various gastric tumors in a defined subset of the patient population at low risk of lymph node metastasis and amenable to endoscopic resection,may require revision considering upcoming data given the high success rate of en bloc resection by experienced endoscopists.Moreover,endoscopic surveillance protocols for precancerous gastric lesions will continue to be refined by systematic reviews and meta-analyses of further research.However,the lack of familiarity with subtle endoscopic changes associated with EGC,as well as longer procedural time,evolving resection techniques and tools,a steep learning curve of such high-risk procedures,and lack of coding are issues that do not appeal to many gastroenterologists in the field.This review summarizes recent advances in the endoscopic management of gastric neoplasms,with special emphasis on diagnostic and therapeutic methods and their future prospects.

Usefulness of artificial intelligence in gastric neoplasms

Recently,studies in many medical fields have reported that image analysis based on artificial intelligence(AI)can be used to analyze structures or features that are difficult to identify with human eyes.To diagnose early gastric cancer,related efforts such as narrow-band imaging technology are on-going.However,diagnosis is often difficult.Therefore,a diagnostic method based on AI for endoscopic imaging was developed and its effectiveness was confirmed in many studies.The gastric cancer diagnostic program based on AI showed relatively high diagnostic accuracy and could differentially diagnose non-neoplastic lesions including benign gastric ulcers and dysplasia.An AI system has also been developed that helps to predict the invasion depth of gastric cancer through endoscopic images and observe the stomach during endoscopy without blind spots.Therefore,if AI is used in the field of endoscopy,it is expected to aid in the diagnosis of gastric neoplasms and determine the application of endoscopic therapy by predicting the invasion depth.

Efficacy and safety of 0.4 percent sodium hyaluronate for endoscopic submucosal dissection of gastric neoplasms

AIM:To evaluate the efficacy and safety of sodium hyaluronate solution(SH) in endoscopic submucosal dissection(ESD) of gastric neoplasms.METHODS:A prospective multicenter randomized,double blind,controlled trial was designed and utilized in this study.A total of 76 patients with 5-20 mm sized gastric neoplasms were enrolled at three academic hospitals in South Korea from June 2011 to October 2011.Patients were randomly assigned to the 0.4% sodium hyaluronate or control groups.All lesions underwent endoscopic ESD.ESD was performed with 0.4%SH and normal saline(NS) solution for submucosal injection.Efficacy was assessed using en bloc resection and the number of additional injections.Secondary evaluation variables were the volume of injection material,steepness of mucosal elevation,bleeding rate,procedural time and operator satisfaction.Finally,the safety was assessed by analyzing adverse events during the study.RESULTS:The usefulness rate in the 0.4%SH group and the controlled group had statistically significant difference under intention to treat(ITT) analysis(90.91% vs 61.11% P = 0.0041).Under per protocol(PP),the usefulness rate is statistically significant different(93.10% vs 61.76%,P = 0.0036).The difference in volume of the solution injected between 0.4%SH group and the controlled group and NS group was also statistically significant under intention to treat and per protocol analysis(ITT:0.03 ± 0.02 mL vs 0.06 ± 0.03 mL,P = 0.0003,PP:0.03 ± 0.02 mL vs 0.06 ± 0.03 mL,P = 0.0004).Satisfaction above the grade good was significantly higher in the SH group under intention to treat and per protocol analysis(ITT:90.91% vs 61.11%,P = 0.0041,PP = 93.11% vs 61.77%,P = 0.0022).Adverse events above grade 3 were not noticed in either group.All adverse events were treated and were judged as not associated with the submucosal injection solutions.CONCLUSION:0.4%SH solution is a safe and effective agent that doesn't cause any significant adverse events and is useful for submucosal injection during ESD.

Secondary endoscopic submucosal dissection for locally recurrent or incompletely resected gastric neoplasms

AIM To investigate the feasibility and safety of secondary endoscopic submucosal dissection(ESD) for residual or locally recurrent gastric tumors. METHODS Between 2010 and 2017, 1623 consecutive patients underwent ESD for gastric neoplasms at a single tertiary referral center. Among these, 28 patients underwent secondary ESD for a residual or locally recurrent tumor. Our analysis compared clinicopathologic factors between primary ESD and secondary ESD groups. RESULTS The en bloc resection and curative rate of resection of secondary ESD were 92.9% and 89.3%, respectively. The average procedure time of secondary ESD was significantly longer than primary ESD(78.2 min vs 55.1 min, P = 0.004), and the adverse events rate was not significantly different but trended slightly higher in the secondary ESD group compared to the primary ESD group(10.7% vs 3.8%, P = 0.095). Patients who received secondary ESD had favorable outcomes without severe adverse events. During a mean follow-up period, no local recurrence occurred in patients who received secondary ESD. CONCLUSION Secondary ESD of residual or locally recurrent gastric tumors appears to be a feasible and curative treatment though it requires greater technical efficiency and longer procedure time.

Clinical importance of colonoscopy in patients with gastric neoplasm undergoing endoscopic submucosal dissection

AIM To evaluate the usefulness of total colonoscopy(TCS) for patients undergoing gastric endoscopic submucosal dissection(ESD) and to assess risk factors for colorectal neoplasms.METHODS Of the 263 patients who underwent ESD at our department between May 2010 and December 2013, 172 patients undergoing TCS during a one-year period before and after ESD were targeted. After excluding patients with a history of surgery or endoscopic therapy for colorectal neoplasms, 158 patients were analyzed. Of the 868 asymptomatic patients who underwent TCS during the same period because of positive fecal immunochemical test(FIT) results, 158 patients with no history of either surgery or endoscopic therapy for colorectal neoplasms who were matched for age and sex served as the control group for comparison.RESULTS TCS revealed adenoma less than 10 mm in 53 patients(33.6%), advanced adenoma in 17(10.8%), early colorectal cancer in 5(3.2%), and advanced colorectalcancer in 4(2.5%). When the presence or absence of adenoma less than 10 mm, advanced adenoma, and colorectal cancer and the number of adenomas were compared between patients undergoing ESD and FITpositive patients, there were no statistically significant differences in any of the parameters assessed. The patients undergoing ESD appeared to have the same risk of colorectal neoplasms as the FIT-positive patients. Colorectal neoplasms were clearly more common in men than in women(P = 0.031). Advanced adenoma and cancer were significantly more frequent in patients with at least two of the following conditions: hypertension, dyslipidemia, and diabetes mellitus(P = 0.019).CONCLUSION In patients undergoing gastric ESD, TCS appears to be important for detecting synchronous double neoplasms. Advanced adenoma and cancer were more common in patients with at least two of the following conditions: hypertension, dyslipidemia, and diabetes mellitus. Caution is therefore especially warranted in patients with these risk factors.

Clutch Cutter knife efficacy in endoscopic submucosal dissection for early gastric neoplasms

AIM To compare the outcomes of endoscopic submucosal dissection(ESD) for gastric neoplasms using Clutch Cutter(ESD-C) or other knives(ESD-O).METHODS This was a single-center retrospective study. Gastric neoplasms treated by ESD between April 2016 and October 2017 at Kitakyushu Municipal Medical Center were reviewed. Multivariate analyses and propensity score matching were used to reduce biases. Covariates included factors that might affect outcomes of ESD, including age, sex, underlying disease, anti-thrombotic drugs use, tumor location, tumor position, tumor size, tumor depth, tumor morphology, tumor histology, ulcer(scar), and operator skill. The treatment outcomes were compared among two groups. The primary outcome was ESD procedure time. Secondary outcomes were en bloc, complete, and curative resection rates, and adverse events rates including perforation and delayed bleeding.RESULTS A total of 155 patients were included in this study; 44 pairs were created by propensity score matching. Background characteristics were quite similar among two groups after matching. Procedure time was significantly shorter for ESD-C(median; 49 min) than for ESD-O(median; 88.5 min)(P < 0.01). However, there was no significant difference in treatment outcomes between ESD-C and ESD-O including en bloc resection rate(100% in both groups), complete resection rate(100% in both groups), curative resection rate(86.4% vs 88.6%, P = 0.730), delayed bleeding(2.3% vs 6.8%, P = 0.62) and perforation(0% in both groups).CONCLUSION ESD-C achieved shorter procedure time without an increase in complication risk. Therefore, ESD-C could become an effective ESD option for gastric neoplasms.

Characteristics of metachronous gastric neoplasms after curative endoscopic submucosal dissection for early gastric neoplasms

Background:With the wide application of endoscopic submucosal dissection(ESD)for early gastric neoplasms,metachronous gastric neoplasms(MGN)have gradually become a concern.This study aimed to analyze the characteristics of MGN and evaluate the treatment and follow-up outcomes of MGN patients.Methods:A total of 814 patients were retrospectively enrolled.All these patients were treated by ESD for early gastric cancer or gastric dysplasia between November 2006 and September 2019 at The First Medical Center of Chinese People’s Liberation Army General Hospital.The risk factors for MGN were analyzed using Cox hazard proportional model.Moreover,the cumulative incidence,the correlation of initial lesions and MGN lesions,and the treatment and follow-up outcomes of MGN patients were analyzed.Results:A total of 4.5%(37/814)of patients had MGN after curative ESD.The 3-,5-,and 7-year cumulative incidences of MGN were 3.5%,5.1%,and 6.9%,respectively,and ultimately reaching a plateau of 11.3%at 99 months after ESD.There was no significant correlation between initial lesions and MGN lesions in terms of gross type(P=0.178),location(long axis:P=0.470;short axis:P=0.125),and histological type(P=0.832).Cox multivariable analysis found that initial multiplicity was the only independent risk factor of MGN(hazard ratio:4.3,95%confidence interval:2.0-9.4,P<0.001).Seventy-three percent of patients with MGN were treated by endoscopic resection.During follow-up,two patients with MGN died of gastric cancer with lymph node metastasis.The disease-specific survival rate was significantly lower in patients with MGN than that in patients without MGN(94.6%vs.99.6%,P=0.006).Conclusions:The MGN rate gradually increased with follow-up time within 99 months after curative gastric ESD.Thus,regular and long-term surveillance endoscopy may be helpful,especially for patients with initial multiple neoplasms.

Risk factors of major intraoperative bleeding and postoperative bleeding associated with endoscopic submucosal dissection for gastric neoplasms

Background:Endoscopic resection bleeding(ERB)classification was proposed by the authors’team to evaluate the severity of intraoperative bleeding(IB)during endoscopic submucosal dissection(ESD).This study aimed to evaluate the application of ERB classification and to analyze the risk factors of major IB(MIB)and postoperative bleeding(PB)associated with ESD for gastric neoplastic lesions.Methods:We retrospectively enrolled a total of 1334 patients who underwent ESD between November 2006 and September 2019 at The First Medical Center of Chinese People’s Liberation Army General Hospital.All patients were divided into the non-MIB group(including ERB-0,ERB-controlled 1[ERB-c1],and ERB-c2)and the MIB group(including ERB-c3 and ERB-uncontrolled[ERB-unc])according to the ERB classification.Risk factors of major MIB and risk factors of PB were analyzed using a logistic regression model.Results:Among the 1334 patients,773(57.95%)had ERB-0,477(35.76%)had ERB-c1,77(5.77%)had ERB-c2,7(0.52%)had ERB-c3,and no patients had ERB-unc.The rate of PB in patients with IB classifications of ERB-0,ERB-c1,ERB-c2,and ERB-c3 were 2.20%(17/773),3.35%(16/477),9.09%(7/77),and 2/7,respectively.In multivariate analysis,proximal location(odds ratio[OR]:1.488;95%confidence interval[CI]:1.045-3.645;P=0.047)was the only significant risk factor of MIB.Chronic kidney disease(CKD)(OR:7.844;95%CI:1.637-37.583;P=0.010)and MIB(ERB-c3)(OR:13.932;95%CI:2.585-74.794;P=0.002)were independent risk factors of PB.Conclusions:Proximal location of lesions was a significant risk factor of MIB.Additionally,CKD and MIB(ERB-c3)were independent risk factors of PB.More attention should be paid to these high-risk patients for MIB and PB.

Clinicopathological characteristics and prognosis of 232 patients with poorly differentiated gastric neuroendocrine neoplasms

BACKGROUND Poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)include gastric neuroendocrine carcinoma(NEC)and mixed adenoneuroendocrine carcinoma,which are highly malignant and rare tumors,and their incidence has increased over the past few decades.However,the clinicopathological features and outcomes of patients with PDGNENs have not been completely elucidated.AIM To investigate the clinicopathological characteristics and prognostic factors of patients with PDGNENs.METHODS The data from seven centers in China from March 2007 to November 2019 were analyzed retrospectively.RESULTS Among the 232 patients with PDGNENs,191(82.3%)were male,with an average age of 62.83±9.11 years.One hundred and thirteen(49.34%)of 229 patients had a stage III disease and 86(37.55%)had stage IV disease.Three(1.58%)of 190 patients had no clinical symptoms,while 187(98.42%)patients presented clinical symptoms.The tumors were mainly(89.17%)solitary and located in the upper third of the stomach(cardia and fundus of stomach:115/215,53.49%).Most lesions were ulcers(157/232,67.67%),with an average diameter of 4.66±2.77 cm.In terms of tumor invasion,the majority of tumors invaded the serosa(116/198,58.58%).The median survival time of the 232 patients was 13.50 mo(7,31 mo),and the overall 1-year,3-year,and 5-year survival rates were 49%,19%,and 5%,respectively.According to univariate analysis,tumor number,tumor diameter,gastric invasion status,American Joint Committee on Cancer(AJCC)stage,and distant metastasis status were prognostic factors for patients with PDGNENs.Multivariate analysis showed that tumor number,tumor diameter,AJCC stage,and distant metastasis status were independent prognostic factors for patients with PDGNENs.CONCLUSION The overall prognosis of patients with PDGNENs is poor.The outcomes of patients with a tumor diameter>5 cm,multiple tumors,and stage IV tumors are worse than those of other patients.

Gastric neuroendocrine neoplasms: A review

Gastric neuroendocrine neoplasms(g-NENs)or neuroendocrine tumors are generally slow-growing tumors with increasing incidence.They arise from enterochromaffin like cells and are divided into four types according to clinical characteristic features.Type 1 and 2 are gastrin dependent,whereas type 3 and 4 are sporadic.The reason for hypergastrinemia is atrophic gastritis in type 1,and gastrin releasing tumor(gastrinoma)in type 2 g-NEN.The diagnosis of g-NENs needs histopathological investigation taken by upper gastrointestinal endoscopy.g-NENs are positively stained with chomogranin A and synaptophysin.Grading is made with mitotic index and ki-67 proliferation index on histopathological analysis.It is crucial to discriminate between types of g-NENs,because the management,treatment and prognosis differ significantly between subtypes.Treatment options for g-NENs include endoscopic resection,surgical resection with or without antrectomy,medical treatment with somatostatin analogues,netazepide or chemotherapy regimens.Follow-up without excision is another option in appropriate cases.The prognosis of type 1 and 2 g-NENs are good,whereas the prognosis of type 3 and 4 g-NENs are close to the prognosis of gastric adenocancer.

Gastric neuroendocrine neoplasms type 1: A systematic review and meta-analysis

BACKGROUND To date, the histopathological parameters predicting the risk of lymph node (LN) metastases and local recurrence, associated mortality and appropriateness of endoscopic or surgical resection in patients with gastric neuroendocrine neoplasms type 1 (GNENs1) have not been fully elucidated. AIM To determine the rate of LN metastases and its impact in survival in patients with GNEN1 in relation to certain clinico-pathological parameters. METHODS The PubMed, EMBASE, Cochrane Library, Web of Science and Scopus databases were searched through January 2019. The quality of the included studies and risk of bias were assessed using the Newcastle-Ottawa Scale (NOS) in accordance with the Cochrane guidelines. A random effects model and pooled odds ratios (OR) with 95%CI were applied for the quantitative meta-analysis. RESULTS We screened 2933 articles. Thirteen studies with 769 unique patients with GNEN1 were included. Overall, the rate of metastasis to locoregional LNs was 3.3%(25/769). The rate of LN metastases with a cut-off size of 10 mm was 15.3% for lesions > 10 mm (vs 0.8% for lesions < 10 mm) with a random-effects OR of 10.5 (95%CI: 1.4 -80.8;heterogeneity: P = 0.126;I2 = 47.5%). Invasion of the muscularis propria was identified as a predictor for LN metastases (OR: 17.2;95%CI: 1.8-161.1;heterogeneity: P = 0.165;I2 = 44.5%), whereas grade was not clearly associated with LN metastases (OR: 2;95%CI: 0.3-11.6;heterogeneity: P = 0.304;I2 = 17.4%). With regard to GNEN1 local recurrence, scarce data were available. The 5-year disease-specific survival for patients with and without LN metastases was 100% in most available studies irrespective of the type of intervention. Surgical resection was linked to a lower risk of recurrence (OR: 0.3;95%CI: 0.1-1.1;heterogeneity: P = 0.173;I2 = 31.9%). The reported complication rates of endoscopic and surgical intervention were 0.6 and 3.8%, respectively. CONCLUSION This meta-analysis confirms that tumor size ≥ 10 mm and invasion of the muscularis propria are linked to a higher risk of LN metastases in patients with GNEN1. Overall, the metastatic propensity of GNEN1 is low with favorable 5- year disease-specific survival rates reported;hence, no clear evidence of the prognostic value of LN positivity is available. Additionally, there is a lack of evidence supporting the prediction of local recurrence in GNEN1, even if surgery was more often a definitive treatment.

Gastric dysplasia may be an independent risk factor of an advanced colorectal neoplasm

AIM: To evaluate the relationship between gastric dysplasia and Helicobacter pylori (H pylori) and the occurrence of colorectal adenoma, and to defi ne the necessity for colonoscopy in patients with gastric dysplasia or H pylori infection.METHODS: From May 2005 to February 2008, 133 patients with established gastric dysplasia by gastroduo-denoscopy (EGD) were additionally investigated by colonoscopy. The authors compared results with those of 213 subjects who underwent both EGD and colonoscopy during the same period at the author’s Health Promotion Center as a control group. H pylori infection was evaluated in both the gastric dysplasia and control groups.RESULTS: The mean age of all 346 study subjects was 54.1 ± 10.5 years, and there were 258 (73%) men and 87 (27%) women. No signif icant difference was found between the H pylori positive and negative subjects in terms of the prevalence of colorectal adenoma and advanced colorectal adenoma (P = 0.261). Patients with gastric dysplasia showed no elevated risk of colorectal adenoma (OR = 0.910, 95% CI: 0.587-1.411, P = 0.738), but had a signif icantly higher risk of having advanced colorectal adenoma (OR = 3.382, 95% CI: 1.700-6.342, P = 0.000).CONCLUSION: The study emphasizes the need for colon surveillance in patients with gastric dysplasia, regardless of H pylori infection.

Nomogram based on tumor-associated neutrophil-tolymphocyte ratio to predict survival of patients with gastric neuroendocrine neoplasms

AIM To assess the predictive value of the tumor-associated neutrophil-to-lymphocyte ratio in terms of the clinical outcomes of patients with gastric neuroendocrine neoplasms after radical surgery.METHODS Data were retrospectively collected from 142 patients who were diagnosed with gastric neuroendocrine neoplasms and who underwent radical gastrectomy at our department from March 2006 to March 2015. These data were retrospectively analyzed, and a receiver operating characteristic curve analysis was used to identify the optimal value of the tumorassociated neutrophil-to-lymphocyte ratio. Univariate and multivariate survival analyses were used to identify prognostic factors. A nomogram was then applied to predict clinical outcomes after surgery.RESULTS The tumor-associated neutrophil-to-lymphocyte ratio was significantly associated with tumor recurrence, especially with liver metastasis and lymph node metastasis(P < 0.05 for both), but not with clinical characteristics(P > 0.05 for all). A multivariate Cox regression analysis identified the tumor-associatedneutrophil-to-lymphocyte ratio as an independent prognostic factor for recurrence-free survival and overall survival(P < 0.05 for both). The concordance index of the nomograms, which included the tumorassociated neutrophil-to-lymphocyte ratio, Ki-67 index, and lymph node ratio, was 0.788(0.759) for recurrence-free survival(overall survival) and was higher than the concordance index of the traditional TNM staging system [0.672(0.663)].CONCLUSION The tumor-associated neutrophil-to-lymphocyte ratio is an independent prognostic factor in patients with gastric neuroendocrine neoplasms. Nomograms that include the tumor-associated neutrophil-to-lymphocyte ratio, Ki-67 index, and lymph node ratio have a superior ability to predict clinical outcomes of postoperative patients.

miR-126过表达和ADAM9基因沉默对胃癌SGC-7901细胞生物学行为的影响及其机制

目的:探讨微小RNA-126(miR-126)过表达和解整联蛋白金属蛋白酶9(ADAM9)基因沉默对胃癌细胞生物学行为的影响,并阐明其作用机制。方法:体外培养人胃低分化腺癌SGC-7901细胞和人正常胃黏膜上皮NGEC细胞,提取细胞中总RNA,采用实时荧光定量PCR(RT-qPCR)法检测2种细胞中miR-126和ADAM9 mRNA表达水平。将处于对数生长期的SGC-7901细胞分为miR-126过表达组(miR-126-OE组)和ADAM9基因沉默组(ADAM9 siRNA组),以LipofectamineTM 2000为载体分别转染miR-126模拟物(miR-126 mimics)和敲低ADAM9的RNA寡核苷酸,并设置相应的阴性对照组。采用噻唑蓝(MTT)法检测各组细胞增殖活性,细胞划痕实验检测各组细胞迁移率,Transwell小室实验检测各组细胞的迁移细胞数和侵袭细胞数,Western blotting法检测各组细胞中E-钙黏蛋白、N-钙黏蛋白和波形蛋白表达水平。TargerScan网站预测miR-126的靶基因并通过双荧光素酶报告基因实验验证miR-126和ADAM9的靶向调控关系,采用RT-qPCR法和Western blotting法检测转染miR-126 mimics后SGC-7901细胞中ADAM9 mRNA和蛋白表达水平。结果:RT-qPCR法检测,与人正常胃黏膜上皮NGEC细胞比较,胃癌SGC-7901细胞中miR-126表达水平明显降低(P<0.05),而ADAM9mRNA表达水平明显升高(P<0.05)。MTT法检测,SGC-7901细胞过表达miR-126或沉默ADAM9基因48和72 h后,与相应阴性对照组比较,miR-126 OE组和ADAM9 siRNA组细胞增殖活性均明显降低(P<0.05或P<0.01)。细胞划痕实验检测,与相应阴性对照组比较,48 h后miR-126 OE组和ADAM9 siRNA组细胞迁移率明显降低(P<0.05)。Transwell小室实验检测,与相应阴性对照组比较,miR-126 OE组和ADAM9 siRNA组迁移细胞数和侵袭细胞数明显减少(P<0.05或P<0.01)。Western blotting法检测,与相应阴性对照组比较,miR-126-OE组和ADAM9 siRNA组细胞中E-钙黏蛋白表达水平明显升高(P<0.05或P<0.01),而N-钙黏蛋白和波形蛋白表达水平明显降低(P<0.05或P<0.01)。靶基因预测,ADAM9的3´-UTR含有与miR-126-3p互补的核苷酸序列。双荧光素酶报告基因实验,ADAM9是miR-126靶向负调控的下游基因。SGC-7901细胞转染miR-126 mimics 48 h后,与mimics NC组比较,miR-126 OE组细胞中ADAM9 mRNA和蛋白表达水平均明显降低(P<0.05或P<0.01)。结论:胃癌SGC-7901细胞中miR-126低表达而ADAM9基因高表达。miR-126过表达可抑制胃癌SGC-7901细胞增殖活性、迁移和侵袭能力,其机制可能与miR-126靶向负调控ADAM9并抑制胃癌细胞的上皮-间质转化(EMT)进程有关。

黏蛋白MUC13对胃癌预后及生物学行为的影响

目的:探讨黏蛋白MUC13在胃癌(GC)患者中的预后价值以及对GC细胞生物学行为的影响。方法:TCGA数据库分析MUC基因在GC组织中的表达水平。采用Spearman秩相关分析MUC基因之间表达的相关性,GO功能富集和京都基因与基因组百科全书(KEGG)通路富集探究MUC基因潜在的生物学功能。基于单因素COX回归筛选与GC预后显著相关的MUC基因。通过免疫荧光检测MUC13的表达水平,并分析其与GC预后等临床病理特征的关系。siRNA敲低GC细胞中MUC13后,利用CCK-8、集落形成以及Transwell实验观察其对GC细胞增殖、迁移和侵袭的影响。结果:MUC1、MUC2、MUC3A、MUC4、MCU5B、MUC12、MUC13等基因在GC组织中表达均显著上调(P<0.05),主要富集在消化系统过程、上皮结构维持、顶端质膜、唾液分泌等途径。其中,MUC13与GC患者的不良预后(Log-rank P<0.05)、年龄(P<0.001)及肿瘤大小(P=0.035)密切相关。细胞学实验表明敲低MUC13后,GC细胞的增殖能力明显下降(P<0.05),但迁移和侵袭能力无显著变化(P>0.05)。结论:高表达的MUC13与胃癌的不良预后密切相关,参与肿瘤进展的调控,是胃癌潜在的治疗靶点和预后标志物。

基于JAK/STAT信号通路探讨PRELID1表达在胃癌恶性生物学行为中的作用

目的探讨相关进化和淋巴兴趣域蛋白1(PRELID1)在胃癌组织中的表达及对预后的影响,并分析其影响胃癌细胞增殖和侵袭能力的机制。方法利用TCGA数据库和111例胃癌患者的临床数据分析PRELID1在胃癌组织中的表达,并分析PRELID1表达与临床病理特征的关系及对预后的影响。生物信息学技术预测PRELID1的生物学功能,并进一步采用体外和体内实验验证。体外实验检测慢病毒调控胃癌细胞系(MGC803)中PRELID1的表达,并观察其对胃癌细胞增殖、迁移和侵袭的影响。利用裸鼠皮下成瘤体内实验观察PRELID1表达对胃癌组织生长的影响。结果PRELID1在胃癌组织中的表达显著高于癌旁组织(P<0.001)且与Ki67增殖指数呈正相关(P<0.001)。Cox回归模型分析显示,PRELID1高表达是影响胃癌患者根治术后5年生存率的独立危险因素(HR=2.336;95%CI=1.354~4.029)。基因富集结果显示,PRELID1的功能与细胞增殖和JAK/STAT信号有关。CCK-8和Transwell实验发现上调PRELID1表达可促进胃癌细胞的增殖(P=0.016)、迁移(P=0.016)和侵袭(P=0.025),下调其表达则抑制胃癌细胞的增殖(P=0.026)、迁移(P=0.048)和侵袭(P=0.029);裸鼠皮下成瘤实验发现上调PRELID1表达可促进胃癌组织的生长(P=0.047),下调其表达结果相反(P=0.005)。Western blot法检测结果显示,上调PRELID1表达可促进胃癌细胞和胃癌组织中JAK和STAT蛋白的表达(P均<0.05),下调则抑制(P均<0.05)。结论PRELID1在胃癌组织中呈高表达且与预后不良相关,其可能通过上调JAK/STAT信号调控胃癌细胞的增殖、迁移和侵袭。

1024×1024重建矩阵结合迭代重建算法在胃部CT血管成像中的应用

目的 探究1 024×1 024重建矩阵结合迭代重建(Karl)算法在胃部血管及肿瘤供血动脉CT血管成像中的应用价值。资料与方法 前瞻性收集大连医科大学附属第一医院2022年3—6月行胃部CT血管成像的胃部肿瘤患者30例,对CT扫描图像原始数据进行分组重建。A组采用常规512×512矩阵结合Karl 5级重建;B组采用1 024×1 024大重建矩阵结合不同等级Karl算法重建,分为B1(Karl 5)、B2(Karl 7)及B3(Karl 9)3个亚组。在轴位图像上测量胃左动脉起始部的腹主动脉、腹腔干、脾动脉、肝动脉及同层面腹壁皮下脂肪组织的CT值和SD值,计算信噪比(SNR)、对比噪声比(CNR)。由2名观察者采用5分法评估各组图像质量。结果 2名观察者主观评价一致性较好(Kappa=0.782~0.789,P<0.05),B1~B3组图像主观评分均优于A组,B2组得分最高(二维评分:χ^(2)=27.309、24.250;三维评分:χ^(2)=21.964、21.294;P均<0.05),30例患者中25例见胃动脉系统参与肿瘤供血,B2组各血管的清晰显示率均优于A组;A与B1、B2组各血管CT值差异无统计学意义(t=-1.918~2.720,P>0.05),B2组较A组血管SD值、SNR、CNR和背景噪声值,除腹主动脉SD、肝动脉CNR外差异均无统计学意义(t=-5.909~5.768,P>0.05);B1~3组图像随着Karl算法等级提高,SD值逐渐降低(F=2.881~27.109,P<0.05),SNR、CNR逐渐升高(F=3.612~12.149,P<0.05)。结论 1 024×1 024重建矩阵结合Karl 7级算法可以改善图像质量,增强胃部微细血管及肿瘤供血动脉分支的显示效果,在临床上有很好的应用价值。

Management of gastric mucosa-associated lymphoid tissue lymphoma in patients with extra copies of the MALT1 gene

AIM To identify the clinical features of gastric mucosaassociated lymphoid tissue(MALT) lymphoma with extra copies of MALT1.METHODS This is a multi-centered,retrospective study. We reviewed 146 patients with MALT lymphoma in the stomach who underwent fluorescence in situ hybridization analysis for t(11;18) translocation. Patients were subdivided into patients without t(11;18) translocation or extra copies of MALT1(Group A,n = 88),patients with t(11;18) translocation(Group B,n = 27),and patients with extra copies of MALT1(Group C,n = 31). The clinical background,treatment,and outcomes of each group were investigated.RESULTS Groups A and C showed slight female predominance,whereas Group B showed slight male predominance. Mean ages and clinical stages at lymphoma diagnosis were not different between groups. Complete response was obtained in 61 patients in Group A(69.3%),22 in Group B(81.5%),and 21 in Group C(67.7%). Helicobacter pylori(H. pylori) eradication alone resulted in complete remission in 44 patients in Group A and 13 in Group C. In Group B,14 patients underwent radiotherapy alone,which resulted in lymphoma disappearance. Although the difference was not statistically significant,event-free survival in Group C tended to be inferior to that in Group A(P = 0.10).CONCLUSION Patients with t(11;18) translocation should be treated differently from others. Patients with extra copies of MALT1 could be initially treated with H. pylori eradication,similar to patients without t(11;18) translocation or extra copies of MALT1.

Relationship between clinicopathological features and mucin phenotypes of advanced gastric adenocarcinoma

AIM: To investigate a relationship between the clinicopathological features and mucin phenotypes in advanced gastric adenocarcinoma (AGA). METHODS: Immunohistochemical staining was performed to determine the mucin phenotypes in 38 patients with differentiated adenocarcinomas (DACs), 9 with signet-ring cell carcinomas (SIGs), and 48 with other diffuse-type adenocarcinomas (non-SIGs) of AGA. The mucin phenotypes were classified into 4 types: gastric (G), gastrointestinal (GI), intestinal, and unclassified. RESULTS: The G-related mucin phenotypes were highly expressed in all the histological subtypes of AGA. The expression of the GI phenotype in SIG patients was lower than that in DAC patients (P = 0.02), and this phenotype was observed in 56% of the non-SIG patients in the intramucosal layer. Among non-SIG cases, the expression of the GI phenotype was significantly higherin patients with extended adenocarcinomas and those with positive rates of lymph node metastasis. There was no difference between the expressions of the G and other GI phenotypes factors. Among DAC and non-SIG patients, there were no differences between the survival rates of the corresponding patient groups. CONCLUSION: The GI phenotype might possess more invasive characteristics than the G phenotype in nonSIG. Neither of the phenotypes indicated a poor prognosis of DAC and non-SIG.