Colon adenoma features and their impact on risk of future advanced adenomas and colorectal cancer

AIMTo review the evidence on the association between specific colon adenoma features and the risk of future colonic neoplasia [adenomas and colorectal cancer (CRC)]. METHODSWe performed a literature search using the National Library of Medicine through PubMed from 1/1/2003 to 5/30/2015. Specific Medical Subject Headings terms (colon, colon polyps, adenomatous polyps, epidemiology, natural history, growth, cancer screening, colonoscopy, CRC) were used in conjunction with subject headings/key words (surveillance, adenoma surveillance, polypectomy surveillance, and serrated adenoma). We defined non-advanced adenomas as 1-2 adenomas each 25% villous histology or high-grade dysplasia. A combined endpoint of advanced neoplasia included advanced adenomas and invasive CRC. RESULTSOur search strategy identified 592 candidate articles of which 8 met inclusion criteria and were relevant for assessment of histology (low grade vs high grade dysplasia, villous features) and adenoma size. Six of these studies met the accepted quality indicator threshold for overall adenoma detection rate > 25% among study patients. We found 254 articles of which 7 met inclusion criteria for the evaluation of multiple adenomas. Lastly, our search revealed 222 candidate articles of which 6 met inclusion criteria for evaluation of serrated polyps. Our review found that villous features, high grade dysplasia, larger adenoma size, and having ≥ 3 adenomas at baseline are associated with an increased risk of future colonic neoplasia in some but not all studies. Serrated polyps in the proximal colon are associated with an increased risk of future colonic neoplasia, comparable to having a baseline advanced adenoma. CONCLUSIONData on adenoma features and risk of future adenomas and CRC are compelling yet modest in absolute effect size. Future research should refine this risk stratification.

Metabolic syndrome, lifestyle risk factors, and distal colon adenoma: A retrospective cohort study

AIM: To investigate relationships between colorectal adenoma incidence, metabolic syndrome (MS) components and lifestyle factors. METHODS: We conducted a retrospective cohort study using data from individuals who had multiple sigmoidoscopies for colon cancer at the Health Promotion Center of Ulsan University Hospital in Korea from 1998 to 2007. RESULTS: By multivariate analysis, the incidence of distal colon adenoma was increased by more than 1.76 times in individuals with at least one component of MS compared to those without a component of MS. After adjustment for age, gender, smoking, drinking, and physical exercise, only high body mass index (BMI) was significantly associated with the incidence of distal colon adenoma (Hazard ratio 1.66, 95% confidence interval 1.05-2.62). CONCLUSION: Our results suggest that high BMI may increase the risk of colorectal adenoma in Korean adults.

Differential expression of nucleolin in colon adenoma and adenocarcinoma

Objective The aim of the study was to investigate the discrepancy in nucleolin expression between colon adenoma and colon adenocarcinoma,explore the role of nucleolin expression in the carcinogenesis of colon adenocarcinoma,and determine the correlation of the nucleolin expression level with histological grade in colon adenocarcinoma.Methods In total,80 cases of colon adenocarcinoma with cancer-adjacent colon mucosa and 60 cases of colon adenomas were examined by immunohistochemistry using an antibody against nucleolin.Nucleolin expression levels in these groups were compared.The correlation between the nucleolin expression level and grade of colon adenocarcinoma was analyzed.Results Nucleolin expression is located in the nuclei of colon adenocarcinoma,colon adenoma,and cancer-adjacent colon mucosa tissues with different intensities.A semiquantitative evaluation using the Allred scoring system showed that the nucleolin immunostaining score in colon adenocarcinoma(7.8 ± 0.1) was significantly higher than those in colon adenoma(6.3 ± 0.2) and cancer-adjacent colon mucosa(5.4 ± 0.1;P < 0.01).The nucleolin immunostaining score in colon adenoma was significantly higher than that in cancer-adjacent colon mucosa(P < 0.01).Nucleolin expression levels in well-differentiated and moderately differentiated adenocarcinoma(6.8 ± 0.2) were significantly lower than those in poorly differentiated adenocarcinoma(8.0 ± 0.1;P < 0.01).Conclusion Increased nucleolin expression may play an important role in the process of malignant transformation of colon adenocarcinoma and predicts a poor prognosis.

Effect of a high-fat diet in development of colonic adenoma in an animal model

AIM: To investigate the effect of a high-fat diet in the formation of the precursors of colorectal cancer using an animal model.

Disparities of conjugating protective enzyme activities in the colon of patients with adenomas and carcinomas

AIM:To investigate the metabolic enzymatic capacity of the colon mucosa to detoxify noxious carcinogenic compounds.METHODS:We investigated the activity of 2 conjugating enzymes-the microsomal uridine glucuronosyltransferase(UGT)and the cytosomal glutathione S-transferase(GST)in the uninvolved mucosa of the colon transversum and sigmoideum in patients with adenomatous polyps and colorectal cancer.Biopsies were taken from the mucosa during colonoscopies which were done for clinical(diagnostic)reasons.After storage,the biopsy material was homogenized and after differential centrifugation the enzyme assays were performed with 4-nitrophenol(UGT)and 1-chloro 2,4-dinitrobenzene(GST)as substrates.RESULTS:About 48 patients were included of which28 had adenomas and 20 had colorectal carcinomas confirmed by histopathology.Enzyme activities were expressed as nmol/mg per minute protein for the GST and as pmol/mg per minute protein for the UGT.Analysis of variance(F-test)indicated that both enzymes were more widely distributed in adenoma than in cancer patients.The means±SD were smaller for cancer patients:GST for adenomas 268±152 vs 241±69 for carcinomas and UGT for adenomas 197±200 vs 150±86 for carcinomas.CONCLUSION:Compared to patients with adenomatous colon polyps those with colorectal carcinoma exhibited a lower capacity of detoxifying enzyme metabolism and their activities clustered over a smaller range.

Pyogenic liver abscess associated with large colonic tubulovillous adenoma

Pyogenic liver abscesses usually occur in association with a variety of diseases. Rarely, liver abscess has been reported as the presenting manifestation of colonic tubulovillous adenoma. We report two cases of pyogenic liver abscess without hepatobiliary disease or other obvious etiologies except that one had a history of diabetes mellitus （DM）. The pathogen in the patient with DM was Klebsiella pneumonia （KP）. In both of the patients, Ueus developed about two to three weeks after the diagnosis of liver abscess. Colonoscopy revealed large polypoid tumors with pathological findings of tubulovillous adenoma in both cases. Two lessons were learned from these two cases： （1） an underlying cause should be aggressively investigated in patients with cryptogenic liver abscess; （2） DM could be one of the etiologies but not necessarily the only cause of KP liver abscess.

Identification of differentially expressed genes in normal mucosa,adenoma and adenocarcinoma of colon by SSH

AIM: To construct subtracted cDNA libraries and further identify differentially expressed genes that are related to the development of colorectal carcinoma(CRC). METHODS: Suppression subtractive hybridization(SSH) was done on cDNAs of normal mucosa, adenoma and adenocarcinoma tissues from the same patient. Three subtracted cDNA libraries were constructed and then hybridized with forward and backward subtracted probes for differential screening. Positive clones from each subtracted cDNA library were selected for sequencing and BLAST analysis. Finally, virtual Northern Blot confirmed such differential expression. RESULTS: By this way, there were about 3-4 X 10(2) clones identified in each subtracted cDNA library, in which about 85% positive clones were differentially screened. Sequencing and BLAST homology search revealed some clones containing sequences of known gene fragments and several possibly novel genes showing few or no sequence homologies with any known sequences in the database. CONCLUSION: All results confirmed the effectiveness and sensitivity of SSH. The differentially expressed genes during the development of CRC can be used to shed light on the pathogenesis of CRC and be useful genetic markers for early diagnosis and therapy.

Significance of EZH2 and BMI-1 Protein Expression in Carcinogenesis of Colon Serrated Adenoma

Objective:To observe the significance of EZH2 and BMI-1 protein expression in the carcinogenesis process of colon serrated adenoma(SSA/P).Methods:Hematoxylin-eosin(HE)staining was used to observe the morphological characteristics of normal tissues,hyperplastic polyp(HP),SSA/P and colon cancer.Immunohistochemical staining was used to detect the expression of EZH2 and BMI-1 protein.The relative expression of EZH2 and BMI-1 was detected by qRT-PCR.Results:Compared with normal tissues,HP and colon cancer tissues,SSA/P showed serrated glandular hyperplasia,glandular dilatation,and deep nuclear staining,which had certain atypia.The positive expression rates of EZH2 and BMI-1 protein were 53.3%and 56%,which were close to those of colon cancer(66.7% and 76.6%)and higher than those of normal group and HP(16% and 8%,P<0.05).The relative expression of EZH2 and BMI-1 in SSA/P tissue was significantly higher than that in normal group and HP,but lower than that in carcinogenesis group(P<0.05).Conclusion:EZH2 and BMI-1 play an important role in the carcinogenesis of colon serrated adenoma,and can be used as the primary screening index before carcinogenesis.

基于“痰浊内阻”与“脂代谢紊乱”的联系论治结肠腺瘤复发与恶变

结直肠腺瘤作为结直肠癌的重要癌前病变,内镜下切除虽作为首要治疗手段,但腺瘤复发率较高,如何预防腺瘤的发生,阻断腺瘤癌序列的进展是我们的研究方向。中医理论中“痰浊内阻”是结肠腺瘤发生与复发的主要原因,并且“痰浊”与“脂代谢”二者联系密切,因此本文将就“痰浊内阻”与“脂代谢紊乱”在结肠腺瘤中的联系进行讨论,探讨结肠腺瘤“痰浊内阻”的现代生物学内涵。通过探讨二者之间的联系可为临床治疗结肠腺瘤提供思路,同时还可将其运用到其他有关痰浊内阻、脂代谢紊乱的疾病中,以扩展临床诊治思维。

结直肠腺瘤合并高级别上皮内瘤变的危险因素分析

目的探讨结直肠腺瘤(colorectal adenoma,CRA)合并高级别上皮内瘤变(high-grade intraepithelial neoplasia,HGIN)的独立危险因素。方法选取2022年1—12月于福建省立医院南院消化内镜中心接受全结肠镜检查且病理结果明确为CRA的256例住院患者。分析患者的基本信息,包括性别、年龄、身体质量指数(body mass index,BMI)、相关基础疾病病史、息肉部位和形态学信息、息肉术后病理信息等,采用单因素、多因素logistic回归分析CRA合并HGIN发生的危险因素。结果单因素logistic回归分析发现,年龄对CRA合并HGIN的影响差异有统计学意义(OR=1.037,95%CI 1.006~1.069,P=0.019);腺瘤数目对CRA合并HGIN的影响差异有统计学意义(OR=0.188,95%CI 0.065~0.543,P<0.001);腺瘤分叶状、病理组织类型、腺瘤部位、腺瘤形态、黏膜表面情况均对CRA合并HGIN的影响差异有统计学意义(P<0.001)。多因素logistic回归分析发现,高龄、病理组织类型为含绒毛状成分腺瘤、黏膜表面粗糙、糜烂均与CRA合并HGIN发病率高相关(P<0.05)。结论高龄、病理组织类型为含绒毛状成分腺瘤、黏膜表面粗糙、糜烂是CRA合并HGIN的独立危险因素。

高通量RNA测序技术分析结肠腺瘤转变为结肠癌的关键基因

目的:通过RNA测序技术分析比较正常结肠组织、结肠腺瘤及癌组织中基因表达谱的差异,识别从结肠腺瘤发展为结肠癌过程中的关键基因,并探究其潜在机制。方法:对同一患者的正常结肠组织、腺瘤及癌组织进行RNA测序分析,识别在结肠癌中显著表达、腺瘤组织中不显著表达的差异基因并进行GO和KEGG功能富集分析。结果:在结肠癌中显著表达、腺瘤组织中不显著表达的差异基因有4307个,其中5个差异最大的基因是EPYC、LINC01614、MCEMP1、NOX4、CLEC5A。对这些基因进行GO和KEGG功能富集分析发现,主要富集于生物过程调节、细胞过程调节、蛋白质结合等生物学过程和癌症通路、PI3K-Akt信号通路、MAPK信号通路等。结论:EPYC、LINC01614、MCEMP1、NOX4、CLEC5A等多个基因参与结肠腺瘤到结肠癌发展的过程,这些基因有望成为结直肠癌的治疗靶点。

Expression And Clinical Significance of Glucose Regulated Proteins GRP78 And GRP94 in Human Colon Cancer

Objective： To investigate the expression of glucose regulated proteins GRP78 and GRP94 in human colon cancer. Methods： Tissues of resected primary colon cancer, colon adenoma and normal tissue were investigated. Protein expression was detected with immunohistochemical staining, mRNA expression levels of GRP78 and GRP94 were determined by semiquantitative reverse transcriptase polymerase chain reaction （RT-PCR） after mRNA extraction. Results： The expression of GRP94 and GRP78 was significantly higher in colon cancer when compared to those in colon adenoma and normal tissue （P〈0.01）. GRP94 mRNA and protein expression was found to be in close relationship with the grade of differentiation, Dukes stages, lymph node involvement and remote metastasis in colon cancer （P〈0.01）, but no relationship with gender and age （P〉0.05）. GRP78 mRNA and protein expression increased with cancer progression along the normal tissue-adenoma-cancer sequence, but showed no association with grade of differentiation, Dukes stages, lymph node involvement, remote metastasis, gender and age （P〉0.05）. The mRNA expression of GRP78 and GRP94 was consistent with the proteins （P〈0.01）, but there is no correlation between overexpression of GRP78 and GRP94 （P〉0.05）, and the patients with both strong GRP78 and GRP94 protein expression did not show advanced tumor stages （P〉0.05）. Conclusion： Overexpression of GRP78 and GRP94 was found in colon cancer. Overexpression of GRP94 was closely related to cellular differentiation, Dukes stages, invasion and metastasis.

外周血相关指标在结肠癌和结肠腺瘤鉴别诊断中的临床价值研究

目的 探讨外周血中性粒细胞与白细胞比值(NWR)、淋巴细胞与白细胞比值(LWR)、癌胚抗原、糖类抗原125(CA125)在结肠癌和结肠腺瘤鉴别诊断中的临床价值。方法 收集2015年4月至2022年8月于山东第一医科大学附属省立医院确诊为结肠癌并行结肠癌根治术的129例结肠癌患者作为结肠癌组,随机收集同期结肠腺瘤患者129例作为结肠腺瘤组,回顾性分析比较2组患者的临床资料和外周血NWR、LWR、癌胚抗原、CA125水平,分析外周血4项指标与结肠癌病理特征的关系;绘制受试者工作特征(ROC)曲线,分析NWR、LWR、癌胚抗原、CA125单独及联合检测在结肠癌和结肠腺瘤鉴别诊断中的临床价值。结果 结肠癌组NWR、癌胚抗原、CA125水平均高于结肠腺瘤组,LWR低于结肠腺瘤组,差异均有统计学意义(均P<0.05)。浸润深度超过肌层的结肠癌患者癌胚抗原高于未超过肌层的患者,肿瘤直径≥7 cm患者外周血LMR低于肿瘤直径<7 cm的患者,而NWR、CA125水平高于肿瘤直径<7 cm的患者,差异均有统计学意义(均P<0.05)。ROC曲线分析结果显示,与单独检测[NWR曲线下面积(AUC)=0.746,95%置信区间:0.707~0.814;LWR AUC=0.739,95%置信区间:0.681~0.792;癌胚抗原AUC=0.572,95%置信区间:0.509~0.633;CA125 AUC=0.635,95%置信区间:0.573~0.694]相比,NWR、LWR、癌胚抗原和CA125联合检测可以提高对结肠癌与结肠腺瘤患者鉴别诊断的效能(AUC=0.799,95%置信区间:0.745~0.846)。结论 NWR、LWR、癌胚抗原和CA125联合检测对鉴别诊断结肠癌与结肠腺瘤患者具有一定的预测价值,可以辅助结肠癌诊断。

基于结肠癌组织芯片的腺苷酸活化蛋白激酶α表达及其意义初析

目的利用结肠癌组织芯片,研究腺苷酸活化蛋白激酶α(AMPKα)在正常结肠黏膜、腺瘤、腺癌及转移性结肠癌组织中的表达及临床病理学意义。方法采用SABC免疫组织化学法检测结肠癌组织芯片组织中AMPKα蛋白的表达情况,并利用Image J软件对阳性强度及阳性率进行半定量分析。结果与对应隐窝腺体比较,AMPKα在正常结肠黏膜中表面上皮的表达较高(t=3.053,P=0.030)。与正常黏膜比较,AMPKα在管状腺瘤组织中表达较低(t=5.545,P=0.014)。与正常黏膜及远端黏膜表面上皮分别比较,AMPKα在腺癌组织中表达较低(t=3.159,P=0.006;t=4.503,P=0.047)。AMPKα表达与结肠组织病变分类呈正相关(r=0.336,P<0.001),与腺癌不同临床分期无关(r=0.470,P=0.260),与异型增生/上皮内瘤变分级呈负相关(r=-0.453,P=0.028),亦与结肠癌病理分级呈负相关(r=-0.340,P=0.042)。结论伴随正常结肠黏膜上皮的成熟分化,AMPKα的表达呈增加趋势,并在黏膜表面上皮中显著高表达,在结肠腺瘤、腺癌和转移癌中AMPKα表达降低,提示AMPKα可能在抑制结肠腺癌的发生和发展中发挥积极作用。

内镜下黏膜切除术治疗结肠憩室腺瘤的疗效分析

背景:当结肠腺瘤累及憩室时,憩室内的炎症状态会增加腺瘤性病变的异型增生风险,故结肠憩室腺瘤更易发生恶变,需切除腺瘤以避免结肠癌结局,改善预后。目的:探讨内镜下黏膜切除术(EMR)治疗结肠憩室腺瘤的有效性和安全性。方法:连续收集2018年6月—2022年1月于杭州市临安区第一人民医院接受EMR治疗的14例结肠憩室腺瘤(憩室内部或憩室附近)病例,分析其临床特征和结局。主要结局指标为并发症,包括出血、穿孔和电凝综合征,次要结局指标为整块切除率、完全切除率和局部复发率。结果:14例结肠憩室腺瘤患者中,A型(憩室旁型)13例,B型(憩室内型)1例;病灶直径为(0.76±0.25)cm;手术时间为(19.67±5.33)min;组织学类型以管状腺瘤为主,病理性质以上皮内瘤变多见。1例(7.1%)患者发生迟发性出血,1例(7.1%)发生电凝综合征,未见穿孔事件。整块切除率、完全切除率均为100%。术后1年内10例复查结肠镜,均未发现局部复发。结论:EMR治疗结肠憩室腺瘤具有安全、有效的特点,但抗血小板药服用史和同时累及阑尾孔、憩室的结肠腺瘤患者需警惕术后并发症。

内镜下结肠黏膜切除术治疗结肠腺瘤的临床疗效分析

目的分析内镜下结肠黏膜切除术治疗结肠腺瘤的临床疗效。方法选取某院2020年3月~2023年3月纳入的80例结肠腺瘤患者,按照随机数字法分为对照组(n=40)和观察组(n=40),其中对照组采用常规内镜下电凝电切手术治疗,观察组采用内镜下结肠黏膜切除术治疗。评估两组患者手术相关指标、手术治疗结果、手术治疗情况。结果治疗后,观察组手术时间及平均住院天数明显短于对照组,且肿瘤完全切除,观察组手术切除率高于对照组(P<0.05);治疗后,两组患者的迟发性出血发生率经比较差异无统计学意义(P>0.05),观察组术后穿孔及术中出血明显少于对照组(P<0.05);治疗后,观察组术后残留率、残留复发率及术后复发率均低于对照组,术后并发症明显更少(P<0.05)。结论内镜下结肠黏膜切除术治疗可以有效缩短住院天数和手术时间,提高腺瘤完全切除率,且残留率较低,可以减少并发症的发生,具有较高的安全性。

结肠腺瘤内镜切除术后复发的影响因素分析

目的 分析结肠腺瘤内镜切除术后复发的影响因素。方法 收集2020年7月至2022年8月在桂林市人民医院消化内科住院,行结肠腺瘤内镜切除术并经病理确诊为结肠腺瘤的182例患者的临床资料。所有患者均行内镜下切除术治疗,根据术后是否复发分为复发组和未复发组,记录患者的一般临床特征及腺瘤特征,分析结肠腺瘤术后复发的影响因素。结果 182例患者中,复发43例,未复发139例,复发率为23.6%。两组的年龄、吸烟、糖尿病史、非酒精性脂肪性肝病(NAFLD)史比较,差异具有统计学意义(P<0.05)。两组的腺瘤直径、腺瘤数量、腺瘤病理类型比较,差异具有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,年龄≥60岁、吸烟、腺瘤数量≥3个、腺瘤病理类型为管状绒毛状腺瘤是术后结肠腺瘤复发的独立危险因素(P<0.05)。结论 结肠腺瘤内镜切除术后存在一定复发率,年龄≥60岁、吸烟、腺瘤数量≥3个、病理类型为管状绒毛状腺瘤是术后结肠腺瘤复发的独立危险因素。

Clear cell adenocarcinoma of the colon:A case report and review of literature

A primary clear cell adenocarcinoma of the colon is a rare oncologic entity. We herein report a case of such a tumor of the sigmoid colon in a 71-year-old woman who was successfully treated by an endoscopic polypectomy in our hospital. We also reviewed the published reports regarding cases of primary clear cell tumors in the colon.

Efficacy of cap-assisted colonoscopy according to lesion location and endoscopist training level

AIM: To evaluate the efficacy of cap-assisted colonoscopy(CAC) for detection of colorectal polyps and adenomas according to the lesion location and endoscopist training level.METHODS: Patients 20 years or older, who underwent their first screening colonoscopy in a single tertiary center from May 2011 to December 2012 were enrolled in this study. All patients underwent either CAC or standard colonoscopy(SC), and all of the procedures were performed by 11 endoscopists(8 trainees and 3 experts). All procedures were performed with highdefinition colonoscopes and narrow band imaging. The eight trainees had experiences of performing 150 to 500 colonoscopies, and the three experts had experiences of performing more than 3000 colonoscopies. A 4-mmlong transparent cap was attached to the end of a colonoscope in the CAC group. We retrospectively evaluated the number of polyps and adenomas, polyp detection rate(PDR), and the number of adenomas and adenoma detection rate(ADR) according to the lesion location and endoscopist training level between CAC and SC. We also evaluated the number of polyps and adenomas according to their size between CAC and SC.RESULTS: Overall, PDR and ADR using CAC were significantly higher than those using SC for both whole colon(48.5% vs 40.7%, P = 0.012; 35.7% vs 28.3%, P = 0.012) and right-side colon(35.3% vs 26.6%, P = 0.002; 27.0% vs 16.9%, P < 0.001). The number of polyps and adenomas per patient using CAC was significantly higher than that using SC for both the whole colon(1.07 ± 1.59 vs 0.82 ± 1.31, P = 0.008; 0.72 ± 1.32 vs 0.50 ± 1.01, P = 0.003) and right-side colon(0.66 ± 1.18 vs 0.41 ± 0.83, P < 0.001; 0.46 ± 0.97 vs 0.25 ± 0.67, P < 0.001). In the trainee group, the PDR and ADR using CAC were significantly higher than those using SC for both the whole colon(46.7% vs 39.7%, P = 0.040; 33.9% vs 26.0%, P =0.012) and right-side colon(34.2% vs 26.5%, P = 0.015; 25.3% vs 15.9%, P = 0.001). In the expert group, the PDR and ADR using CAC were significantly higher than those using SC only for the right-side colon(42.1% vs 27.0%, P =0.035; 36.8% vs 21.0%, P = 0.020).CONCLUSION: CAC is more effective than SC for detection of colorectal polyps and adenomas, especially when performed by trainees and when the lesions are located in the right-side colon.

Colonic manifestations of PTEN hamartoma tumor syndrome: Case series and systematic review

AIM: To investigate our clinical experience with the colonic manifestations of phosphatase and tensin homolog on chromosome ten (PTEN) hamartoma tumor syndrome (PHTS) and to perform a systematic literature review regarding the same.