Synchronous manifestation of colorectal cancer and intraductal papillary mucinous neoplasms

High rates of extrapancreatic malignancies,in particular colorectal cancer(CRC),have been detected in patients with intraductal papillary mucinous neoplasm(IPMN).So far,there is no distinct explanation in the literature for the development of secondary or synchronous malignancies in patients with IPMN.In the past few years,some data related to common genetic alterations in IPMN and other affiliated cancers have been published.This review elucidated the association between IPMN and CRC,shedding light on the most relevant genetic alterations that may explain the possible relationship between these entities.In keeping with our findings,we suggested that once the diagnosis of IPMN is made,special consideration of CRC should be undertaken.Presently,there are no specific guidelines regarding colorectal screening programs for patients with IPMN.We recommend that patients with IPMNs are at high-risk for CRC,and a more rigorous colorectal surveillance program should be implemented.

Analysis of 72 patients with colorectal high-grade neuroendocrine neoplasms from three Chinese hospitals

BACKGROUND Colorectal high-grade neuroendocrine neoplasms(HGNENs)are rare and constitute less than 1%of all colorectal malignancies.Based on their morphological differentiation and proliferation identity,these neoplasms present heterogeneous clinicopathologic features.Opinions regarding treatment strategies for and improvement of the clinical outcomes of these patients remain controversial.AIM To delineate the clinicopathologic features of and explore the prognostic factors for this rare malignancy.METHODS This observational study reviewed the data of 72 consecutive patients with colorectal HGNENs from three Chinese hospitals between 2000 and 2019.The clinicopathologic characteristics and follow-up data were carefully collected from their medical records,outpatient reexaminations,and telephone interviews.A survival analysis was conducted to evaluate their outcomes and to identify the prognostic factors for this disease.RESULTS According to the latest recommendations for the classification and nomenclature of colorectal HGNENs,61(84.7%)patients in our cohort had poorly differentiated neoplasms,which were categorized as high-grade neuroendocrine carcinomas(HGNECs),and the remaining 11(15.3%)patients had well differentiated neoplasms,which were categorized as high-grade neuroendocrine tumors(HGNETs).Most of the neoplasms(63.9%)were located at the rectum.More than half of the patients(51.4%)presented with distant metastasis at the date of diagnosis.All patients were followed for a median duration of 15.5 mo.In the entire cohort,the median survival time was 31 mo,and the 3-year and 5-year survival rates were 44.3%and 36.3%,respectively.Both the univariate and multivariate analyses demonstrated that increasing age,HGNEC type,and distant metastasis were risk factors for poor clinical outcomes.CONCLUSION Colorectal HGNENs are rare and aggressive malignancies with poor clinical outcomes.However,patients with younger age,good morphological differentiation,and without metastatic disease can have a relatively favorable prognosis.

Perivascular epithelioid cell neoplasm of the colon

A 17-year-old female presented with rectal bleeding from an ulcerated sigmoid mass in 1994.Initial pathological evaluation revealed a rare clear cell neoplasm of the colon,possibly originating from kidneys,adrenals,lung or a gynecologic source as a metastatic lesion.Extensive imaging studies were negative,and over the next 15 years,she remained well with no recurrence.The original resected neoplasm was reviewed and reclassified as a perivascular epithelioid cell neoplasm (PEComa).Although the long-term natural history of PEComas requires definition,increased clinical and pathological awareness should lead to increased recognition of an apparently rare type of colonic neoplasm that likely occurs more often than is currently appreciated.

No association between cyclooxygenase-2 and uridine diphosphate glucuronosyltransferase 1A6 genetic polymorphisms and colon cancer risk

AIM:To investigate the association of variations in the cyclooxygenase-2(COX2) and uridine diphosphate glucuronosyltransferase 1A6(UGT1A6) genes and non-steroidal anti-inflammatory drugs(NSAIDs) use with risk of colon cancer.METHODS:NSAIDs,which are known to reduce the risk of colon cancer,act directly on COX2 and reduce its activity.Epidemiological studies have associated variations in the COX2 gene with colon cancer risk,but others were unable to replicate this finding.Similarly,enzymes in the UGT1A6 gene have been demonstrated to modify the therapeutic effect of NSAIDs on colon adenomas.Polymorphisms in the UGT1A6 gene have been statistically shown to interact with NSAID intake to influence risk of developing colon adenomas,but not colon cancer.Here we examined the association of tagging single nucleotide polymorphisms(SNPs) in the COX2 and UGT1A6 genes,and their interaction with NSAID consumption,on risk of colon cancer in a population of 422 colon cancer cases and 481 population controls.RESULTS:No SNP in either gene was individually statistically significantly associated with colon cancer,nor did they statistically significantly change the protective effect of NSAID consumption in our sample.Like others,we were unable to replicate the association of variants in the COX2 gene with colon cancer risk(P > 0.05),and we did not observe that these variants modify the protective effect of NSAIDs(P > 0.05).We were able to confirm the lack of association of variants in UGT1A6 with colon cancer risk,although further studies will have to be conducted to confirm the association of these variants with colon adenomas.CONCLUSION:Our study does not support a role of COX2 and UGT1A6 genetic variations in the development of colon cancer.

No association between phosphatase and tensin homolog genetic polymorphisms and colon cancer

AIM: To investigate the association between single nucleotide polymorphisms (SNPs) in the phosphatase and tensin homolog (PTEN) tumor suppressor gene and risk of colon cancer. METHODS: We utilized a population-based casecontrol study of incident colon cancer individuals (n= 421) and controls (n = 483) aged ≥ 30 years to conduct a comprehensive tagSNP association analysis of the PTEN gene. RESULTS: None of the PTEN SNPs were statistically significantly associated with colon cancer when controlled for age, gender, and race, or when additionally adjusted for other known risk factors (P > 0.05). Haplotype analyses similarly showed no association between the PTEN gene and colon cancer. CONCLUSION: Our study does not support PTEN as a colon cancer susceptibility gene.

Incidence of colorectal neoplasms among male pilots

AIM: To assess the prevalence of colorectal neoplasms(adenomas, advanced adenomas and colorectal cancers) among Israeli military and commercial airline pilots.METHODS: Initial screening colonoscopy was performed on average-risk(no symptoms and no family history) airline pilots at the Integrated Cancer Prevention Center(ICPC) in the Tel-Aviv Medical Center. Visualized polyps were excised and sent for pathological examination. Advanced adenoma was defined as a lesion >10 mm in diameter, with high-grade dysplasia or villous histology. The results were compared with those of an age- and gender-matched random sample of healthy adults undergoing routine screening at the ICPC.RESULTS: There were 270 pilots(mean age 55.2 ± 7.4 years) and 1150 controls(mean age 55.7 ± 7.8 years). The prevalence of colorectal neoplasms was 15.9% among the pilots and 20.6% among the controls(P = 0.097, χ2 test). There were significantly more hyperplastic polyps among pilots(15.5% vs 9.4%, P = 0.004) and a trend towards fewer adenomas(14.8% vs 20.3% P = 0.06). The prevalence of advanced lesions among pilots and control groups was 5.9% and 4.7%, respectively(P = 0.49), and the prevalence of cancer was 0.7% and 0.69%, respectively(P = 0.93).CONCLUSION: There tends to be a lower colorectal adenoma, advanced adenoma and cancer prevalence but a higher hyperplastic polyp prevalence among pilots than the general population.

Role of Genetic Ancestry in Oropharyngeal Squamous-Cell Carcinoma: A Cross-Sectional Study in Brazil

Background: HPV infection represents an important etiologic factor for Oropharyngeal Squamous Cell Carcinoma (OPSCC). The different ethnic backgrounds could be related to different susceptibility to Human Papillomavirus (HPV). The aim of our study was to assess the whole of genetic ancestry in HPV status in OPSCC patients. Methods: We conducted a cross-sectional study on patients with OPSCC admitted to the Barretos Cancer Hospital, Brazil from 2014 to 2019. Of these, DNA extraction was performed on 40 patients and genetic ancestry was assessed using a specific panel of 46 informative ancestry markers. Results: We observed a predominance of European ancestry (63%), followed by African (18%), Amerindian (9%) and Asian (8%) both in the OPSCC HPV-positive and HPV-negative group. We did not find any statistically significant differences between the HPV-positive and HPV-negative OPSCC groups in relation to European (p = 0.499), African (p = 0.448), Asian (p = 0.275) or Amerindian (p = 0.836) ancestry. Conclusions: We found a predominance of European ancestry, both in the HPV-positive and HPV-negative groups. In our study, we did not find statistically significant differences between HPV-positive or HPV-negative groups in relation to ancestry.

Genetic polymorphisms in genes regulating cell death and prognosis of patients with rectal cancer receiving postoperative chemoradiotherapy

Objective:The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment.This study determined the effects of genetic variations in genes involved in apoptosis,pyroptosis,and ferroptosis on the prognosis of patients with locally advanced rectal cancer receiving postoperative chemoradiotherapy(CRT).Methods:The Sequenom MassARRAY was used to detect 217 genetic variations in 40 genes from 300 patients with rectal cancer who received postoperative CRT.The associations between genetic variations and overall survival(OS)were evaluated using hazard ratios(HRs)and 95%confidence intervals(CIs)computed using a Cox proportional regression model.Functional experiments were performed to determine the functions of the arachidonate 5-lipoxygenase(ALOX5)gene and the ALOX5 rs702365 variant.Results:We detected 16 genetic polymorphisms in CASP3,CASP7,TRAILR2,GSDME,CASP4,HO-1,ALOX5,GPX4,and NRF2 that were significantly associated with OS in the additive model(P<0.05).There was a substantial cumulative effect of three genetic polymorphisms(CASP4 rs571407,ALOX5 rs2242332,and HO-1 rs17883419)on OS.Genetic variations in the CASP4 and ALOX5 gene haplotypes were associated with a higher OS.We demonstrated,for the first time,that rs702365[G]>[C]represses ALOX5 transcription and corollary experiments suggested that ALOX5 may promote colon cancer cell growth by mediating an inflammatory response.Conclusions:Polymorphisms in genes regulating cell death may play essential roles in the prognosis of patients with rectal cancer who are treated with postoperative CRT and may serve as potential genetic biomarkers for individualized treatment.

SLC6A9对结直肠癌细胞生长和对5-FU药物敏感性的影响

目的:研究溶质载体家族6成员9(solute carrier family 6 member 9,SLC6A9)表达对结直肠癌细胞增殖、迁移和5-氟尿嘧啶(5-fluorouracil,5-FU)药物敏感性的影响。方法:TCGA数据库分析、实时荧光定量PCR和Western blot分析检测SLC6A9在结肠癌组织、正常结肠细胞系(NCM460)和结直肠癌细胞系(SW620、HCT116、HT29、Lovo和SW480)中的表达。将SCL6A9过表达质粒及阴性对照(SLC6A9 OE、Vector)转染HT29细胞,将SCL6A9小干扰RNA及阴性对照(SLC6A9 siRNA1#、siRNA2#和Scramble)转染SW620细胞。划痕愈合实验和Transwell实验检测各组细胞的迁移、侵袭能力。Western blot和细胞免疫荧光检测EMT相关蛋白E-cadherin、Vimentin的表达水平。利用CCK-8法和构建裸鼠移植瘤模型检测SLC6A9过表达对结直肠癌细胞5-FU药物敏感性的影响。结果:与正常结肠组织和NCM460细胞相比,SLC6A9在结肠癌组织和结直肠癌细胞系中低表达(均P<0.05)。SLC6A9过表达引起E-cadherin蛋白表达增加,Vimentin蛋白水平降低,抑制结直肠癌细胞的迁移、侵袭(P<0.05)。SLC6A9低表达引起E-cadherin蛋白表达降低,Vimentin蛋白水平增加,促进结直肠癌细胞的迁移、侵袭能力(P<0.05)。SLC6A9过表达提高了5-FU的药物敏感性,并使肿瘤生长缓慢,质量减轻(P<0.05)。而SLC6A9低表达降低了5-FU的药物敏感性(P<0.05)。结论:SLC6A9过表达能够抑制结直肠癌细胞的迁移、侵袭和EMT进程,并增强5-FU对结直肠癌细胞的药物敏感性。

全腹腔镜下肠吻合与辅助切口肠吻合在右半结肠癌根治术中的临床疗效对比

目的:对比分析全腹腔镜下肠吻合与辅助切口肠吻合在腹腔镜右半结肠癌根治术中的临床疗效。方法:回顾分析2017年1月至2022年10月收治的拟手术治疗的右半结肠癌患者的临床资料,根据消化道重建方式分为观察组(全腹腔镜下肠吻合)与对照组(辅助切口肠吻合)。收集两组患者临床资料(年龄、性别、体质指数)、手术时间、术中出血量、手术切口长度、淋巴结清扫数量、术后疼痛评分、术后首次排气时间与排便时间、术后下床活动时间、切口愈合时间、住院时间及术后并发症发生率。结果:共纳入152例患者,其中观察组74例,对照组78例。与对照组相比,观察组术后疼痛评分低,手术切口、术后首次排气时间、术后首次排便时间、术后下床行走时间、切口愈合时间短,差异有统计学意义(P<0.05);两组手术时间、淋巴结清扫数量、术中出血量及术后并发症发生率差异无统计学意义(P>0.05)。结论:与腹腔镜辅助切口肠吻合术相比,全腹腔镜肠吻合的临床疗效更佳,值得临床推广。

结肠癌病人血清S100钙结合蛋白A12、可溶性晚期糖基化终产物受体水平与肠道菌群失调及化疗效果的关系

目的探讨结肠癌病人血清S100钙结合蛋白A12(S100A12)、可溶性晚期糖基化终产物受体(sRAGE)水平与肠道菌群失调及化疗效果的相关性。方法选择2020年12月至2021年12月黄河水利委员会黄河中心医院收治的116例中、晚期结肠癌病人作为结肠癌组,另选取在该院同期健康体检人员120例作为对照组。采用酶联免疫吸附测定(ELISA)检测血清S100A12、sRAGE水平,检测病人肠道菌群,并对病人化疗后进行随访,Pearson法分析结肠癌病人血清S100A12、sRAGE水平与菌群失调相关性,受试者操作特征曲线(ROC曲线)分析化疗前血清S100A12、sRAGE水平对结肠癌化疗效果的诊断价值。结果与对照组比较,结肠癌组病人化疗前血清S100A12、sRAGE水平显著升高(P<0.05)。与化疗前菌群正常组[(265.34±45.78)μg/L、(381.54±36.75)ng/L]比较,菌群失调Ⅰ度组[(301.52±56.95)μg/L、(440.63±48.71)ng/L]、菌群失调Ⅱ度组[(339.29±52.35)μg/L、(432.75±49.20)ng/L]病人血清S100A12、sRAGE水平显著升高(P<0.05);与菌群失调Ⅰ度组比较,菌群失调Ⅱ度组病人血清S100A12、sRAGE水平显著升高(P<0.05)。相关性分析显示,结肠癌病人血清S100A12、sRAGE水平与大肠杆菌、粪肠球菌数量呈正相关(P<0.05),与双歧杆菌、乳酸杆菌数量呈负相关(P<0.05)。与化疗前比较,结肠癌病人化疗后血清S100A12、sRAGE水平显著降低(P<0.05);与化疗缓解组[(272.33±55.36)μg/L、(403.24±40.54)ng/L]比较,化疗无效组[(330.09±42.64)μg/L、(482.85±43.61)ng/L]病人化疗前血清S100A12、sRAGE水平显著较高(P<0.05)。血清S100A12、sRAGE联合诊断结肠癌化疗无效的曲线下面积(AUC)为0.91[95%CI:(0.84,0.96),P<0.001],灵敏度为86.05%,特异度为80.82%。结论结肠癌病人血清S100A12、sRAGE升高,与肠道菌群失调及化疗效果有关,对化疗疗效评估与预后评价有一定指导意义。

结肠癌中Hsp90α的表达及临床意义

目的探讨热休克蛋白90α(heat shock protein 90α,Hsp90α)在结肠癌中的表达及潜在的临床价值。方法采用生物信息学和免疫组化法分析结肠癌中Hsp90α的表达水平,及其与临床病理学特征、预后和免疫细胞浸润水平的关系;采用CCK-8细胞增殖实验和平板克隆实验检测敲除Hsp90AA1前后结肠癌细胞的增殖能力。结果生物信息学分析结果显示,Hsp90AA1在结肠癌组织中异常高表达,其表达水平越高,患者预后越差;Hsp90AA1表达与CD4^(+)T细胞(Th2)、CD8^(+)T细胞、髓样抑制细胞、Tregs细胞、中性粒细胞、巨噬细胞、M1巨噬细胞、M2巨噬细胞的浸润水平呈正相关;免疫组化结果显示结肠癌组织中Hsp90α表达明显高于癌旁正常组织,Hsp90α表达与患者性别、肿瘤大小、位置、分化程度、TNM分期、淋巴结转移、脉管癌栓、神经侵犯、远处转移等无关(P>0.05),与结肠癌患者年龄具有相关性(P<0.05)。Hsp90α高表达是影响结肠癌患者预后的独立危险因素。细胞实验结果显示,敲除Hsp90AA1可抑制结肠癌细胞的生长及增殖能力。结论Hsp90α在结肠癌中高表达,可能是结肠癌预后不良的潜在分子学标志物。

结肠神经内分泌肿瘤临床病理和预后分析

目的探讨结肠神经内分泌肿瘤(colonic neuroendocrine neoplasms,CNENs)的临床病理特征,并分析其预后相关因素。方法回顾性收集2012年1月至2022年12月华中科技大学同济医学院附属协和医院收治的28例CNENs病人资料,分析左半结肠和右半结肠神经内分泌肿瘤的临床特征差异,采用Kaplan-Meier曲线进行生存分析,并总结影响CNENs病人预后的临床因素。结果28例病人中男性18例、女性10例,年龄52.0~64.0岁,中位年龄为57.0岁。肿瘤长径<2 cm者5例,≥2 cm者23例。28例病人中19例肿瘤位于右半结肠,9例位于左半结肠,对比左半结肠神经内分泌肿瘤,位于右半结肠者肿瘤长径较大、T分期较晚(均P<0.05)。28例病人中行内镜下黏膜切除术2例,内镜黏膜下剥离术追加外科手术局部切除1例,内镜黏膜下剥离术追加根治性切除术1例,根治性切除术12例,姑息性切除术7例,未行手术治疗5例。T1期病人6例,T3期病人5例,T4期病人17例。20例行根治性切除/姑息性切除+淋巴结清扫术的病人中,15例经病理学证实伴有淋巴结转移。28例病人中10例伴有远处转移。28例病人均获得随访,中位随访时间为34.5个月(3.0~118.0个月)。随访期间11例病人因CNENs疾病进展死亡;28例病人中7例为不伴远处转移的结肠神经内分泌瘤(colonic neuroendocrine tumors,CNETs)病人,接受原发肿瘤切除术后均获得长期生存。预后单因素分析结果提示肿瘤长径、病理分类、浸润深度和M分期(均P<0.05)与肿瘤特异性生存率相关。在多因素分析中,M分期与预后显著相关[HR=8.958,95%CI(2.241,35.811),P=0.002]。结论CNENs转移率高,预后整体较差。对不伴有远处转移的CNETs,原发肿瘤切除术疗效好。

光谱CT多参数成像术前预测结肠癌神经及脉管侵犯状态的价值

目的:探讨光谱CT多参数成像术前预测结肠癌神经侵犯(PNI)及脉管侵犯(LVI)状态的价值。方法:搜集2021年9月至2022年9月在昆明医科大学第一附属医院行光谱CT扫描并经术后病理确诊为结肠癌的64例患者的临床及影像资料,根据术后病理中PNI/LVI的状态分为阳性组(29例)和阴性组(35例)。测量光谱CT动脉期、静脉期40 keV、90 keV单能级图像上病灶的CT值(CT40keV、CT90keV)、碘浓度(IC)、标准化碘浓度(NIC)、有效原子序数(Zeff)及标准化有效原子序数(NZeff),并计算光谱曲线斜率λ。比较两组间各光谱参数的差异,绘制受试者工作特征(ROC)曲线并计算曲线下面积(AUC)、敏感度、特异度及最佳阈值,以评估各参数的预测效能。结果:结肠癌PNI/LVI阳性组的动脉期和静脉期光谱CT定量参数CT40keV、IC、NIC、Zeff、NZeff及λ均高于阴性组,差异均有统计学意义(P均<0.05),而两组间动脉期和静脉期的CT90keV差异无统计学意义(P均>0.05)。ROC曲线分析结果显示,动脉期各参数预测结肠癌PNI/LVI状态的效能高于静脉期,其中以动脉期IC的预测效能最佳,其AUC值、敏感度和特异度分别为0.783(95%CI:0.672~0.894)、82.76%和65.71%。结论:光谱CT定量参数CT40keV、IC、NIC、Zeff、NZeff及λ在术前预测结肠癌PNI/LVI状态中具有一定价值,以动脉期IC的预测效能最佳。

SH2B3基因在髓系肿瘤中的突变位点及频率分析

目的:分析SH2B接头蛋白3(SH2B3)基因在髓系肿瘤中的突变位点及频率。方法:回顾性分析2017年11月至2022年11月首都医科大学宣武医院血液内科髓系肿瘤相关基因靶向DNA测序结果,筛选出携带SH2B3基因突变的患者,收集患者人口学资料及临床资料,分析SH2B3基因突变类型、突变位点、发生频率、共突变基因以及与疾病间的关系。结果:测序结果来自1005例患者,有19例患者检测到SH2B3基因突变,其中错义突变18例(94.74%),无义突变1例(5.26%),10例患者同时伴发其他突变(52.63%),突变等位基因频率(VAF)分布于0.03-0.66;发生频率最高的突变为p.Ile568Thr(5/19,26.32%),平均VAF为0.49,涉及1例MDS/MPN-RS(伴SF3B1突变)、1例MDS-U(伴SF3B1突变)、1例再生障碍性贫血伴PNH克隆(伴PIGA和KMT2A突变)、2例MDS-MLD(其中1例伴SETBP1突变);其余突变包括2例p.Ala567Thr(10.53%),p.Arg566Trp、p.Glu533Lys、p.Met437Arg、p.Arg425Cys、p.Glu314Lys、p.Arg308*、p.Gln294Glu、p.Arg282Gln、p.Arg175Gln、p.Gly86Cys、p.His55Asn和p.Gln54Pro各1例。结论:SH2B3基因在髓系肿瘤中突变位点分布较广,重现性低,其中p.Ile568Thr突变发生率较高,常与其他疾病特征性突变共存。

单中心腹腔镜与开腹手术治疗T_(3)~T_(4a)期结肠癌的近远期疗效比较

目的:比较腹腔镜与开腹手术治疗T_(3)~T_(4a)期结肠癌围术期疗效及远期生存情况。方法:选取2018年1月1日至2019年12月31日采用腹腔镜与开腹手术治疗的T_(3)~T_(4a)期结肠癌患者,分为腹腔镜组(n=102)与开腹组(n=43),分析两组围手术期资料、术后并发症、总生存期、无瘤生存期、1年与3年生存率及无瘤生存率、总生存率、总无瘤生存率、肿瘤复发转移情况。结果:两组患者基线资料差异无统计学意义(P>0.05)。腹腔镜组术中出血量少于开腹组[50.00(20.00,50.00)mL vs. 50.00(50.00,100.00)mL,P<0.001],获取淋巴结数量多于开腹组[17.00(14.00,22.00)枚vs. 14.00(11.00,20.00)枚,P=0.018],术后恢复进食时间[3.00(3.00,4.00)d vs. 4.00(3.00,6.00)d,P<0.001]、排气时间[3.00(3.00,3.00)d vs. 4.00(3.00,5.00)d,P<0.001]短于开腹组,术后总体并发症与不完全肠梗阻发生率低于开腹组(32.35%vs. 51.16%,3.92%vs. 16.28%,P<0.05)。两组术后1年、3年生存率及无瘤生存率、总生存率、总无瘤生存率、肿瘤复发转移率差异无统计学意义(P>0.05)。在T_(4a)亚组中,腹腔镜组与开腹组的各项生存指标差异均无统计学意义(P>0.05)。结论:腹腔镜手术治疗T_(3)~T_(4a)期结肠癌是安全、可行的,更利于术后恢复,可取得与开腹手术相当的肿瘤治疗效果。

直径<10 mm结直肠息肉发生高危腺瘤的风险因素分析

目的探讨直径<10 mm结直肠息肉发生高危腺瘤的相关风险因素。方法选取2019年10月至2021年3月解放军总医院第一医学中心和解放军总医院海南医院接受结肠镜检查的患者作为研究对象。根据腺瘤数量和病理特征,将患者分为高危腺瘤组和非高危腺瘤组。分析高危腺瘤发生的风险因素。结果本研究共1267例患者纳入统计分析,其中高危腺瘤组341例(26.9%),非高危腺瘤组926例(73.1%)。高危腺瘤组的年龄(45~<75岁)、男性、饮酒史、吸烟史、频繁食用腌制食品、高盐饮食、慢性病史、结直肠息肉史及最大息肉直径(>5~<10 mm)占比高于非高危腺瘤组(P<0.05)。年龄(45~<75岁)、男性、高盐饮食、偶发肛门坠胀、慢性病史,及最大息肉直径(>5~<10 mm)为高危腺瘤发生的危险因素(OR>1,P<0.05)。结论年龄(45~<75岁)、男性、高盐饮食、偶发肛门坠胀、慢性病史,及最大息肉直径(>5~<10 mm)是直径<10 mm结直肠息肉高危腺瘤发生的影响因素,为内镜医师评估风险及有针对性应用“切除和丢弃策略”提供了基础。

Rap1 GTP酶激活蛋白对结肠癌细胞增殖、侵袭和迁移作用的影响

目的探讨Rap1 GAP在结肠癌组织中的表达及与临床病理特征和预后的相关性。方法采用免疫组化EnVision两步法检测125例结肠癌组织中Rap1 GAP蛋白表达水平,应用Western blot法检测结肠癌细胞系(LOVO、HCT116、SW480)和正常结肠上皮细胞HCoEPiC中Rap1 GAP蛋白表达。通过慢病毒转染LOVO、HCT116和SW480细胞,分别下调、上调Rap1 GAP的表达,根据不同处理分为空载组(sh-NON、LV-NON)、sh-Rap1 GAP组(低表达Rap1 GAP)和LV-Rap1 GAP组(过表达Rap1 GAP),Western blot法验证细胞转染效率;采用MTT实验和Transwell实验分别检测各组细胞的增殖、侵袭和迁移能力。结果125例结肠癌标本中,Rap1 GAP缺失表达者83例(66.4%),高于癌旁对照组织(7.2%)(P<0.001)。Rap1 GAP缺失表达率与肿瘤分化程度(χ^(2)=6.152,P=0.011)、是否伴黏液腺癌(χ^(2)=4.908,P=0.028)有关,与患者性别、年龄、肿瘤发生部位、临床分期、淋巴结转移均无关(P>0.05)。Western blot结果显示,与HCoEPiC(0.189±0.081)细胞相比,LOVO(0.238±0.008)细胞中Rap1 GAP蛋白表达增高,HCT116(0.064±0.002)和SW480(0.152±0.026)细胞中Rap1 GAP蛋白表达降低(F=159.6,P<0.05)。LOVO细胞转染Rap1 GAP低表达慢病毒后,sh-Rap1 GAP-1组(0.733±0.071)、sh-Rap1 GAP-2组(0.559±0.136)和sh-Rap1 GAP-3组(0.606±0.037)Rap1 GAP蛋白表达水平明显低于LOVO组(1.880±0.129)(F=49.57,P<0.05)。与sh-NON组(1.260±0.109)相比,sh-Rap1 GAP-2组(1.569±0.059)和sh-Rap1 GAP-3组(1.548±0.087)细胞72 h增殖能力明显提高(F=28.36,P<0.05),其侵袭和迁移能力明显增高(P<0.05)。HCT116细胞转染Rap1 GAP过表达慢病毒后,与LV-NON组(0.485±0.097)相比,LV-Rap1 GAP组(1.395±0.137)Rap1 GAP蛋白表达明显较高(P<0.05)。MTT实验结果显示,与LV-NON组(0.652±0.047)相比,LV-Rap1 GAP组(1.212±0.038)细胞增殖能力降低,其侵袭和迁移能力明显降低(P<0.05)。SW480细胞的转染结果及增殖、侵袭和迁移能力与HCT116细胞一致。结论Rap1 GAP缺失表达率与结肠癌分化程度、是否伴黏液腺癌有关,上调Rap1 GAP表达能抑制结肠癌细胞增殖、侵袭和迁移能力,可为探究结肠癌的发生、发展机制提供理论依据。

结肠癌患者550例3年期生存分析及预后影响因素回归模型构建

目的探讨结肠癌患者550例3年期生存情况及预后影响因素,并构建回归模型。方法回顾性分析我院接受手术治疗后出院的结肠癌患者550例的临床资料,根据随访3年后是否存活将其分为预后不良组(死亡,134例)和预后良好组(生存,416例)。统计3年期生存情况,比较2组临床资料,并采用多因素Cox回归分析法分析影响结肠癌患者预后的危险因素,构建Cox回归模型。结果随访3年后,550例结肠癌患者有416例生存,3年生存率为75.64%。预后不良组年龄>60岁、分化程度低、腺鳞癌、未分化癌、Dukes分期C期、D期、右半结肠癌、有家族史、有并发症、有淋巴结转移、血清癌胚抗原水平异常、手术中间入路、淋巴结清扫个数<12个、术中出血量≥200 mL的患者占比分别为79.85%、48.25%、14.18%、10.45%、33.58%、65.67%、85.82%、22.39%、95.52%、59.96%、71.64%、67.16%、58.96%、89.55%,均高于预后良好组的52.40%、16.59%、1.20%、1.44%、2.64%、0.00%、41.83%、9.13%、84.62%、28.37%、31.25%、33.17%、41.11%、9.86%;已婚的患者占比为24.63%,低于预后良好组的75.48%(P<0.05)。多因素Cox回归分析结果显示,年龄>60岁、Dukes分期C、D期、右半结肠癌、有淋巴结转移、术中出血量≥200 mL是结肠癌患者预后不良的独立危险因素(P<0.05)。并构建预测模型结果显示,内部验证一致性指数为0.852(95%CI:0.819~0.885),校正曲线显示预测值与观察值具有良好的一致性。结论年龄>60岁、Dukes分期C、D期、右半结肠癌、有淋巴结转移、淋巴结清扫个数<12个、术中出血量≥200 mL是结肠癌患者预后不良的危险因素,其Cox回归模型有效且拟合效果较好,临床针对伴有以上情况的患者可给予相应的治疗及干预措施,以改善预后。

肿瘤免疫评分联合中性粒细胞与淋巴细胞比值、 血小板与淋巴细胞比值对结肠癌术后预后的价值研究

目的探究免疫评分(IS)单独及联合外周血炎症标志物对结肠癌病人术后预后的预测价值。方法以2013年1月至2019年12月在山西医科大学第一医院接受结肠癌根治术81例为研究对象,进行为期5年的跟踪随访。收集病人所有的临床病理资料,并通过免疫组化对所有病人术后病理标本进行免疫评分。行χ^(2)检验、Kaplan-Meier生存分析、Cox回归、构建列线图(nomogram)模型和时间依赖的受试者操作特征曲线(tROC曲线)等分析比较临床病理因素、免疫评分、外周血炎症标志物等与病人总生存期(OS)和无病生存期(DFS)的关系。结果生存分析结果显示,高免疫评分水平与病人的TNM分期(38例Ⅰ~Ⅱ期,43例Ⅲ~Ⅳ期,P=0.006)、术前糖类抗原199(64例CA199≤35μg/L,17例CA199>35μg/L,P=0.038)有关。免疫评分(IS≥3比IS<3)、中性粒细胞与淋巴细胞比值(NLR≤2.82比NLR>2.82)、血小板与淋巴细胞比值(PLR≤113.15比PLR>113.15)、术前糖类抗原199(CA199)(CA199≤35μg/L比CA199>35μg/L)是病人的独立预后因素。将有预后价值的变量整合,建立OS和DFS的列线图预测模型,模型C指数为0.79和0.76,校准曲线均表现出良好的一致性。tROC曲线也证明了该列线图模型预测结肠癌术后的预后价值高于单一指标和传统的TNM分期系统,其曲线下面积(AUC)分别为0.88(3年OS)、0.85(5年OS)、0.84(3年DFS)、0.82(5年DFS)。结论免疫评分联合NLR、PLR、CA199对结肠癌病人术后预后有较高的预测价值,可为结肠癌预后判断及治疗方案的选择提供依据,值得临床推广应用。