粪便钙卫蛋白在结直肠癌中的研究进展

粪便钙卫蛋白(fecal calprotectin, FC)是一种由肠腔内炎性细胞分泌的生物活性蛋白,有抗微生物活性、抗感染等作用,通过其含量高低可反映肠道的炎症状态,其在炎性肠病中的作用已被应用于临床实践.近年来,关于FC在结直肠癌(colorectal cancer, CRC)中的应用研究逐渐增多,相关研究结果显示FC可用于CRC的筛查以及和其他肠道器质性疾病的鉴别,同时, FC的浓度与CRC的分期、发生部位以及手术可能有一定的相关性,但仍需要进一步通过高质量、大样本研究以明确.本文就FC在CRC中的研究进展作一综述.     

联合检测粪便癌胚抗原和钙卫蛋白诊断大肠癌的临床价值

目的联合检测粪便中癌胚抗原（CEA）及钙卫蛋白,探讨其诊断大肠癌的临床应用价值。方法收集北京军区总医院消化内镜中心接受肠镜检查病人的新鲜粪便标本共177例,其中大肠癌48例,结直肠息肉51例,功能性肠病78例。采用ELISA法半定量检测粪便中钙卫蛋白及癌胚抗原浓度,比较其在不同组中的差异;应用ROC曲线确定最佳临界值,并对两个检测指标进行综合评价。结果大肠癌组粪便钙卫蛋白及CEA含量的中位数分别为470（0．9—1380．61）μg,／g,19．42（0．46～109．78）μg／g,高于其余组,差异有统计学意义（P〈0．05）;肿瘤发生部位不同的患者粪便钙卫蛋白及CEA的水平无明显差异（P〉0．05）;ROC曲线分析提示：以12．09μg／g为临界点,CEA诊断大肠癌的灵敏度为73％,特异度为56％;以104．2μg／g为临界点,钙卫蛋白诊断大肠恶性肿瘤的灵敏度为90．1％,特异度为54．2％;钙卫蛋白联合CEA诊断大肠癌的灵敏度为97．3％,特异度为30．35％。结论粪便钙卫蛋白及CEA检测大肠癌有较高的敏感性,且不受肿瘤部位的影响,可以作为门诊筛查大肠癌的标志物。     

粪便钙卫蛋白在溃疡性结肠炎诊断中的作用价值

溃疡性结肠炎(ulcerative colitis,UC)是常见的肠道疾病。目前的诊断主要依靠肠镜,但是肠镜检查患者要承受一定的痛苦。本文对最新的检测指标钙卫蛋白(calprotectin,CP)在UC诊断中的作用作一综述。     

粪便钙卫蛋白检测在肠道疾病诊断中的价值

钙卫蛋白(calprotectin)是近年来新发现的一种急性炎症标志物,最早于1980年从中性粒细胞中分离发现,是一种杂合性的钙结合蛋白,具有抗蛋白酶的活性,并因具有螯合锌离子的能力而具有抗热性。钙卫蛋白是中性粒细胞更新的标志物,具有抗微生物、调节免疫、抗增殖、传递信号等多种生物学功能,在许多炎症情况下升高。研究发现,炎症性肠病(IBD)患者粪便中的钙卫蛋白水平明显高于结肠癌患者及肠易激综合征(IBS)患者,并且同患者病变程度呈正相关。因此,可以作为一项诊断指标区分IBD、结肠癌、IBS,并用来监测IBD活动性,对疾病的复发、治疗效果具有重要指导意义。     

粪便钙卫蛋白检测在结肠息肉中的应用价值

结肠癌是一个很重要的健康问题,在全球有很高的发病率。结肠息肉是结肠癌的一种癌前病变,尤其是腺瘤性息肉,因此提高对结肠息肉的诊治水平,可以降低结肠癌的发生。钙卫蛋白作为急性炎性细胞活化的标志物,目前已有大量研究证实粪钙卫蛋白在胃肠道炎症性病变中高表达,特别是对炎症性肠病的病情活动评估及预测复发等方面已有较明确结论。结肠息肉作为肠道炎症病变的结果,也有研究证实结肠息肉患者粪便中钙卫蛋白水平是升高的,现综述如下。     

粪便钙卫蛋白联合粪便免疫化学试验在溃疡性结肠炎患者黏膜愈合中的诊断价值

目的 探讨粪便钙卫蛋白(FC)联合粪便免疫化学试验(FIT)在诊断溃疡性结肠炎(UC)患者黏膜愈合(MH)的临床应用价值。方法 前瞻性纳入2020年9月至2021年6月首都医科大学附属北京友谊医院消化内科门诊就诊UC患者60例。根据Mayo内镜评分(MES)将UC患者分成黏膜未愈合组(MES≥2,n=39)和黏膜愈合组(MES≤1,n=21)。利用酶联免疫吸附试验(ELISA)测定FC水平,利用全自动粪便血红蛋白分析仪测定各组FIT水平。利用受试者工作特征(ROC)曲线评估FC和FIT单独或联合检测对UC患者黏膜愈合的判断效能。结果 纳入60例UC患者,中位年龄37.5岁,其中男性占58.3%,临床缓解期患者占40.0%。黏膜愈合组FC、FIT水平均低于黏膜未愈合组(P<0.01)。在黏膜未愈合UC患者中,FC联合FIT检测预测的ROC曲线下面积为0.846(95%CI∶0.749～0.943),高于单独FC或FIT检测[0.770(95%CI∶0.636～0.905),cut off值281.8μg/g(P=0.001)或0.833(95%CI∶0.731～0.936),cut...     

粪便钙卫蛋白对儿童溃疡性结肠炎诊断和治疗的指导作用

目的探讨粪便钙卫蛋白对儿童溃疡性结肠炎(UC)诊断及治疗的指导作用。方法选取UC患儿57例(UC组),单纯腹泻患儿30例(腹泻组),健康儿童60例(健康对照组)。留取粪便,采用ELISA法检测钙卫蛋白。UC组采用"升阶梯"方案(美沙拉嗪无效时加用激素,继而加用单克隆抗体)治疗,比较治疗前后粪便钙卫蛋白变化,分析钙卫蛋白诊断UC的效能及其与治疗的关系。结果 UC组、腹泻组、健康对照组中位粪便钙卫蛋白分别为307.93、124.95和19.17μg/g,UC组明显高于腹泻组和健康对照组(P均<0.01),腹泻组与健康对照组比较无统计学差异(P>0.05);UC组活动期、缓解期患儿中位粪便钙卫蛋白分别为333.53、273.50μg/g,P<0.05;ROC曲线分析显示粪便钙卫蛋白升高的临界值为175.53μg/g,对应诊断UC的最佳灵敏度和特异度分别为77.2%和87.9%。UC组治疗后活动期患儿中位粪便钙卫蛋白明显下降;中位粪便钙卫蛋白≥307.93μg/g者激素使用率、用药时间长于<307.93μg/g者(P均<0.05)。结论粪便钙卫蛋白诊断儿童UC准确、无创、安全,有助于临床选择治疗药物及判断治疗效果。     

粪便钙卫蛋白判断消化性溃疡活动性的临床价值

目的探讨粪便钙卫蛋白（FCP）判断消化性溃疡（PU）活动性的临床价值,并与常规胃镜检查结果行对比研究。方法胃镜确诊消化性溃疡患者62例,胃镜检查后3d内留取粪便5～10g,应用ELISA法检测粪便钙卫蛋白;同时收集患者病史及临床资料。正常对照组30例,均为健康体检正常的成人。结果62例PU组FCP检测值（154．72μg／g）显著高于正常对照组（25．18μg／g）（P〈0．001）;PU组活动期FCP检测值（318．34μg／g）与瘢痕期（54．10μg／g）、对照组（25．18μg／g）相比较也均有统计学意义（P〈0．01）;后两者之间的差异无统计学意义（P〉0．05）。FCP检测值与溃疡部位、大小、数目之间无明显关系（P〉0．05）。PU组中上消化道出血者FCP检测值（1257．41μg／g）显著高于其他症状者（92．77μg／g）（P〈0．001）。结论FCP的表达水平与消化性溃疡患者溃疡活动性及临床表现密切相关,FCP可作为检测消化性溃疡患者溃疡活动性指标之一。     

粪便钙卫蛋白在IBS与IBD鉴别诊断中的意义

目的:研究粪钙卫蛋白在炎症性肠病(inflammatory bowel disease,IBD)与肠易激综合征(irritable bowel syndrome,IBS)鉴别诊断中的意义.方法:收集中国人民解放军北京军区总医院消化内镜中心接受肠镜检查患者的新鲜粪便标本共92例,其中溃疡性结肠炎(UC)23例、克罗恩病(CD)4例、IBS 55例、健康人20例.采用ELISA法半定量检测粪便中钙卫蛋白浓度.结果:健康人粪钙卫蛋白浓度为77.15±160.9μg/g,IBS患者为46.08±131.97 μg/g,IBD患者为851.34±522.19 μg/g.IBS患者和健康人粪钙卫蛋白浓度差异无显著差异(P>0.05); IBD与IBS和健康人粪钙卫蛋白水平有显著差异(P<0.001).以60 μg/g为临界值时鉴别IBD与IBS的敏感性86.7%,特异性为96.3%.结论:粪便钙卫蛋白含量检测作为一种非侵入性筛选试验,为临床鉴别IBD和IBS提供了手段.     

粪便钙卫蛋白检测在炎症性肠病患者中的意义

<正>炎症性肠病(inflammatory bowel diseases,IBD)包括克罗恩病(Crohn’s disease,CD)和溃疡性结肠炎(ulceralive colitis,UC),是一种慢性非特异性肠道炎症性疾病,以反复复发为特点,对于IBD疾病的管理,一直是临床医生面临的难题,目前临床上常用的评估病情手段有内镜、血清学指标、影像     

Diagnostic accuracy of one or two faecal haemoglobin and calprotectin measurements in patients with suspected colorectal cancer

Background: The role of faecal biomarkers in patients at ‘high risk’ of colorectal cancer (CRC) is not yet defined. Pre-analytical factors, such as heterogeneity of biomarker distribution within faeces, may influence their optimisation in clinical practice. We undertook to determine whether repeat or combined biomarker testing improves diagnostic accuracy for CRC or clinically significant disease.

Methods: Patients referred with suspected CRC provided two separate faecal samples each for faecal immunochemical testing (FIT) and faecal calprotectin (FC) prior to investigation. Diagnostic accuracy of FIT and FC were evaluated based on final diagnoses.

Results: Five hundred fifteen patients completed a full colorectal evaluation. The optimal cut-off for CRC using a single FIT was ≥12 µgHb/g faeces (84.6% sensitivity, 88.5% specificity). For two FIT, the cut-off was ≥43 µgHb/g faeces if either and ≥2 µgHb/g faeces if both were positive. There was no advantage in their diagnostic accuracy compared with a single FIT. FC had a lower diagnostic accuracy for CRC than FIT, which was not improved by repeat FC. No benefit was identified with FIT-FC combined.

For CRC, significant adenomatous polyps and organic enteric disease combined, FIT and FC performed similarly to each other but were poorer predictors (AUC 0.677 and 0.660). There was no uplift in diagnostic accuracy when the tests were repeated or combined.

Conclusion: This study supports using a single FIT at a cut-off close to that recommended by NICE DG30 to improve diagnostic accuracy for ‘two-week wait’ patients referred with suspected CRC.     

Utility of faecal calprotectin analysis in adult inflammatory bowel disease

The inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis, are chronic relapsing, remitting disorders. Diagnosis, along with assessment of disease activity and prognosis present challenges to managing clinicians. Faecal biomarkers, such as faecal calprotectin, are a non-invasive method which can be used to aid these decisions. Calprotectin is a calcium and zinc binding protein found in the cytosol of human neutrophils and macrophages. It is released extracellularly in times of cell stress or damage and can be detected within faeces and thus can be used as a sensitive marker of intestinal inflammation. Faecal calprotectin has been shown to be useful in the diagnosis of IBD, correlates with mucosal disease activity and can help to predict response to treatment or relapse. With growing evidence supporting its use, over the last decade this faecal biomarker has significantly changed the way IBD is managed.     

异时性多原发结直肠癌临床特点分析31例

目的:探讨异时性多原发结直肠癌的临床特点, 为临床诊治提供参考.方法:回顾性总结31例异时性多原发结直肠癌的临床资料, 分析肿瘤发生、分布及治疗与预后.结果:31例患者, 平均5.1年出现次发癌, 平均3.8年后3例出现第3癌, 平均3.5年后2例再发第4癌. 45.2%的患者合并存在腺瘤. 59.5%的首发癌位于直肠、乙状结肠;大部分次发癌的分化程度、病理分期好于首发癌或与之相同;首发癌术后平均存活8.3年, 5年生存率84.8%.结论:大多数异时性多原发结直肠癌的首发癌位于直肠及乙状结肠. 合并存在腺瘤是发生该病的危险因素, 根治术后应进行定期复查.     

结直肠类癌内镜下诊断及治疗51例

目的:探讨结直肠类癌的内镜下诊断及治疗.方法:收集1986-04/2008-08我院经结肠镜检查并病理证实的类癌51例.分析其形态学特点、结肠镜下治疗及预后.结果:结直肠类癌男性明显多于女性(1.83:1),平均年龄53.0±13.2岁,直肠最多见(86.3%),最大径多小于1.0 cm(74.5%),内镜下多表现为典型的黏膜下肿物,色黄,质硬或韧,活动度差,≥2.0 cm多发生转移,≤1.0 cm者EMR法切除均无复发,6例术前行超声内镜检查,明确内镜下治疗的可能性.结论:掌握内镜下类癌的特点有助于提高肉眼诊断,深凿活检或EMR切除活检有助于提高诊断率,≤1.0 cm的类癌内镜下切除安全、有效.     

Faecal calprotectin and faecal occult blood tests in the diagnosis of colorectal carcinoma and adenoma

BACKGROUND AND AIMS: Testing for faecal occult blood has become an accepted technique of non-invasive screening for colorectal neoplasia but lack of sensitivity remains a problem. The aim of this study was to compare the sensitivity and specificity of faecal calprotectin and faecal occult blood in patients with colorectal cancer and colonic polyps. METHODS: Faecal calprotectin and occult blood were assessed in 62 patients with colorectal carcinoma and 233 patients referred for colonoscopy. The range of normality for faecal calprotectin (0.5-10.5 mg/l) was determined from 96 healthy subjects. RESULTS: Median faecal calprotectin concentration in the 62 patients with colorectal carcinoma (101 mg/l, 95% confidence interval (CI) 57-133) differed significantly from normal (2.3 mg/l, 95% CI 1.6-5.0) with 90% of patients having elevated levels (normal <10 mg/l) whereas only 36/62 (58%) had positive faecal occult bloods. There was no significant difference in faecal calprotectin levels when considering location or Dukes' staging of tumour. Percentage positivity of faecal occult bloods was significantly higher for Dukes' stage C and D cancers compared with Dukes' A and B. In the colonoscopy group, 29 patients with adenomatous polyps were detected in whom the median faecal calprotectin was 12 mg/l (95% CI 2.9-32). Sensitivity for detection of adenomatous polyps was 55% using the calprotectin method and 10% using faecal occult blood testing. The overall sensitivity and specificity of calprotectin for colorectal cancer and adenomatous polyps as a combined group was 79% and 72%, respectively, compared with a sensitivity and specificity of faecal occult blood of 43% and 92%. CONCLUSIONS: Faecal calprotectin is a simple and sensitive non-invasive marker of colorectal cancer and adenomatous polyps. It is more sensitive than faecal occult blood tests for detection of colorectal neoplasia at the cost of a somewhat lower specificity.     

Fecal excretion of calprotectin in colorectal cancer: relationship to tumor characteristics

BACKGROUND: The aim of this study was to evaluate fecal calprotectin in patients treated for colorectal cancer. Furthermore, the changes in fecal calprotectin concentration from before to after surgery were investigated. METHODS: In 155 patients with newly diagnosed colorectal cancer, two spot samples were taken from the same feces on two consecutive days. RESULTS: Three ways of evaluating calprotectin excretion were compared, (1st spot 1st stool; maximum of 1st spot 1st stool and 2nd spot 1st stool; maximum of 1st spot 1st stool and 1st spot 2nd stool) and gave similar results with median fecal calprotectin values 47 mg/l, 52 mg/l and 54 mg/l, respectively. Median calprotectin concentration did not differ significantly between different tumor stages, although the levels were slightly lower in Dukes stage A tumor than in the rest of the stages. Neither were there any differences in the concentrations related to the localization, size or the histological grading of the carcinoma. As the currently used cut-off level for fecal calprotectin is 10 mg/l, 87% of all patients had elevated fecal calprotectin. Seventy-nine percent of the patients had levels above 15 mg/l and 74% had levels above 20 mg/l (1st spot 1st stool). In patients who delivered fecal samples after the operation the calprotectin value fell significantly from a preoperative median value of 45 mg/l to 14 mg/l after the resection. CONCLUSIONS: The majority of patients with colorectal cancer have increased fecal concentration of calprotectin. One single fecal spot seems to be sufficient for determination of the calprotectin level. Measurement of fecal calprotectin may possibly become of value as a marker for colorectal cancer, although calprotectin, similar to fecal occult blood (FOB) tests, is a non-specific test for colorectal pathology, also being elevated in inflammatory bowel diseases. Further investigation of its specificity is therefore needed.     

Diagnosing colorectal cancer and inflammatory bowel disease in primary care: The usefulness of tests for faecal haemoglobin,faecal calprotectin,anaemia and iron deficiency. A prospective study

Objective: Abdominal complaints are common reasons to consult primary care but they are seldom caused by colorectal cancer (CRC), high-risk adenomas (HRAs), or inflammatory bowel disease (IBD). Reliable diagnostic aids would be helpful in deciding which patients to refer for bowel imaging. Our aim was to assess the value of a faecal immunochemical test (FIT) and a faecal calprotectin (FC) test in detecting CRC, HRAs and IBD in primary care, and the value of combining these tests with anaemia and iron-deficiency tests.

Materials and methods: This prospective study included 373 consecutive patients that received a FIT or a FC test ordered by a primary care physician. We collected samples for FITs, FC tests, full blood counts and iron-deficiency tests. Physicians were instructed to refer patients with a positive FIT or FC test (cut-off ≥100μg/g) for bowel imaging. The patients’ presenting symptoms were recorded. Patients were followed for 2 years.

Results: The best test for detecting CRC and IBD was the combination of the FIT and haemoglobin concentration. This test had a sensitivity, specificity, positive predictive value and negative predictive value of 100%, 61.7%, 11.7% and 100%, respectively. The FIT detected a significantly larger proportion of CRC, HRAs and IBD than the FC test (0.92 versus 0.46, 95% confidence interval 0.22–0.67).

Conclusion: A negative FIT combined with a normal haemoglobin concentration could rule out CRC and IBD with a high degree of safety. This could be useful in prioritising referrals for bowel imaging from primary care.     

Increased faecal calprotectin predicts recurrence of colonic diverticulitis

Background and aims

Colonic diverticulitis shows a high recurrence rate, but the role of faecal markers in predicting recurrence is unknown. The aim of this study was to investigate the role of faecal calprotectin (FC) in predicting recurrence of diverticulitis.

Patients/methods

A prospective cohort study was performed on 54 patients suffering from acute uncomplicated diverticulitis (AUD) diagnosed by computerized tomography (CT). After remission, patients underwent to clinical follow-up every 2 months. After remission and during the follow-up, FC was analysed. Recurrence of diverticulitis was defined as return to our observation due to left lower-quadrant pain with or without other symptoms (e.g. fever), associated with leucocytosis and/or increased C-reactive protein (CRP). Presence of diverticulitis was confirmed by means of CT.

Results/findings

The mean follow-up was 20 months (range 12–24 months). Forty-eight patients were available for the final evaluation, and six patients were lost to follow-up. During follow-up, increased FC was detected in 17 (35.4 %) patients and diverticulitis recurred in eight patients (16.7 %). Diverticulitis recurred in eight (16.7 %) patients: seven (87.5 %) patients showed increased FC during the follow-up, and only one (12.5 %) patient with recurrent diverticulitis did not show increased FC. Diverticulitis recurrence was strictly related to the presence of abnormal FC test during follow-up.

Conclusions

In the present prospective study, increased FC was found to be predictive of diverticulitis recurrence.     

Effect of oral diclofenac intake on faecal calprotectin

Background. NSAIDs are a known source of increased faecal calprotectin (FC) levels. Currently, there is a lack of knowledge about how long it takes for an increased FC level to return to normal after NSAID intake. Objective. The aim was to investigate how oral diclofenac intake affects FC levels and assess how long it takes for an increased FC level to return to normal after oral diclofenac intake. Material and methods. Thirty healthy volunteers received diclofenac 50 mg three times daily for 14 days. Participants provided a stool sample on Days 0, 2, 4, 7, 14 during intake and Days 17, 21, 28 after discontinuation. FC levels were then followed at 7-day intervals until normalization. Results. During diclofenac intake, eight participants (27%) had FC levels exceeding the upper limit of normal (median, 76 μg/g; range, 60–958 μg/g), corresponding to 8.3% of measurements. FC was not constantly increased and became normal in most participants during diclofenac intake. FC levels were on average significantly higher during intake (M = 9.5, interquartile range (IQR) = 13.4) than on baseline (M = 7.5, IQR = 0.0), p = 0.003. After discontinuation, two participants had increased FC on Days 17 and 21, respectively. No significant differences in FC levels were found between baseline and measurements after discontinuation. Two weeks after discontinuation, all participants had normal FC levels. Conclusions. Short-term oral diclofenac intake is associated with increased FC levels. However, the likelihood of an increased test result is low. Our results suggest that 2 weeks of diclofenac withdrawal is sufficient to get an uninfluenced FC test result.