Objective: To investigate the significance of quantitative fecal immunochemical test (FIT) for opportunistic screening of colorectal neoplasia, and to propose the most optimal thresholds to improve the screening level of early colorectal neoplasia. Methods: The opportunistic screening participants were recruited from the Department of Gastroenterology & GI Endoscopy Center of the Seventh Medical Center of PLA General Hospital, and stool sample was collected before colonoscopy and the quantitative FIT was analyzed by OC-MICRO analysator for each patient. We assessed test performance in detecting colorectal neoplasia (advanced adenoma and CRC)with different thresholds on sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results: A total of 1 448 objects were enrolled in this study, including 714 male (49.3%)and 734 female (50.7%).All participants were classified according to the result of colonoscopy and pathology, and 242 cases of colorectal neoplasia were found, containing 157 advanced adnoma and 85 colorectal cancer. The FIT threshold increased from 50 μg/L to 200 μg/L, while the positivity rate dropped from 11.5% to 8.6% and the sensitivity in detecting colorectal neoplasia dropped from 47.9% to 38.8%. However, the specificity increased from 96.8% to 98.2% and the positive predictive value increased from 82.3% to 87.0%.The miss rate of colorectal cancer increased from 11.8% (n=10) to 17.6% (n=15) along with the increase in FIT thresholds, but the miss rate of 100 μg/L and 150 μg/L was the same as 12.9% (n=11). Conclusions: Quantitative FIT,which is simple and fast,with the threshold of 100 μg/L for opportunistic screening, has a high sensitivity and specificity for the diagnosis of colorectal neoplasia,and is an important index in screening and diagnosis of colorectal neoplasia.目的： 探讨定量免疫法便潜血试验（FIT）在结直肠肿瘤伺机性筛查中的意义，提出最适宜的阈值，提高结直肠肿瘤的早期筛查水平。 方法： 以解放军总医院消化内镜中心就诊拟行结肠镜检测的人群为研究对象进行伺机性筛查，患者结肠镜检查前留取晨起自然便，应用OC-MICRO全自动便潜血分析仪进行免疫法便潜血试验，对便潜血结果进行分析，分别计算不同阳性阈值下的敏感性、特异性、阳性预测值（PPV）、阴性预测值（NPV）。 结果： 最终纳入研究对象1 448例，其中男714例（49.3%），女734例（50.7%），根据结肠镜和病理结果共检测出结直肠肿瘤242例，其中进展性腺瘤157例、结直肠癌85例。FIT阈值从50 μg/L升至200 μg/L，阳性率由11.5%降至8.6%，FIT检测结直肠肿瘤的敏感性随FIT阈值升高由47.9%降至38.8%，但是特异性由96.8%升高至98.2%，并且阳性预测值由82.3%升高至87.0%。结直肠癌的漏检率随FIT阈值升高，由11.8%（n=10）增高至17.6%（n=15），但是阳性阈值100 μg/L和150 μg/L的漏检率相同12.9%（n=11）。 结论： 免疫法便潜血阈值100 μg/L用于伺机性筛查对进展性腺瘤和结直肠癌的诊断具有较高的敏感性和特异性，该方法操作简便、检测快捷，是较好的大肠良恶性疾病筛查和诊断的参考指标。.
To investigate the effect of estrogen on MMR gene expression in colon cancer cells COLO205.By employing semi-quantitative RT-PCR and Western blotting techniques, changes in the expression of MMR genes (hMLH1 and hMSH2) induced by different levels of estradiol (E2) and ICI182.780, an estrogen receptor inhibitor, was investigated in cultured COLO205 cells. The effect was then verified by real time RT-PCR.E2 enhanced the expression of hMLH1 in COLO205 cells at transcriptional level, and a dose-response relationship was established when the concentration of E2 was between 10(-12);-10(-8); mol/L. The enhancement was suppressed by the estrogen receptor inhibitor ICI182.780. On the other hand, there was no significant effect of E2 on hMSH2 expression in COLO205 cells.E2 can increase the expression of hMLH1 in colon cancer cells COLO205, and this finding sheds new light on the mechanism of estrogen protecting against colon cancer by regulating MMR system.
To investigate the validity and safety of different doses of non-steroidal anti-inflammatory drugs (NSAID) in attempting to maintain the regression of colorectal adenomas in patients with familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC).Twenty-two FAP patients who were willing to receive celecoxib were randomly divided into 2 groups 400 mg/d group (n = 8, taking celecoxib 400 mg/d) and 200 mg/d group (n = 10, taking celecoxib 200 mg/d). Four FAP patients who refused celecoxib and selected aspirin 80 mg/d instead. Six HNPCC patients were given celecoxib 400 mg daily. The treatment lasted for 24 months in all groups. The efficacy was evaluated respectively by the number and grade of polyps by coloscopy every 3 months in the first year and every 6 months in the second year.Either dose of celecoxib could reduce polyps in the FAP patients, with a polyps reduction rate of 86.6% (280/323) in the 400 mg group, significantly higher than that in the 200 mg group [51.81% (129/249) of the aspirin group]. In 5 of the 6 HNPCC patients the polyps completely vanished after 9 months of treatment. Side effects, such as arrhythmia, angina pectoris, and nervous headache, were observed in the celecoxib 400 mg/d group. The side effects could be reversed by decreasing the dose of celecoxib or using aspirin instead. Only one patient in the celecoxib 200 mg/d group showed side effects.Celecoxib 400 mg daily is more effective but has more side effects. At first the patients should be treated with celecoxib 200 mg daily for a long time, or 400 mg/d in the first 6 months and then with a daily dose of 200 mg/d to maintain the treatment effects. Soluble aspirin has similar effects.
To explore the optimal therapeutic effect of infliximab (IFX) upon inflammatory bowel disease.Eight patients with inflammatory bowel disease (IBD), including 5 Crohn's disease (CD) and 3 ulcerative colitis (UC), were treated with IFX of 5 mg/kg body weight at 0, 2 and 6 weeks, followed by scheduled maintenance therapy every 8 weeks and followed up for a long-term period. Of these patients, 5 cases were resistant to corticosteroid, 2 cases corticosteroid dependency and one naive patient.All patients responded well to the scheduled program of 5 mg/kg infusion of IFX. Two CD cases achieved a complete remission. Two CD patients responded clinically; one was difficult to judge the result; of the UC patients, one achieved a complete remission and 2 responded. There were no serious side effects during the course of therapy.Selecting the proper drug indications and therapeutic protocol, determining the doses and course of IFX on the basis of therapeutic response, combining IFX with other immunomodulators (esp. budesonide) and assessing the therapeutic efficacy of IFX by endoscopic mucosa healing rather than symptoms prevent disease recurrence and decrease side effects.
Objective To investigate the characteristics of APC gene germline mutation in Chinese patients with familial adenomatous polyposis ( FAP). Methods The genomic DNA was extracted from peripheral venous blood drawn from probands of 14 Chinese FAP families from Beijing, Hebei, Henan,Anhui, Inner Mongolia, Shanxi and Fujian. The APC gene was amplified by PCR and underwent direct sequencing. Large fragment deletion was detected by multiplex ligation-dependent probe amplification (MLPA) only in micromutation-negative samples found by sequencing. Results APC gene micromutations were found in 9 probands and the mieromutation detection rate was 64. 3%, including 6 frameshift mutations, 2 splicing mutations and 1 nonsense mutation. Large fragment deletions of APC gene were detected in 2 probands ( 14. 3% ). The total mutation detection rate of micromutation and large fragment deletion was 78. 6%. Four novel micmromutations and 2 novel large fragment deletions were found, including c. 2336-2337insT, c. 3923-3929delAAGAAAA, c. 532-2A>T, c. 4179-4180GAdelinsT, large fragment deletions of exons 11 and 10A and large fragment deletion of exon 15 start. Conclusions In Chinese FAP patients, the germline mutation type of APC gene is variable; the majority is of frameshift mutation. The most common mutation site is exon 15. The mutation detection rate of APC gene can be boosted effectively by direct sequencing in combination with MLPA.
Key words:
Adenomatous pelyposis coli; Genes, APC; Mutation; Gene deletion; Gene amplification
To investigate the expression of Cyclooxygenase (COX)-2 and the relationship between cox-2, mismatch repair gene (MMR) proteins and microsatellite instability (MSI) in HNPCC.Twenty-eight cases of adenomas and 14 cases of carcinomas were collected from 33 HNPCC families patients by colonoscopy. Sporadic adenomas (n = 32) and carcinomas (n = 24) were used as a control group. The expressions of COX-2 and mismatch repair gene hMLH1, hMSH2, hMSH6 proteins were examined by immunohistochemistry. MS1 were analyzed by using PCR with BAT25, BAT26, D2S123, D5S346 and D17S250 loci.The COX-2 high-expression rates were 53.6% (15/28) and 42.9% (6/14) in HNPCC adenomas and carcinomas, and were 62.5% (20/32) and 91.7% (22/24) in sporadic adenomas and carcinomas. COX-2 expression was lower in HNPCC carcinomas than that of sporadic carcinomas (P < 0.05). MMR deficiency rate and positive rate of MSI-H were both 71.4% (10/14) respectively in HNPCC carcinomas. It was higher than that in sporadic colorectal carcinomas [both 12.5% (3/24)]. Eight (80.0%) COX-2 low-expression were observed in 10 HNPCC carcinomas with MMR-deficient system while 4 cox-2 high-expression cases were observed in 4 HNPCC carcinomas with MMR-proficient system. COX-2 expression was lower in HNPCC carcinomas and adenomas, sporadic carcinomas with MMR-deficient system than that of MMR-proficient (P < 0.05). The COX-2 low-expression rates were 80.0% (8/10), 66.7% (12/18) and 66.7% (2/3) in HNPCC adenomas, HNPCC carcinomas and sporadic carcinomas with MSI-H. Cox-2 expression was lower in HNPCC and sporadic carcinomas (adenocarcinomas) with MSI-H than that of MSS (P < 0.05).Compared with sporadic carcinomas, the COX-2 expression was lower in HNPCC carcinomas. There was negative correlation between COX-2 expression and MMR-deficient (MSI-H). The detection of COX-2, MMR protein and MSI is of important significance in further studying the pathogenesis and interventional therapy of colorectal neoplasms.
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