家族性腺瘤性息肉病恶变1例

家族性腺瘤性息肉病是一种遗传性疾病,癌变率较高。本文通过对家族性腺瘤性息肉病的内镜特点进行分析,总结其临床特征,探讨家族性腺瘤性息肉病的早期诊断和治疗。结肠镜检查可了解家族性腺瘤性息肉病结肠受累的部位和程度,为治疗及预后评价提供依据。通过家族调查可发现早期病例,内镜下治疗效果满意。     

家族性腺瘤性息肉病1例

<正>家族性腺瘤性息肉病(familial adenomatous polyposis, FAP)是一种罕见常染色体显性遗传性疾病，特征性表现为结直肠黏膜出现数百甚至数千枚大小不等的腺瘤性息肉。息肉最常出现在生命的第2或第3个10年，多数在40岁左右出现癌变，占所有结直肠癌的1%左右^[1]。同时，还会发生肠外器官如肝脏、肾上腺、甲状腺、中枢神经系统等器官癌变，严重威胁患者的健康。笔者收治1例41岁男性FAP患者，     

家族性腺瘤性息肉病的认识进展

家族性腺瘤性息肉病（familial adenomatous polyposis,FAP）的发病率约为7.4／10万^[1],以多发性腺瘤性息肉为主要特征,多数患者在青少年时期发病。随着年龄的增长,息肉数目增多,体积增大,癌变危险性增高。癌变可为多灶性、同时性,且通常转移早、预后差。     

家族性腺瘤性息肉病及其癌变的化学预防

<正>家族性腺瘤性息肉病(familial adenomatous polyposis,FAP)是一种常染色体显性遗传性疾病,多数在青年时就发展为多发腺瘤性结直肠息肉。任其发展,必然进展为结直肠癌(colorectal cancer,CRC)。目前认为最安全的预防FAP患者发展为CRC的方法,就是当息肉发育时外科手术切除结     

舒林酸长期治疗家族性腺瘤性息肉病的临床研究

目的观察长期服用舒林酸对家族性腺瘤性息肉病(FAP)患者结直肠腺瘤消退的作用及其安全性。方法FAP患者口服舒林酸400mg/d,12个月内每3个月结肠镜复查一次,观察结直肠息肉的变化。对有效者,继续服用舒林酸维持治疗,维持剂量按300mg/d到200mg/d到150mg/d依次减少。减药中如果腺瘤数目增加,则将药量增至上一剂量。结果18例FAP患者在治疗12个月后结直肠内息肉显著减少,平均维持治疗时间为(35.5±17.7)个月。最后一次复查时息肉数目均较治疗前明显减少[从治疗前的(854±920)个降到(13±20)个](P<0.01)。舒林酸的有效维持量为150～300mg/d,平均剂量为(262.5±56.9)mg/d。治疗期间肠道中出现微小扁平隆起和红斑。活检病理显示治疗后管状腺瘤比例增加,腺瘤异型程度下降(P<0.01)。5例患者停药后腺瘤复发,2例再次服药后腺瘤再次消退。长期服用舒林酸的常见不良反应是结肠黏膜糜烂,没有发现严重的不良反应。结论舒林酸长期维持治疗可使FAP患者结直肠腺瘤保持长期显著消退状态。最小有效维持量150mg/d～300mg/d不等,有个体差异。长期用药安全性好。初步提示停用舒林酸后腺瘤有复发倾向,但再次用药仍有效。     

家族性腺瘤息肉病用舒林酸长期治疗的前瞻性研究

家族性腺瘤息肉病 (ＦＡＰ)患者行全结肠切除和回肠直肠吻合术 (ＩＲＡ)后直肠残端常有肿瘤复发 ,作者评价用舒林酸 (Ｓｕｌｉｎｄａｃ ,一种非类固醇类抗炎药 )维持患者残留直肠段免于腺瘤复发的长期效果和毒性。方法　 1 2例ＦＡＰ患者 ,平均年龄 3 7 1岁。有至少 5个直肠腺瘤 ,已行ＩＲＡ。过去 3个月内用非类固醇类抗炎药超过 1周 ,妊娠 ,白细胞计数 <4× 1 0 9/Ｌ ,有消化性溃疡史、胃肠道出血史、恶性病史、阿司匹林过敏史者均除外。投药前作可屈式乙状直肠镜检查 ,以后每 4个月随访 1次 ,计数结直肠息肉总数 ,并从粘膜和息肉取活检标…     

直肠家族性腺瘤性息肉与癌组织中COX—2蛋白表达及意义

用流式细胞仪（FCM）检测19例直肠家族性腺瘤性息肉病（FAP）及39例直肠癌患者癌组织的环氧合酶-2（COX-2）蛋白表达。结果表现，18（94.74%)例息肉组织COX-2蛋白阳性表达，39（100%）例癌组织COX-2蛋白均阳性表达，提示COX-2蛋白表达检测在诊断监测，化学预防息肉癌变过程中可能具有重要意义。     

腹腔镜全结直肠切除治疗家族性腺瘤性息肉病伴癌变

目的 探讨腹腔镜辅助全结直肠切除手术在家族性腺瘤性息肉病(FAP)伴癌变中的安全性、可行性。方法 3例FAP伴癌变病例施行腹腔镜辅助全结直肠切除手术,总结手术经验,观察手术安全性、术后恢复情况以及短期随访结果。取同期开腹全结肠切除手术8例作为对照组。结果 腹腔镜组3例均顺利施行腹腔镜辅助全结肠、直肠切除术,无中转开腹手术病例,平均手术时间243.33(200-310)min,显著长于开腹组(P=0.028)。 平均术中出血量146.66(90-200)ml,肛门排气时间为术后1.33 d,住院时间14 d,略短于开腹组,尚未达统汁学差异;平均手术切口长度腹腔镜组为4.33 cm,显著短于开腹组19.38 cm(P<0.01)。腹腔镜组3例术后无严重并发症,术后均证实为FAP伴癌变,随访时间分别为25、15、10个月,无肿瘤局部复发与远处转移。结论 由具丰富腹腔镜外科经验的医师施行腹腔镜辅助全结直肠切除术治疗FAP安全、可行、有效,但需要进一步的手术病例积累及随机对照研究。     

Autosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH

Familial adenomatous polyposis (FAP) and attenuated FAP are autosomal dominant disorders characterised by multiple colorectal adenomas and cancers. Both are caused by inherited mutations in the APC gene, and management includes genetic testing, colonoscopic surveillance, and prophylactic surgery for the relatives of index cases. Among 614 families recorded in six regional registers of polyposis in the UK, we identified 111 with neither dominant transmission nor evidence of APC mutation. Molecular genetic analysis showed that 25 had biallelic mutations of the MYH gene. Since our data show that MYH polyposis can be transmitted as an autosomal recessive trait, a change in genetic counselling, testing, and surveillance is needed.     

Immunohistochemical expression of MYH protein can be used to identify patients with MYH-associated polyposis

BACKGROUND & AIMS: MYH-associated polyposis is a recently described, autosomal-recessive disease characterized by multiple colorectal adenomas and cancer. There are only few immunohistochemical studies of the MYH protein. We investigated the expression pattern of the MYH protein to evaluate whether a immunohistochemical approach could be used in clinical practice to screen patients for germline mutations in the MYH gene. METHODS: The expression of MYH, MSH2, MLH1, and MSH6 proteins was studied by immunohistochemistry in 20 samples (colorectal adenomas or cancer) from 18 patients with biallelic MYH mutation, in 11 samples from patients with germline adenomatous polyposis coli (APC) mutations, in 20 samples from patients with sporadic colorectal cancers, and in 10 samples from patients with normal colonic mucosa without malignancies. RESULTS: In all cases the mismatch repair proteins were expressed normally. Nuclear and cytoplasmic immunoreactivity for the MYH protein were observed in normal colorectal mucosa, in sporadic colorectal carcinomas, and in adenomas and carcinomas from patients carrying APC germline mutations. Adenomas and carcinomas from patients with MYH biallelic mutation showed a different pattern of expression: a strong granular cytoplasmic staining was observed without any nuclear expression. The same immunophenotype was observed in the surrounding normal mucosa. CONCLUSIONS: Patients with biallelic MYH mutations showed disappearance of staining from the nucleus, and segregation of immunoreactivity in the cytoplasm, both in neoplastic and surrounding healthy mucosa. Because this pattern of expression seems to be specific for biallelic mutations, it follows that immunohistochemistry might be used in clinical practice to screen patients at risk for MYH-associated polyposis.     

Hyperplastic polyposis syndrome: phenotypic presentations and the role of MBD4 and MYH

BACKGROUND & AIMS: Hyperplastic polyposis syndrome (HPS) is defined phenotypically with multiple, large and/or proximal hyperplastic polyps. There is no known germ-line predisposition. We aimed to characterize the clinicopathologic features of 38 patients with HPS and explore the role of germ-line mutations in the base excision repair genes MBD4 and MYH. METHODS: Utilizing clinical databases of The Royal Melbourne Hospital Bowel Cancer Surveillance Service and the Familial Cancer Clinic, 38 patients with HPS were recruited. The patients were analyzed for age at first diagnosis, features of hyperplastic polyposis, family histories of polyposis and colorectal cancer (CRC), coexisting adenomas, serrated adenomas, incidence of CRC, and microsatellite instability in the tumours. Mutation analysis of MBD4 and MYH were performed. RESULTS: Serrated adenomas were common (26%), and 19 (50%) of the 38 patients had a first-degree relative with CRC. Family history of HPS was uncommon, with only 2 cases found. Ten patients developed CRC, and 3 required surgery for polyposis. No pathogenic mutations in MBD4 were detected in the 27 patients tested, but 6 single nucleotide polymorphisms of uncertain functional significance were identified. Pathogenic biallelic MYH mutations were detected in 1 patient. CONCLUSIONS: Mutations in MBD4 are unlikely to be implicated in HPS; MYH mutations should be studied, especially when adenomas occur in the same patient. The clinical, histopathologic, and molecular findings of this study should contribute to our understanding of HPS and its relationship to the serrated neoplasia pathway.     

High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis

BACKGROUND & AIMS: Inherited colorectal polyposis has been linked to constitutive mutations of the APC tumor suppressor gene. Recently, germline mutations in the base excision repair gene MYH have been associated with a recessively inherited form of the disease. The aim of this study was to evaluate germline mutation frequencies of both MYH and APC susceptibility genes in Italian patients with attenuated familial adenomatous polyposis. METHODS: The analysis was performed in 14 unrelated patients by using the protein truncation test for APC and genomic DNA sequencing for MYH. RESULTS: Overall, we identified 7 of 14 (50%) mutation carriers. Two patients were heterozygotes for an APC truncating mutation (2 of 14 [14%]), whereas 5 proved to be homozygotes or compound heterozygotes for MYH gene alterations (5 of 14 [36%]). Two MYH missense mutations, Y165C and G382D, already found to be frequent among patients from northern Europe, were also preponderant in our survey. Individuals with APC-associated syndrome showed a dominant family history of polyposis, whereas patients with MYH-associated disease were either apparently sporadic cases or had a family history consistent with recessive inheritance. MYH biallelic mutation carriers were up to 60% (5 of 8) among patients showing at least 30 adenomas and a family history with no vertical transmission of polyposis. CONCLUSIONS: On the basis of our data, patients with attenuated familial adenomatous polyposis with >30 adenomas and no obvious vertical transmission of the disease should be considered for MYH gene testing.     

沙粒病毒及所致人类疾病的研究进展

沙粒病毒(Arenaviruses)属于沙粒病毒科(Arenaviridae),现分为爬行动物沙粒病毒属(Reptarenavirus,RARV)、哈特曼病毒属(Hartmanivirus,HARV) 和哺乳动物沙粒病毒属(Mammarenavirus,MARV) 3个属,分别以爬行动物和啮齿动物为宿主。沙粒病毒,特别是MARV可引起人类病毒性出血热,主要分布于非洲和美州,近几年来,亚洲也有病例报道,特别是我国鼠类中也证实存在一类新型沙粒病毒的感染,引起人们的关注。本文就沙粒病毒的结构、分类、疫苗、治疗及所致人类疾病的研究进展进行了综述。     

巴贝虫棒状体蛋白的研究进展

巴贝虫是一类专性的细胞内寄生的顶复门原虫,是人和动物的重要病原。这类原虫具有相似的亚细胞结构并能分泌与入侵相关的保守蛋白,尤其是在入侵宿主细胞阶段分泌的棒状体相关蛋白被认为是保护寄生虫入侵和繁殖的关键分子,其在虫体入侵的纳虫空泡形成过程中发挥重要作用。随着基因组学和蛋白质组学技术的不断发展,其相关研究也越来越深入。因此,本文就目前研究较多的牛巴贝虫、羊巴贝虫、吉氏巴贝虫、双芽巴贝虫和东方巴贝虫等棒状体相关蛋白的研究现状进行了综述。