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。     

莫沙必利与培菲康联合治疗功能性便秘的疗效观察

目的观察莫沙必利与培菲康联合治疗功能性便秘的临床疗效。方法采用随机对照研究,将95例功能性便秘患者随机分为3组:A组为治疗组,共33例,口服莫沙必利5mg/次,3次/d,培菲康1260mg/次,2次/d;对照组分为B、C2组,B组30例,口服莫沙必利5mg/次,3次/d;C组32例,口服培菲康1260mg/次,2次/d。疗程均为5周。4周后复查肝肾功能,记录不良反应情况,观察症状缓解情况并回访复发情况,作对比分析。结果治疗4周后,莫沙必利与培菲康联合治疗组的有效率为88.2%,明显优于单用培菲康及莫沙必利治疗组,有显著性差异(P<0.05),且治疗组与对照组间复发率的差别也有显著性意义(P<0.05)。治疗后均未发现明显不良反应。结论莫沙必利与培菲康联合治疗功能性便秘疗效满意,不良反应少,是目前治疗功能性便秘的可行方案。     

头孢噻肟钠与培菲康联合治疗肝硬化自发性腹膜炎的疗效分析

目的分析头孢噻肟钠联合培菲康治疗肝硬化自发性腹膜炎(spontaneous bacterial peritonitis,SBP)的临床疗效和不良反应。方法选取西安市第四医院就诊的84例肝硬化SBP患者,依据治疗方案不同分为:研究组41例,应用头孢噻肟钠联合培菲康治疗;对照组43例,仅应用头孢噻肟钠治疗。两组疗程均为14 d,比较两组患者临床疗效及不良反应的差异。结果与对照组相比,研究组的显效率、有效率及总有效率显著较高(P0.05),发热、腹痛、腹胀、腹部压痛及腹水菌群等临床表现缓解时间明显较短(P0.05),且肝功能衰竭、低血压性休克及病死率显著减少(P0.05)。结论头孢噻肟钠联合培菲康治疗肝硬化SBP疗效显著,不良反应少。     

不同时机加用培菲康联合三联疗法根除幽门螺杆菌疗效比较

[目的]探讨培菲康干预根除幽门螺杆菌(Hp)效果以及不同时机加用培菲康的干预情况。[方法]选择160例经标准三联疗法根除Hp不成功的患者,将其随机分为4组。甲组:采用标准三联疗法:阿莫西林1g+埃索美拉唑20mg+左氧氟沙星200mg,治疗时间14d;乙组:先服用培菲康420mg,疗程14d,之后再实施甲组方案;丙组:在甲组的方案实施中同时加用培菲康420mg,疗程与甲组相同;丁组:先实施甲组方案14d之后,再服用14d的培菲康420mg。比较4组的疗效以及伴随其中的不良临床症状产生的情况。[结果]甲组、乙组、丙组、丁组Hp根除率意向性分析(ITT)分别为75.0%、87.5%、90.0%、87.5%,符合方案集分析(PP)分别为76.9%、92.1%、92.3%、89.7%。乙组、丙组、丁组ITT和PP均明显高于甲组,差异有统计学意义(P0.05),而乙组、丙组、丁组间比较,均差异无统计学意义(P0.05)。甲组、乙组、丙组、丁组不良反应发生率分别为40.0%、20.0%、10.0%、22.5%,甲组的不良反应率高于乙组、丙组、丁组(P0.05);乙组、丁组高于丙组(P0.05)。[结论]标准三联疗法联合培菲康对根除Hp的补救治疗效果较好,其中标准三联疗法和培菲康同时服用不良反应最低,临床的推广价值比较高。     

奥沙拉嗪联合培菲康对溃疡性结肠炎患者IL-8的影响

将60例溃疡性结肠炎患者随机分成两组,对照组给予柳氮磺胺吡啶口服,治疗组给予奥沙拉嗪联合培菲康口服,疗程均为8周.比较两组总疗效、临床活动指数、IL-8的变化情况.结果 治疗组总疗效、临床活动指数、IL-8均较对照组有显著改善.认为改善趋化因子IL-8的表达可能是奥沙拉嗪联合培菲康治疗溃疡性结肠炎的机制之一.     

培菲康联合马来酸曲美布丁对脓毒症患者肠黏膜屏障功能的影响

目的探讨培菲康联合马来酸曲美布丁对脓毒症患者肠黏膜屏障功能的影响。方法选择2012年7月至2014年11月该院重症医学科收治的脓毒症患者90例,按照随机数字表法分成对照组和观察组,每组45例。对照组患者在基础治疗及对症治疗基础上口服或鼻饲生理盐水,观察组患者在对照组基础上加用培菲康联合马来酸曲美布丁治疗,疗程为10 d。分别于治疗前、后采用酶联免疫吸附测定法检测患者血清中二胺氧化酶(DAO)活性、肠型脂肪酸结合蛋白(IFABP)和D-乳酸含量,比较两组治疗后临床疗效。结果经过1个疗程治疗后,两组患者血清中DAO、IFABP和D-乳酸含量明显低于治疗前,同时观察组患者血清的上述指标显著低于对照组(P0.05);观察组患者总有效率〔93.33%(42/45)〕明显高于对照组〔57.78%(26/45)〕(P0.05)。结论培菲康联合马来酸曲美布丁可以降低脓毒症患者血清中相关指标,改善脓毒症患者的肠黏膜屏障功能,具有较好的临床疗效。     

培菲康联合三联疗法根除幽门螺杆菌疗效观察

目的探讨阿莫西林、呋喃唑酮及雷贝拉唑联合培菲康根除幽门螺杆菌（Hp）的临床疗效。方法 180例消化性溃疡或糜烂性胃炎患者,随机分为三组,每组60例。A组：雷贝拉唑20mg＋克拉霉素0.5＋阿莫西林1.0每天2次,疗程10d;B组：雷贝拉唑20mg＋阿莫西林1.0＋呋喃唑酮0.2,每天2次,疗程10d;C组：雷贝拉唑20mg每天2次＋阿莫西林1.0＋呋喃唑酮0.2,每天2次＋培菲康420mg,每天3次（与抗生素分开服,相隔至少2h）,疗程10d。活动期溃疡患者抗Hp治疗后继服雷贝拉唑20mg,每天1次,共3周。抗Hp治疗结束至少1月后复查Hp。结果 A、B、C三组的Hp根除率分别为75%、88.3%和91.7%,A组与B组、A组与C组组间相比差异有统计学意义,（P〈0.05）。A、B两组不良反应发生率差异有统计学意义（P〈0.05）,C组未见不良反应。结论阿莫西林、呋喃唑酮及雷贝拉唑联合培菲康根除Hp,疗效高,安全实用。     

小剂量红霉素联合微生态制剂治疗早产儿喂养不耐受疗效观察

目的探讨小剂量红霉素联合微生态制剂治疗早产儿喂养不耐受临床疗效。方法将124例出现喂养不耐受早产儿随机分为微生态制剂治疗组(微生态组)、小剂量红霉素治疗组(红霉素组)、两药联合治疗组(联合组)和对照组,每组32例。4组均给予常规治疗,微生态组给予培菲康,1/2粒/次,3次/d,口服;红霉素组静滴红霉素3～5 mg/kg,1次/d;联合组口服培菲康+红霉素静滴。结果红霉素组总有效率为68.7%,微生态组总有效率为65.6%,联合组总有效率为90.6%,均高于对照组(P均<0.01),而联合组总有效率分别高于微生态组及红霉素组(P均<0.05)。结论小剂量红霉素联合微生态制剂治疗早产儿喂养不耐受疗效确切,安全可靠。     

黛力新治疗无明显精神症状的腹泻型感染后肠易激综合征30例

目的:观察黛力新联合培菲康治疗无明显精神症状的腹泻型感染后肠易激综合征的疗效和安全性.方法:将60例无明显精神症状的腹泻型感染后肠易激综合征患者分为2组,每组病例均30例.联合治疗组采用黛力新联合培菲康治疗:对照组单用培菲康治疗.治疗2 wk后,比较药物疗效和安全性.结果:联合治疗组总有效率90.0%,单用培菲康组总有效率60.0%,联合治疗组总有效率明显优于单用培菲康对照组(P＜0.05),两组患者均未发现明显的不良反应.结论:黛力新联合培菲康治疗无明显精神症状的腹泻型感染后肠易激综合征安全、有效.     

培菲康辅助序贯疗法根除幽门螺杆菌的临床观察

目的比较序贯疗法联合培菲康与序贯疗法治疗幽门螺杆菌（Hp）阳性十二指肠溃疡的疗效与安全性。方法选取84例经胃镜检测证实为Hp阳性十二指肠溃疡病例,随机分为治疗组与对照组,两组均前5d予雷贝拉唑、阿莫西林,后5d予雷贝拉唑、替硝唑、克拉霉素治疗。随后两组均进行雷贝拉唑巩固治疗4周,治疗组全程均辅加培菲康,疗程结束后均行复查。结果疗程结束时,治疗组溃疡愈合率95.12%,对照组93.02%（P〉0.05）;Hp根除率治疗组97.56%,明显高于对照组81.40%,且具有显著性差异（P〈0.05）;治疗组不良反应明显少于对照组（P〈0.05）。结论两组溃疡愈合率相当,但培菲康提高了序贯疗法的Hp根除率,且不良反应少,耐受好,安全。     

舒林酸对家族性腺瘤性息肉病的疗效及作用机制的探讨

目的观察舒林酸对家族性腺瘤息肉病（ＦＡＰ）的临床疗效。并探讨其可能的作用机制。方法通过全结肠镜及结肠造影观察１０例ＦＡＰ患者服用舒林酸４００ｍｇ／ｄ后３、６、９、１２个月全结肠腺瘤的数目、大小的变化,并用免疫组织化学方法检测用药前后腺及平坦粘膜中增殖细胞核抗原（ｐｒｏｌｉｆ－ｅｒａｔｉｎｇ ｃｅｌｌ ｎｕｃｌｅａｒ ａｎｔｉｇｅｎ,ＰＣＮＡ）和Ｂｃｌ－２的表达。结果用药后３、６、９、１２个月较用药     

Analysis of K-ras, APC, and beta-catenin in aberrant crypt foci in sporadic adenoma, cancer, and familial adenomatous polyposis

BACKGROUND & AIMS: We have previously shown that aberrant crypt foci (ACF) are the putative precursor lesions of colorectal adenomas and subsequent cancer in humans using magnifying endoscopy. The present study was designed to investigate these genetic alterations in ACF biopsy specimens from normal subjects, familial adenomatous polyposis (FAP) or sporadic patients. METHODS: The non-FAP cases included 34 normal subjects, 35 colorectal adenoma patients, and 19 colorectal cancer patients; there were 4 FAP patients. Biopsies were performed on ACF by magnifying endoscopy. K-ras mutations were analyzed by 2-step polymerase chain reaction and restriction fragment length polymorphism, APC mutations by in vitro-synthesized protein assay, and beta-catenin mutations by direct sequencing. Full-length APC and beta-catenin were detected by immunofluorescence. RESULTS: In non-FAP cases, K-ras mutations were detected in 82% (89/106) of nondysplastic ACF and 63% (17/27) of dysplastic ACF. APC mutation and beta-catenin accumulation were not detected in non-FAP ACF, whereas in adenoma of these patients, positivity of APC mutation and beta-catenin accumulation were 78% (24/31), and that of K-ras mutation was 65% (20/31). FAP patients showed K-ras mutations in only 13% (1/8) of dysplastic ACF, which is the predominant form of ACF found in FAP. In FAP patients, somatic APC mutations were found in 100% of dysplastic ACF, as they are in adenoma. The frequency of K-ras mutations was 73% (8 of 11) in FAP adenoma. CONCLUSIONS: The data suggest that in sporadic colorectal carcinogenesis, assuming the biological implication of ACF as a precursor of adenomas, there is a route where K-ras mutation mainly occurs during the formation of ACF, which then become adenomas wherein APC mutation occurs. In FAP, however, somatic mutation of APC predominantly occurs during ACF formation, followed by K-ras mutation.     

Rectal epithelial apoptosis in familial adenomatous polyposis patients treated with sulindac

BACKGROUND: Sulindac regresses colorectal adenomas in patients with familial adenomatous polyposis (FAP), although the mechanism of polyp regression is unclear. AIMS: To determine whether differences occur in alteration of rectal epithelial apoptotic index and expression of apoptosis related proteins in FAP patients treated with sulindac compared with placebo. PATIENTS: Twenty one FAP patients; 12 had not undergone colectomy. METHODS: Patients with FAP were treated with sulindac 150 mg orally twice a day for three months (n=10) or placebo (n=11). Colorectal polyp number was determined and biopsies of the normal rectal mucosa were performed before and after three months of treatment. Response to treatment and alteration of the apoptotic ratio (index in base of crypt divided by index in surface epithelium) were evaluated. Bcl-2, bax, p21/WAF-1, and p53 proteins were assessed semiquantitatively by immunohistochemistry. RESULTS: Significant decreases in polyp number and in the apoptotic ratio were seen in patients treated with sulindac compared with controls. The mean percentage change in polyp number from baseline was -46% in the sulindac group and +13% in the placebo group (p=0.005). Mean percentage change in the apoptotic ratio was -8% and +25% in the sulindac and placebo treated patients, respectively (p=0.004). No differences in expression or compartmentalisation of apoptosis related proteins were noted between treatment groups. CONCLUSIONS: Sulindac regression of colorectal adenomas is accompanied by alteration of the rectal epithelial apoptotic ratio with relative increase in apoptosis in surface cells compared with the deeper crypt. The utility of the apoptotic ratio as an intermediate biomarker for colorectal tumorigenesis deserves further study.     

High frequency of K-ras mutations in sporadic colorectal adenomas.

The frequency of activating mutations at codons 12 and 13 of the K-ras gene was investigated in 57 sporadic adenomas from 47 patients using the polymerase chain reaction and oligonucleotide hybridisation assay. Sixty eight per cent of the adenomas tested were positive for K-ras mutations. This high frequency, combined with the lack of a correlation between mutations and adenoma size, suggest that K-ras mutations occur earlier in the adenoma-carcinoma sequence than has previously been suggested. The high frequency observed in sporadic adenomas contrasts with the reported low frequency (18%) in adenomas from patients with familial adenomatous polyposis (FAP), suggesting a possible difference in the molecular genesis of FAP and non-FAP adenomas. Finally, it was found that adenomas from patients with a personal history of colorectal cancer were more likely to contain a K-ras mutation than those from patients with no such history. This is a new finding and worthy of further study.     

凋亡相关基因caspase-9、Bcl-2在大肠腺瘤和大肠癌中的表达及意义

目的 探讨凋亡相关基因caspase-9和Bcl-2在大肠腺瘤、大肠癌中的表达及意义。方法 应用免疫组化S-P法检测56例大肠癌、48例大肠腺瘤及20例正常大肠黏膜中的caspase-9和Bcl-2蛋白的表达。用TUNEL法检测细胞调亡。结果 正常大肠黏膜、大肠腺瘤和大肠癌中caspase-9的阳性表达率分别为5.00％、33.33％、64.29％,其表达率在三者间有显著性差异(P<0.01)。Bcl-2在正常大肠黏膜、大肠腺瘤和大肠癌中的阳性表达率分别为15.00％、87.50％、60.71％,三者间亦有显著性差异(P<0.01)。caspase-9,Bcl-2的表达与肿瘤的分化程度有关(P<0.01),与Dukes分期无关(P>0.05)。正常大肠黏膜、腺瘤和大肠癌中凋亡指数有显著性差异(P<0.01),凋亡指数与肿瘤的分化程度有关(P<0.01),与Dukes分期无关(P>0.05)。caspase-9,Bel-2的表达与凋亡指数有密切联系(P<0.01)。结论 在大肠癌形成过程中,caspase-9,Bcl-2参与了肿瘤形成的共同通道;肿瘤早期阶段细胞凋亡的异常和增生过度,楞能是大肠癌的发病原因之一。     

大肠肿瘤的基因表达及与细胞凋亡的抑制关系

目的探讨 bcl-2和 P53蛋白在大肠肿瘤中的表达及与细胞凋亡关系。方法用免疫组化方法观察了45例大肠腺瘤和61例大肠癌中 bcl-2和 P53蛋白的表达。结果正常大肠粘膜中 bcl-2和 p53均未见表达,而大肠腺瘤及大肠癌阳性率均较正常明显增加(P<0.01)。大肠腺瘤 p53表达随腺瘤大小增加而增加,其中≥20 mm 组阳性率(77.8%)显著高于<10 mm 组(35.0%,P<0.05)。P53蛋白阳性率也随不典型增生程度增加而增高。p53表达与大肠癌分化程度及 Duke 分期有关。大肠癌细胞凋亡指数与 bcl-2阳性表达呈负相关。大肠腺瘤中 bcl-2和 P53蛋白的表达也呈负相关。结论 bcl-2蛋白表达对大肠癌前病变.腺瘤的增殖有一定意义,p53在大肠腺瘤癌变和大肠癌进展中起重要作用,它们是参与细胞凋亡的良好指标。     

Synchronous primary carcinomas of the ampulla of Vater and ascending colon in a patient with multiple flat adenomas

Multiple primary cancers occurring in the same patients have been reported to represent 1.8–3.9% of all cancers. The majority of all patients reported to have had a combination of simultaneous neoplastic changes in the ampulla of Vater and the colon showed familial adenomatous polyposis (FAP) syndrome. Variants of familial adenomatous polyposis coli are: attenuated adenomatous polyposis coli (AAPC, previously also known as flat adenoma syndrome) and multiple adenoma coli. AAPC is characterized clinically by many, but usually fewer than 100, colonic lesions that are characteristically slightly elevated and plaque-like, with a reddish surface and sometimes central depression. Genetically it represents an extremely rare variant of FAP. Another group of individuals, so-called multiple adenoma patients, have a phenotype similar to AAPC, but most have no demonstrable germ-line adenomatous polyposis coli mutation, as do patients with FAP or AAPC. However, there have been only a few reports that discussed concurrent neoplastic changes in the ampulla of Vater and colon in patients with multiple colonic flat adenomas, but without the florid phenotype of classical FAP. We present rare clinical course of a patient with multiple (more than 60) flat adenomas in the proximal colon and two primary cancers: of the ampulla of Vater and of the ascending colon. This patient and his family history did not show polyposis compatible with FAP or hereditary nonpolyposis colorectal cancer (HNPCC) syndrome.     

Serrated adenoma in familial adenomatous polyposis: relation to germline APC gene mutation

BACKGROUND: Serrated adenoma is a precursor of colorectal cancer. AIM: To clarify possible genotype-phenotype correlations of serrated adenomas in familial adenomatous polyposis (FAP). Patients: Eleven patients from eight families with FAP. METHODS: We performed total colonoscopy with multiple biopsies in patients. Neoplasia with a serrated glandular structure was regarded as a serrated adenoma. In each patient, germline mutations of the APC gene were determined. Colonic phenotype was compared with germline mutations of the APC gene. RESULTS: Serrated adenomas were found in three patients. These patients had macroscopic polyps <100 in number. Pedigrees with serrated adenomas had the truncating germline APC mutation at codon 161, 332, or 1556 while in the other pedigrees mutations were found between codons 554 and 1324. CONCLUSIONS: In FAP, serrated adenoma may be a phenotype characteristic of the attenuated form.     

Whole-gene APC deletions cause classical familial adenomatous polyposis, but not attenuated polyposis or "multiple" colorectal adenomas

Familial adenomatous polyposis (FAP) is a dominantly inherited colorectal tumor predisposition that results from germ-line mutations in the APC gene (chromosome 5q21). FAP shows substantial phenotypic variability: classical polyposis patients develop more than 100 colorectal adenomas, whereas those with attenuated polyposis (AAPC) have fewer than 100 adenomas. A further group of individuals, so-called "multiple" adenoma patients, have a phenotype like AAPC, with 3-99 polyps throughout the colorectum, but mostly have no demonstrable germ-line APC mutation. Routine mutation detection techniques fail to detect a pathogenic APC germ-line mutation in approximately 30% of patients with classical polyposis and 90% of those with AAPC/multiple adenomas. We have developed a real-time quantitative multiplex PCR assay to detect APC exon 14 deletions. When this technique was applied to a set of 60 classical polyposis and 143 AAPC/multiple adenoma patients with no apparent APC germ-line mutation, deletions were found exclusively in individuals with classical polyposis (7 of 60, 12%). Fine-mapping of the region suggested that the majority (6 of 7) of these deletions encompassed the entire APC locus, confirming that haploinsufficiency can result in a classical polyposis phenotype. Screening for germ-line deletions in APC mutation-negative individuals with classical polyposis seems warranted.