遗传性非息肉病性结直肠癌患者围手术期护理

遗传性非息肉病性结直肠癌(hereditary nonpolyposis cancer,HNPCC)是一种常染色体显性遗传性肿瘤疾病,占所有结直肠癌的2%～7%[1],错配修复(mismatch repair,MMR)基因突变是该病的遗传学基础,临床以发病年龄早,多原发癌多见,以右半结肠癌为主.1990年国际HNPCC协作组制订阿姆斯特丹标准,同时具备以下3个条件可诊断为本病:(1)家族中至少有3例组织病理学证实的结直肠癌者,其中有1例必须是另外2例的一级亲属,需除外家族性腺瘤病;(2)结直肠癌必须是累及连续的2代人;(3)至少有1例结直肠癌患者发病早于50岁.1993年日本提出新的修改标准为符合以下2组标准之一者皆可诊断为本病:(1)家族中一级亲属中有3个或3个以上结直肠癌患者;(2)家族中有2个结直肠癌患者伴有以下情况之一:①癌发病年龄在50岁以下;②右侧结肠癌;③有同时或异时多原发结直肠癌;④有其他器官癌.依照上述标准我们收集温州地区12个HNPCC家系,现报告如下.     

15个遗传性非息肉性大肠癌家系的临床分析

目的探讨遗传性非息肉性大肠癌（HNPCC）的临床特点和治疗措施。方法回顾分析15个HNPCC家系的临床资料。结果①50岁以前发病者占58．33％（28／48），中位发病年龄45．3岁；②右半结肠癌占43．72％（21／48）；③低分化癌占47．91％（23／48）；④肠外癌的种类：胃癌5例，鼻咽癌、胶质瘤、宫颈癌、食管癌各1例。结论HNPCC发病年龄较散在大肠癌年轻；发病部位以右半结肠癌最多；低分化癌比例高；垂直传递特征突出。对HNPCC主张行全结肠切除或结肠直肠切除。     

孕妇肾绞痛的观察与护理

遗传性非息肉病性结直肠癌(hereditary nonpolyposis cancer，HNPCC)是一种常染色体显性遗传性肿瘤疾病，占所有结直肠癌的2％～7％，错配修复(mismatch repair，MMR)基因突变是该病的遗传学基础，临床以发病年龄早，多原发癌多见，以右半结肠癌为主。1990年国际HNPCC协作组制订阿姆斯特丹标准，同时具备以下3个条件可诊断为本病：(1)家族中至少有3例组织病理学证实的结直肠癌者，     

非典型的遗传性非息肉病性结直肠癌10家系报道

目的了解中国人的非典型遗传性非息肉病性结直肠癌 (HNPCC)的临床及病理特点 ,并对标准进行讨论。方法随访非典型HNPCC患者共 10家系 2 0例。结果第 1癌的发病平均年龄为 49岁 ,直肠结肠多见 ,占 65 .8% ,18例行手术治疗 ,切除率为 90 % ,术后病理粘液癌为 3例 (15 % ) ,Dukes分期 A期 1例 ,B期 6例 ,C期 6例 ,D期 7例 ,1年、3年、5年及 10年的生存率为 86.0 2 %、61.70 %、3 8.11%及 2 5 .81%。结论非典型 HNPCC是一种发病早、预后较好的大肠癌 ,Amsterdam标准作为 HNPCC的工作标准过于严格。     

遗传性非息肉病性结直肠癌的诊断和治疗进展

遗传性非息肉病性结直肠癌（heredilary nonpolyposis colorectal cancer．HNPCC）是一种常染色体显性遗传疾病，占所有大肠癌的5-15％。HNPCC义称Lynch综合征或家族性癌综合征，通常可以分为Lynch Ⅰ综合征和LynchⅡ综合征两大类。Lvneh Ⅰ综合症又称遗传部位特异性结直肠癌（hereditary sitespecific coloreetal cancer，HSSCC），在这类家系中大肠癌是唯一的恶性肿瘤，往往发病比较早，70％病变位于近端结肠，常见同步或异步的大肠癌。Lynch Ⅱ综合征又称癌症家族综合征（cancer family syndrome，CFS），     

遗传性非息肉病性大肠癌16个家系60例报告

遗传性非息肉病性结直肠癌（hereditary nonpolyposis colorectal cancer，HNPCC）是一种常染色体显性遗传的综合征，又被称为Lynch综合征，占结直肠癌的1％～6％。作者共发现16家系60例HNPCC，现与随机收集散发性大肠癌（SCRC）35例作一对照分析。     

微卫星不稳定检测在新疆地区人群HNPCC家系筛查中的应用

目的通过微卫星不稳定性(MSI)检测在中国新疆地区人群遗传性非息肉病性结直肠癌(HNPCC)家系筛查,为临床筛查提供相关依据。方法通过聚合酶链反应-单链构象多态性(PCR-SSCP)技术对新疆地区的HNPCC家系组(A组12例)、可疑HNPCC家系组(B组10例)及散发型大肠癌(C组20例)进行检测及分析。结果 HNPCC家系、可疑HNPCC家系组及散发型大肠癌高度微卫星不稳定(MSI-H)情况分别为83.3%、50.0%、10.0%,HNPCC家系、可疑HNPCC家系组分别较散发型大肠癌高度微卫星不稳定情况高(P<0.05),差异有统计学意义。结论 MSI与HNPCC情况高度相关,作为HNPCC筛查的重要手段,对指导临床有重要意义。     

遗传性非息肉病性大肠癌的诊治及随访(附1例典型家系报告)

遗传性非息肉病性大肠癌（hereditary non-polyposis colorectal cancer，HNPCC）即Lynch综合征，属常染色体显性遗传性疾病，根据有无肠外肿瘤分为Lynch综合征Ⅰ和Lynch综合征Ⅱ型。该病约占大肠癌病例的5％～15％，近年来文献报道病例数有增多趋势，我科最近发现1个HNPCC家系。本文通过探讨对该病例的诊治及随访经验，结合复习国内外新近文献，以期提高医生对该病的认识，做到早期诊断，早期治疗。现介绍病例如下。     

遗传性非息肉病性结直肠癌研究进展

遗传性非息肉病性结直肠癌(hereditary nonpolyp-osis colorectal cancer,HNPCC)是一种常染色体显性遗传性疾病,也叫Lynch综合征,占全部结直肠癌的5%~10%[1,2]。由于此病的临床特征、诊断、治疗以及预后与散发大肠癌有所不同,近年来与之相关的研究已受到普遍关注。本文复习近年     

腹腔镜下结直肠癌根治切除术21例围术期护理

2003后11月～2009年10月,我们为21例直肠癌患者行腹腔镜下结、直肠癌根治切除术,并给予精心围术期护理,均取得满意效果.现报告如下. 1 资料与方法 1.1 临床资料 本组21例,男15例,女6例;年龄56～72岁.临床病程7～15个月,术前均经肠镜及病理证实为肠腺癌Dukes分期均为B期.其中8例直肠癌患者行腹腔镜下腹-会阴直肠癌切除术,11例乙状结肠癌行腹腔镜下乙状结肠癌切除术,2例升结肠癌行腹腔镜下手助式右半结肠癌切除术.本组21例手术均获成功,无中转术式,无天重并发症.     

Hereditary nonpolyposis colorectal cancer (Lynch syndrome): molecular pathogenesis and clinical approaches to diagnosis and management for nurses

Hereditary nonpolyposis colorectal cancer (HNPCC), also referred to as Lynch syndrome, is the most common form of hereditary colorectal cancer and is responsible for 2% to 4% of all colorectal cancers in the Western hemisphere. Generally characterized by early-onset colorectal carcinoma with a mean age of presentation of 40 to 45 years, it can also manifest with extracolonic adenocarcinomas and cancers of the endometrium, ovaries, stomach, pancreas, small intestine, hepatobiliary tract, upper uroepithelial tract, brain, and skin. HNPCC is autosomal dominant and carries an 80% lifetime risk of cancer development. This review addresses the molecular underpinnings of HNPCC while providing a concise approach to clinical detection, diagnosis, and management of patients who may or may not test positive for an HNPCC-causing mutation. Although applicable to any patient-care setting in which cancer may be observed, this review specifically addresses the role of nurses in detecting, diagnosing, and clinically managing HNPCC.     

Hereditary colorectal cancers

Individuals with one of the highest known risks of developing colorectal cancer are members of hereditary colorectal cancer families. Familial adenomatous polyposis (FAP) and hereditary nonpolyposis colon cancer (HNPCC) are the most commonly recognized hereditary colorectal cancer syndromes. Surveillance, family identification, and education are of major importance. Genetic screening holds further promise.     

Prophylactic Colectomy in Patients with Hereditary Nonpolyposis Colorectal Cancer

Prophylactic colectomy is indicated in patients whose colons are at very high risk of developing cancer. Familial adenomatous polyposis (FAP) is the best example of a situation where prophylactic surgery is clearly necessary to prevent cancer, and has been shown to be effective in doing so. Recent advances in the molecular genetics of colorectal cancer have allowed presymptomatic diagnosis of patients with another dominantly inherited syndrome, hereditary nonpolyposis colorectal cancer (HNPCC). Prior to this, prophylactic colectomy had not been a consideration for patients in HNPCC families.     

Spectrum of germ-line MLH1 and MSH2 mutations in Austrian patients with hereditary nonpolyposis colorectal cancer

BACKGROUND: Germ-line mutations in mismatch repair genes are associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, which is characterized by susceptibility to cancer of the colon, endometrium, small bowel or urothelium at an unusually young age and with a high degree of penetration in all generations. MATERIAL AND METHODS: One hundred and nine individuals from 46 Austrian families who fulfilled the Amsterdam criteria (n = 29) or at least one of the Bethesda guidelines (n = 17) were analyzed for mutations in MLH1 and MSH2. Microsatellite instability was determined in the tumors of index persons and affected relatives. RESULTS AND CONCLUSION: High-grade instability was present in 60.6% of the tumor samples from index patients. Twenty-three germ-line DNA sequence variants in 24/46 families and four somatic mutations in three tumors were detected in MLH1 and MSH2. Fifteen mutations are novel. None of the newly identified germ-line variants was found in 100 alleles of healthy control individuals. We were able to characterize two intronic variants (MLH1 c.589-10T>A; MSH2 c.367-1G>A) with regard to their effect on mRNA. Both created new splice sites that replaced the regular ones. Germ-line mutations occurred in 44.8% of the families fulfilling the Amsterdam criteria and in 35.3% of the Bethesda patients. The detection of a pathogenic mutation was strongly correlated with microsatellite instability in the tumor DNA (p=0.007). This study is the first comprehensive report of mutations in mismatch repair genes in Austrian patients with HNPCC.     

Automated and simultaneous identification of microsatellite instability by fluorescence-based polymerase chain reaction (PCR) in four loci

Genomic instability is sometimes due to impairment of DNA repair systems, which results in a change in the number of microsatellite repeats in tumor cells, produced by slippage during DNA replication. Such abnormal repeats are manifested as microsatellite instability (MSI). We have devised a simple assay using four-color fluorescence for the detection of MSI by an automatic sequencer. Using this method, MSI and loss of heterozygosity (LOH) at four microsatellite loci can be identified simultaneously. We have also developed an algorithm and software for automated analysis of MSI and LOH with this method. Using our method for the detection of MSI in four microsatellite loci and the algorithm and software that we developed, 18 (94.7%) of 19 patients with hereditary nonpolyposis colorectal cancer (HNPCC), meeting the Amsterdam Minimum Criteria, were found to exhibit MSI.     

Low colonic glutathione detoxification capacity in patients at risk for colon cancer

BACKGROUND: Colon carcinogenesis is a multifactorial process influenced by hereditary as well as environmental factors. The glutathione/glutathione S-transferase detoxification system in the colon is important for protection against carcinogens. We investigated the levels of glutathione/glutathione S-transferase in normal colon mucosa of patients with colorectal cancer and in patients at high risk for colorectal cancer compared with those in healthy controls. MATERIALS AND METHODS: Glutathione content was analyzed by high-performance liquid chromatography, and glutathione S-transferase enzyme activity by spectrophotometric determination with 1-chloro 2,4-dinitrobenzene. Normal colon tissue of patients with colon adenoma (n = 64), colorectal cancer (n = 37), familial adenomatous polyposis (FAP; n = 19), hereditary non-polyposis colorectal cancer families with (HNPCC+Ad; n = 34) or without (HNPCC-Ad; n = 33) adenoma was investigated. RESULTS: Glutathione levels were significantly lower in the normal colon mucosa of patients with cancer, FAP, HNPCC-Ad or HNPCC+Ad compared with adenoma patients or healthy controls. Glutathione S-transferase enzyme activity in the distal colon was significantly lower in patients with cancer or FAP compared with the adenoma patients or healthy controls, whereas values in carcinoma patients were significantly lower compared with both the HNPCC-Ad and HNPCC+Ad groups. CONCLUSIONS: An association of low colonic glutathione/glutathione S-transferase activity levels and high clinical risk for the development of colorectal cancer was observed. This low glutathione detoxification capacity might contribute to the colon cancer risk.     

Diagnosis of microsatellite instability-positive colorectal cancer

The continuing increase in knowledge regarding the genetic basis of carcinogenesis has led to diverse efforts to exploit this knowledge clinically, primarily in the form of predictive genetic testing. In conjunction with family history, gene tests are intended to improve individual cancer risk assessment. At present, genetic testing for colorectal cancer (CRC) risk--in the form of microsatellite instability (MSI) screening and DNA sequencing--is applied in hereditary nonpolyposis colorectal cancer (HNPCC). In this inherited colorectal tumor syndrome, determining the genetic status may result in an individually tailored surveillance program and prophylactic treatment, reducing cancer morbidity and mortality.     

Heterogeneous staining for mismatch repair proteins during population-based prescreening for hereditary nonpolyposis colorectal cancer

The aim of this study was to determine the frequency of microsatellite instability (MSI(+)) in tumors from a population-based series of young colorectal cancer patients and its correlation with the loss of expression of mismatch repair (MMR) proteins. The BAT-26 mononucleotide repeat was used to screen for MSI(+) in all colorectal cancers diagnosed in Western Australia throughout a 5-year period in patients <60 years of age. MSI(+) was found in 75 of 1003 (7.5%) cases, of which six contained a concomitant mutation in BRAF and were therefore excluded from further investigations as possible hereditary nonpolyposis colorectal cancer. Immunohistochemistry was used to evaluate expression of the four major MMR proteins (MLH1, MSH2, MSH6, and PMS2) in the remaining 69 MSI(+) tumors. Complete loss of MLH1 and PMS2 expression or of MSH2 and MSH6 expression was found in 35 (51%) and 17 (25%) cases, respectively, whereas other patterns of complete loss were observed in eight cases (12%). Eight tumors (12%) were initially recorded as showing normal expression, but on review seven were reclassified as having abnormal staining because of heterogeneous patterns of MMR loss. Three of these seven cases had previously been found to have germline mutations. Because of possible misinterpretation of heterogeneous immunohistochemistry staining for MMR protein loss, MSI testing is recommended as the initial screen for population-based detection of hereditary nonpolyposis colorectal cancer.     

Endoscopic management of familial colonic neoplasia

Heredity plays an important causative role in a large percentage of colorectal cancers. Clinical recognition of the hereditary polyposis syndromes, hereditary nonpolyposis colorectal cancer, and common familial colorectal cancer is essential because screening, surveillance, and treatment among affected individuals and their family members differs from that recommended for the general population. More intensive cancer screening and surveillance is required if premature death is to be avoided. Genetic testing is commercially available for most of the hereditary colorectal cancer syndromes and can greatly facilitate the management of patients if properly undertaken.