Familial colorectal cancer and the screening of family members

A case-control study was undertaken of the family histories of colorectal cancer in 128 patients with colorectal cancers and those of 61 patients with colorectal adenomas and matched surgical control patients who were attending a regional surgical service in Western Australia. One family with multiple polyposis of the colon was excluded from the study. A history of colorectal cancer in one or more first-degree relatives was associated with a relative risk of colorectal cancer of 2.5 (95% confidence interval, 0.8 to 8.0), of adenoma of 2.0 (95% confidence interval, 0.5 to 8.0) and of any colorectal neoplasm of 2.3 (95% confidence interval, 0.9 to 5.6). Four patients with colorectal cancer and one patient with colorectal adenoma had more than one first-degree relative with colorectal cancer, whereas no control subject gave this history. The five families that were represented by these cases each showed some other features of non-polyposis familial colorectal cancer. It was estimated that familial factors could explain 60% of colorectal cancer in persons with a family history of the disease in a first-degree relative and 5% of colorectal cancer in the population as a whole. Haemoccult II tests were posted to 629 living first-degree relatives of the patients with colorectal cancers and adenomas; 44% of these relatives returned the completed tests. Four relatives with positive results of tests both before and after dietary restriction were investigated; all four subjects had colorectal adenomas. In addition, one subject had a short segment of ulcerative colitis. A further mailing of Haemoccult II tests one year later gave a 39% response rate; no further cases of colorectal neoplasia were found. One relative developed carcinoma of the caecum 10 months after a negative result in the first round of Haemoccult screening. Persons with two or more first-degree relatives with colorectal cancer, with or without other features of non-polyposis familial colorectal cancer, are at a high risk of the development of colorectal cancer. The comparatively-poor response to an offer of Haemoccult II testing and its known insensitivity and lack of specificity suggest that it is not a satisfactory method of screening these high-risk subjects.     

DukesA、B期大肠癌术后总生存率及无瘤生存率分析

目的探讨DukesA、B期大肠癌术后总生存率及无瘤生存率,分析相关因素对预后影响。方法2000年2月-2003年2月年间收治初发大肠癌病例,行首次根治术临床病理分期为DukesA及B期者65例,术后采用门诊、电话、信访方式随访至2008年2月,以COX回归比例风险模型对预后进行相关因素分析。结果全组5年总生存率及无瘤生存率分别为89．6％及80．9％,其中DukesA期病例总生存率及无瘤生存率均优于DukesB期（P〈0．01）。经过单因素分析提示与DukesA、B期无瘤生存率相关因素包括年龄（P=0．008）、组织类型（P=0．025）、肿瘤大小（P：0．036）、肿瘤部位（P=O．040）、术后化疗（P=0．005）等,将以上差异有统计学意义的变量再进入COX风险比例模型行多因素分析,提示肿瘤浸润深度（Wald卡方=4．949,P=0．026）及远处转移（Wald卡方=3．995,P=0．046）是与无瘤生存率相关的独立性影响因素。结论肿瘤浸润深度、远处转移是影响DukesA、B期大肠癌无瘤生存率的独立影响因素,随着肿瘤浸润深度的加深,术后辅助化疗可能有助于改善预后。     

A study of the relationship between frequency of allelic deletion of chromosome 17p and late-stage colorectal carcinoma

Alterationofthep53tumorsuppressorgene(TPo3)isprobablyoneofthemostcommongeneticfeaturesofhumancancerll'Zj,andcanbedetectedinawidevarietyofcancertypes.Inactivationoftumorsupprcssorgenebypointmutation,geneamplification,generearrangementOIchromosomalallelicdeletion(allelicdeletion);andchangesinDNAcontentarecommongeneticchangesfoundinmalignantcells[3j.Manytypesoftumorhavechromosomaldeletionsthatarcnonrandomanddifferentinpattern[#j.FrequentallelicdeletionofchromosomeslpIsp,oq,17p,18qand22q['.'jh…     

SSTR2、Livin 和 Survivin 在结肠癌组织中的表达及其意义

探讨生长抑素受体 2（SSTR2）,凋亡抑制因子 Livin 和存活素（Survivin）在结肠正常黏膜、结肠腺瘤、癌旁组织及结肠癌组织中的表达水平的变化规律及临床意义。方法 采用逆转录聚合酶链反应（RT-PCR）方法检测收集到的 30 例结肠正常黏膜、30 例结肠腺瘤、30 例结肠癌旁组织、30 例结肠癌组织中SSTR2、Livin 和 Survivin mRNA 的表达情况,对其表达水平进行测定,分析不同组织表达阳性率及表达强度的差别。结果 结肠癌标本中 Livin 和 Survivin mRNA 阳性表达率与结肠腺瘤比较明显升高,差异有统计学意义（ <0.05）。而 SSTR2mRNA 的阳性表达率与结肠腺瘤比较明显降低,,差异有统计学意义（ <0.05）。Livin和 Survivin mRNA 表达水平在结肠正常黏膜、结肠腺瘤、结肠瘤旁组织、结肠癌组织为逐渐增高趋势,而SSTR2mRNA 为逐渐下降趋势。结论 SSTR2、Livin 和 Survivin 在结肠黏膜从腺瘤到癌的转变过程中起着重要作用。     

潜血试验对人群大肠病变的普查意义

为验证潜血试验对人群大肠癌普查的筛检效果,在对4337例年龄在35岁以上的人群进行潜血试验的同时,作了全乙状结肠镜和部分全结肠镜检查。结果表明,肠镜病变检出率在非筛选人群为10.1％,在筛选人群中方13.3％,共查出大肠癌10例(含早期大肠癌5例),腺瘤167例,非腺瘤息肉131例,慢性肠炎171例。1％联苯胺试验阳性率为6.0％,检出60％大肠癌及3.9％腺瘤;免疫双扩试验阳性率为3.4％,检出40％大肠癌及2.0％腺瘤;SPA免疫潜血试验阳性率为14.7％,检出80％大肠癌(包括3例早期癌)及42.2％腺瘤。结果提示,潜血试验确能检出一些包括早期大肠癌在内的肠道肿瘤病变,尤以SPA免疫潜血试验敏感性最强。虽然潜血试验存在一定的漏检率(1％联苯胺为40％,免疫双扩为60％,SPA法为20％),但鉴于该法简易、经济,作为大规模大肠癌普查筛检.仍不失为一种值得推广的积极措施。     

Caspase-3基因在大肠癌、大肠腺瘤中的表达及其与细胞凋亡的关系

目的探讨大肠癌、大肠腺瘤中Caspase-3基因的表达及其与细胞凋亡的关系。方法采用免疫组化S-P法和原位末端标记法分别检测28例大肠癌、10例大肠腺瘤及5例正常大肠黏膜中Caspase-3基因的表达水平及细胞凋亡。结果Caspase-3基因在大肠癌、大肠腺瘤和正常黏膜组织中表达分别为46．4％（13／28）、60．0％（6／10）、80.0％（4／5），三者之间有显著性差异（P〈0．01）。大肠癌、大肠腺瘤中细胞凋亡指数显著高于正常黏膜组织（P〈0．01），凋亡指数与肿瘤的分化程度有关（P〈0．01），与病理类型、Dukes分期无关。大肠癌、大肠腺瘤中Caspase-3基因表达与细胞凋亡指数密切相关，阳性表达的细胞平均凋亡指数明显高于阴性表达的平均凋亡指数（P〈0．01），而正常黏膜组织中二者无显著性差异（P〉0．05）。结论肿瘤早期阶段的细胞凋亡异常和过度增生，可能是大肠癌的发病原因之一，作为细胞凋亡的调控因子，Caspase-3可能在大肠癌的发生发展中起重要作用。     

整合素连接激酶在结肠癌中的表达情况

目的:探讨整合素连接激酶(ILK)在结肠癌的发生发展中的作用。方法:采用免疫组织化学方法对84例结肠肿瘤中ILK的表达进行检测。结果:ILK在正常结肠黏膜阴性表达;在结肠腺瘤中75%表达;结肠原位癌中83.3%;在浸润性结肠癌中100%表达。ILK在结肠浸润性癌与原位癌表达差异有统计学意义,在不同分级、分期、浸润深度、淋巴结转移比较,差异有统计学意义(P<0.05)。结论:ILK在结肠肿瘤的进展、侵袭、转移上都有着重要的意义,可以作为结肠癌的预后指标。     

Comparative evaluation of investigations for colorectal carcinoma in symptomatic patients.

We studied 154 patients presenting with significant colonic symptoms and subsequently diagnosed to have colorectal carcinoma. They were investigated by faecal occult blood tests, fibresigmoidoscopy, double contrast barium enema (DCBE) and colonoscopy. Faecal occult blood tests (Haemoccult) alone were positive in 26% of patients with Dukes'' A, in 69% with Dukes'' B and in 64% with Dukes'' C lesions. DCBE alone identified the lesion in 32% of Dukes'' A, 79% of Dukes'' B and 81% of Dukes'' C carcinomas. Fibresignoidoscopy diagnosed colorectal malignancy in 84% of patients with Dukes'' A, 90% with Dukes'' B and 81% with Dukes'' C stage. A diagnostic yield of 88% for Dukes'' A, 96% for Dukes'' B and 100% for Dukes'' C carcinomas was seen with colonoscopy. Detection rate for all stages of carcinoma was greater than 95% when fibresigmoidoscopy and DCBE were used together. Faecal occult blood tests and DCBE alone are inadequate in diagnosing early malignancy in symptomatic patients. Fibresigmoidoscopy and DCBE used in conjunction compare favourably with the technically difficult procedure of colonoscopy and should routinely be undertaken in these patients before malignancy can confidently be excluded.     

DukesA、B期大肠癌术后复发及转移的危险因素分析

目的探讨Dukes A期及B期大肠癌术后局部复发或者远处转移的危险因素。方法对2000年2月-2003年2月间首次实施根治性手术的Dukes A期及B期者65例,随访至2008年2月。局部复发的诊断应用肠镜及病理检查,远处转移的诊断应用B超或CT检查。结果全组患者术后5年共3例局部复发,复发率4.8%（3/65）。6例发生肿瘤远处转移,转移率9.6%（9/65）。肿瘤部位（R=-0.257,P=0.039）及局部浸润深度（R=-0.339,P=0.006）与复发相关。肿瘤局部浸润深度（R=-0.255,P=0.04）、神经受累（R=0.251,P=0.044）、术后放疗（R=0.307,P=0.013）、术后化疗（R=-0.431,P=0.007）与肿瘤远处转移相关。结论较早期的大肠癌患者根治术后仍有复发或者转移的可能性,术后化疗可减小Duke B期大肠癌患者术后转移的发生     

The screening model for early diagnosis of colorectal cancer in general population]

In this study, 75,813 asymptomatic individuals above 30 in Jiashan County of Zhejiang Province were recruited in the screening program. Based on results of risk assessment using a mathematical model (expressed as AD value) and Reverse Passive Hemagglutination Fecal Occult Blood test (RPHA FOB). 62,667 subjects (82.7%) who completed two procedures were divided into 4 groups: 1) AD greater than or equal to 0.3 FOB (+) accounts for 1.2% of total; 2) AD less than 0.3 FOB (+) 3.0%; 3) AD greater than or equal to 0.3 FOB (-) 26.8%; 4) AD less than 0.3 FOB (-) 68.9%. Individuals in groups 1 and 2 were subjected to 60 cm fiberoptic colonoscopic examination; and those of group 3 with AD greater than or equal to 0.5 or with AD less than 0.5 but a positive repeated FOB test was also eligible for 60 cm colonoscopy. Out of 4,299 eligible subjects 3,162 were examined with 60 cm sigmoidoscopy (73.6%). 21 cases of colorectal cancer and 331 cases of polyps (including 75 adenomas) were detected. Among 21 cancers known of Dukes' stages 10 were at early stages (10 Dukes' A and 5 Dukes' B) accounting for 71.5%. According to the screening protocol individuals with negative 60 cm colonoscopic findings and consistently positive FOB results indicate that the lesion may be located above the spleen flexure and require a full fiberoptic colonoscopic examination (150 cm) and/or x-ray air-barium enema.     

577例直肠癌病理与临床预后关系的研究

目的:探讨直肠癌的病理分型与临床预后的关系。方法:根据WHO国际肿瘤组织学分类及Dukes分期标准,回顾性研究了577例直肠癌的临床病理资料。结果:溃疡型335例,隆起型228例,浸润型14例。其中高分化腺癌104例,大多数为Dukes A期。中分化腺癌309例,与分期无明显差异。低分化腺癌71例,粘液腺癌78例,印戒细胞癌10例,均多数为C期。未分化癌,鳞癌各2例,均为C期。1例类癌为A期。结论:直肠癌的病理组织学分型与Dukes分期及临床预后有密切关系。     

遗传性非息肉病性结直肠癌中环氧合酶2的表达及与错配修复基因表达和微卫星不稳定的相关性

目的 探讨遗传性非息肉病性结直肠癌(HNPCC)腺瘤及癌组织中环氧合酶2(COX-2)的表达及其与错配修复(MMR)基因蛋白表达、微卫星不稳定(MSI)之间的关系.方法 来源于33个HNPCC家系的大肠腺瘤28例、大肠癌14例,随机留取经病理确诊的32例散发大肠腺瘤和24例散发大肠癌标本作为对照;采用免疫组织化学和PCR技术,检测腺瘤及癌组织中COX-2、MMR基因(hMLH1、hMSH2、hMSH6)蛋白表达及BAT-25、BAT-26、D2S123、D5S346、D17S250 5个微卫星位点的MSI状态.结果 COX-2在HNPCC腺瘤及癌组织中高表达率分别为53.6%(15/28)、42.9%(6/14),在散发大肠腺瘤和大肠癌中高表达率分别为62.5%(20/32)、91.7%(22/24),HNPCC癌组织中的COX-2表达明显低于散发大肠癌(P＜0.05).HNPCC大肠癌中MMR蛋白表达缺失率、高度微卫星不稳定(MSI-H)发生率[均为71.4%(10/14)]明显高于散发大肠癌[均为12.5%(3/24),均P＜0.05].10例MMR蛋白表达缺失的HNPCC大肠癌中,8例为COX-2低表达;4例MMR蛋白表达阳性的HNPCC大肠癌全部为COX-2高表达.在MMR表达缺失的HNPCC大肠癌、HNPCC腺瘤、散发大肠癌中COX-2的表达均显著少于MMR表达阳性者(均P＜0.05).MSI-H的HNPCC大肠癌、HNPCC大肠腺瘤、散发大肠癌中COX-2低表达率分别为80.0%(8/10)、66.7%(12/18)、66.7%(2/3);与微卫星稳定(MSS)组比较差异均有统计学意义(均P＜0.05).结论 与散发性大肠癌相比,COX-2在HNPCC大肠癌组织中表达明显减少;COX-2在大肠腺瘤及癌组织中的表达率与MMR蛋白表达缺失和MSI-H呈明显的负相关;COX-2、MMR蛋白表达、MSI的检测对于进一步研究大肠肿瘤的发病途径及干预治疗具有重要意义.     

吻合口上下双管引流法对左侧结肠癌梗阻患者一期术后肠黏膜屏障功能的影响

目的确定经肛吻合口上下双管引流对左侧结肠癌梗阻患者一期术后肠黏膜屏障功能的影响,为其在临床上预防吻合口漏的应用提供依据。方法分为术后扩肛组(A)、经肛吻合口上下双管引流组(B)两个组,观察梗阻性左侧结肠癌梗阻患者一期切除术后血浆内毒素(ET)及肿瘤坏死因子(TNF)的变化。结果术后A、B两组ET、TNF均呈下降趋势,与术前比较有显著差异(P<0.01),自术后3天,B组患者各指标开始显著低于A组(P<0.05)。结论经肛吻合口上下双管引流能有效减少肠道内毒素的吸收及降低TNF水平,间接反映了该法可以促进左侧结肠癌伴梗阻患者一期术后肠黏膜屏障功能的恢复,可做为预防吻合口漏的有效方法。     

p53蛋白在甲状腺乳头状癌中的表达及临床意义

目的　研究ｐ５３蛋白在甲状腺乳头状腺癌中的表达,并探讨其能否成为甲状腺乳头状腺癌的独立预后因素。方法　应用免疫组化方法,对４０例甲状腺乳头状腺癌、１０例甲状腺滤泡型腺瘤和１０例甲状腺正常组织进行了ｐ５３蛋白表达的研究,并对可能影响甲状腺乳头状腺癌病人预后的有关因素进行了ｌｏｇｒａｎｋ单因素生存分析和Ｃｏｘ逐步回归多因素生存分析。结果　７例（１７．５％）甲状腺癌的ｐ５３蛋白表达阳性,而甲状腺滤泡型腺瘤及正常组织的表达均为阴性;表达阳性的病人其术后复发率较表达阴性者明显升高,差异有显著性（Ｐ＜０．０５）;经ｌｏｇｒａｎｋ检验及Ｃｏｘ逐步回归多因素生存分析,提示ｐ５３蛋白阳性表达病人术后复发的风险比是阴性表达者的４．３２４８８倍,差异有显著性（Ｐ＜０．０５）。结论　ｐ５３蛋白在甲状腺乳头状腺癌中有一定的表达,表达阳性的病人其术后复发率较表达阴性者明显升高,ｐ５３蛋白阳性表达是甲状腺癌术后复发的预后指标。建议应加强对此类病人的治疗和随访工作。     

纵隔胸膜在中上段食管癌中的应用

目的探讨纵隔胸膜在中上段食管癌中应用的意义。方法选择肿瘤外科手术切除中上段食管癌482例,分为A、B两组。A组230例:2006年8月以前未缝合纵隔胸膜组;B组252例:2006年8月以后缝合组。两组患者肿瘤均位于食管中上段,其临床病理分期如下:Ⅰ期107例,Ⅱa期148例,Ⅱb期143例,Ⅲ期84例。结果所有患者均手术顺利,无近期死亡。吻合口瘘A组13例,B组4例;胸闷不适A组37例,B组13例。两组比较差异有统计学意义(P<0.05),改善了患者术后生存质量。严重的反流性食管炎、肺部感染、肺不张、切口感染等并发症在本研究组中差异无统计学意义(P>0.05)。结论在中上段食管癌,采用纵隔胸膜覆盖,明显减少吻合口瘘和胸闷不适的发生;而且操作简单,易于推广。     

DNA content and its relationship with pathology and prognosis of colorectal carcinoma.

The DNA content of 181 colorectal cancers was investigated by flow cytometry on paraffin-embedded specimen. The relationship of flow cytometric DNA patterns of colorectal cancer to Dukes's stage, histological type and grade, tumor size and patient's prognosis were analysed. The DNA aneuploid carcinomas were found in 53.04% of the patients (hypodiploid 22.10%, hyperdiploid 20.99%, polyploid 9.94%). Diploidy was found in 46.96% of the patients with colorectal cancer. The proportions of aneuploidy were significantly lower in the patients with Dukes' stage A (25.00%) and B (47.14%) than those with Dukes' stage C (64.71%) and D (68.42%). Aneuploid frequency was higher in the patients with poorly differentiated adenocarcinoma (84.62%), mucinous adenocarcinoma (62.50%) and tubular adenocarcinoma (52.75%) than those with villous adenocarcinoma (22.86%). The proportion of aneuploidy was significantly higher in the patients with poorly differentiated tumor (71.79%) than in those with moderately (50.00%) and well differentiated tumors (44.83%). Five-year survival rate of the patients with DNA aneuploid tumors was 33.80% compared with 66.67% of those with diploid tumors. Analysis of Cox regression revealed that DNA ploidy and Dukes' stage significantly influenced the patient's prognosis. It is suggested that DNA ploidy might be an important prognostic factor in colorectal cancer.

     

Community care compared with hospital outpatient care for hypertensive patients

Three hundred and seventy-six patients with treated diastolic blood pressures of less than 105 mm Hg and no history of accelerated hypertension or renal failure were selected from among those attending the Hammersmith Hospital hypertension clinic. Their average lying treated blood pressure was 146 mm Hg systolic and 90 mm Hg diastolic and average age 56 years; 18% were black, 6% Asian, and 76% white. The patients were mostly having multiple treatment, 90% receiving a diuretic, 35% methyldopa, 33% propranolol, 18% atenolol, 9% hydrallazine, and 7% bethanidine. They were randomly allocated to either two years of further hospital outpatient care or referred back to their general practitioners. During the two years 19 (10%) of the 187 patients followed up in hospital defaulted and three had their treatment discontinued. Twelve (6%) of the 189 followed up by their general practitioners defaulted from follow-up and nine had their treatment discontinued. At the end of the trial the average lying blood pressure was 148 mm Hg systolic and 88 mm Hg diastolic in the hospital group and 149 mm Hg systolic and 90 mm Hg diastolic in the general practice group. The change in blood pressure was calculated for each individual and showed an average fall of 1.6 mm Hg in standing diastolic pressure in the hospital group and a rise of 1.4 mm Hg in the general practice group (p less than 0.05). The 90% confidence limits for a difference in standing diastolic pressure between the groups were 1 and 5 mm Hg with the pressure lower in the hospital group. General practice care was not quite as effective in controlling blood pressure as continued specialist supervision over two years in this selected group of treated outpatients with mild or moderate hypertension, but these results show that the discharge back to general practitioners of patients who are well controlled after hospital treatment is a sensible policy.     

204例大肠息肉的免疫组织化学研究

本文采用4种抗结肠癌单克隆抗体CL-2、CL-4、MC_3和MC_5检测了204例大肠息肉。结果显示,4种抗体的相应抗原在正常大肠粘膜为阴性表达,在炎性与幼年性息肉以及单纯性腺瘤阳性表达低,而在腺瘤不典型增生和腺癌癌变阳性表达较高,提示其阳性率与不典型增生有关(P<0.01),4种抗体的相应抗原在大肠癌组织中占优势,且对判定癌前病变的抗原表达有一定的价值,可作为早期判断腺瘤癌变的参考。     

Management of colonic polyps by colonoscopic polypectomy

Colonoscopic polypectomy is an important therapeutic advance as it enables most colonic polyps to be removed entirely and studied pathologically and has virtually replaced surgical treatment. The clinical and pathological features of patients with colonic polyps treated by colonoscopic polypectomy over a five-year period are reported. Seventy-four patients (37 men, 37 women) with a mean age of 57 years had 109 polyps removed by snare polypectomy. Rectal bleeding was the predominant symptom and was present in 63.5%. Lower abdominal pain was present in 12%. The majority of polyps were located in the sigmoid (38.5%) and descending (40.3%) colon. Ninety-five polyps were pedunculated and 14 were sessile. Of the neoplastic polyps, 61.6% were pure tubular adenomas, 25.2% were mixed tubulo-villous adenomas and 1% were pure villous adenomas. There were no complications arising from colonoscopy or snare polypectomy. Colonoscopic polypectomy is a safe, reliable and cost-effective therapeutic procedure that has revolutionized the management of pre-cancerous neoplastic colonic polyps.