家族性腺瘤性息肉病,基因检测早筛查

家族性腺瘤性息肉病是一种导致结肠、直肠等部位出现息肉的疾病。大多数患者有数百至数千个息肉,平均死亡年龄40岁,如不予治疗,几乎所有患者在39岁前会发展为结肠癌,约占结直肠癌患者的1%。不过,也有部分患者临床表现为息肉出现时间延迟、发生数目较少、结直肠癌转化年龄较晚(平均55岁)的,称为减弱型家族性腺瘤性息肉病。     

警惕肠道息肉癌变

肠道“息肉”是指肠子里长出的各种隆起物。从医学上讲，这种息肉分肿瘤性和非肿瘤性两种。前一种叫“腺瘤”：后一种息肉不是肿瘤，包括炎性息肉、增生性息肉等，它们与癌没有什么关系。一般来说，“家族性腺瘤性息肉病”癌变的可能性最大。这种腺瘤可以引发腹痛、腹泻、便血，也可能没有任何症状，直到癌变后才被发现。有研究发现，80％的这类病人会出现“先天性视网膜色素性上皮增生”。作为一种标志，高危者可以通过眼睛的检查（眼底镜检查），发现是否患有该病的线索。同时，在这类“腺瘤”中，有些会合并存在皮肤、肌肉、骨骼或脑肿瘤，有的合并有皮肤和黏膜黑斑块（手掌和口唇的色素沉着），有些伴有指甲萎缩、脱发。由于息肉长在肠内，不经过特殊检查无法确诊，但仍然可以根据上面的那些信号，提醒患者及时就医。由于这种病有家族聚集性，因而如果家族中有一个人确诊，其他成员便应进行相关检查。除了“家族性腺瘤性息肉病”，通过显微镜检查，如果发现腺瘤是“绒毛状腺瘤”，也会存在一定的癌变可能。     

家族性腺瘤性息肉病预防性手术的临床价值分析

目的对家族性腺瘤性息肉病预防性手术的临床价值进行评价分析.方法随机抽取在2009年1月—2012年6月间该院收治的家族性腺瘤性息肉患者病例72例,将其分成对照组和观察组,分别采取常规方法进行治疗和预防性外科手术方法进行治疗,而后对这两组患者的治疗效果进行对比分析.结果观察组患者的临床治疗效果显著优于对照组,且两组差异具有统计学意义(P<0.05).手术方式涉及有结、直肠切除术、永久性回肠造瘘术;全结肠、直肠黏膜剥出、回肠储袋-肛管吻合术;次全结肠切除、回-直肠吻合术+直肠息肉电灼术.结论对家族性腺瘤性息肉病预防性手术治疗能够有效提高治疗有效率,值得临床给予关注.     

35例家族性腺瘤性息肉病的临床特点分析

目的 总结家族性腺瘤性息肉病(FAP)的临床表现、病理及内镜下特征,探讨FAP的诊断和治疗.方法 回顾性分析35例FAP患者的临床表现、病理及内镜检查等资料.结果 35例患者中28例(80.O%)有家族史;临床表现以腹泻最为多见,占74.3%(26/35);直肠及左半结肠腺瘤性息肉分布密集,直肠腺瘤癌变率高.结论 FAP临床表现无特异性,主要依靠大肠内发现成百上千枚腺瘤性息肉进行诊断,肠外表现有助于诊断,结肠镜检查是安全可靠的早期诊断手段.     

非类固醇抗炎药防治家族性腺瘤性息肉病进展

1983年,Waddell和Loughry首次报道,苏灵达(sulindac)使4例家族性腺瘤性息肉病(familialadenomatosis polyposis,FAP)患者直肠腺瘤性息肉消退。近10年来,一些动物癌发生模型应用非类固醇抗炎药(nonsteroid anti-infla-m matory drugs,NSAIDS)治疗的结果支持上述的报道。而且,一些病例报告和有关人的对照性研究也证实NSAIDS可使腺瘤消退,虽然有几种假说已取得了某些进展,但NSAIDS化学预防结直肠癌的机制迄今尚未完全阐明。1 家族性腺瘤性息肉病 结直肠腺瘤消退主要在FAP患者中得到证实。FAP及一常     

积极监测, 硬纤维瘤治疗的首选

硬纤维瘤,又称侵袭性纤维瘤病、韧带样纤维瘤病,是一种缓慢生长的比较罕见的良性肿瘤.据估计每年在百万人口中发生3.7例新病例.它发生于肌肉、腱膜和深筋膜等处,十分坚硬. 目前,病因并没有完全弄清楚,考虑可能与下列因素有关:①外伤,临床发现某些硬纤维瘤患者发病前,发病部位有外伤史;②雌激素水平升高,硬纤维瘤好发于女性,有些女性患者在绝经后,硬纤维瘤可自然消退,提示硬纤维瘤的发生可能与雌激素升高有关;③家族性腺瘤性息肉病,有报道家族性腺瘤性息肉病的致病基因——APC基因,与硬纤维瘤的的致病基因有关联.     

折刀位结直肠全切除治疗家族性腺瘤性息肉病一例

家族性腺瘤性息肉病是一种5号位常染色体显性遗传性疾病,表现为整个大肠布满大小不一的腺瘤,如不及时治疗,终将发生癌变。目前尚无折刀位结直肠全切除的报道。我们最近对1例家族性腺瘤性息肉病患者实施了折刀位结直肠全切除术,效果良好,现报道如下。     

非甾类抗炎药防治家族性腺瘤性息肉病进展

１９８３年,Ｗａｄｄｅｌ和Ｌｏｕｇｈｒｙ［１］首次报道,苏灵达使４例家族性腺瘤性息肉病（Ｆａｍｉｌｉａｌａｄｅｎｏｍａｔｏｕｓｐｏｌｙｐｏｓｉｓ,ＦＡＰ）患者直肠腺瘤性息肉消退。近十年来,一些动物癌发生模型应用非甾类抗炎药（ＮＳＡＩＤｓ）治疗的结果...     

息肉切除是否等于解除“癌前警报”

近年来，我国大肠癌发病率逐年增加。国内外大量研究显示，80％以上大肠癌与肠息肉有直接关联。肠息肉被公认为是大肠癌的“癌前病变”，且十分容易复发。因此．一旦检查息有肠息肉，病人切不要掉以轻心，即使摘除了，也需要定期到医院随访．以早期发现、早期诊断、早期治疗大肠癌。临床上根据息肉的特征，将息肉分为增生性息肉、炎症性息肉、腺瘤样息肉以及家族性息肉病。     

一个大型胆囊结石病家系的遗传特征及流行病学分析

目的调查某胆囊结石(胆石)病家系的遗传特点及流行病学特征。方法对该家系进行问卷调查、体格检查及实验室检查。结果该家系四代共113人(男55人,女58人),胆石患者33例(男13例,女20例),女性发病率(34.48%)高于男性(23.64%),但差异无统计学意义。和先证者有血缘关系的亲属中Ⅱ、Ⅲ代发病率52%,明显高于配偶的发病率(20%),P=0.003。先证者Ⅰ级亲属遗传度86.38%±46.46%。患者平均体重指数(25.06±2.59)kg/m2,显著高于非胆石病者平均体重指数(22.69±3.24)kg/m2,P=0.012。胆石病患者中有高血压、高血脂病史者明显多于非胆石病者,差异有统计学意义,P值分别为<0.01和0.017。糖尿病病史、饮酒习惯、喜油腻饮食在胆石病患者和非胆石病者中无差异。胆石病患者血糖平均值(5.35±0.77)mmol/L。血胆固醇和甘油三酯在胆石病患者和非胆石病者中无差异。结论该家系胆石病具有明显家族聚集性,符合常染色体显性遗传特点;性别、肥胖、高血压和高血脂病史是该家系的危险因素。     

我国高影响因子医学期刊临床试验注册和发表机制实施现状分析

【目的】 分析我国高影响因子医学期刊临床试验注册和发表机制的实施现状,为该机制的合理实施提供参考。【方法】 选择20种高影响因子医学期刊为调查对象,对其前瞻性临床试验论文的临床试验注册相关内容进行调查,并且进一步验证临床试验注册号的正确性、论文报道内容和临床试验注册内容的一致性。【结果】 376篇前瞻性临床试验论文中,仅28篇(7.4%)标注临床试验注册机构和注册号。其中,4篇(14.3%)论文的临床试验注册相关内容与期刊稿约要求不一致,4篇(14.3%)论文的临床试验注册号错误,3篇(10.7%)论文的发表内容和临床试验注册内容不一致。11种(55.0%)期刊的稿约中要求标注临床试验注册机构和注册号,但均未作强制性要求。【结论】 我国医学期刊对临床试验注册和发表机制的执行不严格,仅遵循自愿原则。医学期刊编辑和临床研究者对临床试验注册的重视程度均有待提高。医学期刊可根据自身的情况,有针对性地实施临床试验注册和发表机制。     

Digestive polyposis. Retrospective study of 20 cases

BACKGROUND: Three main polyposis syndromes are transmitted as an autosomal dominant disorder: familial adenomatous polyposis (FAP), juvenile polyposis syndrome (JPS) and Peutz-Jeghers syndrome. AIM: Evaluate this management of digestive polyposis. METHODS: Our study included 20 patients which were collected in th departements of pathology surgery and garstroenterology of MT Maarmouri's Hospital, Nabeul city. RESULTS: We reported 15 cases of adenomatous polyposis with 2 family groups. We identified a family group of JPS with 3 members and 2 cases of Peutz-Jeghers syndrome. We found 11 cases of colonic adenocarcinoma out of the 15 patients affected by adenomatous polyposes. FAP is a generalized disorder involving the entire colorectum segment with numerous extra-colonic manifestations. The risk to develop colonic cancer is 100%. JPS is characterised by the development of numerous gastrointestinal juvenile polyps and occurs usually before 20 years old, the progression to cancer is rarely observed. CONCLUSION: Peutz-Jeghers syndrome consists in hamartomatous polyps associated to a characteristic mucosal pigmentation. The patients are usually young adults and have an increased incidence of cancer in extradigestive sites.     

Genetics of colorectal cancer. I. Non-polyposis and polyposis forms of hereditary colorectal cancer]

About 5% of colorectal cancer cases are due to an autosomal dominant genetic predisposition with high penetrance. In this condition, the patient is carrier of a pathogenic gene mutation present in all body cells which can be transmitted to descendants, a so-called germ line mutation. The mutation is usually present in a tumour suppressor gene. Three subgroups of hereditary colorectal cancer can be distinguished on the basis of the clinical characteristics: (a) syndromes without polyposis (mostly hereditary non-polyposis colorectal carcinoma; HNPCC), (b) syndromes with adenomatous polyposis (mostly familial adenomatous polyposis; FAP) and (c) syndromes with hamartomatous polyposis. Recently, the main gene defects which underlie these syndromes were identified. Consequently, it is possible in approximately half the families with HNPCC or FAP in patients with colorectal cancer to demonstrate the causative gene defect and subsequently, by blood testing of healthy relatives to determine who is and is not a carrier of this hereditary condition. Thus, preventive measures can be directed toward family members with a demonstrable high risk of large bowel cancer.     

Current concepts in the genetics of hereditary and sporadic colorectal cancer and the role of genetics in patient management. Hereditary colorectal cancers

Colorectal cancer (CRC) is the second leading cause of mortality of malignant diseases in Hungary and according to the incidence and prevalence of CRC Hungary is second among European countries. Hence, it is of outstanding interest to know the current concepts on pathogenesis and genetical background of CRC, as well as incorporate this knowledge in the everyday practice. In the first part of the review authors address the genetic background of hereditary colorectal cancer syndromes. In fact, a positive family history may be found in 20-30% and genetically defined trait (e.g. familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC) and Peutz-Jeghers-syndrome (PJS)) is responsible for 3-5% of all colon cancers. Germline mutations of tumor suppressor gene, APC (5q21) are found in 70-90% of the cases. Until now more than 300 mutations were identified. Though a typical mutation was not found, the location of the mutation is associated to the clinical phenotype and prognosis. Of note, beside APC mutations, biallelic mutations of the MYH gene may be found in a subset of individuals with FAP. The diagnosis of HNPCC is based on family history and the presence of Amsterdam I-Il or Bethesda criteria. The genetic background and clinical phenotype of the syndrome is heterogeneous. Mutations of different mismatch repair genes (mainly hMLH1 or hMSH2) may be identified in most cases. Genetic testing is advised in first degree relatives of FAP patients, if genetic testing is not available colonoscopic surveillance should be done starting at the age of 10-12 years. Due to the high number of mutation genetic testing is difficult in HNPCC families and colonoscopic screening should be advised to affected families.     

Clinical spectrum and incidence of neuro-borreliosis in the Netherlands

OBJECTIVE: To determine the clinical spectrum and incidence of neuroborreliosis in the Netherlands. DESIGN: Retrospective. METHOD: All neurological practices in 106 hospital locations in the Netherlands were asked to look for patients with the codes 'other neurological infections' or 'Borrelia burgdorferi' in their Diagnosis & Treatment Combinations registration or the Neurological Coding System, respectively, concerning the year 2001, then to identify the patients with neuroborreliosis and to send a copy of the correspondence with the family doctor and the laboratory data on these patients, after making them anonymous, for data extraction. Pleocytosis in the cerebrospinal fluid combined with a positive test for IgM or IgG antibodies of B. burgdorferi in the serum or cerebrospinal fluid was used as the criterion for the diagnosis neuroborreliosis. RESULTS: Forty-seven (44%) neurological practices did not respond and twenty-two (21%) either did not use any kind of diagnosis registration system or linkage between the registration and the patient file was impossible. Of the 37 (35%) neurological practices that provided information, 17 had diagnosed neuroborreliosis in 30 patients, 20 of whom met the specified criteria. Fifteen (75%) patients had a radiculopathy, 8 (40%) a peripheral facial palsy and 3 (15%) a myelopathy. CONCLUSION: The clinical spectrum of patients with neuroborreliosis was consistent with that described in Denmark. The incidence of neuroborreliosis found was 3.6 per million inhabitants. The real incidence was probably higher because the registration systems used allowed patients with neuroborreliosis to be booked under other (symptomatic) diagnostic codes, paediatricians were not involved in the study, and relatively few participating neurologists practiced in high-risk areas for tick bites and erythema migrans. The low incidence of neuroborreliosis in combination with a high background level of seropositivity in the population implies a low predictive value of positive Borrelia serology. It is therefore essential that when neuroborreliosis is suspected, the cerebrospinal fluid should always be investigated.     

Cost-minimization analysis of genetic testing versus clinical screening of at-risk relatives for familial adenomatous polyposis

OBJECTIVE: Familial adenomatous polyposis (FAP) is a well-known hereditary colorectal cancer-predisposing syndrome. Genetic testing for colorectal cancer risk is now part of standard medical practice, but very little is known about the economic impact of this technology. The aim of this study was to assess, from a healthcare system perspective, the direct costs of two strategies for screening at-risk relatives of FAP patients: clinical screening versus genetic testing for FAP. METHODS: A systematic review of the literature was carried out. Additional information was gathered from experts in research and clinical laboratories and in hospital departments. A decision tree was constructed to compare per-person and per-family costs of the two strategies for screening at-risk relatives of FAP patients. Sensitivity analysis was performed to assess the stability of the model across the full range of plausible values for all key parameters. RESULTS: According to the decision analysis, with FAP screening starting at puberty, the average screening costs are $3,181 and $2,259 (Canadian dollars), respectively, for the clinical screening and the genetic testing strategies. Genetic screening is cost saving up to a first screening age of 36. Sensitivity analysis shows that the results of the baseline analysis hold across a variety of assumptions concerning the parameter values. CONCLUSIONS: The genetic testing strategy is cost saving relative to the clinical screening alternative. Apart from its lower costs, it is associated with many other benefits. Accordingly, under predefined conditions, predictive genetic testing seems to be the optimal screening strategy for FAP.     

Under-diagnosis of alcohol-related problems and depression in a family practice in Japan

Aim

The aim of this survey was to assess the accuracy of a family physician's diagnosis of depression and alcoholism.

Methods

Consecutive new adult patients attending a family practice in Japan between April 2004 and August 2006 were enrolled. Excluded were those with dementia or visual disturbance, and emergency cases. Participants completed a questionnaire regarding their complaints and socio-demographics. A research nurse conducted the Japanese version of the Mini-International Neuropsychiatric Interview (J-MINI) in the interview room. The doctor independently performed usual practice and recorded his own clinical diagnoses. A researcher listed the clinical diagnoses and complaints, including J-MINI or clinically-diagnosed alcoholism and depression, using the International Classifications for Primary Care, Second Edition (ICPC-2) and calculated kappa statistics between the J-MINI and clinical diagnoses.

Results

Of the 120 adult first-visit patients attending the clinics, 112 patients consented to participate in the survey and were enrolled. Fifty-one subjects were male and 61 female, and the average age was 40.7 ± 13.2 years. Eight alcohol-related disorders and five major depressions were diagnosed using the J-MINI, whereas no cases of alcoholism and eight depressions were diagnosed by the physician. Clinically overlooked patients tended to have acute illnesses like a common cold. Concordance between the clinical and research diagnosis was achieved only for three episodes of Major depression, resulting in a kappa statistic of 0.43.

Conclusion

Although almost half of the major depressions were identified, all alcoholism was missed. A mental health screening instrument might be beneficial in family practice, especially to detect alcoholism.     

两种千伏级立体平面图像引导放射治疗系统临床一致性研究

目的:对比研究千伏(kV)级iScout图像引导放射治疗定位系统和射波刀Xsight脊柱追踪系统基于骨骼二维-三维(2D-3D)图像配准算法的临床一致性。方法:选取医院收治的30例行第四代射波刀Xsight脊柱追踪系统治疗的患者临床数据资料,采用配置i Scout系统成像几何参数,生成数字重组透视图像作为配准参考图像,加载Xsight系统影像板投影图像,应用i Scout系统骨骼定位方法实现2D-3D图像配准,计算患者病灶位置偏移。参照Xsight系统定位配准数据,选取3个平移头脚(S/I)、左右(L/R)和前后(A/P),以及3个转角绕头脚(Roll)、绕左右(Pitch)和绕前后(Yaw)3个方向共6个自由度作为评价参数,记录并对比两个系统的配准结果。结果:获取30例患者数据资料生成的分别由A、B投影图像构成564组投影图像,分析记录Xsight系统和iScout系统配准结果的差值,S/I、L/R和A/P的3个平移结果的差值分别为(0.100.24)mm、(-0.060.32)mm和(0.110.21)mm;Roll、Pitch和Yaw的3个转角结果的差值分别为(-0.010.35)、(0.070.23)和(0.010.24)。散点分布图显示两个系统6个自由度定位配准结果差值集中分布在0.5之间。结论:iScout系统与Xsight系统均基于kV级X射线2D-3D图像配准立体定位引导技术,临床比对结果一致性好。     

Ferrous ammonium phosphate (FeNH4PO4) as a new food fortificant: iron bioavailability compared to ferrous sulfate and ferric pyrophosphate from an instant milk drink

Purpose

The main purpose of this study was to establish bioavailability data in humans for the new (Fe) fortification compound ferrous ammonium phosphate (FAP), which was specially developed for fortification of difficult-to-fortify foods where soluble Fe compounds cannot be used due to their negative impact on product stability.

Methods

A double-blind, randomized clinical trial with cross-over design was conducted to obtain bioavailability data for FAP in humans. In this trial, Fe absorption from FAP-fortified full-cream milk powder was compared to that from ferric pyrophosphate (FPP) and ferrous sulfate. Fe absorption was determined in 38 young women using the erythrocyte incorporation dual stable isotope technique (⁵⁷Fe, ⁵⁸Fe).

Results

Geometric mean Fe absorption from ferrous sulfate, FAP and FPP was 10.4, 7.4 and 3.3 %, respectively. Fe from FAP was significantly better absorbed from milk than Fe from FPP (p < 0.0001). Fe absorption from FAP was significantly lower than Fe absorption from ferrous sulfate, which was used as water-soluble reference compound (p = 0.0002). Absorption ratios of FAP and FPP relative to ferrous sulfate as a measure of relative bioavailability were 0.71 and 0.32, respectively.

Conclusions

The results of the present studies show that replacing FPP with FAP in full-cream milk could significantly improve iron bioavailability.