家族性腺瘤性息肉病的外科治疗

家族性腺瘤性息肉病（family adenomatous polyposis,FAP）属常染色体显性遗传疾病,目前被认为是癌前病变,而且癌变往往为多发性、多中心性。我们收集了28例FAP患者的临床资料,就FAP的临床特点和外科治疗进行探讨。     

家族性腺瘤性息肉病

对１９７９年６月至１９９１年６月间收治的２０例家族性腺瘤性息肉病（ＦＡＰ）进行临床分析。有家族史者１０例，占５０％。１６例癌变，占８０％。术前均经肠镜检查确诊。３例行预防性结、直肠次全切除或全切除，已分别存活６、７、１３年；７例行结肠或直肠癌根治加结、直肠次全切除或全切除，３年、５年生存率为８５．７％（６／７）与５７．２％（４／７）；姑息性结肠或直肠癌切除者均于１年内死亡。共有９例结、直肠次全切除或全切除后行回肠贮袋成形术，无术中死亡及严重并发症，术后大便功能恢复较好。结果提示，ＦＡＰ的大肠腺瘤易癌变，且较早。早期诊断并行预防性结、直肠次全切除或全切除可防治癌变，回肠贮袋成形术可提高病人生活质量     

家族性腺瘤性息肉病相关的硬纤维瘤

目的 总结家族性腺瘤性息肉病（familial adenomatous polyposis,FAP）相关的硬纤维瘤（desmoid tumours,DT）的临床病理特点,提高认识,探讨合理的治疗方法 .方法 回顾性分析总结了从1981年10月至2005年5月住院治疗的50例FAP发生的5例DT的临床病理资料,并结合文献分析.结果 男3例,女2例,年龄在31～47岁,平均36.6岁,4例在首次结直肠手术后出现,距离首次手术的时间间隔1～3年,平均2.3年,1例在FAP首次行结直肠手术时发现,4例无明显症状,1例反复发作肠梗阻及腹腔感染症状.腹壁DT 2例,腹腔DT 1例,同时腹壁和腹腔DT 2例.2例腹壁DT切除术后12年和11年分别出现残余结直肠腺瘤癌变,但未见DT复发.1例术中发现的肠系膜根部DT,仅行切取活检,但术后5年患者死于直肠癌转移时DT仍稳定.1例腹壁和腹腔DT,行腹壁DT切除,乙状结肠造口术,术后8年患者死亡,原因不明.另1例腹壁和腹腔DT患者仅行活检术,3年后患者死于DT所致的肠梗阻和败血症.结论 FAP相关的DT的治疗应个体化对待,腹壁DT应及时切除,治疗效果好,腹腔DT应根据分期选择合理的治疗方案.     

云南省家族性腺瘤性息肉病APC基因胚系突变的研究

目的研究云南省家族性腺瘤性息肉病(FAP)APC基因胚系突变的特点。方法收集云南地区10个FAP家系,抽取10例先证者的外周静脉血,提取脱氧核糖核酸(DNA),应用聚合酶链反应(PCR)方法扩增APC基因,应用DNA自动测序仪进行测序。结果 10例FAP先证者中,1例检出APC基因致病突变,此突变存在于APC基因第15外显子上c.3587 C>A(S1196X);随后对检出突变的先证者家系中另外8名成员进行该突变位点筛查,其中7人有突变。结论云南地区FAP患者APC基因致病突变检出率明显低于国内外报道;未检出APC基因致病突变的FAP患者可能存在其他发病的因素。     

三器械联合应用于IPAA治疗家族性腺瘤性息肉病的体会

目的 总结家族性腺瘤性息肉病(FAP)的诊断和二器械联合IPAA外科治疗经验。方法 回顾分析19例FAP的临床资料及IPAA手术治疗效果。结果 所有患者预后良好，无明显并发症的发生，术后大便控制能力良好，术后癌变率与传统手术无差异，手术时间缩短、手术难度降低。结论 三器械联合IPAA手术是治疗FAP的最佳方法，易于推广。     

中国人231例家族性腺瘤性息肉病术式选择的Meta分析

目的：荟萃分析中国人家族性腺瘤性息肉病（FAP）的临床特征及手术术式。方法：以“家族性腺瘤性息肉病”为检索词，电脑检索2000～2006年国内公开发表的中文文献，统一纳入和排除标准，对所得资料进行荟萃分析。结果：男137例（59．3％），女94例（40．7％），男：女=1．46：1。有明确家族性腺瘤性息肉病家族史者占51．2％，平均发病年龄27．8岁，腺瘤癌变率为47．5％，腺瘤癌变者平均年龄35．9岁。术式选择全结肠直肠切除＋末端回肠腹壁造口术（TPA）60例（26．0％），全结肠部分直肠切除＋回肠直肠吻合术（IRA）63例（27．3％），全结肠直肠切除＋回肠肛管吻合术（IAA）12例（5．2％），全结肠直肠切除＋回肠储袋肛管吻合术（IPAA）19例（8．2％），全结肠部分直肠切除＋残留直肠黏膜剥脱＋经直肠肌鞘回肠肛管吻合术22例（9．5％），全结肠部分直肠切除＋残留直肠黏膜剥脱＋经直肠肌鞘回肠储袋肛管吻合术47例（20．3％），部分结肠或直肠切除术8例（3．5％）。结论：FAP是临床常见的多发生于结直肠的遗传性疾病，但文献报道不多，病例数较少；腺瘤发病早，癌变比率高；症状主要为大便习惯改变；诊断主要靠下消化道造影及纤维结肠镜检查；术式选择时应根据患者具体情况采用个体化手术方式；良性者预后较好，已癌变者预后也较原发结直肠癌为好。     

舒林酸治疗家族性腺瘤性息肉病患者结直肠 腺瘤的长期疗效观察

 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以及对 结直肠中残存腺瘤组织病理学表现的影响。方法　根据家族史和结肠镜检确诊FAP 患者,经患者同意 后每天口服舒林酸400 mg。患者定期复查结肠镜评价疗效,对残存息肉进行活检病理组织学检查。结 果　18 例FAP 患者接受舒林酸长期治疗,平均维持治疗时间为(65. 3 ±31. 6) 月。最后一次复查时息肉 数目均较治疗前明显减少( P = 0. 02) 。舒林酸治疗前FAP 患者结直肠腺瘤活检标本中,管状腺瘤占活 检腺瘤总数的86. 5 % ,绒毛管状腺瘤占13. 0 % ,绒毛状腺瘤占0. 5 %。异型程度为Ⅰ级、Ⅱ级、Ⅲ级的腺 瘤分别占40. 0 %、43. 5 %和11. 5 %。治疗后获得的腺瘤标本中,管状腺瘤占活检腺瘤总数的97. 7 % ,绒 毛管状腺瘤占2. 3 %。与治疗前相比差异有统计学意义( P < 0. 01) 。异型程度为Ⅰ级、Ⅱ级、Ⅲ级的腺瘤 分别占48. 9 %、48. 1 %和3. 0 % ,与治疗前相比异型程度显著下降( P < 0. 01) 。但是,有1 名患者自行将 舒林酸减至每天100 mg ,一年后发生结肠癌。结论　舒林酸长期维持治疗可使家族性腺瘤性息肉病患 者结直肠腺瘤保持长期显著消退状态,结直肠残存腺瘤异型程度下降,绒毛管状腺瘤减少。但是腺瘤消 退与维持剂量有关,剂量过小无效,而且舒林酸对腺瘤的消退作用是不完全的,患者仍需定期复查肠镜, 早期发现结直肠癌。     

回肠储袋直肠肌鞘内肛管吻合术治疗家族性腺瘤性息肉病

家族性腺瘤性息肉病(familial adenomatous polyposis,FAP)是由于5号染色体上APC基因突变引起的一种常染色体显性遗传病,75％～80％有家族史[1].通过家系调查,对高危亲属的追踪管理、肠镜监测,可以发现早期病例,行预防性手术效果满意.回肠储袋直肠肌鞘内肛管吻合术是功能性和根治性手术的最佳选择,但容易发生吻合口瘘、肌间脓肿及吻合口狭窄等并发症.本研究采用改进的回肠储袋直肠肌鞘内肛管吻合术治疗家族性腺瘤性息病患者,效果良好,并发症少,疗效满意.     

Id2在小鼠家族性腺瘤性息肉病发生中的作用

研究DNA结合抑制物2(inhibitor of DNA binding2, Id2) 在 Apc^Δ716/+小鼠家族性腺瘤性息肉病(familial adenomatous polyposis,FAP)发生中的作用。方法 Id2基因缺失的基因工程小鼠和家族性腺瘤性息肉病模型Apc^Δ716/+小鼠杂交后,统计Apc^Δ716/+小鼠与Apc^Δ716/+Id2^－／－杂交小鼠小肠肠道息肉的数目及总负荷,通过Western blot及原位杂交技术测定腺瘤性息肉Id2的表达。结果 腺瘤性息肉组织中Id2 蛋白及mRNA表达明显升高,相比ApcΔ716/+Id2野生型小鼠,Apc^Δ716/+Id2^－／－杂交小鼠肠道息肉总数目与不同大小的肠道息肉数目有明显减少（P均＜0.05）。结论 肠道腺瘤性息肉组织中Id2表达升高,Id2的缺失能抑制ApcΔ716/+小鼠肠道腺瘤性息肉的发生,Id2在人类家族性腺瘤性息肉病中可能发挥着促进肠道息肉形成的作用。     

家族性腺瘤性息肉病的诊断及外科治疗研究进展

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。肠镜检查和基因检测为患者提供了早期诊断和治疗的机会,基因诊断是FAP诊断的发展方向,是进一步研究FAP发病机制的关键。全结直肠切除、回肠贮袋-肛管吻合术（ileal pouch-anal anastomosis,IPAA）和结直肠次全切除、回肠-直肠吻合术（ileorectal anastomosis,IRA）是治疗FAP的主要手术方式,尤其是腹腔镜的应用,为外科医生提出了新的机遇和挑战,新术式的提出及其安全性和有效性需要在临床工作中验证并持续改进和发展。FAP的结直肠外表现不可忽视,尤其是十二指肠癌及壶腹癌和硬纤维瘤（desmoid tumour,DT）,已成为导致患者死亡的重要原因。本文就FAP的诊断及外科治疗方面进行综述。      

Familial Adenomatous Polyposis (FAP) and Other Polyposis Syndromes

There have been significant advances in our knowledge about the molecular changes that precede and accompany the development of inherited predispositions to colorectal cancer. In this review the clinical relationship to the molecular changes associated with the polyposis syndromes is presented. The aim is to put into context the diverse findings that have been shown to be associated with the development of colorectal cancer in persons who harbor a predisposition to develop disease at unusually early ages. The main focus will be on familial adenomatous polyposis as it serves as a model disease and is the most extensively studied of all of the polyposis syndromes. In addition some information is provided that explains the relationship between a germline change in one gene and what consequences that can have for a particular cell and the development of disease.     

Evaluation of Endoscopic Characteristics of Upper Gastrointestinal Polyps in Patients with Familial Adenomatous Polyposis

Background: Familial adenomatous polyposis (FAP) is a disease inherited in an autosomal dominant fashion. Most FAP patients develop upper gastrointestinal polyps; especially those in the antrum and duodenum are usually neoplastic. The aim of this study was to evaluate the prevalence of gastroduodenal polyps in Iranian FAP patients. Materials and Methods: 28 patients affected by FAP underwent front-view and side-view endoscopy. Papillary biopsies were performed in all patients. Location of polyps, their number and size, pathology study, patient general information (gender, age, family history of FAP or colorectal cancer and gastroduodenal polyps) were analyzed. Results: Gastric polyps were seen in 39.3 % of patients. Some 72.7% of the affected individuals had fundic gland polyps and 36.36% had hyperplastic polyps. Duodenal adenoma was observed in 25% of patients. While 57% of patients had tubular adenoma with low grade dysplasia, 42.8% showed tubulovillous adenoma with low grade dysplasia. Conclusions: Findings of this study indicated that the prevalence of gastroduodenal polyps in FAP patients is high and dysplasia may be evident in duodenal polyps. Therefore, it appears that routine gastroduodenal endoscopy in FAP patients is necessary.     

Chromosome Changes in Desmoid Tumors Developed in Patients with Familial Adenomatous Polyposis

Chromosome analyses were performed on benign desmoid tumors obtained from two female patients with familial adenomatous polyposis (FAP), one of whom was diagnosed as having Gardner syndrome (GS). The modal chromosome number was 46 in both specimens, and detailed Q-banding analysis in Case 1 (GS) revealed a clonal abnormality of an interstitial deletion of the long arm of chromosome 5, del(5)(q2lq31). The deleted region included an assigned locus for an FAP major gene (5q21-q22). All of the metaphases analyzed in this case showed an extra segment of bright fluorescence on the short arm of chromosome 15, but this unusual chromosome (15p +) was observed in both peripheral lymphocyte and skin fibroblast cultures from the patient, indicating that the 15p+ was constitutional in nature. In Case 2, no clonal rearrangements were Identified and most cells had a normal karyotype. However, two cells showed rearrangements involving a 17q with non-identical breakpoints, one of which was observed as a solitary chromosome change. Based on the present findings in Case 1 and those reported so far, the chromosomal defect on 5q might be one of the causal genetic events primarily associated with the development of both benign desmoid tumors and colorectal adenomas and carcinomas in FAP patients.     

Analysis of Small Fragment Deletions of the APC gene in Chinese Patients with Familial Adenomatous Polyposis,a Precancerous Condition

Background: : Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease mainly causedby mutations of the adenomatous polyposis coli (APC) gene with almost complete penetrance. These colorectalpolyps are precancerous lesions that will inevitable develop into colorectal cancer at the median age of 40-yearold if total proctocolectomy is not performed. So identification of APC germline mutations has great implicationsfor genetic counseling and management of FAP patients. In this study, we screened APC germline mutationsin Chinese FAP patients, in order to find novel mutations and the APC gene germline mutation characteristicsof Chinese FAP patients. Materials and Methods: The FAP patients were diagnosed by clinical manifestations,family histories, endoscope and biopsy. Then patients peripheral blood samples were collected, afterwards,genomic DNA was extracted. The mutation analysis of the APC gene was conducted by direct polymerasechain reaction (PCR) sequencing for micromutations and multiplex ligation-dependent probe amplification(MLPA) for large duplications and/or deletions. Results: We found 6 micromutations out of 14 FAP pedigrees,while there were no large duplications and/or deletions found. These germline mutations are c.5432C>T(p.Ser1811Leu), two c.3926_3930delAAAAG (p.Glu1309AspfsX4), c.3921_3924delAAAA (p.Ile1307MetfsX13),c3184_3187delCAAA(p.Gln1061AspfsX59) and c4127_4126delAT (p.Tyr1376LysfsX9), respectively, and alldeletion mutations resulted in a premature stop codon. At the same time, we found c.3921_3924delAAAA andtwo c.3926_3930delAAAAG are located in AAAAG short tandem repeats, c3184_3187delCAAA is located in theCAAA interrupted direct repeats, and c4127_4128 del AT is located in the 5’-CCTGAACA-3’ ,3’-ACAAGTCC-5palindromes (inverted repeats) of the APC gene. Furthermore, deletion mutations are mostly located at condon1309. Conclusions: Though there were no novel mutations found as the pathogenic gene of FAP in this study,we found nucleotide sequence containing short tandem repeats and palindromes (inverted repeats), especiallythe 5 bp base deletion at codon 1309, are mutations in high incidence area in APC gene.     

In the Beginning There Was Colectomy: Current Surgical Options in Familial Adenomatous Polyposis

Multiple colonic polyps, almost guaranteed colorectal cancer by the age of forty-five and an increased risk of non-colonic cancers characterise the autosomal dominant condition Familial Adenomatous Polyposis (FAP) [1]. The patients and families faced with such a diagnosis present many difficult management challenges, both surgical and non-surgical. We discuss the current surgical options for treatment of the more significant manifestations of FAP arising in the colorectum and duodenum as well as desmoid disease     

Somatic Mutation of the APC Gene in Thyroid Carcinoma Associated with Familial Adenomatous Polyposis

We report the existence of both germline and somatic mutations of the APC gene in thyroid carcinomas from familial adenomatous polyposis (FAP) patients. One papillary thyroid carcinoma from a 20-year-old woman, with germline mutation of the APC gene (TCA to TGA at codon 1110), showed a somatic mutation of AAAAC deletion between codons 1060 and 1063. Another somatic mutation of CAG to TAG at codon 886 was also found in one of multiple thyroid carcinomas from a 26-year-old woman with attenuated FAP and germline mutation at codon 175 (C deletion). This is the first evidence that total absence of the normal function of the APC gene is involved in development of thyroid carcinomas in FAP.     

The Mutation Spectrum and Two Novel Point Mutations in the APC Gene in Vietnamese Patients with Familial Adenomatous Polyposis

Background: Familial adenomatous polyposis (FAP) is a hereditary disorder primarily caused by germline mutations in the APC gene. The most common type of mutation in the APC gene is point mutation, while deletion mutation is much less frequent. The current study was conducted to investigate the mutation spectrum of the APC gene in Vietnamese FAP patients. Methods: Patients with the clinical diagnosis of FAP on colorectal endoscopy were screened for mutations in the APC gene using Sanger sequencing. Those who exhibited no point mutation subsequently underwent MLPA assay to detect deletion and duplication mutations. Besides, the relatives of patients with mutated APC genes were recruited for detecting carrier status. Results: Sixty-three patients with clinical colorectal polyposis were recruited. Mutations in the APC gene were detected in 26/63 patients (41.3%). Genetic analysis of 105 asymptomatic relatives of these 26 patients found mutations in the APC gene in 55 individuals (52.4%). Conclusion: We successfully established the APC gene mutation spectrum in Vietnamese FAP patients for the first time. Of importance, we discovered two novel point mutations in the APC gene. The high prevalence of carrier status in asymptomatic family members of patients with mutation emphasizes the crucial role of appropriate genetic screening for early diagnosis, surveillance, and preventive measurements.     

Nuclear Localization of Immunoreactive β-Catenin Is Specific to Familial Adenomatous Polyposis in Papillary Thyroid Carcinoma

Thyroid carcinoma is the first symptom in some patients with familial adenomatous polyposis (FAP). We evaluated the cellular localization of β-catenin in thyroid carcinomas associated (n=4) or not associated (n=173) with FAP, since loss of functional protein of the adenomatous polyposis coli (APC) gene leads to nuclear accumulation of β-catenin in adenomas and carcinomas of the FAP colon. Immunoreactive β-catenin was demonstrated at the cell membrane of glandular cells of the non-neoplastic thyroid and non-FAP carcinomas. On the other hand, cytoplasmic and nuclear accumulation of β-catenin is specific to FAP-associated papillary carcinomas. The abnormality in the APC/β-catenin pathway is thus also important in FAP-associated thyroid carcinoma, and β-catenin immunohistochemistry is a feasible screening method to identify occult FAP in young patients with thyroid tumors.     

Congenital Hypertrophy of Retinal Pigment Epithelium for Diagnosis of Familial Adenomatous Polyposis - the First FAP registry in Iran

Objective: Familial adenomatous polyposis (FAP), an autosomal dominant inherited disorder is characterized by the presence of multiple adenomatous colorectal polyps, which can develop into cancer during early adulthood. Therefore, early diagnosis is essential. Most FAP patients have several extracolonic manifestations, including congenital hypertrophy of the retinal pigment epithelium (CHRPE). Whereas genetic markers may provide the main route to detection of ‘‘at risk’’ subjects , at present this approach is clearly limited and searches for a noninvasive phenotypic marker continue to be high priority.The aim of this study was to describe the pattern of distribution of CHRPE lesions and evaluate their diagnostic value in FAP patients and their family members in a local population. Methods: A total of 23 FAP patients and 26 relatives belonging to 12 families at high risk of developing FAP were subjected to colonoscopic and ophthalmological examination. Result: Retinal examinations demonstrated prevalences of CHRPE in FAP patents and their siblings of 78% and 38%, respectively. We were able to illustrate a significant correlation between FAP disease and the presence of retinal lesions. Sensitivity and specificity of CHRPE as a screening test to detect the presence of FAP are 78.3% and 61.5%, respectively, with a positive predictive value of 64.3% and a negative predictive value of 76.2 %. A "lesion form" significant difference was found between FAP and normal participants.Spearman nonparametric analysis revealed no correlation between age and number or size of lesions. Conclusion: Multiple CHRPE lesions are a diagnostic feature of FAP patients They are specific and sensitive clinical markers of this disease (specificity 60% and sensitivity 77%).