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。      

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。     

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.     

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.     

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18例报道

探讨家族性腺瘤性息肉病的临床特点和治疗问题。方法 对1984-2002年收治的18例病人进行回顾性分析。结果 有家族史者9例,癌变8例。手术方式:全结肠直肠切除8例,其中回肠造口2例,回肠储袋肛管吻合6例;结肠次全切除6例,其中回肠直肠吻合5例,升结肠肛管吻合1例;结肠部分切除2例;Miles术1例,结肠会阴造口1例。结论 认识该病的临床特点,根据息肉的分布特点和有无癌变等选择不同的手术方式,首选结直肠全切回肠储袋肛管吻合术。     

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。     

家族性腺瘤性息肉病癌变的治疗体会

家族性腺瘤性息肉病（ｆａｍｉｌｉａｌａｄｅｎｏｍａｔｏｕｓｐｏｌｙｐｏｓｉｓ，ＦＡＰ）是１种比较少见的遗传性大肠疾病，符合Ｍｅｎｄｅｌｉａｎ定律，属常染色体显性遗传，外显率为８０％～１００％［１］。一般认为ＦＡＰ是基因突变引起的，基因定位于５号染色体的长臂上（５ｑ２１、２２）［２］，如不手术治疗，最终将癌变。我院自１９８９年１２月至１９９８年１２月，采用全大肠切除、直肠肌鞘内回肠肛管吻合改进术式治疗２８例ＦＡＰ患者，其中７例有癌变，效果满意。１　资料与方法１．１　一般资料本组ＦＡＰ癌变患者７例，…     

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。     

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。     

Total gastrectomy with isoperistaltic jejunal interposition flap for symptomatic management of gastric polyposis from familial adenomatous polyposis

Patients with familial adenomatous polyposis (FAP) oftentimes have extracolonic polyps. The patient discussed in this case report had innumerable gastric polyps which were significantly affecting his ability to tolerate oral intake and his overall nutrition. Medical management was not sufficiently controlling his symptoms; therefore we proceeded with surgical intervention. We discuss the use of a total gastrectomy with an Isoperistaltic jejunal interposition flap for the symptomatic management of gastric polyposis. We describe the technique used and benefits to this specific procedure when it comes to long term outcome, complications, and monitoring.     

Brain tumors in individuals with familial adenomatous polyposis: a cancer registry experience and pooled case report analysis

BACKGROUND: Most individuals with Familial Adenomatous Polyposis (FAP) harbor mutations in the APC gene on chromosome 5q21. They are at an increased risk of brain tumors, including cerebellar medulloblastoma, when compared with the general population (Brain Tumor Polyposis-BTP Type 2). Genotype-phenotype correlations between APC gene mutations and central nervous system (CNS) tumors have, thus far not been successful. Herein the authors have pooled their registry experience in BTP type 2 with the published reports. METHODS: The authors analyzed their established hereditary CRC Registry for brain tumors in FAP pedigrees (56 families, 213 individuals), pooled their patients with BTP and known APC mutations with those reported thus far elsewhere, and compared the resulting mutation distribution of FAP-BTP with the mutation distribution for APC mutations in the US. RESULTS: Twenty-eight patients from 24 families were accrued, the most common brain tumor in BTP was medulloblastoma (60%) predominantly in females (12:5) under the age of 20 (mean age 14.7 SD 9.2). Other histologic subtypes included astrocytoma and ependymoma. Analysis of the pooled APC mutation data by Chi-square test of association shows an odds ratio of 3.7 (P < .005) for all brain tumor subtypes and 13.1 (P < .001) for medulloblastoma in patients harboring segment 2 APC mutation (codons 679-1224) compared to nonsegment 2 mutation. CONCLUSIONS: In patients with FAP and identifiable APC gene mutation, CNS tumors, especially medulloblastoma which developed in most cases during childhood, are more common in females with FAP and APC gene mutation in codons 686-1217. Further studies are necessary to determine if this observation and the natural history of medulloblastoma in children justifies novel, aggressive, targeted screening of at-risk individuals.     

Restorative proctocolectomy and ileal pouch-anal anastomosis for familial adenomatous polyposis revisited

Since restorative proctocolectomy (RPC) with ileal-pouch anal anastomosis (IPAA) removes the entire diseased mucosa, it has become firmly established as the standard operative procedure of choice for familial adenomatous polyposis (FAP). Many technical controversies still persist, such as mesenteric lengthening techniques, close rectal wall proctectomy, endoanal mucosectomy vs. double stapled anastomosis, loop ileostomy omission and a laparoscopic approach. Despite the complexity of the operation, IPAA is safe (mortality: 0.5–1%), it carries an acceptable risk of non-life-threatening complications (10–25%), and it achieves good long-term functional outcome with excellent patient satisfaction (over 95%). In contrast to the high incidence in patients operated for ulcerative colitis (UC) (15–20%), the occurrence of pouchitis after IPAA seems to be rare in FAP patients (0–11%). Even after IPAA, FAP patients are still at risk of developing adenomas (and occasional adenocarcinomas), either in the anal canal (10–31%) or in the ileal pouch itself (8–62%), thus requiring lifelong endoscopic monitoring. IPAA operation does not jeopardise pregnancy and childbirth, but it does impair female fecundity and has a low risk of impairment of erection and ejaculation in young males. The latter can almost completely be avoided by a careful “close rectal wall” proctectomy technique. Some argue that low risk patients (e.g. <5 rectal polyps) can be identified where ileorectal anastomosis (IRA) might be reasonable. We feel that the risk of rectal cancer after IRA means that IPAA should be recommended for the vast majority of FAP patients. We accept that in some very selected cases, based on clinical and genetics data (and perhaps influenced by patient choice regarding female fecundity), a stepwise surgical strategy with a primary IPA followed at a later age by a secondary proctectomy with IPAA could be proposed.     

Desmoids in familial adenomatous polyposis are monoclonal proliferations

Desmoids are poorly-understood, locally aggressive, non-metastasizing fibromatoses that occur with disproportionate frequency in patients with familial adenomatous polyposis (FAP). Their nature is controversial with arguments for and against a neoplastic origin. Neoplastic proliferations are by definition monoclonal, whereas reactive processes originate from a polyclonal background. We examined clonality of 25 samples of desmoid tissue from 11 female FAP patients by assessing patterns of X-chromosome inactivation to calculate a clonality ratio. Polymerase chain reaction (PCR) amplification of a polymorphic CAG short tandem repeat (STR) sequence adjacent to a methylation-sensitive restriction enzyme site within the human androgen receptor (HUMARA) gene using fluorescent-labelled primers enabled analysis of PCR products by Applied Biosystems Genescan II software. Twenty-one samples from nine patients were informative for the assay. Samples from all informative cases comprised a median of 66% (range 0-75%) clonal cells but from the six patients with a clonality ratio < or =0.5 comprised a median of 71% (65-75%) clonal cells. FAP-associated desmoid tumours are true neoplasms. This may have implications in the development of improved treatment protocols for patients with these aggressive tumours.     

Evaluation of management of desmoid tumours associated with familial adenomatous polyposis in Dutch patients

Background:

The optimal treatment of desmoid tumours is controversial. We evaluated desmoid management in Dutch familial adenomatous polyposis (FAP) patients.

Methods:

Seventy-eight FAP patients with desmoids were identified from the Dutch Polyposis Registry. Data on desmoid morphology, management, and outcome were analysed retrospectively. Progression-free survival (PFS) rates and final outcome were compared for surgical vs non-surgical treatment, for intra-abdominal and extra-abdominal desmoids separately. Also, pharmacological treatment was evaluated for all desmoids.

Results:

Median follow-up was 8 years. For intra-abdominal desmoids (n=62), PFS rates at 10 years of follow-up were comparable after surgical and non-surgical treatment (33% and 49%, respectively, P=0.163). None of these desmoids could be removed entirely. Eventually, one fifth died from desmoid disease. Most extra-abdominal and abdominal wall desmoids were treated surgically with a PFS rate of 63% and no deaths from desmoid disease. Comparison between NSAID and anti-estrogen treatment showed comparable outcomes. Four of the 10 patients who received chemotherapy had stabilisation of tumour growth, all after doxorubicin combination therapy.

Conclusion:

For intra-abdominal desmoids, a conservative approach and surgery showed comparable outcomes. For extra-abdominal and abdominal wall desmoids, surgery seemed appropriate. Different pharmacological therapies showed comparable outcomes. If chemotherapy was given for progressively growing intra-abdominal desmoids, most favourable outcomes occurred after combinations including doxorubicin.     

Balance between endoscopic and genetic information in the choice of ileorectal anastomosis for familial adenomatous polyposis

BACKGROUND AND OBJECTIVES: The number of rectal polyps and the site of mutations in the APC (Adenomatous polyposis coli) gene have been used to guide the surgical management in patients with familial adenomatous polyposis (FAP). The aim of this study is to assess the utility of the APC mutation screening compared to the degree of the rectal polyposis in surgical decision making. METHODS: The post-surgical courses of 25 patients submitted to subtotal colectomy with ileorectal anastomosis (IRA) were reviewed. Preservation of the rectum was prospectively decided on the basis of well-defined endoscopic criteria. The number of rectal polyps was assessed preoperatively and every 6-12 months. APC gene was screened for mutations by heteroduplex analysis, single strand conformation polymorphism, in vitro synthesized protein (IVSP), and DNA sequencing. Patients negative for APC mutations were tested for MYH mutations. RESULTS: On the basis of preoperative polyp rectal count we categorized patients as follows: Group I, 5 or fewer adenomas; Group II, 6-9 adenomas; Group III, 10 or more adenomas. After a follow-up ranging from 12 to 225 months we have observed a significant difference of recurrent rectal adenomas between Groups I-II versus III. No difference was detected among patients of Group I and II. The mean number of adenomas/year/patient was 0.67, 1.62, and 9.29 for Group I, II, and III, respectively. Carpeting polyposis of the rectal stump developed in three patients with APC mutation at codon 1309 and two of them needed later proctectomy. Diffuse rectal polyposis was observed in one patient with mutation at exon 9 who had 10 small polyps at time of surgery. Mutation at the 5'-end of APC (codons 144-232), mutation of MYH and unknown APC or MYH mutation were correlated with a low number of polyps both at presentation and follow-up. No IRA patients developed rectal cancer. CONCLUSIONS: In our experience fewer than 10 rectal polyps at presentation can predict a favorable outcome after IRA. Identification of specific germ-line APC or MYH mutation can address the choice of surgical treatment.     

Profuse familial adenomatous polyposis with an Adenomatous Polyposis Coli exon 3 mutation

The attenuated form of familial adenomatous polyposis coli (AAPC) is associated with mutations in the adenomatous polyposis coli (APC) gene which cluster in the 5 region of the gene. It has been proposed that a 'genotype–phenotype boundary' exists at codons 159–163, and mutations that are 5 of this boundary will produce AAPC. Herein we document a three-generation family with an exon 3 mutation well to the 5 side of the proposed boundary, in which two affected individuals have had, in their 40s, a profuse form of familial adenomatous polyposis coli. We conclude that the codon 159–163 'boundary' is indicative rather than definitive. These two patients also had postoperative intra-abdominal adhesions, severely so in one.