今日の臨床サポート

大腸ポリポーシス

著者: 飯田聡 東京都保健医療公社 豊島病院

監修: 杉原健一 東京医科歯科大学大学院

著者校正/監修レビュー済:2019/08/09
患者向け説明資料

概要・推奨   

  1. FAP患者の大腸内視鏡検査は10歳代前半から開始されることが勧められる(推奨度1)。
  1. 典型的FAPに対する予防的大腸切除を施行する時期は、性別、大腸腺腫の密度、癌化の有無、随伴病変、患者の社会的背景など総合的に考慮したうえで決定する(推奨度2)。
  1. 典型的FAPに対する予防的大腸切除の標準術式は大腸全摘・回腸嚢肛門(管)吻合であるが、直腸に腺腫の数が少ない場合は結腸全摘・回腸直腸吻合が推奨される(推奨度1)。
  1. 閲覧にはご契約が必要 となり ます。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約
  1. 閲覧にはご契約が必 要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。
閲覧にはご契
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
飯田聡 : 特に申告事項無し[2021年]
監修:杉原健一 : 講演料(大鵬薬品)[2021年]

改訂のポイント:
  1. 遺伝性大腸癌診療ガイドライン2016に基づき、一部修正を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 大腸粘膜に生じた異常増殖性病変を大腸腺腫と呼び、その腺腫が多発したものを大腸ポリポーシスという(通常100個以上)。
  1. 腺腫の組織像(腺腫性、過誤腫性など)と遺伝性をもとにした分類が行われている。
 
消化管ポリポーシスの分類

腺腫の組織系と遺伝性を基にした分類

 
  1. 代表的な疾患である家族性腺腫性ポリポーシス(FAP)は、全大腸癌の約1%の割合であり、放置すれば必ず大腸癌が生じる。
  1. FAPは常染色体優性遺伝の形式をとり、第5染色体長腕に存在するAPC遺伝子の変異により生じる。
  1. FAPで大腸外病変として、胃ポリープ、十二指腸腺腫、小腸腺腫、骨腫、デスモイド、網膜色素上皮肥厚(CHRPE)、甲状腺腫がある。
問診・診察のポイント  
  1. 家族歴・既往歴の有無を確認する。可能な限り詳細なものが望ましく、家系図は非常に有用である。

今なら12か月分の料金で14ヶ月利用できます(個人契約、期間限定キャンペーン)

11月30日(火)までにお申込みいただくと、
通常12ヵ月の使用期間が2ヶ月延長となり、14ヵ月ご利用いただけるようになります。

詳しくはクリック
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: Marry H Nieuwenhuis, Steffen Bülow, Jan Björk, Heikki J Järvinen, Charlotte Bülow, Marie Luise Bisgaard, Hans F A Vasen
雑誌名: Dis Colon Rectum. 2009 Jul;52(7):1259-63. doi: 10.1007/DCR.0b013e3181a0d33b.
Abstract/Text PURPOSE: Genetic information may help preoperatively select patients with familial adenomatous polyposis for either colectomy with ileorectal anastomosis or proctocolectomy with ileal pouch-anal anastomosis. Although complicated, the latter procedure has a low long-term risk of rectal cancer.
METHODS: Data were obtained from four national polyposis registries. On the basis of previously described genotype-phenotype correlations, patients were divided into three genotype groups predicting attenuated, intermediate, and severe polyposis phenotypes. Cumulative risks of secondary proctectomy and rectal cancer after primary colectomy were calculated using the Kaplan-Meier method.
RESULTS: Four hundred and seventy-five polyposis patients with a previous colectomy were included. Cumulative risks of secondary proctectomy 20 years after primary colectomy were 10%, 39%, and 61% in the attenuated, intermediate, and severe genotype groups, respectively (P < 0.05, groups compared separately). Cumulative risks of rectal cancer after primary colectomy were 3.7%, 9.3%, and 8.3%, respectively, in the three groups (P > 0.05, groups compared separately).
CONCLUSION: Mutation analysis may be used to predict the risk of secondary proctectomy after primary colectomy in familial adenomatous polyposis. Patients with severe genotypes have a high risk of reoperation after primary colectomy and will benefit from primary proctocolectomy with ileal pouch-anal anastomosis. The risk of rectal cancer after primary colectomy was not significantly different between the three groups.

PMID 19571702  Dis Colon Rectum. 2009 Jul;52(7):1259-63. doi: 10.1007/・・・
著者: F M Giardiello, J D Brensinger, M C Luce, G M Petersen, M C Cayouette, A J Krush, J A Bacon, S V Booker, J A Bufill, S R Hamilton
雑誌名: Ann Intern Med. 1997 Apr 1;126(7):514-9.
Abstract/Text BACKGROUND: Germline mutation in a gene on chromosome 5 (the adenomatous polyposis coli gene) causes familial adenomatous polyposis of the colorectum. Phenotypic manifestations of this condition vary, but the exact relation of the phenotype to the mutation site along the gene has not been fully described.
OBJECTIVE: To determine how the location of mutations along a gene that is associated with multiple colorectal polyps (the adenomatous polyposis coli gene) is related to the phenotypic expression of the syndrome in families.
DESIGN: Prospective cohort study.
SETTING: Polyposis registry.
PATIENTS: 20 patients from 7 families that had mutations in the adenomatous polyposis coli gene that were located toward the 5' end of codon 158 (proximal 5' families), were compared with 52 patients from 7 families that had mutations downstream from codon 158, in codons 179 to 625 (distal 5' families).
MEASUREMENTS: Sex, age at diagnosis of familial adenomatous polyposis, number of polyps at first examination of the colon, distribution of polyps, age at diagnosis of colorectal cancer, and location of colorectal cancer.
RESULTS: Mutations that were proximal to codon 158 were found in 7 of 112 families (6%). At the first examination of the colon, 8 of 17 (47%) patients in proximal 5' families and 9 of 48 (19%) patients of similar ages in distal 5' families were found to have fewer than 100 adenomas (P = 0.029). The distribution of polyps was frequently right-sided in patients in proximal 5' families (P = 0.001). The cumulative probability of survival without colorectal cancer was greater for patients in proximal 5' families (P = 0.041).
CONCLUSIONS: Families with adenomatous polyposis that have proximal 5' mutations of the adenomatous polyposis coli gene are more likely to have a heterogeneous phenotype with delayed development of colonic polyposis and colorectal cancer than are families with distal 5' mutations of the gene. Management should include genotyping of patients who are at risk, colonoscopic surveillance of genotypically positive persons, and prophylactic colectomy if several adenomas are found.

PMID 9092316  Ann Intern Med. 1997 Apr 1;126(7):514-9.
著者: Gerald S Hernegger, Harvey G Moore, Jose G Guillem
雑誌名: Dis Colon Rectum. 2002 Jan;45(1):127-34; discussion 134-6.
Abstract/Text PURPOSE: Familial adenomatous polyposis is a well-described, autosomal dominant, inherited syndrome characterized by diffuse polyposis of the colon and rectum as well as various upper gastrointestinal and extraintestinal manifestations. A subset of patients present with fewer colorectal polyps, later age of onset of polyps and cancer, and a predilection toward involvement of the proximal colon. This variant of familial adenomatous polyposis is known as attenuated familial adenomatous polyposis. The purpose of this review is to summarize current knowledge regarding this poorly understood entity and propose guidelines for diagnosis, surveillance, and surgical management.
METHODS: The MEDLINE database was searched from 1985 onward using the keywords, "attenuated familial adenomatous polyposis," "AFAP," "adenomatous polyposis coli gene," and "APC gene." Additional articles were identified through the reference sections of retrieved papers. All papers that pertained to attenuated familial adenomatous polyposis or mutations in the APC gene producing an attenuated phenotype were included.
RESULTS: Attenuated familial adenomatous polyposis is transmitted in an autosomal dominant fashion. Several distinct mutations within the APC gene have been associated with an attenuated phenotype, but variability of disease expression within kindreds possessing identical mutations makes classification difficult. Polyps are diagnosed at a mean age of 44 years, with cancer diagnosed at a mean of 56 years of age. Frequent involvement of the proximal colon necessitates the use of colonoscopy for surveillance, and infrequent involvement of the rectum supports the role of a total abdominal colectomy and ileorectal anastomosis.
CONCLUSIONS: Although currently recognized as a distinct clinical entity, attenuated familial adenomatous polyposis may be part of a spectrum of disease that includes familial adenomatous polyposis and is caused by different mutations within the APC gene. Because of its unique characteristics, yet apparent overlap with familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, increased awareness of attenuated familial adenomatous polyposis should improve diagnosis, surveillance, and treatment strategies in this unique subset of familial polyposis syndromes.

PMID 11786778  Dis Colon Rectum. 2002 Jan;45(1):127-34; discussion 134・・・
著者: O M Sieber, S Segditsas, A L Knudsen, J Zhang, J Luz, A J Rowan, S L Spain, C Thirlwell, K M Howarth, E E M Jaeger, J Robinson, E Volikos, A Silver, G Kelly, S Aretz, I Frayling, P Hutter, M Dunlop, T Guenther, K Neale, R Phillips, K Heinimann, I P M Tomlinson
雑誌名: Gut. 2006 Oct;55(10):1440-8. doi: 10.1136/gut.2005.087106. Epub 2006 Feb 4.
Abstract/Text BACKGROUND: Attenuated familial adenomatous polyposis (AFAP) is associated with germline mutations in the 5', 3', and exon 9 of the adenomatous polyposis coli (APC) gene. These mutations probably encode a limited amount of functional APC protein.
METHODS AND RESULTS: We found that colonic polyp number varied greatly among AFAP patients but members of the same family tended to have more similar disease severity. 5' Mutants generally had more polyps than other patients. We analysed somatic APC mutations/loss of heterozygosity (LOH) in 235 tumours from 35 patients (16 families) with a variety of AFAP associated germline mutations. In common with two previous studies of individual kindreds, we found biallelic changes ("third hits") in some polyps. We found that the "third hit" probably initiated tumorigenesis. Somatic mutation spectra were similar in 5' and 3' mutant patients, often resembling classical FAP. In exon 9 mutants, in contrast, "third hits" were more common. Most "third hits" left three 20 amino acid repeats (20AARs) on the germline mutant APC allele, with LOH (or proximal somatic mutation) of the wild-type allele; but some polyps had loss of the germline mutant with mutation leaving one 20AAR on the wild-type allele.
CONCLUSIONS: We propose that mutations, such as nt4661insA, that leave three 20AARs are preferentially selected in cis with some AFAP mutations because the residual protein function is near optimal for tumorigenesis. Not all AFAP polyps appear to need "three hits" however. AFAP is phenotypically and genetically heterogeneous. In addition to effects of different germline mutations, modifier genes may be acting on the AFAP phenotype, perhaps influencing the quantity of functional protein produced by the germline mutant allele.

PMID 16461775  Gut. 2006 Oct;55(10):1440-8. doi: 10.1136/gut.2005.0871・・・
著者: H F A Vasen, G Möslein, A Alonso, S Aretz, I Bernstein, L Bertario, I Blanco, S Bülow, J Burn, G Capella, C Colas, C Engel, I Frayling, W Friedl, F J Hes, S Hodgson, H Järvinen, J-P Mecklin, P Møller, T Myrhøi, F M Nagengast, Y Parc, R Phillips, S K Clark, M Ponz de Leon, L Renkonen-Sinisalo, J R Sampson, A Stormorken, S Tejpar, H J W Thomas, J Wijnen
雑誌名: Gut. 2008 May;57(5):704-13. doi: 10.1136/gut.2007.136127. Epub 2008 Jan 14.
Abstract/Text BACKGROUND: Familial adenomatous polyposis (FAP) is a well-described inherited syndrome, which is responsible for <1% of all colorectal cancer (CRC) cases. The syndrome is characterised by the development of hundreds to thousands of adenomas in the colorectum. Almost all patients will develop CRC if they are not identified and treated at an early stage. The syndrome is inherited as an autosomal dominant trait and caused by mutations in the APC gene. Recently, a second gene has been identified that also gives rise to colonic adenomatous polyposis, although the phenotype is less severe than typical FAP. The gene is the MUTYH gene and the inheritance is autosomal recessive. In April 2006 and February 2007, a workshop was organised in Mallorca by European experts on hereditary gastrointestinal cancer aiming to establish guidelines for the clinical management of FAP and to initiate collaborative studies. Thirty-one experts from nine European countries participated in these workshops. Prior to the meeting, various participants examined the most important management issues according to the latest publications. A systematic literature search using Pubmed and reference lists of retrieved articles, and manual searches of relevant articles, was performed. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described herein may be helpful in the appropriate management of FAP families. In order to improve the care of these families further, prospective controlled studies should be undertaken.

PMID 18194984  Gut. 2008 May;57(5):704-13. doi: 10.1136/gut.2007.13612・・・
著者: A H Kartheuser, R Parc, C P Penna, E Tiret, P Frileux, L Hannoun, B Nordlinger, J Loygue
雑誌名: Surgery. 1996 Jun;119(6):615-23.
Abstract/Text BACKGROUND: The choice between ileal pouch-anal anastomosis (IPAA) and ileorectal anastomosis (IRA) in the treatment of patients with familial adenomatous polyposis remains controversial. The aims of this study were to assess our 10-year experience with proctocolectomy, endoanal mucosectomy, construction of an ileal reservoir pouch, and IPAA in a series of 171 patients with familial adenomatous polyposis and to compare the functional results after IPAA with those after IRA.
METHODS: Data from patients treated by IPAA at one institution were prospectively accumulated from October 1983 to October 1993. Medical records of 171 consecutive patients were studied regarding morbidity and functional results. These functional results were compared with those of a series of 23 patients who underwent IRA at the same institution.
RESULTS: One patient (0.6%) died after operation. Sixty-two patients (36%) had concomitant colorectal carcinoma, 36 of which tumors were invasive (15 stage A, 13 stage B, and 8 stage C). Forty-six patients (27%) had at least one postoperative complication, with 14 patients requiring reoperation (8%). Twenty-six patients (15%) had obstruction. Seven patients (4%) had pelvic sepsis, and one had transient impotence (0.6%). Only two patients (1%) had a typical episode of pouchitis. The mean follow-up was 29 months (range, 3 to 100 months); 101 patients were monitored for more than 1 year. Little difference was noted between bowel function after IRA and that after IPAA. The mean daytime stool frequency after IPAA was 4.2 with 26% of patients having an average of 1 bowel movement at nighttime, compared with a stool frequency of 3.0 and 13% of patients having night evacuation after IRA. Daytime continence was normal for 98% of patients after IPAA and for all the patients after IRA. Nighttime continence was normal in 96% and 98% of patients, respectively.
CONCLUSIONS: Morbidity and functional results after IPAA for familial adenomatous polyposis do not differ from those reported after IRA. For this reason and because of the risk of rectal cancer after ileorectal anastomosis, IPAA with endoanal mucosectomy is our first choice in the treatment of patients with familial adenomatous polyposis.

PMID 8650601  Surgery. 1996 Jun;119(6):615-23.
著者: D M Eccles, P W Lunt, Y Wallis, M Griffiths, B Sandhu, S McKay, D Morton, J Shea-Simonds, F Macdonald
雑誌名: Arch Dis Child. 1997 Nov;77(5):431-5.
Abstract/Text Familial adenomatous polyposis (FAP) is a dominantly inherited predisposition to the development of many hundreds to thousands of adenomatous polyps of the colon. The mean age of onset is around 15 years, symptoms may arise in the third decade, and the median age for the development of colonic cancer is 35-40 years. Prophylactic colectomy reduces the risk of death from colorectal cancer to such an extent that late sequelae such as upper gastrointestinal tumours have become the main cause of mortality in appropriately managed patients. The age at which colonic surveillance begins reflects the natural history of the disease. Onset of polyp formation and cancer in childhood is very unusual, but has recently been associated with a specific mutation at codon 1309 in exon 15 where a more severe phenotype is sometimes observed. The case histories of two families are reported in which there is childhood onset of polyps in the youngest generation and in one case a carcinoma, in whom mutations have been identified in exon 11 of the APC gene. Several other affected relatives were diagnosed at ages ranging from 5-48 years, some already with a cancer at the time of first screening. Since the aim of screening for colonic polyps is prevention of colonic cancer, family members at risk should be offered genetic assessment and direct mutation testing where this is possible, usually in the early teens. In the absence of a genetic test (the situation in about one third of families) or in a known gene carrier, annual colonoscopy examination is advised from the same age. Clinicians should take note of the family history and be prepared to consider much earlier intervention if symptoms occur in a child with a family history of FAP. Where childhood onset of polyps has occurred, other children at risk in the family must be offered earlier genetic testing and endoscopic surveillance.

PMID 9487968  Arch Dis Child. 1997 Nov;77(5):431-5.
著者: P Rozen, Z Samuel, M Rabau, G Goldman, R Shomrat, C Legum, A Orr-Urtreger
雑誌名: Fam Cancer. 2001;1(2):75-82.
Abstract/Text UNLABELLED: Familial adenomatous polyposis (FAP) is an uncommon, but widespread genetic disorder that develops multiple colonic adenomatous polyps and, if untreated, can lead to large bowel cancer. Little is known about its occurrence and characteristics in the Israeli population.
AIMS: To evaluate FAP prevalence, phenotypic manifestations and compliance for diagnosis and follow-up in our registry.
METHODS: Since 1993 approximately one-half of FAP patients in Israel have been seen and followed-up by us before and/or after colectomy. They and their families were encouraged to have mutation analysis, genetic and/or endoscopic screening.
RESULTS: 37 pedigrees were identified, including 2 non-Jewish. The Jewish ethnic distribution was similar to that of the general population and the point prevalence rate estimated as 28.4/one million Jewish inhabitants. There were 461 first-degree relatives at-risk for FAP. Genetic screening was completed and successful in 28 pedigrees (87.5%), and 73 FAP patients entered the registry. Marked intra- familial phenotypic variations with minimal disease manifestation were noted in 11 patients belonging to 4 pedigrees. Cancer occurred in 15.1% (11 patients), in 10 before FAP diagnosis or during follow- up elsewhere, but one non-compliant patient developed duodenal cancer. One other patient died from a massive, neglected, intra- abdominal desmoid. Compliance for evaluation and follow-up of pedigree members and individual FAP patients was inadequate in 29% and 27%, respectively.
CONCLUSIONS: FAP occurs in the Israeli Jewish population at the expected rate, but is inadequately recognized in non-Jews. The inadequate compliance for screening and post-surgical follow-up needs to be addressed by educating the public, health care workers and Health Insurers.

PMID 14574001  Fam Cancer. 2001;1(2):75-82.
著者: K Ø Olsen, S Juul, S Bülow, H J Järvinen, A Bakka, J Björk, T Oresland, S Laurberg
雑誌名: Br J Surg. 2003 Feb;90(2):227-31. doi: 10.1002/bjs.4082.
Abstract/Text BACKGROUND: Knowledge about the fertility of women suffering from familial adenomatous polyposis (FAP) is scarce and inconclusive. The purpose of this study was to investigate the fecundity of women with FAP before and after operation, and to compare the findings with those of a general population database and women with ulcerative colitis.
METHODS: A questionnaire concerning reproductive experiences and waiting times to pregnancy was sent to all 230 women on the polyposis registers in Denmark, Finland, Sweden and Norway in whom primary surgery had consisted of ileorectal anastomosis or ileal pouch-anal anastomosis. Data on the general population and women with ulcerative colitis came from an existing database. Cox regression and Kaplan-Meier plots were used for analysis.
RESULTS: The fecundity of women with FAP before operation and after colectomy with ileorectal anastomosis was similar to that of the general population. However, fecundity dropped to 54 per cent (P = 0.015) following proctocolectomy with ileal pouch-anal anastomosis, although it was greater than the postoperative fecundity of women with ulcerative colitis.
CONCLUSION: The significant reduction in female fecundity after ileal pouch-anal anastomosis should be communicated to young women with FAP before it is decided which surgical option to follow.

PMID 12555301  Br J Surg. 2003 Feb;90(2):227-31. doi: 10.1002/bjs.4082・・・
著者: Takeo Iwama, Kazuo Tamura, Takayuki Morita, Takashi Hirai, Hirotoshi Hasegawa, Koichi Koizumi, Kazuo Shirouzu, Kenichi Sugihara, Takehira Yamamura, Tetsuichiro Muto, Joji Utsunomiya, Japanese Society for Cancer of the Colon and Rectum
雑誌名: Int J Clin Oncol. 2004 Aug;9(4):308-16. doi: 10.1007/s10147-004-0414-4.
Abstract/Text The clinical situation of familial adenomatous polyposis (FAP) in Japan has changed in the period since the last analysis of data of the Japanese Polyposis Center. To reevaluate our data and elucidate the changes we analyzed the records of the 1390 FAP patients in 900 families registered with the Polyposis Committee of the Japanese Society for Cancer of the Colon and Rectum. In the 13-year period 1990-2003, clinical differences between men and women with FAP diminished. The postoperative prognosis was substantially better in patients without advanced colorectal cancer (stage > or = T2) than in those with early cancer or no cancer. Mean age at death improved from 42.5 years in the period before 1990 to 46.0 years, and it was a result of a decreased proportion of deaths from colorectal cancer. The distribution of colorectal cancer in FAP patients was similar to that in the general population. Desmoid tumors accounted for about 10% of deaths in the recent 13 years (1990-2003). The cumulative risk of rectal cancer in the preserved rectum was 12% at 10 years and 23% at 15 years. The registry system in Japan revealed a new clinical situation in FAP patients, and the findings of this study will be useful to improve the prognosis of patients with FAP.

PMID 15375708  Int J Clin Oncol. 2004 Aug;9(4):308-16. doi: 10.1007/s1・・・
著者: N J H Sturt, M C Gallagher, P Bassett, C R Philp, K F Neale, I P M Tomlinson, A R J Silver, R K S Phillips
雑誌名: Gut. 2004 Dec;53(12):1832-6. doi: 10.1136/gut.2004.042705.
Abstract/Text BACKGROUND: Many patients with familial adenomatous polyposis (FAP) die from desmoid tumours which can arise spontaneously but often appear to be surgically induced by prophylactic colectomy. FAP results from germline adenomatous polyposis coli (APC) gene mutations and desmoids arise following biallelic APC mutation, with one change usually occurring distal to the second beta-catenin binding/degradation repeat of the gene (3' to codon 1399). We have suggested that because families with germline mutations in this region already have the requisite change, they are more likely to develop desmoids. However, there are families with 5' germline mutations where desmoids are common.
PATIENTS AND METHODS: We examined desmoid risk dependent on germline APC mutation, sex, history of abdominal surgery, and family history in FAP patients from the St Mark's Hospital Polyposis Registry.
RESULTS: Overall desmoid prevalence was 15%. Desmoids tended to cluster in susceptible individuals, irrespective of the germline APC mutation. Independent predictors of increased desmoid risk were: germline mutation distal to codon 1399; any family history of disease; and a strong family history of desmoids. A family history of multiple desmoids (>1) increased an individual's own risk of multiplicity. Females had twice the odds of developing desmoids compared with males. There was no significant interaction between any of the three explanatory variables.
CONCLUSIONS: Our results indicate the influence of unknown genetic factors independent of APC in susceptibility to desmoid tumours in FAP. The data have implications in terms of clinical management of FAP patients and assessing the balance between chemoprevention and prophylactic colectomy.

PMID 15542524  Gut. 2004 Dec;53(12):1832-6. doi: 10.1136/gut.2004.0427・・・
著者: Paul Rozen, Finlay Macrae
雑誌名: Fam Cancer. 2006;5(3):227-35. doi: 10.1007/s10689-005-5674-2.
Abstract/Text Familial adenomatous polyposis (FAP) is an autosomal dominant condition mostly due to a mutation of the APC gene on the chromosome 5q. Carriers have an almost 100% chance of developing colorectal cancer after having multiple (typically 100s to 1000s) of adenomatous polyps. It is usually readily identified through this phenotype of multiple adenomas. Correlations between the location of the family-specific mutation on the APC gene and clinical manifestations of the disease are of some assistance in clinical management, though there is heterogeneity in clinical course even between family members with the same mutation. FAP is important to recognize, as there are disease-specific management implications with respect to offering mutational analysis of the APC (and perhaps other) genes for predictive testing of other family members, endoscopic diagnostic procedures, surveillance planning, and surgical management. Extra-colonic manifestations, including duodenal polyposis, desmoid disease and other tumours, can dominate clinical care after colectomy. The inheritable and lethal nature of the disease, together with the availability of effective treatment strategies, makes a sensitive clinical and psychosocial approach important to maximize compliance and good outcomes for all members of affected families.

PMID 16998668  Fam Cancer. 2006;5(3):227-35. doi: 10.1007/s10689-005-5・・・
著者: H F Vasen, P van Duijvendijk, E Buskens, C Bülow, J Björk, H J Järvinen, S Bülow
雑誌名: Gut. 2001 Aug;49(2):231-5.
Abstract/Text BACKGROUND AND AIMS: The choice of colorectal surgery in patients with familial adenomatous polyposis lies between the morbidity of proctocolectomy and ileum-pouch-anal anastomosis (IPAA) and the mortality from rectal cancer after total colectomy and ileorectal anastomosis (IRA). The aims of the present study were: (1) to assess the risk of dying from rectal cancer after IRA, (2) to compare the life expectancy between patients with an IRA and those with an IPAA, and (3) to investigate whether regular endoscopic examination of the rectum leads to detection of cancer at an earlier stage.
METHODS: Clinical and pathological data on 659 patients who underwent colectomy and ileorectal anastomosis were collected from four national polyposis registries-that is, in Denmark, Finland, Sweden, and the Netherlands. Data were analysed using survival analysis methods. Decision analysis was used to compare the life expectancy between patients with an IRA and those with an IPAA.
RESULTS: A total of 47 patients developed rectal cancer after IRA. The risk of dying from rectal cancer was 12.5% (95% confidence interval 7.1--17.9%) by age 65. Compared with IRA, IPAA would lead to an increase in life expectancy of 1.8 years. Seventy five per cent of patients with rectal cancer had a negative rectoscopy within 12 months before the diagnosis.
CONCLUSION: IRA is associated with substantial mortality due to rectal cancer. Follow up examinations of the rectum does not have sufficient preventive effect on morbidity and mortality of rectal cancer.

PMID 11454800  Gut. 2001 Aug;49(2):231-5.
著者: Alex Kartheuser, Pierre Stangherlin, Dimitri Brandt, Christophe Remue, Christine Sempoux
雑誌名: Fam Cancer. 2006;5(3):241-60; discussion 261-2. doi: 10.1007/s10689-005-5672-4.
Abstract/Text 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.

PMID 16998670  Fam Cancer. 2006;5(3):241-60; discussion 261-2. doi: 10・・・
著者: L Bertario, A Russo, P Radice, L Varesco, M Eboli, P Spinelli, A Reyna, P Sala
雑誌名: Ann Surg. 2000 Apr;231(4):538-43.
Abstract/Text OBJECTIVE: To identify factors influencing the occurrence of cancer in the rectal remnant in patients with familial adenomatous polyposis (FAP) after colectomy and ileorectal anastomosis (IRA).
SUMMARY BACKGROUND DATA: The risk for rectal cancer in patients with FAP after colectomy and IRA remains a major concern.
METHODS: Between 1955 and 1997, 371 patients (206 men, 165 women) from the Registry of Hereditary Colorectal Tumors underwent colectomy and IRA as a primary surgical procedure. Survival was estimated using the Kaplan-Meier method. Cox proportional hazard models were fitted to assess the relative excess risk of rectal cancer and to control for confounding factors. A multivariate analysis was performed to assess the relation between cancer risk in the rectum and sex, age, number of rectal polyps, colon cancer, and APC germline mutation.
RESULTS: Median follow-up was 81 months. Eighty-nine patients (24%) had colon cancer at the time of surgery. The APC mutation was found in 200 patients. In 27 patients, cancer developed in the retained rectum 1 to 26 years after surgery. The incidence of rectal carcinoma appears to increase with time: at 10, 15, and 20 years after surgery, the cumulative risk was 7.7%, 13.1%, and 23.0%, respectively. Multivariate analysis identified as independent predictors the presence of colon cancer at IRA and a mutation occurring between codons 1250 and 1464; both factors increased the risk nine times.
CONCLUSIONS: The presence of cancer at IRA and APC mutation type are the most important risk factors for the future development of cancer in the rectal remnant in patients with FAP.

PMID 10749615  Ann Surg. 2000 Apr;231(4):538-43.
著者: James Church
雑誌名: Fam Cancer. 2006;5(3):237-40; discussion 262-2. doi: 10.1007/s10689-005-5661-7.
Abstract/Text
PMID 16998669  Fam Cancer. 2006;5(3):237-40; discussion 262-2. doi: 10・・・
著者: J Church, C Burke, E McGannon, O Pastean, B Clark
雑誌名: Dis Colon Rectum. 2001 Sep;44(9):1249-54.
Abstract/Text PURPOSE: Patients with familial adenomatous polyposis need prophylactic colectomy and ileorectal anastomosis or restorative proctocolectomy. Preoperative rectal polyp counts have been used as one factor to determine which operation should be done, triaging patients according to risk of rectal cancer or completion proctectomy after ileorectal anastomosis. This study was designed to examine the reliability of preoperative proctoscopy in predicting familial adenomatous polyposis severity and outcome after ileorectal anastomosis.
METHODS: Familial adenomatous polyposis patients were categorized according to preoperative proctoscopy as follows: Group 1, 5 or fewer adenomas; Group 2, 6 to 19 adenomas; Group 3, 20 or more adenomas. Familial adenomatous polyposis severity was defined as mild if there were < 1,000 polyps in the colon at colectomy and severe if there were > 1,000 polyps.
RESULTS: A total of 213 patients were reviewed, 80 in Group 1, 59 in Group 2, and 74 in Group 3. There was no difference among the groups in mean age at presentation. Patients with fewer than five rectal adenomas were predominately females. They rarely had symptoms (22.8 percent), had mostly mild polyposis (86.5 percent), and in 74 of 80 cases underwent ileorectal anastomosis. Only six underwent restorative proctocolectomy. Of those having an ileorectal anastomosis, five needed later proctectomy, none for cancer. Patients with 6 to 19 rectal polyps were a similar group to those with 5 or fewer. Most were asymptomatic (67.8 percent), most had mild polyposis (81.6 percent), and 54 of 59 underwent ileorectal anastomosis (5 had restorative proctocolectomy). Only 3 of the 54 having ileorectal anastomosis needed subsequent proctectomy, 2 for rectal cancer. The patients with 20 or more rectal polyps were different. They usually presented with symptoms (86 percent), the majority (56.6 percent) had severe polyposis, and only 50 percent (37/74) underwent ileorectal anastomosis, the other half having restorative proctocolectomy. Of the 37 patients with an ileorectal anastomosis, 13 needed later proctectomy (35.1 percent), 4 for cancer (10.8 percent).
CONCLUSION: Fewer than five rectal adenomas at presentation almost always predicts mild disease, and patients do well after ileorectal anastomosis. Twenty or more adenomas usually means severe disease. Patients with 6 to 19 adenomas are often mildly affected, but their phenotype is less benign than that of patients with fewer than five polyps. Although not foolproof, proctoscopy is a useful test in triaging patients with familial adenomatous polyposis according to disease severity.

PMID 11584194  Dis Colon Rectum. 2001 Sep;44(9):1249-54.
著者: O Aziz, T Athanasiou, V W Fazio, R J Nicholls, A W Darzi, J Church, R K S Phillips, P P Tekkis
雑誌名: Br J Surg. 2006 Apr;93(4):407-17. doi: 10.1002/bjs.5276.
Abstract/Text BACKGROUND: Surgery for familial adenomatous polyposis (FAP) aims to minimize cancer risk while providing good functional outcome. Colectomy with ileorectal anastomosis and proctocolectomy with ileal pouch-anal anastomosis both offer this, but there is no clear consensus about which is better.
METHODS: This is a meta-analysis of comparative studies published between 1991 and 2003 reporting early and late postoperative adverse events, functional outcomes and quality of life.
RESULTS: Twelve studies containing 1002 patients (53.4 per cent ileal pouch, 46.6 per cent ileorectal anastomosis) were identified. Bowel frequency (weighted mean difference 1.62 (95 per cent confidence interval (c.i.) 1.05 to 2.20)), night defaecation (odds ratio (OR) 6.64 (95 per cent c.i. 2.99 to 14.74)) and use of incontinence pads (OR 2.72 (95 per cent c.i. 1.02 to 7.23)) were significantly less in the ileorectal group, although faecal urgency was reduced with the ileal pouch (odds ratio 0.43 (95 per cent c.i. 0.23 to 0.80)). Reoperation within 30 days was more common after ileal pouch construction (23.4 versus 11.6 per cent; OR 2.11 (95 per cent c.i. 1.21 to 3.70)). There was no significant difference between the techniques in terms of sexual dysfunction, dietary restriction, or postoperative complications. Rectal cancer was a diagnosis only in the ileorectal group (5.5 per cent).
CONCLUSION: Ileal pouch and ileorectal anastomoses have individual merits. Further research is needed to determine which most benefits patients with FAP.

PMID 16511903  Br J Surg. 2006 Apr;93(4):407-17. doi: 10.1002/bjs.5276・・・
著者: Anne Lyster Knudsen, Marie Luise Bisgaard, Steffen Bülow
雑誌名: Fam Cancer. 2003;2(1):43-55.
Abstract/Text Over the last decade, a subset of familial adenomatous polyposis (FAP) patients with a milder course of disease termed attenuated familial adenomatous polyposis (AFAP) has been described. AFAP is not well-defined as a disease entity - the reports on AFAP are largely casuistic or only deal with a few kindreds--and the diagnostic criteria and methods of investigation differ markedly. The true incidence and frequency of AFAP is not known. The mutations in APC associated with AFAP have mainly been detected in three parts of the gene: in the 5' end (the first five exons), in exon 9 and in the distal 3' end. The main features of AFAP are 100 or less colorectal adenomas with a tendency to rectal sparing, a delay in onset of adenomatosis and bowel symptoms of 20-25 years, a delay in onset of colorectal cancer (CRC) of 10-20 years and death from CRC of 15-20 years, and although the lifetime penetrance of CRC appears to be high, CRC does not seem to develop in nearly all affected patients. A more limited expression of the extracolonic features is seen, but gastric and duodenal adenomas are frequently encountered. Colonoscopy is preferred to sigmoidoscopy, should begin at the age of 20-25 years and no upper age limit of stopping surveillance is justified. Regular esophago-gastro- duodenoscopy (EGD) is recommended. Until further research has provided us with a more substantiated knowledge about AFAP changes in current surveillance and treatment are not recommended. Prophylactic colectomy with ileorectal anastomosis (IRA) is recommended in most patients.

PMID 14574166  Fam Cancer. 2003;2(1):43-55.
著者: Randall W Burt, Mark F Leppert, Martha L Slattery, Wade S Samowitz, Lisa N Spirio, Richard A Kerber, Scott K Kuwada, Deborah W Neklason, James A Disario, Elaine Lyon, J Preston Hughes, William Y Chey, Raymond L White
雑誌名: Gastroenterology. 2004 Aug;127(2):444-51.
Abstract/Text BACKGROUND & AIMS: An attenuated form of familial adenomatous polyposis has been described, but the phenotype remains poorly understood.
METHODS: We performed genetic testing on 810 individuals from 2 attenuated familial adenomatous polyposis kindreds harboring an identical germline adenomatous polyposis coli gene mutation. Colonoscopy was performed on mutation-positive persons.
RESULTS: The disease-causing mutation was present in 184 individuals. Adenomatous polyps were present in 111 of 120 gene carriers who had colonoscopy at an average age of 41 years. The median number of adenomas was 25 (range, 0-470), with striking variability of polyp numbers and a proximal colonic predominance of polyps. Colorectal cancer occurred in 27 mutation carriers (average age, 58 years; range, 29-81 years), with 75% in the proximal colon. The cumulative risk of colorectal cancer by age 80 was estimated to be 69%. An average of 3.4 recurrent polyps (range, 0-29) were found in the postcolectomy rectal remnant over a mean of 7.8 years (range, 1-34 years), with 1 rectal cancer.
CONCLUSIONS: This investigation shows that attenuated familial adenomatous polyposis in the kindreds examined shows a much smaller median number of polyps than typical familial adenomatous polyposis, a wide variability in polyp number even at older ages, and a more proximal colonic location of polyps and cancer, yet it is associated with an extremely high risk of colon cancer. The phenotype of attenuated familial adenomatous polyposis mimics typical familial adenomatous polyposis in some cases but in others is difficult to distinguish from sporadic adenomas and colorectal cancer, thus making genetic testing particularly important.

PMID 15300576  Gastroenterology. 2004 Aug;127(2):444-51.
著者: G Steinbach, P M Lynch, R K Phillips, M H Wallace, E Hawk, G B Gordon, N Wakabayashi, B Saunders, Y Shen, T Fujimura, L K Su, B Levin, L Godio, S Patterson, M A Rodriguez-Bigas, S L Jester, K L King, M Schumacher, J Abbruzzese, R N DuBois, W N Hittelman, S Zimmerman, J W Sherman, G Kelloff
雑誌名: N Engl J Med. 2000 Jun 29;342(26):1946-52. doi: 10.1056/NEJM200006293422603.
Abstract/Text BACKGROUND: Patients with familial adenomatous polyposis have a nearly 100 percent risk of colorectal cancer. In this disease, the chemopreventive effects of nonsteroidal antiinflammatory drugs may be related to their inhibition of cyclooxygenase-2.
METHODS: We studied the effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on colorectal polyps in patients with familial adenomatous polyposis. In a double-blind, placebo-controlled study, we randomly assigned 77 patients to treatment with celecoxib (100 or 400 mg twice daily) or placebo for six months. Patients underwent endoscopy at the beginning and end of the study. We determined the number and size of polyps from photographs and videotapes; the response to treatment was expressed as the mean percent change from base line.
RESULTS: At base line, the mean (+/-SD) number of polyps in focal areas where polyps were counted was 15.5+/-13.4 in the 15 patients assigned to placebo, 11.5+/-8.5 in the 32 patients assigned to 100 mg of celecoxib twice a day, and 12.3+/-8.2 in the 30 patients assigned to 400 mg of celecoxib twice a day (P=0.66 for the comparison among groups). After six months, the patients receiving 400 mg of celecoxib twice a day had a 28.0 percent reduction in the mean number of colorectal polyps (P=0.003 for the comparison with placebo) and a 30.7 percent reduction in the polyp burden (the sum of polyp diameters) (P=0.001), as compared with reductions of 4.5 and 4.9 percent, respectively, in the placebo group. The improvement in the extent of colorectal polyposis in the group receiving 400 mg twice a day was confirmed by a panel of endoscopists who reviewed the videotapes. The reductions in the group receiving 100 mg of celecoxib twice a day were 11.9 percent (P=0.33 for the comparison with placebo) and 14.6 percent (P=0.09), respectively. The incidence of adverse events was similar among the groups.
CONCLUSIONS: In patients with familial adenomatous polyposis, six months of twice-daily treatment with 400 mg of celecoxib, a cyclooxygenase-2 inhibitor, leads to a significant reduction in the number of colorectal polyps.

PMID 10874062  N Engl J Med. 2000 Jun 29;342(26):1946-52. doi: 10.1056・・・
著者: Francis M Giardiello, Vincent W Yang, Linda M Hylind, Anne J Krush, Gloria M Petersen, Jill D Trimbath, Steven Piantadosi, Elizabeth Garrett, Deborah E Geiman, Walter Hubbard, G Johan A Offerhaus, Stanley R Hamilton
雑誌名: N Engl J Med. 2002 Apr 4;346(14):1054-9. doi: 10.1056/NEJMoa012015.
Abstract/Text BACKGROUND: Familial adenomatous polyposis is caused by a germ-line mutation in the adenomatous polyposis coli gene and is characterized by the development of hundreds of colorectal adenomas and, eventually, colorectal cancer. Nonsteroidal antiinflammatory drugs can cause regression of adenomas, but whether they can prevent adenomas is unknown.
METHODS: We conducted a randomized, double-blind, placebo-controlled study of 41 young subjects (age range, 8 to 25 years) who were genotypically affected with familial adenomatous polyposis but phenotypically unaffected. The subjects received either 75 or 150 mg of sulindac orally twice a day or identical-appearing placebo tablets for 48 months. The number and size of new adenomas and side effects of therapy were evaluated every four months for four years, and the levels of five major prostaglandins were serially measured in biopsy specimens of normal-appearing colorectal mucosa.
RESULTS: After four years of treatment, the average rate of compliance exceeded 76 percent in the sulindac group, and mucosal prostaglandin levels were lower in this group than in the placebo group. During the course of the study, adenomas developed in 9 of 21 subjects (43 percent) in the sulindac group and 11 of 20 subjects in the placebo group (55 percent) (P=0.54). There were no significant differences in the mean number (P=0.69) or size (P=0.17) of polyps between the groups. Sulindac did not slow the development of adenomas, according to an evaluation involving linear longitudinal methods.
CONCLUSIONS: Standard doses of sulindac did not prevent the development of adenomas in subjects with familial adenomatous polyposis.

PMID 11932472  N Engl J Med. 2002 Apr 4;346(14):1054-9. doi: 10.1056/N・・・
著者: Patricia McGettigan, David Henry
雑誌名: JAMA. 2006 Oct 4;296(13):1633-44. doi: 10.1001/jama.296.13.jrv60011. Epub 2006 Sep 12.
Abstract/Text CONTEXT: Evidence that rofecoxib increases the risk of myocardial infarction has led to scrutiny of other nonsteroidal anti-inflammatory drugs (NSAIDs). Regulatory agencies have provided variable advice regarding the cardiovascular risks with older nonselective NSAIDs.
OBJECTIVE: To undertake a systematic review and meta-analysis of controlled observational studies to compare the risks of serious cardiovascular events with individual NSAIDs and cyclooxygenase 2 inhibitors.
DATA SOURCES: Searches were conducted of electronic databases (1985-2006), scientific meeting proceedings, epidemiological research Web sites, and bibliographies of eligible studies.
STUDY SELECTION: Eligible studies were of case-control or cohort design, reported on cardiovascular events (predominantly myocardial infarction) with cyclooxygenase 2 inhibitor, NSAID use, or both with nonuse/remote use of the drugs as the reference exposure. Of 7086 potentially eligible titles, 17 case-control and 6 cohort studies were included. Thirteen studies reported on cyclooxygenase 2 inhibitors, 23 on NSAIDs, and 13 on both groups of drugs.
DATA EXTRACTION: Two people independently extracted data and assessed study quality with disagreements resolved by consensus.
DATA SYNTHESIS: Data were combined using a random-effects model. A dose-related risk was evident with rofecoxib, summary relative risk with 25 mg/d or less, 1.33 (95% confidence interval [CI], 1.00-1.79) and 2.19 (95% CI, 1.64-2.91) with more than 25 mg/d. The risk was elevated during the first month of treatment. Celecoxib was not associated with an elevated risk of vascular occlusion, summary relative risk 1.06 (95% CI, 0.91-1.23). Among older nonselective drugs, diclofenac had the highest risk with a summary relative risk of 1.40 (95% CI, 1.16-1.70). The other drugs had summary relative risks close to 1: naproxen, 0.97 (95% CI, 0.87-1.07); piroxicam, 1.06 (95% CI, 0.70-1.59); and ibuprofen, 1.07 (95% CI, 0.97-1.18).
CONCLUSIONS: This review confirms the findings from randomized trials regarding the risk of cardiovascular events with rofecoxib and suggests that celecoxib in commonly used doses may not increase the risk, contradicts claims of a protective effect of naproxen, and raises serious questions about the safety of diclofenac, an older drug.

PMID 16968831  JAMA. 2006 Oct 4;296(13):1633-44. doi: 10.1001/jama.296・・・
著者: I Heiskanen, I Kellokumpu, H Järvinen
雑誌名: Endoscopy. 1999 Aug;31(6):412-6. doi: 10.1055/s-1999-41.
Abstract/Text BACKGROUND AND STUDY AIMS: The advantage of endoscopic surveillance and treatment of duodenal polyposis is still unclear in familial adenomatous polyposis (FAP). The aim of this study was to evaluate the progression patterns of duodenal polyposis and the results of treatment.
PATIENTS AND METHODS: In our institution, the 98 FAP patients included in the prospective follow-up study underwent at least one upper endoscopic examination, carried out with few exceptions, by a single surgeon endoscopist. The progression patterns of duodenal polyposis, the cumulative risk of severe duodenal polyposis and duodenal cancer as well as the results of surgical treatment were evaluated during a median follow-up of 11 years.
RESULTS: Duodenal adenomas were detected in 78 patients corresponding to a cumulative lifetime incidence of 97%. The stage of adenomatosis progressed in 52 (73 %) of the 71 patients who underwent repeated endoscopies. The cumulative risks of stage IV adenomatosis and duodenal carcinoma were 30% and 4 %, respectively. Excisional treatment through open duodenotomy resulted in significant stage regression but was followed by new progression. In all patients the median interval for progression by one stage varied from 4 to 11 years.
CONCLUSIONS: Duodenal adenomas almost invariably occur in FAP; endoscopic surveillance is thus warranted to anticipate severe progression and malignant transformation. Excisional surgical treatment can, however, give only transient stage reduction.

PMID 10494676  Endoscopy. 1999 Aug;31(6):412-6. doi: 10.1055/s-1999-41・・・
著者: S Bülow, J Björk, I J Christensen, O Fausa, H Järvinen, F Moesgaard, H F A Vasen, DAF Study Group
雑誌名: Gut. 2004 Mar;53(3):381-6.
Abstract/Text BACKGROUND: The prevalence of duodenal carcinoma is much higher in familial adenomatous polyposis (FAP) than in the background population, and duodenal adenomatosis is found in most polyposis patients.
AIMS: To describe the long term natural history of duodenal adenomatosis in FAP and evaluate if cancer prophylactic surveillance of the duodenum is indicated.
METHODS: A prospective five nation study was carried out in the Nordic countries and the Netherlands.
PATIENTS: A total of 368 patients were examined by gastroduodenoscopy at two year intervals during the period 1990-2001.
RESULTS: At the first endoscopy, 238 (65%) patients had duodenal adenomas at a median age of 38 years. Median follow up was 7.6 years. The cumulative incidence of adenomatosis at age 70 years was 90% (95% confidence interval (CI) 79-100%), and of Spigelman stage IV 52% (95% CI 28-76%). The probability of an advanced Spigelman score increased during the study period (p<0.0001) due to an increasing number and size of adenomas. Two patients had asymptomatic duodenal carcinoma at their first endoscopy while four developed carcinoma during the study at a median age of 52 years (range 26-58). The cumulative incidence rate of cancer was 4.5% at age 57 years (95% CI 0.1-8.9%) and the risk was higher in patients with Spigelman stage IV at their first endoscopy than in those with stages 0-III (p<0.01).
CONCLUSIONS: The natural course of duodenal adenomatosis has now been described in detail. The high incidence and increasing severity of duodenal adenomatosis with age justifies prophylactic examination, and a programme is presented for upper gastrointestinal endoscopic surveillance.

PMID 14960520  Gut. 2004 Mar;53(3):381-6.
著者: A D Spigelman, C B Williams, I C Talbot, P Domizio, R K Phillips
雑誌名: Lancet. 1989 Sep 30;2(8666):783-5.
Abstract/Text 102 patients with familial adenomatous polyposis underwent upper gastrointestinal endoscopy as a screening test for gastroduodenal adenomas. 100 had duodenal abnormalities (dysplasia in 94, and hyperplasia in 6), usually in the second and third parts of the duodenum (91%). The periampullary area was abnormal in 87 of 97 patients who had a biopsy specimen taken from this site (dysplasia 72, hyperplasia 13, and inflammation 2). By contrast, gastric dysplasia was found in only 6 patients. Classification of duodenal polyposis on a 5-grade scale (stages 0-IV), based on polyp number, size, histology, and severity of dysplasia, showed that 11 had stage IV disease: these patients are at greatest risk of malignant change and require close surveillance. The pattern of dysplasia observed in the upper gastrointestinal tract resembled the pattern of mucosal exposure to bile.

PMID 2571019  Lancet. 1989 Sep 30;2(8666):783-5.
著者: L A A Brosens, J J Keller, G J A Offerhaus, M Goggins, F M Giardiello
雑誌名: Gut. 2005 Jul;54(7):1034-43. doi: 10.1136/gut.2004.053843.
Abstract/Text
PMID 15951555  Gut. 2005 Jul;54(7):1034-43. doi: 10.1136/gut.2004.0538・・・
著者: Emilio Morpurgo, Gary C Vitale, Susan Galandiuk, Jennifer Kimberling, Craig Ziegler, Hiram C Polk
雑誌名: J Gastrointest Surg. 2004 Jul-Aug;8(5):559-64. doi: 10.1016/j.gassur.2004.03.001.
Abstract/Text The aim of this study was to evaluate the clinical characteristics of patients with familial adenomatous polyposis (FAP) undergoing surgical treatment over a 10-year period and specifically to evaluate the incidence and clinical outcome of patients treated for duodenal adenomas. Patients with FAP who underwent surgical treatment for colonic polyposis at the University of Louisville from January 1992 to July 2002 were investigated. Surgical treatment included colectomy and ileal J-pouch-anal anastomosis (IPAA) or completion proctectomy with or without IPAA in those who had previously undergone subtotal colectomy elsewhere. All patients underwent screening gastroduodenoscopy at 3-year intervals beginning at the time of diagnosis or referral. Postoperative morbidity, mortality, and functional outcome were evaluated, as well as the occurrence of extracolonic manifestations and results of treatment for duodenal adenomas when required. Fifty-four patients were included in the study (mean age 28 +/- 2 years). Twenty-seven of them (50%) underwent colectomy and IPAA as the initial operation. Twenty-seven patients had previously undergone subtotal colectomy. Eight of these 27 patients had cancer in the rectum, of which three were T4 and one was T2N1 cancer. Twenty-two patients underwent a completion proctectomy and three required abdominoperineal resection. Twenty of the 54 patients developed duodenal adenomas. The mean age of diagnosis of duodenal disease was not significantly different from that of patients who were still free of duodenal polyps (40 +/- 11 vs. 34 +/- 12 years). Seven of these 20 patients underwent local excision of duodenal polyps (either endocopically or transduodenally); four of these patients developed recurrent disease. Six patients underwent pancreaticoduodenectomy for duodenal adenomas with severe dyplasia. These patients experienced an increased number of bowel movements, from five per day (range 4 to 8) to 10 per day (range 6 to 15). One patient required pouch excision and end ileostomy to control diarrhea. Our data demonstrate the following: (1) patients with FAP who have undergone prior subtotal colectomy and ileorectal anastomosis have a high risk of developing advanced cancer in the rectal stump; (2) duodenal adenomas are common in patients with FAP and may occur at an early age; (3) screening duodenoscopy should be initiated at the time of diagnosis of FAP; (4) local excision of duodenal adenomas is associated with a high risk of local recurrence; and (5) even though pancreaticoduodenectomy is the treatment of choice for advanced duodenal adenomas, this procedure may adversely affect pouch function in some patients.

PMID 15239991  J Gastrointest Surg. 2004 Jul-Aug;8(5):559-64. doi: 10.・・・
著者: T Iwama, Y Mishima, J Utsunomiya
雑誌名: Ann Surg. 1993 Feb;217(2):101-8.
Abstract/Text The authors reviewed the case records of 1050 familial adenomatous polyposis (FAP) patients who were registered at their institution. The organ-specific morbidity and mortality rates of malignant tumor in FAP patients were compared with those of the general population of Japan, and the prognosis after rectum-preserving operation also was calculated. The cumulative prevalence of colorectal carcinoma at the age of 44 years was 0.52 for men and 0.61 for women. The observed/expected morbidity ratio was 20.9 (95% confidence interval, 10.8-36.6) for thyroid carcinoma, 3.08 (2.03-7.75) for gastric carcinoma, and 295 (263-330) for colorectal carcinoma. The observed/expected mortality ratios was 250 (112-447) for periampullary and small intestinal carcinoma, 3.43 (1.77-6.0) for gastric carcinoma, and 210 (183-241) for colorectal carcinoma. The risk of rectal carcinoma after ileorectal anastomosis was 13% (8.5-17.5%) at 10 years and 37% at 20 years. The results clarified the impact of FAP on the carcinogenesis in several organs as a whole including preserved rectum, and suggested a direction of the rational treatment of FAP.

PMID 8382467  Ann Surg. 1993 Feb;217(2):101-8.
著者: A L Knudsen, S Bülow
雑誌名: Fam Cancer. 2001;1(2):111-9.
Abstract/Text Desmoid tumours (DT) are rare benign tumours that do not metastasise, but tend to invade locally. DT are frequently seen in patients with familial adenomatous polyposis (FAP), and diagnosis and treatment are often difficult. Surgical trauma, genetic predisposition and hormonal factors are considered to be correlated with the development and growth of DT. In patients with FAP, 50% of the tumours are localised intra-abdominally, and 85-100% of these are mesenteric. DT frequently present as non- tender, slowly growing masses. The symptoms are abdominal pain, vomiting, diarrhoea or haematochezia. Mesenteric DT can cause small bowel obstruction or ischaemia, hydronephrosis or form fistulas. Diagnosis is obtained through biopsy and the extension is determined by a CT-scan. Surgical excision is recommended in patients with DT in the abdominal wall. First line treatment of mesenteric DT is a NSAID in combination with tamoxifen. Surgery may be considered in case of a small and well-defined DT with no signs of invasion of vital structures, and in cases of imminent bowel ischaemia or obstruction. The prognosis in mesenteric DT is serious, and improvement of the therapeutic strategy awaits current international studies.

PMID 14574007  Fam Cancer. 2001;1(2):111-9.
著者: Marry H Nieuwenhuis, Wouter De Vos Tot Nederveen Cappel, Akke Botma, Fokko M Nagengast, Jan H Kleibeuker, Elisabeth M H Mathus-Vliegen, Evelien Dekker, Jan Dees, Juul Wijnen, Hans F A Vasen
雑誌名: Clin Gastroenterol Hepatol. 2008 Feb;6(2):215-9. doi: 10.1016/j.cgh.2007.11.011.
Abstract/Text BACKGROUND & AIMS: Desmoid tumors are a severe extracolonic manifestation in familial adenomatous polyposis (FAP). Identification of risk factors might be helpful in the management of FAP patients with such tumors. The aim of this study was to assess potential risk factors for the development of desmoids in a cohort of Dutch FAP patients.
METHODS: The medical records of 735 FAP patients were analyzed for the occurrence of desmoids. Relative risks and survival times were calculated to assess the influence of potential risk factors (female sex, family history, mutation site, abdominal surgery, and pregnancy) on desmoid development.
RESULTS: Desmoid tumors were identified in 66 of the 735 patients (9%). The cumulative risk of developing desmoids was 14%. No correlation was found between specific adenomatous polyposis coli mutation sites and desmoid development. Patients with a positive family history for desmoids had a significant increased risk to develop this tumor (30% vs 6.7%, P < .001). No association was found between female sex or pregnancy and desmoid development. Most desmoid patients (95%) had undergone previous abdominal surgery. In a substantial proportion of patients with an ileorectal anastomosis, it was impossible to convert the ileorectal anastomosis to an ileal pouch-anal anastomosis as a result of desmoid development.
CONCLUSIONS: A positive family history of desmoids is an evident risk factor for developing desmoids. Most desmoids develop after colectomy. No correlation was found between desmoids and the adenomatous polyposis coli gene mutation site, female sex, and pregnancy. Ileal pouch-anal anastomosis is the appropriate type of surgery in FAP patients with a positive family history for desmoids.

PMID 18237870  Clin Gastroenterol Hepatol. 2008 Feb;6(2):215-9. doi: 1・・・
著者: S Bülow
雑誌名: Gut. 2003 May;52(5):742-6.
Abstract/Text BACKGROUND AND AIMS: The Danish Polyposis Register was established in 1971 with the aim of improving the poor prognosis of familial adenomatous polyposis (FAP), and in 1975 the register became national. The aim of the present study was to evaluate the prevalence of colorectal cancer and survival rate in FAP patients before and after the establishment of the Danish Polyposis Register.
PATIENTS AND METHODS: The Danish Polyposis Register was established by collecting information on probands and construction of their pedigrees. Family members at risk were offered prophylactic endoscopic and molecular genetic examination, and affected individuals were treated by colectomy.
RESULTS: At the end of 2001, the Danish Polyposis Register included 434 patients from 165 families. The incidence rate was 1.90x10(-6) and the prevalence rate 4.65x10(-5). Colorectal cancer on the basis of FAP constituted 0.07% of all colorectal cancers in the 1990s. Colorectal cancer was diagnosed in 170/252 probands (67%) and in 5/182 call-up patients (3%) (p<0.001). The cumulative crude survival was 94% in call-up patients compared with 44% in probands (p<0.0001). A comparison of two periods, 1900-1975 and 1976-2001, demonstrated a decreased prevalence of colorectal cancer from 60% to 27% (p<0.0001), and an increased use of colectomy from 52% to 93% (p<0.00001). The cumulative crude survival in FAP showed substantial improvement with time (p<0.00001).
CONCLUSION: Since the establishment of the Danish Polyposis Register, the prevalence of colorectal cancer has decreased considerably and the prognosis has improved substantially. The work of the Danish Polyposis Register is probably the main cause of this improvement.

PMID 12692062  Gut. 2003 May;52(5):742-6.
著者: A K Gurbuz, F M Giardiello, G M Petersen, A J Krush, G J Offerhaus, S V Booker, M C Kerr, S R Hamilton
雑誌名: Gut. 1994 Mar;35(3):377-81.
Abstract/Text Desmoids are rare, benign fibromatous lesions, which can arise in patients with familial adenomatous polyposis (FAP), a disorder caused by germline adenomatous polyposis coli (APC) gene mutation. This study investigated the risk of desmoids in FAP, the relation between specific APC gene mutations and desmoid formation, and the clinical characteristics of FAP patients with desmoids. Eighty three of 825 FAP patients (10%) from 49 of 161 kindreds (30%) had desmoids. The absolute risk of desmoids in FAP patients was 2.56/1000 person years; comparative risk was 852 times the general population. APC gene mutations were similar in families with and without desmoids. The female/male ratio was 1.4 (p = NS). Previous abdominal surgery was noted in 68% of patients with abdominal desmoids (55% developed within five years postoperatively). Desmoid risk in FAP family members of a desmoid patient was 25% in first degree relatives v 8% in third degree relatives. Desmoids are a comparatively common complication of FAP associated with surgical trauma and familial aggregation. Desmoid development was not linked to specific APC gene mutations and was not found predominantly in women. Studies of chemopreventive therapy, given within five years after abdominal surgery, should be considered in FAP patients with a family history of desmoid disease.

PMID 8150351  Gut. 1994 Mar;35(3):377-81.
著者: R Caspari, S Olschwang, W Friedl, M Mandl, C Boisson, T Böker, A Augustin, M Kadmon, G Möslein, G Thomas
雑誌名: Hum Mol Genet. 1995 Mar;4(3):337-40.
Abstract/Text An earlier study has shown that FAP patients with mutations in codons 136-302 of the APC gene do not develop congenital hypertrophy of the retinal pigment epithelium (CHRPE), whereas those with mutations in codons 463-1387 regularly do. Here we present data on 36 patients from 20 families with mutations in codons 1445-1578. These patients lack CHRPE. Furthermore, with the exception of three prepubertal children all patients with mutations in codons 1445-1578 developed desmoid tumours. This relationship between certain extracolonic manifestations and site of the APC mutation points to a specific role of the APC protein in different tissues.

PMID 7795585  Hum Mol Genet. 1995 Mar;4(3):337-40.
著者: L Bertario, A Russo, P Sala, M Eboli, M Giarola, F D'amico, V Gismondi, L Varesco, M A Pierotti, P Radice, Hereditary Colorectal Tumours Registry
雑誌名: Int J Cancer. 2001 Mar 20;95(2):102-7.
Abstract/Text Desmoids represent the most important cause of death, after colorectal cancer, in patients affected with familial adenomatous polyposis (FAP), an inherited disease due to mutations in the APC gene. The aims of our study were to estimate the risk of developing desmoids in FAP patients and to evaluate the association between desmoids and different risk factors. The occurrence of desmoids, colorectal cancer and other extra-colonic manifestations were assessed in 897 FAP patients, 653 of whom were also investigated for APC mutations. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were computed using an unconditional multiple logistic regression model. Desmoids developed in 107 patients (11.9%), with a cumulative risk of 20.6%. Females had a significantly higher risk than males (OR = 2.1; 95% CI 1.4-3.1). Family history of desmoids (OR = 8.75; 95% CI 5.66-13.51), osteomas (OR = 2.9; 95% CI 1.8-4.8) and epidermoid cysts (OR = 1.8; 95% CI 1.1-3.2) was also significantly associated with the occurrence of disease. Subjects with APC mutations beyond codon 1444 had a 12-fold increased risk, compared with patients with mutations located upstream. Mutations beyond codon 1309 conferred a 17-fold higher risk, compared with mutations upstream codon 452. Multivariate analysis identified as independent predictors mutation beyond codon 1444 (OR = 6.2; 95% CI 2.5-15.8), family history of desmoids (OR = 5.8; 95% CI 3.1-10.6), female gender (OR = 2.1; 95% CI 1.1-3.8) and the presence of osteomas (OR = 1.9; 95% CI 1.1-3.4). Our results indicate that integrating genetic and clinical data is helpful in defining subgroups of patients at higher risk for desmoids, who may benefit from specific prevention programs.

Copyright 2001 Wiley-Liss, Inc.
PMID 11241320  Int J Cancer. 2001 Mar 20;95(2):102-7.
著者: A R Latchford, N J H Sturt, K Neale, P A Rogers, R K S Phillips
雑誌名: Br J Surg. 2006 Oct;93(10):1258-64. doi: 10.1002/bjs.5425.
Abstract/Text BACKGROUND: Desmoid tumours affect 10-25 per cent of patients with familial adenomatous polyposis and represent a major cause of morbidity and mortality. Surgery for intra-abdominal desmoids has traditionally been used as a last resort or to manage obstructive complications. The aim was to review 10 years of desmoid surgery in patients with familial adenomatous polyposis from a single centre.
METHODS: Patients who had surgery for desmoid disease between 1994 and 2004 were identified from the Polyposis Registry database and their hospital notes reviewed.
RESULTS: Twenty patients had surgery to remove 32 desmoid tumours (16 intra-abdominal, 12 abdominal wall, four extra-abdominal). Complete clearance was achieved in 19 tumours and, of these, clinically significant recurrence occurred in eight. There was no difference in recurrence rates for site or sex. There was no operative mortality. Intra-abdominal desmoid resection was associated with a mean resection of 45.55 (range 10-200) cm of small bowel. One patient required long-term parenteral feeding. Median follow-up was 5 (range 0.6-10) years. During this period, one patient died (metastatic duodenal cancer); there was no mortality from desmoid disease.
CONCLUSION: Surgery for intra-abdominal desmoids in selected patients is less hazardous than previously reported. Surgery for abdominal wall and extra-abdominal tumours is safe. However, disease recurrence remains a major problem.

PMID 16952208  Br J Surg. 2006 Oct;93(10):1258-64. doi: 10.1002/bjs.54・・・
著者: S K Clark, R K Phillips
雑誌名: Br J Surg. 1996 Nov;83(11):1494-504.
Abstract/Text Clinical desmoid disease affect approximately 10 per cent of patients with familial adenomatous polyposis (FAP); the subclinical rate is unknown. Desmoids are probably neoplastic rather than regenerative in origin and may arise in association with germline or somatic mutations at or beyond codon 1444 of the APC gene. Intra-abdominal desmoids behave unpredictably but are an important cause of death in those with FAP. Signal intensity on magnetic resonance imaging reflects tumour cellularity, which in part determines progression, and this may help management. Surgical treatment of advanced desmoids is hazardous, but medical treatments have limited success. Chemotherapy with doxorubicin and dacarbazine is currently under evaluation.

PMID 9014661  Br J Surg. 1996 Nov;83(11):1494-504.
著者: N Julian H Sturt, Susan K Clark
雑誌名: Fam Cancer. 2006;5(3):275-85; discussion 287-8. doi: 10.1007/s10689-005-5675-1.
Abstract/Text Desmoid tumours are rare neoplasms of fibroblastic origin which arise with disproportionate frequency in patients with familial adenomatous polyposis (FAP). They are thought to develop in about 10-25% of FAP patients and may be the leading cause of death amongst those who have undergone colectomy. Risk factors include trauma, having a distal germline APC mutation, having a family history of desmoids, and probably oestrogens. In very high-risk individuals there may be a case for delay of colectomy or chemoprophylaxis at the time of surgery. Desmoids are now known to be true neoplasms but with normal telomere length and telomerase activity. FAP-associated tumours seem to carry biallelic APC mutations, one of which lies in the distal part of the gene. Such loss of wild-type APC seems to occur relatively late in tumour development. It is likely that beta-catenin plays an important role in tumourigenesis. FAP-associated desmoids tend to arise in the abdomen or abdominal wall. CT scanning gives the best information on tumour anatomy whilst T2-weighted MRI indicates likely behaviour. Treatment may simply consist of observation. Otherwise, usual first-line therapy is with sulindac with or without an anti-oestrogen. Cytotoxic chemotherapy is an option in unresectable tumours. Surgery is a reasonable first-line treatment in abdominal wall tumours but is risky for intra-abdominal tumours and may necessitate massive small bowel resection. Desmoids are the greatest remaining challenge in the management of FAP and further research into their aetiology needs to be combined with multicentre clinical trials of new treatments in order to improve management of the disease.

PMID 16998673  Fam Cancer. 2006;5(3):275-85; discussion 287-8. doi: 10・・・
著者: Anika Hansmann, Claudia Adolph, Tilmann Vogel, Andreas Unger, Gabriela Moeslein
雑誌名: Cancer. 2004 Feb 1;100(3):612-20. doi: 10.1002/cncr.11937.
Abstract/Text BACKGROUND: Desmoid tumors are mesenchymal nonmetastasizing neoplasms. Although rare in the general population, they are a common extracolonic manifestation of familial adenomatous polyposis (FAP). Because of high tumor recurrence rates, surgery has been less than satisfactory in the treatment of desmoid tumors. In the current study, high doses of tamoxifen in combination with sulindac were used to treat severe desmoid tumors to avoid surgery.
METHODS: Since 1992, 25 patients at Heinrich Heine University (Dusseldorf, Germany) were treated with a combination of tamoxifen and sulindac. In the current study, 17 patients with FAP-associated and 8 patients with sporadic desmoid tumors received 120 mg of tamoxifen and 300 mg of sulindac daily. Every 6 months, the protracted course of desmoid growth was measured by computed tomography and/or magnetic resonance imaging scans. Tumor responses were characterized as progressive disease, stable disease (SD), partial regression (PR), and complete regression (CR).
RESULTS: Of the group of patients who received tamoxifen and sulindac as a primary treatment, all three patients with sporadic desmoid tumors demonstrated cessation of growth, and 10 of the 13 patients with FAP-associated tumors achieved either a PR or CR. In the sporadic desmoid tumor group, eight of nine patients developed tumor recurrences after undergoing surgery at other institutions. Of these, two patients had SD and two patients had a PR to CR.
CONCLUSIONS: The patients with desmoid tumors who were managed conservatively with high-dose tamoxifen and sulindac had the best outcome. Desmoid tumor recurrence after surgery was high and in the FAP-associated tumor group, therapy with tamoxifen and sulindac was found to be less successful. Based on this experience, the authors recommended high-dose tamoxifen and sulindac as the primary treatment for patients with FAP-associated desmoid tumors. However, to our knowledge, the best approach after surgical intervention for patients with sporadic desmoid tumors remains to be determined.

Copyright 2003 American Cancer Society.
PMID 14745880  Cancer. 2004 Feb 1;100(3):612-20. doi: 10.1002/cncr.119・・・

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから