Quality of Life After Ileal Pouch-Anal Anastomosis and Ileorectal Anastomosis in Patients With Familial Adenomatous Polyposis

PURPOSE Differences in conventional outcomes such as functional results and the rate of complications have caused a controversy about whether the ileal pouch anal anastomosis or the ileorectal anastomosis is the preferred surgical treatment for patients with familial adenomatous polyposis. We therefore sought to ascertain not only the surgical results but also the perceptions of patients about their outcomes. METHODS Between 1981 and 1998, 152 patients at our institution had an ileal pouch-anal anastomosis and 32 patients had an ileorectal anastomosis for familial adenomatous polyposis. Of these 184 patients, 173 were sent a study-specific quality-of-life questionnaire and the Short Form 36 health survey to determine their health-related quality of life. RESULTS Ninety-four ileal pouch patients and 21 ileorectal patients returned the surveys. No difference was found in early postoperative complications, 5-year probability for complications, or functional results after either procedure. On the Short Form 36 health survey, the ileorectal patients had a lower mental health summary score compared with that of the ileal pouch patients but a similar physical health summary score. The study-specific questionnaire found both groups to have a comparable quality of life. CONCLUSION Because ileal pouch-anal anastomosis has the advantage of removing as much at-risk tissue as possible with similar functional results and better mental health, it may be considered the preferred operation for most patients with familial adenomatous polyposis. Presented at the 18th World Congress of Digestive Surgery, Hong Kong, China, December 8 to 11, 2002.     

Ileoanal Pouch Neoplasia in Familial Adenomatous Polyposis: An Underestimated Threat

PURPOSE Ileal pouch-anal anastomosis is one of the two main options available for the surgical treatment of patients with familial adenomatous polyposis. Its main advantage is the minimal risk of rectal cancer but a possible Achilles heel is the recurrence of epithelial neoplasia at the ileal pouch-anal anastomosis and within the ileal pouch. The significance of ileoanal anastomotic and ileal pouch adenomas is not yet fully appreciated, and there is a false sense of security about this operation. The consequences of worsening pouch polyposis are serious in that endoscopic treatment is unlikely to be an effective way of controlling it. This study has been done to alert those caring for patients with familial adenomatous polyposis to the looming danger of pouch polyposis and to suggest ways to deal with it.METHODS Studies reporting ileoanal pouch adenomas, ileal pouch-anal anastomotic cancers, and ileal pouch cancers in patients with familial adenomatous polyposis were reviewed. Reports of adenomas in Kock pouches and in Brooke ileostomies in the setting of familial adenomatous polyposis were included. The primary end points of the study were the time between pouch construction and the diagnosis of neoplasia, the age of the patients at the diagnosis of neoplasia, and the severity of the neoplasia.RESULTS There were 18 studies reporting pouch neoplasia, 15 with adenomas, and 3 with cancer. Ten were case reports, five were retrospective studies, and three were prospective studies. All three prospective studies showed that the incidence of pouch adenomas increases with time of follow-up and that the severity of the polyposis varies. The median time from pouch construction to diagnosis of pouch adenomas was 4.7 years and the range was 0.5 to 12 years. There were six studies reporting eight patients with cancer at the ileal pouch-anal anastomosis, diagnosed a median of 8 years after pouch construction (range, 3–20 years). One-half of the cancers were locally advanced (T4) and one-half were not (T1 or T2). One-half followed stapled anastomosis and one-half were after mucosectomy. There were eight case reports of cancer described in an ileostomy in patients with familial adenomatous polyposis. The median time from ileostomy construction to the ileostomy cancers was 25 (range, 9–40) years.DISCUSSION The combination of fecal stasis, adenomatous epithelium, and a germline APC mutation is a potent recipe for epithelial neoplasia. There is increasing evidence that this happens in an ileostomy but that the process is much faster in an ileal pouch. Endoscopic treatment of ileal adenomas is likely to be difficult, reducing the options for their control to excising the entire pouch or chemoprevention.Reprints are not available.     

Impact of Screening Examinations on Survival in Familial Adenomatous Polyposis

Background: Prophylactic family screening and surgery has improved the outcome of patients with familial adenomatous polyposis (FAP) largely preventing deaths due to colorectal cancer. The present study compared the mortality rates and causes of death of FAP patients diagnosed by symptoms (probands) or by family screening (call-up). Methods: The study comprised all 236 FAP patients registered in the Finnish Polyposis Registry until the end of June 1998. There were 116 probands and 120 call-up patients with a median age of 36.8 and 22.8 at diagnosis and median follow-up times of 6.3 and 9.9 years, respectively. Cumulative crude and relative survival estimates were calculated for each group and the causes of death were determined. Results: The life expectancy was significantly better in the call-up group than in the probands after colectomy (P < 0.001). The survival rates of the call-up group equaled those expected for a comparable group in the general population up to 18 years after colectomy. The main cause ofdeath was colorectal cancer accounting for 54 out of 68 deaths: four in the call-up group (all rectal stump cancer) and 50 in probands. Upper GI-tract cancer caused four deaths (periampullary cancer two, stomach cancer two) and two deaths were due to postoperative pulmonary embolism. Conclusion: The survival of FAP patients is significantly improved by prophylactic screening and surgery. Further improvement may be possible by using restorative proctocolectomy instead of colectomy and ileorectal anastomosis and by regular upper GI-tract endoscopic surveillance.     

A Comparison of Adverse Events and Functional Outcomes After Restorative Proctocolectomy for Familial Adenomatous Polyposis and Ulcerative Colitis

Purpose Restorative proctocolectomy is the procedure of choice for patients undergoing proctocolectomy for familial adenomatous polyposis or ulcerative colitis. This meta-analysis was designed to identify differences in adverse events and functional outcomes between these two groups. Methods Studies published between 1986 and 2003 that compared outcomes between patients with familial adenomatous polyposis and ulcerative colitis were included. Meta-analytical techniques using random effect models were used to compare short-term and long-term adverse events as well as functional outcomes between the groups. Results Nineteen studies comprising 5,199 patients (familial adenomatous polyposis, 782; ulcerative colitis, 4,417) were analyzed. There were no significant differences in immediate postoperative adverse events between the two groups. Pouch-related fistulation was significantly increased in the ulcerative colitis group (10.5 percent vs. familial adenomatous polyposis 4.8 percent; odds ratio 2.31; P < 0.001). There was no significant difference in pouch failure between the two groups (ulcerative colitis 5.8 percent vs. familial adenomatous polyposis 4.5 percent; odds ratio 1.22; P = 0.43). The incidence of pouchitis was significantly greater in the ulcerative colitis group (30.1 vs. 5.5 percent; odds ratio 6.44; P < 0.001). Patients with familial adenomatous polyposis had a significant advantage in stool frequency with one less motion per 24 hours (95 percent confidence interval, 0.21–1.76; P = 0.01). Conclusions In contrast to studies reporting similar outcomes for patients undergoing restorative proctocolectomy for familial adenomatous polyposis or ulcerative colitis, the present meta-analysis suggested that patients with ulcerative colitis are at greater risk of pouch-related fistulation and pouchitis. Although there was an increase in the 24-hour stool frequency in the ulcerative colitis group, this may be accounted for by the younger age at surgery in the familial adenomatous polyposis group. Henry S. Tilney is sponsored by a research grant from The Royal College of Surgeons of England. Read at the meeting of the Association of Surgeons of Great Britain and Ireland, Edinburgh, Scotland, May 3 to 5, 2006.     

Investigation of APCMutations in a Turkish Familial Adenomatous Polyposis Family by Heterodublex Analysis

PURPOSE Familial adenomatous polyposis is an autosomal dominant disease characterized by the presence of 100 or more colorectal adenomatous polyps. Mutations in the adenomatous polyposis coli gene are primarily responsible for the development of this disease. This study was designed to investigation of adenomatous polyposis coli (APC) gene mutations in members of familial adenomatous polyposis family to identify individuals at risk of the disease.METHODS We examined one patient with familial adenomatous polyposis and 21 family members including one affected person from familial adenomatous polyposis and 20 nonsymptomatic persons. We studied E, D, F, and G segments of exon 15 of the adenomatous polyposis coli gene by heteroduplex analysis.RESULTS We used silver staining method for staining. We found a mutation for five persons at segment F of exon 15 of the adenomatous polyposis coli gene. Two of them were affected by colorectal cancer, one of whom was the proband, and the other three were nonsymptomatic family members. The pathogenetic mutation was a T deletion at codon 1172, causing a frameshift in the adenomatous polyposis coli gene, as a result of the sequencing analysis of these cases.CONCLUSIONS Investigation of adenomatous polyposis coli gene mutations is very important for the identification of genetic susceptibility to colorectal cancer and for the definition of tumor developing at an early stage. Furthermore, the identification of this mutation for the first time in a Turkish family will be useful to foster further studies on familial adenomatous polyposis in Turkey.     

Mutation Spectrum of Familial Adenomatous Polyposis Patients in Turkish Population: Identification of 3 Novel APC Mutations

BackgroundFamilial adenomatous polyposis (OMIM #175100) and MUTYH-associated polyposis (OMIM #608456) are rare cancer-prone disorders characterized by hundreds of adenomatous polyps in the colon and rectum, which have a high probability of malignant transformation. Attenuated familial adenomatous polyposis is a variant of familial adenomatous polyposis, which is a term used for the condition in which patients have less than 100 colorectal polyps. Germline heterozygous Adenomatous polyposis coli (APC) and biallelic MUTYH (mutY DNA glycosylase) pathogenic variations are responsible for familial adenomatous polyposis and MUTYH-associated polyposis respectively. The aim of this study is to discuss the clinical manifestations of patients having pathogenic APC and MUTYH variations.MethodsWe included 27 probands who have more than 10 colonic polyps in this study. After evaluation of their clinical and family histories, the probands were screened for APC and MUTYH variations via next generation sequencing. The family members of the probands carrying pathogenic variations were screened via Sanger sequencing. ResultsAmong 27 probands, pathogenic APC and MUTYH variations were detected in 3 and 6 probands respectively. In the APC gene, 3 novel truncating variations (p.Leu360*, p.Leu1489Phefs*23, and p.Leu912*) were detected in 3 unrelated probands. In the MUTYH gene, only 2 distinct pathogenic variations were detected (p.Pro295Leu and p.Glu480del) in the homozygous or compound heterozygous state.ConclusionIn this study, molecular etiology was clarified in 9 familial polyposis patients. The p.Pro295Leu and p.Glu480del variations seem to be common in the Turkish population and may be considered as a first-step genetic test in Turkish familial polyposis patients showing autosomal recessive inheritance. However more studies are needed to reveal the exact frequency of these variations.     

Progressive Duodenal Adenomatosis in a Familial Adenomatous Polyposis Pedigree with APC Mutation at Codon 1556

PURPOSE: In familial adenomatous polyposis, genotype-duodenal phenotype correlations have not been clearly understood. We identified the adenomatous polyposis coli gene mutation in a family pedigree with severe duodenal adenomatosis. METHODS: Among 53 familial adenomatous polyposis families, we found a pedigree composed of five affected members with severe duodenal adenomatosis. Clinical manifestations of the family members were reviewed. The adenomatous polyposis coli gene of four members were screened by polymerase chain reaction-based single strand conformation polymorphism or protein truncation test. RESULTS: The family was characterized by sparse colorectal polyposis, osteomas, and epidermal cysts. However, there were intrafamilial variabilities in the occurrence of fundic gland polyposis, congenital hypertrophy of the retinal pigment epithelium, and desmoids. All the members had duodenal adenomatosis in their second or third decades, and the adenomatosis in three members progressed during surveillance. A frameshift mutation was found at codon 1556 of the adenomatous polyposis coli gene in two members, and the equivalent mutation was confirmed by protein truncation test in another two. CONCLUSIONS: Distal 3 mutation of the adenomatous polyposis coli gene seems to contribute to severe duodenal adenomatosis in familial adenomatous polyposis. Specification of the adenomatous polyposis coli gene mutation may be a clue for surveillance strategy for duodenal adenomatosis in patients with familial adenomatous polyposis.     

Large Villous Adenomas Arising in Ileal Pouches in Familial Adenomatous Polyposis: Report of Two Cases

A restorative proctocolectomy or ileal pouch procedure is one of the main surgical options for patients with familial adenomatous polyposis. The main premise underlying the recommendation of a pouch procedure rather than an ileorectal anastomosis is that it minimizes the risk of rectal cancer. Several studies have evaluated the risk of developing pouch adenomas. There also have been reports of pouch cancers, although the long-term risk of malignancy cannot yet be quantified. Most pouch polyps reported have been small tubular adenomas with mild dysplasia. A 19-year-old female with familial adenomatous polyposis had a colectomy and ileorectal anastomosis. Progressive rectal polyposis led to a restorative proctocolectomy at aged 38 years. Four years later, a large, 3-cm × 2-cm, villous adenoma was identified in the mid pouch, which was resected endoscopically. A 32-year-old male with familial adenomatous polyposis had a restorative proctocolectomy. Ten years after surgery, pouch endoscopy revealed several large, villous adenomas arising from the pouch mucosa. These advanced polyps may present a significant risk for cancer development and require close endoscopic surveillance. These findings strengthen the recommendation for careful regular endoscopic surveillance of familial adenomatous polyposis pouches and the evaluation of management and treatment strategies for pouch adenomas.     

Familial Adenomatous Polyposis in Children Younger than Age Ten Years: A Multidisciplinary Clinic Experience

Purpose Children with familial adenomatous polyposis have a greater mortality and morbidity in the first decade of life compared with the general population. Some children with a more severe disease phenotype present early with colorectal adenomata and may require colectomy at an early age. We present our multidisciplinary clinic experience with familial adenomatous polyposis in children younger than age ten years at the time of presentation. Methods A cross-sectional analysis was performed on all patients with suspected or confirmed familial adenomatous polyposis presenting in the first decade of life and followed by the multidisciplinary Pediatric Hereditary Polyposis Clinic at our institutions. Analysis included demographics, clinical presentation and course, gene mutation testing, endoscopic-histologic findings, and surgical outcome. Results Twenty-two children (11 males) presented with suspected or confirmed familial adenomatous polyposis. Two were discharged from follow-up after negative adenomatous polyposis coli gene mutation testing. The rest underwent annual hepatoblastoma surveillance through age ten years with negative findings. Twelve patients presented with symptoms: six had de novo familial adenomatous polyposis. Seven had gastrointestinal hemorrhage and went on to colonoscopy. Four patients with adenomatous polyposis coli gene mutation at codon 1309 were referred for colectomy before age ten years. Referral to colectomy was earlier in patients with 1309 mutation and with de novo familial adenomatous polyposis. Conclusions Children with familial adenomatous polyposis younger than age ten years may present presymptomatically for disease surveillance. Familial adenomatous polyposis with adenomatous polyposis coli gene mutation at codon 1309 entails a risk of a more aggressive phenotype; early colectomy may be indicated in children harboring this gene mutation. Supported in part by the Edna Ittner Research Fund.     

Familial Adenomatous Polyposis and Mental Retardation Caused by a de novo Chromosomal Deletion at 5q15-q22: Report of a Case

Familial adenomatous polyposis, caused by mutations in the adenomatous polyposis coli gene located at chromosome 5q21, is an autosomal dominant syndrome characterized by polyposis of the colon and rectum and nearly 100 percent progression to colorectal cancer. We report a case of familial adenomatous polyposis and mental retardation caused by a chromosomal deletion at 5q15-q22. Chromosomal analysis is considered part of the evaluation of children with mental retardation and developmental delay. The resulting karyotypes from high-resolution chromosomal analysis can help characterize large deletions, some of which involve known tumor suppressor genes. Because familial adenomatous polyposis may arise from de novo chromosomal deletions involving the adenomatous polyposis coli gene locus, individuals with chromosomal deletions involving 5q21 should be considered at-risk for familial adenomatous polyposis and offered standard screening with flexible sigmoidoscopy by 10 to 12 years of age. Supported, in part, by the Grace J. Fippinger Foundation, the William Bianco Trust, and the Ferdinand Koch Fund. Presented at the meeting of the Collaborative Groups of the Americas on Inherited Colorectal Cancer, Baltimore, Maryland, October 13 to 14, 2002.     

Liposome-Mediated Adenomatous Polyposis Coli Gene Therapy: A Novel Anti-Adenoma Strategy in Multiple Intestinal Neoplasia Mouse Model

PURPOSE Familial adenomatous polyposis is a highly penetrant, autosomal dominant disease resulting from a germline mutation of the adenomatous polyposis coli gene. Besides colorectal polyps and cancer, more than 90 percent of familial adenomatous polyposis patients also develop duodenal polyposis with an approximately 5 percent lifetime risk of malignant transformation. Because adenomatous polyposis coli protein has a gatekeeper role in the adenoma–carcinoma sequence, replacing its function may reduce polyp formation. We studied the functional outcome of per-oral, liposome-mediated adenomatous polyposis coli gene replacement therapy in a multiple intestinal neoplasia mouse model.METHODS Twenty multiple intestinal neoplasia mice, heterozygous for the human homologue adenomatous polyposis coli gene, were randomly assigned to three groups: no treatment (n = 8); control plasmid containing green fluorescence protein reporter gene (n = 6); and plasmid containing the full-length adenomatous polyposis coli gene (n = 6). For the adenomatous polyposis coli–treated and green fluorescence protein reporter gene–treated groups, each mouse received the appropriate plasmid complexed with liposome, administered twice per week by oral gavage regime. Treatment lasted four weeks and all animals were killed at the end of treatment period with harvesting of intestinal tissue for polyp number estimation.RESULTS There was a statistically significant 25 percent reduction in the total number of polyps in the adenomatous polyposis coli–treated (73.1 ± 1.4) group compared with untreated control (97.8 ± 5.3, P < 0.01, Tukey test) and multiple intestinal neoplasia mice treated with control green fluorescence protein gene (103.3 ± 1.7, P < 0.01, Tukey test).CONCLUSION Adenomatous polyposis coli gene dysfunction underlies tumorigenesis in familial adenomatous polyposis patients and multiple intestinal neoplasia mice. This in vivo study provides evidence to support a novel anti-adenoma strategy using enteral adenomatous polyposis coli gene replacement therapy.Reprints are not available.J. Lee was supported by a grant from the Cancer Research United Kingdom.Presented at the meeting of the Association of Coloproctology of Great Britain and Ireland, Manchester, United Kingdom, July 3 to 5, 2002.     

Familial Adenomatous Polyposis and Extracolonic Cancer

Our purpose is to focus attention on the cancer family history, coupled with an understanding of the natural history and extracolonic tumor spectrum of familial adenomatous polyposis (FAP), through a family study. This family report provides an example of how colorectal cancer (CRC) can be prevented by knowledgeable gastroenterologists and colorectal surgeons who educate and compassionately counsel members of high-risk families so that their compliance with diagnostic screening and, ultimately, with protection through prophylactic colectomy, is achieved. A working pedigree of this extended family was constructed through interviews with the proband, followed by questionnaires sent to all primary and secondary relatives. Appropriately signed permission forms enabled us to secure pertinent medical and pathology records in order to ensure accuracy of historical information. Integral extracolonic tumors included medulloblastoma, papillary thyroid carcinoma, hepatoblastoma, and desmoid tumors. We conclude that, due in part to improved longevity as a result of being spared CRC, several family members have developed certain FAP integral extracolonic cancers.     

Sulphomucin Expression in Ileal Pouches: Emerging Differences Between Ulcerative Colitis and Familial Adenomatous Polyposis Pouches

Purpose We characterized the expression of sialomucin and sulphomucin in pouches fashioned for familial adenomatous polyposis and ulcerative colitis. We correlated sulphomucin expression with bacterial colonization and mucosal inflammation. Methods Ethical approval and informed consent were obtained. Mucosal biopsies from 9 patients with familial adenomatous polyposis and 12 with ulcerative colitis were obtained. Sulphomucin levels were assessed by using the high iron-diamine stain. Mucous gel layer composition was correlated with villous height, crypt depth, and total mucosal thickness. Mucous gel layer composition was correlated with acute and chronic inflammatory infiltrates. Colonization by a panel of seven bacterial species (including sulphate reducing bacteria) was established and correlated with sulphomucin levels. Results High-iron-diamine positivity (i.e., sulphomucin expression) was greater in ulcerative colitis pouch mucous gel (2.083 ± 0.5 vs. 0.556 ± 0.4, P = 0.003). Sulphomucin expression correlated with reduced crypt depth, villous height, and total mucosal thickness. In the ulcerative colitis group, chronic inflammatory infiltrate scores were significantly greater for high-iron-diamine-positive patients. Colonization by sulphate reducing bacteria was increased in high-iron-diamine-positive patients. Conclusions Sulphomucin expression is increased in the mucous gel layer of the ulcerative colitis pouch compared with that of the familial adenomatous polyposis pouch. Sulphomucin expression is associated with colonization by sulphate-reducing bacteria and increased chronic inflammation. Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 6, 2007.     

The Mutation Spectrum of the <Emphasis Type="Italic">APC</Emphasis> Gene in Turkish Patients with Familial Adenomatous Polyposis

Purpose Familial adenomatous polyposis, an autosomal-dominant disease characterized by the presence of 100 or more colorectal adenomatous polyps, results from mutations in the adenomatous polyposis coli tumor suppressor gene. This study was designed to investigate adenomatous polyposis coli gene mutations in members of Turkish families with familial adenomatous polyposis to constitute an adenomatous polyposis coli mutation spectrum for the Turkish population and to determine specific biomarkers for use in the early diagnosis of familial adenomatous polyposis. Methods We investigated adenomatous polyposis coli gene mutations in six unrelated families with familial adenomatous polyposis by using heteroduplex analysis and DNA sequencing. Results We identified three different mutations in six families. Of these one is known and two are novel: 1018T>C and 1309delGAAAA. The mutation of a T to C transversion at codon 1018 does not cause an alteration in the meaning of the codon; however, it was determined that this silent mutation does cause the formation of new exonic splicing enhancers (ESEs) motifs on a mutated sequence by using ESEfinder program. Conclusions This study contributes to enlarging the adenomatous polyposis coli gene mutations spectrum and to defining new biomarkers for the early diagnosis of Turkish patients with familial adenomatous polyposis. Supported by Society of Investigation and Prevention of Genetic Diseases. Reprints are not available.     

Colectomy and Ileorectal Anastomosis is still an Option for Selected Patients with Familial Adenomatous Polyposis

Purpose  The risk of rectal cancer after colectomy and ileorectal anastomosis may be reduced in the last decades, as patients with severe polyposis now have an ileoanal pouch. We have reevaluated the risk of rectal cancer and proctectomy for all causes according to the year of operation. Methods  On the basis of the year of operation in 776 patients with ileorectal anastomosis and 471 pouch patients in Denmark, Finland, Holland, and Sweden, the “pouch period” was defined to start in 1990. Ileorectal anastomosis follow-up data was captured by May 31, 2006. The cumulative risk of rectal cancer and proctectomy was compared before and after 1990 by Kaplan-Meier analysis. Results  In the prepouch period 56/576 patients (10 percent) developed rectal cancer, vs. 4/200 (2 percent) in the pouch period. Neither the cumulative risk of rectal cancer (p = 0.07) nor the cumulative risk of proctectomy (p = 0.17) changed. However, in females the cumulative risk of rectal cancer (p = 0.04) and of proctectomy (p = 0.03) were lower in the pouch period. Conclusions  Since the introduction of the ileoanal pouch rectal cancer has decreased after ileorectal anastomosis, but only statistically significant in females. This indicates that ileorectal anastomosis may still be justified in selected patients with mild adenomatosis, especially in young females. Presented at the meeting of the International Society for Gastrointestinal Hereditary Tumours (InSiGHT), Yokohama, Japan, March 28 to 30, 2007. Reprints are not available.     

A Multimodality Approach to Successful Ileal Pouch Desmoid Excision with Pouch Salvage: Report of a Case

Desmoid tumors occur infrequently in patients who undergo proctocolectomy for familial adenomatous polyposis but may result in significant morbidity and mortality depending on the sight of desmoid location. A case of successful ileal pouch salvage using a multimodality approach for treatment of a large ileal pouch associated desmoid tumor is presented. This approach used neoadjuvant chemotherapy to induce a partial response, followed by complete surgical excision with pouch preservation. This is the first reported case of combined chemotherapy and surgical treatment of a desmoid tumor involving an ileal pouch, and the second reported successful attempt at surgical excision with pouch salvage.