Natural history of colonic polyposis in young patients with familial adenomatous polyposis

doi:10.1016/j.gie.2018.05.021

Gastrointestinal Endoscopy

Volume 88, Issue 4, October 2018, Pages 726-733

https://doi.org/10.1016/j.gie.2018.05.021 Get rights and content

Background and Aims

Proctocolectomy prevents colorectal cancer in familial adenomatous polyposis (FAP). Colorectal polyp progression is one of the indications for surgery. No data exist regarding the natural history of colorectal polyposis in young patients with FAP. This study examined the rate of polyposis progression and factors associated with it.

Methods

Patients with FAP <30 years old who had undergone ≥2 colonoscopies since 2000 were identified. Rate of polyposis progression was calculated by review of polyp counts obtained from baseline and last colonoscopy, accounting for any polyps removed during the observation period. Endoscopic and non-endoscopic factors affecting the rate of polyposis progression were evaluated. Multivariate analysis was performed to identify factors associated with rate of polyposis progression.

Results

One hundred sixty-eight patients (52% female; median age, 13.5 years) were included. Median rate of polyposis progression was 25.4 polyps/year (interquartile range, 9.5-69.8). Highest median rate of polyposis progression (89 polyps/year) was associated with mutation in codon 1309. The rate of polyposis progression was independently associated with the location of mutation in the adenomatous polyposis coli gene, the number of polyps at the initial colonoscopy, and exposure to chemoprevention. Of the 39.9% of patients who underwent surgery, an increase in polyp number was the most common indication (53.7%).

Conclusions

The rate of polyposis progression in young patients with FAP varies with a median of about 25 new polyps per year. Progression is associated with distinct factors, which can be used in discussion with patients regarding the need for and timing of prophylactic colorectal surgery.

Introduction

Familial adenomatous polyposis (FAP) is caused by a deleterious germline mutation in the adenomatous polyposis coli (APC) tumor suppressor gene.¹ The leading cancer risk in FAP is colorectal cancer (CRC).² Prophylactic proctocolectomy effectively prevents CRC and results in a similar life expectancy to the general population up to 18 years after surgery.3, 4 The optimal time for surgery should be early enough to prevent CRC but at the same time minimize the impact of surgery on quality of life, financial, academic, psychosocial, and physical factors.5, 6, 7

Published guidelines recommend surgery if CRC or colorectal symptoms are present,⁸ but the indications in asymptomatic patients are less clear. Guidelines suggest surgery for a significant increase in polyp burden,⁸ but “significant increase in polyp burden” is not well defined. This study aims to quantify the natural history of polyposis in young patients with FAP and to determine factors associated with polyp progression.

Section snippets

Methods

The Cleveland Clinic Sanford R. Weiss, MD, Center for Hereditary Colorectal Neoplasia maintains an Institutional Review Board-approved database (Cologene). This database, which exists within the David G. Jagelman Inherited Colorectal Cancer Registry, contains demographic, genetic, and procedural information on patients diagnosed with hereditary CRCs. Data on patients who consent to enroll in the registry are entered by the hereditary colon cancer registrars (L.L. and M.O.). The Cologene

Baseline characteristics

One hundred sixty-eight patients were included. The median age at FAP diagnosis was 13.5 years, and 51.8% of the patients were female. Median BMI was normal (21.7 kg/m²). Sixty-three patients (39.9%) underwent surgery after a median of 3.5 years of surveillance, at a median age of 18.3 years. In patients who did not have surgery, the median time of surveillance was 2.9 years. Colectomy with ileorectal anastomosis was the most frequent surgical procedure (69.8%) followed by proctocolectomy with

Discussion

This large, single-center study of patients with FAP reports the natural history of colorectal polyposis in patients undergoing surveillance colonoscopy and factors that have an impact on polyposis progression. Controlling for the effect of polypectomy and chemoprevention, the rate of polyposis progression was 25.4 polyps/year and the rate was associated with both clinical and genotypic factors. A genotype-based definition of severe FAP and the level of the polyp count at initial colonoscopy

Conclusions

We have demonstrated the natural history of colorectal polyposis in young patients with FAP. Patients with FAP at our center undergo colonoscopic surveillance until there is a compelling reason to perform surgery. Although a significant increase in polyp number is an indication recommended by guidelines, it has heretofore not been defined. Factors associated with the rate of polyposis progression include the number of polyps at first colonoscopy, the use of chemopreventive agents (sulindac,

References (24)

R. Burt et al.
Genetic testing for inherited colon cancer
Gastroenterology
(2005)
S.E. Kerr et al.
APC germline mutations in individuals being evaluated for familial adenomatous polyposis: a review of the Mayo Clinic experience with 1591 consecutive tests
J Mol Diagn
(2013)
M.H. Nieuwenhuis et al.
Correlations between mutation site in APC and phenotype of familial adenomatous polyposis (FAP): a review of the literature
Crit Rev Oncol Hematol
(2007)
M. Cruz-Correa et al.
Long-term treatment with sulindac in familial adenomatous polyposis: a prospective cohort study
Gastroenterology
(2002)
Y. Niv et al.
Adenocarcinoma in the rectal segment in familial polyposis coli is not prevented by sulindac therapy
Gastroenterology
(1994)
M. De Rosa et al.
Alternative splicing and nonsense-mediated mRNA decay in the regulation of a new adenomatous polyposis coli transcript
Gene
(2007)
P.M. Lynch et al.
A proposed staging system and stage-specific interventions for familial adenomatous polyposis
Gastrointest Endosc
(2016)
I. Heiskanen et al.
Impact of screening examinations on survival in familial adenomatous polyposis
Scand J Gastroenterol
(2000)
H.J. Jarvinen
Epidemiology of familial adenomatous polyposis in Finland: impact of family screening on the colorectal cancer rate and survival
Gut
(1992)
K.O. Olsen et al.
Female fecundity before and after operation for familial adenomatous polyposis
Br J Surg
(2003)

V.N. Tudyka et al.

Surgical treatment in familial adenomatous polyposis

Ann Gastroenterol

(2012)

L. Andrews et al.

Impact of familial adenomatous polyposis on young adults: quality of life outcomes

Dis Colon Rectum

(2007)

Cited by (23)

The importance of genetics for timing and extent of surgery in inherited colorectal cancer syndromes
2022, Surgical Oncology
Citation Excerpt :
The shortest length of time to surgery was in the group with the large APC deletions [21]. In another study, Sarvepalli et al. correlated pathogenic variant location on the APC gene with rate of polyposis progression in FAP patients, and ultimately indications of surgical intervention [22]. They noted that mutations occurring between codon 1309 and 1389 were associated with a high rate of polyposis progression (>60 polyps/year), with the codon 1309 mutation having the highest rate at 89 polyps/year.
Approximately 5% of colorectal cancers arise within an inherited colorectal cancer syndrome, with known underlying genetic etiologies. These syndromes increase the risk of colorectal and extracolonic cancers. Identification of a specific genetic pathogenic variant defines the syndrome, and quantifies the elevated risks compared to the general population. Thus, knowing and understanding the risks associated with each pathogenic variant allows for risk-stratification and a more individualized management strategy. These factors influence both the timing of surgery and the extent of colorectal surgery for patients with these syndromes. Familial Adenomatous Polyposis (FAP) is a dominantly inherited polyposis syndrome caused by pathogenic variant in the APC gene and results in a near 100% chance of developing colorectal cancer if not treated. There is a genotype-phenotype correlation in which the affected gene locus is associated with severity of polyposis and the risk of desmoid disease. Prophylactic surgery ranging from total abdominal colectomy or total proctocolectomy is recommended before cancer develops. Lynch syndrome is a non-polyposis inherited syndrome caused by a pathogenic variant in MLH1, MSH2, MSH6, or PMS2. Although prophylactic colectomy in Lynch syndrome is uncommon, total abdominal colectomy as prophylaxis in the setting of colon cancer is recommended due to the likelihood of metachronous colorectal cancer. This article reviews the role of genetics surgical decision making with respect to the timing and extent of surgery within the hereditary colorectal cancer syndromes.
Characterizing Pediatric Familial Adenomatous Polyposis in Patients Undergoing Colectomy in the United States
2022, Journal of Pediatrics
Citation Excerpt :
Guidelines recommend prophylactic colectomy in late teens to early twenties; however, they acknowledge clinical and personal circumstances impact colectomy timing. Available data from adult institutions and polyposis centers suggest that most patients undergo colectomy at an age consistent with guideline recommendations.13-15 Our data demonstrate a median age of 14 years at time of colectomy, which is similar to previously reported pediatric data but younger than suggested in published guidelines or reported from major polyposis centers.16-18
To characterize a multi-institutional cohort of pediatric patients who underwent colectomy for familial adenomatous polyposis (FAP).
In this retrospective cohort study, diagnosis and procedure codes were used to identify patients who underwent colectomy for FAP within the Pediatric Health Information System (PHIS). The inclusion criteria were validated at 3 children’s hospitals and applied to PHIS to generate a cohort of patients with FAP between 2 and 21 years who had undergone colectomy between 2009 and 2019. Demographics, clinical and surgical characteristics, and endoscopic procedure trends as identified through PHIS are described. Descriptive and comparative statistics were used to analyze data.
Within the PHIS, 428 pediatric patients with FAP who underwent colectomy were identified. Median age at colectomy was 14 years (range 2-21 years); 264 patients (62%) received an ileal pouch anal anastomosis and 13 (3%) underwent ileorectal anastomosis. Specific anastomotic surgical procedure codes were not reported for 151 patients (35%). Endoscopic assessment at the surgical institution occurred in 40% of the cohort before colectomy and in 22% of the cohort following colectomy.
In this cohort, colectomy took place at an earlier age than suggested in published guidelines. Ileal pouch anal anastomosis is the predominant procedure for pediatric patients with FAP who underwent colectomy in US pediatric centers. Endoscopic assessment trends before and after surgery suggest that the surgical institution plays a limited role in the care of this population.
Ten-year impact of pancreaticoduodenectomy on bowel function and quality of life of patients with ileal pouch-anal anastomosis for familial adenomatous polyposis
2020, HPB
Citation Excerpt :
Quantitative data were expressed as the median and interquartile range (IQR), and values were compared using the Mann–Whitney U test. Qualitative data were reported as frequencies and percentages and compared using the χ2 test or the Fisher exact test, as appropriate. All of the tests were two sided.
Patients with familial adenomatous polyposis (FAP) carry a risk of duodenal adenocarcinoma. These patients, who already have an ileal pouch-anal anastomosis (IPAA), sometimes require pancreaticoduodenectomy (PD). This work aims to evaluate the long-term consequences of the combination of PD + IPAA.
All patients with IPAA due to FAP who underwent PD from 1991 to 2017 were included (PD + IPAA group). Patients were matched 1:1 according to age, sex, ASA score and presence of colorectal cancer. Fecal continence and quality of life (QoL) were assessed using the Wexner score and the EORTC-QLQ-C30 questionnaire.
Thirty-two PD + IPAA patients were matched with thirty-two IPAA-only patients. In each group, the response rate to the questionnaire was 78% (25/32). No differences were noted between PD + IPAA and IPAA-only groups in terms of daytime fecal frequency (6.0 vs 6.0; p = 0.362), Wexner score (3/20 vs 4/20; p = 0.984) and global QoL score (83.3/100 vs 83.3/100; p = 0.401). In the PD + IPAA group, 26% of patients developed diabetes a median period of 10.0 years after PD. The global QoL for these patients was significantly altered (p = 0.011), while daytime fecal frequency was unaffected (p = 0.092) as fecal continence (p = 0.475).
In FAP patients with IPAA, PD does not affect bowel function or QoL.
Reassessing colectomy in young patients with familial adenomatous polyposis
2018, Gastrointestinal Endoscopy
Diffuse benign inflammatory gastric polyps: A rare case in a young female: Case report and review of the literature
2023, Frontiers in Surgery
Surgical treatment of familial adenomatous polyposis in children: cross-sectional study
2023, Koloproktologia

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: DISCLOSURE: Dr Burke received research support from Cancer Prevention Pharmaceuticals. B. Leach, Speakers Bureau for Myriad Speakers Bureau and Advisory Board for Invitae. All other authors disclosed no financial relationships relevant to this publication.

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Original articleClinical endoscopyNatural history of colonic polyposis in young patients with familial adenomatous polyposis

Background and Aims

Methods

Results

Conclusions

Introduction

Section snippets

Methods

Baseline characteristics

Discussion

Conclusions

Gastroenterology

J Mol Diagn

Crit Rev Oncol Hematol

Gastroenterology

Gastroenterology

Gene

Gastrointest Endosc

Impact of screening examinations on survival in familial adenomatous polyposis

Scand J Gastroenterol

Epidemiology of familial adenomatous polyposis in Finland: impact of family screening on the colorectal cancer rate and survival

Gut

Female fecundity before and after operation for familial adenomatous polyposis

Br J Surg

Surgical treatment in familial adenomatous polyposis

Ann Gastroenterol

Impact of familial adenomatous polyposis on young adults: quality of life outcomes

Dis Colon Rectum

Original article
Clinical endoscopy
Natural history of colonic polyposis in young patients with familial adenomatous polyposis