Volume 74 - 2011 - Fasc.3 - Symposium
FAPA - Familial Adenomatous Polyposis Association The Belgian Polyposis Registry
Familial adenomatous polyposis (FAP) is an auto- somal dominant disease that affects about 1 in 10 000 to 1 in 8 000 individuals. The underlying genetic defect is a mutation in the APC (Adenomatous Polyposis Coli) gene. If left untreated, this condition inevitably leads to colorectal cancer and a nationwide and systematic screening for asymptomatic gene carriers is therefore of paramount importance.
Familial adenomatous polyposis : clinical presentation, detection and surveillance
Colorectal cancer (CRC) is a leading cause of cancer related death in the western countries. It remains an important health problem, often under-diagnosed. The symptoms can appear very late and about 25% of the patients are diagnosed at metastatic stage. Familial adenomatous polyposis (FAP) is an inherited colorectal cancer syndrome, characterized by the early onset of hundred to thousands of adenomatous polyps in the colon and rectum. Left untreated, there is a nearly 100% cumulative risk of progression to CRC by the age of 35-40 years (1,2), as well as an increased risk of various other malignancies. CRC can be pre- vented by the identification of the high risk population and by the timely implementation of rigid screening programs which will lead to special medico-surgical interventions. (Acta gastroenterol. belg., 2011, 74, 415-420).
The genetics of familial adenomatous polyposis (FAP) and MutYH-associated polyposis (MAP)
FAP is characterized by 100-1000s of adenomatous polyps in colon and rectum, and is in 70% of the patients associated with extracolonic manifestations. Attenuated FAP (AFAP) is a less severe form of FAP, marked by the presence of < 100 polyps and a later onset of colorectal cancer (CRC).
(A)FAP is caused by autosomal dominantly inherited mutations in the APC (Adenomatous polyposis coli) gene, a tumour suppres- sor gene that controls ss-catenin turnover in the Wnt pathway. De novo occurrence is reported in 30-40% of the patients. Mutations are detected in 85% of classical FAP families, while only 20%-30% of AFAP cases will exhibit a germline APC mutation.
MUTYH is the second (A)FAP-related gene and is involved with base-excision repair of DNA damaged by oxidative stress. MUTYH mutations are inherited in an autosomal recessive way and account for 10%-20% of classical FAP cases without an APC mutation and for 30% of AFAP cases.
Genotype-phenotype correlations exist for mutations in the APC gene, however, contradictions in the literature caution against the sole use of the genotype for decisions regarding clinical manage- ment.
Once the family's specific APC mutation is identified in the proband, predictive testing for first degree relatives is possible from the age of 10 to 12 years on. For AFAP, relatives are tested at age 18 and older. Opinions about the appropriate ages at which to initiate genetic testing may vary.
Physicians must have a discussion about prenatal testing with patients in childbearing age. They may either opt for conventional prenatal diagnosis (amniocentesis or chorionic villous sampling) or for preimplantation genetic diagnosis (PGD). (Acta gastroenterol. belg., 2011, 74, 421-426).
Different surgical strategies in the treatment of familial adenomatous polyposis : what's the role of the ileal pouch-anal anastomosis ?
Background and study aims : Restorative coloproctectomy (RCP) with ileal pouch-anal anastomosis (IPAA), is one of the surgical responses to the crucial question of prophylactic treatment in familial adenomatous polyposis (FAP). No consensus has been reached, until now, to choose between IPAA and ileo-rectal anasto- mosis (IRA), the rectal sparing prophylactic colectomy. This paper aims to review the latest issues related to IPAA and highlights its specificities compared to IRA.
Methods : PubMed database was searched using the following search items: familial adenomatous polyposis, surgery, ileal pouch-anal anastomosis, ileo-rectal anastomosis. Papers published between 1978 and 2010 were selected.
Results : Absence of mortality, acceptable morbidity and good functional results combined to high quality of life have promoted the IPAA technique. New technical issues such as the double sta- pled technique, mesenteric lengthening, omission of temporary protective stoma can be addressed almost systematically for these patients. A laparoscopic approach, lessening the body image impact, has proven to be as effective and safe as the open approach to perform IPAA. Further advantages of laparoscopic IPAA rely on the lower adhesion formation resulting in less small bowel occlu- sion. Sexuality, fertility and childbirth are important functional issues often cited as threatened by the pelvic manoeuvres of the IPAA technique which can be prevented by close rectal wall dissec- tion and a laparoscopic approach.
Conclusion : IPAA offers the best available prophylaxis in FAP patients. Technical enhancements in IPAA will most probably decrease the functional risks. Thus IPAA remains the alternative to IRA for the prophylactic treatment of FAP. Nevertheless, based on the latest evidence, the choice between both procedures is still mat- ter of debate. (Acta gastroenterol. belg., 2011, 74, 427-434).
Different surgical strategies in the treatment of familial adenomatous polyposis : what's the role of the ileorectal anastomosis ?
Prophylactic (procto-) colectomy is the treatment of choice to reduce the risk of colorectal cancer in FAP patients with multiple adenomas. Because patients present at young age, rectum-sparing surgery is sometimes advocated, so that there is no pelvic dissection with impact on quality of life, preserved pelvic innervation and sexual function and fertility. The main disadvantage of a total colectomy with an ileorectal anastomosis (IRA) is a rectal cancer risk of 50% at the age of 50 years and a cumulative risk of 25,8% after 25 years of follow-up. Therefore, this procedure should be reserved for patients with an unaffected rectum. There should be no discussion to perform a primary IPAA in patients with multiple rectal adenomas (> 20) or those with a severe dysplastic or large (> 3 cm) rectal adenoma or a cancer elsewhere in the colon. A patient with an IRA should undergo yearly follow-up by recto- scopy. (Acta gastroenterol. belg., 2011, 74, 435-437).
Psychological implications of living with familial adenomatous polyposis
Background and study aims : Psychosocial implications of living with FAP remain largely unexplored. This article reviews available literature on three topics : 1) Implications of living with FAP 2) genetic testing and reproductive decision-making and 3) family communication.
Patients and methods: Papers published until 2009 about psychosocial and behavioral issues in FAP were identified.
Results : Psychometric data indicate that FAP patients and at-risk relatives as a group do not exhibit clinical symptoms of mental health problems after clinical or genetic diagnosis. However, some subgroups revealed to be more vulnerable to dis- tress. AlsO. concerns related to the disease and its consequences were reported.
While interest in prenatal diagnosis or preimplantation genetic diagnosis seems to be high it is important to study actual uptake because this may reveal to be much lower.
Family members are an important source of information and the few available data suggest that family communication is problematic.
The findings described have several shortcomings. They were obtained from only a few studies often conducted using specific or mixed study groups, originating from the 90ties and mostly cross- sectional in nature.
Conclusions : For clinical practice, it is important to have more research data on how FAP patients at different ages cope with the disease, on the impact of genetic testing on reproductive decision- making and on family communication. Results reported here need to be confirmed by additional research and new themes need to be explored. (Acta gastroenterol. belg., 2011, 74, 438-444).
Quality of care indicators in rectal cancer
Quality of health care is a hot topic, especially with regard to cancer. Although rectal cancer is, in many aspects, a model onco- logic entity, there seem to be substantial differences in quality of care between countries, hospitals and physicians. PROCARE, a Belgian multidisciplinary national project to improve outcome in all patients with rectum cancer, identified a set of quality of care indicators covering all aspects of the management of rectal cancer. This set should permit national and international benchmarking, i.e. comparing results from individual hospitals or teams with national and international performances with feedback to partici- pating teams. Such comparison could indicate whether further improvement is possible and/or warranted. (Acta gastroenterol. belg., 2011, 74, 445-450).