Materiały źródłowe

• #1 Familial Adenomatous Polyposis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538233/

  Familial adenomatous polyposis ranks as the second most common inherited polyposis syndrome. With an estimated incidence ranging between 1 in 5000 and 1 in 18,000 and affecting men and women equally, FAP accounts for approximately 1% of colorectal cancer cases. Approximately 20% to 30% of individuals diagnosed with FAP lack a documented family history and instead display de novo APC mutations. The incidence rates of attenuated FAP and other FAP variants remain unknown. […] According to National Cancer Comprehensive Network guidelines, patients who test positive for an APC gene mutation should undergo annual sigmoidoscopy or colonoscopy from age 10 to 15. Screening for extracolonic manifestations of FAP is essential and includes the following measures: Upper endoscopy to examine the stomach and duodenum at 20 to 25 years. Screening may start earlier if a patient undergoes colectomy before this age. The endoscopy should adequately visualize the ampulla of Vater. Annual abdominal palpation to assess for desmoid tumors. In patients who have undergone colectomy and have a family history of desmoid tumors, abdominal imaging with a computed tomography (CT) or MRI scan may be used after colectomy. Annual thyroid examinations and ultrasounds are conducted starting in the late teenage years for thyroid cancer screening. Insufficient data exist to recommend surveillance for CNS tumors, hepatoblastoma, and pancreatic cancers.

• #2 Orphanet: Familial adenomatous polyposis

  https://www.orpha.net/en/disease/detail/733

  Familial adenomatous polyposis (FAP) is characterized by the development of hundreds to thousands of adenomas in the rectum and colon during the second decade of life. […] FAP has a birth incidence of about 1/8,300, manifests equally in both sexes, and accounts for less than 1% of colorectal cancer (CRC) cases. In the EU, prevalence is estimated at 1/11,300-1/37,600. […] Patients with FAP carry a 100% risk of CRC. However, this risk is reduced significantly when patients enter a screening-treatment program.

• #3 Clinical manifestations and diagnosis of familial adenomatous polyposis – UpToDate

  https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-familial-adenomatous-polyposis

  Familial adenomatous polyposis (FAP) has an estimated prevalence of 1 in 8000 to 1 in 18,000 and accounts for less than 1 percent of all colorectal cancers in the United States. It affects males and females equally and has a worldwide distribution. […] This topic will review the genetics, clinical manifestations, and diagnosis of FAP and its variants (attenuated FAP [AFAP], and gastric adenocarcinoma and proximal polyposis of the stomach [GAPPS]), all of which are due to a germline mutation (ie, pathogenic variant) in the Adenomatous Polyposis Coli (APC) gene. Surveillance strategies for FAP and the clinical features and diagnosis of MUTYH-associated polyposis and the hamartomatous polyposis syndromes are discussed separately.

• #4 Familial Adenomatous Polyposis | Concise Medical Knowledge

  https://www.lecturio.com/concepts/familial-adenomatous-polyposis/

  Familial adenomatous polyposis (FAP) is the most common of the polyposis syndromes, which is a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, associated with other extracolonic features. […] The average age at onset of polyposis in FAP is 16 years. […] The average age at onset of CRC is 39 years. […] Both sexes are equally affected. […] Management is with a surveillance program and colectomy. […] Prevalence varies: 1 in 6000 to 1 in 35,000. […] 2nd most common inherited colorectal cancer syndrome. […] Only 30% of patients with FAP have no family history. […] FAP has been described in all races. […] Lifetime risk of CRC: 100%. […] Gastric polyps: up to 90%. […] Ampulla of Vater adenocarcinoma: 10%. […] Desmoid tumors: up to 20%. […] Thyroid tumors: 2%. […] Hepatoblastoma: 1.6%.

• #5 Familial adenomatous polyposis epidemiology and demographics – wikidoc

  https://www.wikidoc.org/index.php/Familial_adenomatous_polyposis_epidemiology_and_demographics

  The prevalence of familial adenomatous polyposis is approximately 3 to 10 per 100,000 individuals in the Europe. […] In 1975, the incidence of familial adenomatous polyposis is approximately 13 per 100,000 individuals with a surgical mortality rate of 4400 per 100,000 individuals (4.4%) in Sweden. […] The mean age for developing colon polyps in patients with familial adenomatous polyposis is 13 years. […] Patients in their first and second decades usually develop familial adenomatous polyposis. […] All the patients with familial adenomatous polyposis without treatment will develop colorectal cancer by age of 39. […] There is no racial predilection to familial adenomatous polyposis. […] Familial adenomatous polyposis affects men and women equally. […] Familial adenomatous polyposis is a rare disease that tends to affect individuals worldwide.

• #6 Familial adenomatous polyposis | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-4-22

  Familial adenomatous polyposis (FAP) is characterized by the development of many tens to thousands of adenomas in the rectum and colon during the second decade of life. FAP has an incidence at birth of about 1/8,300, it manifests equally in both sexes, and accounts for less than 1% of colorectal cancer (CRC) cases. In the European Union, prevalence has been estimated at 1/11,300-37,600. […] In many countries there are local FAP registries; however it is difficult to obtain accurate nation-wide data. In the UK, Reed and Neel presented a detailed genetic study in 1955 and calculated the incidence of FAP at birth to be 1:8,300. In 1975, Alm presented an incidence rate of 1:7,645 in Sweden. […] In 2009, the European Medicines Agency (EMEA) estimated that FAP affected approximately 3-10/100,000 people in the European Union which is equivalent to 11,300 – 37,600 individuals. Clinically, FAP manifests equally in both sexes by the late teens and in the twenties age group.

• #6 Familial adenomatous polyposis | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-4-22

  By the late teens or early twenties, colorectal cancer prophylactic surgery is advocated. The recommended alternatives are total proctocolectomy and ileoanal pouch or ileorectal anastomosis for AFAP. […] Individuals with FAP carry a 100% risk of CRC; however, this risk is reduced significantly when patients enter a screening-treatment program.

• #7 Familial adenomatous polyposis – Wikipedia

  https://en.wikipedia.org/wiki/Familial_adenomatous_polyposis

  The incidence of the mutation is between 1 in 10,000 and 1 in 15,000 births. By age 35 years, 95% of individuals with FAP (100 adenomas) have polyps. Without colectomy, colon cancer is virtually inevitable. The mean age of colon cancer in untreated individuals is 39 years (range 34-43 years). […] Attenuated FAP arises when APC is defective but still somewhat functional. As a result, it retains part of its ability to suppress polyps. Therefore, attenuated FAP manifests as colorectal cancer unusually late (age 40-70, average=55), and typically with few, or at least far fewer polyps (typically 30), than the more usual version of FAP, at an age when FAP is no longer considered much of a likelihood or risk according to usual FAP epidemiology. […] Monitoring involves the provision of outpatient colonoscopy, and occasionally upper gastric tract esophagogastroduodenoscopy (EGD, to search for premalignant gastric or duodenal cancers), typically once every 13 years, and/or a genetic blood test to definitively confirm or deny susceptibility. A small number of polyps can often be excised (removed) during the procedure if found, but if there are more severe signs or numbers, inpatient surgery may be required.

• #8 Familial Adenomatous Polyposis: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/175377-overview

  Familial adenomatous polyposis (FAP) is the most common adenomatous polyposis syndrome. It is an autosomal dominant inherited disorder characterized by the early onset of hundreds to thousands of adenomatous polyps throughout the colon. If left untreated, all patients with this syndrome will develop colon cancer by age 35-40 years. In addition, an increased risk exists for the development of other malignancies. […] Estimates vary from 1 case in 6,850 persons to 1 case in 31,250 persons. […] The average age of onset of polyposis in FAP is 16 years, whereas the average age of onset for colorectal cancer is 39 years. […] Patients with untreated FAP have a median life expectancy of 42 years. Life expectancy is extended greatly in those treated with colectomy. […] The cumulative probability of developing any type of noncolorectal cancer, mostly periampullary tumors, is 11% by age 50 years and 52% by age 75 years.

• #9 Familial adenomatous polyposis | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/familial-adenomatous-polyposis-1?embed_domain=external.radpair.com%252527%25255B0%25255D%252527%25255B0%25255Dfavicon.ico&lang=us

  Familial adenomatous polyposis syndrome affects 1 in 10,000 people. The average age of presentation is 16 years. […] Familial adenomatous polyposis syndrome accounts for 0.5% of colorectal cancer cases with ~7% of familial adenomatous polyposis carriers developing colorectal cancer by age 21, and almost every carrier developing colorectal cancer by 35-40 years.

• #10 Familial Adenomatous Polyposis (FAP): Symptoms, Diagnosis, Risks

  https://my.clevelandclinic.org/health/diseases/16993-familial-adenomatous-polyposis-fap

  Familial adenomatous polyposis (FAP) is a hereditary syndrome that raises your risk of developing colorectal cancer to nearly 100%. […] To manage this risk, healthcare providers usually recommend complete removal of the colon (total colectomy) and sometimes the rectum, too (proctocolectomy). […] Without treatment, the risk of developing colorectal cancer with familial adenomatous polyposis is close to 100%. […] Children in families known to be affected by the syndrome begin yearly colonoscopy screenings at the age of 10. […] Familial adenomatous polyposis is rare, estimated to affect about 1 in 8,000 people. […] For classic FAP, guidelines recommend yearly colonoscopies starting at age 10 and continuing until your colectomy. […] For AFAP, yearly screenings should begin by age 20. […] Without timely treatment, the median life expectancy is 42 years. […] But with appropriate care, you can live a normal life.

• #11 Aggressive mutation in a familial adenomatous polyposis syndrome family: when phenotype guides clinical surveillance – Neffa – Journal of Gastrointestinal Oncology

  https://jgo.amegroups.org/article/view/17468/html

  Polyps usually present during young adolescence, whereas cancer diagnosis frequently appears in young adulthood. Extra-colonic malignancies are also part of the syndrome, such as: papillary thyroid cancer (23%), hepatoblastoma (12%), medulloblastoma; (1%), pancreatic (1%), gastric (12%), and duodenal cancer (412%). FAP associated-gastric lesions are: fundic gland polyps, gastric adenomas, and gastric cancers. […] The main death causes in these patients regarding extra-colonic lesion are as follows: desmoid tumours (9.9%), duodenal cancer (5.6%), and gastric cancer (2.8%). […] Once a patient is clinically diagnosed as FAP, a genetic study must be performed since the genotype helps guide surveillance. Although there is some heterogeneity in clinical manifestations of FAP, even among family members with the same APC gene mutation, the correlation between the site of the mutation within the gene and the clinical manifestations of the disease is useful for the clinical management of affected patients.

• #12 Endoscopic Surveillance and Treatment of Upper GI Tract Lesions in Patients with Familial Adenomatous Polyposis—A New Perspective on an Old Disease

  https://www.mdpi.com/2073-4425/13/12/2329

  In FAP patients, there is a significant risk of extracolonic malignancies, especially originating from the small bowel, mainly duodenum, but also the risk of stomach cancer is increased in comparison with that of the population. Duodenal malignancy, desmoid tumors, and CRC are the leading causes of death in these patients. The cumulative risk of duodenal cancer by age of 60 is estimated between 4.5 and 5.3%. Colon endoscopy surveillance and prophylactic colectomy have strongly reduced mortality due to colorectal cancer and have improved the survival of FAP patients, leading to an increased need for surveillance of extracolonic malignancies in the duodenum and stomach. Endoscopic surveillance of FAP patients is a safe and effective way to diagnose precancerous lesions, for example, in the stomach, duodenal, and ampullary adenomas. Moreover, endoscopic resection techniques are the minimally invasive option to treat most of the benign lesions and early cancer in the upper GI tract. However, surveillance recommendations in the upper GI tract are still not completely clear and lack strong evidence.

• #12 Endoscopic Surveillance and Treatment of Upper GI Tract Lesions in Patients with Familial Adenomatous Polyposis—A New Perspective on an Old Disease

  https://www.mdpi.com/2073-4425/13/12/2329

  Familial adenomatous polyposis (FAP) is an autosomal dominant disease caused by a germline mutation in the adenomatous polyposis coli (APC) gene. Patients with FAP develop up to thousands of colorectal adenomas as well as lesions in the upper GI tract. In FAP, the upper digestive lesions include gastric fundic gland polyps (FGPs), antrum adenomas, duodenal or small intestinal adenomas, and carcinoma. Patients, after colectomy, are still at significant risk for extracolonic malignancies. Advances in endoscope resolution and optical enhancement technologies allow endoscopists to provide assessments of benign and malignant polyps. For this reason, in the past decades, endoscopic resection techniques have become the first line of treatment in patients with polyps in the upper GI, whereby polyps and even early cancers can be successfully cured. In FAP patients, endoscopic ampullectomy appears to be a safe and effective way of treating patients with ampullary tumors. According to current indications, endoscopic retrograde cholangiopancreatography (ERCP) and stenting of the main pancreatic duct follow ampullectomy.

• #13 Diagnosis, surveillance, and treatment strategies for familial adenomatous polyposis: rationale and update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5019104/

  Familial adenomatous polyposis is characterized by the development of multiple (100) colorectal adenomas throughout the colorectum. […] Individuals with a family history of this disease who have not been diagnosed should be advised to attend genetic counseling and to enroll in appropriate clinical and genetic surveillance programs. […] Patients with FAP should be enrolled in a lifetime surveillance program to detect these disorders. […] Genetic testing for the APC gene mutation is one of the screening strategies for FAP. Individuals with a family history of FAP (first-degree relatives of FAP patients) should undergo genetic counseling and screening for FAP between the ages of 10 and 12 years to identify carriers of the APC gene mutation. […] Surveillance and treatment strategies should be determined on the basis of each patient’s personal history.

• #13 Diagnosis, surveillance, and treatment strategies for familial adenomatous polyposis: rationale and update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5019104/

  Unaffected patients with a family history of mutation and with a known APC disease-causing mutation should be recommended for flexible sigmoidoscopy or colonoscopy every 12 months beginning at 10-15 years of age. […] Esophagogastroduodenoscopy (EGD) should be advised for individuals with FAP either by the age of 25 years or before colectomy and EGD should be repeated every 1-3 years. […] The frequency of EGD depends on the severity of the duodenal adenoma, which can be determined using the Spigelman staging criteria. […] Surveillance intervals can be adjusted or treatment initiated in patients with FAP and duodenal adenomatosis according to the Spigelman stage. […] Progress in endoscopic technology in the current decade has provided more detailed and broad-ranging information on the extent of comorbidities related to FAP. […] Further study will elucidate the potential of these new endoscopic technologies to enhance surveillance strategies for FAP.

• #14 Familial adenomatous polyposis: Screening and management of patients and families – UpToDate

  https://www.uptodate.com/contents/familial-adenomatous-polyposis-screening-and-management-of-patients-and-families

  Individuals at-risk for FAP include: First-degree relatives of those with FAP. Individuals with >10 cumulative colorectal adenomas or colorectal adenomas in combination with extracolonic features associated with FAP (eg, duodenal/ampullary adenomas, desmoid tumors, papillary thyroid cancer, retinal pigment epithelium hamartomas associated with FAP (RPEH-FAP), epidermal cysts, or osteomas).

• #15 Familial Adenomatous Polyposis Workup: Approach Considerations, Imaging Studies, Laboratory Studies

  https://emedicine.medscape.com/article/175377-workup

  The initial assessment is the collection of a family history of cancers and premalignant gastrointestinal conditions and should provide enough information to develop a preliminary determination of the risk of a familial predisposition to cancer. […] Patients who meet the clinical criteria for a syndrome as well as those with identified pathogenic germline mutations should receive appropriate surveillance measures in order to minimize their overall risk of developing syndrome-specific cancers. […] The International Society for Gastrointestinal Hereditary Tumors (InSIGHT) has proposed a staging system and stage-specific interventions for FAP. […] Genetic testing for a germline mutation in the APC gene should be considered in individuals with 10-20 adenomas in their lifetime, furthermore in patients with a strong family history of polyposis; larger numbers of adenomas is associated with a greater likelihood of FAP.

• #15 Familial Adenomatous Polyposis Workup: Approach Considerations, Imaging Studies, Laboratory Studies

  https://emedicine.medscape.com/article/175377-workup

  A few patients with clinical FAP have a genetic mutation that cannot be identified, and their first-degree relatives cannot be screened genetically and will require life-time clinical screenings. […] Periodic ultrasounds or abdominal computed tomography scans are used to check for intra-abdominal desmoid tumors and pancreatic cancer. […] Periodic ultrasound of the thyroid: This imaging study is considered because of the increased risk of thyroid cancer. It can supplement the recommended annual physical examination of the thyroid.

• #16

  https://link.springer.com/article/10.1007/s44197-023-00171-8

  Familial adenomatous polyposis (FAP) syndrome has a near-100% lifetime risk of colorectal cancer. Early surveillance and prophylactic surgery have been advocated to reduce this risk. However, the surveillance practices among FAP individuals in Saudi Arabia are unknown. […] The compliance rate toward both pre-operative colonoscopy and upper endoscopy were 78%. However, 38% and 27% compliance rates were observed toward initial and post-operative colonoscopy, respectively. The compliance rate was 14% toward thyroid ultrasound. […] Due to the high penetrance of CRC, the national comprehensive cancer network (NCCN) recommends surveillance of FAP individuals and at-risk relatives by high-quality colonoscopy in its guidelines. This has to be performed annually starting at the age of 10-15 years.

• #16

  https://link.springer.com/article/10.1007/s44197-023-00171-8

  Poor overall compliance was observed, particularly toward thyroid ultrasound. The highest compliance was found toward pre-operative colonoscopy and upper endoscopy. The compliance rates to initial and post-operative colorectal surveillance were 38% and 27%, respectively. […] The compliance of FAP individuals toward recommended surveillance is poorly documented in the literature with most studies focusing on compliance toward colonoscopy. […] Our study highlights the lack of surveillance compliance among FAP individuals despite the availability of standardized clinical guidelines. Enhancing patients awareness of their condition and promoting genetic testing and surveillance among family members should be emphasized in the Kingdom.

• #17 Colorectal Cancer Screening and Surveillance in Individuals at Increased Risk | AAFP

  https://www.aafp.org/pubs/afp/issues/2018/0115/p111.html

  Individuals who have a first-degree relative with hereditary nonpolyposis colorectal cancer should begin colonoscopy at 25 years of age and repeat colonoscopy every one to two years. […] In persons with a family history of adenomatous polyposis syndromes, screening should begin at 10 years of age or in a person’s mid-20s, depending on the syndrome; repeat colonoscopy is typically required every one to two years. […] Familial adenomatous polyposis is defined as having 100 or more synchronous advanced adenomas inherited in an autosomal dominant manner. […] The prevalence is about three in 100,000. […] Screening with flexible sigmoidoscopy should begin around 10 years of age. […] If an adenoma is identified on sigmoidoscopy, colonoscopy should be performed. […] Colonoscopy should be performed annually if colectomy is delayed more than one year after polyps are found.

• #17 Colorectal Cancer Screening and Surveillance in Individuals at Increased Risk | AAFP

  https://www.aafp.org/pubs/afp/issues/2018/0115/p111.html

  If a genetic mutation has been found, flexible sigmoidoscopy or colonoscopy should be performed annually. […] If genetic testing has not yet been performed or is negative, annual screening should be performed until 24 years of age, then every two years until 34 years of age, then every three years until 44 years of age, and every three to five years thereafter. […] Attenuated familial adenomatous polyposis is defined as 10 to 99 synchronous advanced adenomas with a proximal colonic distribution inherited in an autosomal dominant manner. […] Screening colonoscopy should begin in the late teens to mid-20s and be performed every one to two years. […] MUTYH-associated polyposis is caused by a mutation in the MUTYH gene and is defined as typically fewer than 100 advanced adenomas inherited in an autosomal recessive pattern.

• #18 Familial Adenomatous Polyposis – Genetic Syndromes Associated With Colorectal Cancer – Colorectal Polyps and Genetic Syndromes Associated With Colorectal Cancer – Intestinal Diseases – Gastrointestinal Diseases – Gastroenterology – Diseases – McMaster T

  https://empendium.com/mcmtextbook/chapter/B31.II.4.72.6.5.2.

  Familial adenomatous polyposis (FAP) is an autosomal dominant disease caused by a germline mutation in the APC gene (chromosome 5). In the classic form of the disease, the large intestine of the patient has 1000 adenomatous polyps and the risk of developing colorectal cancer during a lifetime is 100%. […] In carriers of the APC gene mutation, colonoscopy or flexible sigmoidoscopy should be performed every 1 to 2 years starting at 12 to 15 years of age until prophylactic proctocolectomy is performed (indicated before the age of 25). In patients with AFAP colonoscopy should be performed every 1 to 2 years, starting at 18 to 20 years of age. If the patient defers surgery for AFAP because of a manageable polyp burden, they can increase the interval of their surveillance colonoscopies to every 3 years starting at 35 years old.

• #19 2020 ASGE Recommendations for Endoscopy in Familial Adenomatous Polyposis Syndromes – Gastroenterology Advisor

  https://www.gastroenterologyadvisor.com/features/american-society-for-gastrointestinal-endoscopy-guidelines-for-fap-map-ipaa-ira/

  In patients with confirmed AFAP, surveillance colonoscopy with polypectomy is recommended at 1- to 2-year intervals as it may prevent the need for future surgery in patients with low polyp burden. […] Patients with low polyp burden can be adequately managed with polypectomy, and the ASGE recommends surveillance colonoscopy in patients with MAP at intervals of 1 to 2 years. […] Surveillance after surgery is necessary due to the increased risk for adenomas in the ileum, rectal cuff, and anal transition zone. […] The ASGE recommends endoscopy of the pouch or ileoscopy in patients with IPAA at 1- to 2-year intervals, while patients with IRA should undergo sigmoidoscopy at 6-month to 1-year intervals indefinitely. […] Screening and surveillance endoscopy are recommended and include random biopsy sampling of suspicious lesions and complete resection of polyps measuring 1 cm to assess for dysplasia and malignancy. […] Endoscopic management is recommended to identify and follow patients with duodenal polyposis in order to assess for dysplasia and accurate Spigelman stage.

• #20 Duodenal adenoma surveillance in patients with familial adenomatous polyposis

  https://www.wjgnet.com/1948-5190/full/v7/i10/950.htm

  Duodenal adenomas tend to occur approximately 15 years after the appearance of colonic adenomas. […] Duodenal adenomas have been found in 30%-92% of FAP patients, with a lifetime risk approaching 100%. […] The frequency of detecting duodenal adenomas in FAP patients may vary depending on endoscopic technique and the method of tissue sampling. […] The risk of malignancy increases with size, location (ampullary) and adenomatosis severity. […] Thus, between the existence of an almost 100% lifetime risk of developing duodenal adenomatosis and the cumulative incidence rates of Spigelman stage IV disease and carcinoma (4% to 10%), there is a clear need for careful follow-up and surveillance of this population. […] Surveillance is the most advantageous in stage IV patients, as their risk of duodenal carcinoma ranges from 7%-36% compared to non-stage IV patients, who have an overall risk of 5%. […] The majority of large studies have shown that the risk of advanced duodenal adenomatosis (stage IV) increases with age. […] Therefore, endoscopic surveillance programs should be performed according to the following published recommendations.

• #21 APC (Familial adenomatous polyposis) – risk management

  https://www.eviq.org.au/cancer-genetics/adult/risk-management/178-apc-familial-adenomatous-polyposis-risk-ma

  Without polypectomy and/or colectomy polyps eventually become malignant. […] Multiple studies have demonstrated that surveillance colonoscopy from early childhood with appropriately timed colectomy reduces CRC incidence and mortality. […] The natural history of polyposis supports annual surveillance in classical FAP. […] It also supports surveillance by either sigmoidoscopy or colonoscopy until polyps are first detected, and then by colonoscopy. […] In AFAP polyps have a more proximal colonic preponderance and colonoscopy should be used for surveillance (not sigmoidoscopy). […] The American College of Gastroenterology recommends hepatoblastoma surveillance from birth to age 7 years. However, there is substantial controversy about surveillance as the absolute risk of hepatoblastoma is small and there is no evidence of benefit of surveillance.

• #21 APC (Familial adenomatous polyposis) – risk management

  https://www.eviq.org.au/cancer-genetics/adult/risk-management/178-apc-familial-adenomatous-polyposis-risk-ma

  The risk management of an individual with a pathogenic variant in two or more genes that confer a predisposition to cancer should also be individualised. […] The choice of risk management strategy should take into account current age, other health issues and age-related cancer risk. Risks and benefits of interventions should be discussed with an experienced medical professional. […] The impact of lifestyle on general cancer risks should be discussed e.g. exercise most days for at least 30 minutes at moderate or strenuous intensity, maintain a healthy weight, have a healthy diet, limit alcohol intake, do not smoke and avoid excessive sun exposure. […] In classic FAP extensive colonic adenomatous polyposis is typically evident early in the second decade of life (but can develop earlier).

• #22 Role of endoscopy in patients with familial adenomatous polyposis | Frontline Gastroenterology

  https://fg.bmj.com/content/13/e1/e72

  Familial adenomatous polyposis (FAP) is a hereditary disease that, without intervention, will cause nearly all patients to develop colorectal cancer by the age of 45. […] Endoscopy is an essential part of the multidisciplinary management of FAP to aid the early identification or prevention of advanced gastrointestinal malignancy. […] The prevalence of FAP is estimated to be 1 in 10000 and accounts for 2%5% of CRC. […] Without prophylactic colorectal surgery, CRC will develop in all patients with FAP at a mean age between 35 and 45. […] Duodenal polyps also eventually develop in nearly all patients (88%98%) with two-thirds of patients harbouring ampullary adenomas also. […] The combination of endoscopic surveillance and surgery for FAP have caused a significant decrease in CRC incidence and mortality.

• #22 Role of endoscopy in patients with familial adenomatous polyposis | Frontline Gastroenterology

  https://fg.bmj.com/content/13/e1/e72

  A systemic review of 30 non-randomised studies including 8016 patients compared CRC incidence and mortality in screened and symptomatic patients with FAP: all studies showed an improvement in both long-term survival and CRC incidence. […] European databases have demonstrated the development of colorectal adenomas between the ages of 12 and 17 years leading to European and UK guidance recommending the age to start lower gastrointestinal endoscopy surveillance between the ages of 1214. […] The risk of polyps developing in an IPAA has been shown to be 45%51% at 10 years, however, there is a very low risk of developing CRC (0%1.9%) in the same time period. […] With the risk of duodenal polyposis and duodenal cancer being recognised in FAP, AFAP and MAP upper gastrointestinal endoscopic surveillance is recommended.

• #22 Role of endoscopy in patients with familial adenomatous polyposis | Frontline Gastroenterology

  https://fg.bmj.com/content/13/e1/e72

  Nearly all patients with FAP will eventually develop duodenal adenomas with studies estimating levels of 88%98% and with duodenal cancer risk estimated to be 18% at by the age of 75. […] Consensus guidance in the UK, Europe and USA agree that upper gastrointestinal surveillance should start at age 25. […] The endoscopist plays a key role in the care of patients with FAP. The combination of endoscopic surveillance and recognition of factors that require referral for therapy or surgery are an essential part of the multidisciplinary management of patients with FAP.

• #23 P113 Duodenal surveillance in familial adenomatous polyposis: adherence to the ESGE guidelines in a tertiary center | Gut

  https://gut.bmj.com/content/71/Suppl_1/A96.2

  Familial adenomatous polyposis (FAP) is an autosomal dominant condition with germline mutation in the APC gene. In addition to the colonic manifestation around 50-90% of carriers develop duodenal polyps although only a minority develop duodenal cancer with a cumulative risk ranging from 4-10% by the age of 60. The ESGE guidelines recommends starting endoscopic duodenal surveillance for patients with FAP at the age of 25. […] Adherence to the ESGE guidelines was suboptimal in our cohort of patients but most of our experience predates the guidelines.

• #24 Polyposis registries – Wikipedia

  https://en.wikipedia.org/wiki/Polyposis_registries

  Polyposis registries exists for the purpose of understanding the genetic disease familial adenomatous polyposis. The registries provide a service to doctors for identification, surveillance and management of families and individuals with high colorectal cancer risk from Familial Adenomatous Polyposis (FAP) and Hereditary Non-Polyposis Colorectal Cancer (HNPCC). […] Polyposis registries have been used in numerous academic studies to assess morbidity and mortality of colorectal cancer related to FAP, and use of registry data has resulted in improved treatment and reduced mortality from polyposis-related colorectal cancer. […] Guidelines for the surveillance and management of familial adenomatous polyposis (FAP): a world wide survey among 41 registries.

• #25 A Personalized Surveillance and Intervention Protocol for Patients With Familial Adenomatous Polyposis That Have Undergone (Procto)Colectomy | Clinical Research Trial Listing

  https://www.centerwatch.com/clinical-trials/listings/NCT04678011/a-personalized-surveillance-and-intervention-protocol-for-patients-with-familial-adenomatous-polyposis-that-have-undergone-proctocolectomy

  With the proposed study, the investigators aim to provide evidence for personalized endoscopic surveillance for patients with FAP that have undergone (procto)colectomy with construction of an IRA/ISA or IPAA with the goal to prevent development of advanced neoplasia (AN) by endoscopically removing lesions before they progress to AN.

• #26 Screening and surveillance for hereditary colorectal cancer

  https://www.irjournal.org/journal/view.php?doi=10.5217/ir.2023.00112

  Colonoscopy is the primary method for screening and surveillance of FAP. According to the American Society for Gastrointestinal Endoscopy recommends colonoscopy screening should begin at the age of 10-12 years, with annual follow-ups, for individuals at risk for FAP. The frequency of follow-up colonoscopies may be individualized based on the number of polyps found. An attenuated phenotype ( 100 adenomas) may not require frequent colonoscopies, unlike a classical phenotype ( 100 adenomas). Individuals with a confirmed diagnosis of atypical FAP often develop CRC at a later age. Screening is recommended to begin in late teens to the early 20s and colonoscopy should be performed every 1-2 years. According to the NCCN guidelines, endoscopic surveillance after surgery can vary depending on the type of surgery performed. Patients who have undergone colectomy with ileorectal anastomosis (IRA) should undergo endoscopy for evaluation of the rectum every 6-12 months depending on the number of polyps. Patients who have undergone total proctocolectomy with ileal pouch-anal anastomosis (IPAA) should undergo annual endoscopic evaluations of the ileal pouch and rectal cuff, depending on the polyp burden. The frequency of surveillance should be shortened to every 6 months for large, flat polyps with villous histology and/or high-grade dysplasia. In addition to colonoscopy, imaging techniques such as virtual colonoscopy (CT colonography) or MRI may be used as adjuncts to screen for polyps in patients with FAP. These noninvasive methods provide detailed images of the colon and other FAP-related organs and can be particularly useful in cases where colonoscopy is contraindicated or not well tolerated.

• #27 Attenuated Familial Adenomatous Polyposis: A Novel Treatment with Celecoxib – Practical Gastro

  https://practicalgastro.com/2016/02/06/attenuated-familial-adenomatous-polyposis-a-novel-treatment-with-celecoxib/

  Attenuated familial adenomatous polyposis is characterized by multiple adenomatous polyps that develop later in life and prompt close screening due to a high propensity of malignant transformation. […] There still exists nearly 100% incidence of colorectal cancer with these patients, averaging roughly 10-15 years past time of initial presentation and care must be taken to continue aggressive surveillance of disease burden. […] In 2001, FDA approved the use of COX-II inhibitors for chemoprophylaxis in patients with Familial Adenomatous Polyposis (FAP) due to several randomized clinical trials showing significant tumor reduction. […] It is still unclear whether reduction of polyps early in the disease process offers protection against malignant transformation later in life. […] It may bring about more risks involved in patients with multiple comorbidities given the FDA black box warning of increased incidence of gastrointestinal bleeding with use of NSAIDs as well as the adverse cardiovascular effects of MI and stroke. […] This treatment for aFAP may be a novel non-surgical approach to this disease, and should be further investigated.

• #28 Updated perspectives on the diagnosis and management of FAP | TACG

  https://www.dovepress.com/updated-perspectives-on-the-diagnosis-and-management-of-familial-adeno-peer-reviewed-fulltext-article-TACG

  Prophylactic colectomy and endoscopic surveillance currently constitute the best choice for cancer prevention in FAP. […] Chemopreventive medicines work to reduce or delay the risk of cancer by targeting the pathways that lead to cancer development. […] Despite the association between total colectomy with ileorectal anastomosis and development of rectal cancer, there is less possibility of desmoid tumor development in this type of operation. […] The mTOR pathway along with two new treatment targets, REC-4881 and obeticholic acid, which are being investigated by an ongoing clinical study, are promising targets for the future.

• #29 Early Trial Shows REC-4881 Reduces Polyp Burden by 43 Percent in Rare Genetic Cancer Disorder – CTOL Digital Solutions

  https://www.ctol.digital/news/rec-4881-trial-reduces-polyp-burden-genetic-cancer/

  Recursions Early Trial Data Reveals Promising Efficacy in Familial Adenomatous PolyposisBut Challenges Loom in Turning a Niche Asset Into a Scalable Franchise. […] FAP affects approximately 50,000 individuals in the U.S. and EU5. […] Despite advances in endoscopy and surgical prophylaxis, most face the prospect of multiple operations, impaired quality of life, and a lifetime tethered to surveillance. […] REC-4881 has given Recursion its first tangible shot at a commercial product in a competitive, high-stakes space. […] In a landscape dominated by surgery and surveillance, this could be the first true systemic option for FAP.

• #30 Familial adenomatous polyposis: clinical presentation, detection and surveillance

  https://lirias.kuleuven.be/55235

  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, as well as an increased risk of various other malignancies. […] CRC can be prevented 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.

• #31

  https://step2.medbullets.com/gastrointestinal/120176/familial-adenomatous-polyposis

  Average age of presentation with symptoms is 36 years. […] Average age of first polyp is 16 years. […] Start screening with sigmoidoscopy at age 12 annually. […] Inevitable progression to colorectal cancer if no surgery. […] Almost normal prognosis with colonic screening and colectomy.

• #32 Familial Adenomatous Polyposis: Alarming Symptoms, Causes, Types, Diagnosis and Treatment – OncoDaily

  https://oncodaily.com/oncolibrary/cancer-types/familial-adenomatous-polyposis

  The progression of FAP through these stages underscores the importance of early detection and regular screening. By catching the disease in its early stages (Stage 0 or I), patients can undergo less invasive treatments like polypectomy or chemoprevention, significantly reducing the risk of progression to Stage III or IV. […] Regular screenings are the most effective way to prevent FAP-related cancers. Since FAP leads to the development of hundreds to thousands of polyps in the colon, which can become cancerous, early detection is vital. Colonoscopy is the gold standard for familial adenomatous polyposis management and screening. […] Research has demonstrated that early detection of FAP and timely surgical intervention can lead to a 99% reduction in colorectal cancer incidence among affected individuals (Ditonno et al, published in International Journal of Molecular Sciences, 2023). Screening protocols have drastically improved survival rates, with the 5-year survival rate for early-stage FAP patients exceeding 95% (Lynch et al, published in Gastrointest Endosc, 2017). For those who delay screenings and develop advanced colorectal cancer, the 5-year survival rate drops to around 65% (Ditonno et al, published in International Journal of Molecular Sciences, 2023). Therefore, consistent and early screenings are the most critical factors in improving outcomes for FAP patients.

• #33 Familial adenomatous polyposis: a case report | Journal of Medical Case Reports | Full Text

  https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-024-04724-8

  Individuals at risk for FAP include first-degree relatives of those with FAP and individuals with 10 cumulative colorectal adenomas or colorectal adenomas in combination with extracolonic features associated with FAP. […] Considering the increasing number of locally advanced and advanced cases of colorectal cancer (CRC) in low- and middle-income countries (LMICs), there is an urgent need to implement screening strategies for early disease detection. […] There is a lack of standard diagnostic facilities in Ethiopia, generating a cancer delay in Ethiopia, which causes increased mortality due to locally advanced presentation. […] Our FAP case report signifies there is an urgent need to develop national cancer screening in LMICs. […] Developing screening policies for CRC will involve many factors, including workforce, medical equipment, and cost-effectiveness varying across LMICs, as well as increasing health literacy and educating the general population to discuss cancer in the community and detect it early by recognizing signs and symptoms.

• #34 Multiomic analysis of familial adenomatous polyposis reveals molecular pathways associated with early tumorigenesis | Nature Cancer

  https://www.nature.com/articles/s43018-024-00831-z

  Familial adenomatous polyposis (FAP) is a genetic disease causing hundreds of premalignant polyps in affected persons and is an ideal model to study transitions of early precancer states to colorectal cancer (CRC). […] Familial adenomatous polyposis (FAP) is an ideal system in which to study early events during CRC formation for multiple reasons. […] Persons with FAP have a nearly 100% lifetime risk of developing invasive adenocarcinomas and, thus, often have their entire colon removed as prophylactic treatment once the number of polyps that develop becomes unmanageable through endoscopic surveillance. […] Accordingly, molecular analysis of multiple benign and dysplastic polyps from the same person, as well as normal mucosa can reveal the mechanisms by which APC mutations initiate premalignant polyps and their transition to a malignant state across a common germline genetic background.

• #34 Multiomic analysis of familial adenomatous polyposis reveals molecular pathways associated with early tumorigenesis | Nature Cancer

  https://www.nature.com/articles/s43018-024-00831-z

  This rich open-access multiomic, multisample dataset also provides a valuable scientific resource to the community, complementing the existing datasets on sporadic CRCs. […] Dysregulation of the arachidonic acid pathway is particularly interesting because it is involved in inflammation and can be suppressed by aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), a treatment for persons with FAP to slow polyp progression and reduce CRC formation. […] Our results provide a molecular explanation for the therapeutic strategy for FAP treatment. […] The transition of polyps to dysplasia was characterized by proteomic and transcriptomic alterations that were predominantly downregulated; functional enrichment was nearly entirely composed of downregulated pathways. […] This rich multimodal dataset illuminates the steps involved in precancer formation and transition to malignancy at unprecedented resolution and should serve as a valuable resource for the community.

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