Patient with familial adenomatous polyposis. All statements are correct except 2. Treatment should be surgical when polyposis is observed. At 40 years of age is the usual point of incidence of cancer.

Patient with familial adenomatous polyposis. All statements are correct except [HIDDEN]. Treatment should be surgical when polyposis is observed. At 40 years of age is the usual point of incidence of cancer.

A 30-year-old man with a family history of a father who died at 38 years of age from colon cancer. A colonoscopy is performed and shows hundreds of adenomas throughout the colon. Which of the following statements is false?

The patient has familial adenomatous polyposis.

The most appropriate management is annual follow-up colonoscopy and colectomy at age 40.

If the patient does not undergo surgical treatment, he/she will almost certainly develop colorectal cancer.

First degree relatives should be studied.

The patient's children have a 50% risk of suffering the same disease.

Clinical inquiries. What's the most effective way to screen patients with a family history of colon cancer?

The best approach for screening patients hinges on the number, degree, and age of relatives diagnosed with colorectal cancer (CRC) or adenomatous polyps (AP). Screening should begin at 40 years of age for patients with a family history of CRC or AP in at least 1 first-degree relative or CRC in at least 2 second-degree relatives. Patients at highest risk-who have 1 first-degree relative diagnosed with CRC or AP before 60 years of age or multiple first-degree relatives diagnosed at any age-should begin screening with colonoscopy at 40 years of age or 10 years younger than the earliest affected relative and undergo a repeat colonoscopy every 5 years. Patients who have a first-degree relative diagnosed with CRC or AP after 60 years of age or 2 or more second-degree relatives with CRC should start screening at 40 years of age, with routine options and follow-up intervals. (Routine options and follow-up intervals include any of the following 3 regimens: annual high-sensitivity fecal occult blood testing, sigmoidoscopy every 5 years combined with high-sensitivity fecal occult blood testing every 3 years, or screening colonoscopy every 10 years.).

An unusually severe phenotype for familial adenomatous polyposis.

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

Colorectal Cancer Screening and Surveillance in Individuals at Increased Risk.

Individuals at increased risk of developing colorectal cancer include those with a personal or family history of advanced adenomas or colorectal cancer, a personal history of inflammatory bowel disease, or genetic polyposis syndromes. In general, these persons should undergo more frequent or earlier testing than individuals at average risk. Individuals who have a first-degree relative with colorectal cancer or advanced adenoma diagnosed before 60 years of age or two first-degree relatives diagnosed at any age should be advised to start screening colonoscopy at 40 years of age or 10 years younger than the earliest diagnosis in their family, whichever comes first. In individuals with ulcerative colitis or Crohn disease with colonic involvement, colonoscopy should begin eight to 10 years after the onset of symptoms and be repeated every one to three years. 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. Screening colonoscopy should begin at eight years of age in individuals with Peutz-Jeghers syndrome. If results are normal, colonoscopy can be repeated at 18 years of age and then every three years. Persons with sessile serrated adenomatous polyposis should begin annual colonoscopy as soon as the diagnosis is established.

Familial adenomatous polyposis.

Familial adenomatous polyposis represents approximately 1% of all colorectal tumours and is caused by germline mutations in the adenomatous polyposis coli (APC) gene. A 38-year-old lady presented with abdominal pain, diarrhoea and iron deficiency anemia. There was no history of colorectal cancer in the family. Colonoscopy showed hundreds of polyps throughout the colon sparing the rectum, and an ulcerative tumour of the sigmoid colon. The diagnosis was familial adenomatous polyposis (FAP) and adenocarcinoma of the sigmoid colon. Colectomy with ileorectal anastomosis was performed and later on she was given chemotherapy and advice life long surveillance. The patient had one brother and one sister, without clinical symptoms. The brother had a single hyperplastic rectal polyp, while the sister refused colonoscopy. The patient has 2 sons, the elder son had normal colonoscopic findings, and the younger son was also diagnosed as a patient of FAP and referred for colectomy.

Colonoscopy for screening and follow up of patients with a family history of colorectal cancer.

To determine the minimum family history of colorectal cancer (CRC), which justifies colonoscopy and to establish whether further colonic assessment is necessary after a negative screening colonoscopy. A retrospective review of every colonoscopy undertaken for family screening at the Royal Berkshire and Battle Hospitals, Reading between October 1996 and July 2004. Four hundred and thirty-two patients (261 women) with an average age of 48 years (range 14-84) were screened. Three cancers in patients over the age of 60 years and 49 adenomas were found in 37 patients. Twenty three of 281 (8%) patients with a 'low-risk' family history (one in 12 or less lifetime risk of developing CRC) had either a cancer or an adenoma. Eighteen of 151 (12%) patients with a 'high-risk' family history (one in 10 or greater) had a similar positive colonoscopy. Thirteen of 15 patients who had an adenoma aged under 45 years had a high-risk family history. Seventy-three patients subsequently underwent two or more follow-up colonoscopies. There were 22 adenomatous polyps found in 12 patients (16%) at the first screening, nine adenomas in seven patients in the second colonoscopy and four adenomas found in four patients in all subsequent colonoscopies. Patients with a low-risk family history have a similar adenoma pick-up to that of the general population. These patients need not be screened below the age of 50 unless symptomatic. Follow up of low-risk family history (FH) patients with a negative screening colonoscopy is unlikely to be beneficial.

[Effectiveness and costs of screening colonoscopy].

Screening colonoscopy is always indicated when rectosigmoidoscopy reveals an adenoma, since this lesion roughly doubles the patient's risk of contracting colonic cancer. Follow-up should be performed at intervals of about three years after endoscopic removal of all colorectal polyps. Repeated screening examinations are recommended for the following genetic diseases that carry an increased risk of colorectal carcinoma: familial adenomatous polyposis (FAP) and its genetic variant, hereditary non-polyposis colorectal cancer syndrome (HNPCC) and hamartomatous polyposis syndromes (e.g. Peutz-Jeghers). Also in the case of familial "sporadic" carcinoma of the colon, regular screening colonoscopies for first degree relatives are recommended. Although the use of regular screening colonoscopies in patients with a long history of extensive ulcerative colitis is controversial, the recent results support such examinations. While the benefit of screening colonoscopy or sigmoidoscopy of the general population from the age of 50 onward must be affirmed, it should be weighed against the costs involved in such an undertaking. At the present time, the American Cancer Society recommends that from the age of 50 onward, the annual fecal test for occult blood should be supplemented by sigmoidoscopy performed every three to five years.

Colorectal polyp

Several genes have been associated with polyposis, such as GREM1, MSH3, MLH3, NTHL1, RNF43 and RPS20. Familial adenomatous polyposis Familial adenomatous polyposis (FAP) is a form of hereditary cancer syndrome involving the APC gene located on chromosome q521. The syndrome was first described in 1863 by Virchow on a 15-year-old boy with multiple polyps in his colon. The syndrome involves development of multiple polyps at an early age and those left untreated will all eventually develop cancer. The gene is expressed 100% in those with the mutation and it is autosomal dominant. 10% to 20% of patients have negative family history and acquire the syndrome from spontaneous germline mutation. The average age of newly diagnosed patient is 29 and the average age of newly discovered colorectal cancer is 39. It is recommended that those affected undergo colorectal cancer screening at younger age with treatment and prevention are surgical with removal of affected tissues.

[Value of screening of familial adenomatous polyposis for the prevention of colorectal cancer].

Familial adenomatous polyposis coli is a hereditary autosomal dominant disease which spontaneously and inevitably leads to degeneration of colorectal adenomas and requires preventive surgical treatment. The aim of this study was to evaluate the age of colorectal degeneration and the need for a screening technique in family members. Between 1983 and 1989, 141 patients were treated for familial adenomatous polyposis in our surgical center. Mean age at surgery was 32 years and 64 patients (45.4 percent) had a colorectal carcinoma. Thirty had an in situ tumor (mean age: 30 years) and 34 had an invasive adenocarcinoma (mean age: 45 years), 7 of whom died of their cancer. No colonic cancer was found in patients younger than 20. Thirty-eight percent of the patients under 40 years of age, 73 percent of the patients older than 40 years and 81 percent of those older than 50 had an adenocarcinoma. Fifty percent of the patients with carcinoma were younger than 40 years and 7 percent were less than 25 years old. Seventy-one patients were symptomatic at the time of operation (mean age: 40 years), 32 (45 percent) had a colonic cancer. In 70 patients, familial adenomatous polyposis was detected by screening (mean age: 24) and 2.8 percent had a colonic carcinoma. We conclude that the age-related risk of developing colonic carcinoma requires prophylactic surgery in asymptomatic patients before 20 years of age, and that routine familial screening would be of some benefit.

Failure to diagnose hereditary colorectal cancer and its medicolegal implications: a hereditary nonpolyposis colorectal cancer case.

We describe a patient who had precancerous colonic symptoms and a positive family history of multiple occurrences of early-onset colorectal cancer in her first-degree and second-degree relatives consistent with hereditary nonpolyposis colorectal cancer. Hereditary nonpolyposis colorectal cancer diagnosis had not been made before her diagnosis of carcinoma of the cecum with liver metastasis. She died at age 20, leading to litigation. Controversies about standards of care, their malpractice implications, and pertinent legal issues are discussed. Review of the medical and family history was made by the expert witness (HTL) with appropriate documentation of the chronology of symptoms, as derived from depositions. These documents revealed that the patient's mother had repeatedly discussed with the caregivers her concern about the family history of colon cancer and the need for appropriate surveillance. The patient's colonic symptoms progressed for a period of three years. Flexible sigmoidoscopy was performed by a nonphysician. The physician who ordered the procedure considered this appropriate because isolated polyps were reported in the patient's father and paternal uncle, which apparently led him to believe that the diagnosis was familial adenomatous polyposis. During litigation procedures, a pedigree was constructed and found to be consistent with hereditary nonpolyposis colorectal cancer. The case was settled in favor of the plaintiff before trial. It is essential to understand the natural history of hereditary nonpolyposis colorectal cancer, inclusive of the need for surveillance colonoscopy in patients at increased risk by virtue of their position in their family pedigree.

A screening clinic for relatives of patients with colorectal cancer in a district general hospital.

A family cancer screening clinic was set up to screen and counsel subjects at above average risk of developing colorectal cancer. Criteria for referral were one first degree relative under 50 years or two of any age with colorectal cancer. Pedigree information was used to estimate lifetime risks of developing colorectal cancer and offer appropriate screening: colonoscopy for high risks (greater than 1 in 10), faecal occult blood testing for lower risks. One hundred and eleven subjects from 76 families were seen over four years. Forty two families gave a pedigree consistent with dominantly inherited non-polyposis colorectal cancer syndrome (HNPCC). Three subjects from one family were found to have familial adenomatous polyposis. Ninety two colonoscopies yielded 21 patients with polyps (12 had tubular adenomas, including one with early malignant invasion). Thirty three per cent (four of 12) of the tubular adenomas were beyond the reach of a flexible sigmoidoscope. Three hundred and forty two further high risk relatives were identified from the family history.

Villous Adenoma -- Treatment / Management

Average risk (no first-degree relative to colon cancer): Colonoscopy at age 50 No adenoma or carcinoma, repeat in 10 years One to two small (no more than 1 cm) tubular adenomas with low-grade dysplasia, repeat in 5 to 10 years Three to ten adenomas, or a large (at least 1 cm) adenoma, or any adenomas with high-grade dysplasia or villous features, repeat in 3 years. More than ten adenomas on a single exam, repeat within 3 years Increased risk (positive family history in the first-degree relative before age 60, or in two or more first-degree relatives at any age if not a hereditary syndrome) Colonoscopy at age 40, or 10 years before the youngest case in the immediate family (whichever is earlier). Repeat with above surveillance guidelines with the caveat that maximum time between screening should be 5 years. High-risk (hereditary colon cancer/polyposis syndromes): FAP: Annual flexible sigmoidoscopy; if genetically proven FAP, consider colectomy.

Colorectal cancer

Those with a family history in two or more first-degree relatives (such as a parent or sibling) have a two to threefold greater risk of disease and this group accounts for about 20% of all cases. A number of genetic syndromes are also associated with higher rates of colorectal cancer. The most common of these is hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome) which is present in about 3% of people with colorectal cancer. Other syndromes that are strongly associated with colorectal cancer include Gardner syndrome and familial adenomatous polyposis (FAP). For people with these syndromes, cancer almost always occurs and makes up 1% of the cancer cases. A total proctocolectomy may be recommended for people with FAP as a preventive measure due to the high risk of malignancy. Colectomy, removal of the colon, may not suffice as a preventive measure because of the high risk of rectal cancer if the rectum remains. The most common polyposis syndrome affecting the colon is

Serrated polyposis syndrome

First degree relatives of people with SPS are at a higher risk of colorectal cancer and SPS. As such, these individuals should undergo screening with colonoscopy beginning at the earliest of the following: 40 years of age, the age of the youngest diagnosis of SPS in the family, or 10 years younger than the earliest CRC related to SPS. Repeat colonoscopy should be performed at 5 year intervals. Prognosis The overall risk of colorectal cancer is about 19.9%. However, the risk of cancer varies widely and depends on age, polyp burden, phenotype and the presence of dysplasia on histology. Endoscopic surveillance can decrease the risk of progression to cancer.

Colonoscopy -- Indications

Patients with a high risk of developing colorectal cancer receive the screening procedure before the age of 50 years, and it is repeated every 1, 2, or 5 years based upon the primary risk and findings during the procedure. Examples of high-risk populations include a history of inflammatory bowel disease, a family history of colorectal cancer at age <60 years, hereditary polyposis (Such as Peutz Jegher syndrome and Familial Adenomatous Polyposis, caused by an APC gene mutation) and non-polyposis syndromes (LYNCH I and II), and surveillance after resection of colorectal cancer. Individuals with first degree relatives diagnosed with colon cancer are encouraged to undergo their first colonoscopy at age 40, or 10 years prior to the age the relative was diagnosed, whichever comes first. Elective colonoscopy is performed for reasons such as known or occult gastrointestinal bleeding or stool positive for occult blood, unexplained changes in bowel habits, patterns, iron deficiency anemia or weight loss in elderly patients, persistent abdominal pain, suspected inflammatory or infectious colitis and barium enema showing radiographic structural abnormalities.

Familial adenomatous polyposis in children younger than age ten years: a multidisciplinary clinic experience.

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. 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. 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. 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.

Management of Portuguese patients with hyperplastic polyposis and screening of at-risk first-degree relatives: a contribution for future guidelines based on a clinical study.

Hyperplastic polyposis (HP) is a rare condition characterized by the presence of multiple hyperplastic polyps in the colon, which has been associated to an increased risk of colorectal cancer (CRC). Guidelines for management of this disease remain, so far, undefined. To evaluate, in symptomatic patients with HP, phenotypic characteristics as well as results of a screening program in their at-risk first-degree relatives. Pedigree information and clinical and endoscopic data of 14 patients with HP was studied. SEVENTEEN AND METHODS: at-risk first-degree relatives from six families were also invited to perform screening colonoscopy. Twelve of fourteen (86%) patients had fewer than 100 colorectal polyps. Polyps' sizes ranged from 2 to 25 mm and were uniformly distributed through the whole colon in 43% of the patients. Hyperplastic polyps predominated, but 11/14 (79%) patients also harbored serrated as well as classic adenomatous polyps. CRC was present in 6/14 (43%) of the patients at the time of diagnosis. Familial history of CRC/polyps was positive in 6/12 (50%) of cases. Colonoscopy in at-risk relatives disclosed polyps in 10/17 (59%) of cases with at least one additional patient having criteria for HP. Although small, this series demonstrates that a high level of suspicion is needed to diagnose the HP syndrome, in which serrated adenomas seem to be the hallmark. Although an elevated percentage of CRC was observed in this series of symptomatic patients with HP, prospective studies in asymptomatic individuals are needed to clearly quantify the risk of CRC in patients with HP. Because familial aggregation of HP was present in 3/12 (25%) of kindreds, screening colonoscopy should be offered to first-degree relatives.

The natural history of familial adenomatous polyposis syndrome: a 24 year review of a single center experience in screening, diagnosis, and outcomes.

Understanding the natural history of Familial Adenomatous Polyposis (FAP) will guide screening and aid clinical management. Patients with FAP, age ≤20years presenting between 1987 and 2011, were reviewed for presentation, diagnosis, extraintestinal manifestations, polyp burden, family history, histology, gene mutation, surgical intervention, and outcome. One hundred sixty-three FAP patients were identified. Diagnosis was made by colonoscopy (69%) or genetic screening (25%) at mean age of 12.5years. Most children (58%) were asymptomatic and diagnosed via screening due to family history. Rectal bleeding was the most common (37%) symptom prompting evaluation. Colon polyps appeared by mean age of 13.4years with >50 polyps at the time of diagnosis in 60%. Cancer was found in 1 colonoscopy biopsy and 5 colectomy specimens. Family history of FAP was known in 85%. 53% had genetic testing, which confirmed APC mutation in 88%. Extraintestinal manifestations included congenital hypertrophy of the retinal pigment epithelium (11.3%), desmoids (10.6%), osteomas (6.7%), epidermal cysts (5.5%), extranumerary teeth (3.7%), papillary thyroid cancer (3.1%), and hepatoblastoma (2.5%). Six patients died secondary to FAP. Clinical presentation and manifestations in pediatric FAP are variable. We suggest an individualized patient-oriented screening algorithm that allows for earlier screening and appropriate management.

Surgery_Schwartz

of first-degree relatives of FAP patients beginning at age 10 to 15 years has been the traditional mainstay of screening. Today, following genetic counseling, APC gene testing may be used to screen family members, pro-viding an APC mutation has been identified. If APC testing is positive in a relative of a patient with a known APC mutation, annual flexible sigmoidoscopy beginning at age 10 to 15 years is done until polyps are identified. If APC testing is negative, the relative can be screened starting at age 50 years per average-risk guidelines. If APC testing is refused or unavailable, or if a mutation cannot be identified, annual flexible sigmoidoscopy beginning at age 10 to 15 years is performed until age 24 years. Screening flexible sigmoidoscopy is then done every 2 years until age 34 years, every 3 years until age 44 years, and then every 3 to 5 years.FAP patients are also at risk for the development of adeno-mas anywhere in the gastrointestinal tract, particularly in the

Colonic adenoma risk in familial colorectal cancer--a study of six extended kindreds.

Most colorectal cancers (CRCs) arise from adenomatous polyps, but the effects of CRC family history on adenoma risk are not well known. This issue is clinically relevant since several medical societies currently recommend earlier and more rigorous colorectal screening for individuals with a strong family history of CRC. Colonoscopies were performed in 236 first-, second-, and third-degree relatives of 40 index CRC cases from six large kindreds selected from a large population database. The kindreds were selected for significantly greater risk of CRCs compared with the overall population. Known hereditary colon cancer syndromes were clinically and genetically excluded. Thirty-seven percent of relatives were found to have adenomas on colonoscopy. The average age of diagnosis for colon cancer was 63 yr and advanced adenomas 56 yr. Independent predictors of adenomatous polyps in the relatives were advancing age (P < 0.0001), male gender (P < 0.001), and greater degree of relation to CRC cases (P < 0.01). There was no significant predilection of colorectal tumors for the right or left colon. A higher degree of relationship to CRC cases was a significant predictor of having simple and advanced adenomas, but not hyperplastic polyps after adjustment for age and gender. These data support the current recommendations for colonoscopy starting before the age of 50 yr in individuals with a strong family history of CRC.

Family history of colorectal adenomatous polyps and increased risk for colorectal cancer.

The risk for colorectal cancer among family members of patients with colorectal cancer is well established, but the risk among family members of patients with colorectal adenomas is less well established. To examine the risk for colorectal cancer among first-degree relatives of patients with adenoma compared with that among first-degree relatives of controls without adenoma. Reconstructed cohort study. Three university-based colonoscopy practices in New York City. 1554 first-degree relatives of 244 patients with newly diagnosed adenomas and 2173 first-degree relatives of 362 endoscopically normal controls. Structured interviews were used to obtain family history. Adjusted relative risks (RR) were estimated from Cox proportional hazards regression models. The risk for colorectal cancer was elevated (RR, 1.74 [95% CI, 1.24 to 2.45]) among first-degree relatives of patients with newly diagnosed adenomas compared with the risk among first-degree relatives of controls. This increased risk was the same for parents (RR, 1.58 [CI, 1.07 to 2.34]) and siblings (RR, 1.58 [CI, 0.81 to 3.08]). First-degree relatives of patients with adenomas did not have elevated risk for other cancers. The risk for colorectal cancer among family members increased with decreasing age at diagnosis of adenoma in probands. Among first-degree relatives of patients who were 50 years of age or younger when the adenoma was diagnosed, the risk was more than four times greater (RR, 4.36 [CI, 2.24 to 8.51]) than that among first-degree relatives of patients who were older than 60 years of age when the adenoma was diagnosed. First-degree relatives of patients with newly diagnosed adenomas, particularly of patients who are 50 years of age or younger at diagnosis, are at increased risk for colorectal cancer and should undergo screening similar to that recommended for relatives of patients with colorectal cancer.

What is the appropriate screening protocol in Lynch syndrome?

Lynch syndrome families have a substantial risk of developing colorectal cancer (CRC). The recommended surveillance protocol includes colonoscopy every 2 years from age 20-25 years. It is yet unknown whether annual screening of patients aged 40-60 years is more effective than bi-annual screening, whether patients who had an adenoma removed should be re-examined after a year and whether surveillance of second-degree relatives is indicated. The aim of this study was to address these issues. All carriers of a mismatch repair gene mutation who participated in the surveillance program were selected from the Dutch Lynch syndrome registry. The results of colonoscopy were prospectively collected. A total of 666 mutation carriers were identified in 110 families. Fourty-one CRCs were detected during endoscopic follow-up, of which 34 (83%) were diagnosed between age 40 and 60 years. In five of 34 patients, CRC was diagnosed within 1 year after colonoscopy, eight cancers were diagnosed between 1 and 2 years and the remaining tumors more than 2 years after colonoscopy. All eight CRCs detected between 1 and 2 years were at local stage. At least one adenoma was diagnosed at 141 examinations. The risk of developing CRC during follow-up in carriers with an adenoma was similar as in carriers without an adenoma at the previous colonoscopy. 280 parent-child couples with at least one Lynch syndrome-related carcinoma were identified in 110 families. In only 19 (6.8%) of these couples, CRC developed earlier in the child than an Lynch syndrome-associated cancer in the parent. The current surveillance protocol, i.e., bi-annual colonoscopy in first-degree relatives independent of age and endoscopic findings, appears to be appropriate.

Attenuated familial adenomatous polyposis is a form of familial adenomatous polyposis, a cancer syndrome. It is a pre-malignant disease that can develop into colorectal cancer. A patient will have fewer than a hundred polyps located typically in right side of the colon. Cancer might develop as early as the age of five, though typically presents later than classical FAP. See also Familial adenomatous polyposis Birt–Hogg–Dubé syndrome Cowden syndrome Cronkhite–Canada syndrome Juvenile polyposis MUTYH Peutz–Jeghers syndrome References External links Gastrointestinal cancer Hereditary cancers

Familial adenomatous polyposis

Epidemiology 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. Comparison of FAP variants This table compares the different subtypes of FAP:

Screening for familial colorectal cancer: the need for continuing education. A case report.

A 37 year old female patient was diagnosed with sigmoid colon cancer in our clinic five years ago (January 1998). The family history revealed three deaths due to colorectal cancer (maternal grandmother, mother's sister and patient's sister), and the patient's mother had been diagnosed with adenomatous polyps (endoscopically removed). Histopathological diagnosis was moderate / poorly differentiated adenocarcinoma. Resection of sigmoid colon was performed and adjuvant chemotherapy was carried out, with uneventful evolution. The patient was annually followed-up (colonoscopy, abdominal ultrasound, laboratory tests). The last admission was in January 2003. No recurrence or metastases were found. The patient's mother, who was admitted at the same time, had been diagnosed with urinary bladder tumor. Subjects with a personal or family history of colorectal cancer should routinely have a colonoscopy beginning from age 40 or earlier. It is important for such patients to be followed-up closely not only for recurrence or metastases, but also for detection and treatment of a second primary cancer at an early stage

Clinical identification and long-term surveillance of 22 hereditary non-polyposis colon cancer Italian families.

To assess the efficacy of a hereditary non-polyposis colon cancer (HNPCC) identification and surveillance policy. Familial clustering of colorectal cancer (CRC) and extracolonic cancers (ECs) was investigated in 1520 consecutive CRC patients and relatives. HNPCC was identified by Amsterdam criteria, and individuals at risk were offered biennial colonoscopy and other examinations, starting from age 25 years. Twenty-two HNPCC families were identified. The CRC prevalence was 27.8% (121/435), decreasing from 59.4% in the first generation to 24.4% and 8% in the second and third generation, respectively. Twenty-nine patients had multiple CRC and 34 patients (in 12 families) had ECs.A total of 199/331 at-risk individuals accepted surveillance. The mean follow-up was 48+/-32 months. CRCs were detected at first surveillance in four out of 199 surveilled individuals (2%); in two surveilled individuals (1%), three CRCs developed during follow-up. The overall CRC incidence was 7/199 (3.5%) in surveilled individuals and 5/132 (3.7%) in unsurveilled individuals. CRCs were less advanced in surveilled than in unsurveilled patients. Eleven individuals had 22 adenomas (one with high-grade dysplasia). Three individuals had adenomas at first surveillance; two of them and eight more individuals during surveillance. Seven surveilled individuals and six unsurveilled individuals, all belonging to families with a history of EC, had EC during the study period. All patients with CRC detected by surveillance are alive. One of the unsurveilled patients who had CRC died 18 months after the diagnosis. Data confirm the importance of the family history collected in each patient with CRC for identification of HNPCC and support the efficacy of repeated colonoscopies for early diagnosis and prevention of CRC in at-risk members. Reasons for surveillance failure could be an accelerated progression of small adenomas and a lesion missing at colonoscopy. Longer follow-up is required to assess the efficacy of surveillance for EC.

Risk stratification for colorectal cancer and implications for screening.

In addition to the well-recognized syndromes described (FAP, HNPCC) clusters of colorectal cancers occur in families much more often than would be expected by chance. This familial clustering in about 10-20% of colorectal cancers has implications for screening because the immediate family members of a patient with apparent sporadic colorectal cancer have a twofold to threefold increased risk of the disease. The magnitude of the risk depends on the age at diagnosis of the index case, the degree of kinship of the index case to the at-risk case, and the number of affected relatives. In addition to screening the easily identifiable high-risk groups such as FAP and HNPCC, care should be taken to recognize intermediate-risk patients and to provide them with appropriate screening recommendations. Because the molecular basis and the natural history of these intermediate-risk patients are largely unknown, screening recommendations are as yet more empirical. If a person has a first degree relative with colon cancer, average risk colon cancer screening is recommended, but starting at age 40 years. The decreased age is given because the risk at age 40 for those with an affected first-degree relative is similar to the risk at age 50 for the general population. An individual with two first-degree relatives affected with colon cancer or one first-degree relative diagnosed under the age of 60 y should have colonoscopy beginning at age 40, or 10 years younger than the earliest case in the family. Colonoscopy should be repeated every five years if negative. An even stronger family history of colon cancer syndromes of colon cancer should suggest the consideration of one of the inherited syndromes.

Colorectal cancer screening for patients with a family history of colorectal cancer or adenomas.

To review and summarize the recently developed Canadian Association of Gastroenterology screening recommendations for patients with a family history of colorectal cancer (CRC) or adenoma from a family medicine perspective. A systematic review and meta-analysis was performed to synthesize knowledge regarding family history and CRC. The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE were searched with the following MeSH terms: <icolorectal cancers or neoplasms, screen or screening or surveillance,</i and <ifamily or family history.</i Known hereditary syndromes were excluded. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to establish certainty in reviewed evidence. Most recommendations are conditional recommendations with very low-quality evidence. Individuals who have 1 first-degree relative (FDR) with CRC or an advanced adenoma diagnosed at any age are recommended to undergo colonoscopy every 5 to 10 years starting at age 40 to 50 years or 10 years younger than the age at diagnosis of the FDR, although fecal immunochemical testing at an interval of every 1 to 2 years can be used. Individuals with FDRs with non-advanced adenomas or a history of CRC in second-degree relatives should be screened according to average-risk guidelines. Lifestyle modification can statistically significantly decrease risk of CRC and should be considered in all patients. These guidelines acknowledge the many factors that can increase an individual's risk of developing CRC and allow for judgment to be employed depending on the clinical scenario. Lifestyle advice already given to patients for weight, blood pressure, and heart disease management will reduce the risk of CRC if implemented, and this combined with more targeted screening for higher-risk individuals will hopefully be successful in decreasing CRC mortality in Canada.

Colonoscopy

Subsequent rescreenings are then scheduled based on the initial results found, with a five- or ten-year recall being common for colonoscopies that produce normal results. People with a family history of colon cancer are often first screened during their teenage years. Among people who have had an initial colonoscopy that found no polyps, the risk of developing colorectal cancer within five years is extremely low. Therefore, there is no need for those people to have another colonoscopy sooner than five years after the first screening. Some medical societies in the US recommend a screening colonoscopy every 10 years beginning at age 50 for adults without increased risk for colorectal cancer. Research shows that the risk of cancer is low for 10 years if a high-quality colonoscopy does not detect cancer, so tests for this purpose are indicated every ten years.

Colonoscopy surveillance of individuals at risk of familial colorectal cancer.

Individuals with first degree relatives affected with colorectal cancer (CRC) at a young age, or more than one relative affected but who do not fulfil the Amsterdam criteria for a diagnosis of hereditary non-polyposis colon cancer (HNPCC), are believed to be at an increased risk of CRC. However, there is a paucity of prospective data on the potential benefit of colonoscopic surveillance in such groups categorised by empiric family history criteria. We report a prospective study of 448 individuals seeking counselling about their perceived family history of CRC. Following pedigree tracing, verification, and risk assignment by genetic counsellors, colonoscopy was undertaken for those at a moderate or high risk (HNPCC). Those classified as low risk were reassured and discharged without surveillance. Here we report our findings at the prevalence screen in the 176 patients of the 448 assessed who underwent colonoscopy. Fifty three individuals had a family history that met Amsterdam criteria (median age 43 years) and 123 individuals were classed as moderate risk (median age 43 years). No cancers were detected at colonoscopy in any group. Four individuals (8% (95% confidence limits (CL) 0.4-15%)) in the high risk group had an adenoma detected at a median age of 46 years and all four were less than 50 years of age. Five (4% (95% CL 0.6- 8%)) of the moderate risk individuals had an adenoma at a median age of 54 years, two of whom were less than 50 years of age. These findings indicate that the prevalence of significant neoplasia in groups defined by family history is low, particularly in younger age groups. These prospective data call into question the value of colonoscopy before the age of 50 years in moderate risk individuals.

Surgery_Schwartz

history of this disease (average-risk population) is approximately 6%, but rises to 12% if one first-degree relative is affected and to 35% if two first-degree relatives are affected. Age of onset also impacts risk, and a diagnosis before the age of 50 years is associated with a higher incidence in family members. Screening colonoscopy is recommended every 5 years beginning at age 40 years or begin-ning 10 years before the age of the earliest diagnosed patient in the pedigree. While there are no specific genetic abnormalities that are associated with familial colorectal cancer, any of the defects found in either the LOH pathway or MSI pathway may be present in these patients.Prevention: Screening and SurveillanceBecause the majority of colorectal cancers are thought to arise from adenomatous polyps, preventive measures focus on identi-fication and removal of these premalignant lesions. In addition, many cancers are asymptomatic, and screening may detect these tumors at an early and

A scoring system for the strength of a family history of colorectal cancer.

Family history of colorectal cancer is associated with an increased risk for the disease, although there are many combinations of family history that are hard to correlate with risk status. A scoring system for family history of colorectal cancer was designed to make risk more readily quantifiable. A colonoscopy database was used to test the following points system: each first-degree relative with colorectal cancer = 3 points; each second-degree relative with colorectal cancer = 1 point. Families with one or more first-degree relative affected under 50 years of age = an extra 3 points. Families with one or more second-degree relative affected under 50 years of age = an extra 1 point. Families with multiple relatives on the same side of the family = an extra 3 points (first-degree relatives), 1 point (second-degree relatives), or 2 points (first-degree and second-degree relatives). Points were added and categories defined as follows: low risk, 1 to 4 points; medium risk, 5 to 7 points; high risk, 8 to 10 points; very high risk, >10 points. A control group of average-risk patients having screening colonoscopy was used. Categories were compared in number of adenomas, hyperplastic polyps, and cancers. The records of 992 patients were used to test the system. Mean adenomas per patient per group were 0.4 for controls, 1.0 for low risk, 1.0 for medium risk, 1.7 for high risk, and 1.7 for very high risk. Cancers per group were 2 of 196 for controls, 8 of 513 for low risk, 3 of 171 for medium risk, 3 of 84 for high risk, and 1 of 28 for very high risk. The score categories were combined to produce revised risk levels of low (score 1 to 7) and high (>7). Average adenomas per patient in the revised categories were 0.4 (control), 1.0 (low risk), and 1.7 (high risk). The odds ratio of having one to two adenomas was 1.73 (1.19-2.50, 95% confidence limits) in the low-risk group and 2.39 (1.41-4.01) in the high-risk group. Odds ratios for having three or more adenomas were 5.70 (2.44-13.32) in the low-risk group and 10.35 (3.97-26.97) in the high-risk group. In the two-category system proposed here of quantifying familial risk of colorectal cancer, patients having less than 8 points were at low risk and those with 8 or more were at high risk. Surveillance and chemoprevention protocols can be designed through use of these risk categories. A scoring system for family history of colorectal cancer can make risk assessment easier and facilitate both collaborative studies and patient triage into appropriate screening programs.

First-degree relatives of patients with advanced colorectal adenomas have an increased prevalence of colorectal cancer.

The risk of colorectal cancer in relatives of patients with adenomatous colonic polyps is not well defined. This study assessed whether finding colonic neoplasia during screening colonoscopy was related to the family history of colorectal cancer among the participants' parents and siblings. Self-reported family history of colorectal cancer was recorded for all participants in a screening colonoscopy study. The size and location of all polyps were recorded before their removal and histologic examination. Participants were grouped according to the most advanced lesion detected. Three thousand one hundred twenty-one patients underwent complete colonoscopic examination. Subjects with adenomas were more likely to have a family history of colorectal cancer than were subjects without polyps (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.09-1.70). The finding of a small (<1 cm) tubular adenoma as the most advanced lesion was associated with only a modest increase in the OR of colorectal cancer in family members (OR, 1.26; 95% CI, 0.99-1.61), but the presence of an advanced adenoma was associated with a higher OR (OR, 1.62;5% CI, 1.16-2.26). Younger age of adenoma diagnosis was not related to a higher prevalence of a family history of colorectal cancer. Relatives patients with advanced colorectal adenomas have an increased risk of colorectal cancer. Individuals with advanced colorectal adenomas should be counseled about the increased risk of colorectal cancer among their relatives.