Gastrointestinal polyposis syndromes for the general gastroenterologist
|
|
- Shanon Fitzgerald
- 5 years ago
- Views:
Transcription
1 TRAINING MATTERS CURRICULUM BASED CLINICAL REVIEWS Gastrointestinal polyposis syndromes for the general gastroenterologist Joanna J Hurley, 1,2 Iain Ewing, 3 Julian R Sampson, 2 Sunil Dolwani 1 1 Department of Gastroenterology, University Hospital Llandough, Penarth, UK 2 Insitute of Medical Genetics, Cardiff University, Cardiff, UK 3 Department of Gastroenterology, North Middlesex University Hospital, London, UK Correspondence to Dr Joanna J Hurley, Department of Gastroenterology, University Hospital Llandough, Penlan Road, Penarth CF64 2XX, UK; Joanna.hurley@wales.nhs.uk Received 15 March 2013 Revised 15 May 2013 Accepted 16 May 2013 To cite: Hurley JJ, Ewing I, Sampson JR, et al. Frontline Gastroenterology Published Online First: [ please include Day Month Year] doi: /flgastro ABSTRACT The occurrence of colonic polyps is a common phenomenon; however, where there are numerous adenomas or other polyps, and/or the patient is at a relatively young age, an inheritable form of gastrointestinal polyposis should be considered. Patients can present via different referral routes, for example, at colonoscopy where multiple polyps are detected, following a personal diagnosis of colorectal cancer, or by family screening. This article outlines the important considerations in the diagnosis of a polyposis syndrome and key diagnostic features to consider. It will also describe the underlying genetic factors associated with the common polyposis syndromes, including classical familial adenomatous polyposis (FAP), attenuated FAP, MUTYH-associated adenomatous polyposis, Peutz Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome and serrated polyposis, and the subsequent management of each condition. INTRODUCTION Hereditary gastrointestinal (GI) polyposis syndromes account for about 1% of all cases of colorectal cancer (CRC) and are the most common cause of hereditary colon cancer after hereditary nonpolyposis colon cancer (HNPCC). Recognition and accurate diagnosis are crucial not just because of the risk of developing cancer (both within and outside of the GI tract) and the implications for family members, but because patients will benefit from regular endoscopic surveillance aiming to reduce the risk of cancer development. There are many different clinical entities within the spectrum of the polyposis syndromes, some of which are well characterised clinically and genetically. The current gastroenterology curriculum (box 1) requires that UK trainees must understand the relevance of genetics to clinical practice, knowing the basis of clinical genetics and patterns of inheritance and be able to apply this knowledge to identify the genetic factors underlying disease in individual patients in order to direct appropriate management. However, the polyposis syndromes often present diagnostic difficulties, as the germline mutation may not always be demonstrable, and some forms of colorectal polyposis have no known genetic basis. Presentation can be at any age and the clinical manifestations of each syndrome can vary enormously, even within the same family. The challenge therefore is to achieve a diagnosis based on the available clinical, endoscopic and histological evidence, family history and where appropriate, molecular genetic testing. This article aims to guide the reader through the initial diagnostic considerations in the diagnosis of a patient presenting with multiple colorectal polyps; outlining the key clinical features of the polyposis syndromes and highlighting the subsequent implications in management of patients and their families. IS THIS A POLYPOSIS SYNDROME OR MULTIPLE COLORECTAL POLYPS? The investigation of symptoms such as a change in bowel habits, rectal bleeding or non-specific abdominal complaints may lead to the finding of multiple colorectal polyps at colonoscopy or flexible sigmoidoscopy. 1 The number of polyps required for a diagnosis of polyposis has not been clearly defined; individual diagnostic criteria are described for some of the conditions. Detailed family history is important (and may be the reason for referral for colonoscopy), and there are extraintestinal signs (detailed in box 2) that may indicate the possibility of a polyposis syndrome. Hurley JJ, et al. Frontline Gastroenterology 2013;0:1 9. doi: /flgastro
2 TRAINING MATTERS Downloaded from on February 20, Published by group.bmj.com Box 1 Gastroenterology curriculum 2010 Competency 2.a clinical genetics and epidemiology A trainee should: know the basis of clinical genetics, including both classical and molecular genetics understand the patterns of inheritance of gastrointestinal and liver diseases be aware of the developing understanding of how genetic factors may be important in a growing number of diseases understand how techniques of molecular biology can explain predisposition to disease be able to describe genetic and environmental causes for disease be able to identify genetic and environmental factors underlying disease in individual patients and to advise them accordingly Seeks advice from appropriate specialists, including referral for genetic counselling where appropriate Individually, the syndromes are rare and may show overlapping phenotypes, the polyps may differ morphologically from their sporadic counterparts and two or more different types of polyps may occur in the same patient. 2 However, the majority of conditions can be recognised on the basis of number and distribution of polyps in the GI tract and the histological subtype of polyps. It is important to examine a large enough number of polyps in order to ascertain the predominant type, as more than one polyp type may occur; multiple biopsies of different polyps should be taken. Specialist GI pathologist input should be sought where there are diagnostic uncertainties. In general, a framework for diagnosis is outlined in figure 1. Once a diagnosis is suspected, molecular Box 2 Extraintestinal symptoms in gastrointestinal polyposis syndromes are as follows: Congenital hypertrophy of the retinal pigment epithelium familial adenomatous polyposis (FAP). Perioral pigmentation Peutz Jeghers syndrome. Multiple cutaneous and subcutaneous lipomas FAP. Sebaceous gland tumours (adenoma, epithelioma and carcinoma) MUTYH-associated adenomatous polyposis, FAP. Hepatoblastoma and medulloblastoma FAP. Gardner s syndrome (now regarded as a phenotypic variant of FAP) association of jaw osteomas with sebaceous cysts, particularly of the scalp, and multiple colonic polyps. Dental abnormalities such as supernumerary teeth and multiple epidermoid cysts also occur. genetic testing can be undertaken in the index patient where appropriate. The presence of greater than 100 colorectal adenomatous polyps and dominant inheritance warrants analysis of the adenomatous polyposis coli (APC) gene, and if this fails to detect a mutation, MUTYH should be tested. Where there are adenomas in an apparently sporadic patient and/or in several siblings, molecular genetic analysis begins with the investigation of MUTYH, and if no mutation is detected, then the APC gene should be analysed. 3 Where there are clinically evident cases of familial adenomatous polyposis (FAP), the APC mutation detection rate is 80% to 90%. 4 In patients with attenuated FAP (AFAP), approximately one-third have an APC mutation, one-third an MUTYH mutation and one-third no mutation. 5 However, while demonstration of a mutation provides information for the differential diagnosis, it is not likely to predict the course of the disease in each individual. Tests for other mutations, including the STK11 (LKB1) gene in Peutz Jeghers syndrome, SMAD4 and BMPRIA genes in juvenile polyposis syndrome (JPS) and PTEN in Cowden syndrome, should be performed in a targeted manner and again depend on the clinical and histological features. Identification of a mutation can determine the risk of inheritance (autosomal dominant vs recessive) and allows predictive testing of at-risk asymptomatic individuals. When a germline mutation is identified, mutation-specific testing can be performed for family members, and is usually initiated after discussion of the benefits and disadvantages during individual genetic counselling (figures 2 and 3). FAMILIAL ADENOMATOUS POLYPOSIS FAP is an autosomal dominant disorder caused by a germline mutation in one of the APC alleles located within chromosome region 5q21 22,and occurs in approximately 1/ live births. Fifteen to twenty per cent of FAP cases are de novo, without clinical or genetic evidence of FAP in the parents, with recent studies indicating the presence of mosaicism in approximately 15% of such cases. 6 Multiple (>100) adenomas develop in the colorectum during childhood and adolescence, and there is virtually a 100% lifetime risk of developing CRC. The average age of CRC at diagnosis is 39 years if left untreated. Gastric fundic gland polyps (FGPs) and antral adenomas also occur, but studies show no increased incidence of gastric cancer in Europe. 7 There are also several extraintestinal manifestations, which include congenital hypertrophy of the retinal pigmented epithelium, epidermoid cysts and malignant thyroid, liver and brain tumours. Desmoid tumours, histologically benign tumours of the connective tissue, occur in 10% to 15% and can lead to life-threatening complications due to their size and encroachment onto vital structures. They commonly arise in the abdominal wall and intraabdominally in FAP. The role of surgery is 2 Hurley JJ, et al. Frontline Gastroenterology 2013;0:1 9. doi: /flgastro
3 TRAINING MATTERS Figure 1 Suggested initial management for the patient with suspected gastrointestinal polyposis. controversial, as there is a high recurrence rate. Current first-line treatment is sulindac in combination with tamoxifen, followed by second-line treatment with chemotherapy and radiotherapy if there is no response. However, this is based on evidence from non-randomised, non-controlled studies. 7 Evidence suggests that the risk of developing CRC before the age of 20 years is low, 8 although the presence of symptoms, including rectal bleeding, mucous discharge, loose stools and abdominal or back pain, should prompt urgent endoscopic investigation at any age. Endoscopic surveillance comprises a 2-yearly flexible sigmoidoscopy starting at age years until adenomas are detected. Then, they should undergo annual colonoscopy until colectomy is planned. The treatment of colonic polyposis is surgery usually once florid polyposis has developed. There are no guidelines regarding the exact timing of surgery, but in general, this should occur when large numbers of adenomas develop or where there is high-grade dysplasia. Most patients with classical FAP undergo surgery between ages 15 and 25 years, with the options of a total colectomy with ileorectal anastomosis (IRA) and proctocolectomy with ileal pouch anal anastomosis (IPAA). Figure 2 Multiple sigmoid adenomas in a patient with MUTYH-associated adenomatous polyposis. Figure 3 Large caecal hyperplastic polyp. Hurley JJ, et al. Frontline Gastroenterology 2013;0:1 9. doi: /flgastro
4 TRAINING MATTERS Downloaded from on February 20, Published by group.bmj.com The decision on the type of colorectal surgery depends on many factors, including age, desire to have children and the severity of rectal polyposis, following comprehensive discussion about the available surgical options and the natural history of the condition. If an IRA is performed, patients need endoscopic examination of the rectum every 3 6 months depending on the severity of their rectal polyps. Patients with IPAA may also develop adenomas and possibly cancer in their pouch and require 6 12-month endoscopic follow-up. 7 The duodenum is the second most common site for adenoma development in FAP with duodenal adenomas found in 30% to 70%, and a risk of developing duodenal carcinoma of 5%. 9 Age appears to be the most important risk factor. Data show no association between mutation site and severity of duodenal disease. Surveillance of the upper GI tract is recommended from ages years, with additional use of a side-viewing endoscope to allow detailed examination of the ampulla, as this is a common site for adenomas. The surveillance interval depends on the Spigelman classification, 10 which is outlined in table 1, where points are accumulated for number, size, histology and degree of dysplasia of polyps. Table 2 illustrates the recommended surveillance intervals. Stage I (1 4 points) reflects mild disease, with stage III IV (6 points or more) implying severe duodenal polyposis seen in approximately 20% of patients. There is no consensus on how to treat patients with duodenal polyposis; options include endoscopic and surgical treatments; however, recurrence rates of adenomas following endoscopic treatment (including snare polypectomy, thermal ablation and photodynamic therapy) are in the magnitude of 50% and there is a high rate of complications. Similarly, local surgical treatment (duodenotomy with polypectomy and/or ampullectomy) has a high recurrence rate, but may be of benefit in younger patients with advanced duodenal polyposis in order to postpone major surgery. 11 In patients with stage IV disease found at repeated surveillance procedures, there is an indication for radical prophylactic surgery such as pancreaticoduodenectomy or pancreassparing duodenectomy; however, both carry significant morbidity and mortality. There is an attenuated form of FAP (AFAP) characterised by the development of fewer adenomas and later onset of CRC; years later than in classical FAP. 7 Only a quarter of patients show a known APC mutation. A recent international collaborative study 12 found that the most common extracolonic manifestation was gastroduodenal lesions, but only 12% had duodenal adenomas. They also proposed the following diagnostic criteria for AFAP: (1) a dominant mode of inheritance and (2) 3 99 colorectal adenomas at age 20 years or over. Surveillance with colonoscopy is recommended every 2 years from ages years, as localised right-sided adenoma development has been described in this cohort. Duodenal surveillance and management depend on the severity of the duodenal polyposis. MUTYH-ASSOCIATED ADENOMATOUS POLYPOSIS MUTYH-associated adenomatous polyposis (MAP) is an autosomal recessive disease caused by inherited mutations in the MUTYH gene, the human homologue of the Escherichia coli muty gene, located on the short arm of chromosome 1. The disease was first discovered in 2002 by a research group in Cardiff, Wales. 13 MUTYH is a base excision repair DNA glycosylase that helps protect cells against the mutagenic effects of guanine oxidation. Patients who carry two germline mutations in the MUTYH gene have a predisposition to polyp formation due to an increased rate of somatic APC mutations. 14 Studies have shown biallelic MUTYH mutations in 26% to 29% of patients with polyps, 7 and in these families it is cost effective to perform genetic screening, since 2% of the normal population is heterozygous for an MUTYH mutation; a child of a biallelic mutation carrier has a 1% chance of inheriting two mutated MUTYH alleles. 15 However, the true prevalence of MAP remains unclear, and the phenotypic characteristics are still being determined. The lifetime CRC risk if untreated is approaching 100% (average age of 47 years at diagnosis of CRC), with preponderance for the right side of the colon. It is recommended that colonoscopy surveillance begin at age years at an interval of 2 years. Because of the smaller numbers of adenomas, some patients may be amenable to endoscopic removal of polyps, but if surgery is required then an IRA is appropriate to remove the cancer risk. If rectal polyposis is severe, then an IPAA is indicated. Table 1 polyposis Spigelman classification of the severity of duodenal 1 Point 2 Points 3 Points No. of polyps >20 Polyp size (mm) >10 Histology Tubulous Tubulovillous Villous Dysplasia Mild Moderate Severe Stage 0=0 points; stage I=1 4 points; stage II=5 6 points; stage III=7 8 points; stage IV=9 12 points. Table 2 Recommended upper GI endoscopic surveillance intervals in relation to Spigelman classification Spigelman classification Surveillance interval (years) 0/I 5 II 3 III 1 2 IV Consider surgery GI, gastrointestinal. 4 Hurley JJ, et al. Frontline Gastroenterology 2013;0:1 9. doi: /flgastro
5 TRAINING MATTERS The extracolonic features of MAP include duodenal adenomas (estimated at 17%) and gastric fundal polyps, as well as sebaceous gland adenomas, epitheliomas, ovarian, bladder, skin and breast cancers, but in contrast to FAP, desmoid tumours are rare. Despite the fact that the frequency of duodenal adenomas is less than in FAP, the increases in relative risk and lifetime risk of duodenal cancer ( 5%) are similar. The natural history of duodenal polyposis in MAP is less well defined than that in FAP, as patients who have developed duodenal cancers have done so on a background of no or minimal duodenal polyposis. The current recommendation based on available evidence is that upper GI surveillance should begin at years, following the Spigelman classification; however, limited knowledge about duodenal disease progression raises significant concerns about the subsequent management and further research is required. PEUTZ-JEGHERS SYNDROME P JS is an autosomal dominant hamartomatous polyposis characterised by multiple polyps, particularly in the small bowel (60% to 90%), and associated mucocutaneous pigmentation, especially of the vermilion border of the lips. The incidence is between 1 in and 1 in live births. The polyps are characteristic, but the frequent coexisting synchronous adenomas may lead to delayed or missed diagnosis. In addition, small bowel polyps may show histological pseudo-invasion, which may be mistaken for invasive cancer. 16 Colonic polyps are present, as well as gallbladder, bronchi, bladder and ureteral polyps. Polyp-related symptoms usually begin in childhood in approximately one-third before the age of 10 years and by 20 years in 50% of patients and include GI bleeding, anaemia and abdominal pain due to intussusception, infarction or obstruction. A clinical diagnosis may be made when any one of the following criteria is present: (1) two or more histologically confirmed Peutz Jeghers (PJ) polyps; (2) any number of PJ polyps detected in one individual who has a family history of Peutz Jeghers Syndrome (PJS) in a close relative; (3) characteristic mucocutaneous pigmentation where there is a family history of PJS in a close relative; or (4) any number of PJ polyps in an individual who also have characteristic mucocutaneous pigmentation. Of patients who fulfilled one of these criteria, 94% had a mutation detected for the gene encoding a serine-threonine kinase, STK11 (LKB1), 17 thought to be a tumour suppressor gene. However, its function is complex and as yet not fully clarified, with no demonstrable genotype phenotype correlation. There is a substantial risk of both GI and extra-gi cancers in PJS, but despite a proposed hamartoma adenoma carcinoma pathway, the manner in which cancer arises and the role of the PJS polyp in the development of cancer remain controversial. Oesophageal, gastric, small bowel, colonic, breast, gynaecological, pancreatic and lung cancers can occur, with a cumulative risk of all cancers of 85% by the age of 70 years. Therefore, surveillance protocols in PJS have two main objectives to detect large GI polyps that may cause the GI symptoms described above, which usually occur in childhood and to detect early stage cancer that develops largely in the adult population. Current surveillance protocols are controversial and not evidence based; however, recommendations following a systematic review on the evidence for screening in PJS 16 are summarised in box 3. Endoscopic polypectomy either with upper GI endoscopy, colonoscopy or double-balloon enteroscopy can reduce polyp-related complications rather than reduce cancer risk. In addition, in any patient who undergoes a laparotomy (emergency or elective), intraoperative enteroscopy and clearance of all polyps are recommended to avoid multiple surgical resections and longer term complications of short bowel syndrome. JUVENILE POLYPOSIS SYNDROME JPS affects between 1 in and 1 in and is also inherited in an autosomal dominant manner. It can present in children or adults, usually with rectal bleeding. Solitary juvenile polyps ( JP) (intestinal juvenile-type hamartomatous polyps) are seen in the colorectum of 2% of children and adolescents and usually carry no harm. The polyp number may range from 5 to 200 and coexisting adenomas may occur. JPS can be diagnosed if there are greater than five JP in the colorectum or multiple JP throughout the GI tract or one or more JP and a positive family history of JPS. In 60% of families with a diagnosis confirmed clinically, there are mutations of the SMAD4 or BMPRIA genes; however, sporadic cases can arise. A recently published series found extraintestinal features in 30% of patients, 18 which include cardiac, vascular and cranial abnormalities, cleft palate and polydactyly; and routine cardiovascular examination is an important part of clinical follow-up. Although there is an increased risk of GI cancer, the exact magnitude of risk is yet to be defined, and data are lacking as to whether endoscopic surveillance and Box 3 Summary of recommendations for gastrointestinal (GI) surveillance in PJS: Baseline upper GI endoscopy/colonoscopy at age 8 years. If no polyps detected, continue every 3 years until age 50 years. If no polyps detected, repeat at age 18 years and then 3-yearly until age 50 years. Colonoscopy every 1 2 years after the age of 50 years. Video capsule endoscopy every 3 years from the age of 8 years. Hurley JJ, et al. Frontline Gastroenterology 2013;0:1 9. doi: /flgastro
6 TRAINING MATTERS Downloaded from on February 20, Published by group.bmj.com polypectomy prevent cancer. After review of all surveillance procedures and outcomes in JPS patients, St Marks Polyposis Registry 18 suggests upper GI endoscopy and lower GI endoscopy 1 3-yearly according to severity from age 12 years. In the setting of a carpet of polyps, surgical intervention should be considered. SMAD4 mutations are associated with a severe gastric polyposis and cancer, but currently, there is not enough evidence available to support mutation-guided surveillance intervals. COWDEN SYNDROME This is an autosomal dominant condition, where there is a germline mutation of the PTEN gene on chromosome 10q23. Oral and cutaneous hamartomas, thyroid, breast and endometrial tumours, autoimmune thyroiditis, macrocephaly and mental retardation are documented manifestations. GI polyposis is common and can occur throughout the entire tract; however, the frequency of colon involvement is unclear. Hamartomatous colon polyps, which can histologically resemble juvenile or Peutz Jeghers polyps, are thought to predominate. However, a wide variety of other polyp types have been described, including adenomas, inflammatory, hyperplastic, lymphoid, ganglioneuromatous and leiomyomatous polyps. Traditionally, these polyps were believed to have a very low rate of malignant potential; however, evidence is growing that patients with Cowden syndrome are indeed at increased risk of colorectal neoplasm. In a recent series of 13 patients, two were diagnosed as having CRC. 19 No consensus recommendations are available for CRC screening, but the authors suggest a baseline colonoscopy should be carried out at age 35 years until further data are available. SERRATED POLYPOSIS In addition to the classical adenoma carcinoma sequence, a proposed serrated neoplasia pathway describes the progression of serrated polyps (hyperplastic polyps, sessile serrated adenomas and traditional serrated adenomas) to CRC, 20 Previously known as hyperplastic polyposis syndrome, serrated polyposis (SP) reflects the spectrum of serrated lesions not just hyperplastic that have been described in this condition, and is associated with CRC. However, no genetic abnormality has been consistently demonstrated to correlate with the phenotype. The WHO criteria for diagnosis are at least five serrated polyps proximal to the sigmoid colon with two or more of these being >10 mm or any number of serrated polyps proximal to the sigmoid colon in an individual who had a firstdegree relative with SP or >20 serrated polyps of any size but distributed throughout the colon. 21 The optimal treatment and surveillance programme remain undefined. Recently, Rex et al 22 recommended that screening colonoscopy be performed in firstdegree relatives aged 40 years or beginning at an age 10 years younger than the age at diagnosis of the youngest affected relative. They suggest colonoscopy be performed at 5-year intervals or more frequently if polyps are found. Two recent studies have attempted to describe the clinical and pathological features of SP during endoscopic surveillance. In their multicentre study of 77 patients, Boparai et al 23 described a CRC rate of 28.5% at initial lower GI endoscopy, and the calculated cumulative risk of CRC during surveillance was 7% at 5 years (in intact colons). CRC was detected in polyps as small as 4 mm, suggesting removal of all polyps seems advisable. If this is not feasible, surgical resection should be considered. A significant (23%) miss rate of polyps was also noted, suggesting advanced imaging techniques such as chromoendoscopy may be of additional value. Edelstein et al 24 described outcomes in 44 SP patients undergoing surveillance, and described an unrelenting and rapid development of colorectal neoplasia and significant risk of CRC. Also, recurrence of polyps in retained colorectal segments occurred rapidly post segmental colonic resection. Interestingly, no gastroduodenal lesions were found in this study, in contrast to other defined polyposis syndromes. Based on their findings, Edelstein et al have tried to refine the surveillance intervals for SP proposing annual colonoscopy surveillance in patients with intact colons and biannual endoscopic evaluation in retained colorectal segments following segmental colonic resection with removal of polyps at the time of these procedures. Young and Parry 25 recommend surgery when polyps cannot be controlled endoscopically, particularly if adenomatous features are present; in addition to this, Edelstein also suggests that clinicians should consider colectomy when sessile serrated adenomas, traditional serrated adenomas or adenomas are encountered in those patients where there are >20 polyps of any size throughout the colon. Although traditionally thought to be a rare condition, estimated at 1:3000 to 1: , the Oxford (English) Bowel Cancer Screening Programme population has reported a high prevalence of SP of 0.66%, a 20-fold increase compared with the estimated rate in the general population. 26 It is important to ensure cases are not missed and that surveillance is carried out appropriately. FURTHER CONSIDERATIONS FGPs arise in FAP as a result of APC mutation, and if found on upper GI endoscopy should prompt consideration of lower GI investigation to exclude FAP if the patient is under the age of 40 years, has numerous FGPs (although there is no defined number that should warrant further investigation) or where there is dysplasia found after biopsy. Although not a hereditary condition, diffuse GI polyposis (typically hamartomas, but adenomas have been reported) can occur in Cronkhite Canada syndrome. It is associated with 6 Hurley JJ, et al. Frontline Gastroenterology 2013;0:1 9. doi: /flgastro
7 TRAINING MATTERS dystrophic changes in the fingernails, alopecia, cutaneous hyperpigmentation, diarrhoea, weight loss, protein losing enteropathy and abdominal pain. Gastric and CRCs have been reported, but there is currently not enough evidence to suggest an optimal surveillance programme. In approximately half of families, the cause of adenomatous polyposis remains elusive after genetic testing. 2 Multiple colorectal adenomas have also been described in patients with acromegaly and hereditary mixed polyposis syndrome, as well as being synchronous in other polyposis syndromes. Hereditary nonpolyposis CRC (HNPCC, Lynch syndrome) can be considered as a differential diagnosis if there are a very small number of colorectal adenomas present (<30). Although it has been proposed that most patients with multiple adenomas appear to represent the high end of the range of sporadic adenomas, 1 given the numbers of patients with multiple adenomas who test negative for any known mutation, additional adenoma susceptibility genes are likely to exist. The emerging techniques of next-generation sequencing technology aim to provide further opportunities to extend molecular genetic analysis in these cases. There is no genetic testing available for SP, and this remains a clinical diagnosis. Each case of multiple adenomas should be managed appropriately taking into account the endoscopic findings and morbidity of the patients. Currently, following adenoma removal at endoscopy (or surgically), further colonoscopic surveillance is recommended by the British Society of Gastroenterology 27 depending on the size and number of polyps resected. CONCLUSION The more typical the clinical and histological features of the polyposis, the more likely a mutation will be identified. The mutation rate falls significantly when diagnostic criteria are not fulfilled. Adenomas can occur in other polyposis syndromes highlighting the importance of multiple biopsies at endoscopy to elucidate the predominant histological features. The key diagnostic criteria and current recommended surveillance have been described for each condition. The offer of genetic counselling should complement any Figure 4 Duodenal adenoma. diagnosis of a polyposis syndrome, and in particular, predictive testing in conditions where this is possible. Multiple choice questions 1. You receive a letter from a general practitioner (GP) requesting a colonoscopy on a 55-year-old woman, whose sister has been diagnosed with MAP following a colonoscopy in the Bowel Cancer Screening Programme. She is otherwise well; her only past medical history is that of depression and anxiety. Both parents are dead, but did not have any known colorectal disease. Which of the following statements is the most accurate? A. You should organise an urgent colonoscopy for the patient. B. There is a 50% chance this patient also has MAP. C. Presymptomatic genetic testing is indicated for all first-degree relatives. D. Presymptomatic testing should be directly requested by the GP. E. Her past history of depression is not a risk factor for psychological distress in presymptomatic testing. Answer: C Once a germline mutation has been identified, presymptomatic testing becomes available for all family members. The patient does not require any surveillance procedures until a mutation is identified, unless she has symptoms that warrant further investigation. MAP is an autosomal recessive disease, and so she has a 1:4 chance of inheriting the condition (assuming both parents were carriers); she has a 50% chance of being a carrier of the mutation. Presymptomatic testing should be initiated after discussion of all the pros and cons in individual genetic counselling sessions. In particular, poor socioeconomic background, elevated pretest anxiety, lack of information, young age and an individual tendency towards anxiety and depression are known risk factors for psychological distress, although do not preclude presymptomatic genetic testing. 2. A 32-year-old man with FAP attends for duodenal surveillance. The finding of a 10 mm adenoma using a forward-viewing gastroscope in the duodenum is demonstrated in figure 4. The histology report shows a tubulovillous adenoma with low-grade (mild) dysplasia. What further management should you advise? A. He should commence on Celecoxib. B. That he requires a further surveillance upper GI endoscopy in 3 years. C. That he requires a further surveillance upper GI endoscopy in 1 2 years. D. That he requires urgent referral for a pancreaticoduodenectomy. E. Removal of this polyp endoscopically is associated with low complication rates. Hurley JJ, et al. Frontline Gastroenterology 2013;0:1 9. doi: /flgastro
8 TRAINING MATTERS Downloaded from on February 20, Published by group.bmj.com Answer 2: B This is Spigelman stage II disease, and he will need further surveillance in 3 years time. For Spigelman stage 0/Idisease,follow-upisat5years,andforSpigelman stage III disease, this interval is reduced to 1 2 years. In early duodenal disease, the risks of surgery far outweigh the risk of malignant progression, and this is not severe enough to warrant major prophylactic surgery. Cox-2 inhibitors (Celecoxib) are thought to exert an anti-neoplastic effect by inhibiting the prostaglandin-related cellular functions such as angiogenesis and cell proliferation. The use of Celecoxib in duodenal polyposis may be considered justifiable for Spigelman stages III and IV, even though the available evidence is conflicting, especially if patients are young because the endoscopic and surgical treatment options are associated with significant complications and recurrence. They should only be considered in patients with no cardiovascular risk factors until more data are available. There is an increased risk of haemorrhage following endoscopic mucosal resection in the upper GI tract as compared with during colonoscopy. Therefore, patients with only a few small duodenal polyps(spigelmanstagesiandii)whohavealowriskof developing duodenal cancer may only require follow-up and not adenoma eradication. Even for those with Spigelman stage II III polyposis, the high recurrence rates when treated endoscopically, which can be up to 100% in some series, may make it difficult to justify complete adenoma removal. Patients should be counselled as to these complication rates if the aim is to try to achieve local disease control in those with stage II III disease. 3. This 23-year-old man presented via the rapid access rectal bleeding service. At flexible sigmoidoscopy, this polyp was detected in the sigmoid colon, as shown in figure 5. At subsequent colonoscopy, he was found to have five other similar lesions. All of these statements below are accurate, except A. this polyp required a biopsy at the time of flexible sigmoidoscopy B. nearly all cases where these polyps are found have a mutation found on molecular genetic testing C. this polyp does not require endoscopic removal D. a family history should be taken E. predictive gene testing of his 4-year-old son is appropriate if a mutation is found on molecular genetic testing. Answer 3: B This is a hamatomatous juvenile-type polyp, which has presented in a young adult with rectal bleeding. Biopsy may help distinguish it from a sporadic polyp, as syndromic polyps may differ morphologically. In this case, a colonoscopy was helpful in order to ascertain if any other polyps were present. Family history is essential as one of the diagnostic criteria of JPS is any number of JP and a positive family history. In 40% of patients with JPS, there is no known pathological genetic mutation found. St Marks Hospital Polyposis Registry recommends that predictive genetic testing should be considered in at-risk children from the age of 4 years. Although the true cancer risk is not well defined, it has been shown that these polyps become dysplastic and undergo adenomatous change over time, and it seems reasonable that polypectomy should be undertaken to prevent cancer development. Solitary JP can be left alone. 4. The following is true of the cancer risk in FAP: A. Without surgery, the average age of diagnosis is 29 years. B. The risk of thyroid cancer is in the order of 10% to 15% C. First-degree relatives of affected patients require a one off colonoscopy at age 25 years. D. It takes on average years from the first development of adenomas to the development of colorectal malignancy. E. Patients with a mutation at codon 1309 have a milder form of FAP and should undergo total colectomy with IRA. Answer 4: D In FAP left untreated, the average age of CRC development is 39 years, years after the first development of adenomas. The risk of thyroid cancer in FAP is 2% to 3%; however, there is no consensus as to specific surveillance. In first-degree relatives of affected patients (high-risk members), in families where there is a known APC mutation, colonoscopic surveillance should be carried out lifelong because the penetrance of disease is almost 100%. Where there is no known APC mutation, high-risk members should have surveillance continued until age 50 years. Patients who have mutations at codon 1309 have been described to have a severe form of FAP, and an IPAA may be advised due to the risk of developing severe rectal polyposis. Figure 5 Juvenile polyp in the sigmoid colon. Contributors JJH wrote the manuscript. IE reviewed and revised the manuscript. JRS and SD reviewed and gave final approval. Competing interests None. Provenance and peer review Not commissioned; externally peer reviewed. 8 Hurley JJ, et al. Frontline Gastroenterology 2013;0:1 9. doi: /flgastro
9 TRAINING MATTERS REFERENCES 1 Jass JR. Colorectal polyposes: from phenotype to diagnosis. Pathol Res Pract 2008;(204): Spier I, Aretz S. Gastrointestinal polyposis syndromes. Internist (Berl) 2012;53: Tops CMJ, Wijen J, Hes FJ. Introduction to the molecular and clinical genetics of colorectal cancer syndrome. Best Pract Res Clin Gastroenterol 2009;23: Vasen HF, Moslein G, Alonso A, et al. Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer). J Med Genet 2007;44: Neilsen M, Hes FJ, Nagengast FM, et al. Germline mutations in APC and MUTYH are responsible for the majority of families with attenuated familial adenomatous polyposis. Clin Genet 2005;42: Hes FJ, Neilsen M, Bik EC, et al. Somatic APC mosaicism: an underestimated cause of polyposis coli. Gut 2008;57: Vasen HF, Moslein G, Alonso A, et al. Guidelines for the clinical management of familial adenomatous polyposis (FAP). Gut 2008;57: Bussey HJ. Familial polyposis coli. Baltimore: The John Hopkins University Press, Vasen HF, Bulow S, Myrhoj T, et al. Decision analysis in the management of duodenal adenomatosis in familial adenomatous polyposis. Gut 1997;40: Spigelman AD, Williams CB, Talbot IC et al. Upper gastrointestinal cancer in patients with familial adenomatous polyposis (FAP). Lancet 1989;2: Brosens LA, Keller JJ, Offerhaus GJ et al. Prevention and management of duodenal polyps in familial adenomatous polyposis. Gut 2005;54: Knudsen AL, Tomlinson I Bulow et al. Attenuated familial adenomatous polyposis: results from an international collaborative study. Colorectal Disease 2010;12:e Al-Tassan N, Chmiel NH, Maynard J et al. Inherited variants of MYH associated with somatic G:C-T:A mutations in colorectal tumours. Nature Genetics 2002;30: Jones S, Lambert S, Williams GT et al. Increased frequency of the k-ras G12C mutation in MYH polyposis colorectal adenomas. Br J Cancer 2004;90: Neilsen M, Hes FJ, Vasen HF et al. Cost-utility analysis of genetic screening in families of patients with germline MUTHY mutations. BMC Med Genet 2007;8: Beggs AD, Latchford AR, Vasen HF et al. Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut 2010;59: Aretz S, Stienen D, Ulhaas S et al. High proportion of large genomic STK11 deletions in Peutz-Jaghers syndrome. Hum Mutat 50025;26: Latchford AR, Neale K, Phillips RK et al. Juvenile Polyposis syndrome: a study of genotype, phenotype and long term outcome. Dis Colon Rectum 2012;55: Stanich PP, Owens VL, Sweetser S et al. Colonic polyposis and neoplasia in Cowden Syndrome. Mayo Clin Proc 2011;86: Makinen MJ. Colorectal serrated adenocarcinoma. Histopathology 2007;50:131e Snover DC, Ahnen DJ, Burt RW et al. Serrated polyp of the colon and rectum and serrated polyposis. In: Bosman FT, Carneiro F, Hruban RH et al.eds.who classification of tumors of the digestive system. Sterling, VA: Stylus Publishing, Rex DK, Ahnen DJ, Baron JA et al. Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol 2012;107: Boparai KS, Mathus-Vliegen EM, Koornstra JJ et al. Increased colorectal cancer risk during follow-up in patients with hyperplastic polyposis syndrome:a multicentre cohort study. Gut 2010;59: Edelstein DL, Axilbund JE, Hylind LM et al. Serrated polyposis: rapid and relentless development of colorectal neoplasia. Gut 2013;62: Young JP, Parry S. Hyperplastic polyposis syndrome and risk of colorectal cancer. Nat Rev Gastroenterol Hepatol 2010;7: 594e5. 26 Biswas S, Ellis AJ, Guy R et al. High prevalence of hyperplastic polyposis syndrome (serrated polyposis) in the NHS bowel cancer screening programme. Gut 2013;62: Cairns SR, Scholefield JH, Steele RJ et al. Guidelines for colorectal cancer screening and surveillance in moderate and high risk patients. Gut 2010;59: Hurley JJ, et al. Frontline Gastroenterology 2013;0:1 9. doi: /flgastro
10 Gastrointestinal polyposis syndromes for the general gastroenterologist Joanna J Hurley, Iain Ewing, Julian R Sampson and Sunil Dolwani Frontline Gastroenterol published online June 14, 2013 Updated information and services can be found at: References alerting service These include: This article cites 23 articles, 10 of which you can access for free at: #BIBL Receive free alerts when new articles cite this article. Sign up in the box at the top right corner of the online article. Notes To request permissions go to: To order reprints go to: To subscribe to BMJ go to:
Pathology reports, related operative reports and consult letters must be provided with a request for assessment.
Page 1 of 6 Polyposis Syndromes Inherited risk for colorectal cancer is associated with a number of polyposis syndromes (genes), some of which are well-defined and others are less common. Identification
More informationGENETIC MANAGEMENT OF A FAMILY HISTORY OF FAP or MUTYH ASSOCIATED POLYPOSIS. Family Health Clinical Genetics. Clinical Genetics department
GENETIC MANAGEMENT OF A FAMILY HISTORY OF FAP or MUTYH ASSOCIATED POLYPOSIS Full Title of Guideline: Author (include email and role): Division & Speciality: GUIDELINES FOR THE GENETIC MANAGEMENT OF A FAMILY
More informationFamilial Adenomatous Polyposis
Familial Adenomatous Polyposis 1 in 10,000 incidence 100 s to 1000 s of colonic adenomas by teens Cancer risk: colon, gastric, duodenum (periampulla), small bowel, pancreas, papillary thyroid, childhood
More informationClassification of polyposis syndromes two major groups. Adenomatous polyposis syndromes. Hamartomatous polyposis syndromes
Hereditary polyposis syndromes Classification of polyposis syndromes two major groups adenomatous and non-adenomatous polyposis syndromes Adenomatous polyposis syndromes Familial adenomatous polyposis(fap)
More informationFamilial and Hereditary Colon Cancer
Familial and Hereditary Colon Cancer Aasma Shaukat, MD, MPH, FACG, FASGE, FACP GI Section Chief, Minneapolis VAMC Associate Professor, Division of Gastroenterology, Department of Medicine, University of
More informationFamilial and Hereditary Colon Cancer
Familial and Hereditary Colon Cancer Aasma Shaukat, MD, MPH, FACG, FASGE, FACP GI Section Chief, Minneapolis VAMC Associate Professor, Division of Gastroenterology, Department of Medicine, University of
More informationGI Polyp syndromes in children. Screening and surveillance, surgery.
Dr Warren Hyer Consultant Paediatric Gastroenterologist St Mark s Hospital, UK GI Polyp syndromes in children Screening and surveillance, surgery. No conflict of interests to declare Objectives Understand
More informationFor identification, support and follow up related to Familial Gastrointestinal Cancer conditions. South Island Cancer Nurses Network September 2013
For identification, support and follow up related to Familial Gastrointestinal Cancer conditions South Island Cancer Nurses Network September 2013 Who are we? Specialist multidisciplinary team: Nurse coordinators,
More informationPENETRANCE ACTIONABILITY SIGNIFICANCE/BURDEN OF DISEASE NEXT STEPS. YES ( 1 of above) YES (Proceed to Stage II)
Stage I: Binning Dashboard GENE/GENE PANEL: APC ACTIONABILITY 1. Is there a qualifying resource, such as a practice guideline or systematic review, for the genetic condition? 2. Does the practice guideline
More informationHereditary Colorectal Cancer Syndromes Miguel A. Rodriguez-Bigas, MD
Hereditary Colorectal Cancer Syndromes Miguel A. Rodriguez-Bigas, MD Living Beyond Cancer A-Z January 12,2019 Hereditary CRC Syndromes Objectives are to discuss the : Most common Hereditary CRC syndromes
More informationB Base excision repair, in MUTYH-associated polyposis and colorectal cancer, BRAF testing, for hereditary colorectal cancer, 696
Index Note: Page numbers of article titles are in boldface type. A Adenomatous polyposis, familial. See Familial adenomatous polyposis. Anal anastomosis, ileal-pouch, proctocolectomy with, in FAP, 591
More informationCancer Genomics 101. BCCCP 2015 Annual Meeting
Cancer Genomics 101 BCCCP 2015 Annual Meeting Objectives Identify red flags in a person s personal and family medical history that indicate a potential inherited susceptibility to cancer Develop a systematic
More informationcolorectal cancer Colorectal cancer hereditary sporadic Familial 1/12/2018
colorectal cancer Adenocarcinoma of the colon and rectum is the third most common site of new cancer cases and deaths in men (following prostate and lung or bronchus cancer) and women (following breast
More informationColonic Polyp. Najmeh Aletaha. MD
Colonic Polyp Najmeh Aletaha. MD 1 Polyps & classification 2 Colorectal cancer risk factors 3 Pathogenesis 4 Surveillance polyp of the colon refers to a protuberance into the lumen above the surrounding
More informationYES NO UNKNOWN. Stage I: Rule-Out Dashboard ACTIONABILITY PENETRANCE SIGNIFICANCE/BURDEN OF DISEASE NEXT STEPS. YES ( 1 of above)
Stage I: Rule-Out Dashboard GENE/GENE PANEL: SMAD4, BMPR1A DISORDER: Juvenile Polyposis Syndrome HGNC ID: 6670, 1076 OMIM ID: 174900, 175050 ACTIONABILITY PENETRANCE 1. Is there a qualifying resource,
More informationRisk of Colorectal Cancer (CRC) Hereditary Syndromes in GI Cancer GENETIC MALPRACTICE
Identifying the Patient at Risk for an Inherited Syndrome Sapna Syngal, MD, MPH, FACG Director, Gastroenterology Director, Familial GI Program Dana-Farber/Brigham and Women s Cancer Center Associate Professor
More informationACG Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes
ACG Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes Sapna Syngal, MD, MPH, FACG, 1,2,3 Randall E. Brand, MD, FACG, 4 James M. Church, MD, FACG, 5,6,7
More informationOPEN ACCESS TEXTBOOK OF GENERAL SURGERY
OPEN ACCESS TEXTBOOK OF GENERAL SURGERY COLORECTAL POLYPS P Goldberg POLYP A polyp is a localised elevated lesion arising from a epithelial surface. If it has a stalk it is called a pedunculated polyp
More informationColorectal Cancer Syndromes. Barbara Jung, MD AGAF Associate Professor and Chief University of Illinois at Chicago
Colorectal Cancer Syndromes Barbara Jung, MD AGAF Associate Professor and Chief University of Illinois at Chicago Outline Colon cancer General Genetics, Risk, Screening Specific Syndromes, when to suspect,
More informationColonic polyps and colon cancer. Andrew Macpherson Director of Gastroentology University of Bern
Colonic polyps and colon cancer Andrew Macpherson Director of Gastroentology University of Bern Improtance of the problem of colon cancers - Epidemiology Lifetime risk 5% Incidence/10 5 /annum (US Detroit
More informationEndoscopic techniques for surveillance and treatment of FAP
Endoscopic techniques for surveillance and treatment of FAP Evelien Dekker MD PhD Department of Gastroenterology & Hepatology Academic Medical Center Amsterdam The Netherlands FAP: endoscopic surveillance
More informationGI EMERGENCIES Acute Abdominal Pain
GI EMERGENCIES Acute Abdominal Pain Marcia Cruz-Correa, MD, PhD, AGAF. FASGE Associate Professor of Medicine, Biochemistry, Surgery Director Translational Research University of Puerto Rico Comprehensive
More informationHereditary Gastric Cancer
Hereditary Gastric Cancer Dr Bastiaan de Boer Consultant Pathologist Department of Anatomical Pathology PathWest Laboratory Medicine, QE II Medical Centre Clinical Associate Professor School of Pathology
More informationAlberta Colorectal Cancer Screening Program (ACRCSP) Post Polypectomy Surveillance Guidelines
Alberta Colorectal Cancer Screening Program (ACRCSP) Post Polypectomy Surveillance Guidelines June 2013 ACRCSP Post Polypectomy Surveillance Guidelines - 2 TABLE OF CONTENTS Background... 3 Terms, Definitions
More informationBowelGene. How do I know if I am at risk? Families with hereditary bowel cancer generally show one or more of the following clues:
BowelGene BowelGene What is hereditary bowel cancer? Bowel cancer (also known as colorectal cancer) is the fourth most common cancer in the UK. Unfortunately 1 in 19 women and 1 in 14 men will develop
More informationCOLON CANCER GENETICS (FOR SURGEONS) Mark W. Arnold MD Chief, Division of Colon and Rectal Surgery Professor of Surgery The Ohio State University
COLON CANCER GENETICS (FOR SURGEONS) Mark W. Arnold MD Chief, Division of Colon and Rectal Surgery Professor of Surgery The Ohio State University 1. I am a surgeon; of course I have nothing to disclose.
More informationGHUK BowelGene_2017.qxp_Layout 1 22/02/ :22 Page 3 BowelGene
GHUK BowelGene_2017.qxp_Layout 1 22/02/2017 10:22 Page 3 BowelGene BowelGene What is hereditary bowel cancer? Bowel cancer (also known as colorectal cancer) is the fourth most common cancer in the UK.
More informationLIST OF ABBREVIATIONS
Gastroenter oenterology 2005 Royal College of Physicians of Edinburgh Screening and surveillance for upper and lower gastrointestinal cancer JN Plevris Consultant Gastroenterologist and Honorary Senior
More informationHereditary GI tumor syndromes ACG guidelines of genetic testing and management. Dr. med. Henrik Csaba Horváth PhD
Hereditary GI tumor syndromes ACG guidelines of genetic testing and management Dr. med. Henrik Csaba Horváth PhD Genetic testing and management of hereditary GI tumor syndromes June 29, 2016 2 Clinical
More informationColorectal Cancer and Hereditary Colon Cancer Syndromes Carol A. Burke, M.D.
Colorectal Cancer and Hereditary, FACG, FACP Sanford R. Weiss MD Center for Hereditary Colorectal Neoplasia Digestive Disease Institute Cleveland Clinic, Cleveland, Ohio 1 Objectives Review the molecular
More informationCOLON CANCER & GENETICS VERMONT COLORECTAL CANCER SUMMIT NOVEMBER 15, 2014
COLON CANCER & GENETICS VERMONT COLORECTAL CANCER SUMMIT NOVEMBER 15, 2014 WENDY MCKINNON, MS, CGC CERTIFIED GENETIC COUNSELOR FAMILIAL CANCER PROGRAM UNIVERSIT Y OF VERMONT MEDICAL CENTER 1 CHARACTERISTICS
More informationPathology perspective of colonic polyposis syndromes
Pathology perspective of colonic polyposis syndromes When are too many polyps too many? David Schaeffer Head and Consultant Pathologist, Department of Pathology and Laboratory Medicine, Vancouver General
More informationGenetic Testing for Familial Gastrointestinal Cancer Syndromes. C. Richard Boland, MD La Jolla, CA January 21, 2017
Genetic Testing for Familial Gastrointestinal Cancer Syndromes C. Richard Boland, MD La Jolla, CA January 21, 2017 Disclosure Information C. Richard Boland, MD I have no financial relationships to disclose.
More informationFACT SHEET 49. What is meant by a family history of bowel cancer? What is bowel cancer? What causes bowel cancer?
Important points The most important factors that can influence an individual s chance of developing bowel cancer are getting older and having a family history of bowel cancer A family history of bowel
More informationColorectal Neoplasia. Dr. Smita Devani MBChB, MRCP. Consultant Physician and Gastroenterologist Aga Khan University Hospital, Nairobi
Colorectal Neoplasia Dr. Smita Devani MBChB, MRCP Consultant Physician and Gastroenterologist Aga Khan University Hospital, Nairobi Case History BT, 69yr male Caucasian History of rectal bleeding No change
More informationWhat All of Us Should Know About Cancer and Genetics
What All of Us Should Know About Cancer and Genetics Beth A. Pletcher, MD, FAAP, FACMG Associate Professor of Pediatrics UMDNJ- New Jersey Medical School Disclosures I have no relevant financial relationships
More informationResident Seminar Aug 19 th, 2015 Colon: Neoplastic. Scott Rieder Dr. Colquhoun
Resident Seminar Aug 19 th, 2015 Colon: Neoplastic Scott Rieder Dr. Colquhoun Objectives Medical Expert: 1. The biologic basis of colon neoplasia 2. Colon cancer screening (guidelines and evidence) 3.
More informationThe Genetics of Familial Polyposis
The Genetics of Familial Polyposis Thursday, September 24 th 2015 Kara Semotiuk, MS, (C)CGC & Laura Winter, MSc, CGC Genetic Counsellors at the FGICR Familial Polyposis Familial Can run in the family related
More informationDisclosure. Polyps in Pediatrics. Learning Objectives. Case Presentation I. Case Presentation II
Disclosure Polyps in Pediatrics I have no relationships with commercial companies to disclose. Sonal Desai, MD Division of Pediatric Gastroenterology May 31, 2013 Pediatric Grand Rounds Learning Objectives
More informationGenetic Testing for Lynch Syndrome and Other Inherited Colon Cancer Syndromes
Genetic Testing for Lynch Syndrome and Other Inherited Colon Cancer Syndromes Policy Number: 2.04.08 Last Review: 1/2019 Origination: 1/2004 Next Review: 1/2020 Policy Blue Cross and Blue Shield of Kansas
More informationMr Chris Wakeman. General Surgeon University of Otago, Christchurch. 12:15-12:40 Management of Colorectal Cancer
Mr Chris Wakeman General Surgeon University of Otago, Christchurch 12:15-12:40 Management of Colorectal Cancer Bowel cancer Chris Wakeman Colorectal Surgeon Christchurch Sam Simon (Simpsons) Elizabeth
More information27
26 27 28 29 30 31 32 33 34 35 Diagnosis:? Diagnosis: Juvenile Polyposis with BMPR1A Mutation 36 Juvenile Polyposis Syndrome Rare Autosomal Dominant Disorder with Multiple Juvenile Polyps in GI Tract Juvenile
More informationManagement of higher risk of colorectal cancer. Huw Thomas
Management of higher risk of colorectal cancer Huw Thomas Colorectal Cancer 41,000 new cases pa in UK 16,000 deaths pa 60% 5 year survival Adenoma-carcinoma sequence (Morson) Survival vs stage (Dukes)
More informationPrevention of Bowel Cancer: which patients do I send for colonoscopy?
Prevention of Bowel Cancer: which patients do I send for colonoscopy? Dr Chris Groves Consultant Gastroenterologist and Honorary Senior Lecturer St George s Hospital and Medical School Director, SW London
More informationScreening & Surveillance Guidelines
Chapter 2 Screening & Surveillance Guidelines I. Eligibility Coloradans ages 50 and older (average risk) or under 50 at elevated risk for colon cancer (personal or family history) that meet the following
More informationJoint Session with ACOFP and Cancer Treatment Centers of America (CTCA): Cancer Screening: Consensus & Controversies. Ashish Sangal, M.D.
Joint Session with ACOFP and Cancer Treatment Centers of America (CTCA): Cancer Screening: Consensus & Controversies Ashish Sangal, M.D. Cancer Screening: Consensus & Controversies Ashish Sangal, MD Director,
More informationMichele Bettinelli RN Maria Scholz RN Sandra Scolaro RN
Michele Bettinelli RN Maria Scholz RN Sandra Scolaro RN Objectives Define Peutz-Jeghers Syndrome (PJS) Describe the management and treatment of PJS Discuss the patient experience associated with the diagnosis
More informationRazvan I. Arsenescu, MD Assistant Professor of Medicine Division of Digestive Diseases EARLY DETECTION OF COLORECTAL CANCER
Razvan I. Arsenescu, MD Assistant Professor of Medicine Division of Digestive Diseases EARLY DETECTION OF COLORECTAL CANCER Epidemiology of CRC Colorectal cancer (CRC) is a common and lethal disease Environmental
More informationCaring for Patients at Risk for Hereditary Colorectal Cancer
February 05, 2007 By Karen Greco, PhD, RN, ANP [1] About 6% of colorectal cancers are caused by genetic mutations associated with hereditary colorectal cancer syndromes. The most common hereditary cancer
More informationEARLY DETECTION OF COLORECTAL CANCER. Epidemiology of CRC
Razvan I. Arsenescu, MD Assistant Professor of Medicine Division of Digestive Diseases EARLY DETECTION OF COLORECTAL CANCER Epidemiology of CRC Colorectal cancer (CRC) is a common and lethal disease Environmental
More informationColon Cancer Screening & Surveillance. Amit Patel, MD PGY-4 GI Fellow
Colon Cancer Screening & Surveillance Amit Patel, MD PGY-4 GI Fellow Epidemiology CRC incidence and mortality rates vary markedly around the world. Globally, CRC is the third most commonly diagnosed cancer
More informationSerrated Polyps and a Classification of Colorectal Cancer
Serrated Polyps and a Classification of Colorectal Cancer Ian Chandler June 2011 Structure Serrated polyps and cancer Molecular biology The Jass classification The familiar but oversimplified Vogelsteingram
More informationACG Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes
PRACTICE GUIDELINES nature publishing group 223 CME ACG Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes Sapna Sy nga l, MD, M PH, FAC G 1, 2, 3, R and
More informationHEREDITARY COLORECTAL CANCER AND POLYPOSIS SYNDROMES
gastrointestinal tract and abdomen HEREDITARY COLORECTAL CANCER AND POLYPOSIS SYNDROMES Jose G. Guillem, MD, MPH, FACS, and John B. Ammori, MD* The majority of cases of inherited colorectal cancer (CRC)
More informationGeneral Surgery Grand Grounds
General Surgery Grand Grounds University of Colorado Health Sciences Center Case Presentation December 24, 2009 Adam Lackey, PGY-5 J.L. - 2111609 27 YO female with chief complaint of abdominal pain. PMHx:
More informationIndex. Note: Page numbers of article titles are in boldface type.
Index Note: Page numbers of article titles are in boldface type. A Abdominal surgery prior as factor in laparoscopic colorectal surgery, 554 555 Abscess(es) CRC presenting as, 539 540 Adenocarcinoma of
More informationGeneral Session 7: Controversies in Screening and Surveillance in Colorectal Cancer
General Session 7: Controversies in Screening and Surveillance in Colorectal Cancer Complexities of Pathological Assessment: Serrated Polyps/Adenomas Carolyn Compton, MD, PhD Professor of Life Sciences,
More informationDuodenal adenomas Management. Dr Stratis Alexandridis Consultant Gastroenterologist BRI
Duodenal adenomas Management Dr Stratis Alexandridis Consultant Gastroenterologist BRI Introduction Ampullary and non ampullary polyps of the duodenum are diagnosed within and outside genetic syndromes.
More informationSCREENING FOR BOWEL CANCER USING FLEXIBLE SIGMOIDOSCOPY REVIEW APPRAISAL CRITERIA FOR THE UK NATIONAL SCREENING COMMITTEE
SCREENING FOR BOWEL CANCER USING FLEXIBLE SIGMOIDOSCOPY REVIEW APPRAISAL CRITERIA FOR THE UK NATIONAL SCREENING COMMITTEE The Condition 1. The condition should be an important health problem Colorectal
More informationJournal of Pediatric Gastroenterology and Nutrition, Publish Ahead of Print
Journal of Pediatric Gastroenterology and Nutrition, Publish Ahead of Print DOI : 10.1097/MPG.0000000000002247 Management of familial adenomatous polyposis in children and adolescents: Position Paper from
More informationObjectives. Definitions. Colorectal Cancer Screening 5/8/2018. Payam Afshar, MS, MD Kaiser Permanente, San Diego. Colorectal cancer background
Colorectal Cancer Screening Payam Afshar, MS, MD Kaiser Permanente, San Diego Objectives Colorectal cancer background Colorectal cancer screening populations Colorectal cancer screening modalities Colonoscopy
More informationFINAL HISTOLOGICAL DIAGNOSIS: Villo-adenomatous polyp with in-situ-carcinomatous foci (involving both adenomatous and villous component).
SOLITARY VILLO ADENOMATOUS POLYP WITH CARCINOMATOUS CHANGES RECTUM: A Divvya B 1, M. Valluvan 2, Rehana Tippoo 3, P. Viswanathan 4, R. Baskaran 5 HOW TO CITE THIS ARTICLE: Divvya B, M. Valluvan, Rehana
More informationSurveying the Colon; Polyps and Advances in Polypectomy
Surveying the Colon; Polyps and Advances in Polypectomy Educational Objectives Identify classifications of polyps Describe several types of polyps Verbalize rationale for polypectomy Identify risk factors
More informationHyperplastische Polyps Innocent bystanders?
Hyperplastische Polyps Innocent bystanders?? K. Geboes P th l i h O tl dk d Pathologische Ontleedkunde, KULeuven Content Historical Classification Relation Hyperplastic polyps carcinoma The concept cept
More informationHereditary Colorectal Polyposis and Cancer Syndromes: A Primer on Diagnosis and Management
CLINICAL AND SYSTEMATIC S 1509 CME Hereditary Colorectal Polyposis and Cancer Syndromes: A Primer on Diagnosis and Management Pr iyan ka Kant h, M D, M S 1, Jade Grimmett, MS2, 3, Mar j an C hampi ne,
More informationBowel obstruction and tumors
Bowel obstruction and tumors Intestinal Obstruction Obstruction of the GI tract may occur at any level, but the small intestine is most often involved because of its relatively narrow lumen. Causes: Hernias
More informationACG Clinical Guideline: Colorectal Cancer Screening
ACG Clinical Guideline: Colorectal Cancer Screening Douglas K. Rex, MD, FACG 1, David A. Johnson, MD, FACG 2, Joseph C. Anderson, MD 3, Phillip S. Schoenfeld, MD, MSEd, MSc (Epi), FACG 4, Carol A. Burke,
More informationGastric Polyps. Bible class
Gastric Polyps Bible class 29.08.2018 Starting my training in gastroenterology, some decades ago, my first chief always told me that colonoscopy may seem technically more challenging but gastroscopy has
More informationPatologia sistematica V Gastroenterologia Prof. Stefano Fiorucci. Colon polyps. Colorectal cancer
Patologia sistematica V Gastroenterologia Prof. Stefano Fiorucci Colon polyps Colorectal cancer Harrison s Principles of Internal Medicine 18 Ed. 2012 Colorectal cancer 70% Colorectal cancer CRC and colon
More informationContent. Diagnostic approach and clinical management of Lynch Syndrome: guidelines. Terminology. Identification of Lynch Syndrome
of Lynch Syndrome: guidelines 17/03/2009 Content Terminology Lynch Syndrome Presumed Lynch Syndrome Familial Colorectal Cancer Identification of Lynch Syndrome Amsterdam II criteria Revised Bethesda Guidelines
More informationThe Role of the Surgical Pathologist in the Diagnosis of Rare Polyposis Syndromes 1. Lynch Syndrome
The Role of the Surgical Pathologist in the Diagnosis of Rare Polyposis Syndromes Dr Christophe Rosty. Envoi Pathology and University of Queensland, Brisbane, QLD, Australia. Email: c.rosty@uq.edu.au Presented
More informationGenetic testing all you need to know
Genetic testing all you need to know Sue Clark Consultant Colorectal Surgeon, St Mark s Hospital, London, UK. Colorectal cancer Familial 33% Polyposis syndromes
More informationUvA-DARE (Digital Academic Repository) Serrated polyps of the colon and rectum Hazewinkel, Y. Link to publication
UvA-DARE (Digital Academic Repository) Serrated polyps of the colon and rectum Hazewinkel, Y. Link to publication Citation for published version (APA): Hazewinkel, Y. (2014). Serrated polyps of the colon
More informationA Patient s Guide to risk assessment. Hereditary Colorectal Cancer
A Patient s Guide to risk assessment Hereditary Colorectal Cancer Hereditary Cancer Testing: Is it Right for You? Overview of Syndromes This workbook is designed to help you decide if hereditary cancer
More informationWHAT IS A GENE? CHROMOSOME DNA PROTEIN. A gene is made up of DNA. It carries instructions to make proteins.
WHAT IS A GENE? CHROMOSOME E GEN DNA A gene is made up of DNA. It carries instructions to make proteins. The proteins have specific jobs that help your body work normally. PROTEIN 1 WHAT HAPPENS WHEN THERE
More informationFAMILIAL ADENOMATOUS POLYPOSIS (COLORECTAL CANCER) PREFERRED MODEL OF CARE AND CRITERIA FOR REFERENCE CENTRES
FAMILIAL ADENOMATOUS POLYPOSIS (COLORECTAL CANCER) PREFERRED MODEL OF CARE AND CRITERIA FOR REFERENCE CENTRES Coordinator: Alex Kartheuser (Colorectal Surgery, Cliniques universitaires St-Luc, UCL) Authors
More informationClinical UM Guideline
Subject: Guideline #: Current Effective Date: 06/28/2016 Status: Revised Last Review Date: 05/05/2016 Description This document addresses colonoscopy, an endoscopic procedure which allows direct visual
More informationDuring the past decade the genetic etiology of all of. Genetic Testing for Inherited Colon Cancer
GASTROENTEROLOGY 2005;128:1696 1716 Genetic Testing for Inherited Colon Cancer RANDALL BURT*, and DEBORAH W. NEKLASON*, *Huntsman Cancer Institute, Salt Lake City; and Departments of Medicine and Oncological
More informationJOURNAL OF CASE REPORTS 2014;4(2):
JOURNAL OF CASE REPORTS 2014;4(2):395-399 Juvenile Polyposis Syndrome -Two Case Reports Samuel Essoun 1, Jonathan CB Dakubo 2, Antoinette A Bediako-Bowan 2 From the Department of Surgery, 1 Korle Bu Teaching
More informationThe American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Inherited Polyposis Syndromes
CLINICAL PRACTICE GUIDELINES The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Inherited Polyposis Syndromes Daniel Herzig, M.D. Karin Hardimann, M.D.
More informationHST.161 Molecular Biology and Genetics in Modern Medicine Fall 2007
MIT OpenCourseWare http://ocw.mit.edu HST.161 Molecular Biology and Genetics in Modern Medicine Fall 2007 For information about citing these materials or our Terms of Use, visit: http://ocw.mit.edu/terms.
More informationNeoplastic Colon Polyps. Joyce Au SUNY Downstate Grand Rounds, October 18, 2012
Neoplastic Colon Polyps Joyce Au SUNY Downstate Grand Rounds, October 18, 2012 CASE 55M with Hepatitis C, COPD (FEV1=45%), s/p vasectomy, knee surgery Meds: albuterol, flunisolide, mometasone, tiotropium
More informationSummary. Cezary ŁozińskiABDF, Witold KyclerABCDEF. Rep Pract Oncol Radiother, 2007; 12(4):
Rep Pract Oncol Radiother, 2007; 12(4): 201-206 Original Paper Received: 2006.12.19 Accepted: 2007.04.02 Published: 2007.08.31 Authors Contribution: A Study Design B Data Collection C Statistical Analysis
More informationHistorical. Note: The parenthetical numbers in the Clinical Indications section refer to the source documents cited in the References Section below.
Clinical UM Guideline Subject: Colonoscopy Guideline #: CG-SURG-01 Current Effective Date: 01/21/2015 Status: Revised Last Review Date: 05/15/2014 Description Colonoscopy describes the direct visual inspection
More informationInherited colon cancer and other inherited cancer predispositions. Dr Anne De Leener Centre de Génétique Humaine
14.20-15.00 Inherited colon cancer and other inherited cancer predispositions Dr Anne De Leener Centre de Génétique Humaine INHERITED COLORECTAL CANCER (CRC) Colorectal cancer 5% 1% 10% 84% Sporadic Familial
More informationCANCER GENETICS PROVIDER SURVEY
Dear Participant, Previously you agreed to participate in an evaluation of an education program we developed for primary care providers on the topic of cancer genetics. This is an IRB-approved, CDCfunded
More informationGenetic Testing for Lynch Syndrome and Other Inherited Colon Cancer Syndromes
Genetic Testing for Lynch Syndrome and Other Inherited Colon Cancer Syndromes Policy Number: 2.04.08 Last Review: 1/2018 Origination: 1/2004 Next Review: 1/2019 Policy Blue Cross and Blue Shield of Kansas
More informationMEDICAL POLICY SUBJECT: GENETIC TESTING FOR INHERITED SUSCEPTIBILITY TO COLORECTAL CANCER. POLICY NUMBER: CATEGORY: Laboratory Test
MEDICAL POLICY SUBJECT: GENETIC TESTING FOR INHERITED SUSCEPTIBILITY TO COLORECTAL CANCER POLICY NUMBER: 2.02.11 CATEGORY: Laboratory Test EFFECTIVE DATE: 09/16/99 REVISED DATE: 04/19/01, 05/16/02, 06/19/03,
More informationHow common are mutations in the MSH2 gene? 1. Mutations that cause Lynch syndrome are rare found in approximately 1 in 370 individuals.
The gene is a tumor suppressor gene. Tumor suppressor genes slow down cell division, repair DNA mistakes, or tell cells when to die. When they don't work properly, cells can grow out of control, which
More informationThe pathology of hereditary polyposis syndromes
Histopathology 2015, 66, 78 87. DOI: 10.1111/his.12590 REVIEW The pathology of hereditary syndromes Marco Novelli Department of Histopathology, UCLH NHS Foundation Trust, London, UK Novelli M (2015) Histopathology
More informationBUY ONE GENE, GET ONE 30 FREE! G E N E P A N E L T E S T I N G F O R H E R E D I T A R Y C A N C E R : G E T T I N G I T R I G H T THIS COULD BE YOU ONE DAY SOON: Starting out in your new OB/Gyn practice
More informationWHAT IS A GENE? CHROMOSOME DNA PROTEIN. A gene is made up of DNA. It carries instructions to make proteins.
WHAT IS A GENE? CHROMOSOME GENE DNA A gene is made up of DNA. It carries instructions to make proteins. The proteins have specific jobs that help your body work normally. PROTEIN 1 WHAT HAPPENS WHEN THERE
More informationThe molecular genetics of colorectal cancer
1 Department of Gastroenterology, North Middlesex University Hospital, London, UK 2 Institute of Molecular Genetics, Cardiff University 3 Department of Gastroenterology, Queen s Hospital Romford, London,
More informationGenetic Testing for Lynch Syndrome and Inherited Intestinal Polyposis Syndromes
Genetic Testing for Lynch Syndrome and Inherited Intestinal Polyposis Syndromes Policy Number: 2.04.08 Last Review: 1/2014 Origination: 1/2004 Next Review: 1/2015 Policy Blue Cross and Blue Shield of Kansas
More informationHans F. A. Vasen, Ian Tomlinson and Antoni Castells
Clinical management of hereditary colorectal cancer syndromes Hans F. A. Vasen, Ian Tomlinson and Antoni Castells REVIEWS Abstract Hereditary factors are involved in the development of a substantial proportion
More informationThis is the portion of the intestine which lies between the small intestine and the outlet (Anus).
THE COLON This is the portion of the intestine which lies between the small intestine and the outlet (Anus). 3 4 5 This part is responsible for formation of stool. The large intestine (colon- coloured
More informationPolicy Specific Section: Medical Necessity and Investigational / Experimental. October 14, 1998 March 28, 2014
Medical Policy Genetic Testing for Colorectal Cancer Type: Medical Necessity and Investigational / Experimental Policy Specific Section: Laboratory/Pathology Original Policy Date: Effective Date: October
More informationWEO CRC SC Meeting. Barcelona, Spain October 23, 2015
WEO CRC SC Meeting Barcelona, Spain October 23, 2015 Identification of serrated polyposis syndrome in the context of population-based CRC screening programs Evelien Dekker Academic Medical Center Amsterdam,
More informationDetecting and managing hereditary colorectal cancer syndromes in your practice
PERSONALIZING PATIENT CARE CME CREDIT EDUCATIONAL OBJECTIVE: Readers will assess their patients personal and family histories and suspect hereditary colorectal cancer syndromes if red flags are present
More information