Familial Adenomatous Polyposis Registry Research Articles

Identifying factors associated with detection of sessile gastric polyps in patients with familial adenomatous polyposis.

Background and study aims Gastric cancer (GC) is increasingly reported and a leading cause of death in patients with familial adenomatous polyposis (FAP). Identifying features in patients with FAP who harbor sessile gastric polyps, likely precursors to GC, may lead to alterations in endoscopic surveillance in those patients and allow endoscopic intervention to decrease the risk of GC. The aim of this study was to identify demographic and clinical factors in patients with FAP who harbor sessile gastric polyps. Patients and methods We retrospectively compared demographic, clinical, and endoscopic features in consecutive adult patients with FAP who presented for a surveillance endoscopy at a tertiary-care center with a FAP registry who harbor sessile gastric polyps to those without them. Sessile gastric polyps included pyloric gland adenomas, gastric adenomas, hyperplastic polyps, and fundic gland polyps with high-grade dysplasia. We also display the location of germline APC pathogenic variants in patients with and without sessile gastric polyps. Results Eighty patients with FAP were included. Their average age was 48 years and 70 % were male . Nineteen (24 %) had sessile gastric polyps. They were older ( P < 0.03), more likely to have a family history of GC ( P < 0.05), white mucosal patches in the proximal stomach ( P < 0.001), and antral polyps ( P < 0.026) compared to patients without a gastric neoplasm. No difference in Spigelman stage, extra-intestinal manifestations, or surgical history was note. 89 % of patients with a gastric neoplasm had an APC pathogenic variant 5’ to codon 1309. Conclusions Specific demographic, endoscopic, and genotypic features are associated with patients with FAP who harbor sessile gastric polyps. We recommend heightened awareness of these factors when performing endoscopic surveillance of the stomach with resection of gastric neoplasia when identified.

Barriers to thyroid cancer screening with ultrasound in patients with familial adenomatous polyposis

To identify barriers to care in patients with familial adenomatous polyposis (FAP) that have not undergone ultrasound for thyroid cancer (TC) screening. Case series and survey. A study was conducted examining referral patterns for thyroid ultrasound (TUS) in FAP patients for TC screening. Patients with FAP seen at our institution were identified using International Classification of Diseases, Ninth Revision and Tenth Revision codes. Chart review was performed for TUS and the results were recorded. Patients and healthcare providers were surveyed to determine barriers to TUS and opportunities for improvement. Thirteen out of 35 patients surveyed (37%) were told by a healthcare provider that TUS was recommended for TC screening. The incidence for TC in FAP patients ranges from 15 to 12%, whereas the general population risk is 0.02% to 1%. In our series, one patient of 12 (8%) had TC. Barriers to care included poor patient education about the risk of TC in FAP and miscommunication among specialties for referral for TUS. Also, patients enrolled in a FAP registry have improved care, as they are more likely to undergo TUS than those not enrolled. FAP patients are at a higher risk of developing TC. Therefore, it is important for these patients to be informed and follow the recommended guideline to get a baseline TUS for screening as well as receive better patient education about the risk of TC and improved communication among specialties. Additionally, patients enrolled in a FAP registry are more likely to undergo ultrasound for TC screening, so there needs to be more centralized coordination for the multidisciplinary care of this disease. NA Laryngoscope, 129:2436-2441, 2019.

Clinical characteristics and outcomes in familial adenomatous polyposis patients with a long-term treatment of celecoxib: a matched cohort study

Familial adenomatous polyposis (FAP) is a rare genetic disease. Without treatment, FAP patients have a 100% lifetime risk of developing colorectal cancer. This study was conducted to evaluate the effect of celecoxib treatment in prolonging the time to FAP-related events and to document the safety profile of the long-term use of celecoxib (≥6months) in FAP patients. FAP patients receiving celecoxib in routine clinical practice were individually matched with historical/concurrent FAP patients not receiving celecoxib. The study population included patients aged 12years or older registered in national and regional FAP registries in Denmark, the United States, Spain, and Canada. Descriptive statistics were used to summarize dose and duration among celecoxib treated patients. The primary study endpoints, time-to-next-FAP events, were examined with Kaplan-Meier method. Fifty four celecoxib-treated patients were recruited and a matched control was identified for 13 of these patients. The Kaplan-Meier estimated probability of not having a polypectomy 12 and 60months post- ileorectal anastomosis in the celecoxib-treated patients (n=33) was 60.6% and 42.2%, respectively. The estimated probability of not having a polypectomy 6-60months post-ileal pouch-anal anastomosis the celecoxib-treated patients (n=24) was 100%. The median total daily dose of celecoxib was 698.9mg with the majority treated more than 24months. Five celecoxib-treated patients experienced 6 serious adverse events with one of these events (rash) considered related to celecoxib. Long term celecoxib treatment appeared to be well tolerated in FAP patients with or without FAP-related surgeries.

Quality of Life Ten and More Years After Restorative Proctocolectomy for Patients With Familial Adenomatous Polyposis Coli

Few studies on long-term quality of life after restorative proctocolectomy and ileal pouch-anal anastomosis have been published. Most of them survey a mixed patient population of familial adenomatous polyposis and ulcerative colitis. The present study analyzes long-term results more than 10 years after ileal pouch-anal anastomosis for patients with familial adenomatous polyposis, exclusively. One hundred thirty-five patients who underwent ileal pouch-anal anastomosis more than 10 years ago were identified from the prospective familial adenomatous polyposis registry at Heidelberg University hospital. They received the German version of the health-specific Short Form 36 Health Survey and the disease-specific Gastrointestinal Quality of Life Index by mail. To assess the impact of disease-specific factors, 10 questions asking for ability to work, current medication, pouchitis, and extracolonic manifestations of familial adenomatous polyposis were added to the Gastrointestinal Quality of Life Index questionnaire. Among 84 patients who answered the questionnaires the median follow-up was 13.4 years (range, 10.3-23.8 y).The results of the Short Form 36 Health Survey were comparable to a German normative population in all dimensions, whereas the overall score for the Gastrointestinal Quality of Life Index was significantly reduced compared with healthy individuals (111.8 vs 120.8, P = .0014). Carcinoma at the time of ileal pouch-anal anastomosis, desmoid tumors, or duodenal adenomas had no significant influence on quality of life. More than 7 bowel movements during the daytime were found to reduce quality of life significantly (103.5 vs 115, P = .0127). More than 2 defecations per night diminished the score further (101 vs 125, P < .0001). Patients younger than 40 years at the time of ileal pouch-anal anastomosis had significantly better results than older patients (120 vs 109.5, P = .0076). Ileal pouch-anal anastomosis is a safe surgical procedure with a high quality of life comparable to that of a normative population after long-term follow-up of patients with familial adenomatous polyposis.

A Familial Adenomatous Polyposis (FAP) patient education conference and its impact on patients and families

Background Individuals with familial adenomatous polyposis (FAP) require increased lifelong surveillance due to the high risk of colorectal cancer and extracolonic features. Despite the existence of well-established surveillance guidelines, studies have shown that lack of patient knowledge is a major hurdle to adherence. Patient education conferences represent an avenue for patients to obtain disease-specific information directly from experts. There is ap aucity of data addressing the educational needs and characteristics of individuals who attend such conferences and the impact on their FAP-related knowledge. Methods Individuals with FAP identified through the institution’s FAP registry and their family members were invited to attend an educational conference. Adult attendees were provided IRB approved baseline and follow-up surveys as part of their conference packets. The paired surveys were matched through the use of a unique survey identifier and contained items pertaining to demographic and clinical history, FAP knowledge, and effectiveness of the conference and presenters. Results Of the 50 conference attendees, 35 (70%) completed baseline assessments, and 32 (64%) completed the postconference counterpart. Respondents’ median age was 51 (range: 24 72), and 66% were female. Nineteen (54%) indicated that they had FAP, of which 12 (63%) had undergone colorectal surgery. Fundic gland polyps, duodenal polyps, and desmoid tumors were present in 9 (47%), 11 (58%), and 3 (16%) affected participants, respectively. Hepatoblastoma, duodenal cancer, and osteomas were reported in 1 individual each. Regarding surveillance, 14 (74%) and 13 (68%) of the affected respondents received upper and lower GI surveillance at least once every 3 years, respectively. Participants indicated that among healthcare professionals, their primary sources of information on FAP were primary care physicians (n=15), surgeons (n=12) and/or genetic counselors (n=13). Additional sources of information included internet based resources (n=32), print materials (n=22), and/or other individuals familiar with FAP (n=27). Respondents scored on average 69% correct on a 14-item measure of FAP-related knowledge prior to the conference; post-conference responses showed a statistically significant increase in mean scores (mean=77%, p<0.05). Thirty-one of post-conference respondents (97%) agreed or strongly agreed with items affirming conference effectiveness. Most attendees stated that the FAP conference provided them with information critical to informed medical decision making. All respondents stated a desire to attend future FAP conferences.

Fundic Gland Polyp Dysplasia Is Common in Familial Adenomatous Polyposis

Fundic gland polyps (FGPs) are common in familial adenomatous polyposis (FAP) but have been considered nonneoplastic. Gastric carcinoma arises from FGPs in FAP presumably from a dysplasia-carcinoma pathway. Our study examined the prevalence of FGPs and FGP dysplasia in FAP and identified endoscopic or demographic features associated with FGPs and dysplasia. Demographic and endoscopic information were obtained prospectively from 75 consecutive subjects undergoing upper-endoscopic surveillance for FAP. Systematic biopsy specimens of FGPs, normal-appearing fundic mucosa, and antral mucosa for Helicobacter pylori were obtained. Multivariable analysis assessed the association of demographic or endoscopic factors with the presence of FGP or FGP dysplasia. FGPs were detected in 88% of subjects and were dysplastic in 41% (38% low grade, 3% high grade). H pylori infection was rare in subjects with vs without FGPs (1.5% vs 33.3%, P = .005). In the multivariable analysis larger FGP size (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.1-14.4), higher stage of duodenal polyposis (OR, 2.3; 95% CI, 1.2-4.5), and antral gastritis (OR, 11.2; 95% CI, 1.2-103.9) were associated with FGP dysplasia. Exposure to acid-suppressive medications was associated with a marked decrease in dysplastic FGPs (OR, 0.14; 95% CI, 0.03-0.64). The majority of FAP patients have FGPs and nearly half will have dysplastic FGPs. There is an inverse relationship between H pylori and FGPs. FGP dysplasia is associated with larger polyp size, increased severity of duodenal polyposis, and antral gastritis. Acid-suppressive therapy use appears protective against dysplasia in FGPs.

Is Internet Information Adequate to Facilitate Surgical Decision-Making in Familial Adenomatous Polyposis?

Prophylactic surgery decisions are difficult. Supplemental information improves patients' knowledge, promoting active participation in decision-making. Our objective was to examine internet information regarding prophylactic surgery for familial adenomatous polyposis to determine its adequacy in facilitating patient participation in surgical decision-making. We searched the internet for information on surgery for familial adenomatous polyposis, using an intentionally simple strategy to represent patients' searches. We examined the first 50 sites from each search, assessing each for content by using predefined criteria. Every site was evaluated by two investigators (kappa 0.71) by using the DISCERN criteria, a tool for evaluating quality of health information. Search-efficiency was calculated. Searches revealed 307,138 "hits"; 20 sites met inclusion criteria. GOOGLE demonstrated the highest search-efficiency (28 percent). Sites were maintained by general health pages (35 percent), hospitals (30 percent), professional organizations (15 percent), familial adenomatous polyposis registries (10 percent), and government (10 percent). Only 40 percent had been developed and/or updated within two years. Most included basic information regarding risk, symptoms, diagnosis, as well as discussion of familial adenomatous polyposis-associated diseases and surveillance (80-100 percent). Although 90 percent of sites presented surgical treatment options, only 60 percent provided details. Few provided information regarding postoperative bowel function (40 percent), sexual function (20 percent), or fertility (5 percent). Seven (35 percent) were identified as being of "good/excellent" quality. Only four were patient-oriented; variable information was provided. Internet information regarding surgical treatment of familial adenomatous polyposis is sparse, and insufficient to support active patient participation in decision-making. Despite the time and financial commitment required, development of high-quality internet resources may be justified given the lack of adequate patient-oriented information currently available.

Long-Term Follow-Up of Patients With Familial Adenomatous Polyposis Undergoing Pancreaticoduodenal Surgery

Adenomatous polyps and adenocarcinomas of the periampullary region are the most common upper gastrointestinal neoplasms encountered in familial adenomatous polyposis (FAP) patients. Tumors arising from the liver, biliary tract, and pancreas have also been reported. The purpose of this study was to review the clinical outcome of FAP patients after pancreaticoduodenal surgery for periampullary neoplasms. Of the 61 individuals participating in our prospective FAP registry, 8 underwent surgical resection of periampullary neoplasms between 1987 and 1998. The charts of these individuals were reviewed for clinical indications, type of pancreaticoduodenal surgery, postoperative complications, and outcome. Of the 8 patients identified, 7 had pancreaticoduodenectomy and 1 had duodenotomy with ampullectomy. The indications for surgery were periampullary cancer (3), severe dysplasia within a duodenal villous tumor (4), and solid-pseudopapillary tumor of the pancreas (1). At the time of pancreaticoduodenal surgery, patients ranged in age from 29–65 years, and all but one had undergone colorectal surgery, on average 16 years beforehand. Pancreatic ascites after a pylorus-sparing pancreaticoduodenectomy was the only surgical complication. At a median follow-up of 70.5 months (range 37–162), 2 patients had died, neither from their periampullary neoplasm. The patient treated by local excision subsequently developed gastric cancer arising from a polyp and went on to gastrectomy. Another patient developed confluent benign jejunal adenomas just beyond the gastroenteric anastomosis almost 12 years after pancreaticoduodenectomy for severe dysplasia of a duodenal villous adenoma. Pancreaticoduodenectomy is a safe and appropriate surgical option for FAP patients with duodenal villous tumors containing severe dysplasia or carcinoma. Postoperative morbidity was minimal and there was no perioperative mortality. Good long-term prognosis can be expected in completely resected patients although subsequent proliferative and/or neoplastic lesions may still be detected in the gastrointestinal tract with prolonged follow-up. ( J Gastrointest Surg 2002;6:671–675)

The clinical course of intra‐abdominal desmoid tumours in patients with familial adenomatous polyposis

Desmoid tumours are benign growths of fibro-aponeurotic tissue that are rare in the general population but pose problems in patients with familial adenomatous polyposis (FAP). Many reports of patients with desmoid tumours are unhelpful because of small numbers, inclusion of patients with and without FAP, failure to separate tumours in different sites and use of a wide variety of treatment combinations. The purpose of this study was to avoid some of these deficiencies by reviewing the clinical course of a large number of patients, all of whom have intra-abdominal desmoids and FAP. The medical records of patients with intra-abdominal desmoids treated at this institution were identified through the database in the David G. Jagelman FAP Registry and reviewed. Only patients who received all or part of their treatment at the Cleveland Clinic were included. Protocols for desmoid follow up call for periodic measurement of the dimensions of the tumour, either by clinical examination or on computed tomography (CT) scan. The interval between examinations ranges from 3 months to 2 years, depending on the presence of symptoms and the rate at which the tumour is growing. A change in greatest diameter of >50% is deemed significant growth or regression. Seventy patients with intra-abdominal desmoid tumours in the setting of FAP were identified. Mean age at desmoid diagnosis was 31 years; there were 24 men and 46 women. A family history of desmoids was present in 53% of families known to have FAP. Abdominal wall tumours were also present in 18 patients. Most desmoids presented after surgery (53/70) and multiple tumours were found in 24 patients. The commonest presentation of desmoid tumours was as an abdominal mass. One third of patients had no symptoms at presentation. Treatment included surgery (32), medicine (41) chemotherapy (10) and radiation (4). Eleven patients received no treatment. At the time of review 12 patients were dead (11 from desmoids), 15 were symptomatic and 41 asymptomatic. In seven cases the desmoid disappeared, two spontaneously, two after excision, and three after chemotherapy. Thirty-four patients were being treated at the time of review, 29 with sulindac. The outcome in these cases shows that most intra-abdominal desmoid tumours in FAP are indolent mass lesions that may vary a little in size and do not cause serious harm to the patient. Medical treatments are usually ineffective; surgery is at best unwise and at worst the cause of disastrous complications. A small proportion of desmoids grow rapidly and usually lead to the patient's death. For these patients, anti-sarcoma type chemotherapy is the only hope.

Negative genetic test result in familial adenomatous polyposis: clinical screening implications.

The goal of genetic testing is to define individual risk, which in turn may guide clinical management. Thirty-two international familial adenomatous polyposis registries were surveyed regarding their approach to a specific clinical management question. There were 30 respondents. Respondents declared their clinical policy for an at-risk, first-degree relative who undergoes direct mutation analysis and does not have an APC gene mutation known to be present in his or her family. Nineteen of 30 (63.3 percent) registries would discharge this negative APC mutation case from clinical screening. Eleven of 30 (37 percent) registries would maintain clinical screening. Reasons offered for maintaining surveillance included the need for additional confirmation of the APC mutation in two affected relatives, the possibility of sampling error or two different mutations in an affected family, limited prospective data, and patient anxiety. The discrepancy in response to the survey suggests that some clinicians are as yet reluctant to accept fully that predictive genetic analysis is a definitive guide to clinical management in familial adenomatous polyposis. Nevertheless, we believe that use of a predictive gene test for familial adenomatous polyposis should alter management, decrease cost, and reduce psychological trauma for the tested individual. Although the benefit of APC analysis is accepted for the positive gene carrier, the challenge remains to reclassify the negative gene carriers who are no longer at risk for familial adenomatous polyposis.

Combined Molecular and Clinical Approaches for the Identification of Families with Familial Adenomatous Polyposis Coli

Using an interdisciplinary clinical and molecular approach, the authors identified APC germline mutations in families with familial adenomatous polyposis (FAP). Correlation of mutation site with disease manifestation and the impact of molecular data on clinical proceedings were examined. Germline mutations in the APC gene predispose to FAP. Established and proposed genotype-phenotype correlations as well as the influence of mutation site on surgical procedures have been reported. The predictive value of APC mutation analysis for disease manifestation and therapeutic decision making needs to be investigated further. One hundred twenty-three kindreds of the local FAP registry were included in this study. CHRPE phenotype was defined as at least one large characteristic lesion or a total of four lesions in both eyes. APC mutations were identified by protein truncation test and automated DNA sequencing from patient lymphocyte DNA and RNA. APC germline mutations were identified in 85/123 families with FAP. They were located between codons 213 and 1581 of the APC gene and displayed distinct genotype-phenotype correlations. CHRPE status facilitated mutation analysis by discriminating regions of interest within the APC coding region. Severe manifestations of desmoids were restricted to mutations between codons 1444 through 1581. Whereas 91% (75/82) of at-risk persons were excluded as mutation carriers, APC germline mutations were detected before clinical examination in 9% (7/82) of at-risk persons. One patient agreed to endoscopy only after mutation detection. This study supports the feasibility of combined molecular and clinical screening of families with FAP and may provide a guideline for routine presymptomatic molecular diagnostics in a clinical laboratory.

Rectal cancer following colectomy and ileorectal anastomosis for familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) has historically been treated by colectomy and ileorectal anastomosis (IRA). Preservation of the rectum allows the subsequent development of cancer in the rectum. The risk of rectal cancer following ileorectal anastomosis in the Australian population has not been published to date. An audit of the Familial Adenomatous Polyposis Registry of Western Australia was undertaken to assess patients who had undergone colectomy and ileorectal anastomosis. Fifty-five patients ranging in age from 13 to 65 years were studied. Seven patients (13%) developed cancer of the rectum with a median follow-up of 10 years (range: 1-31 years). Median interval to diagnosis of carcinoma of the rectum following colectomy and IRA was 10 years. All patients who developed cancer in the retained rectum had rectal polyps. Colon cancer was present in the initial colectomy specimen in 13 patients (of these, five patients developed rectal cancer). Flat polyps were noted in five patients. Four patients with flat polyps developed cancer of the rectum. Total colectomy and IRA should be considered as part 1 of a staged procedure in the patient with FAP. With the exception of the patient with no evidence of rectal polyps, completion proctectomy should be undertaken within 10 years of the initial colectomy.

Adrenal masses in patients with familial adenomatous polyposis.

The aims of this study were 1) to report the characteristics and the clinical outcome of familial adenomatous polyposis (FAP) patients with adrenal masses in the FAP registry at the Cleveland Clinic Foundation and 2) to estimate the prevalence of adrenal masses detected by computed tomography in FAP patients compared with that expected in a normal population. A retrospective review was undertaken of the FAP registry database at our institution. Only 738 patients treated at the Cleveland Clinic Foundation were included in the study. A meta-analysis was conducted to determine the relative risk of adrenal incidentaloma in this series of FAP patients and in a general population as reported in the four largest pertinent studies published in the past 15 years. Fifteen patients (11 females) were identified. Two patients had symptoms related to cortisol hypersecretion (arterial hypertension) and underwent surgery. The final pathology was adrenocortical carcinoma and bilateral nodular hyperplasia. Adrenal masses were found incidentally (incidentalomas) in 13 patients: 12 were detected by computed tomography and one during laparotomy for total abdominal colectomy. Only one patient underwent left adrenalectomy for a 5-cm mass. Pathologic report revealed adrenocortical adenoma. Among the 738 patients considered in this study, only 162 underwent abdominal computed tomographic scan, mainly for assessing intra-abdominal desmoid. The prevalence of incidentaloma in our series compared with that reported in the literature is significantly different (7.4 vs. 0.6-3.4 percent; P < 0.001 (chi-squared test)). Although the presence of other extracolonic manifestations represents a selection bias for computed tomographic study in our series, the incidence of incidentalomas in FAP patients seems to be higher than in a general population. However, incidental detection of an adrenal mass in FAP patients has probably a limited clinical relevance, and the management should be the same as that for the normal population.

Molecular Diagnosis of Familial Adenomatous Polyposis

Familial adenomatous polyposis is an inherited disease characterized by multiple colorectal tumors. The diagnosis has classically been based on the detection of multiple colorectal adenomas. The recent identification of germline mutations of the APC gene in patients with familial adenomatous polyposis makes presymptomatic molecular diagnosis possible, but the widespread distribution of the many mutations within this very large gene have heretofore made the search for such mutations impractical. We describe a novel approach that allows molecular genetic diagnosis in the majority of patients with the disease. We screened 62 unrelated patients from the Johns Hopkins Familial Adenomatous Polyposis Registry for germline APC mutations. Primary screening was accomplished by analysis of protein synthesized in vitro from surrogate APC genes. In addition, the relative amount of transcript from each APC allele was determined with an allele-specific--expression assay. The protein assay revealed truncated protein in 51 of the 62 patients (82 percent). In 3 of the 11 remaining patients, the allele-specific--expression assay revealed significantly reduced expression of one allele of the APC gene. The use of these two assays in combination successfully identified germline APC mutations in 87 percent of the 62 patients. The protein and allele-specific--expression assays provide a practical and sensitive method for molecular diagnosis of familial adenomatous polyposis. This approach will facilitate care, allowing routine testing of subjects at risk and genetic confirmation of spontaneous mutations.

Systemic cytotoxic chemotherapy and radiation therapy for desmoid in familial adenomatous polyposis.

Forty-two of 416 familial adenomatous polyposis (FAP) patients in the FAP registry at the Cleveland Clinic had desmoid tumors. The role of cytotoxic chemotherapy and radiation therapy in the management of these patients was investigated. Eight intra-abdominal desmoid tumors were treated by systemic cytotoxic chemotherapy. Two had complete remission, and one had partial remission. Five patients died as a result of the desmoid tumor or late complications of chemotherapy. Three intra-abdominal desmoids were treated by radiation therapy with no response. Neither cytotoxic chemotherapy nor radiation therapy is recommended as a first-choice treatment for intra-abdominal desmoid tumors in patients with FAP.

Spontaneous mutation in familial adenomatous polyposis

A retrospective review of the familial adenomatous polyposis registry at the Cleveland Clinic Foundation revealed an incidence of spontaneous mutation in familial adenomatous polyposis (FAP) of 22 percent of family kindreds. These patients were reviewed retrospectively and compared with the total FAP population followed at The Cleveland Clinic Foundation with respect to the onset of disease, the incidence of carcinoma in the resected colon, and incidence of extracolonic manifestations. Review of the characteristics and presentations of these patients suggested that these individuals may harbor a more severe form of FAP. This may be due, in part, to the delay in diagnosis and, therefore, a higher rate of development of colorectal carcinoma and possibly duodenal adenomas. There is also a demonstrable higher rate of extracolonic manifestations of FAP present in this subset of patients. When selecting the initial type of prophylactic colonic resection the surgeon should bear in mind the increased incidence of extracolonic manifestations of the disease in this group of patients and their potential for complications.

Brain tumors in familial adenomatous polyposis

Familial adenomatous polyposis was always believed to be a colonic disease of genetic determination with a high risk of development of cancer of the large bowel. Over the years the list of extracolonic manifestations of this disease, both benign and malignant, has amplified. Brain tumors and, in particular, medulloblastoma have not become recognized as major malignant extracolonic manifestations of familial adenomatous polyposis. They are of particular significance because, unlike most of the other manifestations, they occur prior to or early in the development of the colonic manifestations of this disease. This report documents the investigation of 168 kindreds in The Cleveland Clinic Familial Adenomatous Polyposis Registry in a search for those at-risk individuals who developed brain tumors.