Diagnosis Of Familial Adenomatous Polyposis Research Articles

Two Metachronous Neoplasms in the Radiotherapy Fields of a Young Man With Familial Adenomatous Polyposis.

Background: It is recognized that various radiation-induced malignancies often follow childhood radiotherapy. Radiation-induced neoplasms have been shown to occur with increased frequency in syndromes due to mutated tumor suppressor genes. There exist no recommendations for the management of cancer patients with germline APC gene mutations. Preclinical data suggest that APC gene mutations cause enhanced radiosensitivity, but no clinical observations exist that show that patients with this mutation are at higher risk for radiation-induced malignancies. Results: We report the case of a 32-year-old man with a genetic diagnosis of familial adenomatous polyposis (FAP) who initially presented at age 10 with a medulloblastoma treated with radiotherapy and surgery. Radiation-induced papillary thyroid carcinoma followed 13 years later. Finally, radiation-induced soft tissue osteosarcoma occurred with widespread metastasis 20 years thereafter. Conclusions: This is the first report of 2 malignancies in the prior radiotherapy fields of a patient with a genetic diagnosis of FAP. More important, this suggests that APC-defective cells are at an enhanced sensitivity to the carcinogenic effects of radiotherapy compared with APC-proficient cells. This could argue for genetic screening in affected members of these families and for creation of treatment recommendations to more seriously consider the risks of radiation therapy.

A case of pneumatosis cystoides intestinalis mimicking familial adenomatous polyposis

In rare cases the diagnosis of Familial Adenomatous Polyposis (FAP) may not be simple or straightforward. We describe the case of a 54-year man in whom endoscopic and histological features of FAP led to proctocolectomy with ileoanal anastomosis. At anatomical examination, air-filled cystic formations in the submucosa and subserosa of the entire large bowel led to the diagnosis of "Pneumatosis Cystoides Intestinalis", a rare clinical condition featured by the infiltration (or the production) of gas within the intestinal wall. In this case the disease was associated with a long-lasting ingestion of acarbose; as suggested by previous reports, it is possible that gas produced by the fermentation of this unabsorbable carbohydrate penetrates the bowel wall giving origin to cystic formation and to the endoscopic appearance of several polypoid lesions in the large bowel. This report indicates that in rare occasions Pneumatosis Intestinalis can lead to a wrong diagnosis of FAP.

Perinatal Detection of Familial Adenomatous Polyposis

Hepatoblastoma is an uncommon fetal neoplasm that may represent an isolated malignancy or a component of a familial cancer or syndromic diagnosis. A large fetal liver mass was detected on routine ultrasound examination of a 23-year-old woman with thyroid nodules and hypertension. Inferior vena cava compression prompted delivery; postnatal biopsy revealed hepatoblastoma. Maternal thyroid biopsy revealed papillary carcinoma. Neonatal and maternal cytomolecular analysis revealed APC gene disruption at 5q22.2. Pedigree analysis exposed multigenerational colon cancer and thyroid cancer, which in conjunction with genetic testing is consistent with familial adenomatous polyposis. This is a novel means of familial adenomatous polyposis diagnosis. Obstetricians and perinatologists should be alert for familial cancer or syndromic diagnoses presenting as fetal neoplasms.

Dento-osseous anomalies associated to familial adenomatous polyposis mimicking florid cemento-osseous dysplasia

Familial adenomatous polyposis (FAP) is a colorectal cancer syndrome characterized by the development of multiple polyps of the colon and rectum with high risk of malignant transformation. The extraintestinal manifestations such as dento-osseous changes are associated with FAP. This is a case report of a 36-year-old female patient who was referred for dental treatment with the initial diagnosis of florid cemento-osseous dysplasia (FCOD). However, the association of the imaging dento-osseous findings with the medical history confirmed the diagnosis of FAP. The paper illustrates the clinical characteristics and imaging findings associated with FAP, and also discusses misdiagnosis based exclusively on imaging features.

Simultaneous Laparoscopic Subtotal Colectomy and Pancreaticoduodenectomy for Colonic FAP and Ampullary Cancer

Laparoscopic surgery has extended its applications to resection of malignancies with favorable results. We report the first successful simultaneous laparoscopic subtotal colectomy and pancreaticoduodenectomy (PD) in a patient with familial adenomatous polyposis (FAP). A 37-year-old man presented with obstructive jaundice. Gastroscopy and biopsies revealed a large ampullary tubulovillous adenoma with mild dysplasia (Spigelman stage III). A colonoscopy for suspicion of FAP revealed numerous right-sided polyps with left-sided sparing. Computed tomography showed a double duct sign. A simultaneous laparoscopic subtotal colectomy and PD was performed successfully. The operative time was 225 minutes for the colectomy and 390 minutes for the PD. Histology showed an R0 resection of ampullary adenocarcinoma (20 negative nodes) and colonic polyps with low-grade dysplasia. Genetic screening confirmed a diagnosis of FAP. A simultaneous laparoscopic subtotal colectomy and PD in patients with FAP and ampullary neoplasia seems safe with favorable clinical and oncologic outcomes.

MUTYH Associated Polyposis Coli: One Common and One Rare Mutation

A 52-year-old Caucasian male with no significant medical history presented at our Department of Gastroenterology several years ago with vague complaints of abdominal distension, fecal urgency, and occasional hematochezia. There was no abdominal pain or weight loss. Familial history was unremarkable. Digital rectal examination revealed tumor at the tip of the finger, confirmed by rectoscopy as a fragile, non-obstructive lesion surrounded by multiple small polyps. A colonoscopy was performed which showed approximately 100 small sessile or pedunculated polyps throughout the large bowel. At 9 cm from the anal margin a concentric polypoid mass was identified, showing central ulceration. Pathological examination confirmed the presence of an invasive adenocarcinoma with strong CEA immunoreactivity. Biopsies of other polyps disclosed tubulovillous adenomata. Endoscopic ultrasound examination suggested penetration of the cancerous growth into the muscular layer. No metastatic disease was identified by CT examination of the abdomen. Final staging of the rectal tumor was T3N0M0. Considering the numerous polyps visualized by endoscopy, a tentative diagnosis of familial adenomatous polyposis (FAP) was made. In this case, total colectomy is the only curative treatment. Neo-adjuvant chemoradiation therapy was initiated (5-fluorouracil and Mitomycin) to downstage the lesion. Re-evaluation showed a considerable regression of the main rectal lesion, as well as the multiple colonic polyps. A total colectomy was performed with ileo-anal anastomosis and J-pouch construction. The patient is currently in regular follow-up and has no symptoms or signs of recurrent disease. Familial adenomatous polyposis is caused by mutations in the APC gene (adenomatous polyposis coli) located on chromosome 5. To our surprise, we could not identify the most common APC mutations in our patient. Considering the autosomal dominant inheritance of FAP, colonoscopy was also performed in the patient’s three children and found to be negative. In the meantime, his sister was also diagnosed in another hospital with rectal carcinoma and multiple colonic polyps. She was also treated by total colectomy. Taking into account the more recent scientific evidence, a new DNA analysis was performed in our patient. This showed two mutations of the MUTYH gene (Y165C and P391L). In contrast to FAP, MAP (MUTYH associated polyposis) is inherited in an autosomal recessive pattern, providing a solid explanation for the pedigree of our case.

The case of the youngest infant with hepatoblastoma with APC gene mutation

Hepatoblastoma is a rare early malignant liver neoplasm occurring in infants and children. Some cases of hepatoblastoma are associated with genetic conditions such as trisomies of chromosomes 18, Beckwith-Wiedemann syndrome and familial adenomatous polyposis (FAP). The observed increase in the risk of hepatoblastoma in APC (adenomatous polyposis coli) gene mutation carriers is low, not exceeding 1%, which is associated with APC gene mutation located in the region of codons 459-1309, where most mutations identified in families affected by FAP in Poland are found. Tissues obtained from patients with hepatoblastoma but without the diagnosis of FAP show loss of heterozygocity at the locus of APC or MCC (mutated in colorectal cancers) genes. Hepatoblastoma growth is the result of the sequence of changes in genetic material. However, a major role can be ascribed to the Wnt pathway where somatic mutations have been observed in the genes of Bcathenin (CTNNB1, Cathenin (cadherin-associated protein), beta 1.88kD) and AXIN1 (Axis inhibitor 1). We present a case of familial hepatoblastoma in a 3-month-old infant with a constitutional mutation in the APC gene.

Analysis of bacteria from intestinal tract of FAP patients for the presence of APC-like sequences

SummaryBackgroundFamilial adenomatous polyposis (FAP) is a hereditary disease induced by germ-line mutations in the tumor suppressor APC gene. These initiate the early stages of the adenoma-carcinoma sequence in familial, but also in sporadic (in 80% to 90%), colon tumorigenesis. We found the presence of APC-like sequences in bacteria of FAP patients.Material/MethodsWe analyzed bacteria isolated from FAP patients’ rectal swabs. Total bacterial DNA was isolated and analyzed for detection of APC-like sequences using PCR. We also tested DNA homology rate and APC-like protein production.ResultsWe collected blood samples and rectal swabs from patients with confirmed diagnosis of FAP. They were analyzed for presence of sections from exon 15 of the APC gene. Most positive results were found in sections located exactly in the area called the MCR (mutation cluster region), where the highest frequency of APC gene mutations were identified. By sequencing PCR products from bacteria in section F–G together with a patient’s DNA sample and human APC gene, we found a more than 90% DNA homology rate. We also confirmed production of APC-like protein using Western blotting.ConclusionsOur results suggested two hypotheses. The APC-like protein might have same function as a truncated APC product, which is synthesized in most cases of mutations of APC gene in the MCR region in colorectal cancer cells. Alternatively, we can consider the possible existence of horizontal transfer of genetic information between eukaryotic and prokaryotic cells. Our study can be considered as a pilot project. For confirmation of our hypotheses, further research is needed.

Familial Adenomatous Polyposis—Rendering a Diagnosis Based on Recognition of an Unusual Primary Thyroid Neoplasm

It has been well established in the literature that the cribriform-morular variant of papillary thyroid carcinoma (CMVPTC) has been observed with higher frequency in familial adenomatous polyposis (FAP) patients. In the usual setting, patients with FAP are identified based on their germline mutations and the diagnosis of thyroid neoplasm is made after the FAP diagnosis. We herein report a case in which the recognition of a CMVPTC led to the initial diagnosis of FAP. The histological and clinical features of CMVPTC are reviewed with emphasis on its relationship to FAP.

To Divert or Not to Divert

A model could be developed to identify patients who can safely undergo restorative proctocolectomy (RPC) without proximal diversion. Logistic regression analysis was used to identify independent factors favoring omission of ileostomy at the time of RPC. A propensity nomogram was developed and validated using measures of calibration, discrimination, and subgroup analysis. Two tertiary referral centers. A total of 4013 patients undergoing RPC between January 1977 and December 2005 were included in the study sample. The decision to omit loop ileostomy at the time of RPC. After study group exclusions, proximal diversion was performed in 3196 of 3733 patients (85.6%) undergoing RPC; 45.4% of 3733 patients were women. The mean (SD) age at surgery was 37.4 (12.8) years. Ulcerative colitis was the indication for RPC in 2304 patients (61.7%) and familial adenomatous polyposis in 364 patients (9.8%), and a J pouch was performed in 2657 patients (71.2%). The following were found to be associated with ileostomy omission: stapled anastomosis (odds ratio [OR], 6.4), no preoperative corticosteroid use (OR, 3.2), familial adenomatous polyposis diagnosis (OR, 2.6), cancer diagnosis (OR, 3.4), female sex (OR, 1.6), and age at surgery younger than 26 years (OR, 2.1) (P < .01 for all). The model discriminated well (area under the receiver operating characteristic curve, 74.9%), with no significant differences between observed and expected outcomes (P = .49). Omission of proximal diversion demonstrated no significant effect on postoperative adverse events, although it was associated with a 2-day increase in the median length of hospital stay (P < .01). Incorporation of a 5-point nomogram in the preoperative assessment of patients undergoing RPC may aid clinicians in identifying a select group of patients who may be candidates for ileostomy omission during RPC.

A nation‐wide study comparing sporadic and familial adenomatous polyposis‐related desmoid‐type fibromatoses

Desmoid-type fibromatoses are neoplasms of fibroblastic origin, occurring sporadically or associated with familial adenomatous polyposis (FAP) coli. By comparing sporadic and FAP-associated desmoid-type fibromatoses, we tried to identify clinical characteristics, which may indicate FAP. Histopathology data of all Dutch patients with desmoid-type fibromatoses diagnosed between 1999 and 2009 were retrieved from PALGA, the nation-wide network and registry of histopathology in the Netherlands. For calculation of incidence rates, person-years from the general matched population were used. Based on polyp counts in pathological records, the cohort was divided into a FAP group and a non-FAP group. Patient- and tumor characteristics were compared between the two groups. A total number of 519 patients older than 10 years with a confirmed diagnosis of desmoid-type fibromatoses were included. Thirty-nine (7.5%) desmoid patients were documented of having FAP. The incidences of sporadic and FAP-related desmoid-type fibromatoses were 3.42 and 2,784 per million person-years, respectively. The majority of FAP patients developed desmoid-type fibromatoses after the diagnosis of FAP. Having FAP was associated with male gender [odds ratio (OR) 2.0, p = 0.034], desmoid diagnosis at an earlier age (mean 36 vs. 42 years, p = 0.031), and desmoid localization intra-abdominally (OR 18.9, p ≤ 0.001) or in the abdominal wall (OR 4.8, p ≤ 0.001), compared to extra-abdominal desmoid localization. In conclusion, patients with desmoid-type fibromatoses are at risk of underlying FAP. Especially cases with desmoid localization intra-abdominal or in the abdominal wall, and all patients younger than 60 years, have a substantial increased risk and should be referred for colonoscopy.

An Ominous Case of Diarrhea: Familial Adenomatous Polyposis

Purpose: Familial Adenomatous Polyposis (FAP) is an autosomal dominant disease which is caused by a germline mutation in the adenomatous polyposis coli gene (APC) which is located on chromosome 5. It is the most common form of hereditary polyposis syndromes. With an incidence of 1/10000 to 1/30000 live births, FAP diagnosis is based upon the presence of more than 100 adenomatous colorectal polyps. Suggestive symptoms include rectal bleeding, abdominal pain, weight loss and less commonly diarrhea. Case Report: A 24 year old African-American male with no past medical history presented with watery non-bloody diarrhea for two weeks. His family history was significant for colon polyps in his mother (at age 56) and colon cancer in his maternal grandmother (at the age 60). On physical exam, patient was well kempt, moderately built, pale with no skin changes; furthermore, his abdominal examination was unyielding except for a digital rectal examination that was remarkable for guaiac positive stools. Laboratory work-up revealed, hemoglobin of 5.6, MCV of 54 and RDW of 22.4, platelets of 519 along with a peripheral smear showing microcytosis and hypochromia. The iron profile was consistent with severe iron deficiency anemia. The rest of the laboratory values- including ESR, CRP, Chemistry and liver profiles- were within normal limits. His stool studies were completely normal. Subsequently, patient underwent colonoscopy which depicted a large number of polyps scattered throughout the colon. Pathology confirmed the diagnosis of adenomatous polyposis. Patient had an upper endoscopy that showed few fundic polyps and a prominent duodenal papilla. Patient was referred for surgical evaluation for total colectomy. He was advised about the need for regular follow up and endoscopic surveillance; genetic and family counseling were also recommended. Discussion: FAP is an inherited colorectal cancer syndrome and accounts for 1 percent of all cases of colorectal cancer. Patients with FAP develop hundreds to thousands of colon polyps, usually starting in the teens. All patients will develop colorectal cancer by age 40 if left untreated. Extracolonic malignancies are fairly common in FAP with duodenal cancer being the second leading cause of cancer deaths in patients with FAP, once the colon has been removed. Symptoms are quite subtle at times and can be easily missed, especially that the patient population affected by the disease is young and commonly adamant about seeking adequate medical care. Herein, our case highlights that, serious medical disease could present with a subtle and often overlooked symptom like diarrhea.

Familial adenomatous polyposis: mental health, psychosocial functioning and reactions to genetic risk in adolescents

Familial adenomatous polyposis (FAP) in a parent requires diagnostic follow-up and treatment from adolescence in possible gene carriers in order to prevent cancer development. A nationwide sample (n = 22) of adolescent FAP offspring including 85% of eligible individuals aged 11-20 years and their parents were interviewed with regard to adolescent mental health, psychosocial functioning, knowledge about FAP and genetic risk, and experiences with testing and surgery. Thirty-six percent of the FAP offspring fulfilled criteria for a psychiatric diagnosis. For adolescents older than 15 years, this was increased relative to a comparison group with Hirschprung's disease and a general population sample. Neither genetic testing nor FAP diagnosis in adolescent FAP-offspring differentiated significantly between those who fulfilled the criteria and those who did not for psychiatric diagnosis, while a global score of chronic family difficulties did. This may imply that experiencing parental illness more than inheriting FAP is a perceived stressor for adolescent FAP offspring.

Female Fertility After Colorectal Surgery for Familial Adenomatous Polyposis

Information on postoperative fertility problems in female patients with familial adenomatous polyposis (FAP) is scarce. Previous studies in FAP or colitis patients almost uniformly describe a reduction in fertility after ileal pouch-anal anastomosis, compared with ileorectal anastomosis. To describe fertility problems in female FAP patients after colectomy and to investigate the relationship between self-reported fertility problems and the type of operation and other surgery-related factors (eg, comorbid conditions). A questionnaire addressing surgery, fertility problems, and desire to have children was sent to a nationwide sample of FAP patients. Medical data were verified in the FAP-registry of the Netherlands Foundation for the Detection of Hereditary Tumors. Differences between women with and without fertility problems were investigated. Of 138 patients, 23 (17%) reported current or past fertility problems. The prevalence of fertility problems was similar among those who had undergone ileorectal anastomosis, ileal pouch-anal anastomosis, and proctocolectomy with ileostomy. None of the other surgery-related factors, nor desmoid tumors or cancer were associated significantly with the development of fertility problems. Patients reporting fertility problems were significantly younger at diagnosis of FAP (mean, 20 vs. 27 years, P < 0.05) and at the time of the first surgical procedure (mean, 22 vs. 28 years, P < 0.05). The risk of developing postoperative fertility problems is not associated significantly with the type of surgery, indication for surgery, complications, or other comorbid conditions. Postoperative fertility problems are more common among women who had their first surgical procedure at a younger age.

Clinical outcomes of patients with desmoid tumors treated with dacarbazine plus doxorubicin regimen.

e20524 Background: Desmoids are a rare, slow growing, soft-tissue tumors with a locally agressive behavior. These tumors are often unresectable at diagnosis and there is no standard first line chemotherapy. Methods: We present a retrospective review of the outcomes of patients treated with the same regimen comprised by doxorubicin (DOX) 20mg/m2 daily plus dacarbazine (DTIC) 150 mg/m2 daily over four days of drip infusions at a single institution from June 2005 to December 2009. Results: A total of five patients were analyzed. All of them had a diagnosis of familial adenomatous polyposis (FAP). There were three men (60%) and the median age at diagnosis was 30 (range, 18 to 38 years). Four patients had intrabdominal tumors (80%) and were considered unresectable. The protocol DOX plus DTIC was the first line therapy for them. The remaining patient had tumor in abdominal wall and it was resected at diagnosis. This patient received tamoxifen to local relapse that occurred thirty-two months after surgery. In this case, the regimen DOX plus DTIC was used as second line therapy after tamoxifen progression. The median number of cycles was five (range, 3 to 6 cycles). All of the patients seemed to tolerate the chemotherapy well, and none patient showed severe treatment-related toxicity (grade 3 or 4). There were two partial responses and three stable disease. None complete response was observed. All except one were administered meloxicam (10 mg/m2) after chemotherapy. With a median follow-up time of 14,3 months (range, 8.5 to 54 months), only one progression disease occurred at 52 months. Conclusions: In our series of cases, doxorubicin plus dacarbazine was a safe and well tolerated regimen. Despite the low downstaging rates, it seems prolong substantially the time to disease progression in patients with desmoid tumours. No significant financial relationships to disclose.

Allele-Specific Expression of APC in Adenomatous Polyposis Families

Germline mutations in the APC gene cause of most cases of familial adenomatous polyposis (FAP) and a lesser proportion of attenuated FAP (AFAP). Systematic analysis of APC at the RNA level could provide insight into the pathogenicity of identified mutations and the molecular basis of FAP/AFAP in families without identifiable mutations. Here, we analyzed the prevalence of imbalances in the allelic expression of APC in polyposis families with germline mutations in the gene and without detectable mutations in APC and/or MUTYH. Allele-specific expression (ASE) was determined by single nucleotide primer extension using an exon 11 polymorphism as an allele-specific marker. In total, 52 APC-mutation-positive (36 families) and 24 APC/MUTYH-mutation-negative (23 families) informative patients were analyzed. Seventy-six controls also were included. Of the APC-mutation-positive families, most of those in whom the mutation was located before the last exon of the gene (12 of 14) had ASE imbalance, which is consistent with a mechanism of nonsense-mediated decay. Of the APC/MUTYH-mutation-negative families, 2 (9%) had ASE imbalance, which might cause the disease. Normal allele expression was restored shortly after lymphocytes were cultured with puromycin, supporting a 'nonsense-mediated' hypothesis. ASE analysis might be used to determine the pathogenesis of some cases of FAP and AFAP in which APC mutations are not found. ASE also might be used to prioritize the order in which different areas of APC are tested. RNA-level studies are important for the molecular diagnosis of FAP.

Parental attitudes, beliefs, and perceptions about genetic testing for FAP and colorectal cancer surveillance in minors.

Familial adenomatous polyposis (FAP) is the second most common hereditary colorectal cancer syndrome and confers a nearly 100% lifetime risk of developing colorectal cancer. Understanding factors that facilitate and inhibit genetic testing and cancer surveillance in children who are members of families affected by FAP will better equip clinicians to clarify misunderstandings and facilitate appropriate care. The aims of this study were to examine parental attitudes and beliefs regarding endoscopic surveillance and genetic testing in minors at risk for developing FAP. This cross-sectional study includes analyses of qualitative and quantitative interview data collected from parents of children with or at risk for FAP. This report includes data from 28 parents with a total of 51 biological children between 10-17 years of age. The parents had a clinical and/or genetic diagnosis of FAP. Most commonly reported facilitators included provider recommendation (surveillance) and personalized medical management (genetic testing). Most commonly reported barriers included lack of provider recommendation (surveillance) and cost (genetic testing).

Ileal pouch adenocarcinoma after proctocolectomy for familial adenomatous polyposis

Dear Editor: Familial adenomatous polyposis (FAP) is an inherited disease characterized by the development of hundreds of colorectal adenomas, leading to a 100% lifetime risk of colorectal cancer. Thus, a prophylatic proctocolectomy is recommended for patients with FAP to prevent colorectal cancer. Four surgical strategies are available for patients with FAP: proctocolectomy with permanent ileostomy, proctocolectomy with Kock’s pouch continent ileostomy (Kock), colectomy with ileorectal anastomosis (IRA), and restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). IRA produces good functional results, and this surgery is associated with less morbidity than the other procedures. However, continuing endoscopic surveillance for adenomas in the rectum is necessary, and there is a 13% to 25% cumulative risk of rectal cancer after 15 to 25 years, despite surveillance. On the other hand, both Kock’s pouch construction and IPAA (pouch patients) theoretically eliminate the risk of colorectal cancer and adenomas, and perhaps the need for further lower gastrointestinal surveillance. However, development of ileal adenomas in patients who undergo Kock or IPAA procedures is becoming evident. In a recent study, Parc et al. showed the risk of adenoma development in the ileal pouch was 7%, 35%, and 75% at 5, 10, and 15 years of follow-up, respectively. Furthermore, there are a few reports of the development of adenocarcinomas in the pouch of FAP patients. Although most of the cancers that develop in the pouch are likely from residual rectal or anal transitional epithelium, there are four reports of cancers arising from the ileal pouch mucosa in patients with FAP. The etiology of these true pouch cancers seem to be different from the cancers arising from residual rectal or anal transitional epithelium, and the risks associated with these true pouch are controversial. Here, we report two patients with adenocarcinoma developing in the ileal pouch mucosa. A 55-year-old female presented in 1989, at age 46 years, with gastric adenoma with high-grade dysplasia. A barium enema was performed as part of preoperative evaluation which showed a rectal tumor with multiple synchronous colorectal polyps, and a diagnosis of FAP was made. Her parents and four siblings were unaffected, and it seems that she had a de novo genetic mutation. Colonoscopy confirmed the presence of a rectal tumor and multiple colorectal polyps. Biopsy from the rectal tumor showed a well-differentiated adenocarcinoma. An IPAA was performed. The resected colon had an estimated 100 polyps, and the rectum had an estimated 150 polyps. Histology of the surgical specimen confirmed many tubular adenomas distributed throughout the colon and rectum, and a moderately differentiated rectal adenocarcinoma of 45 mm size M. Tajika (*) : T. Nakamura Department of Endoscopy, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan e-mail: mtajika@aichi-cc.jp

Psychological distress and use of psychosocial support in familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is characterized by multiple adenomas in the colorectum with a high risk to develop colorectal cancer. It is unclear whether individuals at risk of FAP experience distress due to this potentially life-threatening disease. This nationwide study assessed: (1) the prevalence of psychological distress; and (2) the need for and use of specialized professional psychosocial support. In this cross-sectional study, all individuals from families at high risk for FAP registered at the Netherlands Foundation for the Detection of Hereditary Tumours were invited to complete a questionnaire assessing, among other issues, generalized, cancer-specific and FAP-specific distress. In total, 525 individuals completed the questionnaire. Approximately 20% of the respondents had moderate to severe levels of FAP-specific distress. Levels of generalized distress were comparable to the general Dutch population. Significantly more individuals with a FAP diagnosis had frequent cancer worries than those at risk of FAP or non-carriers (p=0.02). Distress levels were more strongly associated with psychosocial variables (e.g. perceived cancer risk), than with sociodemographic or clinical variables. Up to 43% of the variance in distress could be explained by all variables combined. Of those moderately to severely distressed, 26% had received specialized professional psychosocial support, while 30% of those did not receive the support they wanted. A substantial minority of individuals reported moderate to severe distress levels associated with FAP. However, only one-third of those received specialized professional psychosocial support. We recommend the use of a screening questionnaire to identify individuals in need of such support.

Relative role of APC and MUTYH mutations in the pathogenesis of familial adenomatous polyposis

Objective. Familial adenomatous polyposis (FAP) is an interesting model for the study of colorectal tumour. Two genes contribute to the FAP phenotype – APC and MUTYH – but their relative role is still undefined. The objective of this study was to evaluate the contribution of the two genes to the pathogenesis of FAP by means of a series of FAP families. Material and methods. Sixty-one unrelated families with a diagnosis of FAP and a total of 187 affected individuals were evaluated. After extracting DNA, APC and MUTYH genes were sequenced. Results. In the whole series of patients, colectomy with ileorectal anastomosis was the most frequent surgery, although the number of patients treated by total proctocolectomy and ileoanal anastomosis was increasing. Duodenal and jejunal-ileal adenomas were present in more than half of the patients. Constitutional mutations were detected in 37 of the 45 families (82.2%); there were 33 families with APC and 4 with MUTYH alterations. Age at onset of polyposis and age at surgery were 10–15 years delayed for carriers of MUTYH mutations; cancer at diagnosis was frequent, and extracolonic manifestations were diagnosed in the majority of MUTYH-positive families. MUTYH-associated polyposis showed the horizontal transmission expected for recessive inheritance (at variance with the dominant pattern seen with APC mutations). Conclusions. At least two genes are associated with the FAP phenotype. APC mutations account for the majority of cases, while MUTYH mutations can be observed in 10% of patients. There are few but definite differences between APC- and MUTYH-associated FAP, such as age at diagnosis and pattern of transmission.