Mortality in patients with familial adenomatous polyposis

The authors identified 132 patients who died with a documented diagnosis of familial adenomatous polyposis (FAP). A review of the medical records, autopsy reports, and in-depth discussion with local physicians and well-informed family members was performed. It was impossible, even after the review, to ascertain the exact cause of death in 22 patients. In the remaining patients, the cause of death was as follows: metastatic colorectal carcinoma, 64 patients (58.2 percent), (colon, 49 [44.5 percent], rectal, 15 [13.6 percent]); desmoid tumors, 12 (10.9 percent); periampullary carcinoma, 9 (8.2 percent); brain tumors, 8 (7.3 percent); perioperative mortalities, 5 (4.5 percent); adrenal carcinoma, 1 (0.9 percent); and abdominal carcinomatosis, 1 (0.9 percent). Ten patients died of causes not related to FAP. The major causes of death in 36 patients who underwent prophylactic colectomy were desmoid tumor and periampullary malignancy. This finding underscores the importance of lifelong surveillance and periodic endoscopic evaluation in patients with FAP.Read at the Tripartite Meeting, Birmingham, United Kingdom, June 19 to 22, 1989.     

Gastroduodenal polyps in patients with familial adenomatous polyposis

A review of the endoscopy reports and pathology results from esophagogastroduodenoscopy (EGD) of all patients with familial adenomatous polyposis (FAP) undergoing such an examination was performed. Two hundred fortyseven patients were identified, with an overall prevalence of duodenal adenomas of 66 percent and of fundic gland polyps of 61 percent. Analysis of our more recent experience (1986 to 1990) shows the prevalence to be 88 percent and 84 percent, respectively. A normal-appearing papilla was adenomatous in 50 percent of cases. No case of periampullary carcinoma developed in patients under surveillance. Routine EGD is indicated for patients with FAP. Duodenal adenomas and fundic gland polyps will occur in the majority of patients.Read at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, May 12 to 17, 1991.     

Desmoid disease in patients with familial adenomatous polyposis

PURPOSE: The aim of this retrospective study was to review the clinical features, and surgical and medical management of patients with familial adenomatous polyposis-associated desmoid tumors. METHODS: From 1980 to 1997, 97 of 780 patients with familial adenomatous polyposis developed desmoid disease. Clinical and demographic data; operative notes; and histologic, radiologic, and follow-up reports were retrieved from patients' medical records. Risk factors for desmoid disease, such as prior surgery, age at desmoid tumor diagnosis, pregnancy, and family history were sought. The outcome after noncytotoxic and cytotoxic therapy was evaluated with respect to improvement of symptoms. RESULTS: There were 38 males with a mean age of 32.1 years and 59 females with a mean age of 29.1 years. A family history of desmoid tumors was found in 41 patients (42 percent), and a history of pregnancy was documented in 33 females (56 percent). The most common clinical presentation was small-bowel obstruction (58 percent). One-half of the desmoids were located in the mesentery, and 32 percent were located in the mesentery and the abdominal wall. Desmoids developed after colectomy in 77 cases (80 percent), after a mean time of 4.6 years. Partial resection of desmoid tumor was performed in 46 patients (47 percent), resection of extra-abdominal desmoid tumors was performed in 17 cases (17 percent), and biopsy only was performed in 34 patients (35 percent). Postoperative morbidity was 23 percent after desmoid tumor resection. Eight patients (8 percent) died of their intra-abdominal desmoid. Mean follow-up time was 5.3 years. Sulindac, tamoxifen, or toremifene therapy was able to alleviate symptoms in only 4 of 31 patients. Symptomatic improvement was noted after chemotherapy in six of ten patients with extremely complex desmoids. CONCLUSION: Desmoid disease was found in 12.4 percent of our patients with familial adenomatous polyposis. In view of the high rate of morbidity, indication for surgery should be limited mainly to acute or chronic small-bowel obstruction, because resection triggers a high recurrence rate. Noncytotoxic therapy was not effective for progressive desmoid tumors, whereas chemotherapy was effective in aggressive cases of intra-abdominal desmoid tumors.Poster presentation at the meeting of the Society for Surgery of the Alimentary Tract during Digestive Disease Week, New Orleans, Louisiana, May 16 to 22, 1998. Read at the meeting of the Royal College of Physicians and Surgeons, Toronto, Ontario, Canada, September 16 to 20, 1998.     

Adrenal masses in patients with familial adenomatous polyposis

PURPOSE: 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. METHODS: 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 metaanalysis 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. RESULTS: 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)). DISCUSSION: 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.     

Serum gastrin values in patients with familial adenomatous polyposis

PURPOSE: An evaluation of the importance of gastrin in the colorectal carcinogenesis in patients with familial adenomatous polyposis was conducted. METHODS: Blood samples from 168 family members of 26 families were investigated for circulating gastrin. Blood was drawn from 65 affected patients, 66 clinically unaffected first-degree relatives, and 37 spouses. RESULTS: We did not find any difference in distribution of serum gastrin among these groups. CONCLUSION: Our results seem to exclude gastrin from being relevant in early carcinogenesis in patients with familial adenomatous polyposis.     

Duodenal adenoma surveillance in patients with familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is a hereditary disorder caused by Adenomatous Polyposis Gene mutations that lead to the development of colorectal polyps with great malignant risk throughout life. Moreover, numerous extracolonic manifestations incorporate different clinical features to produce varied individual phenotypes. Among them, the occurrence of duodenal adenomatous polyps is considered an almost inevitable event, and their incidence rates increase as a patient’s age advances. Although the majority of patients exhibit different grades of duodenal adenomatosis as they age, only a small proportion (1%-5%) of patients will ultimately develop duodenal carcinoma. Within this context, the aim of the present study was to review the data regarding the epidemiology, classification, genetic features, endoscopic features, carcinogenesis, surveillance and management of duodenal polyps in patients with FAP.     

Laparoscopic total abdominal colectomy with ileorectal anastomosis for familial adenomatous polyposis

PURPOSE: This study was undertaken to describe our results in a series of patients undergoing total abdominal colectomy with ileorectal anastomosis (TAC/IRA) using laparoscopic techniques in patients with familial adenomatous polyposis (FAP) and rectal-sparing. Young patients with FAP requiring TAC/IRA may be ideal candidates for minimally invasive surgery, because they are generally thin and have benign disease. They might benefit maximally from the theoretic advantages of these techniques. METHODS: We have performed laparoscopic TAC/IRA in 16 FAP patients (10 females; mean age, 18 years). Procedures were entirely intracorporeal, with a 3-cm to 6-cm specimen extraction incision. RESULTS: Median operative time was 232 (range, 156–285) minutes, and blood loss 175 (range, 50–675) ml. The only intraoperative complication, a twisted ileorectal anastomosis, was noted intraoperatively and revised. There were no conversions to conventional laparotomy. Median postoperative interval to passage of flatus was three days,^1–4 and for bowel movements it was three days.^1–4 Median hospital stay was five days.^3–11 One case of early postoperative small-bowel obstruction was treated nonoperatively, and one case of brachial plexus neuropraxia resolved spontaneously. CONCLUSIONS: Based on this preliminary experience, we believe laparoscopic TAC/ IRA can be a safe and effective treatment for selected patients with FAP. As techniques and instrumentation for laparoscopic colon surgery are perfected, this procedure will likely become an appealing option in the management of patients with FAP. Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996. No reprints are available     

Changing causes of mortality in patients with familial adenomatous polyposis

Widespread use of prophylactic colectomy has resulted in a reduction in the incidence of colorectal cancer in familial adenomatous polyposis (FAP) patients. A retrospective chart review of families registered at the Steve Atanas Stavro Familial Gastrointestinal Cancer Registry in Toronto was performed to determine whether the decrease in the number of patients developing colorectal cancer implies that causes of mortality in FAP patients are shifting to that of extracolonic manifestations of FAP. Information was available on 140 deaths within 158 families and among 461 individuals with FAP. When stratified by decade, from the 1930s to the 1990s, the ratio of deaths caused by extracolonic manifestations of FAP compared with deaths caused by colorectal cancer was noted to have risen. Even though most deaths in FAP patients are still from colorectal cancer, it appears that screening policies and prophylactic colectomy have resulted in a reduction in the number of FAP patients who develop colorectal cancer. Thus, in recent decades, a greater percentage of deaths in FAP patients appears to be attributable to extracolonic manifestations of the disease.     

Papillary thyroid carcinoma in Danish patients with familial adenomatous polyposis

All patients from the nationwide Danish Polyposis Register have been followed up with regard to thyroid carcinoma. During the period 1943–1985, 2/107 Danish women and 0/138 men developed papillary thyroid carcinoma after the diagnosis of familial adenomatous polyposis. The expected number among females was 0.02 resulting in an observed/expected ratio of 100 (95% confidence limits 12–361). Consequently, thyroid carcinoma should be included among the extracolonic lesions, which may develop in any female polyposis patient. However, regular thyroid examination is not indicated, as thyroid carcinoma is uncommon and as the prognosis is excellent.     

Chemoprevention in familial adenomatous polyposis

Familial adenomatous polyposis (FAP) predictably leads to adenomas and eventual adenocarcinomas in the lower gastrointestinal tract and less frequently, the upper gastrointestinal tract. Chemopreventive strategies have been studied in FAP patients to delay the development of adenomas in the upper and lower gastrointestinal tract, as well as to prevent recurrence of adenomas in the retained rectum of patients after prophylactic surgery with colectomy and ileorectal anastamosis (IRA). The nonsteroidal anti-inflammatory drug (NSAID) sulindac and selective cyclooxygenase-2 (COX-2) inhibitor celecoxib reduce polyposis of the retained rectum after colectomy with IRA. Reports of cardiovascular risks of some NSAIDs and selective COX-2 inhibitors have led to promising studies of lower doses in combination with ursodeoxycholic acid, statin, and difluoromethylornithine. Curcumin and eicosapentaenoic acid show efficacy in small clinical trials of FAP chemoprevention. This article will review the concept of chemoprevention and the current clinical literature in FAP chemoprevention.     

Risk estimation in familial adenomatous polyposis using DNA probes linked to the familial adenomatous polyposis gene.

The familial adenomatous polyposis gene has recently been assigned to the long arm of chromosome five through linkage to several 5q DNA probes. These probes can now be used to trace inheritance of the disease gene in affected families. In this study, DNA samples from 152 members of 10 Australian familial adenomatous polyposis families have been examined for restriction fragment length polymorphisms detected by DNA probes C11P11, ECB27, and YN5.48. Linkage analysis confirmed linkage between the familial adenomatous polyposis gene and each probe with a maximum combined LOD score of 2.82 for C11P11, 2.90 for ECB27 and 5.49 for YN5.48 all at a recombination fraction of zero. Risk estimates were determined for the 51 at risk individuals in these families based on their restriction fragment length polymorphism data alone or in addition by including the effect of age dependent penetrance. Thirty two of those at risk (63%) could be assigned specific high (greater than or equal to 95%) or low (less than or equal to 5%) risks of developing familial adenomatous polyposis on the basis of their probe results. When the effect of age dependent penetrance was included, 26 (51%) fell at the extremes of risk (greater than or equal to 99% or less than or equal to 1%). Such estimates provide a sound basis for planning sigmoidoscopic screening of at risk family members and will thus facilitate surveillance in familial adenomatous polyposis families.     

Serrated adenoma in familial adenomatous polyposis: relation to germline APC gene mutation

BACKGROUND: Serrated adenoma is a precursor of colorectal cancer. AIM: To clarify possible genotype-phenotype correlations of serrated adenomas in familial adenomatous polyposis (FAP). Patients: Eleven patients from eight families with FAP. METHODS: We performed total colonoscopy with multiple biopsies in patients. Neoplasia with a serrated glandular structure was regarded as a serrated adenoma. In each patient, germline mutations of the APC gene were determined. Colonic phenotype was compared with germline mutations of the APC gene. RESULTS: Serrated adenomas were found in three patients. These patients had macroscopic polyps <100 in number. Pedigrees with serrated adenomas had the truncating germline APC mutation at codon 161, 332, or 1556 while in the other pedigrees mutations were found between codons 554 and 1324. CONCLUSIONS: In FAP, serrated adenoma may be a phenotype characteristic of the attenuated form.     

Tissue prostaglandin levels in familial adenomatous polyposis patients treated with sulindac

BACKGROUND: Recent work has demonstrated a correlation between frequency of aspirin ingestion and colorectal cancer prevention. Sulindac, another nonsteroidal anti-inflammatory drug (NSAID), has been shown to cause polyp regression and a fall in cell proliferation in patients with familial adenomatous polyposis, who are destined to develop colorectal cancer unless the colon is removed. However, the mode of action of NSAIDs in colorectal carcinogenesis prevention remains to be determined, although a prostaglandin-mediated mechanism seems likely. METHODS: Rectal or duodenal biopsies from 20 patients with familial adenomatous polyposis, who had been randomized to sulindac or placebo, were analyzed for prostaglandin (PG) E₂ and E_2α levels before and after treatment. RESULTS: A significant fall in prostaglandin E₂ and E_2α (P=0.0096; PGE₂, P=0.036; PGF_2α Spearman's rank correlation). CONCLUSIONS: Nonsteroidal antiinflammatory drugs may prevent colorectal cancer by their inhibition of prostaglandin synthesis. Prostaglandins may be implicated in carcinogenesis through an increase in cell proliferation, through immunosuppression, by increasing neovascularization, or via a mutagenic effect.     

Risk of ileal pouch neoplasms in patients with familial adenomatous polyposis

Restorative proctocolectomy is the most common surgical option for patients with familial adenomatous polyposis(FAP). However,adenomas may develop in the ileal pouch mucosa over time,and even carcinoma in the pouch has been reported. We therefore reviewed the prevalence,nature,and treatment of adenomas and carcinoma that develop after proctocolectomy in the ileal pouch mucosa in patients with FAP. In 25 reports that were reviewed,the incidence of adenomas in the ileal pouch varied from 6.7% to 73.9%. Several potential factors that favor the development of pouch polyposis have been investigated,but many remain controversial. Nevertheless,it seems certain that the age of the pouch is important. The risk appears to be 7%to 16% after 5 years,35% to 42% after 10 years,and75% after 15 years. On the other hand,only 21 cases of ileal pouch carcinoma have been recorded in the literature to date. The diagnosis of pouch carcinoma was made between 3 to 20 years(median,10 years) after pouch construction. Although the risk of malignant transformation in ileal pouches is probably low,it is not negligible,and the long-term risk cannot presently be well quantified. Regular endoscopic surveillance,especially using chromoendoscopy,is recommended.     

Rectal epithelial apoptosis in familial adenomatous polyposis patients treated with sulindac

BACKGROUND: Sulindac regresses colorectal adenomas in patients with familial adenomatous polyposis (FAP), although the mechanism of polyp regression is unclear. AIMS: To determine whether differences occur in alteration of rectal epithelial apoptotic index and expression of apoptosis related proteins in FAP patients treated with sulindac compared with placebo. PATIENTS: Twenty one FAP patients; 12 had not undergone colectomy. METHODS: Patients with FAP were treated with sulindac 150 mg orally twice a day for three months (n=10) or placebo (n=11). Colorectal polyp number was determined and biopsies of the normal rectal mucosa were performed before and after three months of treatment. Response to treatment and alteration of the apoptotic ratio (index in base of crypt divided by index in surface epithelium) were evaluated. Bcl-2, bax, p21/WAF-1, and p53 proteins were assessed semiquantitatively by immunohistochemistry. RESULTS: Significant decreases in polyp number and in the apoptotic ratio were seen in patients treated with sulindac compared with controls. The mean percentage change in polyp number from baseline was -46% in the sulindac group and +13% in the placebo group (p=0.005). Mean percentage change in the apoptotic ratio was -8% and +25% in the sulindac and placebo treated patients, respectively (p=0.004). No differences in expression or compartmentalisation of apoptosis related proteins were noted between treatment groups. CONCLUSIONS: Sulindac regression of colorectal adenomas is accompanied by alteration of the rectal epithelial apoptotic ratio with relative increase in apoptosis in surface cells compared with the deeper crypt. The utility of the apoptotic ratio as an intermediate biomarker for colorectal tumorigenesis deserves further study.