Upper gastrointestinal polyps in familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominant disease in which affected family members develop numerous colorectal adenomas with a virtually 100% chance of malignant degeneration unless the colon is prophylactically removed. After colectomy the main cause of death is upper gastrointestinal malignancy. The majority of FAP patients also develop upper gastrointestinal polyps, and especially those in the antrum and duodenum are usually neoplastic. Therefore, surveillance of FAP patients through endoscopy plus biopsy is recommended. The Spigelman classification in which the number of adenomas, the size, architecture and degree of dysplasia account for the scoring system, provides a guide for follow-up in these patients. Molecular genetic markers to assess the risk of upper gastrointestinal cancer in FAP patients are as yet not available.     

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.     

The risk of upper gastrointestinal cancer in familial adenomatous polyposis.

Adenomas with potential for malignancy occur frequently in the upper gastrointestinal tract of patients with familial adenomatous polyposis. However, an assessment of relative risk of upper gastrointestinal cancer in patients with adenomatous polyposis has never been performed. Therefore, the incidence rate of upper gastrointestinal cancer in patients with familial adenomatous polyposis in The Johns Hopkins Registry was compared with the rate of the general population through person-year analysis with adjustment for demographics. There was an increased relative risk of duodenal adenocarcinoma (relative risk, 330.82; 95% confidence limits, 132.66 and 681.49; P less than 0.001) and ampullary adenocarcinoma (relative risk, 123.72; 95% confidence limits, 33.65 and 316.72; P less than 0.001). No significant increased risk was found for gastric or nonduodenal small intestinal cancer. These results indicate that periodic surveillance of the upper gastrointestinal tract for duodenal and periampullary cancer is needed in patients with familial adenomatous polyposis. Prophylactic duodenectomy is a consideration when large adenoma(s) with high-grade dysplasia are identified but awaits risk benefit analysis.     

Gastric and duodenal polyps in familial adenomatous polyposis: a prospective study of the nature and prevalence of upper gastrointestinal polyps.

One hundred patients with familial adenomatous polyposis have prospectively undergone gastroduodenoscopy to identify and characterise polyps found. Forty six patients had polyps in the stomach or duodenum. Thirty five patients had adenomas (33 in duodenum, two in stomach) and 26 patients had fundic gland polyps. Some of these patients had polyps in the stomach and the duodenum. Adenomas in the duodenum were present in 33% of patients studied with Gardner's syndrome variant (p = 0.04). Adenomas were also more common in older patients. As adenomas may be a precursor of adenocarcinoma, routine surveillance of the stomach and duodenum with gastroduodenoscopy is recommended in patients affected with familial adenomatous polyposis.     

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.     

Adenomatous polyps develop commonly in the ileal pouch of patients with familial adenomatous polyposis

PURPOSE: The aim of this study was to establish the prevalence of adenomatous polyps in the ileal pouch of patients with familial adenomatous polyposis. METHOD: Forty-three patients who had an ileal pouch for familial adenomatous polyposis were invited to have a careful endoscopic examination of their pouch, including dye spraying. The number of polyps was recorded, and up to ten were biopsied. In addition, four random biopsy specimens were taken from the proximal and four from the distal pouch. RESULTS: Thirty-three patients with a median age of 36 (range, 14-63) years who had a pouch (5 Kock and 28 pelvic) for a median of 7 (range, 1-19) years accepted the invitation. Twenty-one patients (64 percent) had endoscopically identified polyps, the number of polyps ranging from 1 to 100 (median, 10) and varying in size from 1 to 3 mm. Fourteen patients (42 percent) had adenomatous polyps and 4 of these also had microadenomas on random biopsies. Nine of the 14 patients with adenomas also had lymphoid polyps. Seven patients had lymphoid polyps only and two of these patients had a microadenoma on random biopsy. Four of 12 patients with no visible polyps had microadenomas in their random biopsies. The presence of adenomatous polyps (Pearson's correlation; P < 0.01) increased with the age of the pouch. In total, 20 of 33 (60 percent) patients had adenomas and or microadenomas. CONCLUSION: Adenomatous polyps occur frequently in ileal pouches. These findings are of concern, and therefore, regular surveillance seems warranted until the natural history of these adenomatous polyps is determined.     

Rare combination of familial adenomatous polyposis and gallbladder polyps

Familial adenomatous polyposis is associated with a high incidence of malignancies in the upper gastrointestinal tract (particularly ampullary adenocarcinomas). However, few reports have described a correlation between familial adenomatous polyposis and gallbladder neoplasms. We present a case of a 60-year-old woman with familial adenomatous polyposis who presented with an elevated mass in the neck of the gallbladder (measuring 16 mm × 8 mm in diameter) and multiple small cholecystic polyps. She had undergone a total colectomy for ascending colon cancer associated with familial adenomatous polyposis 22 years previously. The patient underwent laparoscopic cholecystectomy under a preoperative diagnosis of multifocal gallbladder polyps. Pathologic examination of the resected gallbladder revealed more than 70 adenomatous lesions, a feature consistent with adenoma of the gallbladder. This case suggests a requirement for long-term surveillance of the biliary system in addition to the gastrointestinal tract in patients with familial adenomatous polyposis.     

Severe upper gastrointestinal polyposis associated with sparse colonic polyposis in a familial adenomatous polyposis family with an APC mutation at codon 1520

Background—Familial adenomatouspolyposis usually results in colonic polyposis with hundredsto thousands of polyps, congenital hypertrophy of the retinal pigmentepithelium (CHRPE), and variable extracolonic features. Recent reportsindicate that patients with distal mutations between codons 1445 and1578 do not express CHRPE and have a high incidence of desmoid tumours.
Patients—The family studied has an unusualphenotype of sparse colonic polyposis but profuse uppergastrointestinal polyposis. Affected subjects do not have CHRPE.
Methods—The protein truncation testfollowed by sequencing identified a 2 base pair deletion at codon 1520 in the APC gene. This results in a frameshift creating a stop codon 13 codons downstream.
Results—This family demonstrates that sparsecolonic polyposis but severe upper tract polyposis may be associatedwith mutations between codons 1445 and 1578.
Conclusions—Study of duodenal and colonic polypsin further cases with mutations in this region is warranted. Suchmutations may preferentially cause duodenal adenomas and desmoidtumours as somatic mutations in these tumours also occur in thisregion, unlike colorectal tumours where somatic mutations occur moreproximally. This study emphasises the importance of screening the uppergastrointestinal tract even when the colonic disease is mild.

Keywords:familial adenomatous polyposis; duodenal polyps; APCmutations; colorectal polyps

     

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.     

High prevalence of adenomatous polyps of the duodenal papilla in familial adenomatous polyposis

Eighteen consecutive asymptomatic patients with familial adenomatous polyposis (both familial polyposis coli and Gardener's syndrome) were studied over a 12-month period; side-viewing upper endoscopy and biopsy were used to assess the frequency of adenomatous polyps of the duodenal papilla. Nine of the 18 patients demonstrated adenomatous polyps of the papilla, varying in size and appearance from microadenomas in normal-appearing duodenal papillae (two) to a sessile polyp 3 cm in diameter. Two were tubulovillous adenomas (0.5 cm and 2 cm in diameter) and the remainder were tubular adenomas. Severe atypia and malignancy were not encountered. These findings reveal that adenomas of the duodenal papilla are common in individuals with familial adenomatous polyposis. Because of these findings and because of the known risk of periampullary adenocarcinomas and nonmalignant complications of polyps of the duodenal papilla in patients with familial adenomatous polyposis, upper gastrointestinal screening of such patients should include examination of the duodenal papilla with a side-viewing endoscope.     

Frequency of small bowel polyps in patients with duodenal adenoma but without familial adenomatous polyposis

INTRODUCTION: It is uncertain whether patients with duodenal adenomas without familial adenomatous polyposis (FAP) are at greater risk for small bowel neoplasia. We therefore conducted a study to determine the frequency of small bowel polyps in patients with non-papillary duodenal adenomas using capsule endoscopy for small bowel examination. PATIENTS AND METHODS: 14 patients (8 women, 6 men; mean age 67 +/- 10 years; range: 49 - 77 years) with non-papillary duodenal adenomas without FAP were included. All patients underwent wireless capsule endoscopy. The results were compared with an age- and sex-matched cohort of patients undergoing capsule endoscopy for suspected small bowel disease. RESULTS: Overall, 15 polyps ranging between 1 and 8 mm in diameter were detected in eight patients of the study group, whereas no polyps could be identified in the control group. Natural excretion of the capsule within 24 hours was always reported and no complications were reported by any of the patients. Other pathological findings were multiple angiodysplasias in two patients of the study group. In the control group capsule endoscopy detected angiodysplasias in 5 patients with the indication obscure gastrointestinal bleeding, and inflammatory lesions in 2 patients with suspected Crohn's disease. CONCLUSIONS: Based on the results of this prospective study, the frequency of small bowel polyps in patients with duodenal adenomas without familial adenomatous polyposis appears to be increased compared with a control group undergoing capsule endoscopy for other reasons. In none of the patients was the management altered. Follow-up data of these patients will be needed.     

Wireless capsule endoscopy in detecting small-intestinal polyps in familial adenomatous polyposis

AIM: To detect the prevalence of small bowel polyps by wireless capsule endoscopy (WCE) in patients with familial adenomatous polyposis (FAP). METHODS: We examined prospectively 14 patients with FAP to assess the location, size and number of small-intestinal polyps. Patients' age, sex, years of observation after surgery, type of surgery, duodenal polyps and colorectal cancer at surgery were analyzed. RESULTS: During WCE, polyps were detected in 9/14 (64.3%) patients. Duodenal adenomatous polyps were found in nine (64.3%) patients, and jejunal and ileal polyps in seven (50%) and eight (57.1%), respectively. The Spigelman stage of duodenal polyposis was associated with the presence of jejunal and ileal polyps. Identification of the ampulla of Vater was not achieved with WCE. Importantly, the findings of WCE had no immediate impact on the further clinical management of FAP patients. No procedure-related complications were observed in the patients. CONCLUSION: WCE is a promising noninvasive new method for the detection of small-intestinal polyps. Further investigation is required to determine which phenotype of FAP is needed for surveillance with WCE.     

Sulindac causes regression of rectal polyps in familial adenomatous polyposis.

In familial adenomatous polyposis, sulindac-induced polyp regression has been reported by several authors. In this study, the goal was to confirm these results by a randomized, placebo-controlled, double-blind crossover study in 10 patients with rectal polyps that had been previously treated by colectomy and ileorectal anastomosis. Patients received sulindac, 300 mg/day, or placebo during two 4-month periods separated by a 1-month wash-out phase. One patient was not compliant and was excluded. With sulindac, the authors observed a complete (6 patients) or almost complete (3 patients) regression of the polyps. With placebo, the authors observed an increase (5 patients), no change (2 patients), and a relative decrease (2 patients) in the number of polyps. The difference between sulindac and placebo was statistically significant (P less than 0.01). In biopsy specimens of polyps and normal rectal mucosa of 6 patients, the authors conducted an immunohistochemical study of the cellular proliferation index using the Ki 67 monoclonal antibody (Ki 67 index), at the beginning and at the end of each treatment period. They were not able to show a sulindac-induced modification of the Ki 67 index. The authors conclude that sulindac is effective in inducing the regression of rectal polyps in familial adenomatous polyposis.     

Regression of rectal polyps by indomethacin suppository in familial adenomatous polyposis

PURPOSE: The effect of indomethacin suppository on rectal polyps was evaluated in two patients with familial adenomatous polyposis who had undergone total colectomy and ileoproctostomy. METHODS: Both patients received intrarectal administration of 50 mg of indomethacin suppository once or twice daily to control the rectal remnant polyps. RESULTS: With this treatment, an almost complete regression was achieved within three months, in both patients. Polyps recurred after the interruption of indomethacin treatment in one patient. At the present follow-up of two to three years, no cancer has developed. CONCLUSIONS: Indomethacin suppository treatment was effective in controlling rectal remnant polyps in the two patients with familial adenomatous polyposis. Intraluminal administration of indomethacin in suppository form seems more beneficial since it allows for direct contact of the drug with the lesions and produces a high local concentration of the drug.