Familial segregation in the occurrence and severity of periampullary neoplasms in familial adenomatous polyposis

doi:10.1016/S0002-9610(99)80088-9

The American Journal of Surgery

Volume 171, Issue 1, January 1996, Pages 136-141

https://doi.org/10.1016/S0002-9610(99)80088-9 Get rights and content

Background

Familial adenomatous polyposis (FAP) patients often develop periampullary adenomas that may progress to periampullary cancer, a common cause of death in this population. The risk of periampullary cancer in FAP is unclear, and variables that predict the occurrence and severity of periampullary tumors are not well understood. The specific aim of this study was to determine whether the risk of periampullary neoplasia segregates in specific FAP families.

Materials and methods

A total of 144 FAP patients from 74 families were either screened by gastroduodenoscopy (n = 132) or information was obtained from surgical or autopsy reports (n = 12). The severity of periampullary neoplasia was recorded for each patient and graded based on maximum polyp size and histology. Linear regression was used to determine the significance of a number of variables with respect to periampullary neoplasia. A blood sample was available from at least one member of 50 unrelated families and used to detect germline mutations in codons 686 through 1693 of the adenomatous polyposis coli (APC) gene.

Results

Statistically significant familial segregation was found for the incidence and severity of periampullary neoplasia (P <0.02). Age was also a statistically significant variable (P <0.01). No correlation was observed between specific APC germline mutations and periampullary polyp frequency and severity.

Conclusions

The occurrence and severity of periampullary neoplasms in patients with FAP segregates in families. This familial association may be related to as yet unidentified modifier genes or perhaps common environmental factors. These results should prove useful in developing upper gastrointestinal screening protocols for FAP patients at risk for periampullary neoplasia.

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Cited by (56)

Natural history of ampullary adenomas in familial adenomatous polyposis: a long-term follow-up study
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Citation Excerpt :
These findings support watchful waiting as the favored strategy compared with expedited resection for AAs because prolonged follow-up may obviate the need for intervention in most cases. Older age and extracolonic manifestations of FAP have been shown to increase the risk of developing AA22,23; however, factors associated with AA progression are unknown. In the present study, extracolonic malignancy was associated with CSP of AAs, whereas age at AA detection was not associated with CSP.
Ampullary adenomas (AAs), common in familial adenomatous polyposis (FAP), are precursors to ampullary carcinoma. We assessed the natural history of AAs and factors associated with clinically significant progression (CSP).
Consecutive FAP patients with AAs and at least 2 EGDs were identified from a hereditary GI cancer registry. We assessed the incidence of CSP (increase in size to ≥10 mm and/or development of advanced histology) of AAs. Clinical, endoscopic, and pathologic features between patients with CSP and nonprogressors were compared.
One hundred forty-three patients with AAs were included. Over a median follow-up of 7.8 years (interquartile range, 4.3-11.1), 41 patients (28.6%) developed CSP for an incidence of 35 per 1000 patient-years. Of 143 patients, 22 (15.6%) progressed to AAs ≥10 mm, 12 (8.5%) progressed to advanced histology, and 7 (4.9%) progressed both in size and histology. Two patients (1.4%) developed ampullary cancer. Male gender, abnormal appearance of the papilla at initial AA detection, prior cholecystectomy, and personal history of extracolonic malignancy were associated with CSP. Neither Spigelman stage nor the adenomatous polyposis coli gene pathogenic variants were associated with CSP. An intervention specifically for AA and not duodenal polyposis was performed in 24% of patients with AAs, including endoscopic papillectomy in 23 patients and duodenectomy in 3 patients at a median observation of 8.2 years.
Most FAP patients with AAs did not experience CSP or require resection over 8 years of surveillance. Ampullary cancer was rare. Male gender, abnormal appearance of the papilla at AA detection, cholecystectomy, and history of extracolonic malignancy were associated with CSP. Our findings favor endoscopic surveillance of AAs over expedited resection for most patients with FAP.
Ampullary Neoplasia
2018, ERCP, Third Edition
The ampulla of Vater is the most common site of duodenal neoplasia. The most common neoplastic lesion is adenomatous change, although a large number of other pathologies have been reported at this site. The ampulla is a very common site of adenomatous change in familial adenomatous polyposis (FAP) patients, though many sporadic adenomas also occur in this area. Adenomas of the ampulla may undergo malignant change in a manner similar to colorectal adenomas. Periodic inspection of the ampulla and proximal duodenum is part of standard surveillance for patients with FAP syndrome. In the symptomatic patient, presentation is typically a sequelae of obstruction of the biliary and/or pancreatic duct. However, many lesions are detected in asymptomatic patients undergoing gastroscopy or in FAP patients undergoing routine surveillance. Fortunately, many patients present relatively early, often before malignant transformation has occurred. These patients can be managed very successfully with endoscopic resection. Therefore clinical workup is aimed at determining whether overt malignancy is present and whether the lesion is localized to the duodenal wall and thus amenable to endoscopic therapy. Endoscopic ultrasound and ERCP are both useful in this regard. Patients with malignant lesions usually require pancreaticoduodenectomy.
TNM Staging System for Ampullary Carcinomas
2013, ERCP: Second Edition
Ampullary Neoplasia
2013, ERCP
Endoscopic Management of Upper Gastrointestinal Familial Adenomatous Polyposis Syndrome and Ampullary Tumors
2011, Clinical Gastrointestinal Endoscopy, Second Edition
Features of Duodenal Cancer in Patients With Familial Adenomatous Polyposis
2009, Clinical Gastroenterology and Hepatology
Most patients with familial adenomatous polyposis (FAP) develop duodenal adenomas; duodenal cancer is a major cause of mortality in this patient group. We reviewed cases of duodenal cancer in patients with FAP to identify factors that determine long-term cancer risk.
Twenty FAP patients (12 male) were identified from a registry database search. Data from registry and medical notes and endoscopic and histopathologic reports were evaluated.
Of the cancers that developed in these patients, 11 were ampullary and 9 were duodenal. The median age at cancer diagnosis was 53 years. Seventeen patients died (median age at death, 57 y; median survival from diagnosis, 11 mo); the cause of death was metastatic or duodenal/ampullary cancer in 14 patients. Fifteen patients presented symptomatically (including 3 interval cancers while on surveillance). Two were diagnosed at surveillance and 3 were diagnosed during surgery performed for endoscopic features of advanced benign disease. Duodenal cancers were associated with a significantly lower mean colonic polyp count than ampullary cancers (496 ± 282 vs 1322 ± 735; P = .025); there appeared to be familial clustering of this cancer. When endoscopic data were available (n = 11 of 20), all ampullary cancers arose from ampullas greater than 1 cm. The Spigelman stage did not predict risk of ampullary cancer but did predict duodenal cancer (median stage 2 vs stage 4 for duodenal cancer).
Once cancer arises in patients with FAP, prognosis is poor, so cancer prevention should be the main goal. Surveillance intervals should reflect both Spigelman staging and ampullary disease.

View all citing articles on Scopus

^*: Supported by the National Cancer Institute of Canada (BVB, SG).

View full text

Familial segregation in the occurrence and severity of periampullary neoplasms in familial adenomatous polyposis*

Background

Materials and methods

Results

Conclusions

Cell.

Gastroenterology.

Hum Pathol.

Cell.

Mutations of chromosome 5q21 gene in FAP and colorectal cancer patients

Science.

Extra-colonic manifestations of familial adenomatous polyposis

Oncology

Overview of screening and management of familial adenomatous polyposis

Gut

Gastric and duodenal polyps in familial polyposis coli

Gut.

Upper gastrointestinal tract polyps in familial adenomatous coli

Gut.

Upper gastrointestinal neoplasia in familial polyposis

Dig Dis

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

Gut.