Development of duodenal cancer in a patient with familial adenomatous polyposis

A Japanese woman with familial adenomatous polyposis in whom a duodenal ampullary adenoma underwent malignant change during a 10-year follow-up period is reported. After restorative proctocolectomy in 1989, and extensive small bowel resection for desmoid disease in 1991, regular surveillance duodenoscopies, including three to nine biopsies (mean, 4.8) were performed annually or biannually. Until 1995, the endoscopic findings of duodenal polyposis (including an ampullary polyp) did not progress and the histopathology did not worsen. In 1996, there was an increase in the number and size of the duodenal polyps, and the ampulla of Vater looked enlarged. Open surgery was discussed but not proceeded with because of the risk for short bowel syndrome. In January 1998, she was admitted with a diagnosis of acute pancreatitis. Duodenoscopy and radiological examination revealed that an advanced ampullary cancer had developed, and histopathology revealed a well-differentiated adenocarcinoma. Multiple hepatic metastases and ascites led to her death, in June, 1998. This in-vivo demonstration of the adenoma-carcinoma sequence highlights current limitations in the surveillance and treatment of duodenal lesions. Received: June 28, 1999/Accepted March 24, 2000     

Prophylactic pancreaticoduodenectomy for premalignant duodenal polyposis in familial adenomatous polyposis

The frequency of duodenal adenomas in patients with, familial adenomatous polyposis is high. Duodenal adenoma has malignant potential, and duodenal adenocarcinoma is one of the main causes of death in patients who have had previous proctocolectomy. A conservative approach to the treatment of duodenal adenomas (nonsteroidal anti-inflammatory drugs, endoscopy, polypectomy through duodenotomy) is inefficient and unsafe. When invasive cancer occurs in duodenal adenomas, the result of surgery is poor. We have performed prophylactic pancreaticoduodenal resection (PDR) for nonmalignant severe duodenal polyposis in five patients since 1991. No operative mortality was observed. One patient developed a pancreatic fistula which was successfully managed by medical treatment. The mean follow-up was 35 months. All five patients are still alive and have a good functional outcome. Prophylactic PDR may be indicated in familial adenomatous polyposis when duodenal polyposis is severe. Stages III and IV of Spigelman's classification, periampullary adenoma, age above 40, and family history of duodenal cancer are factors that may lead to the decision to perform prophylactic PDR. Accepted: 29 October 1997     

Relapsing acute pancreatitis due to ampullary adenoma in a patient with familial adenomatous polyposis

A patient with familial adenomatous polyposis (FAP) presented with a relapsing attack of acute pancreatitis. Evaluation using computed tomography, ultrasonography, and duodenoscopy revealed an ampullary adenoma, which was classified as Spigelman's stage III according to Spigelman's criteria. The patient underwent a pylorus-resected pancreatoduodenectomy, and has had no abdominal pain suggesting acute pancreatitis for 1 year after surgery. Only a few reports of acute pancreatitis due to ampullary neoplasms in patients with FAP are available. Relapsing acute pancreatitis is another surgical indication for premalignant periampullary neoplasms in FAP.     

Columnar cuff cancer after restorative proctocolectomy for familial adenomatous polyposis

AIMS: Restorative proctocolectomy with ileoanal anastomosis is one of the treatments of choice for patients suffering from familial adenomatous polyposis (FAP). However, any residual rectal mucosa left behind after mucosectomy is at risk for the development of neoplasia. CASE REPORT: A 31 year old male patient with FAP underwent restorative proctocolectomy with a pelvic ileal pouch-anal anastomosis. Seven years later he presented with right inguinal and perianal pain. A diagnosis of invasive columnar cuff carcinoma was made. DISCUSSION: Islets of columnar epithelium may be left behind after restorative proctocolectomy, exposing the patient to later malignant change. This risk must be emphasised and prevented by regular surveillance of the anastomosis.     

Genetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposis

BACKGROUND & AIMS: An attenuated form of familial adenomatous polyposis has been described, but the phenotype remains poorly understood. METHODS: We performed genetic testing on 810 individuals from 2 attenuated familial adenomatous polyposis kindreds harboring an identical germline adenomatous polyposis coli gene mutation. Colonoscopy was performed on mutation-positive persons. RESULTS: The disease-causing mutation was present in 184 individuals. Adenomatous polyps were present in 111 of 120 gene carriers who had colonoscopy at an average age of 41 years. The median number of adenomas was 25 (range, 0-470), with striking variability of polyp numbers and a proximal colonic predominance of polyps. Colorectal cancer occurred in 27 mutation carriers (average age, 58 years; range, 29-81 years), with 75% in the proximal colon. The cumulative risk of colorectal cancer by age 80 was estimated to be 69%. An average of 3.4 recurrent polyps (range, 0-29) were found in the postcolectomy rectal remnant over a mean of 7.8 years (range, 1-34 years), with 1 rectal cancer. CONCLUSIONS: This investigation shows that attenuated familial adenomatous polyposis in the kindreds examined shows a much smaller median number of polyps than typical familial adenomatous polyposis, a wide variability in polyp number even at older ages, and a more proximal colonic location of polyps and cancer, yet it is associated with an extremely high risk of colon cancer. The phenotype of attenuated familial adenomatous polyposis mimics typical familial adenomatous polyposis in some cases but in others is difficult to distinguish from sporadic adenomas and colorectal cancer, thus making genetic testing particularly important.     

Surface structure of single-gland adenoma in familial adenomatous polyposis

Magnifying videoendoscopic observation of a minute lesion with a single IIIL type cryptal orifice was reported. This minute lesion was a single-gland adenoma accompanied histopathologically by a bud of adenomatous gland and was located in the upper part of the mucosa. This finding regarding a pit pattern should make possible the endoscopic diagnosis of a colonic single-gland adenoma.     

Phenotypic differences in familial adenomatous polyposis based on APC gene mutation status

Background—Familial adenomatous polyposis(FAP) is a clinically well defined hereditary disease caused bygermline mutations within the adenomatous polyposis coli (APC) gene.Although several techniques are applied in the mutation analysis of FAPkindreds about 20-50% of cases remain unclear, with no APC mutationidentified (APC negative).
Aims—To delineate phenotypic differences betweenAPC positive and APC negative patients with respect to colonic andextracolonic disease in order to determine whether additionalmechanisms are involved in the pathogenesis of FAP.
Methods—The entire coding region of the APC genewas analysed using single stranded conformation polymorphism andprotein truncation tests in 50 Swiss FAP families with a total of 161affected individuals. Differences in phenotypic manifestation werestatistically evaluated by Student's t test, Fisher'sexact test, and χ² test.
Results—Thirty six families (72%) were APCpositive. Statistically significant differences between APC positiveand APC negative groups were found for the mean age at diagnosis ofcolonic polyposis (35.2 versus 45.3 years, respectively) and for theoccurrence of stomach polyps (14 patients, all APC positive).Additionally, APC negative patients displayed lower polyp numbers atdiagnosis and less extracolonic manifestations.
Conclusions—FAP kindreds without detected APCgene mutations present with a notably milder disease phenotype comparedwith APC positive families, suggesting that different genetic factors might be involved.

Keywords:familial adenomatous polyposis; adenomatouspolyposis coli gene; mutation; colorectal cancer; extracolonicmanifestations

     

Hepatocellular adenoma in a male with familial adenomatous polyposis coli

Hepatocellular adenoma (HA) is a benign liver tumor most frequently occurring in young women using oral contraceptives. We report a rare case of HA in a 27-year-old male patient with familial adenomatous polyposis (FAP). The patient underwent a total colectomy and ileo-rectal anastomosis for FAP in 2003. A preoperative computed tomography scan of the abdomen disclosed a tumor in the left-lobe of the liver, 5.8 cm in diameter. Pathologic examination of a needle biopsy disclosed HA, but he had never used anabolic steroids or other known inducers of HA. The size of the liver mass gradually increased to 8.5 cm during a follow-up period of 38 months, and a left hepatectomy was performed in 2006. Pathology of the resected specimen confirmed the diagnosis of HA. Although FAP is known to be complicated with neoplasia in various extracolonic organs, only five reported cases of HA have developed in patients with FAP, including this case. This is the first report of HA to develop in a male FAP patient.     

Prednisolone therapy for intra-abdominal desmoid tumors in a patient with familial adenomatous polyposis

The management of intra-abdominal desmoid tumors in patients with familial adenomatous polyposis (FAP) is very difficult. Non-steroidal anti-inflammatory drugs (NSAIDs), anti-estrogenic agents, and steroids are most commonly used, because surgical removal of these tumors may result in severe morbidity, with local recurrence being common. We report a patient with FAP and intra-abdominal desmoid tumors that regressed markedly after prednisolone therapy. The patient, a 38-year-old woman, had undergone total colectomy and ileorectal anastomosis with a diagnosis of FAP with colon cancer. Approximately 17 months after the surgery, she noticed an elastic firm lump in the abdominal wall. She also experienced lower abdominal distension. Computed tomography (CT) of the lower abdomen showed an invasive heterogenous low-density mass occupying the intra-abdominal space. She was treated with sulindac, NSAID, at 300 mg/day, the diagnosis being intra-abdominal desmoid tumors. She exhibited an intestinal obstruction about 9 months after the initiation of sulindac therapy. We changed the treatment and began prednisolone (initial dose, 40 mg/day). This treatment was continued for two years; subsequently the lesions regressed markedly. She is currently well, more than 3 years after the withdrawal of prednisolone.     

High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis

BACKGROUND & AIMS: Inherited colorectal polyposis has been linked to constitutive mutations of the APC tumor suppressor gene. Recently, germline mutations in the base excision repair gene MYH have been associated with a recessively inherited form of the disease. The aim of this study was to evaluate germline mutation frequencies of both MYH and APC susceptibility genes in Italian patients with attenuated familial adenomatous polyposis. METHODS: The analysis was performed in 14 unrelated patients by using the protein truncation test for APC and genomic DNA sequencing for MYH. RESULTS: Overall, we identified 7 of 14 (50%) mutation carriers. Two patients were heterozygotes for an APC truncating mutation (2 of 14 [14%]), whereas 5 proved to be homozygotes or compound heterozygotes for MYH gene alterations (5 of 14 [36%]). Two MYH missense mutations, Y165C and G382D, already found to be frequent among patients from northern Europe, were also preponderant in our survey. Individuals with APC-associated syndrome showed a dominant family history of polyposis, whereas patients with MYH-associated disease were either apparently sporadic cases or had a family history consistent with recessive inheritance. MYH biallelic mutation carriers were up to 60% (5 of 8) among patients showing at least 30 adenomas and a family history with no vertical transmission of polyposis. CONCLUSIONS: On the basis of our data, patients with attenuated familial adenomatous polyposis with >30 adenomas and no obvious vertical transmission of the disease should be considered for MYH gene testing.     

Variation of a variation: case report of attenuated familial adenomatous polyposis

BACKGROUND: First described in 1988, attenuated familial adenomatous polyposis (AFAP) is a rare autosomal dominant precancerous condition of the gastrointestinal tract. Few reports have described adenocarcinomatous change in the gastroduodenal region thus far. CASE OUTLINE: We report a case of AFAP presenting with extensive gastric polyposis and ampullary adenocarcinoma in absence of a positive family history of gastrointestinal cancer and a novel mutation.     

Prostanoids, ornithine decarboxylase, and polyamines in primary chemoprevention of familial adenomatous polyposis

BACKGROUND & AIMS: Familial adenomatous polyposis because of germline mutation of the adenomatous polyposis coli gene is characterized by development of colorectal adenomas and, ultimately, colorectal cancer. The usefulness of colorectal mucosal compounds to predict the effect on adenoma development of primary chemoprevention with the nonsteroidal anti-inflammatory drug sulindac was evaluated. METHODS: A randomized, double-blind, placebo-controlled study of 41 subjects genotypically affected with familial adenomatous polyposis but phenotypically unaffected was conducted. Patients received either sulindac or placebo for 48 months, and development of new adenomas was evaluated. The levels of 5 prostanoids, ornithine decarboxylase, and polyamines were measured serially in normal-appearing rectal mucosa. RESULTS: There were no statistically significant differences between treatment groups in baseline levels of prostanoids, ornithine decarboxylase, or polyamines. At conclusion of the study, 4 of 5 prostaglandin levels were statistically significantly lower in the sulindac group than in the placebo group. Among the subset of patients taking sulindac, 3 of 5 prostaglandin levels were statistically significantly lower in patients who were polyp free than in those who developed polyps. By contrast, there were no statistically significant differences in ornithine decarboxylase or polyamines between treatment groups or in those on sulindac who were polyp free compared with those who developed polyps. CONCLUSIONS: Colorectal mucosal prostaglandin levels, but not ornithine decarboxylase or polyamines, may be valuable biomarkers to assess appropriate drug dosage and medication compliance in patients undergoing primary chemoprevention therapy with sulindac. Reduction of mucosal prostaglandin levels may be necessary to achieve chemopreventive benefit from this agent.     

Long-term treatment with sulindac in familial adenomatous polyposis: a prospective cohort study

BACKGROUND & AIMS: Management of patients with familial adenomatous polyposis (FAP) can consist of colectomy with ileorectal anastomosis (IRA). Sulindac, a nonsteroidal anti-inflammatory drug, causes regression of colorectal adenomas in the retained rectal segment of FAP patients, although long-term use of this therapy has not been studied. We evaluated the long-term effectiveness and toxicity of sulindac in attempting to maintain retained rectal segments free of adenomas. METHODS: Twelve FAP patients (5 women), mean age 37.1 years, with IRA received sulindac (mean dosage, 158 mg/day) for a mean period of 63.4 +/- 31.3 months (range, 14-98 months). Number, size, and histologic grade of polyps, side effects, and medication compliance were assessed every 4 months. RESULTS: Seven of 12 patients (58%) remained in the study (6 of these polyp-free) for a mean of 76.9 +/- 27.5 months. Five of 12 patients (42%) withdrew from the trial after a mean follow-up period of 44 +/- 28 months (range, 14-89 months). A significant regression of polyp number was observed in all patients at 12 months (P = 0.039) and at a mean of 63.4 +/- 31.3 months (P = 0.006). Prevention of recurrence of higher-grade adenomas (tubulovillous, villous adenomas) was also observed (P = 0.004). At 35 months of follow-up, 1 patient developed stage III cancer in the rectal stump. The most common side effect was rectal mucosal erosions in 6 patients. CONCLUSIONS: Long-term use of sulindac seems to be effective in reducing polyp number and preventing recurrence of higher-grade adenomas in the retained rectal segment of most FAP patients. Erosions at the IRA site can preclude adequate dose maintenance.     

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.     

Familial adenomatous polyposis and duodenal lymphoma

The occurrence of duodenal polyposis is well recognized in familial adenomatous polyposis. Lymphoid hyperplasia in association with familial adenomatous polyposis usually occurs in the terminal ileum, but it can occur in the duodenum and may be endoscopically difficult to distinguish from an adenoma. A case report is presented in which a 54-yearold male with familial adenomatous polyposis, who 20 years earlier had a subtotal colectomy and ileorectal anastomosis, presented with a large rectal villous tumor and was found to have a duodenal extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The role of lymphoid hyperplasia in the development of mucosa-associated lymphoid tissue lymphoma is discussed, as well as the issue of mucosa-associated lymphoid tissue lymphoma in familial adenomatous polyposis. In cases in which biopsies of polypoid lesions in patients with familial adenomatous polyposis show dense lymphoid aggregates, flow cytometry may assist in the diagnosis.