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.     

Risk of Rectal Cancer in Patients After Colectomy and Ileorectal Anastomosis for Familial Adenomatous Polyposis

PURPOSE: One of the concerns with colectomy and ileorectal anastomosis as a prophylactic procedure for patients with familial adenomatous polyposis is the risk of metachronous rectal cancer, estimated at from 12 to 43 percent. These estimates are based largely on surgeries performed at a time when the only alternative option to ileorectal anastomosis for patients with severe familial adenomatous polyposis was proctocolectomy and ileostomy. This study was designed to test the hypothesis that in the pouch era severe polyposis is now treated by proctocolectomy and ileal pouch-anal anastomosis. Ileorectal anastomosis is performed mostly in mildly affected patients and will therefore carry a very low risk of metachronous rectal cancer. METHODS: Patients undergoing primary prophylactic surgery for familial adenomatous polyposis between 1950 and 1999 were categorized according to the year of their surgery: prepouch era (before 1983) or pouch era (after 1983). Patients undergoing colectomy and ileorectal anastomosis were the focus of the study, and rate of proctectomy and the incidence of rectal cancer were recorded for each group. Data on the severity of the polyposis for each group were abstracted. RESULTS: A total of 197 patients underwent ileorectal anastomosis, 62 in the prepouch era (median follow-up, 212 months; interquartile range, 148 months) and 135 in the pouch era (median follow-up, 60 months; interquartile range, 80 months). Patients in the prepouch era came to surgery at the same median age as those in the pouch era (median age 23.0 years, interquartile ranges 15.5 years for prepouch and 17 years for pouch). Similar proportions of patients in the prepouch era had severe polyposis (49 percent) as in the pouch era (44 percent), although all severely affected patients had an ileorectal anastomosis in the prepouch era vs. 39 percent in the pouch era. Twenty (32 percent) prepouch-era patients underwent proctectomy compared with three (2 percent) pouch-era patients. No pouch-era patient had rectal cancer on follow-up; eight (12.9 percent) prepouch-era patients did. CONCLUSION: Although follow-up is shorter, ileorectal anastomosis for familial adenomatous polyposis performed since 1983 carries a much lower rate of rectal cancer and proctectomy than ileorectal anastomosis performed before this time, when restorative proctocolectomy was not an option. This is related, at least in part, to a greater number of patients with severe polyposis having their rectum initially spared.     

Rectal mucosal ornithine decarboxylase activity in familial adenomatous polyposis after ileorectal anastomosis.

Resection of the colon in patients with familial adenomatous polyposis frequently results in the regression of polyps in the remaining rectum, suggesting a reduction of cellular proliferation. These patients remain at risk of developing rectal cancer but whether this risk increases with time is uncertain. Since ornithine decarboxylase activity is associated with cellular proliferation, mucosal ornithine decarboxylase was measured in rectal biopsy specimens from patients with familial adenomatous polyposis after ileorectal anastomosis (n = 36) and from normal controls (n = 30). The relationship between ornithine decarboxylase activity, age, and time from surgery was also examined. Median ornithine decarboxylase activity in familial adenomatous polyposis patients after ileorectal anastomosis (186, interquartile range (IQR) 107-534 pmol/mg protein/h) was not different from that in control subjects (227, IQR 123-374, p = 0.6). When patients were divided into three equal groups according to age, however, younger patients (< 25 years) had significantly higher activity than both older age groups (p < 0.02). Similarly, when patients were stratified according to the time elapsed since surgery, those who had had surgery less than six years previously had a significantly higher ornithine decarboxylase activity than those in whom a longer time interval had elapsed since surgery (p = 0.02). These results indicate that after colon resection, ornithine decarboxylase activity in patients with familial adenomatous polyposis is similar to that in normal controls but seems to fall over time. This may explain the regression of rectal polyps after colonic resection in this disorder.     

Pancreatic acinar cell carcinoma in familial adenomatous polyposis

Pancreatic carcinoma is rarely associated with familial adenomatous polyposis (FAP). Ten patients with this association have been reported in the literature. However, detailed data were available in only a few cases. The first case of pancreatic acinar cell carcinoma associated with FAP is reported. A 51-year-old man who had undergone total colectomy and ileoproctostomy for colonic polyposis 29 years previously was admitted with a cancer in the residual rectum. Preoperative examinations revealed a tumor in the head of the pancreas. Pancreaticoduodenectomy and very low anterior resection of the rectum were performed. Histologically, the tumor of the pancreas was acinar cell carcinoma. In patients with FAP, we recommend careful surveillance of not only the gastrointestinal tract but also of other organs such as those of the pancreaticobiliary system and the endocrine organs.     

Value of screening of familial adenomatous polyposis for the prevention of colorectal cancer]

Familial adenomatous polyposis coli is a hereditary autosomal dominant disease which spontaneously and inevitably leads to degeneration of colorectal adenomas and requires preventive surgical treatment. The aim of this study was to evaluate the age of colorectal degeneration and the need for a screening technique in family members. Between 1983 and 1989, 141 patients were treated for familial adenomatous polyposis in our surgical center. Mean age at surgery was 32 years and 64 patients (45.4 percent) had a colorectal carcinoma. Thirty had an in situ tumor (mean age: 30 years) and 34 had an invasive adenocarcinoma (mean age: 45 years), 7 of whom died of their cancer. No colonic cancer was found in patients younger than 20. Thirty-eight percent of the patients under 40 years of age, 73 percent of the patients older than 40 years and 81 percent of those older than 50 had an adenocarcinoma. Fifty percent of the patients with carcinoma were younger than 40 years and 7 percent were less than 25 years old. Seventy-one patients were symptomatic at the time of operation (mean age: 40 years), 32 (45 percent) had a colonic cancer. In 70 patients, familial adenomatous polyposis was detected by screening (mean age: 24) and 2.8 percent had a colonic carcinoma. We conclude that the age-related risk of developing colonic carcinoma requires prophylactic surgery in asymptomatic patients before 20 years of age, and that routine familial screening would be of some benefit.     

Rare Coincidence of Familial Adenomatous Polyposis and a Retroperitoneal Fibromyxoid Sarcoma: Report of a Case

Purpose Familial adenomatous polyposis is an autosomal-dominant inherited disease with development of as many as thousands of adenomas within colon and rectum. All untreated patients will develop colorectal adenocarcinoma. A variety of extracolonic manifestations can occur, although malignant tumors are rare. An association of familial adenomatous polyposis and sarcomas was reported in a few cases only. Methods We present the exceptional case of a 24-year-old male with genetically verified familial adenomatous polyposis (deletion of 10 base pairs at position 228–237 of exon 15A). The patient underwent prophylactic subtotal proctocolectomy and ileal-pouch rectal anastomosis in 2003. Two years later, an obstruction of the left ureter caused by a retroperitoneal mass was diagnosed. Results Histopathologic findings after complete tumor resection showed a low-grade fibromyxoid sarcoma. CT scan and clinical follow-up through 15 months postoperatively revealed no recurrent tumor growth. Conclusions To our knowledge, this is the first reported case of familial adenomatous polyposis with metachronous retroperitoneal fibromyxoid sarcoma. Proctocolectomy or total colectomy and complete tumor resection is the treatment of choice in this case. In addition to more common semimalignant retroperitoneal desmoid tumors in familial adenomatous polyposis patients, a malignant soft-tissue tumor also has to be considered for differential diagnosis. Presented at the Cancer Congress of Saxony-Anhalt, Magdeburg, Germany, March, 23 to 24, 2007. Reprints are not available.     

Long-term follow-up after colectomy and ileorectal anastomosis in familial adenomatous polyposis coli. Is there still a place for the procedure?

Forty-four patients with familial adenomatous polyposis coli treated with colectomy and ileorectal anastomosis were studied. Mean age at operation was 27 years. The mean follow-up period was 10 years (median 8 years). Three patients (7%) developed rectal cancer 1, 4, and 24 years after the initial operation, respectively. Proctectomy with ileostomy was performed in one patient, and 7 patients underwent a conversion to an ileoanal procedure for an increasing number of rectal polyps in the rectum stump. Although frequent bowel actions and episodes of diarrhea were common findings in patients after colectomy and ileorectal anastomosis, almost all patients (96%) were more or less satisfied with their quality of life after the procedure. On the basis of our results and the results reported in the literature, colectomy with ileorectal anastomosis is still the operation of choice in selected patients with familial adenomatous polyposis coli. An initial ileal pouch - anal anastomosis, or a conversion to such a procedure after colectomy and ileorectal anastomosis is indicated, depending on the number and size of rectal polyps.     

Local chemotherapy for rectal polyposis: intraluminal administration of 5-fluorouracil for postoperative control of adenomas in the retained rectum in familial polyposis

We administered the anticancer drug 5-fluorouracil locally to treat rectal adenomas in four patients with familial adenomatous polyposis who had undergone total colectomy and ileorectal anastomosis. The drug was administered either in suppository form or in high concentration as a rectal enema. One patient was treated successfully with 5-fluorouracil suppositories without any side effects, but the suppository regimen had to be stopped in three other patients because of severe rectal urgency. However, one of these patients was treated effectively with rectal administration of a high-dose 5-fluorouracil solution. Adenomas near the anastomotic site or dentate line were difficult to treat. Although severe urgency was seen in most patients, we think that the intraluminal administration of anticancer agents may prove effective in treating polyposis of the rectum retained after colectomy in familial polyposis. It deserves further study.     

Familial juvenile polyposis coli; increased risk of colorectal cancer.

Six patients from one family and one solitary patient with juvenile polyposis coli are described. The histological changes in colonic polyps formed a spectrum from juvenile polyps, through focal to extensive adenomatous change, to adenocarcinomas. One patient aged 49 years had an adenocarcinoma of the colon and in another, aged 33, with rectal polyps and metastatic cancer this was suspected although the primary tumour was not located. Two additional patients, aged 19 and 41 years, had severe adenomatous dysplasia in a juvenile polyp. Four patients also had gastroduodenal polyps. The present findings clearly contradict the previous view that juvenile polyposis coli is not premalignant and only rarely needs surgical treatment. As other recent reports also describe frequent occurrence of neoplastic changes in juvenile polyps, colectomy, and ileorectostomy at the age of about 20 years is recommended as the treatment of choice for juvenile polyposis coli, as in patients with familial adenomatosis coli. Follow up should ideally include gastroduodenoscopy and inspection of the rectal remnant at regular intervals.     

Results of ileal J-pouch-anal anastomosis in familial adenomatous polyposis complicated by rectal carcinoma

PURPOSE: Rectal cancer frequently occurs in patients with familial adenomatous polyposis (FAP) and, in some cases, proctocolectomy and ileal pouch-anal anastomosis (IPAA) can be proposed as an alternative to end ileostomy. This study aimed to assess the results of IPAA for familial adenomatous polyposis complicated by rectal carcinoma. PATIENTS AND METHODS: Postoperative morbidity and bowel function following IPAA were assessed in six patients who had a mesorectal excision for rectal cancer. The functional results were compared with those obtained after IPAA in 134 FAP patients without bowel cancer. RESULTS: Carcinomas were located at a mean of 11 cm from the dentate line. There were no postoperative complications. One patient with synchronous hepatic metastases died 6 months after operation and the 5 others were alive without recurrence after a mean follow-up of 29 months. Mean frequency of defecation was 6.5/day (vs. 4.2/day in patients without carcinoma), 86 percent of patients had nocturnal defecation (vs. 50 percent), day and night continence were normal in 66 percent and 33 percent of patients, respectively, compared with 90 percent and 85 percent for IPAA without cancer. Pouch excision was required in one patient for unsatisfactory functional result. CONCLUSION: IPAA can be safely performed for cancer of the upper rectum complicating FAP, but a poor functional outcome related to mesorectal excision has to be expected.     

Familial adenomatous polyposis

PURPOSE: Virtually all untreated patients with familial adenomatous polyposis develop colorectal carcinoma. Thus, prophylactic colectomy is indicated. Detractors of ileal pouch-anal anastomosis prefer ileorectal anastomosis for teenagers because of the potential negative impact of ileal pouch-anal anastomosis on quality of life. The aim of this study was to assess the effects on quality of life of ileal pouch-anal anastomosis in teenagers with familial adenomatous polyposis. METHODS: Between 1981 and 1998, 48 teenagers underwent ileal pouch-anal anastomosis for familial adenomatous polyposis. One patient had proctectomy and ileal pouch-anal anastomosis after previous ileorectal anastomosis. A temporary diverting loop ileostomy was established in 42 patients (87.5 percent). One patient had colonic carcinoma diagnosed preoperatively. Two other patients were found to have unsuspected rectal cancer at surgery. Mean follow-up (± standard deviation) in 43 patients was 80.5±42 months. RESULTS: There was no immediate postoperative mortality. Postoperative complications included pelvic sepsis (3 patients; 1 requiring reoperation) and bleeding (1 patient; no surgery required). One patient died of metastatic colonic carcinoma. Ten patients required reoperation, seven had bowel obstruction, one had portal hypertension, and two required an ileostomy. The mean (± standard deviation) daytime and nighttime stool frequency was 4±1.5 and 1±1, respectively. One patient reported daytime and nighttime incontinence, and two patients reported nighttime incontinence only. No patient experienced impotence or retrograde ejaculation. Social, sexual, sport, housework, recreation, family, travel, and work activities were improved or unchanged in 82.5, 87, 80, 90, 80, 92.5, 77.5, and 89 percent of patients, respectively. Three male patients fathered children, and three female patients had a total of six children after normal pregnancies and deliveries. CONCLUSION: The impact of ileal pouch-anal anastomosis on quality of life was favorable in the majority of teenagers. The risk of rectal cancer should be the major consideration before proposing an operation to teenagers with familial adenomatous polyposis.Poster presentation at The American Society of Colon and Rectal Surgeons' 100th Anniversary and Tripartite Meeting, Washington, D.C., May 1 to 6, 1999.     

Prevalence and Morphology of Pouch and Ileal Adenomas in Familial Adenomatous Polyposis

PURPOSE In familial adenomatous polyposis, the long-term risk of pouch polyposis and potential for pouch cancer are unknown. Our aim was to evaluate prospectively the prevalence, nature, and etiology of pouch ileal adenomas with that of nonpouch ileal adenomas in familial adenomatous polyposis.METHODS Sixty patients with familial adenomatous polyposis pouch, 47 familial adenomatous polyposis patients with ileorectal anastomosis, and 20 younger patients with familial adenomatous polyposis who had prophylactic colectomy were examined with videoendoscopy.RESULTS Adenomatous polyps were found in the pouches of 34 patients (57 percent). A total of 362 polyps were identified (range, 0–50 per patient). A logistic regression model confirmed that there was a significant association between the increasing age of the patient and the presence of pouch adenomas (P < 0.02) and the length of follow-up since pouch surgery (P < 0.05). There was no apparent relationship between the development of pouch adenomas and the severity of either colonic or duodenal polyposis and there were no clear genotype or phenotype correlations. Most polyps were tubular adenomas with mild dysplasia, but 11 patients had more advanced histology, including two patients with large villous adenomas. Nonpouch ileal mucosa was spared from visually observed adenomas, with only 1 of 48 (2 percent) patients with ileorectal anastomosis adenomas and 0 of 20 (0 percent) younger, precolectomy patients having terminal ileal adenomas. However, microadenomas were present on random biopsy in 4 percent to 5 percent of nonpouch ileum.CONCLUSION The risk of pouch cancer in familial adenomatous polyposis is unclear, but follow-up periods since surgery remain relatively short. Long-term endoscopic surveillance of familial adenomatous polyposis pouches is thus recommended along with evaluation of potential therapeutic options for pouch adenomas.I. G. Beveridge and C. J. Groves were supported by Cancer Research UK (formerly the Imperial Cancer Research Fund).     

Long-Term Outcome After Ampullectomy for Ampullary Lesions Associated With Familial Adenomatous Polyposis

PURPOSE Up to 90 percent of patients with familial adenomatous polyposis develop adenomas in the upper gastrointestinal tract. Besides pancreaticoduodenectomy, which remains indicated in duodenal and ampullary cancer, less aggressive surgical procedure (such as ampullectomy) must be evaluated in selected patients with familial adenomatous polyposis patients presenting low-risk benign duodenal adenomas. METHODS From 1995 to 2000, we performed a retrospective, observational study, which included eight patients (5 females) with familial adenomatous polyposis underwent ampullectomy (with frozen sections) for presumed benign polyposis lesions. Six patients had an ileal pouch-anal anastomosis performed 2 to 27 years before ampullectomy. The remaining two patients had ampullectomy during the same operation than ileal pouch-anal anastomosis. RESULTS No patient died postoperatively. Mean hospital stay was 15 ± 6.5 (range, 10–21) days. There was one major complication (pancreatic fistula), which was treated conservatively. Final pathologic examination of the specimens revealed that three patients had a severe dysplasia. Mean follow-up of the patients was 58 ± 37 (range, 24–119) months. During endoscopic follow-up, although all the patients underwent endoscopic resection of duodenal polyps, none presented recurrence at the ampullectomy site. CONCLUSIONS Ampullectomy could be safely proposed in selected familial adenomatous polyposis patients. Our low morbidity and the absence of recurrence after almost five years of follow-up suggests that such conservative treatment could be proposed before pancreaticoduodenectomy in patients with high-risk ampullary adenomas without invasive carcinoma.     

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.     

Effect of sulindac treatment for attenuated familial adenomatous polyposis with a new germline APC mutation at codon 161: report of a case

INTRODUCTION: Patients with familial adenomatous polyposis develop colorectal cancers if left untreated. As indicated in patients with familial adenomatous polyposis, prophylactic colectomy has been recommended even in a milder colonic phenotype referred to as attenuated familial adenomatous polyposis. However, therapeutic strategies in attenuated familial adenomatous polyposis are still controversial. METHODS: We report a patient with attenuated familial adenomatous polyposis who has been treated with sulindac for five years. During the period of observation, she has been carefully followed up by chromoscopic and radiographic surveillance. Immunohistochemical study for cyclooxygenase-2 and genetic analysis in the adenomatous polyposis coli gene was also performed. RESULTS: Continuous administration of sulindac resulted in obvious regression of both colorectal adenomatous polyps and gastric fundic gland polyps, and no cancers developed during the observation period. Immunohistochemical study showed the decrease of cyclooxygenase-2-positive epithelial cells in colorectal polyps by the treatment. The genetic analysis revealed a C to A substitution at nucleotide 481 of her germline adenomatous polyposis coli gene, which resulted in a nonsense mutation at codon 161. CONCLUSIONS: Our case suggests that treatment with sulindac accompanied by intensive colonoscopic surveillance may be a choice of management for attenuated familial adenomatous polyposis.     

Risk factors for rectal cancer morbidity and mortality in patients with familial adenomatous polyposis after colectomy and ileorectal anastomosis

PURPOSE: The aims of the study were to investigate the effects of ileorectal anastomosis and the follow-up program on rectal cancer morbidity and mortality and to identify risk factors that predict the fate of the rectal stump. METHODS: One hundred ninety-five patients with familial adenomatous polyposis on whom an ileorectal anastomosis was performed between 1957 and the end of 1995 were included. Median follow-up time was 14 (range, 1-39) years. The cumulative risks of rectal cancer and rectal excision were estimated using survival analysis. RESULTS: Eighteen patients (9.2 percent) developed cancer, 17 in the retained colorectal segment and one on the ileal side of the anastomosis, and nine died of their cancer during the study period. The cumulative rectal cancer morbidity and mortality 20 years after ileorectal anastomosis was 12.1 percent (95 percent confidence interval = 5.7-18.5) and 7 percent (95 percent confidence interval = 2-12), respectively. The cumulative age-dependent risk of rectal cancer was 22.9 percent (95 percent confidence interval = 11.4-34.5) and 25.7 percent (95 percent confidence interval = 13.2-38.2) at the ages of 60 and 70 years, respectively. The corresponding cumulative mortality was 11.1 percent (95 percent confidence interval = 2.9-19.3) at the age of 70 years. Patients with dense polyposis at colectomy had an increased risk for cancer in the retained colorectal segment compared with patients with intermediate or sparse polyposis (P = 0.04). Sixty-six patients (34 percent) had their rectum removed, and the cumulative rectal excision rate 35 years after ileorectal anastomosis was 65.5 percent (95 percent confidence interval = 53-78). CONCLUSION: Patients on whom ileorectal anastomosis was performed had, despite the high rectal excision rate, a substantial risk of developing cancer in the retained colorectal segment, with an ensuing high mortality. Our results indicate that patients with dense polyposis should undergo restorative proctocolectomy as primary operation for familial adenomatous polyposis. In younger patients with intermediate or sparse polyposis and good expected follow-up compliance, ileorectal anastomosis still is an alternative.     

Attenuated familial adenomatous polyposis: an evolving and poorly understood entity.

PURPOSE: Familial adenomatous polyposis is a well-described, autosomal dominant, inherited syndrome characterized by diffuse polyposis of the colon and rectum as well as various upper gastrointestinal and extraintestinal manifestations. A subset of patients present with fewer colorectal polyps, later age of onset of polyps and cancer, and a predilection toward involvement of the proximal colon. This variant of familial adenomatous polyposis is known as attenuated familial adenomatous polyposis. The purpose of this review is to summarize current knowledge regarding this poorly understood entity and propose guidelines for diagnosis, surveillance, and surgical management. METHODS: The MEDLINE database was searched from 1985 onward using the keywords, "attenuated familial adenomatous polyposis," "AFAP," "adenomatous polyposis coli gene," and "APC gene." Additional articles were identified through the reference sections of retrieved papers. All papers that pertained to attenuated familial adenomatous polyposis or mutations in the APC gene producing an attenuated phenotype were included. RESULTS: Attenuated familial adenomatous polyposis is transmitted in an autosomal dominant fashion. Several distinct mutations within the APC gene have been associated with an attenuated phenotype, but variability of disease expression within kindreds possessing identical mutations makes classification difficult. Polyps are diagnosed at a mean age of 44 years, with cancer diagnosed at a mean of 56 years of age. Frequent involvement of the proximal colon necessitates the use of colonoscopy for surveillance, and infrequent involvement of the rectum supports the role of a total abdominal colectomy and ileorectal anastomosis. CONCLUSIONS: Although currently recognized as a distinct clinical entity, attenuated familial adenomatous polyposis may be part of a spectrum of disease that includes familial adenomatous polyposis and is caused by different mutations within the APC gene. Because of its unique characteristics, yet apparent overlap with familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, increased awareness of attenuated familial adenomatous polyposis should improve diagnosis, surveillance, and treatment strategies in this unique subset of familial polyposis syndromes.     

Effect of Sulindac Treatment for Attenuated Familial Adenomatous Polyposis With a New Germline APC Mutation at Codon 161

INTRODUCTION: Patients with familial adenomatous polyposis develop colorectal cancers if left untreated. As indicated in patients with familial adenomatous polyposis, prophylactic colectomy has been recommended even in a milder colonic phenotype referred to as attenuated familial adenomatous polyposis. However, therapeutic strategies in attenuated familial adenomatous polyposis are still controversial. METHODS: We report a patient with attenuated familial adenomatous polyposis who has been treated with sulindac for five years. During the period of observation, she has been carefully followed up by chromoscopic and radiographic surveillance. Immunohistochemical study for cyclooxygenase-2 and genetic analysis in the adenomatous polyposis coli gene was also performed. RESULTS: Continuous administration of sulindac resulted in obvious regression of both colorectal adenomatous polyps and gastric fundic gland polyps, and no cancers developed during the observation period. Immunohistochemical study showed the decrease of cyclooxygenase-2–positive epithelial cells in colorectal polyps by the treatment. The genetic analysis revealed a C to A substitution at nucleotide 481 of her germline adenomatous polyposis coli gene, which resulted in a nonsense mutation at codon 161. CONCLUSIONS: Our case suggests that treatment with sulindac accompanied by intensive colonoscopic surveillance may be a choice of management for attenuated familial adenomatous polyposis.     

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     

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.