Ellen McGannon

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.

Desmoid Tumors in Familial Polyposis Coli

Desmoid tumors are locally invasive, nonmctastasizing fibrous tumors most frequently seen in patients with familial polyposis coli (FPC). Of 325 patients with FPC treated at the Cleveland Clinic, 29 (8.9%) were found to have a total of 36 desmoid tumors. These tumors occur in young patients (mean age: 29.8 years), particularly women (ratio 3:1), and most appeared after previous colectomy (86%). The majority (72% of all desmoids, 90% of patients) were located within the abdomen, specifically within the mesentery of the small intestine. In most cases, attempts at surgical resection were followed by recurrence, and other previous treatments were similarly ineffective. Six of the 29 patients (21%) died from the desmoid and three died from other causes. The recent use of sulindac (Clinoril

Noncytotoxic drug therapy for intra-abdominal desmoid tumor in patients with familial adenomatous polyposis

) has produced some early encouraging results in four patients with these tumors that have proven so difficult to treat in the past.

Mucosectomy vs. stapled ileal pouch-anal anastomosis in patients with familial adenomatous polyposis: Functional outcome and neoplasia control

OBJECTIVE This study was performed to examine the relation between phenotypic expression in patients with familial adenomatous polyposis (FAP) and the site of mutations in the APC (adenomatous polyposis coli) gene. The ability of APC mutations to predict surgical outcome was also investigated. SUMMARY BACKGROUND DATA Germline mutations in the APC gene cause FAP and can now be identified by direct mutational analysis. Such an analysis can identify affected persons for close surveillance and spare unaffected persons. Phenotypic expression varies within and among FAP kindreds, but certain mutations have been associated with severe disease. Patients with severe polyposis are frequently offered total proctocolectomy rather than colectomy and ileorectal anastomosis out of concern for increased rectal cancer risk. Mutation analysis may offer a more rational basis for these decisions. METHODS The postsurgical courses of 58 patients from 19 FAP kindreds with identified APC gene mutations were reviewed. APC gene mutations were identified by analysis of leukocyte DNA using single-strand conformational analysis and DNA sequencing. FAP severity was defined according to the number of polyps in the colon at the time of resection (< 1000, mild; > 1000, severe). Operations included subtotal colectomy with ileorectal anastomosis (IRA), total proctocolectomy with ileal pouch/anal anastomosis, total proctocolectomy with end ileostomy, and partial colectomy (PC). RESULTS Eight different APC mutations were identified. Mutations at codons 1309 and 1328 in exon 15G were associated with a uniformly severe polyposis phenotype. For other mutations, the phenotype was more variable. Patients with APC mutations at codons 1309 and 1328 more commonly underwent proctectomy. Among the 43 patients who initially underwent either IRA or PC, the rectum was later removed in 8. Seven of these patients had a mutation at codon 1309 or 1328. With one exception, all patients with mutations outside the 1309 or 1328 site who initially had IRA have retained their rectum. CONCLUSIONS Our data support an association between severe polyposis phenotype and mutations at APC gene codons 1309 and 1328. For patients with these mutations, the prognosis for retaining the rectum is poor.

Gastroduodenal polyps in patients with familial adenomatous polyposis

Forty of 416 patients with familial adenomatous polyposis were noted to have intra-abdominal desmoid tumors, and a subgroup of 16 were treated with noncytotoxic drug therapy. Drugs used were sulindac (14 patients), sulindac plus tamoxifen (3 patients), indomethacin (4 patients), tamoxifen (4 patients), progesterone (DEPO-PROVERA®; Upjohn Co., Kalamazoo, MI) (2 patients), and testolactone (1 patient). Therapy with these drugs for continuous periods of six months or more resulted in three complete and seven partial remissions. When treated patients were compared with untreated patients (n=12), there were significant benefits for the treated group, both in reduction of desmoid size and in improvement of symptoms, despite the inherent selection bias against this. Sulindac was the only drug used in enough patients to permit independent evaluation of its effect, with one complete and seven partial reductions of tumor size. Some patients had a delayed response to sulindac, with tumor shrinkage occurring after an initial period of tumor enlargement. When using sulindac for the treatment of desmoid tumors, this phenomenon should be considered.

Risk of rectal cancer in patients after colectomy and ileorectal anastomosis for familial adenomatous polyposis: a function of available surgical options.

PURPOSE: The tradeoff of neoplasia control for better function represented by a stapled ileal pouch‐anal anastomosis is still controversial in patients with familial adenomatous polyposis. We compared outcomes after mucosectomy and hand‐sewn ileal pouch‐anal anastomosis with those after stapled ileal pouch‐anal anastomosis in 119 patients with familial adenomatous polyposis who underwent surgery since 1983. METHODS: Age, gender, length of follow‐up, complications, quality of life, incontinence, urgency, nighttime and daytime seepage, pad usage, necessity of ileostomy, and incidence of adenomas developing in pouch and anal transitional zone were recorded. RESULTS: There were 42 mucosectomy and 77 stapled patients who were followed up for an average of 5.8 and 3.6 years, respectively, with endoscopic surveillance. There was one postoperative death in the stapled group that prohibited long‐term follow‐up. Nine of 42 mucosectomy patients developed pouch adenomas vs. 8 of 76 in the stapled group. Six of 42 patients developed adenomas in the mucosectomized anal transitional zone in the mucosectomy group. Twenty‐one of 76 patients developed adenomas in the anal transitional zone in the stapled group. All were managed with local procedures or further surveillance. One of 76 patients developed cancer in the residual low rectum; this required further resection. Patients with stapled anastomosis had better outcomes in every category. Differences in incontinence, daytime and nighttime seepage, pad usage, and avoidance of ileostomy were statistically significant. All patients with mucosectomy required ileostomy vs. only 40 of 77 patients with stapled anastomosis. CONCLUSION: Familial adenomatous polyposis patients with stapled ileal pouch‐anal anastomosis have better functional outcome and can avoid temporary diversion. This should be balanced against a 28 percent incidence of adenomas in the anal transitional zone.PURPOSE: The tradeoff of neoplasia control for better function represented by a stapled ileal pouch-anal anastomosis is still controversial in patients with familial adenomatous polyposis. We compared outcomes after mucosectomy and hand-sewn ileal pouch-anal anastomosis with those after stapled ileal pouch-anal anastomosis in 119 patients with familial adenomatous polyposis who underwent surgery since 1983. METHODS: Age, gender, length of follow-up, complications, quality of life, incontinence, urgency, nighttime and daytime seepage, pad usage, necessity of ileostomy, and incidence of adenomas developing in pouch and anal transitional zone were recorded. RESULTS: There were 42 mucosectomy and 77 stapled patients who were followed up for an average of 5.8 and 3.6 years, respectively, with endoscopic surveillance. There was one postoperative death in the stapled group that prohibited long-term follow-up. Nine of 42 mucosectomy patients developed pouch adenomasvs. 8 of 76 in the stapled group. Six of 42 patients developed adenomas in the mucosectomized anal transitional zone in the mucosectomy group. Twenty-one of 76 patients developed adenomas in the anal transitional zone in the stapled group. All were managed with local procedures or further surveillance. One of 76 patients developed cancer in the residual low rectum; this required further resection. Patients with stapled anastomosis had better outcomes in every category. Differences in incontinence, daytime and nighttime seepage, pad usage, and avoidance of ileostomy were statistically significant. All patients with mucosectomy required ileostomyvs. only 40 of 77 patients with stapled anastomosis. CONCLUSION: Familial adenomatous polyposis patients with stapled ileal pouch-anal anastomosis have better functional outcome and can avoid temporary diversion. This should be balanced against a 28 percent incidence of adenomas in the anal transitional zone.

Incidence of neoplastic polyps in the ileal pouch of patients with familial adenomatous polyposis after restorative proctocolectomy.

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.

Adrenal masses in patients with familial adenomatous polyposis

AbstractPURPOSE: 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.

Significance of incidental desmoids identified during surgery for familial adenomatous polyposis.

PURPOSE: Although adenomatous polyps and even adenocarcinomas have been found in the terminal ileum of patients with familial adenomatous polyposis, the prevalence of neoplastic changes in the pouches of patients who have undergone restorative proctocolectomy is unknown. The objective of this study was to determine the frequency of pelvic pouch neoplasia in famial adenomatous polyposis patients after restorative proctocolectomy. METHODS: Patients in a polyposis registry who had undergone restorative proctocolectomy were recruited. Demographic, surgical, pathologic, and endoscopic data were obtained from patient records. Video pouchoscopy was done after two enemas and representative biopsies were taken. RESULTS: Of 102 eligible patients, 26 (17 males and 9 females) participated. Median age at ileal pouch-anal anastomosis was 31 (range, 12–58) years. Median follow-up period was 66 (11–156) months. Adenomas were found in the pouch of 11 (42 percent) patients, in the terminal ileum above the pouch in 1 patient, and in the anal canal of 4 patients. Among patients with pouch polyps, three patients had one lesion, three patients had two lesions, and five patients had more than ten lesions. The incidence of polyps increased steadily with time from restorative proctocolectomy. There was no relation between the incidence of pouch polyposis and the severity of colonic or duodenal disease. CONCLUSIONS: Proctocolectomy and ileal pouch-anal anastomosis is associated with a significant risk of pouch neoplasia in familial adenomatous polyposis patients. The severity of pouch adenomas was not related either to the severity of colonic or duodenal disease. The pelvic pouches of all patients with familial adenomatous polyposis who have undergone restorative proctocolectomy should be examined periodically.