Genotype-phenotype correlations in attenuated adenomatous polyposis coli

Germ-line mutations of the tumor suppressor APC are implicated in attenuated adenomatous polyposis coli (AAPC), a variant of familial adenomatous polyposis (FAP). AAPC is recognized by the occurrence of <100 colonic adenomas and a later onset of colorectal cancer (age >40 years). The aim of this study was to assess genotype-phenotype correlations in AAPC families. By protein-truncation test (PTT) assay, the entire coding region of the APC gene was screened in affected individuals from 11 AAPC kindreds, and their phenotypic differences were examined. Five novel germ-line APC mutations were identified in seven kindreds. Mutations were located in three different regions of the APC gene: (1) at the 5' end spanning exons 4 and 5, (2) within exon 9, and (3) at the 3' distal end of the gene. Variability in the number of colorectal adenomas was most apparent in individuals with mutations in region 1, and upper-gastrointestinal manifestations were more severe in them. In individuals with mutations in either region 2 or region 3, the average number of adenomas tended to be lower than those in individuals with mutations in region 1, although age at diagnosis was similar. In all AAPC kindreds, a predominance of right-sided colorectal adenomas and rectal polyp sparing was observed. No desmoid tumors were found in these kindreds. Our data suggest that, in AAPC families, the location of the APC mutation may partially predict specific phenotypic expression. This should help in the design of tailored clinical-management protocols in this subset of FAP patients.     

Familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is an autosomal dominant disease characterized by the development of numerous adenomatous polyps in the colon and rectum with diverse extracolonic manifestations. Recent genetic advances have lead to the sequencing of the FAP gene, with important implications for screening, diagnosis and follow-up. Appropriate management of probands and at-risk patients is of the utmost importance, as untreated carriers will develop colorectal cancer. Identification of FAP families and tracing of pedigrees represent the most important steps. To this end registries are essential, allowing a comprehensive multidisciplinary approach. They have justified their place by decreasing related morbidity and mortality. An overview and discussion of clinical features and management are presented.     

p53 and K-ras status in duodenal adenomas in familial adenomatous polyposis

BACKGROUND: The genetic alterations in patients with familial adenomatous polyposis (FAP) and duodenal adenomas are poorly characterized when compared with data relating to colorectal tumorigenesis in the same patients. METHODS: Point mutation of the K-ras oncogene and point mutation and overexpression of the TP53 tumour suppressor gene were investigated in 32 duodenal polyps (seven without mucosal pathology, 23 with mildly dysplastic adenomas and two with moderately dysplastic adenomas) from 21 patients with FAP. RESULTS: K-ras mutation, TP53 mutation or positive p53 staining were not found in duodenal polyps without histological abnormality. Of 25 duodenal adenomas, K-ras mutation was found in three (two mildly dysplastic, one moderately dysplastic), 20 showed positive p53 immunostaining, and mutation of the TP53 gene was found in one moderately dysplastic adenoma. p53 protein overexpression in duodenal adenomas was significantly more frequent than mutation of either K-ras or TP53 (P < 0.01). CONCLUSION: p53 dysfunction is a hallmark of duodenal adenomas in patients with FAP. Overexpression may indicate DNA damage and thus an early step in tumorigenesis.     

Familial polyposis coli

Familial polyposis coli (FAP) presents multiple adenomas in the large bowel. Also, polyps in the upper gastrointestinal tract are observed in some cases of FAP. Since the risk of developing colorectal cancer is almost 100% in FAP, patients need surgical treatment (colectomy) after a diagnosis of FAP is made. After a gene for FAP (APC gene) was identified, an accurate diagnosis of FAP is becoming possible by examining APC gene, even though patients show no clinical manifestations. Many studies revealed various mutations of APC gene and examined the relation between the site of the germline APC mutation and the phenotypic expression of FAP. These studies suggested that there was a Genotype-Phenotype Correlation in FAP. Some differences of clinical features in FAP, such as profuse type and attenuated type of FAP (AAPC), are now considered to be caused by the difference of the site of the germline APC mutation.     

Results after restorative proctocolectomy and ileal pouch-anal anastomosis in patients with familial adenomatous polyposis and coexisting colorectal cancer

Although the operation of choice for patients with familial adenomatous polyposis (FAP) is restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA), its place in the management of patients with FAP and cancer has not been defined. The authors have reviewed their experience with these patients to determine the safety of IPAA and its efficacy as a cancer operation. The records of 55 patients with FAP who had undergone IPAA were examined. Follow-up studies included an annual questionnaire and physical examination. Eight patients had FAP with coexisting colorectal cancer. Median age at diagnosis was 25 (range 13-46) years, and at operation 33 (range 22-36) years. Of the eight patients (four men), four had colonic cancer and four had rectal cancer. Synchronous colorectal carcinoma was found in two patients. Staging according to the tumor node metastasis classification showed that five patients had stage 1 tumour, two had stage 2 and one had stage 3. Tumours were well, moderately or poorly differentiated in one, five and two patients respectively. During a median follow-up of 56 (range 14-98) months, metastasis developed in the liver of one patient 66 months after surgery. Two patients suffered complications: one had small bowel obstruction and the other mucosal prolapse. Tubular adenomas were found in the pouch of two patients and in the anal transitional zone of one. Pouch function is good to excellent in all surviving patients. Restorative proctocolectomy for patients with FAP and coexisting colorectal cancer can be undertaken with a favourable prognosis and function. It is compatible with curative intent.     

Cell cycle parameters in human colon: comparison between primary and recurrent adenocarcinomas, benign polyps and adjacent unaffected mucosa

The duration of S phase and the labeling index were measured in adenocarcinomas, in polyps and in adjacent unaffected mucosa of a same patient. The in vitro double labeling technique was employed. The S phase duration in tumors was significantly longer than in unaffected mucosa and polyps. This agrees with previously reported data on human skin, colon and rectum and supports the suggestion that a long S phase might correlated with carcinogenesis. The labeling index in the mucosa adjacent to the tumors is higher than previously measured in normal tissue. Following colectomy however, the labeling index in unaffected mucosa and tumor was lower than prior to surgery. This suggests the disappearance of a systemic factor (in the colon?) which positively regulates the proliferative activity in the rectal and colonic musoca. The maintainance of a lengthened S phase duration in the recurrent tumor where L.I. is lowered, indicates that the proliferation rate and the S phase duration are regulated by separate control factors.     

Gastric fundic gland polyps: a morphological study including mucin histochemistry, stereometry, and MIB-1 immunohistochemistry

Fundic gland polyps are benign lesions, composed of a disorderly arrangement of normal gastric corpus cell types, that occur in a large proportion of patients with familial adenomatous polyposis (FAP) but also develop sporadically in non-FAP patients as well. In this study, the authors evaluated and compared the endoscopic, histological, mucin histochemical, and microscopic stereologic features of 77 fundic gland polyps (FGPs) (15 FAP; 62 non-FAP) to determine if FAP-associated and sporadic lesions are histologically distinct. The authors also analyzed the distribution of mitotically active cells and smooth muscle cells in these lesions using MIB-1 and smooth muscle alpha-actin immunohistochemistry in an effort to determine the pathogenesis of these lesions. The results show that, compared with non-FAP cases, FAP patients with FGPs have a lower male-to-female ratio, a younger mean age at diagnosis, and a higher proportion of cases with multiple polyps. However, no differences were detected between FAP and non-FAP-associated FGPs with respect to any endoscopic, morphological, mucin histochemical, or stereometric features. Eighty-six percent of FGPs showed an increase in smooth muscle content, often in a pericystic distribution. MIB-1-positive proliferative cells were observed not only in the foveolar stem cell region, as expected, but also in the epithelium lining the microcysts and in the gland buds located directly adjacent to the microcysts. The authors conclude that FAP and non-FAP-associated FGPs are histologically identical, and propose that proliferation and subsequent differentiation of aberrantly located proliferative cells in these lesions may explain the histogenesis of FGPs.     

Increased stem cell somatic mutation in the non-neoplastic colorectal mucosa of patients with familial adenomatous polyposis

Colorectal tumorigenesis in familial adenomatous polyposis (FAP) results from somatic mutation of either the normal APC allele or another growth control gene in epithelial cells bearing a germline APC defect. The rate at which tumors develop is therefore dependent on the somatic mutation frequency; it is not known whether this is normal or elevated in FAP. We aimed to quantify stem cell somatic mutation in FAP, comparing it with hereditary nonpolyposis colorectal cancer (HNPCC) and Crohn's disease (CD). Stem cell somatic mutation frequency was studied in 47 FAP patients, 5 HNPCC patients, and 13 CD patients, all younger than 49 years, by quantifying crypt-restricted loss of O-acetyltransferase activity in sections of morphologically normal colonic mucosa from individuals heterozygous for this monogenically inherited polymorphism. Median stem cell somatic mutation frequency was significantly higher in FAP than HNPCC (4.2 x 10(-4) v 1.4 x 10(-4), Mann-Whitney U, P < .02). The level in CD (4.0 x 10(-4)) was similar to FAP. Mutated crypts occurred in groups more frequently in FAP (22%) than HNPCC (12%) or CD (10%), suggesting an increase in stem cell division associated with crypt fission in FAP. We conclude that stem cell somatic mutation frequency is raised in non-neoplastic colorectal mucosa in FAP. This is probably related to increased stem cell proliferation and contributes to the high rate of tumor formation in this condition.     

Diagnostic value of fundus examination in familial adenomatous polyposis

BACKGROUND: Multiple, bilateral lesions of congenital hypertrophy of the retinal pigment epithelium (CHRPE) have been described in patients suffering from familial adenomatous polyposis (FAP) since 1980. This study aimed to determine a reliable diagnostic criterion, based on the size and number of retinal CHRPE lesions, allowing the screening of patient carriers of the gene responsible for FAP. METHODS: 32 control subjects and 144 patients belonging to 85 FAP families were studied, divided into 124 carriers of the genetic alteration and 20 non-carriers. RESULTS: In carriers of the deleted gene, multiple, bilateral retinal lesions were consistently observed. Lesion situation, size, shape, and degree of pigmentation were variable however. A positive criterion for FAP was defined as the presence of at least four lesions whatever their size, or at least two lesions one of which is large. This criterion showed a high sensitivity (0.68) and a maximal specificity (1). Within each family, the retinal phenotypic expression was homogeneous. CHRPE lesions were observed in two thirds of the FAP families and absent from the remaining third. CONCLUSION: By using this new positive diagnostic criterion, fundus examination allows early detection of those children carrying the gene responsible for FAP in families positive at ocular examination.     

Upper gastrointestinal disease in patients with familial adenomatous polyposis

BACKGROUND: Upper gastrointestinal disease has become an important aspect in the management of patients with familial adenomatous polyposis (FAP). METHODS: A review of the literature was carried out using Medline. Epidemiology, pathology and treatment options are considered. RESULTS AND CONCLUSION: Despite the fact that over 90 per cent of patients with FAP develop duodenal adenomas, only 5 per cent go on to develop cancer. In the absence of methods to detect who is at risk of cancer, all patients undergo regular endoscopic surveillance at present. Chemoprevention in the form of drug therapy may be the answer to controlling the disease.     

Lack of telomerase in desmoids occurring sporadically and in association with familial adenomatous polyposis

BACKGROUND: Telomerase activity may be required for unlimited growth of cells and is repressed in most somatic tissues, but is detectable in immortal cell lines, germ cells, many malignancies and some benign lesions. Desmoids are proliferative, locally invasive, non-metastasizing fibromatous tumours which rarely regress. They occur frequently in familial adenomatous polyposis (FAP), causing significant morbidity and death. Telomerase activity was assayed in desmoids from patients with and without FAP to assess the role of telomerase in the development of these lesions, and its potential as a prognostic marker and possible target for treatment. METHODS: Protein extracts from 11 desmoids from nine patients with FAP, and ten desmoids from ten patients without FAP, were analysed for telomerase activity by the telomeric repeat amplification protocol, a sensitive polymerase chain reaction-based assay. Six fibrosarcomas and a fibrosarcoma cell line were used as positive controls; all displayed telomerase activity. RESULTS: No telomerase activity was detected in any of the 21 desmoids studied. CONCLUSION: These results indicate that desmoid tumours are one of the intriguing exceptions to the emerging view that re-expression of telomerase activity accompanies the development of preneoplastic and neoplastic tissues, and suggest that alternative mechanisms may operate in these proliferative neoplasms.     

Proliferative patterns of rectal mucosa as predictors of advanced colonic neoplasms in routinely processed rectal biopsies

OBJECTIVES: We sought to determine whether the evaluation of rectal cell proliferation in routinely processed rectal biopsies of apparently normal mucosa can predict the presence of advanced colonic neoplasms. METHODS: Fifty consecutive patients, who did not meet any of the following exclusion criteria, underwent total colonoscopy. Patients with nonadvanced adenomas, inflammatory bowel disease, hereditary predisposition to colonic cancer, or a history of colonic neoplasms were excluded. Patients with neoplasms in the distal 40 cm of the large bowel were also excluded. An adenoma was considered advanced if it had a diameter > 1 cm, or villous or severe dysplasia histology were present. In 26 of the 50 patients (Group A: 16 men, 10 women; mean age, 65 yr) advanced colonic neoplasms (advanced adenomas or cancer) were detected; in the remaining 24 (Group B: 13 men, 11 women; mean age, 66 yr) the large bowel was free of neoplasms. In all patients the proliferative patterns of apparently normal rectal mucosa were evaluated using the monoclonal antibody MIB-1 to assess the expression of Ki-67 antigen in routinely processed tissues. Proliferation index for the entire crypt, as well as proliferation indices for each of the five equal compartments, into which the crypt had been divided longitudinally, were calculated for each patient. RESULTS: The mean proliferation indices were similar between the two groups compared. The mean proliferation index for the upper crypt compartments (4 + 5) in the Group A patients was significantly higher than for those of the Group B patients (p < 0.01). Multivariate stepwise logistic regression analysis revealed that among gender, age, and proliferative parameters, the pattern of cell proliferation in the upper rectal crypt (4 + 5) compartment was the only predictor of advanced colonic neoplasms (beta = 11.01, p < 0.001). CONCLUSIONS: Our data suggest that the evaluation of the upward expansion of the rectal crypt proliferative zone in routinely processed rectal biopsies of apparently normal mucosa appears to predict the presence of advanced colonic neoplasms. These preliminary results should be confirmed in larger studies.     

Oral calcium inhibits rectal epithelial proliferation in familial adenomatous polyposis

Calcium reduces colorectal cell turnover and might therefore protect against neoplasia. The inhibitory effects of dietary calcium were tested in a double-blind controlled trial in patients with familial adenomatous polyposis who had undergone previous abdominal colectomy and ileorectal anastomosis. Patients received supplemental calcium carbonate (1500 mg/day) or placebo tablets for 6 months; sigmoidoscopy was performed before and after treatment. Rectal biopsies were maintained in short-term organ culture, and crypt cell production rate (CCPR) was measured stathmokinetically. A total of 25 patients completed the trial; polyp counts were obtained before and after treatment in all and CCPR values in 16. Calcium treatment reduced the mean (s.e.m.) CCPR from 4.72 (0.48) to 2.42 (0.48) cells per crypt per h (P < 0.05), while values for placebo were unchanged (5.46 (1.21) versus 5.08 (1.17) cells per crypt per h). Calcium had no demonstrable effect on the number, size or distribution of rectal polyps. The ability of oral calcium supplementation to suppress rectal epithelial proliferation supports its potential to prevent development of colorectal carcinoma in high-risk individuals.     

Thermally reversible xyloglucan gels as vehicles for rectal drug delivery

The aim of this study was to investigate the potential application of thermoreversible gels formed by a xyloglucan polysaccharide derived from tamarind seed for rectal drug delivery. Xyloglucan that had been partially degraded by beta-galactosidase to eliminate 44% of galactose residues formed gels at concentrations of between 1 to 2% w/w at gelation temperatures decreasing over the range 27 to 22 degreesC with increasing concentration. The in vitro release of indomethacin and diltiazem from the enzyme-degraded xyloglucan gels followed root-time kinetics over a period of 5 h at 37 degreesC; the diffusion coefficients increasing with temperature increase between 10 and 37 degreesC. The in vitro release of indomethacin from the gels was significantly more sustained than from commercial suppositories. Measurement of plasma levels of indomethacin after rectal administration to rabbits of the gels and commercial suppositories containing an identical drug concentration indicated a broader absorption peak following administration of the gels, and a longer residence time. There was no significant difference in bioavailability of indomethacin when administered by these two vehicles. Morphological studies of rectal mucosa following a single administration of the gels showed no evidence of tissue damage. The results of this study suggest the potential of the enzyme-degraded xyloglucan gels as vehicles for rectal delivery of drugs.     

No evidence for overexpression of the p53 protein and mutations in exons 4-9 of the p53 gene in a large family with adenomatous polyposis

OBJECTIVE: Familial adenomatous polyposis coli (FAP) is an autosomal dominant disease characterized by an early onset of numerous adenomatous polyps of the colon and a high risk of colon carcinoma. The role of the p53 gene in the multistage process of FAP is as yet poorly defined. In the present study, a large family with evidence of polyposis and colon cancer was screened for the mutations of the p53 gene and protein overexpression. METHODS: We examined p53 protein expression from individuals with immunohistochemical techniques using monoclonal antibody PAb1801. Polymerase chain reaction products of exons 4-9 of the p53 were examined from individuals by single strand, conformational polymorphism analysis. RESULTS: We could find no evidence of overexpression and mutations of the p53 in any lesion including adenomas and carcinomas. CONCLUSION: We found that p53 gene alterations do not contribute to the genesis of adenoma or carcinoma of FAP patients for this large family examined.     

Genetic counselling and gene mutation analysis in familial adenomatous polyposis in Western Australia

OBJECTIVE: To assess the provision of accurate pre-symptomatic genetic testing with DNA analysis and appropriate counselling for individuals and families known to be at high risk of developing familial adenomatous polyposis coli (FAP). PATIENTS AND METHODS: Thirty-one families with clinically and pathologically documented FAP were ascertained from the Western Australian Polyposis Registry. DNA was collected from over 200 individuals in these families to establish their genetic risk status for FAP, either by direct mutation analysis, or by linkage analysis. Individuals undergoing DNA testing were given intensive psychosocial support and counselling. RESULTS: In 19 families DNA-based counselling could not be offered because either the adenomatous polyposis coli (APC) gene mutation could not be detected or there were insufficient family members for linkage analysis. Gene testing yielded mutations of the APC gene in 87 individuals from 12 families; by gene tracking (or linkage analysis) in three families and by mutation analysis in the remaining nine (four of which had only one affected individual). DNA results conformed with a definite clinicopathological diagnosis in 27 FAP patients and, of the remaining 60 high-risk subjects tested, 14 had inherited the mutated APC gene. CONCLUSIONS: DNA analysis allowed accurate genetic counselling for 12 of 31 families affected by FAP, thus improving the medical and personal management in asymptomatic people who would otherwise be subjected to the uncertainty of long term surveillance and repeated colonic examinations. In future a superior biomolecular approach to gene mutation analysis, such as the protein truncation test, will facilitate management for most FAP individuals and families.     

Long-term quality of life after continence-preserving proctocolectomy for ulcerative colitis and familial adenomatous polyposis

After ileal pouch-anal anastomosis in patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP), quality of life is a relevant factor for the assessment of the operation's success, in addition to postoperative morbidity and functional outcome. Between 1982 and 1995 restorative proctocolectomy was performed in 453 patients (UC: n = 332; FAP: n = 121) at the Department of Surgery, University of Heidelberg. We studied postoperative quality of life through a long-term follow-up study (median follow-up time 43.2 months). This study 1 year or more following ileostomy closure of persons who had undergone J-pouch anastomosis (n = 243 total; UC n = 185, FAP n = 58) revealed that at the time of follow-up, the underlying disease (UC versus FAP) and successfully treated complications are without influence on the quality of life. The patient's age (P < 0.01) and the presence of unsuccessfully treated complications (P < 0.0001) showed a significant influence on the quality of life. There was a distinct relation between the functional index and the quality of life index (coefficient of correlation r = -0.714). However, quality of life, comparable to that of healthy controls, can be achieved with UC and FAP patients by restorative proctocolectomy only if postoperative complications can be avoided or are successfully treated.     

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 meta-analysis 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.     

Rectal indomethacin potentiates spinal morphine analgesia after caesarean delivery

This double-blind, randomized study was designed to evaluate the use of indomethacin (Indocid, MSD) following caesarean delivery performed under spinal anaesthesia. Thirty ASA I-II women presenting for elective caesarean were recruited. Spinal anaesthesia was performed in a standard manner using hyperbaric bupivacaine, fentanyl and morphine. At the completion of surgery, subjects were administered two rectal suppositories, followed by 12-hourly suppositories for six doses (three days). The study group received 100 mg indomethacin suppositories and controls were given placebo (Anusol). Data collected included Visual Analog Scale (VAS) pain scores at rest and with movement, VAS scores for nausea and itch, and analgesic use. Demographic data were similar in the two groups. Median time to first analgesia (TTFA) was nine hours in the control group v. 39.5 hours in the indomethacin group (P < 0.003). Additional analgesic requests throughout the postoperative period were less in women who received indomethacin: 4 v 11 (P < 0.001). Women who received indomethacin had significantly less pain on the first postoperative day, especially on movement: mean VAS 1.4 v 5.1 (P < 0.00001). There were no reported adverse neonatal or maternal effects from the use of indomethacin. Rectal indomethacin use following caesarean delivery leads to significantly improved pain relief compared with placebo. The combination of spinal morphine and rectal indomethacin leads to high-quality postoperative analgesia.     

Efficacy of the straight endorectal pull-through in the management of familial adenomatous polyposis--a 16-year experience

From 1979 to 1995, 27 patients who had familial adenomatous polyposis (FAP) were treated at the authors' institution. Most patients (n = 23) presented as a result of a previous family history of FAP. Eighteen patients presented with symptomatic colonic disease that included bloody stools (n = 14), diarrhea (n = 10), and abdominal pain (n = 6). Treatment consisted of a total colectomy, rectal mucosectomy, and straight endorectal pull-through (ERPT) in 26 of 27 patients. One patient preferred to undergo an ileoanal J pouch reconstruction. A temporary diverting loop ileostomy was performed in 25 patients and closed at an average of 100 days after the ERPT. Follow-up has been achieved in 100% of the patients and ranges from 6 to 182 months with an average of 48 months. Postoperative complications included partial bowel obstruction (two patients, one requiring enterolysis); and mild pouchitis (one patient). Two of the 27 patients required proctectomy and permanent ileostomy procedures, one for rectal cancer that was present microscopically in the initial rectal specimen from the ERPT and the other because of recurrent anastomotic complications. No patient required revision of the straight pull-through to a pouch or takedown of the pull-through as a result of persistent diarrhea or dissatisfaction. All of the patients are continent, and 80% deny any soiling during bouts of gastroenteritis. The mean number of bowel movements reported was 10 per day at the first postoperative clinic visit with a gradual decreased to six per day after 2 years. Initial use of bulking (62%) and antimotility agents (88%) decreased significantly over the course of follow-up to 29% and 67%, respectively at the most recent follow-up (average, 48 months) of each patient. Pelvic sepsis, which occurs in 8% of most series of patients who have pouches, did not occur in any of our patients. Pouchitis, a common complication with pouches (23%), occurred in only one of the patients and was mild and easily treated medically. This series demonstrates that total colectomy with rectal mucosectomy and straight ERPT eliminates the risk of colorectal cancer and achieves continence with a low complication rate and excellent functional results and patient satisfaction.