ABSTRACT
We report the case of a female found to have mosaicism for mutation in the STK11 gene, with the mutant allele expressed in her gametes, evident by her affected offspring, and in her gastrointestinal tract demonstrated on an excised polyp analysed for diagnosis. Mosaicism for Peutz-Jeghers syndrome (PJS) has been reported in a small number of cases previously but a clinical presentation such as this has not previously been described. This finding of mosaicism was several years after initial investigations failed to identify the same STK11 mutation in this woman whose son was diagnosed with PJS at a young age. This case highlights the importance of considering mosaicism as an explanation for apparent de novo cases of PJS syndrome. It also has implications for genetic counselling, predictive testing and cancer screening.
Subject(s)
Intestinal Polyps/genetics , Mosaicism , Peutz-Jeghers Syndrome/genetics , Protein Serine-Threonine Kinases/genetics , AMP-Activated Protein Kinase Kinases , Child , Colonoscopy , Female , Genetic Testing , Humans , Ileum/diagnostic imaging , Ileum/pathology , Intestinal Polyps/diagnosis , Intestinal Polyps/pathology , Male , Middle Aged , Mothers , Mutation , Peutz-Jeghers Syndrome/diagnosis , Peutz-Jeghers Syndrome/pathologyABSTRACT
We report a familial adenomatous polyposis patient with a known truncating mutation on exon 15 of the APC gene who developed an invasive follicular thyroid cancer in addition to multiple intra-cranial and spinal desmoids. This combination of manifestations has not previously been recorded in the literature.
Subject(s)
Adenomatous Polyposis Coli/complications , Central Nervous System Neoplasms/etiology , Fibromatosis, Aggressive/etiology , Neoplasms, Second Primary/etiology , Thyroid Neoplasms/etiology , Adenomatous Polyposis Coli/genetics , Adenomatous Polyposis Coli/pathology , Adenomatous Polyposis Coli Protein/genetics , Central Nervous System Neoplasms/pathology , Child , Exons/genetics , Fibromatosis, Aggressive/pathology , Humans , Male , Mutation/genetics , Neoplasms, Second Primary/pathology , Prognosis , Thyroid Neoplasms/pathologyABSTRACT
Familial gastrointestinal stromal tumours (GISTs) are rare but otherwise well-characterized tumour syndromes, most commonly occurring on a background of germline-activating mutations in the tyrosine kinase receptor c-KIT. The associated clinical spectrum reflects the constitutive activation of this gene product across a number of cell lines, generating gain-of-function phenotypes in interstitial cells of Cajal (GIST and dysphagia), mast cells (mastocytosis) and melanocytes (hyperpigmentation). We report a three-generation kindred harbouring a c-KIT germline-activating mutation resulting in multifocal GISTs, dysphagia and a complex melanocyte hyperpigmentation and hypopigmentation disorder, the latter with features typical of those observed in Waardenburg type 2 syndrome (WS2F). Sequencing of genes known to be causative for WS [microphthalmia transcription factor (MITF), Pax3, Sox10, SNAI2 ] failed to show any candidate mutations to explain this complex cutaneous depigmentation phenotype. Our case report conclusively expands the clinical spectrum of familial GISTs and shows a hitherto unrecognized link to WS. Possible mechanisms responsible for this novel cause of WS2F will be discussed.
Subject(s)
Gastrointestinal Stromal Tumors/genetics , Neoplastic Syndromes, Hereditary/genetics , Waardenburg Syndrome/genetics , Alleles , Deglutition Disorders/genetics , Deglutition Disorders/pathology , Gastrointestinal Stromal Tumors/pathology , Germ-Line Mutation , Humans , Hyperplasia , Interstitial Cells of Cajal/pathology , Male , Middle Aged , Mutation, Missense , Myenteric Plexus/pathology , Neoplastic Syndromes, Hereditary/pathology , Pedigree , Phenotype , Proto-Oncogene Proteins c-kit/genetics , Proto-Oncogene Proteins c-kit/metabolism , Sequence Analysis, DNA , Waardenburg Syndrome/pathologyABSTRACT
The genetic predisposition Peutz-Jeghers Syndrome (PJS) has been shown to be associated with mutations in the serine threonine kinase 11 (STK11) gene but only a proportion of probands have been shown to harbour changes in the gene. The remaining patients were proposed to be either associated with a second PJS gene or they harboured more cryptic mutations within the STK11 gene itself. With the introduction of the multiplex ligation probe amplification (MLPA) assay, large sequence losses or gains can be more readily identified. In this report we have screened 33 PJS patients from unrelated families, employing a combination of denaturing high-performance liquid chromatography, direct DNA sequencing and the MLPA assay to identify deleterious changes in the STK11 gene. The results revealed that 24 (73%) of patients diagnosed with PJS-harboured pathogenic mutations in the STK11 gene, including 10 (36%) with exonic or whole-gene deletions. No phenotypic differences were identified in patients harbouring large deletions in the STK11 gene compared to patients harbouring missense or nonsense mutations. Mutation analysis in PJS should include techniques such as MLPA to identify large exonic or whole-gene deletions and rearrangements. The high proportion of families with identifiable mutations in the STK11 gene using this range of techniques suggests that most, if not all PJS, is attributable to mutations in the STK11 gene, perhaps including as yet undiscovered changes in promoter or enhancer sequences or other cryptic changes.
Subject(s)
Mutation , Peutz-Jeghers Syndrome/genetics , Protein Serine-Threonine Kinases/genetics , AMP-Activated Protein Kinase Kinases , Adolescent , Adult , Australia , Child , Child, Preschool , DNA Mutational Analysis , Exons , Female , Gene Deletion , Humans , Male , Middle Aged , Nucleic Acid Amplification Techniques , Peutz-Jeghers Syndrome/enzymology , Sequence DeletionABSTRACT
BACKGROUND: Peutz-Jeghers syndrome (PJS) is caused by germline STK11 mutations and characterised by gastrointestinal polyposis. Although small bowel intussusception is a recognised complication of PJS, risk varies between patients. OBJECTIVE: To analyse the time to onset of intussusception in a large series of PJS probands. METHODS: STK11 mutation status was evaluated in 225 PJS probands and medical histories of the patients reviewed. RESULTS: 135 (60%) of the probands possessed a germline STK11 mutation; 109 (48%) probands had a history of intussusception at a median age of 15.0 years but with wide variability (range 3.7 to 45.4 years). Median time to onset of intussusception was not significantly different between those with identified mutations and those with no mutation detected, at 14.7 years and 16.4 years, respectively (log-rank test of difference, chi(2) = 0.58, with 1df; p = 0.45). Similarly no differences were observed between patient groups on the basis of the type or site of STK11 mutation. CONCLUSIONS: The risk of intussusception in PJS is not influenced by STK11 mutation status.
Subject(s)
Intussusception/genetics , Peutz-Jeghers Syndrome/genetics , Protein Serine-Threonine Kinases/genetics , AMP-Activated Protein Kinase Kinases , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Risk FactorsABSTRACT
We assessed the efficacy of a comprehensive programme for stopping smoking in 210 smokers scheduled for surgery, before admission and 3 months after attending a pre-operative clinic. Participants were randomly allocated to receive an intervention incorporating nicotine replacement therapy for patients smoking more than 10 cigarettes per day ("dependent smokers"), or to a control group to receive usual care. Dependent smokers allocated to the intervention group were more likely to report abstinence before surgery than those allocated to receive usual-care (63 (73%) vs. 29 (56%), respectively; OR 2.2 (95% CI 1.0-4.8)), and 3 months after attendance (16 (18%) vs. 3 (5%), respectively; OR = 3.9 (95% CI 1.0-21.7).
Subject(s)
Preoperative Care/methods , Smoking Cessation/methods , Smoking Prevention , Adult , Aged , Female , Health Care Costs , Humans , Male , Middle Aged , Nicotine/therapeutic use , Nicotinic Agonists/therapeutic use , Preoperative Care/economics , Program Evaluation , Smoking Cessation/economics , Tobacco Use Disorder/rehabilitation , Treatment OutcomeABSTRACT
Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant, inherited condition that is characterized primarily by the development of early-onset colorectal cancer and a number of other epithelial malignancies. The underlying genetic basis of the disease is associated with a breakdown of DNA-mismatch repair. There are many genes involved in DNA-mismatch repair, and five of them have been implicated in HNPCC. Two of the genes (hMSH2 and hMLH1) account for the majority of HNPCC families (approximately 60%), and it is not known what the exact contributions of the remaining three genes (hPMS1, hPMS2, and hMSH6) are in relation to this condition. In addition, a sixth gene (hEXO1) has been associated with a disease phenotype that is consistent with HNPCC. Current estimates suggest that all four of these genes, combined, may account for up to 5% of families. In this report, we examine the contribution of hPMS2 and hEXO1 to a well-defined set of families that fulfill the diagnostic criteria for HNPCC. The genes, hPMS2 and hEXO1, were studied by denaturing high performance liquid chromatography (DHPLC) analysis in 21 families that have previously been determined not to have mutations in hMSH2 or hMLH1. hPMS2 accounts for a small proportion of HNPCC families, and none were deemed to be associated with hEXO1. Mutations in hPMS2 appear to account for a small proportion of families adhering to the Amsterdam II criteria, whereas hEXO1 does not appear to be associated with HNPCC.
Subject(s)
Adenosine Triphosphatases/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA Repair Enzymes/genetics , DNA-Binding Proteins/genetics , Exodeoxyribonucleases/genetics , Mutation/physiology , Adaptor Proteins, Signal Transducing , Adult , Aged , Carrier Proteins , Chromatography, High Pressure Liquid , Colorectal Neoplasms, Hereditary Nonpolyposis/epidemiology , DNA Mutational Analysis , DNA Primers , DNA Repair/genetics , Family Health , Genetic Predisposition to Disease/genetics , Humans , Middle Aged , Mismatch Repair Endonuclease PMS2 , Molecular Epidemiology , MutL Protein Homolog 1 , MutS Homolog 2 Protein , Neoplasm Proteins/genetics , Nuclear Proteins , Proto-Oncogene Proteins/geneticsABSTRACT
OBJECTIVE: The consumption of cruciferous vegetables has a protective effect on the development of colorectal cancer. The phytochemical Sulforaphane is an isothiocyanate found almost exclusively in cruciferous vegetables. We have studied the effect of Sulforaphane on cell proliferation of an HT-29 colon cancer cell line. MATERIALS AND METHODS: HT-29 colon cancer cells were cultured in 96-well microtitre plates. Sulforaphane (in concentrations ranging from 0.01 to 0.1 mmol) were added to the wells. Cell proliferation was measured using the colourimetric assay technique. RESULTS: The proliferation of colon cancer cells was significantly reduced by Sulforaphane at concentrations of >/=0.02 mmol. CONCLUSION: These findings may help explain the epidemiologically proven protective effect of vegetables against colon cancer.
Subject(s)
Anticarcinogenic Agents/therapeutic use , Colonic Neoplasms/prevention & control , HT29 Cells/drug effects , Thiocyanates/therapeutic use , Anticarcinogenic Agents/pharmacology , Cell Division/drug effects , Colonic Neoplasms/pathology , Dose-Response Relationship, Drug , Humans , Isothiocyanates , Sulfoxides , Thiocyanates/pharmacologyABSTRACT
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-year-old 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.
Subject(s)
Adenomatous Polyposis Coli/complications , Adenomatous Polyposis Coli/surgery , Duodenal Neoplasms/etiology , Duodenal Neoplasms/pathology , Ileum/surgery , Lymphoma, B-Cell, Marginal Zone/etiology , Lymphoma, B-Cell, Marginal Zone/pathology , Rectum/surgery , Adenomatous Polyposis Coli/pathology , Anastomosis, Surgical , Colectomy , Humans , Intestinal Mucosa/pathology , Male , Middle AgedABSTRACT
AIM: An audit was undertaken to assess whether surgeons were informed of the readmission of their patients with postoperative deep venous thrombosis (DVT), or pulmonary embolus (PE). METHODS: A retrospective medical record review was conducted to detect patients who had an unplanned readmission in which DVT or PE formed part of the diagnosis and the first admission included a surgical procedure. The readmission was to John Hunter Hospital, Newcastle, Australia, a major tertiary referral teaching hospital, and the first admission was to any acute care hospital. The main outcome measures were: (i) hospital and specialty of the admitting doctor, (ii) the type of surgery performed, (iii) the length of time between admissions and (iv) the patient's previous medical history. The medical record was reviewed for documented evidence that the surgeon who performed the procedure was aware of the readmission. RESULTS: Of the 215 patient reviewed, 34 were classified as unplanned readmissions following a surgical procedure. Twenty-four patients (70.6%) were readmitted under a different specialty, three (8.8%) patients were readmitted under the same specialty but under a different surgeon, and seven (20.6%) patients were readmitted under the same surgeon. Of the 27 patients admitted under a different consultant, only 12 (44.4%) had documented evidence that the previous surgeon was aware of the readmission. CONCLUSION: The rate of DVT/PE complications following surgery is underestimated. This may lead to a reduced emphasis in DVT/PE prophylaxis in the mistaken belief that DVT/PE frequency is rarer than it is. Improved communication between teams is necessary to improve care.
Subject(s)
General Surgery , Interprofessional Relations , Patient Readmission , Postoperative Complications , Pulmonary Embolism/etiology , Venous Thrombosis/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Communication , Female , Humans , Length of Stay , Male , Medical Audit , Middle Aged , Outcome Assessment, Health Care , Pulmonary Embolism/drug therapy , Surgical Procedures, Operative , Venous Thrombosis/drug therapy , Warfarin/therapeutic useABSTRACT
OBJECTIVE: Naringenin, a naturally occurring flavonoid found in citrus fruits, is known to have anticarcinogenic properties. We have examined the effect of Naringenin on cell proliferation of an HT-29 colon cancer cell line. METHODS: HT-29 colon cancer cells were cultured in 96-well tissue culture plates. Naringenin concentrations ranging from 0.02 to 2.85 mmol were added to the wells of the Test group. The Control group contained all the elements present in the Test group with the exception of Naringenin. Cell proliferation was measured by colourimetric assay using the 2% WST-1 cell proliferation kit. RESULTS: Significant inhibition of cell proliferation was observed in HT29 colon cancer cells exposed to Naringenin at doses greater than 0.71 mmol. CONCLUSIONS: These results suggest a potential role for citrus fruits as a source of chemoprotective agents for colon cancer.
Subject(s)
Adenocarcinoma/pathology , Antineoplastic Agents/pharmacology , Colonic Neoplasms/pathology , Flavanones , Flavonoids/pharmacology , Cell Division/drug effects , Citrus/chemistry , HT29 Cells/drug effects , HT29 Cells/pathology , HumansABSTRACT
Peutz-Jeghers syndrome (PJS) is a rare cancer predisposition, which is characterized by the presence of hamartomatous polyposis and mucocutaneous pigmentation. A significant proportion of both familial and sporadic forms of this disorder are associated with mutations in the STK11 (serine/threonine kinase 11)/LKB1 gene. In this report we present a series of Australian PJS cases, which suggest that mutations in the STK11 gene do not account for many families or patients without a family history. The most likely explanation is either the presence of another susceptibility gene or genetic mosaicism in the non-familial patients.
Subject(s)
Peutz-Jeghers Syndrome/genetics , Protein Serine-Threonine Kinases/genetics , AMP-Activated Protein Kinase Kinases , Australia , Chromosome Mapping , DNA Mutational Analysis , Female , Genetic Heterogeneity , Humans , Male , Mutation , Sequence AnalysisABSTRACT
OBJECTIVE: To determine the adverse event (AE) rate for surgical patients in Australia. DESIGN: A two-stage retrospective medical record review was conducted to determine the occurrence of AEs in hospital admissions. Medical records were screened for 18 criteria and positive records were reviewed by two medical officers using a structured questionnaire. SETTING: Admissions in 1992 to 28 randomly selected hospitals in Australia. STUDY PARTICIPANTS: Five hundred and twenty eligible admissions were randomly selected from in-patient database in each hospital. A total of 14,179 medical records were reviewed, with 8747 medical and 5432 surgical admissions. MAIN OUTCOME MEASURES: Measures included the rate of AEs in surgical and medical admissions, the proportion resulting in permanent disability and death, the proportion determined to be highly preventable, and the identification of risk factors associated with AEs. RESULTS: The AE rate for surgical admissions was 21.9%. Disability that was resolved within 12 months occurred in 83%, 13% had permanent disability, and 4% resulted in death. Reviewers found that 48% of AEs were highly preventable. The risk of an AE depended on the procedure and increased with age and length of stay. CONCLUSION: The high AE rate for surgical procedures supports the need for monitoring and intervention strategies. The 18 screening criteria provide a tool to identify admissions with a greater risk of a surgical AE. Risk factors for an AE were age and procedure, and these should be assessed prior to surgery. Prophylactic interventions for infection and deep vein thrombosis could reduce the occurrence of AEs in hospitals.
Subject(s)
Hospitals/statistics & numerical data , Iatrogenic Disease/epidemiology , Patient Admission/statistics & numerical data , Surgical Procedures, Operative/adverse effects , Adolescent , Adult , Age Factors , Aged , Australia/epidemiology , Child , Child, Preschool , Disability Evaluation , Health Care Surveys , Hospitals/standards , Humans , Incidence , Infant , Infant, Newborn , Middle Aged , Postoperative Complications/epidemiology , Reoperation/statistics & numerical data , Risk Factors , Surgical Wound Infection/epidemiology , Surveys and QuestionnairesABSTRACT
Up to 20% of colorectal cancers are thought to have a genetic component. Several familial syndromes are known to confer an increased risk for colorectal cancer. Advances in our understanding of these syndromes has improved the care delivered to, and the overall survival of, these patients. Genetic testing has great potential to further improve detection and direct subsequent preventative measures. The diagnosis, management and surveillance issues relating to some of the more commonly encountered syndromes - in particular Familial Adenomatous Polyposis and Hereditary Non-Polyposis Colorectal Cancer - are reviewed.
Subject(s)
Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/genetics , Adenomatous Polyposis Coli/genetics , Australia/epidemiology , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Genetic Counseling , Humans , Medical History Taking , Registries , Risk FactorsABSTRACT
BACKGROUND: Duodenal cancer is one of the leading causes of death in familial adenomatous polyposis (FAP) patients. An endoscopic surveillance programme was therefore initiated in 1988, the outcome of which is described in this paper. METHODS: We report the 10 year follow up of 114 patients with FAP who were prospectively screened for the presence and severity of duodenal adenomas. RESULTS: Six of 114 patients (median age 67 years) developed duodenal adenocarcinoma. Four of these were from 11 patients who originally had Spigelman stage IV disease (advanced duodenal polyposis), which gives a 36% risk within this group of developing cancer. One case of duodenal cancer arose from 41 patients who originally had stage III disease (2%) and one cancer arose from 44 patients with original stage II disease (2%). All six patients have died: five were inoperable and one had recurrence three years after a pancreaticoduodenectomy. There was no association between duodenal cancer and site of germline mutation of the APC gene. CONCLUSIONS: Surveillance for duodenal adenocarcinoma and subsequent early referral for curative surgery has not been effective. Selection of patients with advanced but benign (Spigelman stage IV) duodenal polyposis for prophylactic pancreaticoduodenectomy should therefore be considered and can now be justified on the basis of these results. More comprehensive endoscopic surveillance of high risk (stage III and IV) patients is needed in an attempt to avoid underestimating the severity of duodenal polyposis, and to evaluate the role of endoscopic therapy in preventing advanced disease.
Subject(s)
Adenocarcinoma/genetics , Adenomatous Polyposis Coli/complications , Duodenal Neoplasms/genetics , Adenocarcinoma/diagnosis , Adenocarcinoma/surgery , Adenomatous Polyposis Coli/pathology , Adolescent , Adult , Aged , Disease Progression , Duodenal Neoplasms/diagnosis , Duodenal Neoplasms/surgery , Duodenoscopy , Female , Follow-Up Studies , Humans , Long-Term Care/methods , Male , Middle Aged , Neoplasm Staging , Patient Selection , Prognosis , Prospective StudiesABSTRACT
OBJECTIVE: To observe the effect of Indole-3-carbinol (I3C), a naturally occurring component of cruciferous vegetables, on cell proliferation of a colon cancer cell line. METHODS: Cell proliferation was measured using three different methods; 3H-thymidine incorporation, cell count and colourimetric assay. RESULTS: Each method of measurement revealed that I3C significantly reduced cell proliferation at concentrations of > 0.1 mM. CONCLUSION: The present study demonstrates for the first time the capacity of indole-3-carbinol to inhibit cell proliferation of a colon cancer cell line.
ABSTRACT
PURPOSE: Bile has been implicated in the pathogenesis of duodenal polyps in patients with familial adenomatous polyposis. In vitro experiments have shown that familial adenomatous polyposis bile is capable of producing DNA adducts. This effect can be ameliorated by increasing the pH of the incubate. The aim of this double-blind randomized placebo-controlled trial was to examine the effect of oral ranitidine on duodenal polyposis in a group of patients with familial adenomatous polyposis. METHODS: Twenty-six patients with familial adenomatous polyposis were randomly assigned to ranitidine 300 mg daily or placebo for six months after baseline endoscopy. Polyp counts were performed and biopsy specimens taken to detect DNA adducts by 32P-postlabeling. RESULTS: No difference was seen in polyp numbers (P = 0.9) or relative adduct labeling (P = 0.7) after treatment with ranitidine or placebo. DISCUSSION: Acid suppression therapy does not seem to improve duodenal polyposis despite in vitro findings. On the other hand, ranitidine does not exacerbate actual (or markers of) neoplasia in this highly tumor-prone condition.
Subject(s)
Adenomatous Polyposis Coli/drug therapy , Anti-Ulcer Agents/pharmacology , DNA Adducts , Duodenal Neoplasms/drug therapy , Intestinal Polyps/drug therapy , Ranitidine/pharmacology , Adenomatous Polyposis Coli/genetics , Administration, Oral , Adult , Bile/chemistry , Double-Blind Method , Duodenal Neoplasms/genetics , Endoscopy , Female , Gastric Acid , Humans , Intestinal Polyps/genetics , Male , Treatment OutcomeABSTRACT
PURPOSE: Familial adenomatous polyposis is an inherited colorectal cancer syndrome characterized by the presence of multiple adenomatous colorectal polyps. Molecular studies have revealed that germline mutations in the APC gene are the underlying cause of the disease. The nonsteroidal anti-inflammatory agent sulindac has been shown to reduce the number of colorectal adenomas. Most sulindac trials in the large bowel have focused on the distal colon and relatively little is known about its effect on the proximal colon. Moreover, it is unknown whether the site of the APC mutation affects the efficacy of sulindac. METHODS: This study investigated whether there were regional differences in the effect of sulindac on the colon and whether response to sulindac was dependent on the site of mutation in the APC gene. In an open prospective study 17 patients with familial adenomatous polyposis were treated with 300 mg oral sulindac daily for four months followed by a washout phase of six months. Ten of the patients had an intact colon and seven had rectal stumps only. The number, size, and the degree of dysplasia of the adenomas were evaluated by colonoscopy at entry, end of treatment and end of the study. RESULTS: Overall, a statistically significant decrease in the number of adenomas was observed (120 +/- 112 to 28 +/- 64, P = 0.007). After cessation of sulindac treatment the number of adenomas increased to 48 +/- 44.5, but remained significantly lower than the values observed at baseline. In the ten patients with intact colons, adenomas decreased by sevenfold in the proximal colon (103 +/- 73 to 15.1 +/- 47.4, P = 0.011) and twofold in the distal colon (80 +/- 52 to 29.6 +/- 37.2, P = 0.005). The size of adenomas and the grade of dysplasia also decreased. No correlation could be seen between the APC mutation site and the response to treatment. CONCLUSION: These data indicate that sulindac reduces the number of adenomas in the entire colon and that the effect seems to be more pronounced in the proximal colon.