Effect of aspirin dose on gastrointestinal permeability.

The primary purpose of this study was to determine the aspirin dose that increases gastrointestinal (GI) permeability. A pilot study was also conducted to determine whether the menstrual cycle affects GI permeability. Both portions of the study involved 4 experimental conditions. For the aspirin portion, 8 subjects ingested 0 mg, 325 mg, 650 mg, or 975 mg of aspirin the night before and the morning of an experiment. For the menstrual cycle pilot study, 5 female subjects with regular menstrual cycles were tested for GI permeability on the same day each week for 4 weeks. GI permeability was assessed by the urinary excretion of ingested probes. Sucrose (5 g) was used to determine gastroduodenal permeability. Lactulose (5 g) and rhamnose (2 g) were used to assess small intestinal permeability via the lactulose-to-rhamnose urinary excretion ratio (L/R). The data indicated that the menstrual cycle had no effect on GI permeability. In contrast, gastroduodenal permeability was significantly (P <0.008) increased following a dose of 650 mg aspirin and small intestinal permeability (L/R) was significantly (P <0.008) increased following a dose of 975 mg aspirin. These results suggest healthy individuals should be cautious even with acute aspirin use as it may result in GI barrier dysfunction.

Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications.

More than one million patients will manifest colorectal cancer (CRC) this year of which, conservatively, approximately 3% (approximately 30,700 cases) will have Lynch syndrome (LS), the most common hereditary CRC predisposing syndrome. Each case belongs to a family with clinical needs that require genetic counseling, DNA testing for mismatch repair genes (most frequently MLH1 or MSH2) and screening for CRC. Colonoscopy is mandated, given CRC's proximal occurrence (70-80% proximal to the splenic flexure). Due to its early age of onset (average 45 years of age), colonoscopy needs to start by age 25, and because of its accelerated carcinogenesis, it should be repeated every 1 to 2 years through age 40 and then annually thereafter. Should CRC occur, subtotal colectomy may be necessary, given the marked frequency of synchronous and metachronous CRC. Because 40-60% of female patients will manifest endometrial cancer, tailored management is essential. Additional extracolonic cancers include ovary, stomach, small bowel, pancreas, hepatobiliary tract, upper uroepithelial tract, brain (Turcot variant) and sebaceous adenomas/carcinomas (Muir-Torre variant). LS explains only 10-25% of familial CRC.

Fluid tolerance while running: effect of repeated trials.

This study assessed tolerance to fluid ingestion with repeated sessions of drinking while running. Runners (n = 7; age 22 +/- 2 yr; V O (2max) = 54.4 +/- 7.1 ml/kg/min) performed six 90-min runs (65 % V O (2max); separated by 7 - 11 days). During run 1, subjects drank a glucose-electrolyte solution AD LIBITUM for 1 min every 10 min. During runs 2 - 6, subjects drank a volume of the solution every 10 min equal to their sweat production over 10 min during run 1. Stomach comfort (1 - 4 scale) and gastrointestinal symptoms were also assessed every 10 min. Gastric emptying rate was determined in runs 2 and 6. Subjects consumed more (p < 0.05) fluid during runs 2 - 6 (mean +/- SD; 1247 +/- 162 ml), than during run 1 (508 +/- 476 ml). Stomach comfort improved (p < 0.05) on runs 5 and 6 (1.7 +/- 0.5 mean ranks) compared to run 2 (2.3 +/- 0.5 mean ranks). Gastric emptying rate was not different between runs 2 and 6 (12.0 +/- 1.9 ml/min vs. 12.3 +/- 2.3 ml/min, respectively). These results indicate repeated sessions of drinking at a rate matching sweat rate improves stomach comfort, however, gastric emptying rate does not change under such conditions.

Fluid restriction during running increases GI permeability.

The purpose of this study was to determine gastrointestinal (GI) permeability during prolonged treadmill running (60 min at 70 % V.O2max) with and without fluid intake (3 ml/kg body mass/10 min). Twenty runners (11 males, 9 females; age = 22 +/- 3 (SD) yrs; mean V.O2max = 55.7 +/- 5.0 ml/kg/min) completed four experiments: 1) rest, 2) running with no fluid (NF), 3) running with ingestion of a 4 % glucose solution (GLU), and 4) running with ingestion of a water placebo (PLA). To determine GI permeability, subjects also drank a solution containing 5 g sucrose (S), 5 g lactulose (L), and 2 g rhamnose (R) immediately prior to each trial. Gastroduodenal permeability was determined by urinary S excretion, while small intestinal permeability was determined by the L/R excretion ratio. Percent body mass loss (i.e., dehydration) was negligible during rest, GLU and PLA, while NF resulted in a 1.5 % loss of body mass (p < 0.05). Gastroduodenal and intestinal permeability were significantly (p < 0.008) increased in NF compared to rest. There were no other differences in GI permeability. These results indicate that fluid restriction during 1 h of steady-state running increases GI permeability above resting levels.

Effect of aspirin and ibuprofen on GI permeability during exercise.

This study was conducted to determine the effects of aspirin or ibuprofen on gastrointestinal permeability when combined with exercise. Eight runners completed three 60 min treadmill runs at 70 % VO(2max). For 24 hours prior to each run, subjects ingested aspirin (2 x 325 mg), ibuprofen (2 x 200 mg), or placebo capsules every 6 hours. Immediately before each run, a solution containing 5 g sucrose, 5 g lactulose, and 2 g rhamnose was ingested. Urine produced during each run, and for 4 h afterwards was collected. Urinary excretion of sucrose is an indicator of gastroduodenal permeability. The excretion ratio of lactulose-to-rhamnose assesses small intestinal permeability. Sucrose excretion (%) was greater (p < 0.017) for aspirin (0.37 [0.2 - 0.97]) compared to placebo (0.09 [0.05 - 0.30]) or ibuprofen (0.22 [0.1 - 0.39]) and sucrose excretion for ibuprofen was greater than placebo. The lactulose-to-rhamnose ratio was greater for aspirin (0.09 [0.08 - 0.30]) than placebo (0.065 [0.04 - 0.08]) however ibuprofen (0.08 [0.06 - 0.19]) was not different from aspirin or placebo. These results indicate that with prolonged running, gastroduodenal permeability is increased if aspirin or ibuprofen is used prior to such exercise. Furthermore, aspirin promotes greater gastroduodenal permeability and also increases small intestinal permeability.

Mouth to pouch transit after restorative proctocolectomy: hydrogen breath analysis correlates with scintigraphy.

OBJECTIVES: Fast intestinal transit may be responsible for slow adaptation and unacceptable steady-state function after restorative proctocolectomy. Investigation of GI transit time may be valuable in such a setting. We hypothesized that postprandial hydrogen breath tests may yield transit data that correlate with technetium-labeled meal scintigrams. METHODS: This study compared intestinal transit after a lactulose and bean meal via the breath hydrogen and scintigraphy methods in 21 ileoanal pouch subjects. The meal consisted of baked beans (425 g), 30 ml (20 g) lactulose syrup, 1 mCi 99mtechnetium sulfur colloid in finely chopped liver and 170 ml tap water. The meal contained 120 Kcal (70% carbohydrate, 18% protein and 12% fat). RESULTS: Of 21 pouch subjects, 11 (53%) had breath tests and scintigraphy transit studies that differed by 5-21 min. Three of 21 (14%) scintigraphy mouth to pouch transit times were faster than breath test transits by 43-107 min. Seven of 21 (33%) subjects did not have breath test peaks >10 ppm. Mouth to pouch transit for breath hydrogen (104+/-16 min) and scintigraphy (98+/-7 min) tests had significant correlation (r = 0.96, p < 0.0001) among subjects with alveolar hydrogen peaks and accurate scintigrams (n = 11). Scintigrams were five times more expensive than breath tests. CONCLUSIONS: A peaking hydrogen breath test provides an alternative to scintigraphy for estimating intestinal transit after ileoanal pouch.

Ileoanal pouch function and release of peptide YY.

PURPOSE: This study evaluates peptide tyrosine-tyrosine (PYY), intestinal transit, fecal retention time, and anal sphincter manometry in colectomized patients with ileal pouch-anal anastomosis. METHODS: Plasma and pouch PYY, mouth-to-pouch transit time, fecal retention time, and anal canal pressures were studied in 27 patients with ileoanal pouches a mean of 50 (range, 3-84) months after loop ileostomy closure. RESULTS: Basal and peak postprandial plasma PYY were significantly reduced in patients with pouches compared with controls (P < 0.0001). Pouch PYY was decreased compared with control ileal PYY (P = 0.0003). No significant correlation was noted between intestinal transit and total integrated PYY response in patients with pouches (r=0.36; P=0.06). Fecal retention time was related to postprandial total integrated response of plasma PYY (r=0.43; P=0.02), mouth-to-pouch transit (r=0.87; P < 0.0001), and resting (r=0.44; P=0.02) and squeeze (r=0.62; P=0.0006) anal sphincter pressures. CONCLUSIONS: Colectomized ileoanal patients with pouches showed decreased plasma and pouch PYY compared with controls. Intestinal transit was not significantly related to PYY release. However, prolonged pouch fecal retention was associated with greater PYY release, mouth-to-pouch transit, and anal sphincter pressures.

Colorectal and extracolonic cancer variations in MLH1/MSH2 hereditary nonpolyposis colorectal cancer kindreds and the general population.

PURPOSE: This clinical case review aimed to identify phenotypic variations in colorectal and extracolonic cancer expression between hereditary nonpolyposis colorectal cancer (HNPCC) families with MLH1 and MSH2 germline mutations and the general population. METHODS: Colorectal cancer onset and site distribution were compared among 67 members of MLH1 kindreds, 45 members of MSH2 kindreds, and 1,189 patients from the general population. Synchronous and metachronous cancer rates, tumor stage, extracolonic cancer incidence, and survival were also compared. RESULTS: Mean ages of colorectal cancer onset were 44, 46, and 69 years for MLH1, MSH2, and the general population, respectively (P < 0.001). More proximal and fewer distal colon cancers were noted in HNPCC than the general population (P < 0.001, P = 0.04). Site distribution showed disparity of rectal cancers (8 percent MLH1 vs. 28 percent MSH2; P = 0.01) based on genotypes. Overall, synchronous colorectal cancer rates were 7.4, 6.7, and 2.4 percent for MLH1, MSH2, and the general population, respectively (P = 0.016). Annual metachronous colorectal cancer rates were 2.1, 1.7, and 0.33 percent for MLH1, MSH2, and the general population, respectively (P = 0.041). Colorectal cancer stage presentation was lower in HNPCC than the general population (P = 0.0028). Extracolonic cancers were noted in 33 percent of MSH2 patients, compared with 12 percent of MLH1 patients and 7.3 percent of the general population with colorectal cancers (P < 0.001). Combined MLH1 and MSH2 ten-year survival was 68.7 percent compared with 47.8 percent for the general population (P = 0.009 stage stratified, hazard ratio 0.57). CONCLUSION: The presence of rectal cancer should not preclude the diagnosis of HNPCC, because the incidence of rectal cancer in MSH2 was comparable with that in the general population. Phenotypic variations, including the preponderance of extracolonic cancers in MSH2 patients, did not result in survival differences between genotypic subgroups. These phenotypic features of HNPCC genotypes may have clinical significance in the design of specific screening, surveillance, and follow-up for affected individuals.

Esophageal manometry and 24-hour pH testing in the management of gastroesophageal reflux patients.

BACKGROUND: With rising interest in gastroesophageal reflux disease, an evaluation of the importance of manometry (M) and 24-hour pH testing (pH) for decisions regarding these patients is appropriate. METHODS: Two gastroenterologists and two surgeons were presented with history and physical examination, endoscopy, histology, and esophagram data ("DATA") from 100 patients and asked to make a treatment decision. After some time, either pH or M was added to DATA, and a further decision requested. Finally, DATA plus pH plus M was presented, and a decision was requested. Decisions were evaluated for changes in medical therapy, changes between medical and surgical therapy, and changes in type of surgery offered. RESULTS: Overall, 43% (173 of 400) of decisions were altered by the addition of both M and pH to DATA, with 28.5% (114 of 400) of decisions changed from medical therapy to surgery or vice versa by the addition of both tests to DATA. The addition of M alone changed decisions more often than pH alone especially with regard to the type of surgery offered (P <0.05). CONCLUSIONS: Together, M and pH alter clinical decisions and often alter the decision regarding surgery. Both tests appear important, but M more frequently alters overall management decisions and the type of surgery offered. Despite the need for cost containment, these clinical tools are essential to important decisions regarding the care of patients with gastroesophageal reflux disease.

Effect of vitamin D receptor genotypes on calcium absorption, duodenal vitamin D receptor concentration, and serum 1,25 dihydroxyvitamin D levels in normal women.

It is well established that bone mineral density is under strong genetic control. Recently it was reported that the Bsm I restriction fragment length polymorphism of the vitamin D receptor (VDR) gene could account for up to 75% of the genetic variance in bone mineral density. However, the physiological basis for such an effect has not been established. The VDR gene codes for the vitamin D receptor protein which regulates intestinal calcium absorption. In order to assess the biochemical basis we studied the effect of common allelic variation of the VDR gene on intestinal VDR protein concentration, calcium absorption, and serum 1,25 dihydroxyvitamin D (1,25(OH)2D). Ninety-two Caucasian women were genotyped for Bsm I and Taq I polymorphism at the VDR gene locus. From these we compared 49 young women aged 25-35 years and 43 elderly women aged 65-83 years, who had all three measurements performed. There were no significant differences in intestinal VDR protein concentration, serum 1, 25(OH)2D, or radioactive calcium absorption among VDR genotype groups. Therefore, the small intestine does not seem to be a target for VDR gene polymorphism.

Association between intestinal vitamin D receptor, calcium absorption, and serum 1,25 dihydroxyvitamin D in normal young and elderly women.

The exact mechanism for the decrease in intestinal calcium absorption with age is not yet understood. A decrease with age in serum 1,25-dihydroxyvitamin D (1,25(OH)2D) or a decrease in the intestinal vitamin D receptor (VDR) protein concentration are possible causes. The objective of this study was to examine the effect of age on these factors. Fifty-nine young women age 25-35 years were compared with 41 elderly women age 65-83 years who underwent measurements of VDR, calcium absorption using a 20 mg and 100 mg calcium carrier, and calciotropic hormones. Calcium absorption by both tests was lower in the elderly women compared with the young women (p < 0.05). Serum 1,25(OH)2D and duodenal VDR protein concentration were not significantly different between the two age groups. Serum 1,25(OH)2D correlated with the 20 mg calcium absorption test in both young (r = 0.35, p < 0.007) and elderly women (r = 0.58, p < 0.0001) and with the 100 mg calcium absorption in the elderly (r = 0.32; p < 0.05). VDR did not correlate with calcium absorption in young women or elderly women, nor did VDR correlate with serum 1,25(OH)2D and serum 25-hydroxyvitamin D. In summary, the decrease in calcium absorption cannot be explained by a decrease in intestinal VDR. The correlation between serum 1,25(OH)2D and both calcium absorption tests only accounts for 12-30% of the variance in the age-related change in the calcium absorption tests. Other factors, not yet understood, are responsible for the decline in calcium absorption with age.

Heller myotomy is superior to dilatation for the treatment of early achalasia.

OBJECTIVES: To study the pretreatment characteristics that predispose a patient to rupture and to compare the outcome after dilatation with the outcome after surgical myotomy. DESIGN: A survey of all patients treated for achalasia at the Creighton University Medical Center, Omaha, Neb, during a 16-year period. Clinical examination and testing of consenting patients at 12 months and longer after treatment. SETTING: Tertiary referral center. PATIENTS: Of the 61 patients, 55 were treated with dilatation. Esophageal rupture developed in 8 patients (14.5%) with achalasia after pneumatic dilatation; these patients underwent surgery for the rupture. Dilatation failed in 8 other patients; these patients underwent a surgical myotomy. Six patients underwent a primary surgical myotomy. MAIN OUTCOME MEASURES: Duration of symptoms, weight loss, lower esophageal sphincter resting pressure and relaxation, amplitude and quality of distal esophageal contractions (assessed by manometry), 24-hour esophageal pH, and maximal esophageal diameter (assessed by barium swallow examination). RESULTS: Surgical myotomy at a mean (+/-SEM) of 44.9 +/- 18.6 months alleviated dysphagia in 13 (93%) of the 14 patients compared with only 12 (39%) of the 31 patients after dilatation at a mean (+/-SEM) of 55.0 +/- 11.7 months (P < .001). Of the 14 patients who underwent surgical myotomy, 13 (93%) were able to return to a normal diet compared with only 2 (7%) of the 31 patients who underwent dilatation (P < .001). Compared with patients without perforations, patients with perforations after pneumatic dilatation had pretreatment characteristics consistent with "early" disease: shorter symptom duration (20.1 +/- 5.4 vs 68.9 +/- 4.9 months, P < .001), less weight loss (4.7 +/- 1.2 vs 10.3 +/- 0.8 kg, P < .001), a less dilated esophagus (24.0 +/- 1.8 vs 45.6 +/- 3.0 mm, P < .005), lower lower esophageal sphincter resting pressures (19.3 +/- 2.6 vs 34.2 +/- 1.3 mm Hg, P < .001), a greater percentage of lower esophageal sphincter relaxation (47.6% +/- 4.9% vs 20.7% +/- 2.1%, P < .001), and a lower percentage of synchronous contractions in the distal esophageal body (66.2% +/- 4.9% vs 85.3% +/- 2.3%, P < .005). (All data given as the mean [+/-SEM].) All patients with pneumatic perforations were successfully treated by thoracotomy and surgical repair. CONCLUSIONS: Surgical myotomy provides a better long-term outcome. The early disease stage is associated with perforation after pneumatic dilatation. Surgical myotomy rather than balloon dilatation should be considered in patients with early achalasia.

Genetic counseling in an extended attenauted familial adenomatous polyposis kindred.

OBJECTIVES: To provide DNA-based genetic counseling to family members in the direct genetic lineage of a family fulfilling phenotypical criteria for the autosomal, dominantly inherited, attenuated familial adenomatous polyp (AFAP) syndrome. This enabled highly targeted cancer risk estimation based on cancer phenotype in concert with the presence or absence of the adenomatous polyposis coli (APC) germline mutation. Management recommendations could then be fully responsive to this syndrome's natural history. METHODS: Detailed family history with pathology verification of colonic polyps and cancer was performed on an extended AFAP kindred. Endoscopic gastrointestinal examinations enabled detailed knowledge of the syndrome's upper and lower gastrointestinal tract phenotype. Molecular genetic evaluation of DNA led to the identification of the APC germline mutation which co-segregated with the phenotype. RESULTS: Forty-two members of this extended AFAP family underwent DNA testing, wherein 27 were found to harbor the APC germline mutation,thereby enabling precision in their genetic counseling. Anecdotal examples of this counseling experience, with particular attention to psychological reactions, as well as concerns about such issues as insurance and employer discrimination, have been described. CONCLUSIONS: When DNA-based testing is offered to AFAP family members, genetic counselors must compassionately consider patients' psychological concerns when providing detailed risk status and available surveillance and management programs.

Genetic counseling in a Navajo hereditary nonpolyposis colorectal cancer kindred.

BACKGROUND: Cross-cultural genetic counseling was provided to an extended Navajo Indian family in which the MLH1 gene mutation for hereditary nonpolyposis colorectal cancer (HNPCC) had been identified. The family had been observed by the authors since 1983 and over the years had been provided with intensive education regarding the natural history of HNPCC as well as recommendations for cancer surveillance and management that was responsive to this natural history. METHODS: Following identification of the MLH1 mutation, DNA from family members was evaluated by a reference laboratory (OncorMed, Gaithersburg, MD), where sequences were checked in both the forward and reverse directions against the published sequence for MLH1. The 4bp deletion beginning at the first nucleotide of codon 727 was easily visualized in the heterozygous condition in both affected and predispositional individuals. The family was reeducated as a group and then provided further education individually during genetic counseling sessions, at which time they were appraised of potential penalties, such as insurance and employer discrimination, and psychological sequelae that could result from knowledge of the MLH1 mutation. Strict confidentiality of this information was assured. RESULTS: DNA testing was performed on 51 family members. Twenty-three individuals were counseled, seven of whom were positive for MHL1. Reactions ranged from full acceptance of the genetic implications to traditional Navajo reasoning such as the family had been cursed. CONCLUSIONS: DNA-based genetic counseling requires comparison and empathy, coupled with intensive preeducation regarding potential penalties and advantages that might emanate from this knowledge. Special care must be given to patients' culture, beliefs, and traditions.

Attenuated familial adenomatous polyposis (AFAP). A phenotypically and genotypically distinctive variant of FAP.

BACKGROUND: The usual manifestation of familial adenomatous polyposis (FAP) is hundreds or thousands of colonic adenomas. The authors previously described a colon cancer-prone syndrome characterized by fewer adenomas (1-100), most located in the proximal colon, and upper gastrointestinal lesions, particularly fundic gland polyps and duodenal adenomas. The colonic adenomas are often flat rather than polypoid, a feature emphasized in earlier reports with the term "hereditary flat adenoma syndrome." The syndrome has an autosomal dominant pattern of inheritance and is linked to the adenomatous polyposis coli (APC) locus at 5q. METHODS: This is a descriptive study based on one family that was followed for more than a decade. Total cell RNA was isolated from cultured lymphoblasts, and an in vitro protein synthesis assay was used to detect APC mutations. Sixteen individuals whose APC mutation status was known had sequential endoscopic evaluations. Five patients were given one or more courses of sulindac. RESULTS: There was perfect concordance between clinical affected status and an APC mutation. All affected members generated a 16-kDa polypeptide from the mutant allele, consistent with a 2-base pair deletion at the extreme 5' end of the APC gene. Sixteen mutation-positive individuals underwent upper gastrointestinal endoscopy and colonoscopy; 13 had colonic adenomas, with the number visualized at any one examination ranging from 1 to greater than 50. Upper gastrointestinal examination revealed fundic gland polyps in 15, gastric or duodenal adenomas in 4, and periampullary carcinoma in 1. CONCLUSION: AFAP is a phenotypically distinctive syndrome, differing from classic FAP by having fewer colonic adenomas that tend to be proximally distributed and flat rather than polypoid. The position of the APC germline mutation appears to allow for the molecular differentiation between FAP and the attenuated variant in that the extreme 5' APC mutations are associated with the latter.

Update on the differential diagnosis, surveillance and management of hereditary non-polyposis colorectal cancer.

Hereditary non-polyposis colorectal cancer (HNPCC) is the most common hereditary form of colorectal cancer (CRC), accounting for approximately 10% of the total CRC burden. HNPCC lacks premonitory physical stigmata, thereby making the family history crucial for diagnosis. Advances in molecular genetics during the past 2 years have led to the cloning of four HNPCC genes (MHS2, MLH1, PMS1 and PMS2). It is now possible to provide presymptomatic DNA testing followed by genetic counselling for gene carriers. Some studies have shown that adenomas in HNPCC are larger, more villous, and have more high grade dysplasia than sporadic cases, suggesting an accelerated adenoma-carcinoma sequence. Given the early age of onset and proximal predominance of CRC, we initiate colonoscopy at age 20-25 years and we recommend that it be performed every 1-2 years. The wealth of clinical and molecular genetic knowledge currently available to physicians about HNPCC can be used effectively for cancer control.

An investigation of sources of variation in calcium absorption efficiency.

To examine putative sources of interindividual variation in calcium absorption efficiency, we studied 41 healthy premenopausal women (mean age, 36.4 yr). About half were randomized to pretreatment with supplemental 25-hydroxyvitamin D (25OHD; 20 micrograms/day [corrected] for approximately 34 days) before testing. We measured dietary factors, humoral regulators, intestinal motility, mucosal histology, mucosal vitamin D receptor levels, and calcium absorption efficiency. In winter tests, but not in summer tests, calcium absorption fraction was significantly higher in the pretreated group (mean, 0.465 vs. 0.387). Serum 25OHD, intestinal transit, and urinary calcium to creatinine ratio were all significantly and positively correlated to calcium absorption efficiency. However, neither the level of 1,25-dihydroxyvitamin D receptors in duodenal mucosa nor circulating 1,25-dihydroxyvitamin D was related to calcium absorption efficiency. These findings, which are consistent with other published human data, suggest that 25OHD plays a more prominent role in the regulation of calcium absorption than is generally believed. In a multiple regression model, serum 25OHD, mouth to cecum transit time, and fasting urinary calcium/creatinine ratio explained 44% of the observed variation in calcium absorption efficiency.

Surveillance in Lynch syndrome: how aggressive?

OBJECTIVE: To identify colorectal cancers occurring after colonoscopic screening in patients at risk for Lynch syndrome. METHODS: All cancers in Lynch syndrome families on file at the Creighton University Hereditary Cancer Institute were reviewed for history of prior colonoscopy. RESULTS: Of 225 individuals with 313 colon cancers, six patients from different families had colon cancers arising within 4 1/2 yr of colonoscopic surveillance. Another 17 patients had metachronous colon cancers within 5 yr of resection of their first colon cancer. CONCLUSION: Of 225 colorectal cancer patients from Lynch syndrome families, 10.2% of patients had colorectal cancer within 5 yr of colonoscopy or colon resection. In Lynch syndrome, the potential for interval neoplasms and the malignant potential of missed diminutive adenomas may differ from cases in the general population.