Michael R. Treat

Postoperative immune function varies inversely with the degree of surgical trauma in a murine model.

AbstractBackground: Major surgery through a laparotomy incision is associated with a postoperative reduction in immune function. Studies in rats involving sham procedures suggest that immune function may be preserved after laparoscopy. This study investigates the effects of incision length and exposure method for bowel resection with respect to postoperative immune function as assessed by delayed-type hypersensitivity (DTH) reactions. Methods: Male Sprague Dawley rats (n= 175) were challenged preoperatively, immediately postoperatively, and on postoperative day 2 with an intradermal injection of 0.2 mg phytohemagglutinin (PHA), a nonspecific T-cell mitogen. The averages of two measures of perpendicular diameters were used to calculate the area of induration. Anesthesia control rats underwent no procedure. Minilaparotomy rats underwent a 3.5-cm midline incision. Sham full laparotomy rats underwent a 7-cm midline incision. The open bowel-resection group underwent a cecal ligation and resection through a 7-cm midline incision. In the laparoscopic-assisted resection group a CO2 pneumoperitoneum and four-port technique was utilized to deliver the cecum through a 4-mm port where the cecum was extracorporeally ligated and resected. Results: Preoperative responses were similar in all five groups. Incision length: Full laparotomy group responses were 20% smaller than anesthesia control responses on postoperative day (POD)1 through POD4 (p < 0.02). At no time point were the responses in the minilaparotomy group significantly different from either anesthesia control or full laparotomy group responses. Exposure method: The laparoscopic-assisted resection group responses were 20% larger than open group responses at the time of two of the four postoperative measurements (p < 0.05, both comparisons). At all postoperative time points, open resection group responses were significantly smaller than control responses (p < 0.05, all comparisons), whereas at no time point were laparoscopic group responses significantly different from control responses. Conclusion: We conclude that postoperative cell-mediated immune function varies inversely with the degree of surgical trauma. Results from the minilaparotomy and laparoscopy groups suggest that procedures done through small incisions may result in preservation of postoperative immune function.

Preservation of immune response after laparoscopy

We evaluated the immunologic responses following laparoscopic and open surgery by comparing delayed type hypersensitivity induration size before and after each method of accessing the abdominal cavity. One hundred and thirty-two male Sprague-Dawley rats were sensitized with keyhole limpet hemocyanine (KLH). Animals were challenged with KLH and phytohemaglutanin (PHA) 10 days after sensitization. On day 14 after initial sensitization animals were randomly divided into three groups. Group one served as controls and had no procedure performed, group two underwent peritoneal insufflation with carbon dioxide gas to a pressure of 6–8 mm Hg for one half hour, and rats in group three had a midline laparotomy which was closed after one half hour. Each rat was challenged with KLH immediately and at three days post-operatively. The area of induration in response to each of the challenges was measured with calipers 24 and 48 hours after the challenge. Results of this skin testing showed that the group of animals that underwent laparotomy, despite having normal responses preoperatively, had significantly diminished responses to both KLH and PHA when challenged postoperatively. The insufflated group showed no differences from control animals at any time point examined. We conclude that DTH response in this model is better preserved after laparoscopy than laparotomy.We further conclude that the defect in DTH response is in the effector arm. The question of the clinical significance of these findings is addressed.

Postoperative cell mediated immune response is better preserved after laparoscopic vs open colorectal resection in humans.

BACKGROUND Animal studies have documented significantly better preserved postoperative cell-mediated immune function, as measured by serial delayed-type hypersensitivity (DTH) challenges, after laparoscopic-assisted than after open bowel resection. Similarly, in humans, the DTH responses after open cholecystectomy have been shown to be significantly smaller than preoperative responses; whereas after laparoscopic cholecystectomy, no significant change in DTH response has been noted. The purpose of this study was to assess cell-mediated immune function via serial DTH skin testing in patients undergoing laparoscopic or open colectomy. METHODS A total of 35 subjects underwent either laparoscopic (n = 18) or open colectomy (n = 17) in this prospective but not randomized study. Only patients who were judged to be immunoresponsive by virtue of having responded successfully to a preoperative DTH challenge were eligible for entry in the study. DTH challenges were carried out at three time points in all patients: preoperatively, immediately following surgery, and on the third postoperative day (POD 3). Responses were measured 48 h after each challenge and the area of induration calculated. There were no significant differences between the laparoscopic (LC) and open (OC) colorectal resection groups in regard to demographics, indications for surgery, or type of resection carried out. The percentage of patients transfused was similar in both groups (17%, LC; 12% OC; p = NS). In the LC group, all cases were completed without conversion using minimally invasive methods. There were no perioperative deaths, and the rate of postoperative complications was similar in both groups. The preoperative and postoperative DTH results were analyzed and compared within each surgical group using several methods. RESULTS In regards to the OC group results, the median sum-total DTH responses for the day of surgery challenges (0.44 +/- 69 cm2) and the POD 3 challenges (0.72 +/- 3.37 cm2) were significantly smaller than the preoperative results (3.61 +/- 3.83 cm2, p <0.0005 vs op day and p <0.0003 vs POD 3 results). When the LC group results were similarly analyzed, no significant difference in DTH response was noted between the pre- and the postoperative challenge results. Additionally, when the median percent change from baseline was calculated and considered for the OC groups DTH results, both postoperative challenge time points demonstrated significantly decreased responses when compared to their preoperative results (vs day of surgery, p <0.007; vs POD 3, p <0.006). Similar analysis of the LC groups results yielded nonsignificant differences between the pre- and postoperative responses. Lastly, when the LC and the OC groups median percent change from baseline results were directly compared for each of the postoperative challenges, a significant difference was noted for the POD 0 challenge (LC, -21%; OC 88%; p <0.004) but not for the POD 3 challenge. CONCLUSIONS The postoperative DTH responses of the open surgery patients were significantly smaller than their preoperative responses. This was not the case for the laparoscopic group (a combination of fully laparoscopic and laparoscopic-assisted resections). When the open and laparoscopic groups results are directly compared, regarding the results of the day of surgery DTH challenges, the LC groups median percent change from baseline was significantly less than that observed in the OC group. These results imply that open colorectal resection is associated with a significant suppression of cell-mediated immune response postoperatively, whereas in this study laparoscopic colorectal resection was not. Further human studies are needed to verify these findings and to determine the clinical significance, if any, of this temporary difference in immune function following colon resection.

Better preservation of immune function after laparoscopic-assisted vs . open bowel resection in a murine model

PURPOSE: We evaluated cell-mediated immune function after laparoscopic-assisted and open bowel resection in rats by measuring delayed-type hypersensitivity responses to keyhole limpet hemocyanin (KLH) and phytohemagglutinin (PHA). METHODS: Male Sprague-Dawley rats (n=120) were sensitized to 1 mg of KLH ten days before investigations. Rats were challenged preoperatively, immediately postoperatively, and on postoperative day (POD) 2 with an intradermal injection of 0.3 mg of KLH and 0.2 mg of PHA (at different sites). Averages of two measures of perpendicular diameters (taken 24 and 48 hours postchallenge) were used to calculate the area of induration using the formula for the area of an ellipse, A=(D1/2×D2/2)×π. Anesthesia control animals underwent no procedure (n=40). Open resection group underwent ligation and resection of the cecum (length=2 cm) through a 7 cm midline incision (n=40). In the laparoscopic-assisted resection group, under CO2 pneumoperitoneum (4–6 mmHg), the cecum was identified, dissected free, and exteriorized through a 4 mm port. The cecum was then ligated and resected extracorporeally (n=40). RESULTS: Preoperative responses to both KLH and PHA were the same in all three groups. Furthermore, within each group, postoperative responses were similar. When groups were compared, the anesthesia group responses were significantly greater than the open resection group responses at all time points (P<0.05 for all comparisons). Laparoscopic-assisted resection group responses differed from control at only two of eight postoperative measures. Laparoscopic resection group responses were significantly greater than open resection group responses to challenge with both KLH and PHA on POD1 (P<0.02, for both comparisons) and POD 4 (P<0.05, for both comparisons). CONCLUSIONS: Postoperative cell-mediated immune function is better preserved after laparoscopic-assisted bowel resection than after open resection as assessed by skin antigen testing.

Tissue soldering by use of indocyanine green dye-enhanced fibrinogen with the near infrared diode laser

Anastomoses welded by laser have been strengthened by applying a solder of fibrinogen combined with a laser energy absorbing dye (indocyanine green, maximum absorbance 805 nm) to the anastomotic site before continuous-wave diode laser exposure (808 +/- 1 nm, 4.8 W/cm2). Immediately after creation, the bursting pressures of welds created without fibrinogen (262 +/- 29 mm Hg, n = 11) were significantly less than repairs with fibrinogen (330 +/- 75 mm Hg, n = 11) (p less than 0.05). When repairs performed with fibrinogen were exposed to urokinase (25,000 IU) the bursting pressures were not significantly different from baseline (290 +/- 74 mm Hg, n = 5). Aortotomies closed by suture did not burst but leaked at pressures significantly below those of vessels closed by laser (165 +/- 9 mm Hg, n = 11) (p less than 0.01). Twenty-two repairs soldered with fibrinogen were incorporated into survival studies in rabbits and examined from 1 to 90 days after operation. No anastomotic ruptures, thromboses, or aneurysms were identified. Soldered sites rapidly regenerated a new intimal surface and healed by myofibroblast proliferation. No significant foreign body response was identified; the fibrinogen was resorbed. Laser soldering with exogenous fibrinogen is feasible without topical administration of additional clotting agents, significantly improves the bursting strength of primary laser welded anastomoses, and appears to result from urokinase-resistant fibrinogen cross-linking.

Trocar site recurrence is unlikely to result from aerosolization of tumor cells.

PURPOSE: This study was undertaken to investigate the ability of a high-pressure CO2 environment to aerosolize tumor cells in bothin vitroandin vivo models. (An aerosol is defined as a stable gaseous suspension of insoluble particles.) Also, this study was designed to determine if rapid desufflation is capable of transporting fluid laden with tumor cells. METHODS: The fourin vitro aerosol experiments were performed in an 18.9-l plastic vessel fitted with two 7-mm ports and a compliant latex balloon affixed to the top. After CO2 insufflation, the vessel was desufflated through a sterile soluset containing 25 ml of culture media that was subsequently emptied into a culture dish, incubated for two weeks, and periodicallyassessed for growth. At the bottom of the vessel, one of the following was placed: Study 1 and 2, a suspension of B16 melanoma or colon 26 tumor cells in liquid culture media; Study 3, colon 26 cells in saline solution; Study 4, several pieces of solid colon 26 tumor. In Studies 1 to 3, cell preparations were subjected to the following high-pressure CO2 conditions (pneumo): 1) static pneumo of 15 and 30 mmHg (10 minute dwell); 2) a continuous flow (CF) of CO2 (10 l) while maintaining a pressure of 15 or 30 mmHg in the vessel. In Study 4, only the 30 mmHg static and CF conditions were tested. Between 6 and 12 determinations were performed for each condition and cell preparation.In vivo aerosol experiments consisted of Spraque Dawley rats that received intraperitoneal injections of 10-5 B16 cells in 0.1 ml of liquid media.Two laparoscopic ports were placed in the abdomen, one each for insufflation and desufflation. Study groups were: 1, static CO2 pneumo of 15 mmHg; 2 and 3, continuous CO2 flow (10 l) at a stable pneumo pressure of 5 and 10 mmHg. Desufflation was performedvia the same collecting device and handled in an identical manner to thein vitroexperiments described above. Thein vitro balloon experiment was designed to investigate the ability of desufflation to transport fluid-containing tumor cells; latex balloon model was used. To prevent complete loss of volume on desufflation, a wire coil was placed inside the balloon. Twenty ml of media containing 20×10−6B16 cells was placed in the bottom of the balloon. The balloon was insufflated with 1 to 21 of gas. There were three study groups that differed in the degree to which the cell suspension was agitated before desufflation. Study conditions were as follows: 1) no agitation; 2) moderate agitation to coat the lower walls and coil; 3) maximum agitation to coat the entire balloon. To verify the viability of tumor cells,at the end of eachin vitroandin vivo study, a sample of tumor cells or peritoneal washing was incubated in sterile media. These samples served as positive controls. RESULTS:In vitro aerosol studies consisted of the following. At the end of two weeks of incubation, no tumor growth was noted in any of the 124 test dishes. The 14 control samples all demonstrated tumor growth.In vivo aerosol studies consisted of the following. Zero of 18 experimental dishes grew tumor. All three peritoneal washing samples demonstrated growth.In vitro balloon studies consisted of the following. Zero of 12 test dishes in Groups 1 and 2 demonstrated growth, whereas five of six dishes did so in Group 3 (maximally agitated before desufflation). Again, positive controls all grew tumor cells. SUMMARY: We were unable to demonstrate aerosol formation in any of thein vitroandin vivo studies performed. In the balloon experiment, desufflation-related transport of tumor cells was demonstrated but only when the entire balloon surface was coated with the tumor cell suspension before desufflation. CONCLUSION: Aerosols of tumor cells are not likely to form. Free intraperitoneal tumor cells are most likely found in liquid suspension. Desufflation is a potential means of transport of cell-laden fluid.

Dietary Risk Factors for the Incidence and Recurrence of Colorectal Adenomatous Polyps: A Case-Control Study

Diet has long been thought to be an important factor in the etiology of colorectal cancer. The specific dietary nutrients or factors responsible for this disease, the second leading cause of cancer death in the United States [1], have not, however, been clearly elucidated. Colorectal adenomatous polyps (here referred to as polyps) are generally considered to be precursor lesions for most cases of colorectal carcinoma [2-4]; however, little is known about their risk factors. Since the introduction of fiberoptic endoscopy, especially colonoscopy, attention has focused on the potential for preventing colorectal cancer by screening for and resecting the adenomas [5, 6]. Because of their high recurrence rate after resection [7, 8], these polyps have been used as an end point for the study of potential chemopreventive agents. Four studies have explored potential dietary risk factors for incident colorectal adenomatous polyps [9-12]. No previous observational studies have explored the role of diet or other lifestyle factors in the recurrence of polyps after polypectomy. We discuss the results of a casecontrol study of colorectal polyps among patients from three colonoscopy practices and analyze dietary risk factors for both incident and recurrent polyps. Methods Our study sample included patients having colonoscopy at three colonoscopy practices in New York City between April 1986 and March 1988. In total, 2988 patients were evaluated. Of these, 2443 (81.8%) were eligible for our study (patients had to be between 35 and 84 years of age; reside in New York, New Jersey, or Connecticut; speak English or Spanish; and have colonoscopy to at least the splenic flexure). The colonoscopists completed data sheets indicating the reason for colonoscopy and the clinical findings at the time of colonoscopy. The study pathologist reviewed slides of all suspected neoplastic lesions. All eligible participants received a letter signed by their colonoscopist introducing the study. A trained interviewer then contacted and interviewed participants by telephone. Alternatively, the questionnaire was mailed for self-completion and was followed by a telephone interview to resolve any remaining questions. An earlier study indicated that the results obtained for dietary factors were similar for both interview methods [13]. The interview itself consisted of a general questionnaire that focused on demographic characteristics, medical history, lifestyle, family history, and other topics. The dietary interview consisted of the Block food frequency questionnaire and specified food intake for a period 3 to 5 years before the colonoscopy [14]. Ultimately, 1956 dietary questionnaires were completed (80.1% of eligible patients). Of these, 71% were conducted by telephone, and 29% were returned by mail. An incident case of adenomatous polyps was defined as an eligible participant with no history of colon carcinoma, adenomatous polyps, or inflammatory bowel disease who was found to have one or more pathologically defined polyps on the index colonoscopy. The incident control group consisted of persons who were found to be free of colorectal neoplasia on index colonoscopy and who were without a history of adenomatous polyps, colon cancer, or inflammatory bowel disease. A case of recurrent polyps was defined as an eligible participant with a self-reported history of one or more polyps who had a pathologically confirmed polyp on the index colonoscopy. The recurrent control was defined as a participant whose index colonoscopy showed no colorectal neoplasia but who had a history of one or more polyps. Cases and controls with a history of colorectal cancer or inflammatory bowel disease were excluded. Although we did not have pathologic confirmation of all initial polyps, we did obtain pathology reports on a random sample of 100 recurrent cases and controls and found 97 to be adenomatous. By these criteria, 286 incident cases (162 men and 124 women) and 480 incident controls (210 men and 270 women) were identified, whereas 186 recurrence cases (130 men and 56 women) and 330 recurrence controls (187 men and 143 women) were found. Food item and nutrient data were generated by software programs provided by Block and coworkers [14] at the National Cancer Institute. The main analyses were done using logistic regression modelling and maximum likelihood ratios [15] in the BMDP-LR program. Analyses were conducted separately for men and women. Age, Quetelet index, and caloric intake were entered as covariates for most analyses. A previous study by our group had shown obesity, as measured by Quetelet index, to be a risk factor for polyps among women; the trend for men was not significant [16]. Analyses in which nutrients were standardized per 1000 kilocalories were also done for comparison [17]. For each nutrient or food group, quartiles were defined by review of the control group data; the lowest quartile was given a reference value of 1.0, and odds ratios were calculated for each of the other quartiles, with 95% confidence intervals (CIs) for the highest-to-lowest quartile comparison. The probability of a linear trend was calculated by entering the four quartiles as ordered categories. Results The case and control groups for the incidence and recurrence studies were generally similar in age distribution and education. Table 1 shows a comparison of the characteristics of the case and control groups for both the incident and recurrent groups. Most polyps were 5 mm or larger in size and had at least some degree of atypia. The site distribution of the incident polyps showed a preponderance to the left. Most incident case and control participants had colonoscopy because of overt or occult rectal bleeding. A larger proportion of the recurrent polyps were right-sided (P = 0.005). The time interval from initial polypectomy to index colonoscopy was 4.3 years for cases and 3.7 years for controls (P > 0.2). Table 1. Polyp Characteristics for Incident and Recurrent Cases Tables 2 and 3 show the odds ratios by quartile, using the lowest quartile as the referent group, for some of the 15 nutrients and food groups evaluated. The results for vegetables, red meat, beef, cheese, protein, vitamin C, and carotene are not shown; however, no consistent differences were found. Table 2. Odds Ratios of Incident Polyps by Quartile of Selected Nutrients and Food Groups, Adjusted for Age, Quetelet Index, and Caloric Intake Table 3. Odds Ratios of Recurrent Polyps by Quartile of Selected Nutrients and Food Groups, Adjusted for Age, Quetelet Index, and Caloric Intake Men The only dietary risk factor statistically associated with the risk for colorectal adenomatous polyps in men was caloric intake; however, this association was in a direction opposite to that ordinarily expected [18]. Women In contrast, various dietary factors were observed to be associated with the risk for colorectal adenomatous polyps in women (Tables 2 and 3). Increased saturated fat, decreased fish and chicken, increased meat-to-fish and -chicken ratio, and decreased vitamin A intake increased the risk for incident polyps (Table 2). Increased caloric intake, increased total fat, increased saturated fat, and decreased fiber intake all raised the risk for recurrent polyps in women, whereas vitamin A and carbohydrate intake had borderline protective effects (Table 3). Analyses were also done using nutrient density (nutrient compared with caloric intake) instead of entering calories as a covariate. The results are not shown, but the same risk factors were statistically significant for incident polyps in women, although the estimated odds ratios were larger. In addition, fiber was protective for incident polyps in women (odds ratio, 0.6; CI, 0.3 to 1.1; P = 0.06). The same dietary factors were also associated with recurrent polyps in women, although the odds ratio estimates were again larger. Both vitamin A (odds ratio, 0.5; CI, 0.2 to 1.1; P = 0.06) and carbohydrate intake (odds ratio, 0.4; CI, 0.2 to 1.0; P = 0.001) were more clearly protective. Subgroup Analyses For each of the dietary factors associated with colorectal polyps in women, further subgroup analyses were done for right-sided polyps only, for left-sided polyps only, and for polyps 5 mm or larger in size. Generally, no major variations were observed for the various subgroups, although some reduction was seen in statistical power because of the smaller number of cases. To determine the independent effect of each of the variables found to be associated with polyps in women, we conducted further multiple logistic regression analyses using various dietary factors as covariates. The elevated risk associated with increased consumption of saturated fats remained after adjustment for fiber or vitamin A. Discussion Many studies have suggested that diet plays a role in the etiology of colorectal cancer [19-35]. Evidence suggests that increased consumption of saturated fat is a causal factor and that increased consumption of fiber, (particularly fruit and vegetable fiber) is protective [26]. Similarly, an increased risk has been associated with greater consumption of red meat compared with chicken or fish [19], and a protective effect has been linked to consumption of vegetables [35]. A protective effect of such micronutrients as vitamin A, carotene [32-34], and calcium [27-30] has also been suggested, although the evidence is less compelling. Because adenomatous polyps are known precursors for colorectal cancer, three casecontrol studies [9-11] have explored their association with diet. Despite their limitations, each study has suggested a protective effect for fiber. A recent cohort study [12] of male health professionals found saturated fat and decreased fiber, as well as increased red meat-to-fish and meat-to-chicken ratio, to be risk factors for left-sided incident polyps. A small study by our group also showed that supplemental vitamins had no influence on the development of

Is immune function better preserved after laparoscopic versus open colon resection

The purpose of this preliminary study was to evaluate immunologic responses to laparoscopic vs standard open colon resection and to evaluate possible mediators of any differences found. Specifically, we compared cortisol levels and delayed-type hypersensitivity response after each method of colon resection in a group of 20 pigs.Two groups of 10 animals each were treated in identical fashion including bowel preparation, anesthesia, and postoperative management. The only difference between groups was that one underwent laparoscopic and the other an open colon resection. Blood specimens for cortisol were drawn before, during, and immediately postoperatively as well as at 11A.M. on postoperative days 1 and 2. All animals had been previously immunized as piglets with Sow Bac-E (Oxford Veterinary, Worthington, MN), an antigen preparation of common pig pathogens. At the conclusion of the operative procedure 0.5 cc of the antigen was injected intradermally on the right forelimb of the animals. At 48 and 72 h postoperatively the largest diameters of induration surrounding the injection site were measured and averaged. Cortisol levels were measured in serum samples by radioimmunoassay (Met-Path, Rockville, MD). Statistical significance was determined by t-test.Results of skin antigen testing showed that the group of pigs that underwent laparoscopic resection had a 20% greater response, 1.54 cm±0.28 cm at 48 h and 1.53 cm±0.18 cm at 72 h. For the open-surgery group results were 1.24 cm±0.26 cm at 48 h and 1.32 cm±0.21 cm at 72 h,P<0.05 for the difference between groups at both 48 and 72 h. Cortisol levels were not significantly different between groups at any of the time points.We conclude that T-cell-related immune function in this model, as measured by delayed-type hypersensitivity, is better preserved after laparoscopic than open colon resection. We further conclude that cortisol levels are not responsible for the improved preservation of the immune response. The benefits of improved postoperative immune function may be significant for patients undergoing laparoscopic colon resection.

Helium-neon laser irradiation at fluences of 1, 2, and 4 J/cm2 failed to accelerate wound healing as assessed by both wound contracture rate and tensile strength

Reports in the literature indicate that low energy laser irradiation has a biostimulatory effect on wound healing; however, no mechanism of this effect has been elucidated.

Colonoscopic screening for neoplasms in asymptomatic first-degree relatives of colon cancer patients

Individuals with a family history of colorectal cancer are believed to be at an increased risk of developing colorectal neoplasia. To estimate this risk and the potential yield of screening colonoscopy in this population, we recruited and prospectively colonoscoped 181 asymptomatic first-degree relatives (FDR) of colorectal cancer patients and 83 asymptomatic controls (without a family history of colorectal cancer). The mean ages for the FDR and control groups were 48.2 ± 12.5 and 54.8 ± 11.0, respectively. Adenomatous polyps were detected in 14.4 percent of FDRs and 8.4 percent of controls. Although 92 percent of our FDRs had only one FDR afflicted with colon cancer, those subjects with two or more afflicted FDRs had an even higher risk of developing colonic adenomas (23.8 percent) than those with only one afflicted FDR (13.1 percent). A greater proportion of adenomas was found to be beyond the reach of flexible sigmoidoscopy in the FDR group than in the controls (48 percentvs.25 percent, respectively). Logistic regression analysis revealed that age, male sex, and FDR status were independent risk factors for the presence of colonic adenomatous polyps (RR=2.32, 2.86, and 3.49, respectively;P<0.001). Those at greatest risk for harboring an asymptomatic colonic adenoma are male FDRs over the age of 50 (40 percentts.20 percent for age-matched male controls). Based on probability curves, males with one FDR afflicted with colon cancer appear to have an increased risk of developing a colonic adenoma beginning at 40 years of age. Our results document, for the first time, an increased prevalence of colonoscopically detectable adenomas in asymptomatic first-degree relatives of colon cancer patients, as compared with asymptomatic controls, and support the use of colonoscopy as a routine screening tool in this high-risk group.