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Little polyps: Are they a big problem?
GASTROENTEROLOGY 1997;113:1413–1418
SELECTED SUMMARIES Henry J. Binder, M.D. Selected Summaries Editor Yale University School of Medicine New Haven, Connecticut 08520-8019
STAFF OF CONTRIBUTORS Robert Bresalier, Detroit, MI Hannah Carey, Madison, WI M. Brian Fennerty, Portland, OR Greg Fitz, Denver, CO Guadalupe Garcı´a-Tsao, New Haven, CT
Ian Scott Grimm, Chapel Hill, NC Cyrus Kapadia, New Haven, CT Ronald L. Koretz, Sylmar, CA Pankaj Pasricha, Galveston, TX
LITTLE POLYPS: ARE THEY A BIG PROBLEM? Read T, Read J, Butterly L. Importance of adenomas 5 mm or less in diameter that are detected by sigmoidoscopy. N Engl J Med 1997;336:8–12. Read et al. sought to determine the clinical importance of small polyps by establishing the prevalence of more proximal neoplastic lesions in the colon in an asymptomatic averagerisk population of individuals found to have the diminutive polyp (°5 mm) on screening flexible sigmoidoscopy. Physicians at the Lahey Clinic screened 3496 consecutive patients over a 3-year period, and they were prospectively studied. If a polyp was identified at sigmoidoscopy, it was measured using open biopsy forceps as a reference standard, and a biopsy of the polyp was performed for histology. If the polyp was an adenoma, then colonoscopy was performed within 1 year, but usually within 3 months. At colonoscopy, all polyps were measured and removed and analyzed histologically. Adenomas were classified by size (diminutive, °5 mm; small, 6–10 mm; large, ¢11 mm) and whether they were advanced (¢10 mm in size, villous in histology, moderate to severe dysplasia, or malignant). Patients at increased risk of colonic neoplasia (those with a history of colon cancer or previous adenomatous polyps, inflammatory bowel disease, heme-positive stools, firstdegree relative with colorectal cancer, rectal bleeding, anemia, change in bowel habits, and barium enema or colonoscopy within 5 years) were excluded to study only asymptomatic and average-risk individuals. Of the 3796 individuals screened, 768 (22%) had a distal colonic polyp(s). Of these 768, 311 had a neoplastic lesion, but 90 were excluded because of symptoms or risk factors stated above. Another 18 were excluded because of incomplete data (e.g., lack of colonoscopy), leaving 203 evaluable patients. Of these 203, 137 had a distal diminutive polyp, 52 had a small polyp, and 14 had a large polyp. More proximal adenomas were found in 29%, 29%, and 57% of these groups at colonoscopy, respectively. Six percent of those with a distal diminutive polyp had a proximal advanced lesion vs. 10% of those with a small polyp and 29% of those with a large polyp. Of the 137 patients with a distal diminutive polyp, 4 had cancer found proximally. The number of distal polyps or the
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09-19-97 18:34:46
gasa
William Sandborn, Rochester, MN Mitchell L. Schubert, Richmond, VA Fergus Shanahan, Wilton, Cork, Ireland David I. Soybel, Boston, MA Jacques Van Dam, Boston, MA
age of the individual was not a risk factor for a proximal lesion (P Å 0.11), whereas the size of the distal polyp was predictive of increased risk, with large polyps being greater than diminutive polyps (P Å 0.02). These investigators concluded that patients with a distal diminutive adenomatous polyp had a significant risk of proximal neoplasia, justifying a recommendation of colonoscopy for these individuals. Comment. The risk of significant proximal neoplasia in the colon of patients with small distal colonic polyps and the appropriate management of these individuals has been a controversial, emotional, and widely debated issue. This report by Read et al. will aid those recommending colonoscopy in their argument for an aggressive diagnostic and treatment strategy in these patients. These investigators found that a low-risk lesion in an asymptomatic average-risk group of individuals was associated with the same risk of proximal neoplasia as determined in previous studies of those with an increased risk (Ann Intern Med 1988;109:880–883). In this study, the risk of an advanced lesion (6%–10%) was similar to that found in prior studies, and 2–3-fold the risk predicted by previous autopsy data (Gastroenterology 1989;96:299–306). This study’s data suggest that the finding of a distal adenomatous polyp in any individual (normal or increased risk) undergoing screening flexible sigmoidoscopy should be further evaluated by colonoscopy. What is missing from these data? Ideally, a control population consisting of patients without adenomatous polyps on flexible sigmoidoscopy, who also underwent colonoscopy, should have been included. However, the added morbidity and cost of this control population make it difficult to justify in studies such as this. This problem of the lack of an adequate control population is probably further mitigated by data already existing in the literature of the yield of proximal adenomas in a population of asymptomatic normal-risk individuals undergoing colonoscopy, which showed a similar yield of proximal adenomas as this study (Gastroenterology 1991;100:64– 67). Other problems with the study are the small number of patients found to have adenomatous polyps that subsequently underwent colonoscopy. It is possible that significant differences between the groups would have been shown if a larger population-based study could have been performed. Other data that would have been useful are an economic analysis of the cost of this therapeutic and diagnostic approach. Cost (direct and indirect) per adenomatous polyp or cancer detected could be calculated, allowing cost-effectiveness determinations. Nevertheless, these findings are supportive of the concept of identifying whether a lesion is an adenomatous polyp at the time of flexible
WBS-Gastro
1414 SELECTED SUMMARIES
GASTROENTEROLOGY Vol. 113, No. 4
sigmoidoscopy and, if present, recommending colonoscopy in these patients to remove the index adenoma and identify more proximal lesions. This strategy of removing adenomatous polyps from the colon has been proven effective, by The National Polyp Study, in decreasing colorectal cancer occurrence (N Engl J Med 1993;329:1977–1981). Others have argued that the finding of a distal adenomatous polyp on flexible sigmoidoscopy incurs no increased risk of neoplasia and therefore can possibly be ignored (Ann Intern Med 1993;119:836– 843), but this approach ignores the fact that although risk of colorectal cancer may not be increased, it still remains substantial (a 5%–6% lifetime risk of colorectal carcinoma). Furthermore, some of the studies implying no increased risk of colorectal cancer in this group have had methodological problems (some patients had colonoscopy and polypectomy or fulguration of polyps that may decrease subsequent colorectal cancer occurrence) (N Engl J Med 1992;326:638–662). Outcomes data are lacking for much of these issues, but hopefully will be answered by the ongoing Veterans Administration Cooperative Study #380 (a prospective evaluation of risk factors for large colonic adenomas in asymptomatic subjects) in which demographic data, site of the lesions, histology, and outcome are being obtained in asymptomatic individuals undergoing screening colonoscopy. Until that time, the data of Read et al. justify the clinical recommendation for colonoscopy in patients with any size adenoma found on flexible sigmoidoscopy. Therefore, small polyps remain a big problem both from a disease management standpoint and a health economic standpoint. Within a few years, we should be able to confirm whether this is a big problem or not, as other prospective trials data become available. M. BRIAN FENNERTY, M.D.
A ! B Ú C McClave SA, Greene LM, Snider HL, Makk LJK, Cheadle WG, Owens NA, Dukes LG, Goldsmith LJ (Departments of Medicine and Surgery, University of Louisville School of Medicine and Veterans’ Affairs Medical Center, Louisville, Kentucky). Comparison of the safety of early enteral vs. parenteral nutrition in mild acute pancreatitis. J Parenter Enter Nutr 1997;21: 14–20. Stating that nutritional support plays an important role in the adjunctive management of patients with acute pancreatitis, McClave et al. performed a prospective, randomized controlled trial (PRCT) comparing total parenteral nutrition (TPN) with total enteral nutrition (TEN) provided through an endoscopically placed nasojejunal tube. Both feeding programs were designed to be started within 48 hours of admission. The initial power calculation indicated that 20 patients would have to be entered into each arm to have an 80% chance of seeing a difference of 1.8 days in hospitalization (assuming a standard deviation of 2 days) or a $1000 difference in cost (actually, charges). The study was terminated prematurely, after only 16 patients had been entered into each treatment arm. (Only 30 different patients participated; 2 patients were entered twice, receiving TPN on one occasion and TEN on the other.) The investigators stopped the study because it was taking longer than anticipated and some of the standard deviations were larger than expected (so more than 20 patients would have to
/ 5e21$$0028
09-19-97 18:34:46
gasa
have been enrolled in each arm). At that time, a significant difference had already been seen in one parameter. The majority of the patients were men, and alcohol was the most common cause of the pancreatitis. The disease was generally mild; the mean number of Ranson criteria in each group was 1.3. No differences were seen with regard to pain resolution, nausea and vomiting, or resolution of abnormal enzyme (amylase or lipase) levels. There were two nosocomial infections in each group (12.5%). No patients died in either group. The recipients of the TPN tended to be in the intensive care unit (2.8 { 1.3 vs. 1.3 { 0.9 days) and hospital (11.9 { 2.6 vs. 9.7 { 1.3 days) longer, but these differences were not statistically significant. Hyperglycemia tended to be more of a problem in the TPN group, but, again, this difference was not statistically significant. The charges for the nutritional therapy were significantly lower in the TEN recipients than those with TPN ($761 vs. $3294; P õ 0.005). One patient in the enterally fed group was thought to have had an exacerbation of the pancreatitis because the feeding tube curled back into the stomach, and the enteral feeding was delivered intragastrically. The authors concluded that ‘‘TEN via jejunal feedings should be used preferentially in this disease setting.’’ Comment. Any PRCT addresses a very specific issue, namely, the comparison of the effect of intervention A with intervention B in a defined population of patients. If one of those interventions is no treatment, conclusions can be made about the value of doing something vs. doing nothing. (In other words, does the intervention change the natural history of the disease process?) McClave et al. began with the belief that nutritional support was an important adjunctive therapy in patients with acute pancreatitis (presumably mild disease in particular, because that was the population whom they subsequently studied). Therefore, they elected not to include a no treatment control group but compared one form of nutritional support (TPN) with another (TEN). However, as these investigators noted in their introductory comments, there had been a previous PRCT comparing TPN to no nutritional therapy, in patients with very similar disease characteristics as those entered into this trial (Am J Surg 1987;153:117–124). In that trial, Sax et al. found that the group who received TPN had a longer duration of hospitalization. (Although McClave et al. stated that the TPN group in the Sax trial also had a higher rate of catheter infections, Sax et al. did not compare the two study groups, but rather the rate of catheter infections in the patients with pancreatitis to the rate of such infections in a contemporary set of patients who had received TPN for other reasons.) There is no other useful level 1 (i.e., PRCTs) information regarding the role of nutritional support in pancreatitis. Two other studies are available, but the data are difficult to interpret. One small trial, only available in abstract form (Gastroenterology 1984;86:1119), described 23 patients who were randomized into one of three groups (5% dextrose, 5% dextrose and amino acids, or 5% dextrose and amino acids and fat); no significant differences were found (not surprising, considering the small numbers). One other trial assessed the role of intravenous lipid (Infusionstherapie 1985;12:128–133); again, no differences were found. The justification for the statement of McClave et al. that nutritional support is an important adjunctive therapy rests only on retrospective
WBS-Gastro
SELECTED SUMMARIES Henry J. Binder, M.D. Selected Summaries Editor Yale University School of Medicine New Haven, Connecticut 08520-8019
STAFF OF CONTRIBUTORS Robert Bresalier, Detroit, MI Hannah Carey, Madison, WI M. Brian Fennerty, Portland, OR Greg Fitz, Denver, CO Guadalupe Garcı´a-Tsao, New Haven, CT
Ian Scott Grimm, Chapel Hill, NC Cyrus Kapadia, New Haven, CT Ronald L. Koretz, Sylmar, CA Pankaj Pasricha, Galveston, TX
LITTLE POLYPS: ARE THEY A BIG PROBLEM? Read T, Read J, Butterly L. Importance of adenomas 5 mm or less in diameter that are detected by sigmoidoscopy. N Engl J Med 1997;336:8–12. Read et al. sought to determine the clinical importance of small polyps by establishing the prevalence of more proximal neoplastic lesions in the colon in an asymptomatic averagerisk population of individuals found to have the diminutive polyp (°5 mm) on screening flexible sigmoidoscopy. Physicians at the Lahey Clinic screened 3496 consecutive patients over a 3-year period, and they were prospectively studied. If a polyp was identified at sigmoidoscopy, it was measured using open biopsy forceps as a reference standard, and a biopsy of the polyp was performed for histology. If the polyp was an adenoma, then colonoscopy was performed within 1 year, but usually within 3 months. At colonoscopy, all polyps were measured and removed and analyzed histologically. Adenomas were classified by size (diminutive, °5 mm; small, 6–10 mm; large, ¢11 mm) and whether they were advanced (¢10 mm in size, villous in histology, moderate to severe dysplasia, or malignant). Patients at increased risk of colonic neoplasia (those with a history of colon cancer or previous adenomatous polyps, inflammatory bowel disease, heme-positive stools, firstdegree relative with colorectal cancer, rectal bleeding, anemia, change in bowel habits, and barium enema or colonoscopy within 5 years) were excluded to study only asymptomatic and average-risk individuals. Of the 3796 individuals screened, 768 (22%) had a distal colonic polyp(s). Of these 768, 311 had a neoplastic lesion, but 90 were excluded because of symptoms or risk factors stated above. Another 18 were excluded because of incomplete data (e.g., lack of colonoscopy), leaving 203 evaluable patients. Of these 203, 137 had a distal diminutive polyp, 52 had a small polyp, and 14 had a large polyp. More proximal adenomas were found in 29%, 29%, and 57% of these groups at colonoscopy, respectively. Six percent of those with a distal diminutive polyp had a proximal advanced lesion vs. 10% of those with a small polyp and 29% of those with a large polyp. Of the 137 patients with a distal diminutive polyp, 4 had cancer found proximally. The number of distal polyps or the
/ 5e21$$0028
09-19-97 18:34:46
gasa
William Sandborn, Rochester, MN Mitchell L. Schubert, Richmond, VA Fergus Shanahan, Wilton, Cork, Ireland David I. Soybel, Boston, MA Jacques Van Dam, Boston, MA
age of the individual was not a risk factor for a proximal lesion (P Å 0.11), whereas the size of the distal polyp was predictive of increased risk, with large polyps being greater than diminutive polyps (P Å 0.02). These investigators concluded that patients with a distal diminutive adenomatous polyp had a significant risk of proximal neoplasia, justifying a recommendation of colonoscopy for these individuals. Comment. The risk of significant proximal neoplasia in the colon of patients with small distal colonic polyps and the appropriate management of these individuals has been a controversial, emotional, and widely debated issue. This report by Read et al. will aid those recommending colonoscopy in their argument for an aggressive diagnostic and treatment strategy in these patients. These investigators found that a low-risk lesion in an asymptomatic average-risk group of individuals was associated with the same risk of proximal neoplasia as determined in previous studies of those with an increased risk (Ann Intern Med 1988;109:880–883). In this study, the risk of an advanced lesion (6%–10%) was similar to that found in prior studies, and 2–3-fold the risk predicted by previous autopsy data (Gastroenterology 1989;96:299–306). This study’s data suggest that the finding of a distal adenomatous polyp in any individual (normal or increased risk) undergoing screening flexible sigmoidoscopy should be further evaluated by colonoscopy. What is missing from these data? Ideally, a control population consisting of patients without adenomatous polyps on flexible sigmoidoscopy, who also underwent colonoscopy, should have been included. However, the added morbidity and cost of this control population make it difficult to justify in studies such as this. This problem of the lack of an adequate control population is probably further mitigated by data already existing in the literature of the yield of proximal adenomas in a population of asymptomatic normal-risk individuals undergoing colonoscopy, which showed a similar yield of proximal adenomas as this study (Gastroenterology 1991;100:64– 67). Other problems with the study are the small number of patients found to have adenomatous polyps that subsequently underwent colonoscopy. It is possible that significant differences between the groups would have been shown if a larger population-based study could have been performed. Other data that would have been useful are an economic analysis of the cost of this therapeutic and diagnostic approach. Cost (direct and indirect) per adenomatous polyp or cancer detected could be calculated, allowing cost-effectiveness determinations. Nevertheless, these findings are supportive of the concept of identifying whether a lesion is an adenomatous polyp at the time of flexible
WBS-Gastro
1414 SELECTED SUMMARIES
GASTROENTEROLOGY Vol. 113, No. 4
sigmoidoscopy and, if present, recommending colonoscopy in these patients to remove the index adenoma and identify more proximal lesions. This strategy of removing adenomatous polyps from the colon has been proven effective, by The National Polyp Study, in decreasing colorectal cancer occurrence (N Engl J Med 1993;329:1977–1981). Others have argued that the finding of a distal adenomatous polyp on flexible sigmoidoscopy incurs no increased risk of neoplasia and therefore can possibly be ignored (Ann Intern Med 1993;119:836– 843), but this approach ignores the fact that although risk of colorectal cancer may not be increased, it still remains substantial (a 5%–6% lifetime risk of colorectal carcinoma). Furthermore, some of the studies implying no increased risk of colorectal cancer in this group have had methodological problems (some patients had colonoscopy and polypectomy or fulguration of polyps that may decrease subsequent colorectal cancer occurrence) (N Engl J Med 1992;326:638–662). Outcomes data are lacking for much of these issues, but hopefully will be answered by the ongoing Veterans Administration Cooperative Study #380 (a prospective evaluation of risk factors for large colonic adenomas in asymptomatic subjects) in which demographic data, site of the lesions, histology, and outcome are being obtained in asymptomatic individuals undergoing screening colonoscopy. Until that time, the data of Read et al. justify the clinical recommendation for colonoscopy in patients with any size adenoma found on flexible sigmoidoscopy. Therefore, small polyps remain a big problem both from a disease management standpoint and a health economic standpoint. Within a few years, we should be able to confirm whether this is a big problem or not, as other prospective trials data become available. M. BRIAN FENNERTY, M.D.
A ! B Ú C McClave SA, Greene LM, Snider HL, Makk LJK, Cheadle WG, Owens NA, Dukes LG, Goldsmith LJ (Departments of Medicine and Surgery, University of Louisville School of Medicine and Veterans’ Affairs Medical Center, Louisville, Kentucky). Comparison of the safety of early enteral vs. parenteral nutrition in mild acute pancreatitis. J Parenter Enter Nutr 1997;21: 14–20. Stating that nutritional support plays an important role in the adjunctive management of patients with acute pancreatitis, McClave et al. performed a prospective, randomized controlled trial (PRCT) comparing total parenteral nutrition (TPN) with total enteral nutrition (TEN) provided through an endoscopically placed nasojejunal tube. Both feeding programs were designed to be started within 48 hours of admission. The initial power calculation indicated that 20 patients would have to be entered into each arm to have an 80% chance of seeing a difference of 1.8 days in hospitalization (assuming a standard deviation of 2 days) or a $1000 difference in cost (actually, charges). The study was terminated prematurely, after only 16 patients had been entered into each treatment arm. (Only 30 different patients participated; 2 patients were entered twice, receiving TPN on one occasion and TEN on the other.) The investigators stopped the study because it was taking longer than anticipated and some of the standard deviations were larger than expected (so more than 20 patients would have to
/ 5e21$$0028
09-19-97 18:34:46
gasa
have been enrolled in each arm). At that time, a significant difference had already been seen in one parameter. The majority of the patients were men, and alcohol was the most common cause of the pancreatitis. The disease was generally mild; the mean number of Ranson criteria in each group was 1.3. No differences were seen with regard to pain resolution, nausea and vomiting, or resolution of abnormal enzyme (amylase or lipase) levels. There were two nosocomial infections in each group (12.5%). No patients died in either group. The recipients of the TPN tended to be in the intensive care unit (2.8 { 1.3 vs. 1.3 { 0.9 days) and hospital (11.9 { 2.6 vs. 9.7 { 1.3 days) longer, but these differences were not statistically significant. Hyperglycemia tended to be more of a problem in the TPN group, but, again, this difference was not statistically significant. The charges for the nutritional therapy were significantly lower in the TEN recipients than those with TPN ($761 vs. $3294; P õ 0.005). One patient in the enterally fed group was thought to have had an exacerbation of the pancreatitis because the feeding tube curled back into the stomach, and the enteral feeding was delivered intragastrically. The authors concluded that ‘‘TEN via jejunal feedings should be used preferentially in this disease setting.’’ Comment. Any PRCT addresses a very specific issue, namely, the comparison of the effect of intervention A with intervention B in a defined population of patients. If one of those interventions is no treatment, conclusions can be made about the value of doing something vs. doing nothing. (In other words, does the intervention change the natural history of the disease process?) McClave et al. began with the belief that nutritional support was an important adjunctive therapy in patients with acute pancreatitis (presumably mild disease in particular, because that was the population whom they subsequently studied). Therefore, they elected not to include a no treatment control group but compared one form of nutritional support (TPN) with another (TEN). However, as these investigators noted in their introductory comments, there had been a previous PRCT comparing TPN to no nutritional therapy, in patients with very similar disease characteristics as those entered into this trial (Am J Surg 1987;153:117–124). In that trial, Sax et al. found that the group who received TPN had a longer duration of hospitalization. (Although McClave et al. stated that the TPN group in the Sax trial also had a higher rate of catheter infections, Sax et al. did not compare the two study groups, but rather the rate of catheter infections in the patients with pancreatitis to the rate of such infections in a contemporary set of patients who had received TPN for other reasons.) There is no other useful level 1 (i.e., PRCTs) information regarding the role of nutritional support in pancreatitis. Two other studies are available, but the data are difficult to interpret. One small trial, only available in abstract form (Gastroenterology 1984;86:1119), described 23 patients who were randomized into one of three groups (5% dextrose, 5% dextrose and amino acids, or 5% dextrose and amino acids and fat); no significant differences were found (not surprising, considering the small numbers). One other trial assessed the role of intravenous lipid (Infusionstherapie 1985;12:128–133); again, no differences were found. The justification for the statement of McClave et al. that nutritional support is an important adjunctive therapy rests only on retrospective
WBS-Gastro