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Ileostomy and Heal Carcinoma
February 1989
use of nonsteroidal anti-inflammatory drugs in the Romford area. Br Med J [Clin Resj1985;291:1609-10. 33. Dinoso VP, Meshkipour H, Lorber SH. Gastric mucosal morphology and faecal blood loss during ethanol ingestion. Gut 1973;14:289-92. 34. Chowdhury AR. Malmud LS, Dinoso VP. Gastrointestinal plasma protein loss during ethanol ingestion. Gastroenterology 1977;72:37-40. 35. Wallace J1. Increased resistance of the gastric mucosa to hemorrhagic damage after exposure to an irritant: role of the "mucoid cap" and prostaglandin synthesis. Gastroenterology 1988;94:22-32. 36. Hawkey q, Kemp RT, Walt RP, Baskar NK, Davies J, Filipowicz B. Adaptive cytoprotection: evidence against mediation by prostaglandins. Gut 1985;26:Al147. 37. Foschi D, Toti GL, Del Soldato P, Ferrante F, Galeone M, Rovati V. Adaptive cytoprotection: an endoscopic study in man. Am J GastroenteroI1986;81:1035-7. 38. Ligumsky M, Golanska EM, Hansen DG, Kauffman GL Jr. Aspirin can inhibit gastric mucosal cycio-oxygenase without causing lesions in rats. Gastroenterology 1983;84:756-61. 39. Konturek SJ, Piastucki I, Brzozowski T, et al. Role of prostaglandins in the formation of aspirin-induced gastric ulcers. Gastroenterology 1982;80:4-9. 40. Whittle BJR. The potentiation of taurocholate-induced rat gastric erosions following parenteral administration of cyciooxygenase inhibitors. Br J Pharmacol 1983;80:545-51. 41. Svanes K. Critchlow J, Takeuchi K. Magee D, Ito S, Silen W. Factors influencing reconstitution of frog gastric mucosa: role of prostaglandins. In: Allen A, Flemstrtim G, Garner A. Silen W, Turnberg LA, eds. Mechanisms of mucosal protection in the upper gastrointestinal tract. New York: Raven, 1984:33-9. 42. Rowe PH, Starlinger MH, Kasdon E, Marrone G, Silen W. Effect of simulated systemic administration of aspirin, salicylate, and indomethacin on amphibian gastric mucosa. Gastroenterology 1986;90:559-69. 43. Saairo I. Carter K, Rosen S, Silen W. Effects of ethanol on the in vitro frog gastric mucosa: electrophysiology and acid secretion (abstr). Gastroenterology 1987;92:1607. 44. Barzilai A, Schiessel R. Kivilaakso E, et al. Effect of 16-16dimethyl-prostaglandin Ez on ulceration of isolated amphibian gastric mucosa. Gastroenterology 1980;78:1508-12. 45. Tarnawski A, Brzozowski T, Sarfeh IJ, et al. Prostaglandin protection of human isolated gastric glands against indomethacin and ethanol injury: evidence for direct cellular action of prostaglandin. J Clin Invest 1988;81:1081-9. 46. Terano A, Mach T, Stachura J, Tarnawski A, Ivey KJ. Effect of 16, 16-dimethyl PGE z on aspirin-induced damage to rat gastric epithelial cells in tissue culture. Gut 1984;25:19-25. 47. Terano A, Ota S, Mach T, Hirashi H, Stachura J, Ivey KJ. Prostaglandin protects against taurocholate-induced damage to rat gastric mucosal cell culture. Gastroenterology 1987;92: 669-77. 48. Guth PH, Paulsen G. Prostaglandin cytoprotection does not involve interference with aspirin absorption. Proc Soc Exp Bioi Med 1979;162:128-30. 49. Robert A, Lancaster C, Davis JP, Field SO, Wickrema Sinha AJ, Thornburgh BA. Cytoprotection by prostaglandin occurs in spite of penetration of absolute ethanol into the gastric mucosa. Gastroenterology 1985;88:328-33. 50. Miller T A. The protective effects of prostaglandins against gastric mucosal damage: current knowledge and proposed mechanisms. Am J Physiol 1983;245:G601-23. Reply, The letter of Drs. Robert, Guth, Schmidt, and Miller presents a position that has been espoused repeatedly for the past 10 yr. Most of the differences between the views of these investi-
CORRESPONDENCE
551
gators and those of the undersigned represent either differences of opinion or differences in interpretation of the same data. The purpose of an editorial is to provide a perspective to a given subject and this was the intent of the piece that prompted the letter by Robert et al. While the case for cytoprotection has been widely espoused, only a few authors have previously taken a challenging posture. The editorial presents a reasonably comprehensive review of the data that question the validity of some of the tenets implicit in the concept of cytoprotection. Our readers will need to decide for themselves, on careful review of the data available, the merits of either of these positions. WILLIAM SILEN. M.D.
Beth Israel Hospital Boston, Massachusetts 02215
Ileostomy and Ileal Carcinoma Dear Sir: Suarez and coworkers (1) report on ileal carcinoma developing as an unusual late complication of ileostomy. In normal individuals small bowel tumors are also known to be rare (2), and therefo;e it might be of interest to compare the risk of small bowel cancers in subjects with and without an ileostomy. Using Suarez's references, the average age of all available reported patients with ileostomy-associated carcinoma is 54 ± 10 (SD) yr and the average time from ileostomy to carcinoma is 26 ± 9 (SD) yr. Again, using their estimate of 1000-2000 subjects in the United Kingdom with an ileostomy of this duration and 4 patients with known ileostomy-associated cancer, we estimate that the rate of small bowel cancer in the exposed ileum might range from a low of 8 to a high of 15 per 100,000 patient years. Surely these must be conservative rates because there must be other undetected or unreported ileostomy-associated tumors within this cohort. From incidence figures for 10 male and female cancer registries in the United Kingdom (3) we calculate that the incidence of small bowel cancer in subjects of similar age would be 1.3 ± 1 (SD) cases per 100,000 per year. Thus there appears to be a marked increase in the risk of small bowel cancer after ileostomy, which, as the authors speculate, may be related to altered bacterial flora or mechanical or chemical irritation. ALBERT B. LOWENFELS, M.D.
Professor of Surgery New York Medical College Munger Pavilion Valhalla, New York 10595 1. Suarez V, Alexander-Williams H, O'Connor J, et al. Carcinoma developing in ileostomies after 25 or more years. Gastroenterology 1988;95:205-8. 2. Lowenfels AB. Why are small bowel tumors so rare? Lancet 1973;i:24-6. 3. Waterhouse J, Muir C, Shanmugaratnam I, Powell J, eds. Cancer incidence in five continents. Volume IV. IARC Scientific Publication No. 42. Lyons, France: International Agency for Research on Cancer, 1982.
On the Demise of the Artificial Liver Dear Sir: Whilst the results of "controlled trials" may be used to reinforce a prejudice that charcoal hemoperfusion has little or no role to
use of nonsteroidal anti-inflammatory drugs in the Romford area. Br Med J [Clin Resj1985;291:1609-10. 33. Dinoso VP, Meshkipour H, Lorber SH. Gastric mucosal morphology and faecal blood loss during ethanol ingestion. Gut 1973;14:289-92. 34. Chowdhury AR. Malmud LS, Dinoso VP. Gastrointestinal plasma protein loss during ethanol ingestion. Gastroenterology 1977;72:37-40. 35. Wallace J1. Increased resistance of the gastric mucosa to hemorrhagic damage after exposure to an irritant: role of the "mucoid cap" and prostaglandin synthesis. Gastroenterology 1988;94:22-32. 36. Hawkey q, Kemp RT, Walt RP, Baskar NK, Davies J, Filipowicz B. Adaptive cytoprotection: evidence against mediation by prostaglandins. Gut 1985;26:Al147. 37. Foschi D, Toti GL, Del Soldato P, Ferrante F, Galeone M, Rovati V. Adaptive cytoprotection: an endoscopic study in man. Am J GastroenteroI1986;81:1035-7. 38. Ligumsky M, Golanska EM, Hansen DG, Kauffman GL Jr. Aspirin can inhibit gastric mucosal cycio-oxygenase without causing lesions in rats. Gastroenterology 1983;84:756-61. 39. Konturek SJ, Piastucki I, Brzozowski T, et al. Role of prostaglandins in the formation of aspirin-induced gastric ulcers. Gastroenterology 1982;80:4-9. 40. Whittle BJR. The potentiation of taurocholate-induced rat gastric erosions following parenteral administration of cyciooxygenase inhibitors. Br J Pharmacol 1983;80:545-51. 41. Svanes K. Critchlow J, Takeuchi K. Magee D, Ito S, Silen W. Factors influencing reconstitution of frog gastric mucosa: role of prostaglandins. In: Allen A, Flemstrtim G, Garner A. Silen W, Turnberg LA, eds. Mechanisms of mucosal protection in the upper gastrointestinal tract. New York: Raven, 1984:33-9. 42. Rowe PH, Starlinger MH, Kasdon E, Marrone G, Silen W. Effect of simulated systemic administration of aspirin, salicylate, and indomethacin on amphibian gastric mucosa. Gastroenterology 1986;90:559-69. 43. Saairo I. Carter K, Rosen S, Silen W. Effects of ethanol on the in vitro frog gastric mucosa: electrophysiology and acid secretion (abstr). Gastroenterology 1987;92:1607. 44. Barzilai A, Schiessel R. Kivilaakso E, et al. Effect of 16-16dimethyl-prostaglandin Ez on ulceration of isolated amphibian gastric mucosa. Gastroenterology 1980;78:1508-12. 45. Tarnawski A, Brzozowski T, Sarfeh IJ, et al. Prostaglandin protection of human isolated gastric glands against indomethacin and ethanol injury: evidence for direct cellular action of prostaglandin. J Clin Invest 1988;81:1081-9. 46. Terano A, Mach T, Stachura J, Tarnawski A, Ivey KJ. Effect of 16, 16-dimethyl PGE z on aspirin-induced damage to rat gastric epithelial cells in tissue culture. Gut 1984;25:19-25. 47. Terano A, Ota S, Mach T, Hirashi H, Stachura J, Ivey KJ. Prostaglandin protects against taurocholate-induced damage to rat gastric mucosal cell culture. Gastroenterology 1987;92: 669-77. 48. Guth PH, Paulsen G. Prostaglandin cytoprotection does not involve interference with aspirin absorption. Proc Soc Exp Bioi Med 1979;162:128-30. 49. Robert A, Lancaster C, Davis JP, Field SO, Wickrema Sinha AJ, Thornburgh BA. Cytoprotection by prostaglandin occurs in spite of penetration of absolute ethanol into the gastric mucosa. Gastroenterology 1985;88:328-33. 50. Miller T A. The protective effects of prostaglandins against gastric mucosal damage: current knowledge and proposed mechanisms. Am J Physiol 1983;245:G601-23. Reply, The letter of Drs. Robert, Guth, Schmidt, and Miller presents a position that has been espoused repeatedly for the past 10 yr. Most of the differences between the views of these investi-
CORRESPONDENCE
551
gators and those of the undersigned represent either differences of opinion or differences in interpretation of the same data. The purpose of an editorial is to provide a perspective to a given subject and this was the intent of the piece that prompted the letter by Robert et al. While the case for cytoprotection has been widely espoused, only a few authors have previously taken a challenging posture. The editorial presents a reasonably comprehensive review of the data that question the validity of some of the tenets implicit in the concept of cytoprotection. Our readers will need to decide for themselves, on careful review of the data available, the merits of either of these positions. WILLIAM SILEN. M.D.
Beth Israel Hospital Boston, Massachusetts 02215
Ileostomy and Ileal Carcinoma Dear Sir: Suarez and coworkers (1) report on ileal carcinoma developing as an unusual late complication of ileostomy. In normal individuals small bowel tumors are also known to be rare (2), and therefo;e it might be of interest to compare the risk of small bowel cancers in subjects with and without an ileostomy. Using Suarez's references, the average age of all available reported patients with ileostomy-associated carcinoma is 54 ± 10 (SD) yr and the average time from ileostomy to carcinoma is 26 ± 9 (SD) yr. Again, using their estimate of 1000-2000 subjects in the United Kingdom with an ileostomy of this duration and 4 patients with known ileostomy-associated cancer, we estimate that the rate of small bowel cancer in the exposed ileum might range from a low of 8 to a high of 15 per 100,000 patient years. Surely these must be conservative rates because there must be other undetected or unreported ileostomy-associated tumors within this cohort. From incidence figures for 10 male and female cancer registries in the United Kingdom (3) we calculate that the incidence of small bowel cancer in subjects of similar age would be 1.3 ± 1 (SD) cases per 100,000 per year. Thus there appears to be a marked increase in the risk of small bowel cancer after ileostomy, which, as the authors speculate, may be related to altered bacterial flora or mechanical or chemical irritation. ALBERT B. LOWENFELS, M.D.
Professor of Surgery New York Medical College Munger Pavilion Valhalla, New York 10595 1. Suarez V, Alexander-Williams H, O'Connor J, et al. Carcinoma developing in ileostomies after 25 or more years. Gastroenterology 1988;95:205-8. 2. Lowenfels AB. Why are small bowel tumors so rare? Lancet 1973;i:24-6. 3. Waterhouse J, Muir C, Shanmugaratnam I, Powell J, eds. Cancer incidence in five continents. Volume IV. IARC Scientific Publication No. 42. Lyons, France: International Agency for Research on Cancer, 1982.
On the Demise of the Artificial Liver Dear Sir: Whilst the results of "controlled trials" may be used to reinforce a prejudice that charcoal hemoperfusion has little or no role to