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Red ring sign versus aphthous ulcers of colonic mucosa?
revealed mucosal lymphoid aggregates, normal colonic epithelium, and hyperplastic polyps with some associated focal acute inflammation, but no evidence of aphthous ulceration (Fig. 2). We believe that the lesions seen by us and reported by Hixson are not aphthous ulcers, but are mucosal lymphoid aggregates, which is a normal finding. 2 In contrast to Hixson's patients who had received Fleet Phospho-Soda, our patient had received GoLYTELY. Therefore, these lesions may be unrelated to the type of precolonoscopy preparation used.
Douglas O. Faigel, MD Emma E. Furth, MD Dale R. Bachwich, MD University of Pennsylvania Medical Center Philadelphia, Pennsylvania
REFERENCES 1. Hixson I2. Colorectalulcers associated with sodium phosphate catharsis. Gastrointest Endosc 1995;42:101-2. 2. Fenoglio-Preiser CM, Lantz PE, Listrom MB, Davis M, Ri]ke FO. Gastrointestinal Pathology. New York: Raven Press, 1989.
Red ring sign versus aphthous ulcers of colonic mucosa? To the Editor: We read with interest, "Colorectal ulcers associated with sodium phosphate catharsis," by Dr. Hixson. 1 We suggest that the lesions described may represent the "red ring" or "halo" sign of prominent lymphoid nodules 26 rather than aphthous ulcerations. Dr. Hixson's letter described "small (1 to 3 mm) aphthous ulcers with an erythematous halo" in a number of patients and suggested that they were related to sodium phosphate lavage. The endoscopic photograph published with the letter shows circular red lesions with pale centers, but does not have adequate resolution to allow us to see whether the pale central areas are depressed or consist of exudate, as would be expected with aphthous ulcers. No histologic section is provided, but the microscopic pathology in these cases was described as typically showing "only edema within the lamina propria with extravasation of red blood cells, and focal superficial mucosal disruption, often centered over lymphoid aggregates; inflammatory cell infiltration was minimal and gland architecture intact." The histopathology of aphthous ulcers shows that they are erosive or ulcerating lesions of the mucosa overlying a submucosal or mucosal lymphoid aggregate. 7, s Early lesions, not endoscopically visible as ulcers, show focal loss of epithelium in the base of a crypt, acute inflammatory exudate within the crypt lumen, and macrophage accumulation in the exposed lamina propria or submucosa. When lesions are large enough to be visible endoscopically, the biopsy shows a definite ulcer base, or more extensive area of mucosal loss covered with an exudate consisting of fibrinoid necrotic debris and neutrophils. The lesions in Hixson's reV O L U M E 43, NO. 5, 1996
port were I to 3 mm in diameter and grossly visible, yet the histologic features of ulceration or inflammation in adjacent crypts were not described, suggesting that they may not have been aphthous ulcers. We have observed similar 2 to 3 mm circular red lesions with pale centers at flexible sigmoidoscopy after sodium phosphate enema preparation in the rectum and lower sigmoid colon of a healthy 58-year-old woman without diarrhea or known inflammatory bowel disease. On initial visualization, these lesions appeared to be aphthous ulcers, but on close inspection the pale center was slightly raised and there was no ulceration. Histologic examination demonstrated lymphoid nodules without ulceration, mucosal disruption, or inflammation in adjacent mucosa. The red ring sign is probably a nonspecific indicator of prominent lymphoid aggregates in the colonic mucosa, in as much as it has been described in patients with inflammatory bowel disease, HIV, neoplasms, and in normal patients without diarrheal illness. 2-6 The red ring sign is a circular red ring, 2 to 3 mm in diameter, surrounding a pale 1 mm central area which, on close inspection, is slightly raised. The pale central area is a well-circumscribed lymphoid nodule, and the red ring may be due to hyperemia in mucosal blood vessels. 3, 5 The prevalence of this finding in health or disease is not certain; one report noted the red ring appearance of lymphoid tissue in 6 of 696 colonoscopies. Because this appearance of colonic lymphoid tissue can be found in patients without apparent disease, it is important for endoscopists and pathologists to be aware of the red ring sign so that normal colonic mucosal lymphoid nodules are not mistaken for pathologic lesions such as aphthous ulcers. The endoscopic appearance of these two findings can be quite similar. The common histologic feature of lymphoid aggregates can add to the potential for mistaking prominent lymphoid tissue for aphthous ulcers. It is possible that an erroneous endoscopic and pathologic diagnosis of aphthous ulcers could lead to a mistaken diagnosis of Crohn's disease in a patient with another cause of gastrointestinal symptoms who actually has the red ring sign appearance of colonic lymphoid tissue. Whether the lesions noted in Hixson's report were aphthous ulcers or the red ring sign of prominent lymphoid tissue, it is not clear why they would be associated with sodium phosphate cathartic preparation when they were not noted with polyethylene glycol lavage. Perhaps bowel cleansing with the sodium phosphate preparation was better and allowed visualization of normal mucosal lymphoid tissue not seen with the other preparation. Alternatively, the sodium phosphate preparation may have induced hyperemia 9 around lymphoid nodules, creating the red ring sign.
Mark E. Stark, MD James T. Wolfe, MD Mayo Clinic Jacksonville Jacksonville, Florida
REFERENCES 1. HixsonLJ. Co]orectalulcers associated with sodium phosphate catharsis [Letter]. Gastrointest Endosc 1995;42:101-2. 2. Kimura M, Miki K, Ichinose M, et al. Red ring sign--a new endoscopic finding of inflammatory bowel disease [Abstract]. Gastroenterol 1990;98:A181. GASTROINTESTINAL ENDOSCOPY
529
3. Smith MB, Blackstone MO. Colonic lymphoid nodules: another cause of the red ring sign [Letter]. Gastrointest Endosc 1991; 37:206-7. 4. Straub RF, Wilcox CM, Schwartz DA. Variable endoscopic appearance of colonic lymphoid tissue. J Clin Gastroentero11994; 19:158-65. 5. Wilcox CM. Anorectum. In: Wilcox CM, ed. Atlas of clinical gastrointestinalendoscopy. Philadelphia: W.B. Saunders, 1995: 289-90. 6. Bharadhwaj G, Triadafilopoulos G. Endoscopic appearances of colonic lymphoid nodules: new faces of an old histopathologic entity. Am J Gastroenterol 1995;90:946-50. 7: Lewin KJ, Riddell RH, Weinstein WM. Gastrointestinal pathology and its clinical implications. New York: Igaku-Shoin, 1992:870-5. 8. Gilmour HM. Crohn's disease. In: Whitehead R, ed. Gastrointestinal and esophageal pathology. New York: Churchill Livingstone, 1989:462-4. 9. Meisel JL, Bergman D, Graney D, Saunders DR, Rubin CE. Human rectal mucosa: proctoscopic and morphological changes caused by laxatives. Gastroenterology 1977;72:1274-9.
Preoperative preparation prior to colorectal surgery To the Editor: I r e a d with interest the article by Hixson. 1 In J u l y 1992, we completed a prospective randomized endoscopist-blinded trial in which we compared t h r e e different methods of precolonoscopy bowel cleansing. 2 One h u n d r e d thirty-eight patients received polyethylene glycol, 141 received sulphatefree polyethylene glycol, and 143 p a t i e n t s received the lowvolume sodium phosphate preparation. First, within the 422 age- and sex-matched patients who completed all phases of the trial, there were no clinically significant changes in weight or in any biochemical parameters in any of the patients. The colonic cleansing scores were superior in the sodium phosphate group as were overall acceptance, patient acceptance, and patients' willingness to repeat the same preparation. Because of the clear and highly statistically signfficant superiority of the phosphosoda preparation, it has become our routine precolonoscopy preparation since the conclusion of the trial in J a n u a r y 1993. Between the departments of Colorectal Surgery and Gastroenterology, approximately 4000 colonoscopies have been performed in the 2~2 years since the conclusion of this trial. I a m unaware of any colorectal ulcers associated with sodium phosphate catharsis. Because of the d r a m a t i c superiority of the sodium phosphate p r e p a r a t i o n from the point of view of both the patients a n d the endoscopists, we are in the process of completing a n institutional review b o a r d - a p p r o v e d prospective randomized trial comparing polyethylene glycol with sodium phosp h a t e as the preoperative p r e p a r a t i o n prior to colorectal surgery. This trial h a s now completed a n accrual of 200 patients. Although we r e m a i n e d blinded to the bowel p r e p a r a tion a d m i n i s t e r e d in each case, every surgical specimen was opened in the operating room. N e i t h e r the surgeons nor the pathologists noted ulcers in either gross or microscopic evaluation associated with any p r e p a r a t i o n in any p a t i e n t in this trial. 3 In s u m m a r y , I a m quite confused a n d concerned by the information corresponded by Dr. Hixson. I a m unsure as to the sample size in his study, b u t it m u s t certainly be enormous to have p e r m i t t e d identification of 17 cases of aph530 G A S T R O I N T E S T I N A L E N D O S C O P Y
thous ulcers when we have not seen a single case either endoscopically or in the surgically resected specimen despite using this p r e p a r a t i o n in over 4000 p a t i e n t s in the l a s t several years. Our findings are certainly suppOrted by the findings of V a n n e r et al., 4 Kolts et al., 5 and M a r s h a l l et al. 6 In conclusion, I believe t h a t we have a m p l y addressed the concerns of Dr. Hixson when he stated, "a prospective, randomized, investigator-blinded study with follow-up endoscopy in affected patients would confirm whether sodium phosphate catharsis induces colorectal ulceration compared with polyethylene glycol lavage." The answer to his question is NO, sodium phosphate catharsis did not induce colorectal ulceration in either of our two prospectively randomized trials.
Steven D. Wexner, MD Cleve/and C/inic Florida Fort Lauderdale, Florida
REFERENCES 1. Hixson Id. Colorectal ulcers associated with sodium phosphate catharsis. Gastrointest Endosc 1995;42:101-2. 2. Cohen SM, Wexner SD, Binderow SR, et al. Prospective randomized endoscopic-blindedtrial comparing precolonoscopy bowel cleansing methods. Dis Colon Rectum 1994;37:689-96. 3. Oliviera L, Daniel N, Bernstein M, et al. Mechanical bowel preparation for elective colorectal surgery: a prospective randomized surgeon-blinded trial comparing sodium phosphate (SP) and polyethylene glycol (PEG) based on oral lavage solutions [abstract]. Dis Colon Rectum 1996 (in press). 4. Vanner SJ, MacDonald PH, Paterson WG, et al. A randomized prospective trial comparing oral sodium phosphate with standard polyethylene glycol-basedlavage solution (Golytely)in the preparation of patients for colonoscopy. Am J Gastroenterol 1990;85:422-7. 5. Kolts BE, Lyles WE, Achem SR, et al. A comparison of the effectiveness and patient tolerance of oral sodium phosphate, castor oil, and standard electrolyte lavage for colonoscopy or sigmoidoscopy preparation. Am J Gastroenterol 1993;88:1218-23. 6. Marshall JB, Pineda JJ, Barthel JS, King PD. Prospective randomized trial comparing sodium phosphate solution with polyethylene glycol-electrolytelavage for colonoscopy preparation. Gastrointest Endosc 1993;39:631-4.
Response: As noted in the above letters, the red r i n g or halo sign h a s recently been described by multiple observers in p a t i e n t s without i n f l a m m a t o r y bowel disease. I concur t h a t these endoscopic "lesions" a r e typified histologically by mucosal lymphoid aggregates without f r a n k epithelial ulceration. Within the l a s t year, I have observed a few examples of subtle halo lesions within the distal bowel in p a t i e n t s p r e p a r e d with a polyethylene glycol solution. However, I r e m a i n suspicious t h a t the incidence a n d endoscopic brightness or intensity of the halo sign are g r e a t e r with the sodium phosp h a t e preparation. I base this in p a r t on d a t a t h a t sodium phosphate a p p e a r s to be a mucosal i r r i t a n t i n a s m u c h as it enhances epithelial proliferation in concert with promoting histologic a n d endoscopic i n f l a m m a t o r y changes. 1,2 Conversely, polyethylene glycol does not a l t e r epithelial crypt proliferation or histology. 3, 4 In response to Dr. Wexner, I do not know why these lesions are not seen in Ft. Lauderdale. In reading his original report VOLUME 43, NO. 5, 1996
Douglas O. Faigel, MD Emma E. Furth, MD Dale R. Bachwich, MD University of Pennsylvania Medical Center Philadelphia, Pennsylvania
REFERENCES 1. Hixson I2. Colorectalulcers associated with sodium phosphate catharsis. Gastrointest Endosc 1995;42:101-2. 2. Fenoglio-Preiser CM, Lantz PE, Listrom MB, Davis M, Ri]ke FO. Gastrointestinal Pathology. New York: Raven Press, 1989.
Red ring sign versus aphthous ulcers of colonic mucosa? To the Editor: We read with interest, "Colorectal ulcers associated with sodium phosphate catharsis," by Dr. Hixson. 1 We suggest that the lesions described may represent the "red ring" or "halo" sign of prominent lymphoid nodules 26 rather than aphthous ulcerations. Dr. Hixson's letter described "small (1 to 3 mm) aphthous ulcers with an erythematous halo" in a number of patients and suggested that they were related to sodium phosphate lavage. The endoscopic photograph published with the letter shows circular red lesions with pale centers, but does not have adequate resolution to allow us to see whether the pale central areas are depressed or consist of exudate, as would be expected with aphthous ulcers. No histologic section is provided, but the microscopic pathology in these cases was described as typically showing "only edema within the lamina propria with extravasation of red blood cells, and focal superficial mucosal disruption, often centered over lymphoid aggregates; inflammatory cell infiltration was minimal and gland architecture intact." The histopathology of aphthous ulcers shows that they are erosive or ulcerating lesions of the mucosa overlying a submucosal or mucosal lymphoid aggregate. 7, s Early lesions, not endoscopically visible as ulcers, show focal loss of epithelium in the base of a crypt, acute inflammatory exudate within the crypt lumen, and macrophage accumulation in the exposed lamina propria or submucosa. When lesions are large enough to be visible endoscopically, the biopsy shows a definite ulcer base, or more extensive area of mucosal loss covered with an exudate consisting of fibrinoid necrotic debris and neutrophils. The lesions in Hixson's reV O L U M E 43, NO. 5, 1996
port were I to 3 mm in diameter and grossly visible, yet the histologic features of ulceration or inflammation in adjacent crypts were not described, suggesting that they may not have been aphthous ulcers. We have observed similar 2 to 3 mm circular red lesions with pale centers at flexible sigmoidoscopy after sodium phosphate enema preparation in the rectum and lower sigmoid colon of a healthy 58-year-old woman without diarrhea or known inflammatory bowel disease. On initial visualization, these lesions appeared to be aphthous ulcers, but on close inspection the pale center was slightly raised and there was no ulceration. Histologic examination demonstrated lymphoid nodules without ulceration, mucosal disruption, or inflammation in adjacent mucosa. The red ring sign is probably a nonspecific indicator of prominent lymphoid aggregates in the colonic mucosa, in as much as it has been described in patients with inflammatory bowel disease, HIV, neoplasms, and in normal patients without diarrheal illness. 2-6 The red ring sign is a circular red ring, 2 to 3 mm in diameter, surrounding a pale 1 mm central area which, on close inspection, is slightly raised. The pale central area is a well-circumscribed lymphoid nodule, and the red ring may be due to hyperemia in mucosal blood vessels. 3, 5 The prevalence of this finding in health or disease is not certain; one report noted the red ring appearance of lymphoid tissue in 6 of 696 colonoscopies. Because this appearance of colonic lymphoid tissue can be found in patients without apparent disease, it is important for endoscopists and pathologists to be aware of the red ring sign so that normal colonic mucosal lymphoid nodules are not mistaken for pathologic lesions such as aphthous ulcers. The endoscopic appearance of these two findings can be quite similar. The common histologic feature of lymphoid aggregates can add to the potential for mistaking prominent lymphoid tissue for aphthous ulcers. It is possible that an erroneous endoscopic and pathologic diagnosis of aphthous ulcers could lead to a mistaken diagnosis of Crohn's disease in a patient with another cause of gastrointestinal symptoms who actually has the red ring sign appearance of colonic lymphoid tissue. Whether the lesions noted in Hixson's report were aphthous ulcers or the red ring sign of prominent lymphoid tissue, it is not clear why they would be associated with sodium phosphate cathartic preparation when they were not noted with polyethylene glycol lavage. Perhaps bowel cleansing with the sodium phosphate preparation was better and allowed visualization of normal mucosal lymphoid tissue not seen with the other preparation. Alternatively, the sodium phosphate preparation may have induced hyperemia 9 around lymphoid nodules, creating the red ring sign.
Mark E. Stark, MD James T. Wolfe, MD Mayo Clinic Jacksonville Jacksonville, Florida
REFERENCES 1. HixsonLJ. Co]orectalulcers associated with sodium phosphate catharsis [Letter]. Gastrointest Endosc 1995;42:101-2. 2. Kimura M, Miki K, Ichinose M, et al. Red ring sign--a new endoscopic finding of inflammatory bowel disease [Abstract]. Gastroenterol 1990;98:A181. GASTROINTESTINAL ENDOSCOPY
529
3. Smith MB, Blackstone MO. Colonic lymphoid nodules: another cause of the red ring sign [Letter]. Gastrointest Endosc 1991; 37:206-7. 4. Straub RF, Wilcox CM, Schwartz DA. Variable endoscopic appearance of colonic lymphoid tissue. J Clin Gastroentero11994; 19:158-65. 5. Wilcox CM. Anorectum. In: Wilcox CM, ed. Atlas of clinical gastrointestinalendoscopy. Philadelphia: W.B. Saunders, 1995: 289-90. 6. Bharadhwaj G, Triadafilopoulos G. Endoscopic appearances of colonic lymphoid nodules: new faces of an old histopathologic entity. Am J Gastroenterol 1995;90:946-50. 7: Lewin KJ, Riddell RH, Weinstein WM. Gastrointestinal pathology and its clinical implications. New York: Igaku-Shoin, 1992:870-5. 8. Gilmour HM. Crohn's disease. In: Whitehead R, ed. Gastrointestinal and esophageal pathology. New York: Churchill Livingstone, 1989:462-4. 9. Meisel JL, Bergman D, Graney D, Saunders DR, Rubin CE. Human rectal mucosa: proctoscopic and morphological changes caused by laxatives. Gastroenterology 1977;72:1274-9.
Preoperative preparation prior to colorectal surgery To the Editor: I r e a d with interest the article by Hixson. 1 In J u l y 1992, we completed a prospective randomized endoscopist-blinded trial in which we compared t h r e e different methods of precolonoscopy bowel cleansing. 2 One h u n d r e d thirty-eight patients received polyethylene glycol, 141 received sulphatefree polyethylene glycol, and 143 p a t i e n t s received the lowvolume sodium phosphate preparation. First, within the 422 age- and sex-matched patients who completed all phases of the trial, there were no clinically significant changes in weight or in any biochemical parameters in any of the patients. The colonic cleansing scores were superior in the sodium phosphate group as were overall acceptance, patient acceptance, and patients' willingness to repeat the same preparation. Because of the clear and highly statistically signfficant superiority of the phosphosoda preparation, it has become our routine precolonoscopy preparation since the conclusion of the trial in J a n u a r y 1993. Between the departments of Colorectal Surgery and Gastroenterology, approximately 4000 colonoscopies have been performed in the 2~2 years since the conclusion of this trial. I a m unaware of any colorectal ulcers associated with sodium phosphate catharsis. Because of the d r a m a t i c superiority of the sodium phosphate p r e p a r a t i o n from the point of view of both the patients a n d the endoscopists, we are in the process of completing a n institutional review b o a r d - a p p r o v e d prospective randomized trial comparing polyethylene glycol with sodium phosp h a t e as the preoperative p r e p a r a t i o n prior to colorectal surgery. This trial h a s now completed a n accrual of 200 patients. Although we r e m a i n e d blinded to the bowel p r e p a r a tion a d m i n i s t e r e d in each case, every surgical specimen was opened in the operating room. N e i t h e r the surgeons nor the pathologists noted ulcers in either gross or microscopic evaluation associated with any p r e p a r a t i o n in any p a t i e n t in this trial. 3 In s u m m a r y , I a m quite confused a n d concerned by the information corresponded by Dr. Hixson. I a m unsure as to the sample size in his study, b u t it m u s t certainly be enormous to have p e r m i t t e d identification of 17 cases of aph530 G A S T R O I N T E S T I N A L E N D O S C O P Y
thous ulcers when we have not seen a single case either endoscopically or in the surgically resected specimen despite using this p r e p a r a t i o n in over 4000 p a t i e n t s in the l a s t several years. Our findings are certainly suppOrted by the findings of V a n n e r et al., 4 Kolts et al., 5 and M a r s h a l l et al. 6 In conclusion, I believe t h a t we have a m p l y addressed the concerns of Dr. Hixson when he stated, "a prospective, randomized, investigator-blinded study with follow-up endoscopy in affected patients would confirm whether sodium phosphate catharsis induces colorectal ulceration compared with polyethylene glycol lavage." The answer to his question is NO, sodium phosphate catharsis did not induce colorectal ulceration in either of our two prospectively randomized trials.
Steven D. Wexner, MD Cleve/and C/inic Florida Fort Lauderdale, Florida
REFERENCES 1. Hixson Id. Colorectal ulcers associated with sodium phosphate catharsis. Gastrointest Endosc 1995;42:101-2. 2. Cohen SM, Wexner SD, Binderow SR, et al. Prospective randomized endoscopic-blindedtrial comparing precolonoscopy bowel cleansing methods. Dis Colon Rectum 1994;37:689-96. 3. Oliviera L, Daniel N, Bernstein M, et al. Mechanical bowel preparation for elective colorectal surgery: a prospective randomized surgeon-blinded trial comparing sodium phosphate (SP) and polyethylene glycol (PEG) based on oral lavage solutions [abstract]. Dis Colon Rectum 1996 (in press). 4. Vanner SJ, MacDonald PH, Paterson WG, et al. A randomized prospective trial comparing oral sodium phosphate with standard polyethylene glycol-basedlavage solution (Golytely)in the preparation of patients for colonoscopy. Am J Gastroenterol 1990;85:422-7. 5. Kolts BE, Lyles WE, Achem SR, et al. A comparison of the effectiveness and patient tolerance of oral sodium phosphate, castor oil, and standard electrolyte lavage for colonoscopy or sigmoidoscopy preparation. Am J Gastroenterol 1993;88:1218-23. 6. Marshall JB, Pineda JJ, Barthel JS, King PD. Prospective randomized trial comparing sodium phosphate solution with polyethylene glycol-electrolytelavage for colonoscopy preparation. Gastrointest Endosc 1993;39:631-4.
Response: As noted in the above letters, the red r i n g or halo sign h a s recently been described by multiple observers in p a t i e n t s without i n f l a m m a t o r y bowel disease. I concur t h a t these endoscopic "lesions" a r e typified histologically by mucosal lymphoid aggregates without f r a n k epithelial ulceration. Within the l a s t year, I have observed a few examples of subtle halo lesions within the distal bowel in p a t i e n t s p r e p a r e d with a polyethylene glycol solution. However, I r e m a i n suspicious t h a t the incidence a n d endoscopic brightness or intensity of the halo sign are g r e a t e r with the sodium phosp h a t e preparation. I base this in p a r t on d a t a t h a t sodium phosphate a p p e a r s to be a mucosal i r r i t a n t i n a s m u c h as it enhances epithelial proliferation in concert with promoting histologic a n d endoscopic i n f l a m m a t o r y changes. 1,2 Conversely, polyethylene glycol does not a l t e r epithelial crypt proliferation or histology. 3, 4 In response to Dr. Wexner, I do not know why these lesions are not seen in Ft. Lauderdale. In reading his original report VOLUME 43, NO. 5, 1996