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Disappearance of both MALT lymphoma and hyperplastic polyps in the stomach after eradication of Helicobacter pylori
2796
Letters to the Editor
enema failed, requiring colonoscopy for diagnosis of cecal cancer. A 62-yr-old woman was admitted to our institution in 1998 with bowel obstruction, rectal bleeding, and iron deficiency anemia. Colonoscopy showed a large ulcerated, obstructing sigmoid lesion, which precluded examination of the proximal colon. The patient underwent emergent sigmoid colectomy and diverting colostomy. Surgical exploration did not show any obvious metastasis or metachronous cancer; however, intraoperative colonoscopy was not performed. The patient was discharged with plans for elective, clearance colonoscopy and colonic reanastomosis. After full recovery, the patient declined further intervention because of multiple previous abdominal surgeries and was lost to follow-up until she was referred for surveillance colonoscopy 2 yr later. Colonoscopy performed through the colostomy showed a tight, twisted angulation at 30 cm from the colostomy. Multiple attempts to pass this area using an adult (CF-140L, Olympus, Tokyo, Japan) or pediatric colonoscope (PCF140L, Olympus) failed, and further attempts at colonoscopy were aborted because of hypotension and discomfort. A barium enema was performed, showing an abrupt cutoff of contrast at 30 cm from the colostomy, suggesting an obstruction. Colonoscopy was repeated, this time using an upper endoscope (GIF-140, Olympus), which showed a very tortuous colon without obstruction or stricture. The cecum contained two large sessile polyps, which were confirmed to be adenocarcinoma on biopsy. The patient refused further surgery and is being observed conservatively at this time. To the best of our knowledge, this is the first reported case in which colonoscopy was used to complete the workup after a failed barium enema. We theorize that the combination of tight twists and turns of the colon and poor sealing between the enema catheter and the colostomy resulted in the failure of the barium study. In view of the fact that even contrast would not flow through this region, it is not surprising that colonoscopy failed initially; however, using an upper endoscope, with its greater range of motion and flexibility, allowed us to complete the examination. Although it is limited by the instrument’s shorter length, use of an upper endoscope should be considered in a patient with acute angulation, twists, or turns in the colon that cannot be passed with an adult or pediatric colonoscope. John G. Lee, M.D. Joseph W. Leung, M.D., F.R.C.P. UC Davis Medical Center Sacramento, California Reprint requests and correspondence: John G. Lee, M.D., UCI Medical Center, 101 The City Drive, Orange, CA 92868. Received Apr. 9, 2001; accepted Apr. 23, 2001.
AJG – Vol. 96, No. 9, 2001
Disappearance of Both MALT Lymphoma and Hyperplastic Polyps in the Stomach After Eradication of Helicobacter pylori TO THE EDITOR: This is the first report that confirms the disappearance of both mucosa-associated lymphatic tissue (MALT) lymphoma and hyperplastic polyps in the stomach after eradication of Helicobacter pylori. A 58-yr-old Japanese woman visited our hospital in March, 1997 with a chief complaint of several episodes of epigastralgia. Endoscopic examination revealed two different types of lesions. The first consisted of swollen mucosal folds with congested gastric mucosa on the greater curvature of the middle body (Fig. 1a). A biopsy specimen taken from the lesion showed diffuse proliferation of neoplastic centrocyte cells that were positive for L-26 but negative for UCLH-1 immunostaining in the marginal zone of a lymph follicle. A lymphoepithelial lesion was also noted. The second lesion was multiple gastric polyps on the greater curvature of the gastric body that varied in diameter from 0.2 to 1.5 cm (Fig. 1b). A biopsy specimen from one gastric polyp showed marked hyperplasia of the foveolar epithelium and infiltration of inflammatory cells in the stroma. The presence of H. pylori was determined by the rapid urease test (CLO test, Delta West, Bentley, Australia) and histological examination of the biopsy specimens obtained from the antrum and body.
Figure 1. Endoscopy before eradication of H. pylori showing swelling of the mucosal folds with congested gastric mucosa (a) and multiple gastric polyps (arrows) on the greater curvature of the gastric body (b). (c) Endoscopy at 3 months after eradication of H. pylori showing disappearance of swelling of the mucosal folds. (d) Endoscopy 9 months after eradication of H. pylori showing disappearance of gastric polyps.
AJG – September, 2001
The patient was treated with a 2-wk course of omeprazole, amoxicillin, and clarithromycin. Endoscopy performed about 3 months after the treatment revealed disappearance of swelling of the mucosal folds (Fig. 1c) but the presence of gastric polyps, although the size was reduced. A biopsy specimen from the first lesion on initial endoscopy showed that neoplastic centrocyte cells and the lymphoepithelial lesion had disappeared, and H. pylori was not detected. The CLO test was negative. Complete disappearance of gastric polyps was confirmed by follow-up endoscopy performed 9 months after eradication of H. pylori (Fig. 1d). The posttreatment course was uneventful, and there was no evidence of recurrence of the MALT lymphoma and hyperplastic polyps. Previous studies have reported that eradication of H. pylori could therapeutically influence MALT lymphoma (1) or hyperplastic polyp (2). To our knowledge, this is the first case in which both MALT lymphoma and hyperplastic polyps disappeared after eradication of the micro-organism. Interestingly, MALT lymphoma disappeared earlier than hyperplastic polyps (3 vs 9 months) after eradication of H. pylori in our case. Such a difference probably reflects differences in the pathogeneses of these two lesions. H. pylori may promote inflammation and contribute to the reactive hyperplasia of the gastric mucosa, thereby leading to the formation of hyperplastic foveolar polyps (2), whereas specific activation of T cells by H. pylori and release of cytokines including interleukin 2 may induce B-cell activation and proliferation, resulting in MALT lymphoma (3). Thus, both MALT lymphoma and hyperplastic polyps can regress after eradication of H. pylori. Keiichiro Kume, M.D. Machiko Hirakoba, M.D. Ikuo Murata, M.D., Ph.D. Ichiro Yoshikawa, M.D., Ph.D. Makoto Otsuki, M.D., Ph.D. Third Department of Internal Medicine University of Occupational and Environmental Health, Japan School of Medicine Kitakyushu, Japan
REFERENCES 1. Bayerdorffer E, Neubauer A, Rudolph B, et al. Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. Lancet 1995;345:1591– 4. 2. Ohkusa T, Takashimizu I, Fujiki K, et al. Disappearance of hyperplastic polyps in the stomach after eradication of Helicobacter pylori. Ann Intern Med 1998;129:712–5. 3. Hussell T, Isaacson PG, Crabtree JE, et al. The response of cells from low-grade B-cell gastric lymphomas of mucosa-associated lymphoid tissue to Helicobacter pylori. Lancet 1993;342: 571– 4.
Letters to the Editor
2797
Reprint requests and correspondence: Prof. Makoto Otsuki, M.D., Ph.D., Third Department of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan. Received Apr. 9, 2001; accepted Apr. 23, 2001.
Oral Azathioprine for Steroid Refractory Severe Ulcerative Colitis TO THE EDITOR: We read with interest the pilot study of Mahadevan et al. (1) reporting that a low i.v. loading dose of azathioprine followed by chronic oral azathioprine (dose ⫽ 2 mg/kg) was beneficial in inducing remission and avoiding colectomy in five of nine (65%) patients with steroid refractory ulcerative colitis. They also point out that extrapolation from the i.v. azathioprine Crohn’s disease trial (2) suggests that oral dosing at 2 mg/kg/day could have an equivalent result. The authors suggest that further studies are needed to determine the efficacy of oral azathioprine in inducing remission of severe ulcerative colitis. In a previous study (2), the same group suggested that the assumption that azathioprine acts very slowly (3–5) is probably incorrect. Our observations for steroid refractory severe ulcerative colitis are in agreement with those of Mahadevan et al. However, prejudiced by the axiom that the mean time to respond to azathioprine is 3.1 months (3), we hesitated to support that this assertion may be an overestimate. Between 1991 and 1999 we treated 40 patients with severe ulcerative colitis using the classic Oxford steroid regimen (6). After 7 days of continuous treatment patients were still passing two to four bloody liquid stools a day, were slightly feverish, and on sigmoidoscopy all had moderate to severe disease. The mean (range) of the Ulcerative Colitis Disease Activity Index was 8 (5–12) (Ref. 1). Patients fulfilled widely accepted criteria for failure of the i.v. steroids and were eligible for treatment with i.v. cyclosporine. However, the majority of them did not consent to this treatment, whereas cyclosporine was unsuitable for others, the main reasons being a very low serum cholesterol level and/or living in areas where measuring cyclosporine levels was impossible. As an alternative, patients were given oral azathioprine (2.2 mg/kg/day) from day 8 of the i.v. steroid regimen; the latter was continued for another week and then was replaced by oral prednisolone (40 mg/day), which was tapered by 5 mg/wk over 7 wk. Patients were given mesalazine (0.8 g three times a day) and were observed on a weekly basis with clinical examination, laboratory tests, and, whenever needed, flexible sigmoidoscopy until clinical remission was obtained. Clinical remission was defined as steroid withdrawal and an Ulcerative Colitis Disease Activity Index score of 0. Twenty-four patients (60%) responded favorably to azathioprine and achieved clinical remission by week 12. The mean time to respond was 8 wk (range ⫽ 6 –12). Azathioprine was well tolerated. However, one patient developed a
Letters to the Editor
enema failed, requiring colonoscopy for diagnosis of cecal cancer. A 62-yr-old woman was admitted to our institution in 1998 with bowel obstruction, rectal bleeding, and iron deficiency anemia. Colonoscopy showed a large ulcerated, obstructing sigmoid lesion, which precluded examination of the proximal colon. The patient underwent emergent sigmoid colectomy and diverting colostomy. Surgical exploration did not show any obvious metastasis or metachronous cancer; however, intraoperative colonoscopy was not performed. The patient was discharged with plans for elective, clearance colonoscopy and colonic reanastomosis. After full recovery, the patient declined further intervention because of multiple previous abdominal surgeries and was lost to follow-up until she was referred for surveillance colonoscopy 2 yr later. Colonoscopy performed through the colostomy showed a tight, twisted angulation at 30 cm from the colostomy. Multiple attempts to pass this area using an adult (CF-140L, Olympus, Tokyo, Japan) or pediatric colonoscope (PCF140L, Olympus) failed, and further attempts at colonoscopy were aborted because of hypotension and discomfort. A barium enema was performed, showing an abrupt cutoff of contrast at 30 cm from the colostomy, suggesting an obstruction. Colonoscopy was repeated, this time using an upper endoscope (GIF-140, Olympus), which showed a very tortuous colon without obstruction or stricture. The cecum contained two large sessile polyps, which were confirmed to be adenocarcinoma on biopsy. The patient refused further surgery and is being observed conservatively at this time. To the best of our knowledge, this is the first reported case in which colonoscopy was used to complete the workup after a failed barium enema. We theorize that the combination of tight twists and turns of the colon and poor sealing between the enema catheter and the colostomy resulted in the failure of the barium study. In view of the fact that even contrast would not flow through this region, it is not surprising that colonoscopy failed initially; however, using an upper endoscope, with its greater range of motion and flexibility, allowed us to complete the examination. Although it is limited by the instrument’s shorter length, use of an upper endoscope should be considered in a patient with acute angulation, twists, or turns in the colon that cannot be passed with an adult or pediatric colonoscope. John G. Lee, M.D. Joseph W. Leung, M.D., F.R.C.P. UC Davis Medical Center Sacramento, California Reprint requests and correspondence: John G. Lee, M.D., UCI Medical Center, 101 The City Drive, Orange, CA 92868. Received Apr. 9, 2001; accepted Apr. 23, 2001.
AJG – Vol. 96, No. 9, 2001
Disappearance of Both MALT Lymphoma and Hyperplastic Polyps in the Stomach After Eradication of Helicobacter pylori TO THE EDITOR: This is the first report that confirms the disappearance of both mucosa-associated lymphatic tissue (MALT) lymphoma and hyperplastic polyps in the stomach after eradication of Helicobacter pylori. A 58-yr-old Japanese woman visited our hospital in March, 1997 with a chief complaint of several episodes of epigastralgia. Endoscopic examination revealed two different types of lesions. The first consisted of swollen mucosal folds with congested gastric mucosa on the greater curvature of the middle body (Fig. 1a). A biopsy specimen taken from the lesion showed diffuse proliferation of neoplastic centrocyte cells that were positive for L-26 but negative for UCLH-1 immunostaining in the marginal zone of a lymph follicle. A lymphoepithelial lesion was also noted. The second lesion was multiple gastric polyps on the greater curvature of the gastric body that varied in diameter from 0.2 to 1.5 cm (Fig. 1b). A biopsy specimen from one gastric polyp showed marked hyperplasia of the foveolar epithelium and infiltration of inflammatory cells in the stroma. The presence of H. pylori was determined by the rapid urease test (CLO test, Delta West, Bentley, Australia) and histological examination of the biopsy specimens obtained from the antrum and body.
Figure 1. Endoscopy before eradication of H. pylori showing swelling of the mucosal folds with congested gastric mucosa (a) and multiple gastric polyps (arrows) on the greater curvature of the gastric body (b). (c) Endoscopy at 3 months after eradication of H. pylori showing disappearance of swelling of the mucosal folds. (d) Endoscopy 9 months after eradication of H. pylori showing disappearance of gastric polyps.
AJG – September, 2001
The patient was treated with a 2-wk course of omeprazole, amoxicillin, and clarithromycin. Endoscopy performed about 3 months after the treatment revealed disappearance of swelling of the mucosal folds (Fig. 1c) but the presence of gastric polyps, although the size was reduced. A biopsy specimen from the first lesion on initial endoscopy showed that neoplastic centrocyte cells and the lymphoepithelial lesion had disappeared, and H. pylori was not detected. The CLO test was negative. Complete disappearance of gastric polyps was confirmed by follow-up endoscopy performed 9 months after eradication of H. pylori (Fig. 1d). The posttreatment course was uneventful, and there was no evidence of recurrence of the MALT lymphoma and hyperplastic polyps. Previous studies have reported that eradication of H. pylori could therapeutically influence MALT lymphoma (1) or hyperplastic polyp (2). To our knowledge, this is the first case in which both MALT lymphoma and hyperplastic polyps disappeared after eradication of the micro-organism. Interestingly, MALT lymphoma disappeared earlier than hyperplastic polyps (3 vs 9 months) after eradication of H. pylori in our case. Such a difference probably reflects differences in the pathogeneses of these two lesions. H. pylori may promote inflammation and contribute to the reactive hyperplasia of the gastric mucosa, thereby leading to the formation of hyperplastic foveolar polyps (2), whereas specific activation of T cells by H. pylori and release of cytokines including interleukin 2 may induce B-cell activation and proliferation, resulting in MALT lymphoma (3). Thus, both MALT lymphoma and hyperplastic polyps can regress after eradication of H. pylori. Keiichiro Kume, M.D. Machiko Hirakoba, M.D. Ikuo Murata, M.D., Ph.D. Ichiro Yoshikawa, M.D., Ph.D. Makoto Otsuki, M.D., Ph.D. Third Department of Internal Medicine University of Occupational and Environmental Health, Japan School of Medicine Kitakyushu, Japan
REFERENCES 1. Bayerdorffer E, Neubauer A, Rudolph B, et al. Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. Lancet 1995;345:1591– 4. 2. Ohkusa T, Takashimizu I, Fujiki K, et al. Disappearance of hyperplastic polyps in the stomach after eradication of Helicobacter pylori. Ann Intern Med 1998;129:712–5. 3. Hussell T, Isaacson PG, Crabtree JE, et al. The response of cells from low-grade B-cell gastric lymphomas of mucosa-associated lymphoid tissue to Helicobacter pylori. Lancet 1993;342: 571– 4.
Letters to the Editor
2797
Reprint requests and correspondence: Prof. Makoto Otsuki, M.D., Ph.D., Third Department of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan. Received Apr. 9, 2001; accepted Apr. 23, 2001.
Oral Azathioprine for Steroid Refractory Severe Ulcerative Colitis TO THE EDITOR: We read with interest the pilot study of Mahadevan et al. (1) reporting that a low i.v. loading dose of azathioprine followed by chronic oral azathioprine (dose ⫽ 2 mg/kg) was beneficial in inducing remission and avoiding colectomy in five of nine (65%) patients with steroid refractory ulcerative colitis. They also point out that extrapolation from the i.v. azathioprine Crohn’s disease trial (2) suggests that oral dosing at 2 mg/kg/day could have an equivalent result. The authors suggest that further studies are needed to determine the efficacy of oral azathioprine in inducing remission of severe ulcerative colitis. In a previous study (2), the same group suggested that the assumption that azathioprine acts very slowly (3–5) is probably incorrect. Our observations for steroid refractory severe ulcerative colitis are in agreement with those of Mahadevan et al. However, prejudiced by the axiom that the mean time to respond to azathioprine is 3.1 months (3), we hesitated to support that this assertion may be an overestimate. Between 1991 and 1999 we treated 40 patients with severe ulcerative colitis using the classic Oxford steroid regimen (6). After 7 days of continuous treatment patients were still passing two to four bloody liquid stools a day, were slightly feverish, and on sigmoidoscopy all had moderate to severe disease. The mean (range) of the Ulcerative Colitis Disease Activity Index was 8 (5–12) (Ref. 1). Patients fulfilled widely accepted criteria for failure of the i.v. steroids and were eligible for treatment with i.v. cyclosporine. However, the majority of them did not consent to this treatment, whereas cyclosporine was unsuitable for others, the main reasons being a very low serum cholesterol level and/or living in areas where measuring cyclosporine levels was impossible. As an alternative, patients were given oral azathioprine (2.2 mg/kg/day) from day 8 of the i.v. steroid regimen; the latter was continued for another week and then was replaced by oral prednisolone (40 mg/day), which was tapered by 5 mg/wk over 7 wk. Patients were given mesalazine (0.8 g three times a day) and were observed on a weekly basis with clinical examination, laboratory tests, and, whenever needed, flexible sigmoidoscopy until clinical remission was obtained. Clinical remission was defined as steroid withdrawal and an Ulcerative Colitis Disease Activity Index score of 0. Twenty-four patients (60%) responded favorably to azathioprine and achieved clinical remission by week 12. The mean time to respond was 8 wk (range ⫽ 6 –12). Azathioprine was well tolerated. However, one patient developed a