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Published in: International Journal of Colorectal Disease 6/2008

01-06-2008 | Original Article

Rebampide enema therapy as a treatment for patients with chronic radiation proctitis: initial treatment or when other methods of conservative management have failed

Authors: Tae Oh Kim, Geun Am Song, Sun Mi Lee, Gwang Ha Kim, Jeong Heo, Dae Hwan Kang, Mong Cho

Published in: International Journal of Colorectal Disease | Issue 6/2008

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Abstract

Introduction

Radiation proctitis is a common complication following radiation therapy for pelvic malignancies. There have been no formal trials of treatment for radiation proctitis and a variety of methods are currently used. We assessed the efficacy of rebamipide enema to control symptoms and proctoscopic findings from radiation proctitis.

Materials and methods

Fifteen patients with radiation proctitis were enrolled. Enemas containing 150 mg rebamipide per dosing were administered after morning bowel movement, and always prior to bedtime, twice daily for 4 weeks. The efficacy of treatment was assessed from clinical symptoms (Subjective Objective Management Analysis Scale for Rectal Toxicity) and endoscopic findings.

Results

The mean bleeding score improved from 2.67 to 0.53 (P < 0.01). The mean symptom scores improved in those patients who had pain (0.40 to 0.13), tenesmus (0.40 to 0.20), and stool frequency (0.27 to 0.13). The mean improvement in telangiectasia scores (2.13 to 0.80, P < 0.01), bleeding point scores (1.80 to 0.27, P < 0.01), and friable mucosa scores (1.33 to 0.20, P < 0.01) were all statistically significant. No side effects were noted in any patients.

Conclusion

Rebamipide enema therapy for radiation proctitis is a safe and effective treatment of radiation proctitis. We suggest the value of rebamipide enema in the treatment of radiation proctitis when other conservative management or first treatment has failed.
Literature
1.
go back to reference Beard CJ, Propert KJ, Rieker PP, Clark JA, Kaplan I, Kantoff PW, Talcott JA (1997) Complications after treatment with external-beam irradiation in early-stage prostate cancer patients: a prospective multiinstitutional outcomes study. J Clin Oncol 15:223–229PubMed Beard CJ, Propert KJ, Rieker PP, Clark JA, Kaplan I, Kantoff PW, Talcott JA (1997) Complications after treatment with external-beam irradiation in early-stage prostate cancer patients: a prospective multiinstitutional outcomes study. J Clin Oncol 15:223–229PubMed
2.
go back to reference Crook J, Esche B, Futter N (1996) Effect of pelvic radiotherapy for prostate cancer on bowel, bladder, and sexual function: the patient’s perspective. Urology 47:387–394PubMedCrossRef Crook J, Esche B, Futter N (1996) Effect of pelvic radiotherapy for prostate cancer on bowel, bladder, and sexual function: the patient’s perspective. Urology 47:387–394PubMedCrossRef
3.
go back to reference Johnston MJ, Robertson GM, Frizelle FA (2003) Management of late complications of pelvic radiation in the rectum and anus. Dis Colon Rectum 46:247–259PubMedCrossRef Johnston MJ, Robertson GM, Frizelle FA (2003) Management of late complications of pelvic radiation in the rectum and anus. Dis Colon Rectum 46:247–259PubMedCrossRef
4.
go back to reference Tagkalidis PP, Tjandra J (2001) Chronic radiation proctitis. ANJ J Surg 71:230–237CrossRef Tagkalidis PP, Tjandra J (2001) Chronic radiation proctitis. ANJ J Surg 71:230–237CrossRef
5.
go back to reference Kennedy M, Bruninga K, Mutlu EA, Losurdo J, Choudhary S, Keshavarzian A (2001) Successful and sustained treatment of chronic radiation proctitis with antioxidant vitamins E & C. Am J Gastroenterol 96:1080–1084PubMedCrossRef Kennedy M, Bruninga K, Mutlu EA, Losurdo J, Choudhary S, Keshavarzian A (2001) Successful and sustained treatment of chronic radiation proctitis with antioxidant vitamins E & C. Am J Gastroenterol 96:1080–1084PubMedCrossRef
6.
go back to reference Goldstein F, Khoury J, Thorton JJ (1976) Treatment of chronic radiation enteritis and colitis with salicylazosulfapyridine and systemic corticosteroids. Am J Gastroenterol 65:201–208PubMed Goldstein F, Khoury J, Thorton JJ (1976) Treatment of chronic radiation enteritis and colitis with salicylazosulfapyridine and systemic corticosteroids. Am J Gastroenterol 65:201–208PubMed
7.
go back to reference Kochhar R, Patel F, Dhar A, Sharma SC, Ayyagari S, Aggarwal R, Goenka MK, Gupta BD, Mehta SK (1991) Radiation-induced proctosigmoiditis. Prospective, randomized, double-blind controlled trial of oral sulfasalazine plus rectal steroids versus rectal sucralfate. Dig Dis Sci 36:103–107PubMedCrossRef Kochhar R, Patel F, Dhar A, Sharma SC, Ayyagari S, Aggarwal R, Goenka MK, Gupta BD, Mehta SK (1991) Radiation-induced proctosigmoiditis. Prospective, randomized, double-blind controlled trial of oral sulfasalazine plus rectal steroids versus rectal sucralfate. Dig Dis Sci 36:103–107PubMedCrossRef
8.
go back to reference Kochhar R, Sharma SC, Gupta BB, Mehta SK (1988) Rectal sucralfate in radiation proctitis. Lancet 13:400CrossRef Kochhar R, Sharma SC, Gupta BB, Mehta SK (1988) Rectal sucralfate in radiation proctitis. Lancet 13:400CrossRef
9.
go back to reference Kochhar R, Sriram PV, Sharma SC, Goel RC, Patel F (1999) Natural history of late radiation proctosigmoiditis treated with topical sucralfate suspension. Dig Dis Sci 44:973–978PubMedCrossRef Kochhar R, Sriram PV, Sharma SC, Goel RC, Patel F (1999) Natural history of late radiation proctosigmoiditis treated with topical sucralfate suspension. Dig Dis Sci 44:973–978PubMedCrossRef
10.
go back to reference Vernia P, Fracasso PL, Casale V, Villotti G, Marcheggiano A, Stigliano V, Pinnaro P, Bagnardi V, Caprilli R (2000) Topical butyrate for acute radiation proctitis: randomized crossover trial. Lancet 356:1232–1235PubMedCrossRef Vernia P, Fracasso PL, Casale V, Villotti G, Marcheggiano A, Stigliano V, Pinnaro P, Bagnardi V, Caprilli R (2000) Topical butyrate for acute radiation proctitis: randomized crossover trial. Lancet 356:1232–1235PubMedCrossRef
11.
go back to reference Charneau J, Bouachour G, Person B, Burtin P, Ronceray J, Boyer J (1991) Severe hemorrhagic radiation proctitis advancing to gradual cessation with hyperbaric oxygen. Dig Dis Sci 36:373–375PubMedCrossRef Charneau J, Bouachour G, Person B, Burtin P, Ronceray J, Boyer J (1991) Severe hemorrhagic radiation proctitis advancing to gradual cessation with hyperbaric oxygen. Dig Dis Sci 36:373–375PubMedCrossRef
12.
go back to reference Aihara M, Imagawa K, Funakoshi Y, Ohmoto Y, Kikuchi M (1998) Effects of rebamipide on production of several cytokines by human peripheral blood mononuclear cells. Dig Dis Sci 43:160S–166SPubMed Aihara M, Imagawa K, Funakoshi Y, Ohmoto Y, Kikuchi M (1998) Effects of rebamipide on production of several cytokines by human peripheral blood mononuclear cells. Dig Dis Sci 43:160S–166SPubMed
13.
go back to reference Nagano C, Azuma A, Ishiyama H, Sekiguchi K, Imagawa K, Kikuchi M (2001) Rebamipide suppresses formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide production by inhibiting fMLP-receptor binding in human neutrophils. J Pharmacol Exp Ther 297:388–394PubMed Nagano C, Azuma A, Ishiyama H, Sekiguchi K, Imagawa K, Kikuchi M (2001) Rebamipide suppresses formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide production by inhibiting fMLP-receptor binding in human neutrophils. J Pharmacol Exp Ther 297:388–394PubMed
14.
go back to reference Kishimoto S, Haruma K, Tari A, Sakurai K, Nakano M, Nakagawa Y (2000) Rebamipide, an antiulcer drug, prevents DSS-induced colitis formation in rats. Dig Dis Sci 45:1608–1616PubMedCrossRef Kishimoto S, Haruma K, Tari A, Sakurai K, Nakano M, Nakagawa Y (2000) Rebamipide, an antiulcer drug, prevents DSS-induced colitis formation in rats. Dig Dis Sci 45:1608–1616PubMedCrossRef
15.
go back to reference Watanabe S, Wang XE, Hirose M, Yoshizawa T, Iwazaki R, Oide H, Kitamura T, Miwa H, Miyazaki A, Sato N (1996) Effects of rebamipide on bile acid-induced inhibition of gastric epithelial repair in a rabbit culture model. Aliment Pharmacol Ther 10:927–932PubMedCrossRef Watanabe S, Wang XE, Hirose M, Yoshizawa T, Iwazaki R, Oide H, Kitamura T, Miwa H, Miyazaki A, Sato N (1996) Effects of rebamipide on bile acid-induced inhibition of gastric epithelial repair in a rabbit culture model. Aliment Pharmacol Ther 10:927–932PubMedCrossRef
16.
go back to reference Kleine A, Kluge S, Peskar B (1993) Stimulation of prostaglandin biosynthesis mediates gastroprotective effect of rebamipide in rats. Dig Dis Sci 38:1441–1449PubMedCrossRef Kleine A, Kluge S, Peskar B (1993) Stimulation of prostaglandin biosynthesis mediates gastroprotective effect of rebamipide in rats. Dig Dis Sci 38:1441–1449PubMedCrossRef
17.
go back to reference Coia LR, Myerson RJ, Tepper JE (1995) Late effects of radiation therapy on the gastrointestinal tract. Int J Radiat Oncol Biol Phys 31:1213–1236PubMed Coia LR, Myerson RJ, Tepper JE (1995) Late effects of radiation therapy on the gastrointestinal tract. Int J Radiat Oncol Biol Phys 31:1213–1236PubMed
18.
go back to reference Eifel PJ (2000) Radiation therapy. In: Berek JS, Hacker NF (eds) Practical gynecologic oncology. Lippincott Williams & Wilkins, Philadelphia, PA, pp 117–158 Eifel PJ (2000) Radiation therapy. In: Berek JS, Hacker NF (eds) Practical gynecologic oncology. Lippincott Williams & Wilkins, Philadelphia, PA, pp 117–158
19.
go back to reference Talley NA, Chen F, King D, Jones M, Talley NJ (1997) Short chain fatty acids in the treatment of radiation proctitis. Dis Colon Rectum 40:1046–1050PubMedCrossRef Talley NA, Chen F, King D, Jones M, Talley NJ (1997) Short chain fatty acids in the treatment of radiation proctitis. Dis Colon Rectum 40:1046–1050PubMedCrossRef
20.
go back to reference Baum CA, Biddle WL, Miner PB (1989) Failure of 5-aminosalicylic acid enemas to improve chronic radiation proctitis. Dig Dis Sci 34:758–760PubMedCrossRef Baum CA, Biddle WL, Miner PB (1989) Failure of 5-aminosalicylic acid enemas to improve chronic radiation proctitis. Dig Dis Sci 34:758–760PubMedCrossRef
21.
go back to reference de Parades V, Bauer P, Girodet J, Marteau P, Parisot C, Atienza P (1998) Non-surgical treatment of chronic radiation proctitis. Gastroenterol Clin Biol 22:688–696PubMed de Parades V, Bauer P, Girodet J, Marteau P, Parisot C, Atienza P (1998) Non-surgical treatment of chronic radiation proctitis. Gastroenterol Clin Biol 22:688–696PubMed
22.
go back to reference Kaassis M, Oberti E, Burtin P, Boyer J (2000) Argon plasma for the treatment of hemorrhagic radiation proctitis. Endoscopy 32:673–676PubMedCrossRef Kaassis M, Oberti E, Burtin P, Boyer J (2000) Argon plasma for the treatment of hemorrhagic radiation proctitis. Endoscopy 32:673–676PubMedCrossRef
23.
go back to reference Kleine A, Kluge S, Peskar BM (1993) Stimulation of prostaglandin biosynthesis mediates gastroprotective effect of rebamipide in rats. Dig Dis Sci 38:1441–1449PubMedCrossRef Kleine A, Kluge S, Peskar BM (1993) Stimulation of prostaglandin biosynthesis mediates gastroprotective effect of rebamipide in rats. Dig Dis Sci 38:1441–1449PubMedCrossRef
24.
go back to reference Sun WH, Tsuji S, Tsujii M, Gunawan ES, Kawai N, Kimura A, Kakiuchi Y, Yasumaru M, Iijima H, Okuda Y, Sasaki Y, Hori M, Kawano S (2000) Induction of cyclooxygenase-2 in rat gastric mucosa by rebamipide, a mucoprotective agent. J Pharmacol Exp Ther 295:447–452PubMed Sun WH, Tsuji S, Tsujii M, Gunawan ES, Kawai N, Kimura A, Kakiuchi Y, Yasumaru M, Iijima H, Okuda Y, Sasaki Y, Hori M, Kawano S (2000) Induction of cyclooxygenase-2 in rat gastric mucosa by rebamipide, a mucoprotective agent. J Pharmacol Exp Ther 295:447–452PubMed
25.
go back to reference Suetsugu H, Ishihara S, Moriyama N, Kazumori H, Adachi K, Fukuda R, Watanabe M, Kinoshita Y (2000) Effect of rebamipide on prostaglandin EP4 receptor gene expression in rat gastric mucosa. J Lab Clin Med 136:50–57PubMedCrossRef Suetsugu H, Ishihara S, Moriyama N, Kazumori H, Adachi K, Fukuda R, Watanabe M, Kinoshita Y (2000) Effect of rebamipide on prostaglandin EP4 receptor gene expression in rat gastric mucosa. J Lab Clin Med 136:50–57PubMedCrossRef
26.
go back to reference Takahashi M, Takada H, Takagi K, Kataoka S, Soma R, Kuwayama H (2003) Gastric restitution is inhibited by dexamethasone, which is reversed by hepatocyte growth factor and rebamipide. Alim Pharmacol Ther 18(Suppl 1):126–132CrossRef Takahashi M, Takada H, Takagi K, Kataoka S, Soma R, Kuwayama H (2003) Gastric restitution is inhibited by dexamethasone, which is reversed by hepatocyte growth factor and rebamipide. Alim Pharmacol Ther 18(Suppl 1):126–132CrossRef
27.
go back to reference Watanabe T, Higuchi K, Hamaguchi M, Tanigawa T, Wada R, Tominaga K, Fujiwara Y, Arakawa T (2002) Rebamipide prevents delay of acetic acid-induced gastric ulcer healing caused by Helicobacter pylori infection in Mongolian gerbils. Dig Dis Sci 47:1582–1589PubMedCrossRef Watanabe T, Higuchi K, Hamaguchi M, Tanigawa T, Wada R, Tominaga K, Fujiwara Y, Arakawa T (2002) Rebamipide prevents delay of acetic acid-induced gastric ulcer healing caused by Helicobacter pylori infection in Mongolian gerbils. Dig Dis Sci 47:1582–1589PubMedCrossRef
28.
go back to reference Sakurai K, Osaka T, Yamasaki K (1998) Protection by rebamipide against acetic acid-induced colitis in rats: relationship with its antioxidative activity. Dig Dis Sci 43(9 Sppl):125S–133SPubMed Sakurai K, Osaka T, Yamasaki K (1998) Protection by rebamipide against acetic acid-induced colitis in rats: relationship with its antioxidative activity. Dig Dis Sci 43(9 Sppl):125S–133SPubMed
29.
go back to reference Akamatsu T, Nakamura N, Furuya N, Shimizu T, Gotou A, Kiyosawa K, Katsuyama T, Osumi T, Hirao Y, Miyamoto G (2002) Local gastric and serum concentrations of rebamipide following oral ingestion in healthy volunteers. Dig Dis Sci 47:1399–1404PubMedCrossRef Akamatsu T, Nakamura N, Furuya N, Shimizu T, Gotou A, Kiyosawa K, Katsuyama T, Osumi T, Hirao Y, Miyamoto G (2002) Local gastric and serum concentrations of rebamipide following oral ingestion in healthy volunteers. Dig Dis Sci 47:1399–1404PubMedCrossRef
30.
go back to reference Arakawa T, Watanabe T, Fukuda T, Yamasaki K, Kobayashi K (1995) Rebamipide, novel prostaglandin-inducer accelerates healing and reduces relapse of acetic acid-induced rat gastric ulcer: comparison with cimetidine. Dig Dis Sci 40:2469–2472PubMedCrossRef Arakawa T, Watanabe T, Fukuda T, Yamasaki K, Kobayashi K (1995) Rebamipide, novel prostaglandin-inducer accelerates healing and reduces relapse of acetic acid-induced rat gastric ulcer: comparison with cimetidine. Dig Dis Sci 40:2469–2472PubMedCrossRef
31.
go back to reference Okayama M, Tsubouchi R, Nishio H, Kato S, Takeuchi K (2004) Protective effect of intra-rectal administration of rebamipide on dextran sulfate sodium-induced colitis. Digestion 70:240–249PubMedCrossRef Okayama M, Tsubouchi R, Nishio H, Kato S, Takeuchi K (2004) Protective effect of intra-rectal administration of rebamipide on dextran sulfate sodium-induced colitis. Digestion 70:240–249PubMedCrossRef
32.
go back to reference Nakashima T, Maeda T, Nagamoto H, Kumakura T, Takai M, Mori T (2005) Rebamipide enema is effective for treatment of experimental dextran sulfate sodium induced colitis in rats. Dig Dis Sci 50(Suppl 1):S124–131PubMedCrossRef Nakashima T, Maeda T, Nagamoto H, Kumakura T, Takai M, Mori T (2005) Rebamipide enema is effective for treatment of experimental dextran sulfate sodium induced colitis in rats. Dig Dis Sci 50(Suppl 1):S124–131PubMedCrossRef
33.
go back to reference Miyata M, Kasugai K, Ishikawa T, Kakumu S, Onishi M, Mori T (2005) Rebamipide enema-new effective treatment for patients with corticosteroid dependent or resistant ulcerative colitis. Dig Dis Sci 50(Suppl 1):S119–123PubMedCrossRef Miyata M, Kasugai K, Ishikawa T, Kakumu S, Onishi M, Mori T (2005) Rebamipide enema-new effective treatment for patients with corticosteroid dependent or resistant ulcerative colitis. Dig Dis Sci 50(Suppl 1):S119–123PubMedCrossRef
34.
go back to reference Makiyama K, Takeshima F, Hamamoto T (2005) Efficacy of rebamipide enemas in active distal ulcerative colitis and proctitis: a prospective study report. Dig Dis Sci 50:2323–2329PubMedCrossRef Makiyama K, Takeshima F, Hamamoto T (2005) Efficacy of rebamipide enemas in active distal ulcerative colitis and proctitis: a prospective study report. Dig Dis Sci 50:2323–2329PubMedCrossRef
Metadata
Title
Rebampide enema therapy as a treatment for patients with chronic radiation proctitis: initial treatment or when other methods of conservative management have failed
Authors
Tae Oh Kim
Geun Am Song
Sun Mi Lee
Gwang Ha Kim
Jeong Heo
Dae Hwan Kang
Mong Cho
Publication date
01-06-2008
Publisher
Springer-Verlag
Published in
International Journal of Colorectal Disease / Issue 6/2008
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-008-0453-9

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