Sucralfate R e t e n t i o n Enemas in
Solitary Rectal Ulcer Showkat Ali Zargar, M.D., D.M., Mohammad Sultan Khuroo, M.D., D.M., Rakesh Mahajan,-M.D. From the Department of Gastroenterology, Institute of Medical Sciences, Srinagar (Kashmir), India Zargar SA, Khuroo MS, Mahajan R. Sucralfate retention enemas in solitary rectal ulcer. Dis Colon Rectum 1991;34:455-457.
the typical sigmoidoscopic appearances and histologic criteria 2' 3 w e r e s e e n (Table 1). Symptoms of b l o o d and mucus in stools, altered b o w e l habits, tenesmus, and abdominal or perineal pain w e r e s c o r e d on a 10-point scale. The duration of symptoms ranged from 4 to 48 m o n t h s (mean, 18 months). Rectal b l e e d i n g was the most c o m m o n complaint (n = 6), f o l l o w e d by mucus in the stools (n = 4), t e n e s m u s (n = 4), diarrhea (n = 3), constipation (n -- 3), and pain (n = 2). All d e n i e d history of rectal digitation. Previous treatments had b e e n generally unsatisfactory. The relapse-free p e r i o d with previous therapies varied from 2 to 4 m o n t h s (mean, 2.8 m o n t h s ) . Rectal prolapse was s e e n in o n e patient. Sigm o i d o s c o p y revealed a single ulcer in five patients and two ulcers in o n e patient. Ulcers w e r e oval or linear in shape, shallow with slough, and m e a s u r e d 1.5-3.0 cm in diameter. Ulcers were located o n the anterior rectal wall, 5-11 cm from the anal verge. The m u c o s a a r o u n d the ulcer was slightly nodular in two patients. Each patient was advised to administer sucralfate, 2 g s u s p e n d e d in 30 ml of tap water, twice a day for 6 weeks in the form of r e t e n t i o n enemas. The treatment was e x t e n d e d to 8 weeks if the ulcer did not heal with 6-week therapy. Each patient was instructed h o w to instill the solution through a soft r u b b e r catheter. N o n e r e p o r t e d major leakage of the instillate. Patients had b e e n off all drugs for at least a w e e k b e f o r e starting sucralfate enemas. Patients w e r e assessed clinically every week, by flexible instrument s i g m o i d o s c o p y every 2 weeks by the same endoscopist, and by repeat biopsies at 6 weeks.
The conservative treatment of solitary rectal ulcer is generally unsatisfactory. Six patients, aged 27-54 years, with recurrent solitary rectal ulcer were treated with topical administration of sucralfate in a daily dose of 2 g twice a day for 6 weeks. Four patients experienced complete relief of symptoms and the remaining two patients had marked improvement. Although macroscopic healing of the ulcer was apparent in all, histologic improvement was not appreciable. Five of the six patients remain in remission during a follow-up period of 4-14 months (mean, 8 - 1.5 months). Recurrence was observed in one patient at 5 months, which satisfactorily resolved with sucralfate enemas. From these preliminary observations we infer that solitary rectal ulcer can be effectively treated with topical application of sucralfate. [Key words: Sucralfate; Solitary rectal ulcer] olitary rectal ulcer (SRU) is a rare but distressing condition that usually affects y o u n g adults. >3 T h e r e is no general a g r e e m e n t about its treatment and many empiric therapeutic approaches have b e e n tried including local electrocautery, caustic agents, antibiotics, sulfasalzine, steroid retention enemas, and local excisional surgery, without any obvious or consistent improvement.i, 3 Surgical correction of prolapse of the rectum may be useful in the cases in w h i c h it is present. 4 Sucralfate is a locally acting nonsystemic cytoprotective agent that has b e e n effective in p r o m o t i n g the healing of gastric and d u o d e n a l ulcers.5, s We, therefore, d e c i d e d to u n d e r t a k e a pilot study in patients with SRU to assess w h e t h e r topical administration of sucralfate serves any therapeutic effect.
S
MATERIALS A N D
METHODS
From January 1989 to D e c e m b e r 1989, six consecutive patients with a diagnosis of SUR based o n
RESULTS Four patients a c h i e v e d c o m p l e t e relief of symptoms ( c o m p l e t e clinical remission) and two nearc o m p l e t e remission. Although the latter two patients c o n t i n u e d to have mucus in stools (n = 2) and diarrhea (n = 1), they w e r e fairly satisfied with
Address reprint requests to Dr. Khuroo: Professor and Chairman, Department of Gastroenterology, and Head, Department of Medicine, Institute of Medical Sciences, P.O. Box 27, Srinagar (Kashmir) 190 011 India. 455
456
ZARGAR E T AL
Dis Colon Rectum, June 1991
Table 1. Clinical Characteristics and Results of Sucralfate Enema in Six Patients with SRU Clinical Data Patient
*
At 6 Weeks of Sucralfate Enema
Duration of Remission (months)
Age/Sex
Duration (months)
Symptom Score
Previous Treatment
Symptom Score
1
54 M
48
8
0
Scarring
--
11
2
35 F
8
8
0
11
22 F 22 M
11 12
6 7
1 0
Scarring Petechiae Normal Normal
m
3 4 5
41 F
25
7
2
Scarring minute
6
38 M
4
7
Steroid enemas Metronidazole Electrocautery Steroid enemas Metronidazole Sulfasalazine Metronidazole Cryosurgery Antibiotics Steroid enemas Metronidazole Steroid enemas
0
Erosions Normal
Sigmoidoscopy
Side Effects
m Mild constipation --
6* 7
--
4
6
Refers to time after relapse.
the therapy. Clinical activity disappeared or greatly improved at the end of the second week. Endoscopic healing of the ulcer lesion was observed at 4 and 6 weeks of therapy in three patients each. The residual abnormalities, limited to mild scarring, petichae, or minute erosions, were seen in three patients. Biopsy specimens revealed improvement in the superficial erosions, ulcerations, and inflammatory reaction, but the fibromuscular obliteration of the lamina propria did not display any appreciable changes. One patient experienced increased constipation as an adverse effect of sucralfate; but this, however, subsided after completion of the treatment. All patients were followed up regularly for a mean period of 8 + 1.5 months (range, 4-14 months). Five patients remain in remission during the follow-up period of 4-14 months. Two of these patients revealed no recurrence of the ulcer at sigmoidoscopy performed 3 and 5 months after initial remission. Patient 3 experienced a relapse of symptoms with proven recurrence of SRU at 5 months. Sucralfate enemas, given in the same dosage received previously, produced clinical and morphologic remission at the end of the 4th week. Maintenance therapy was instituted in this patient, receiving one instillation of 2 g of sucralfate suspended in 30 ml of water twice weekly, and he remains in remission at 6 months.
DISCUSSION Sucralfate is a basic aluminum salt of sucrose octasulfate that is poorly absorbed from the gastrointestinal tract in humans. It appears to promote ulcer healing by binding positively charged moieties in the ulcer base, resulting in the formation of viscous coagulum; it also has a cytoprotective role. 3 Topical treatment with sucralfate enemas has been shown to have beneficial effects on ulcerative colitis in a recent abstract 7 and in experimental acetic acid-induced colitis in rats. 8 It has been used in controlling bleeding in radiation proctitis 9 and after colonic polypectomy. ~~ In this preliminary study in which sucralfate was applied in a dosage of 2 g twice a day in patients with SRU, we found marked improvement in clinical symptoms and the macroscopic picture, but no significant histologic improvement. Although one patient relapsed 5 months after treatment, the therapeutic effect was lasting in the remaining patients during an observation period of 4-14 months, but it remains to be seen whether these encouraging results will be maintained in the longer term. We, however, consider this a satisfactory result in these patients who had symptoms over a very long period, because none of them experienced a relapse-free period of more than 4 months with previous therapies. Placebo-controlled trials are diffi-
Vol. 34, No. 6
SUCRALFATE RETENTION ENEMAS
cult to carry out b e c a u s e of the rarity of this disease.a, 3 A d o s e of 2 g twice a day was c h o s e n empirically. A p r o s p e c t i v e study to define the dosage schedule, duration of therapy, and n e e d of m a i n t e n a n c e t h e r a p y n e e d s to b e u n d e r t a k e n .
REFERENCES 1. Haskell B, Rovner H. Solitary ulcer of the rectum. Dis Colon Rectum 1965;8:333-6. 2. Madigan MR, Morson BC. Solitary ulcer of the rectum. Gut 1969;10:871-81. 3. Kennedy DK, Hughes ES, Masterton JP. The natural history of benign ulcer of the rectum. Surg Gynecol Obstet 1977;144:718-20. 4. Schweiger M, Alexander-Williams J. Solitary ulcer syndrome of the rectum: its association with occult rectal prolapse. Lancet 1977;1:170-1.
457
5. Rey JF, Legras B, Verdier A, Vicar F, Gorget C. Comparative study of sucralfate versus cimetidine in the treatment of acute gastroduodenal ulcer. Am J Med 1989;86(suppl 6A): 116-21. 6. Nagashama R. Mechanism of action of sucralfate. J Clin Gastroenterol 1981;3(s, uppl 2): 117-27. 7. Railey SA, Gupta I, Mani V. A comparison of sucralfate and prednisolone enemas in the treatment of active distal ulcerative colitis. Gastroenterology 1988;94:A377. 8. Zahavi I, Avidor I, Marcus H, et al. Effect of sucralfate on experimental colitis in the rat. Dis Colon Rectum 1989;32:95-8. 9. Kochhar R, Sharma SC, Gupta BB, Mehta SK. Rectal sucralfate in radiation proctitis. Lancet 1988;2:400. 10. Bronner MH, Yantis PL. Intracolonic sucralfate suspension for postpo!ypectomy hemorrhage. Gastrointest Endosc 1986;32:362-3.
Solitary Rectal Ulcer Showkat Ali Zargar, M.D., D.M., Mohammad Sultan Khuroo, M.D., D.M., Rakesh Mahajan,-M.D. From the Department of Gastroenterology, Institute of Medical Sciences, Srinagar (Kashmir), India Zargar SA, Khuroo MS, Mahajan R. Sucralfate retention enemas in solitary rectal ulcer. Dis Colon Rectum 1991;34:455-457.
the typical sigmoidoscopic appearances and histologic criteria 2' 3 w e r e s e e n (Table 1). Symptoms of b l o o d and mucus in stools, altered b o w e l habits, tenesmus, and abdominal or perineal pain w e r e s c o r e d on a 10-point scale. The duration of symptoms ranged from 4 to 48 m o n t h s (mean, 18 months). Rectal b l e e d i n g was the most c o m m o n complaint (n = 6), f o l l o w e d by mucus in the stools (n = 4), t e n e s m u s (n = 4), diarrhea (n = 3), constipation (n -- 3), and pain (n = 2). All d e n i e d history of rectal digitation. Previous treatments had b e e n generally unsatisfactory. The relapse-free p e r i o d with previous therapies varied from 2 to 4 m o n t h s (mean, 2.8 m o n t h s ) . Rectal prolapse was s e e n in o n e patient. Sigm o i d o s c o p y revealed a single ulcer in five patients and two ulcers in o n e patient. Ulcers w e r e oval or linear in shape, shallow with slough, and m e a s u r e d 1.5-3.0 cm in diameter. Ulcers were located o n the anterior rectal wall, 5-11 cm from the anal verge. The m u c o s a a r o u n d the ulcer was slightly nodular in two patients. Each patient was advised to administer sucralfate, 2 g s u s p e n d e d in 30 ml of tap water, twice a day for 6 weeks in the form of r e t e n t i o n enemas. The treatment was e x t e n d e d to 8 weeks if the ulcer did not heal with 6-week therapy. Each patient was instructed h o w to instill the solution through a soft r u b b e r catheter. N o n e r e p o r t e d major leakage of the instillate. Patients had b e e n off all drugs for at least a w e e k b e f o r e starting sucralfate enemas. Patients w e r e assessed clinically every week, by flexible instrument s i g m o i d o s c o p y every 2 weeks by the same endoscopist, and by repeat biopsies at 6 weeks.
The conservative treatment of solitary rectal ulcer is generally unsatisfactory. Six patients, aged 27-54 years, with recurrent solitary rectal ulcer were treated with topical administration of sucralfate in a daily dose of 2 g twice a day for 6 weeks. Four patients experienced complete relief of symptoms and the remaining two patients had marked improvement. Although macroscopic healing of the ulcer was apparent in all, histologic improvement was not appreciable. Five of the six patients remain in remission during a follow-up period of 4-14 months (mean, 8 - 1.5 months). Recurrence was observed in one patient at 5 months, which satisfactorily resolved with sucralfate enemas. From these preliminary observations we infer that solitary rectal ulcer can be effectively treated with topical application of sucralfate. [Key words: Sucralfate; Solitary rectal ulcer] olitary rectal ulcer (SRU) is a rare but distressing condition that usually affects y o u n g adults. >3 T h e r e is no general a g r e e m e n t about its treatment and many empiric therapeutic approaches have b e e n tried including local electrocautery, caustic agents, antibiotics, sulfasalzine, steroid retention enemas, and local excisional surgery, without any obvious or consistent improvement.i, 3 Surgical correction of prolapse of the rectum may be useful in the cases in w h i c h it is present. 4 Sucralfate is a locally acting nonsystemic cytoprotective agent that has b e e n effective in p r o m o t i n g the healing of gastric and d u o d e n a l ulcers.5, s We, therefore, d e c i d e d to u n d e r t a k e a pilot study in patients with SRU to assess w h e t h e r topical administration of sucralfate serves any therapeutic effect.
S
MATERIALS A N D
METHODS
From January 1989 to D e c e m b e r 1989, six consecutive patients with a diagnosis of SUR based o n
RESULTS Four patients a c h i e v e d c o m p l e t e relief of symptoms ( c o m p l e t e clinical remission) and two nearc o m p l e t e remission. Although the latter two patients c o n t i n u e d to have mucus in stools (n = 2) and diarrhea (n = 1), they w e r e fairly satisfied with
Address reprint requests to Dr. Khuroo: Professor and Chairman, Department of Gastroenterology, and Head, Department of Medicine, Institute of Medical Sciences, P.O. Box 27, Srinagar (Kashmir) 190 011 India. 455
456
ZARGAR E T AL
Dis Colon Rectum, June 1991
Table 1. Clinical Characteristics and Results of Sucralfate Enema in Six Patients with SRU Clinical Data Patient
*
At 6 Weeks of Sucralfate Enema
Duration of Remission (months)
Age/Sex
Duration (months)
Symptom Score
Previous Treatment
Symptom Score
1
54 M
48
8
0
Scarring
--
11
2
35 F
8
8
0
11
22 F 22 M
11 12
6 7
1 0
Scarring Petechiae Normal Normal
m
3 4 5
41 F
25
7
2
Scarring minute
6
38 M
4
7
Steroid enemas Metronidazole Electrocautery Steroid enemas Metronidazole Sulfasalazine Metronidazole Cryosurgery Antibiotics Steroid enemas Metronidazole Steroid enemas
0
Erosions Normal
Sigmoidoscopy
Side Effects
m Mild constipation --
6* 7
--
4
6
Refers to time after relapse.
the therapy. Clinical activity disappeared or greatly improved at the end of the second week. Endoscopic healing of the ulcer lesion was observed at 4 and 6 weeks of therapy in three patients each. The residual abnormalities, limited to mild scarring, petichae, or minute erosions, were seen in three patients. Biopsy specimens revealed improvement in the superficial erosions, ulcerations, and inflammatory reaction, but the fibromuscular obliteration of the lamina propria did not display any appreciable changes. One patient experienced increased constipation as an adverse effect of sucralfate; but this, however, subsided after completion of the treatment. All patients were followed up regularly for a mean period of 8 + 1.5 months (range, 4-14 months). Five patients remain in remission during the follow-up period of 4-14 months. Two of these patients revealed no recurrence of the ulcer at sigmoidoscopy performed 3 and 5 months after initial remission. Patient 3 experienced a relapse of symptoms with proven recurrence of SRU at 5 months. Sucralfate enemas, given in the same dosage received previously, produced clinical and morphologic remission at the end of the 4th week. Maintenance therapy was instituted in this patient, receiving one instillation of 2 g of sucralfate suspended in 30 ml of water twice weekly, and he remains in remission at 6 months.
DISCUSSION Sucralfate is a basic aluminum salt of sucrose octasulfate that is poorly absorbed from the gastrointestinal tract in humans. It appears to promote ulcer healing by binding positively charged moieties in the ulcer base, resulting in the formation of viscous coagulum; it also has a cytoprotective role. 3 Topical treatment with sucralfate enemas has been shown to have beneficial effects on ulcerative colitis in a recent abstract 7 and in experimental acetic acid-induced colitis in rats. 8 It has been used in controlling bleeding in radiation proctitis 9 and after colonic polypectomy. ~~ In this preliminary study in which sucralfate was applied in a dosage of 2 g twice a day in patients with SRU, we found marked improvement in clinical symptoms and the macroscopic picture, but no significant histologic improvement. Although one patient relapsed 5 months after treatment, the therapeutic effect was lasting in the remaining patients during an observation period of 4-14 months, but it remains to be seen whether these encouraging results will be maintained in the longer term. We, however, consider this a satisfactory result in these patients who had symptoms over a very long period, because none of them experienced a relapse-free period of more than 4 months with previous therapies. Placebo-controlled trials are diffi-
Vol. 34, No. 6
SUCRALFATE RETENTION ENEMAS
cult to carry out b e c a u s e of the rarity of this disease.a, 3 A d o s e of 2 g twice a day was c h o s e n empirically. A p r o s p e c t i v e study to define the dosage schedule, duration of therapy, and n e e d of m a i n t e n a n c e t h e r a p y n e e d s to b e u n d e r t a k e n .
REFERENCES 1. Haskell B, Rovner H. Solitary ulcer of the rectum. Dis Colon Rectum 1965;8:333-6. 2. Madigan MR, Morson BC. Solitary ulcer of the rectum. Gut 1969;10:871-81. 3. Kennedy DK, Hughes ES, Masterton JP. The natural history of benign ulcer of the rectum. Surg Gynecol Obstet 1977;144:718-20. 4. Schweiger M, Alexander-Williams J. Solitary ulcer syndrome of the rectum: its association with occult rectal prolapse. Lancet 1977;1:170-1.
457
5. Rey JF, Legras B, Verdier A, Vicar F, Gorget C. Comparative study of sucralfate versus cimetidine in the treatment of acute gastroduodenal ulcer. Am J Med 1989;86(suppl 6A): 116-21. 6. Nagashama R. Mechanism of action of sucralfate. J Clin Gastroenterol 1981;3(s, uppl 2): 117-27. 7. Railey SA, Gupta I, Mani V. A comparison of sucralfate and prednisolone enemas in the treatment of active distal ulcerative colitis. Gastroenterology 1988;94:A377. 8. Zahavi I, Avidor I, Marcus H, et al. Effect of sucralfate on experimental colitis in the rat. Dis Colon Rectum 1989;32:95-8. 9. Kochhar R, Sharma SC, Gupta BB, Mehta SK. Rectal sucralfate in radiation proctitis. Lancet 1988;2:400. 10. Bronner MH, Yantis PL. Intracolonic sucralfate suspension for postpo!ypectomy hemorrhage. Gastrointest Endosc 1986;32:362-3.
