RESUMO
BACKGROUND: Chronic radiation proctopathy (CRP) is a troublesome complication of radiotherapy to the pelvis for which current treatment modalities are suboptimal. Currently, the application of formalin to the rectal mucosa (AFR) and thermal ablation with argon plasma coagulation (APC) are the most promising options. OBJECTIVE: To compare the efficacy and safety of AFR with APC for CRP. PATIENTS AND METHODS: Records of 22 patients (male to female ratio, 19:3; mean age, 74 years) who received either APC or AFR for chronic hematochezia caused by CRP, and who were evaluated and treated between May 1998 and April 2002, were reviewed. Complete evaluations were made three months after completion of each therapeutic modality. Patients were considered to be responders if there was a 10% increase in hemoglobin from baseline or complete normalization of hemoglobin (male patients, higher than 130 g/L; female patients, higher than 115 g/L) without the requirement for blood transfusion. RESULTS: The mean hemoglobin level before therapy was 107 g/L. Patients received an average of 1.78 sessions for APC and 1.81 sessions for AFR. Eleven patients (50%) were treated with APC alone, eight patients (36%) with AFR alone and three (14%) with both modalities (two with AFR followed by APC, and one with APC followed by AFR). Eleven of 14 patients (79%) in the APC group were responders, compared with three of 11 patients (27%) in the AFR group (P=0.017). In the APC group, seven of 11 responders required only a single session, while in the AFR group, only one patient responded after a single session. Adverse events (nausea, vomiting, flushing, abdominal cramps, rectal pain and fever) occurred in two patients after APC and in nine patients after AFR (P=0.001). In the APC group, the mean hemoglobin level increase was 20 g/L at three months follow-up, compared with 14 g/L in the AFR group. CONCLUSION: This retrospective study suggests that APC is more effective and safe than topical AFR to control hematochezia caused by CRP. Further studies are needed to confirm this observation.
Assuntos
Fotocoagulação a Laser , Lasers de Gás/uso terapêutico , Lesões por Radiação/terapia , Reto/efeitos da radiação , Administração Tópica , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Fixadores , Formaldeído/administração & dosagem , Humanos , Mucosa Intestinal/efeitos da radiação , Masculino , Lesões por Radiação/etiologia , Radioterapia/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Although corticosteroids are effective for induction of remission of Crohn's disease, approximately 20% of patients who respond relapse when steroids are withdrawn and become steroid dependent (Binder 1985). Furthermore, corticosteroids exhibit significant adverse effects. The success of methotrexate as a treatment for rheumatoid arthritis led to its evaluation in patients with refractory Crohn's disease. Methotrexate has been studied for induction of remission of refractory Crohn's disease and has become the principal alternative to azathioprine/6MP therapy. The evidence for its effectiveness has not been subjected to a systematic review. OBJECTIVES: To conduct a systematic review of the evidence for effectiveness of methotrexate for induction of remission in patients with active Crohn's disease in the presence and absence of concomitant steroid therapy. SEARCH STRATEGY: A computer-assisted search of MEDLINE and EMBASE for relevant studies published in English, French, Spanish, Italian and German between 1966 and July 2004. Manual searches of reference lists from potentially relevant papers were performed to identify additional studies. The Cochrane Controlled Trials Register and the IBD Review Group Specialized Trials Register were also searched. SELECTION CRITERIA: Randomized controlled trials involving patients of age > 17 years with refractory Crohn's disease defined by conventional clinical, radiological and endoscopic criteria, which was categorized as being active (Crohn's disease activity index >150). OUTCOME MEASURES: The outcome measure was the rate of induction of remission and complete withdrawal from steroids in the treatment and control groups after > 16 weeks of treatment. A secondary outcome was induction of remission with reduction in steroid dose of at least 50%. Selection of trials: The results of the searches above were reviewed independently by two observers and relevant studies selected according to the predefined selection criteria. Any disagreement among reviewers was resolved by consensus. The same two reviewers assessed the methodological quality of each trial (details of randomization method, including whether intention-to-treat analysis was possible from the published data, number of patients lost to follow-up, and if a blinded outcome assessment was used). A standard data extraction form was used. Appropriateness of combining results: Trials were first reviewed to assess the clinical comparability of trial protocols and study populations. MAIN RESULTS: Five randomized trials were identified. The five studies differed with respect to participants, intervention, and outcomes to the extent that it was considered to be inappropriate to combine the data statistically. Three small studies which employed low doses of methotrexate orally showed no statistically significant difference between methotrexate and placebo/control medication treated patients. One small study which used a higher dose of intravenous/oral methotrexate showed no statistically significant difference between methotrexate and azathioprine. A larger study which employed a higher dose of methotrexate intramuscularly showed substantial benefit (number needed to treat, NNT=5). Adverse effects were more common with high dose intramuscular methotrexate therapy than with placebo. AUTHORS' CONCLUSIONS: There is evidence from a single large randomized trial on which to recommend the use of methotrexate 25 mg intramuscularly weekly for induction of remission and complete withdrawal from steroids in patients with refractory Crohn's disease. Although adverse effects were more common than with placebo, they were not severe. There is no evidence on which to base a recommendation for use of lower dose oral methotrexate.
Assuntos
Doença de Crohn/tratamento farmacológico , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de RemissãoRESUMO
BACKGROUND: Although corticosteroids are effective for induction of remission of Crohn's disease, approximately 20% of patients who respond relapse when steroids are withdrawn and become steroid dependent (Binder 1985). Furthermore, corticosteroids exhibit significant adverse effects. The success of methotrexate as a treatment for rheumatoid arthritis led to its evaluation in patients with refractory Crohn's disease. Methotrexate has been studied for induction of remission of refractory Crohn's disease and has become the principal alternative to azathioprine/6MP therapy. The evidence for its effectiveness has not been subjected to a systematic review. OBJECTIVES: To conduct a systematic review of the evidence for effectiveness of methotrexate for induction of remission in patients with active Crohn's disease in the presence and absence of concomitant steroid therapy. SEARCH STRATEGY: A computer-assisted search of MEDLINE and EMBASE for relevant studies published in English, French, Spanish, Italian and German between 1966 and June 2002. Manual searches of reference lists from potentially relevant papers were performed to identify additional studies. The Cochrane Controlled Trials Register and the IBD Review Group Specialized Trials Register were also searched. SELECTION CRITERIA: Randomized controlled trials involving patients of age > 17 years with refractory Crohn's disease defined by conventional clinical, radiological and endoscopic criteria, which was categorized as being active (Crohn's disease activity index >150). OUTCOME MEASURES: The outcome measure was the rate of induction of remission and complete withdrawal from steroids in the treatment and control groups after 16 weeks of treatment. A secondary outcome was induction of remission with reduction in steroid dose of at least 50%. Selection of trials: The results of the searches above were reviewed independently by two observers and relevant studies selected according to the predefined selection criteria. Any disagreement among reviewers was resolved by consensus. The same two reviewers assessed the methodological quality of each trial (details of randomization method, including whether intention-to-treat analysis was possible from the published data, number of patients lost to follow-up, and if a blinded outcome assessment was used). A standard data extraction form was used. Appropriateness of combining results: Trials were first reviewed to assess the clinical comparability of trial protocols and study populations. MAIN RESULTS: Three randomized placebo-controlled trials were identified. The three studies differed with respect to participants, intervention, and outcomes to the extent that it was considered to be inappropriate to combine the data statistically. Two studies which employed low doses of methotrexate orally showed no statistically significant difference between methotrexate and placebo treated patients, and one which employed a higher dose intramuscularly showed substantial benefit (number needed to treat, NNT=5). Adverse effects were more common with high dose intramuscular methotrexate therapy than with placebo. REVIEWER'S CONCLUSIONS: There is evidence from a single large randomized trial on which to recommend the use of methotrexate 25 mg intramuscularly weekly for induction of remission and complete withdrawal from steroids in patients with refractory Crohn's disease. Although adverse effects are more common than with placebo, they were not severe. There is no evidence on which to base a recommendation for use of lower dose oral methotrexate.