Eficácia da aplicação endoscópica tópica de mitomicina C em estenoses esofágicas cáusticas na população pediátrica: uma revisão sistemática e meta-análise de ensaios clínicos randomizados / Efficacy of endoscopic topical mitomycin c application in caustic esophageal strictures in the pediatric population: a systematic review and meta-analysis of randomized controlled trials

ABSTRACT BACKGROUND: Caustic ingestion and development of esophageal strictures are recognized major public health problems in childhood. Different therapeutic methods have been proposed in the management of such strictures. OBJECTIVE: To evaluate efficacy and risk of endoscopic topical application of mitomycin C in the treatment of caustic esophageal strictures. METHODS: We searched MEDLINE, EMBASE, Central Cochrane, and LILACS databases. The outcomes evaluated were dysphagia resolution rate, number of dilations performed in resolved cases, and the number of dilations performed in all patients. RESULTS: Three randomized clinical trials were included for final analysis with a total of 190 patients. Topical mitomycin C application group showed a significant increase in dysphagia resolution rate, corresponding to a 42% higher dysphagia resolution as compared to endoscopic dilation alone, with statistical significance between the two groups (RD: 0.42 - [CI: 0.29-0.56]; P-value <0.00001). The mean number of dilations performed in resolved cases were significantly less in the topical mitomycin C application group, compared to endoscopic dilations alone, with statistical significance between the two groups (MD: 2.84 [CI: 1.98-3.69]; P-value <0.00001). When comparing the number of dilations in all patients, there was no statistical difference between the two groups (MD: 1.46 [CI: -1.53-4.44]; P-value =0.34). CONCLUSION: Application of topical mitomycin C with endoscopic dilations in caustic esophageal strictures was more effective in dysphagia resolution than endoscopic therapy alone in the pediatric population. Moreover, topical mitomycin C application also reduced the number of dilation sessions needed to alleviate dysphagia without rising morbidity.

RESUMO CONTEXTO: A ingestão de soda cáustica e o desenvolvimento de estenoses esofágicas são reconhecidos como importantes problemas de saúde pública na infância. Diferentes métodos terapêuticos têm sido propostos no manejo dessas estenoses. OBJETIVO: Avaliar a eficácia e o risco da aplicação endoscópica tópica de mitomicina C no tratamento de estenoses esofágicas cáusticas. MÉTODOS: Buscamos as bases de dados MEDLINE, EMBASE, Central Cochrane e LILACS. Os desfechos avaliados foram taxa de resolução da disfagia, número de dilatações realizadas nos casos resolvidos e número de dilatações realizadas em todos os pacientes. RESULTADOS: Três ensaios clínicos randomizados foram incluídos para análise final com um total de 190 pacientes. O grupo de aplicação de mitomicina C tópica apresentou aumento significativo na taxa de resolução da disfagia, correspondendo a uma resolução da disfagia 42% maior em comparação à dilatação endoscópica isolada, com significância estatística entre os dois grupos (RD: 0,42 - [IC: 0,29-0,56]; P-valor <0,00001). O número médio de dilatações realizadas em casos resolvidos foi significativamente menor no grupo de aplicação tópica de mitomicina C, em comparação com as dilatações endoscópicas isoladas, com significância estatística entre os dois grupos (MD: 2,84 [IC: 1,98-3,69]; P-valor <0,00001). Ao comparar o número de dilatações em todos os pacientes, não houve diferença estatística entre os dois grupos (MD: 1,46 [IC: -1,53-4,44]; valor de P=0,34). CONCLUSÃO: A aplicação de mitomicina C tópica com dilatações endoscópicas em estenoses esofágicas cáusticas foi mais eficaz na resolução da disfagia do que a terapia endoscópica isolada na população pediátrica. Além disso, a aplicação tópica de mitomicina C também reduziu o número de sessões de dilatação necessárias para aliviar a disfagia sem aumentar a morbidade.

Cordycepin prevents the esophageal stricture formation in the alkali-burn rat model by exerting anti-inflammatory and antifibrotic effects

ABSTRACT Purpose To investigate the efficacy of cordycepin, an adenosine analogue, on prevention of esophageal damage and stricture formation due to esophageal caustic burns in rat model comparing with prednisolone. Methods Caustic esophageal burn was introduced by 37.5% of NaOH to distal esophagus. Thirty-two Wistar albino rats were divided in four groups: sham rats undergone laparotomy, treated with 0.9% NaCl; control rats injured with NaOH without cordycepin treatment; cordycepin group injured with NaOH, treated with 20 mg/kg cordycepin; prednisolone group injured with NaOH, treated with 1 mg/kg prednisolone for 28 days. Efficacy was assessed by histopathological and immunohistochemical analysis of esophageal tissues. Results Cordycepin treatment significantly decreased inflammation, granulation tissue and fibrous tissue formation and prevented formation of esophageal strictures shown by histopathological damage score and stenosis indexes compared to control group (p < 0.01). These effects are relatively more substantial than prednisolone, probably based on attenuation of elevation of proinflammatory cytokines hypoxia-inducible factor 1-alpha (HIF-1?), tumor necrosis factor alpha (TNF-?), proliferative and fibrotic factor fibroblast growth factor 2 (FGF2) and angiogenic factor vascular endothelial growth factor A (VEGFA) (p < 0.05). Conclusions The findings suggest that cordycepin has a complex multifactorial healing process in alkali-burned tissue, more successful than prednisolone in preventing the formation of esophageal strictures and may be used as a therapeutic agent in the acute phase of esophageal alkali-burn.

The use of mitomycin C in caustic esophagitis in rats

PURPOSE: To evaluate the topical effects of mitomycin C (MMC) in rats, with or without esophageal dilation, in different moments after esophageal caustic injury with NaOH10%. METHODS: Forty eight Wistar rats were divided into six groups: "GS" infusion of 0.9% saline solution in the esophagus; "CG" infusion of 0.9% saline solution in the esophagus, with temporary ligation of the organ; "NTG" induction of a caustic lesion without treatment; "GmmcD0" MMC applied immediately after the caustic injury; "GmmcD14" MMC applied 14 days after the caustic injury; "Gdil+mmcD14" esophageal dilation and application of MMC 14 days after caustic injury. We performed contrast esophagograms of four animals from each group, seven and 21 days after the caustic injury. On day 28, all animals were sacrificed, and histopathological analyses were performed on the esophageal specimens. RESULTS: The contrast images showed total stenosis in NTG and GmmcD0, improving to partial stenosis in GmmcD0. In GmmcD14 and Gdil+mmcD14, two animals of each group improved to partial stenosis. By histopathological analysis, NTG and GmmcD14 presented intermediate damage and GmmcD0 and Gdil+mmcD14 severe damage. CONCLUSION: The use of mitomycin C had beneficial effects specially when applied immediately after the induction of esophageal lesions.

Penfigoide de membranas mucosas com estenose esofágica grave / Mucous membrane pemphigoid with severe esophageal stricture

O penfigoide de membranas mucosas é entidade nosológica encarada como um fenótipo, que engloba várias dermatoses autoimunes com lesões bolhosas subepidérmicas, ocorrendo predominantemente nas membranas mucosas, com êxito cicatricial. O acometimento esofágico no penfigoide de membranas mucosas é raro e observado em pacientes com lesão disseminada. As alterações mais comuns são múltiplas membranas ou constrições esofagianas. No presente relato, os autores apresentam paciente com PMM sem lesões cutâneas e estenose esofágica grave, que entrou em remissão após uso de imunoglobulina venosa.

Mucous membrane pemphigoid (MMP) is a rare nosological entity. MMP consists of a clinical phenotype in which several autoimmune subepidermal bullous diseases are classified. It occurs predominantly in the mucous membranes and usually results in scarring. Esophageal involvement in MMP is rare and is generally seen in patients in whom lesions are widespread. The most common alterations are multiple esophageal membranes or strictures. In the present case, the authors report on a patient with MMP without any skin lesions and with severe esophageal strictures who went into remission following use of intravenous immunoglobulin.

[Effects of using mitomycin-C in treatment of benign esophageal strictures]

Using bouginage or balloon dilatation is the standard treatment for benign esophageal strictures. About two-thirds need repeated dilatations. For preventing recurrent strictures, many medications such as mitomycin-C have been used. Mitomycin-C is a special antibiotic with anti-neoplastic characteristics, which inhibits fibroblast proliferation, reduces collagen production and decreases scar formation. In this study, 12 patients with benign esophageal stricture during Azar 1386 to Bahman 1387 in Imam Khomeini Endoscopy Department were included. Esophageal endoscopy was done and mitomycin-C was applied on the place of stricture using a cotton ball. Then, response to treatment was categorized in three groups of complete response, partial response and non-response to treatment. Average number of using mitomycin-C was 4 +/- 3 times. Mean interval between endoscopies before using mitomycin-C was 3.5 +/- 1 weeks and after using this agent was 8.5 +/- 4.3 weeks. There were 4 cases of complete response, 5 cases of partial response and 3 patients of non-response. Conservative treatments in management of benign esophageal strictures are preferred to more invasive treatments. However, it seems using a topical solution of mitomycin-C carries better responses and reduces the rate of recurrent dilatations

Effect of corticosteroid therapy in esophageal stricture of a child with chronic granulomatous disease

In chronic granulomatous disease [CGD] patients, esophageal stricture is a rare complication and the treatment of choice is still controversial. There are few reports of successful therapy with antibiotics, corticosteroids, multiple balloon dilatations or their combination. We report a 3-three-year-old Iranian boy with recurrent esophageal obstruction due to CGD. The patient transiently responded to dilatation in one occasion and at another time to short term steroid therapy. We observed an excellent response when long term and high dose of corticosteroid was administered. It showed that a long term and high dose steroid therapy is more effective than a short term in a patient with CGD and esophageal stricture

Treatment of gastroesophageal reflux disease

OBJETIVO: Rever a literatura sobre tratamento da doença do refluxo gastroesofágico (DRGE) com ênfase nos aspectos farmacológicos. Identificar particularidades do tratamento farmacológico nas manifestações esofágicas e extra-esofágicas da doença. FONTES DE DADOS: Busca eletrônica na base de dados PubMed/MEDLINE e Cochrane Collaboration. Procurou-se identificar estudos controlados e randomizados publicados a partir de 2000, bem como revisões que representassem consensos e diretrizes publicados nos últimos 10 anos. SíNTESE DOS DADOS: Nenhuma das drogas atualmente usadas no tratamento da DRGE altera comprovadamente o mecanismo principal da doença, ou seja, os relaxamentos transitórios do esfíncter esofágico inferior. O tratamento farmacológico da DRGE com sintomas ou com lesões esofágicas é baseado na inibição da secreção ácida, em particular pelos inibidores da bomba de prótons (IBP). Nas situações em que a hiper-reatividade das vias aéreas inferiores coexiste com sintomas esofágicos da DRGE, a inibição da secreção ácida deve trazer benefícios na condução da doença respiratória se houver uma relação causal; contudo, essa situação não é comum. Quando não coexistem sintomas esofágicos, a pHmetria esofágica de 24 h deve ser realizada previamente ao tratamento farmacológico da DRGE. A melhora dos sintomas respiratórios pode ser tardia em relação aos sintomas esofágicos. A DRGE freqüentemente recorre, e o tratamento farmacológico deve ser repetido ou mantido indefinidamente, conforme a apresentação clínica da doença. CONCLUSÃO: As condutas propostas para o tratamento farmacológico da DRGE na criança são oriundas principalmente de estudos de séries de casos ou de estudos em adultos. Existem poucos estudos controlados e randomizados em crianças. A realização de um número maior desses estudos poderá reafirmar ou introduzir novos aspectos nas condutas propostas.

OBJECTIVE: To review the literature on the treatment of gastroesophageal reflux disease (GERD) with emphasis on pharmacological aspects. To identify particularities of pharmacological treatment of esophageal and extraesophageal manifestations of the disease. SOURCES: Electronic search of the PubMed/MEDLINE and Cochrane Collaboration databases. Controlled and randomized studies published since 2000 and reviews representing consensus positions and directives published within the last 10 years were identified. SUMMARY OF THE FINDINGS: The drugs currently available for the treatment of GERD do not act in the primary mechanism of the disease, i.e., transitory relaxation of the lower esophageal sphincter. Pharmacological treatment of GERD with symptoms or with esophageal injury is based on the suppression of acid secretion, particularly with proton pump inhibitors. When the hyperreactivity of the lower airways coexists with esophageal GERD symptoms, suppression of acid secretions should be of benefit in managing the respiratory disease in the presence of a causal relationship; however, this is not usual. When esophageal symptoms are not present, esophageal 24-hour pH study should be carried out prior to starting pharmacological treatment for GERD. Improvement of respiratory symptoms may be delayed with relation to esophageal symptoms. It is common for GERD to recur and pharmacological treatment should be repeated or continued indefinitely, depending on clinical presentation of the disease. CONCLUSIONS: The strategies that have been proposed for the pharmacological treatment of GERD in children are primarily based on studies of case series or on studies with adults. There have been very few controlled and randomized studies in children. Undertaking a greater number of these studies might reinforce existing aspects or establish new aspects of management.

Primary tuberculous stricture of the oesophagus mimicking carcinoma.

A middle-aged woman presented with progressive dysphagia and weight loss was investigated. A stricture involving the lower third of oesophagus was identified but precise histology of the lesion could not be obtained even after multiple biopsies. The resected specimen showed histology consistent with oesophageal tuberculosis.

Ingesta de cáusticos en la infancia / Ingestion of caustics in infancy

Entre enero de 1978 y diciembre de 1983 fueron asistidos 108 niños por ingestión de sustancias cáusticas. Sólo 86 completaron su seguimiento hasta el alta. En la mitad de los casos el tóxico ingerido fue hidróxido de sodio (soda cáustica). La distribución por edades mostró una mediana de 24 meses. A todos los pacientes se les indicó el mismo esquema de tratamiento. La radiografia contratada de esófago realizada entre el 7- y el 30- día mostró ser pronóstica de las lesiones severas. Se realizó endoscopia esofágica a 31 pacientes durante los primeros días de evolución; 17 tuvieron lesiones de la mucosa esofágica que en 2 de ellos fueron severas y coincidieron con la evolución a la estenosis. Hubo correlación endoscópica/radiológica. Se consideraron pacientes de alto riesgo con probabilidad de desarrolar estenosis, aquellos niños que con el antecedente de ingesta de álcali presenten: a) Retraso mental. b) Lesiones intensas de orofaringe. c) Disfagia inicial que persiste más de 48 horas. Consideramos que la conducta ante todo niño que haya ingerido ese cáustico es: 1) Tratamiento con corticoides durante 15 días. 2) Radiografía contrastada de esófago entre el 7§ y el 10§ día. Si ésta presenta anormalidad, efectuar esofagoscopia y eventual dilatación