Investigação da relação entre achados clínicos e histopatológicos em pacientes com Displasia Neuronal Intestinal tipo B
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Data
2022-02-25
Autores
Gonçalves, Anderson Cesar
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Universidade Estadual Paulista (Unesp)
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A Displasia Neuronal Intestinal do tipo B (DNI-B) é uma entidade patológica, do grupo das doenças neuromusculares gastrointestinais. O diagnóstico de DNI-B é realizado a partir da análise histopatológica das biópsias de reto de pacientes que apresentam constipação intestinal, habitualmente refratária ao tratamento clínico, demonstrando sinais de hiperplasia dos plexos nervosos da submucosa. A indefinição sobre a relação causal entre os achados histológicos e os sintomas clínicos vem sendo apontada como o principal ponto a ser elucidado na investigação científica relacionada à DNI-B. Este parece ser o elo ainda pendente para a real caracterização da DNI-B como uma doença e para o estabelecimento definitivo de seus critérios diagnósticos e possibilidades terapêuticas. Objetivo: investigar a associação entre os achados histopatológicos, identificados em pacientes com DNI-B, e os sintomas clínicos presentes no momento do diagnóstico. Métodos: Trata-se de um estudo de centro único, retrospectivo, não-controlado, descritivo e analítico. Este estudo foi aprovado pelo Comitê de Ética em Pesquisa da Instituição. Foram incluídos 27 pacientes, com idade entre 0 e 15 anos, que haviam recebido o diagnóstico de DNI-B, com base nos critérios histopatológicos propostos no Consenso de Frankfurt (1990) e que haviam sido submetidos a tratamento cirúrgico, por meio de ressecções extensas do cólon e do reto. Os prontuários médicos foram recuperados para obtenção de dados relacionados ao hábito intestinal, presentes no momento do diagnóstico, incluindo o Intestinal Symptom Index (ISI), que é um índice proposto para resumir os sinais e sintomas mais comuns no curso clínico da DNI-B. Foram obtidos, também, dados da análise histopatológica detalhada das peças cirúrgicas. Foi realizada análise fatorial exploratória, aplicando o método de componentes principais para agrupamentos, com rotação Varimax. Foi estabelecido o ponto de corte de 0,5 para as cargas fatoriais. A distribuição dos escores dos dois fatores determinados foi realizada por meio de gráfico de escores. O nível de significância foi de 5% e a análise foi realizada no software SASv. 9.4. Resultados: A análise fatorial exploratória permitiu a investigação das relações entre sintomas clínicos e características histopatológicas. Esta análise determinou 2 fatores principais, que explicam quase a metade das variações possíveis. O Fator 1, responsável pela maior parte das variações explicadas, foi composto por variáveis histopatológicas e por algumas variáveis clínicas de gravidade, como a necessidade de realização de lavagens intestinais e a presença de evacuações com sangue. O Fator 2 foi composto pelos principais sintomas, incluindo o ISI. Após o procedimento de rotação fatorial, foi possível identificar associação entre os principais componentes destes 2 fatores, através de representação gráfica, ficando evidente as relações de proximidade entre os valores do ISI e as alterações histopatológicas associadas à DNI-B, representadas principalmente pela hiperganglionose. Estes componentes levaram à uma mesma direção no gráfico, contribuindo para um mesmo sentido clínico, nas relações investigadas entre sintomas e alterações histopatológicas. Conclusão: Há associação entre sintomas e alterações histopatológicas na DNI-B. Isto reforça a teoria de que a DNI-B seja realmente uma doença, com sintomas específicos e alterações orgânicas no trato gastrointestinal.
Intestinal Neuronal Dysplasia type B (IND-B) is a pathological entity belonging to gastrointestinal neuromuscular diseases. The diagnosis of IND-B is based on the pathological analysis of rectal biopsies from patients with constipation, with signs of submucosal nerve plexus hyperplasia. The lack of definition about the causal relationship between histological findings and clinical symptoms has been pointed as the primary point that needs to be elucidated in the scientific investigation related to IND-B. This point seems to be the link still pending for the accurate characterization of IND-B as a disease and the definitive establishment of its diagnostic criteria and therapeutic possibilities. Objective: to investigate the association between the histopathological findings identified in patients with IND-B and the clinical symptoms present at the time of diagnosis. Methods: This is a single-center, retrospective, uncontrolled, descriptive, and analytical study. The Institution's Research Ethics Committee approved this study. We included 27 patients, aged between 0 and 15 years, who had received the diagnosis of IND-B, based on the pathological criteria proposed in the Frankfurt Consensus (1990), and who had undergone surgical treatment through extensive resections of the colon and rectum. We retrieved medical records to obtain data related to bowel habits present at the time of diagnosis, including the Intestinal Symptom Index (ISI), an index proposed to summarize the most common signs and symptoms in the clinical course of IND-B. Data from the detailed pathological analysis of the surgical specimens were also obtained. Exploratory factor analysis was performed, applying the principal components method for clusters with Varimax rotation. We established a cut-off point of 0.5 for factor loadings. The distribution of scores for the two factors determined was performed using a score chart. The significance level was 5%, and the analysis was performed using the SAS v software. 9.4. Results: Exploratory factor analysis allowed the investigation of the relationship between clinical symptoms and pathological features. This analysis determined two main factors, which explain almost half of the possible variations. Factor 1, responsible for most of the described variations, was composed of pathological variables and some clinical variables of severity, such as the need to perform intestinal washouts and the presence of bloody stools. Factor 2 was composed of the main symptoms, including ISI. After the factorial rotation procedure, we could identify an association between the main components of these two factors through graphic representation, showing the close relationships between the ISI values and the pathological alterations associated with IND-B, represented mainly by hypergangliosis. These components lead to the same direction in the graph, contributing to the same clinical meaning in the investigated relationships between symptoms and pathological alterations. Conclusion: There is an association between symptoms and pathological changes in IND-B, reinforcing the theory that IND-B is a disease with specific symptoms and organic changes in the gastrointestinal tract.
As manifestações clínicas da Doença de Hirschsprung (DH) e a Displasia Neuronal Intestinal tipo B (DNI-B) são consideradas como semelhantes, parte de um mesmo espectro clínico. No entanto, não há estudos que tenham investigado as potenciais diferenças entre as manifestações clínicas apresentadas por pacientes com DH e com DNI-B. Nós decidimos comparar as manifestações clínicas apresentadas por pacientes com DH e com DNI-B, no momento do estabelecimento do diagnóstico etiológico. Pacientes e métodos: Foi realizado um estudo de centro único, retrospectivo, analítico e comparativo. Foram incluídos 119 pacientes com idade entre 0 e 15 anos, que haviam recebido diagnóstico de DH ou DNI-B por meio da análise histopatológica de biópsias de reto, no período de 1998 a 2010. Foram recuperadas as informações dos prontuários médicos destes pacientes, para obtenção de informações demográficas e clínicas, presentes no momento do diagnóstico. Os dados foram comparados estatisticamente, de acordo com as características das variáveis, utilizando-se os testes de Fischer, Qui-quadrado com correção de Yates, Binomial, Mann-Whitney e T de Student. O nível de significância foi de 5%. O estudo foi aprovado pelo Comitê de Ética local. Resultados: 69 pacientes (58.0%) haviam recebido o diagnóstico DH e 50 (42.0%) o de DNI-B. O grupo DH apresentou um número significativamente maior de indivíduos com início dos sintomas no período neonatal (p = 0,001), atraso para eliminação de mecônio (p < 0,001), déficit para ganho de peso (p = 0,02), e que evoluíram com complicações agudas, como enterocolite (p = 0,049) ou abdome agudo obstrutivo (p = 0,031), necessitando mais comumente de cirurgias de urgência (p < 0,001). Os pacientes com DNI-B foram diagnosticados em idades significativamente maiores (p = 0,002) e mais comumente tiveram como principal sintoma, quadros crônicos de constipação intestinal (p = 0,004), com complicações locais como sangramento evacuatório (p = 0,007). Conclusão: Houve diferenças significativas entre o quadro clínico apresentado por pacientes com DH e com DNI-B no momento do diagnóstico etiológico. O conhecimento do quadro clínico mais comumente apresentado para cada uma destas etiologias tem potencial para auxiliar no direcionamento das medidas iniciais, diagnósticas e terapêuticas, que são individualizadas para cada uma destas doenças.
The clinical manifestations of Hirschsprung's Disease (HD) and Intestinal Neuronal Dysplasia type B (IND-B) are considered to be similar, part of the same clinical spectrum. However, there are no studies that have investigated the potential differences between the clinical manifestations presented by patients with HD and with IND-B. We decided to compare the clinical manifestations presented by patients with HD and with IND-B at the time of establishing the etiologic diagnosis. Patients and methods: A single-center, retrospective, analytical, comparative study was performed. We included 119 patients aged 0 to 15 years, who had been diagnosed with HD or IND-B by histopathological analysis of rectal biopsies from 1998 to 2010. Information from the medical records of these patients was retrieved to obtain demographic and clinical information present at the time of diagnosis. The data were compared statistically, according to the characteristics of the variables, using the Fischer, Chi-square with Yates correction, Binomial, Mann-Whitney and Student's t tests. The significance level was 5%. The study was approved by the local Ethics Committee. Results: 69 patients (58.0%) had been diagnosed with HD and 50 (42.0%) with IND-B. The HD group had significantly more individuals with symptom onset in the neonatal period (p = 0.001), delayed meconium clearance (p < 0.001), weight gain deficit (p = 0.02), and who evolved with acute complications such as enterocolitis (p = 0.049) or acute obstructive abdomen (p = 0.031), more commonly requiring emergency surgery (p < 0.001). Patients with IND-B were diagnosed at significantly older ages (p = 0.002) and more commonly had chronic constipation as their main symptom (p = 0.004), with local complications such as evacuative bleeding (p = 0.007). Conclusion: There were significant differences between the clinical picture presented by HD and IND-B patients at the time of etiologic diagnosis. Knowledge of the clinical picture most commonly presented for each of these etiologies has the potential to assist in directing the initial, diagnostic and therapeutic measures, which are individualized for each of these diseases.
Intestinal Neuronal Dysplasia type B (IND-B) is a pathological entity belonging to gastrointestinal neuromuscular diseases. The diagnosis of IND-B is based on the pathological analysis of rectal biopsies from patients with constipation, with signs of submucosal nerve plexus hyperplasia. The lack of definition about the causal relationship between histological findings and clinical symptoms has been pointed as the primary point that needs to be elucidated in the scientific investigation related to IND-B. This point seems to be the link still pending for the accurate characterization of IND-B as a disease and the definitive establishment of its diagnostic criteria and therapeutic possibilities. Objective: to investigate the association between the histopathological findings identified in patients with IND-B and the clinical symptoms present at the time of diagnosis. Methods: This is a single-center, retrospective, uncontrolled, descriptive, and analytical study. The Institution's Research Ethics Committee approved this study. We included 27 patients, aged between 0 and 15 years, who had received the diagnosis of IND-B, based on the pathological criteria proposed in the Frankfurt Consensus (1990), and who had undergone surgical treatment through extensive resections of the colon and rectum. We retrieved medical records to obtain data related to bowel habits present at the time of diagnosis, including the Intestinal Symptom Index (ISI), an index proposed to summarize the most common signs and symptoms in the clinical course of IND-B. Data from the detailed pathological analysis of the surgical specimens were also obtained. Exploratory factor analysis was performed, applying the principal components method for clusters with Varimax rotation. We established a cut-off point of 0.5 for factor loadings. The distribution of scores for the two factors determined was performed using a score chart. The significance level was 5%, and the analysis was performed using the SAS v software. 9.4. Results: Exploratory factor analysis allowed the investigation of the relationship between clinical symptoms and pathological features. This analysis determined two main factors, which explain almost half of the possible variations. Factor 1, responsible for most of the described variations, was composed of pathological variables and some clinical variables of severity, such as the need to perform intestinal washouts and the presence of bloody stools. Factor 2 was composed of the main symptoms, including ISI. After the factorial rotation procedure, we could identify an association between the main components of these two factors through graphic representation, showing the close relationships between the ISI values and the pathological alterations associated with IND-B, represented mainly by hypergangliosis. These components lead to the same direction in the graph, contributing to the same clinical meaning in the investigated relationships between symptoms and pathological alterations. Conclusion: There is an association between symptoms and pathological changes in IND-B, reinforcing the theory that IND-B is a disease with specific symptoms and organic changes in the gastrointestinal tract.
As manifestações clínicas da Doença de Hirschsprung (DH) e a Displasia Neuronal Intestinal tipo B (DNI-B) são consideradas como semelhantes, parte de um mesmo espectro clínico. No entanto, não há estudos que tenham investigado as potenciais diferenças entre as manifestações clínicas apresentadas por pacientes com DH e com DNI-B. Nós decidimos comparar as manifestações clínicas apresentadas por pacientes com DH e com DNI-B, no momento do estabelecimento do diagnóstico etiológico. Pacientes e métodos: Foi realizado um estudo de centro único, retrospectivo, analítico e comparativo. Foram incluídos 119 pacientes com idade entre 0 e 15 anos, que haviam recebido diagnóstico de DH ou DNI-B por meio da análise histopatológica de biópsias de reto, no período de 1998 a 2010. Foram recuperadas as informações dos prontuários médicos destes pacientes, para obtenção de informações demográficas e clínicas, presentes no momento do diagnóstico. Os dados foram comparados estatisticamente, de acordo com as características das variáveis, utilizando-se os testes de Fischer, Qui-quadrado com correção de Yates, Binomial, Mann-Whitney e T de Student. O nível de significância foi de 5%. O estudo foi aprovado pelo Comitê de Ética local. Resultados: 69 pacientes (58.0%) haviam recebido o diagnóstico DH e 50 (42.0%) o de DNI-B. O grupo DH apresentou um número significativamente maior de indivíduos com início dos sintomas no período neonatal (p = 0,001), atraso para eliminação de mecônio (p < 0,001), déficit para ganho de peso (p = 0,02), e que evoluíram com complicações agudas, como enterocolite (p = 0,049) ou abdome agudo obstrutivo (p = 0,031), necessitando mais comumente de cirurgias de urgência (p < 0,001). Os pacientes com DNI-B foram diagnosticados em idades significativamente maiores (p = 0,002) e mais comumente tiveram como principal sintoma, quadros crônicos de constipação intestinal (p = 0,004), com complicações locais como sangramento evacuatório (p = 0,007). Conclusão: Houve diferenças significativas entre o quadro clínico apresentado por pacientes com DH e com DNI-B no momento do diagnóstico etiológico. O conhecimento do quadro clínico mais comumente apresentado para cada uma destas etiologias tem potencial para auxiliar no direcionamento das medidas iniciais, diagnósticas e terapêuticas, que são individualizadas para cada uma destas doenças.
The clinical manifestations of Hirschsprung's Disease (HD) and Intestinal Neuronal Dysplasia type B (IND-B) are considered to be similar, part of the same clinical spectrum. However, there are no studies that have investigated the potential differences between the clinical manifestations presented by patients with HD and with IND-B. We decided to compare the clinical manifestations presented by patients with HD and with IND-B at the time of establishing the etiologic diagnosis. Patients and methods: A single-center, retrospective, analytical, comparative study was performed. We included 119 patients aged 0 to 15 years, who had been diagnosed with HD or IND-B by histopathological analysis of rectal biopsies from 1998 to 2010. Information from the medical records of these patients was retrieved to obtain demographic and clinical information present at the time of diagnosis. The data were compared statistically, according to the characteristics of the variables, using the Fischer, Chi-square with Yates correction, Binomial, Mann-Whitney and Student's t tests. The significance level was 5%. The study was approved by the local Ethics Committee. Results: 69 patients (58.0%) had been diagnosed with HD and 50 (42.0%) with IND-B. The HD group had significantly more individuals with symptom onset in the neonatal period (p = 0.001), delayed meconium clearance (p < 0.001), weight gain deficit (p = 0.02), and who evolved with acute complications such as enterocolitis (p = 0.049) or acute obstructive abdomen (p = 0.031), more commonly requiring emergency surgery (p < 0.001). Patients with IND-B were diagnosed at significantly older ages (p = 0.002) and more commonly had chronic constipation as their main symptom (p = 0.004), with local complications such as evacuative bleeding (p = 0.007). Conclusion: There were significant differences between the clinical picture presented by HD and IND-B patients at the time of etiologic diagnosis. Knowledge of the clinical picture most commonly presented for each of these etiologies has the potential to assist in directing the initial, diagnostic and therapeutic measures, which are individualized for each of these diseases.
Descrição
Palavras-chave
Doença de Hirschsprung, Displasia Neuronal Intestinal tipo B, Histopatológicos, Diferenças Clínicas, Doenças neuromusculares, Constipação intestinal, Reto - Biópsia, Histopatologia