Doença imunoproliferativa do intestino delgado: estudo clínico prospectivo de casuística

Exportado OPUSMade available in DSpace on 2019-08-11T21:02:58Z (GMT). No. of bitstreams: 1 maria_de_lourdes_de_abreu_ferrari.pdf: 1107320 bytes, checksum: a96859e429c968b7022c4a30bc011a56 (MD5) Previous issue date: 14Trata-se de estudo clínico, prospectivo, no qual 24 pacientes com doença imunoproliferativa do intestino delgado (DIPID), selecionados dentre a clientela assistida em centro de referência para doenças gastroenterológicas, no Hospital das Clínicas da UFMG, foram acompanhados durante o período de 1988 a 2004. O estudo teve comoobjetivo investigar as características clínicas, laboratoriais e alguns aspectos epidemiológicos, bem como avaliar a resposta terapêutica e a concordância entre amostras de intestino delgado, obtidas por endoscopia digestiva alta, cápsula de biópsia jejunal peroral e laparotomia, no estadiamento histológico da doença. Houve discretapredominância do sexo feminino (54,2%). A média de idade foi de 33 ± 11,8 anos e a mediana de 33,5 anos. Quanto à cor, 15 (62,5%) eram não brancos e nove (37,5%) brancos. A doença predominou na população de baixo nível sócio-econômico e residente na periferiadas cidades. Utilizando-se os critérios para estadiamento histológico proposto por Galian et al.92, cinco (20,8%) pacientes estavam no estádio A, cinco (20,8%) no B e 14 (58,3%) no C. As manifestações clínicas foram constantes, predominando emagrecimento (95,8%),diarréia (91,7%), dor abdominal (87,5%) e baqueteamento digital (75,0%). Embora a freqüência dessas manifestações tenha sido semelhante nos três estádios, estas se mostraram mais exuberantes nos estádios B e C. Os exames hematológicos e bioquímicosnão se constituíram em exames diagnósticos, mas traduziram a repercussão sistêmica da doença e mostraram-se úteis na avaliação da resposta ao tratamento. As alterações mais freqüentes foram: hipoalbuminemia (83,3%), anemia (62,5%), velocidade dehemossedimentação acelerada (59,2%) e hipocalcemia (54,2%). Esteatorréia foi observada em 77,8% dos casos e a freqüência das infecções por parasitos intestinais, não foi superior àquela observada nos levantamentos populacionais brasileiros. A imunoeletroforese do soro permitiu a identificação de cadeia a-pesada em quatro pacientes do estádio C e de cadeia .- pesada em sete casos, distribuídos pelos três estádios. A imuno-histoquímica da mucosa intestinal permitiu o diagnóstico da forma não secretora da doença de cadeia a-pesada emtrês casos e, em dois, de cadeia .-pesada. O aspecto endoscópico do duodeno foi sugestivo de DIPID em 65% dos casos; nódulos (45%) e ulcerações rasas (15%) foram os padrões mais freqüentemente observados. Trânsito intestinal mostrou-se alterado em todospacientes e configurou-se em exame de grande valor na suspeita diagnóstica. Aspecto nodular (100%), alargamento das pregas da mucosa (79,2%) e irregularidades na periferia da mucosa (41,7%) foram mais freqüentes e mais evidentes nos estádios B e C. Vinte (83,3%) pacientes foram submetidos ao estadiamento cirúrgico. Linfadenomegalia mesentérica (90%), seguida por espessamento (75%) e nódulos (40%) das paredes jejunais, foram as alterações mais comumente observadas. O aspecto histológico da mucosa intestinal, à semelhança do descrito por outros autores, caracterizou-se por denso e difuso infiltrado celular, composto por linfócitos e plasmócitos, levando a desorganização da arquitetura estrutural da mucosa. Atipias celulares e a profundidade variável do infiltrado celular, permeando as diferentes camadas da parede intestinal, foram aspectos característicos dos estádios B e C. Amostras da segunda porção duodenal, obtidas porprocedimento endoscópico, foram diagnósticas em 44,4% dos pacientes, nos estádios B e C. A biópsia jejunal peroral mostrou-se muito útil no diagnóstico e na avaliação da resposta terapêutica, tendo permitido o diagnóstico em 100% dos casos. O material obtido porlaparotomia confirmou o diagnóstico em todos os pacientes e constituiu-se no padrão ouro para o estadiamento histológico. A concordância dos três métodos usados na obtenção das amostras da mucosa intestinal para estadiamento histológico da doença foi avaliada por meio do teste Kappa. Considerando-se os três estádios em conjunto, as biópsias duodenal e jejunal peroral foram pouco concordantes com os resultados da laparotomia. No entanto, boa concordância foi observada na comparação da biópsia jejunal peroral e laparotomia, quando se analisaram em conjunto os estádios B e C. Esse resultado levanta o questionamento da necessidade do procedimento cirúrgico, quando a amostra obtida por biópsia jejunal peroral permite a classificação da doença em um desses dois estádios.Quatro pacientes do estádio A foram tratados com tetraciclina e o outro não recebeu tratamento, pois evoluiu para óbito não relacionado a DIPID. A remissão completa (RC) foi observada em 66,7% desses casos, enquanto remissão parcial (RP) foi obtida em 33,3%.Praticamente, todos pacientes dos estádios B e C receberam ciclosfosfamida, vincristina, prednisona e adriamicina (CHOP) e/ou CHOP acrescido do sulfato de bleomicina. RC foi alcançada em 75% dos casos no estádio B e em 45,5% daqueles no C; RP em 9,1% dospacientes no estádio C; e fracasso terapêutico ocorreu em 25% dos indivíduos do estádio B e em 45,5% dos pacientes no estádio C. A taxa de sobrevida em cinco anos foi de 100% para o estádio A, 75% para o B, e 55% para os casos no estádio C. Ao término do estudo 66,6% dos pacientes encontravam-se vivos. Todos os óbitos ocorreram antes dos 60 meses de acompanhamento. Em nove pacientes a doença de cadeia .-pesada manifestou-se pelo acometimento primário do intestino delgado. Freqüência esta que se mostrou superior àquela referida na literatura.This investigation refers to a prospective clinical study that included 24 patients with immunoproliferative small intestinal disease (IPSID), who were followed up from 1988 to 2004. These patients were selected among those attended in the reference center for gastrointestinal diseases at the University Hospital, Federal University of Minas Gerais,Belo Horizonte, Brazil. The study aimed at the investigation of the clinical and laboratorial characteristics of the disease, some of its epidemiological aspects, the response to treatment, as well as the analysis of the agreement of the histopathological findings observed in the samples of the small bowel obtained by three different ways: upperdigestive endoscopy, peroral jejunal biopsy and laparotomy, in staging the IPSID. The results related to demographic dada showed mild predominance in women (54.2%); mean age of 33 ± 11.8 years and median age of 33.5 years; and moderate predominance in nonwhite(62.5%). The disease was more frequent in the lower social economic class, which includes people who live in the periphery of the cities. Using the criteria for histological staging proposed by Galian et al.92, five (20.8%) patients were in stage A; five (20.8%), in B; and 14 (58.3%), in C. The clinical manifestations were very constant, and the most frequent were: weight loss (95.8%), diarrhea (91.7%), abdominal pain (87.5%), and clubbing fingers (75.0%). The frequency of these manifestations was similar in the three stages, however they were more exuberant in the stages B and C. The hematological and biochemical exams were devoided of diagnostic value; nonetheless they correlated with thesystemic repercussion of the IPSID and proved useful in evaluating the response to the treatment. The most frequent abnormalities were: hypoalbuminemia (83.3%), anemia (62.5%), raised erythrocyte sedimentation rate (59.2%), and hypocalcemia (54.2%). Steatorrhea was observed in 77.8% of the patients, and the frequency of infections byintestinal parasites in these individuals was similar to that observed in Brazilian population, in general. Immunoelectrophoresis performed in serum allowed the identification of the á- heavy chain in four patients belonged to the stage C, and of the ã-heavy chain in sevencases distributed among the three stages. The immunohistochemical staining of the intestinal mucosa permitted the diagnosis of the á-heavy chain non-secretory form of the disease in three cases, and of the ã-heavy chain, in two cases. The endoscopic aspect of theduodenum was suggested of IPSID in 65% of the patients; nodules (45%) and shallow ulcerations (15%) were the most frequent findings. Bowel series showed alterations in all of the patients and proved to be of great value in the approach of suspect cases. Nodules (100%), thickening of the mucosa (79.2%), and irregularity in the periphery of the mucosa (41.7%) were more frequent and more evident in the stages B and C. Twenty (83.3%) patients were submitted to surgical staging. Mesenteric lymphadenopathy (90%), followed by thickening (75%) and nodules (40%) of the jejunum wall were the most common alterations observed. The histopathological aspect of the intestinal mucosa, as described by other authors, was characterized by a dense and diffused cellular infiltration, formed by lymphocytes and plasmocytes, leading to the disruption of the normal architecture of the mucosa. Atypical cells and cellular infiltration involving the different layers of the intestinal wall were characteristic of the stages B and C. Samples from the second portionof the duodenum, obtained by endoscophy, were diagnostic in 44.4% of the cases included in the stages B or C. The peroral jejunum biopsy showed to be very useful in the diagnosis of IPSID and in the evaluation of its therapeutic response. This method provided the diagnosis in 100% of the cases. The material obtained by laparotomy confirmed thediagnosis in all of the patients and was the golden standard for the histophatological staging. The agreement of the three methods used for obtaining the samples of the intestinal mucosa for histological staging of the disease was evaluated by the Kappa test. Considering the three stages together, the duodenum and the peroral jejunum biopsies showed little agreement with the results of laparotomy. Even though, good agreement between the peroral jejunum biopsy and laparotomic findings was observed when considering the stages B and C together. This result raises the question of the necessity of the surgical procedure,when the sample obtained by peroral jejunum biopsy allows the classification of the disease in any of these two stages. Four patients included in stage A were treated with tetracycline whereas the fifth one did not receive any treatment, as he evolved to death not related toIPSID. Complete reemission (CR) was observed in 66.7% of the stage A cases, while partial remission (PR) was obtained in 33.3% of these patients. Virtually, all patients included in stages B and C received cyclophosphamide, vincristine, prednisone, and adriamycin (CHOP) and/or CHOP associated with bleomycin sulfate. CR was reached in75% of the individuals included in stage B, and in 45.5% of those included in stage C; PR was observed in 9.1% of the patients belonged to stage C; and therapeutic failure occurred in 25% of the cases classified as stage B, and in 45.5% of those classified as stage C. Theoverall survival rate in five years was of 100% for stage A, 75% for stage B, and 55% for the cases included in stage C. At the end of the study 66.6% of the patients were alive. All the deaths occurred within the first 60 months of the follow up. In nine patients, the ã-heavy chain disease presented the involvement of the small bowel as the first manifestation. This frequency is higher than that referred in the literature

Intestinal permeability in leukemic patients prior to chemotherapy

Objective:The objective of this study was to evaluate the intestinal barrier function in leukemia patients before the start of the chemotherapy with an intestinal permeability test using lactulose and mannitol as markers.Methods:The study enrolled 20 patients diagnosed with leukemia (acute and chronic). Ten healthy volunteers were also submitted to the test as a control group.Results:The median lactulose/mannitol ratio was 0.019 for the Leukemia Patient Group, whereas in healthy controls the median was 0.009 (p-value = 0.244). The median lactulose/mannitol ratio in acute leukemia patients was 0.034 giving a p-value of 0.069 when compared to healthy controls. This same comparison was made between acute myeloid leukemia patients and healthy controls with a p-value of 0.149. There was no significant difference in the intestinal permeability between acute and chronic leukemia patients (p-value = 0.098).Conclusion:The intestinal barrier function measured using the intestinal permeability test was similar in leukemic patients overall and healthy controls, but a tendency toward a different pattern was found in the intestinal barrier function of acute leukemia patients

Whipple's disease. Report of five cases with different clinical features

A Doença de Whipple (DW) é doença sistêmica rara, de etiologia infecciosa, que acomete o intestino delgado, mas pode afetar virtualmente qualquer órgão. Apresentamos cinco casos com idade que variou entre 20 e 59 anos, sendo quatro do sexo masculino e um feminino. Todos tinham em comum o comprometimento intestinal, associado ou não às manifestações clínicas ligadas a esse orgão. Em uma paciente, foi observada vegetação na válvula tricúspide, sugerindo endocardite pelo Tropheryma whippelii, com desaparecimento das alterações ecocardiográficas após o tratamento. Em um dos pacientes do sexo masculino, o quadro clínico inicial foi de espondilite sorológica negativa e, em momento algum de sua evolução observou-se diarréia. Acometimento ocular associado à mabsorção intestinal e emagrecimento significativo foi evidenciado em um caso. Nos outros dois, a diarréia foi a manifestação clínica principal. Em todos, o diagnóstico foi feito através do estudo histológico por microscopia ótica e eletrônica da mucosa jejunal e, quando indicado, de tecidos extra-intestinais. Após o tratamento com antibioticoterapia, houve remissão completa dos sintomas, em todos os casos. O controle realizado através da microscopia eletrônica de mucosa jejunal, após doze meses de tratamento com sulfametoxazol-trimetropim, mostrou em quatro, o desaparecimento do T. whippelii. O outro paciente abandonou o seguimento.Whipple's disease (WD) is a rare systemic disease of infectious etiology which involves the small intestine but can virtually affect any organ. We present here five cases (four males and one female) ranging in age from 20 to 59 years. All patients had intestinal involvement associated or not with clinical manifestations linked to this organ. Vegetation in the tricuspid valve was observed in one patient, suggesting endocarditis caused by Tropheryma whippelii, with disappearance of the echocardiographic alterations after treatment. In one of the male patients the initial clinical manifestation was serologically negative spondylitis, with no diarrhea occurring at any time during follow-up. Ocular involvement associated with intestinal malabsorption and significant weight loss were observed in one case. In the other two cases, diarrhea was the major clinical manifestation. All patients were diagnosed by histological examination of the jejunal mucosa and, when indicated, of extraintestinal tissues by light and electron microscopy. After antibiotic treatment, full remission of symptoms occurred in all cases. A control examination of the intestinal mucosa performed after twelve months of treatment with sulfamethoxazole-trimethoprim revealed the disappearance of T. whippelii in four patients. The remaining patient was lost to follow-up

Correlation of endoscopic and histological features in adults with suspected celiac disease in a referral center of Minas Gerais, Brazil.

Context - Clinical presentation of celiac disease is extremely variable and the diagnosis relies on serologic tests, mucosal intestinal biopsy and clinic and serologic response to a gluten-free diet. Objectives - To correlate the endoscopic and histological aspects of adult patients with suspicion of celiac disease and to evaluate the interobserver histological agreement. Method - Endoscopic aspects of 80 adult patients were evaluated and correlated with the histological features according the Marsh-Oberhuber classification system. The interobserver histological agreement was based on kappa values. Results - The symptoms of the patients varied largely, with prominence for chronic diarrhea, present in 48 (60%) patients. The endoscopic aspects related with the duodenal villous atrophy had been observed in 32 (40%) patients. There were confirmed 46 cases of celiac disease, with prevalence of 57.5%. The sensitivity, specificity, positive predictive value and negative predictive value of the endoscopic markers for celiac disease diagnosis were of 60.9%, 88.2%, 87.5% and 62.5%. There was moderate interobserver histological agreement (kappa = 0.46). Conclusions - The endoscopic markers of villous atrophy, although not diagnostic, had assisted in the suspicion and indication of the duodenal biopsies for diagnosis proposal. Histology is sometimes contradictory and new biopsies or opinion of another professional can provide greater diagnostic agreemen

Evaluation of inflammatory activity in Crohn’s disease and ulcerative colitis

Crohn’s disease and ulcerative colitis evolve with a relapsing and remitting course. Determination of inflammatory state is crucial for the assessment of disease activity and for tailoring therapy. However, no simple diagnostic test for monitoring intestinal inflammation is available. Noninvasive markers give only indirect assessments of disease activity. Histopathological or endoscopical examinations accurately assess inflammatory activity, but they are invasive, time consuming and expensive and therefore are unsuitable for routine use. Imaging procedures are not applicable for ulcerative colitis. The usefulness of ultrasound and Doppler imaging in assessing disease activity is still a matter of discussion for Crohn’s disease, and an increased interest in computed tomography enterograph (CTE) has been seen, mainly because it can delineate the extent and severity of bowel wall inflammation, besides detecting extraluminal findings. Until now, the available data concerning the accuracy of magnetic resonance enterography in detecting disease activity is less than CTE. Due to this, clinical activity indices are still commonly used for both diseases

Montreal classification of patient operated for Crohn's disease and identification of surgical recurrence predictors

OBJECTIVE: to evaluate Crohn's disease recurrence and its possible predictors in patients undergoing surgical treatment. METHODS: We conducted a retrospective study with Crohn's disease (CD) patients undergoing surgical treatment between January 1992 and January 2012, and regularly monitored at the Bowel Clinic of the Hospital das Clínicas of the UFMG. RESULTS: we evaluated 125 patients, 50.4% female, with a mean age of 46.12 years, the majority (63.2%) diagnosed between 17 and 40 years of age. The ileum was involved in 58.4%, whereas stenotic behavior was observed in 44.8%, and penetrating, in 45.6%. We observed perianal disease in 26.4% of cases. The follow-up average was 152.40 months. Surgical relapse occurred in 29.6%, with a median time of 68 months from the first operation. CONCLUSION: The ileocolic location, penetrating behavior and perianal involvement (L3B3p) were associated with increased risk of surgical recurrence