RESUMO
Celiac disease, an immune-mediated enteropathy induced in genetically susceptible individuals by the ingestion of gluten, is the most frequent disorder associated with splenic hypofunction or atrophy. Defective splenic function affects more than one-third of adult patients with celiac disease, and it may predispose to a higher risk of infections by encapsulated bacteria and thromboembolic and autoimmune complications, particularly when celiac patients have concomitant pre-malignant and malignant complications (refractory celiac disease, ulcerative jejunoileitis and enteropathy-associated T-cell lymphoma). However, the clinical management of patients with celiac disease does not take into account the evaluation of splenic function, and in patients with high degree of hyposplenism or splenic atrophy the prophylactic immunization with specific vaccines against the polysaccharide antigens of encapsulated bacteria is not currently recommended. We critically re-evaluate clinical and diagnostic aspects of spleen dysfunction in celiac disease, and highlight new perspectives in the prophylactic management of infections in this condition.
Assuntos
Doença Celíaca/diagnóstico , Baço/fisiopatologia , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Linfócitos B/citologia , Doença Celíaca/fisiopatologia , Suscetibilidade a Doenças/fisiopatologia , Glutens/metabolismo , Humanos , Imunoglobulina M/metabolismo , Memória Imunológica , Vacinas Pneumocócicas/uso terapêutico , Esplenopatias/complicações , Esplenopatias/diagnóstico , Linfócitos T Reguladores/citologia , Tromboembolia/complicações , Tromboembolia/diagnósticoRESUMO
Tissues exposed to ischemia and reperfusion develop an inflammatory response. We investigate the morphological and immunological changes occurring in the mucosa of a jejunal loop transplanted in the oropharynx of a man undergoing circular pharyngolaryngectomy. Jejunal biopsies were collected during the transplantation procedures (cold and warm ischemia, reperfusion), during the 7 post-operative days through an exteriorized jejunal segment for flap monitoring, and 45 days after transplantation through an upper endoscopy. Matrix metalloproteinase (MMP)-3 and MMP-12 increase was accompanied by a parallel rise in apoptotic enterocytes, and by a concomitant reduction of surface area to volume ratio and enterocyte height. Goblet cell hyperplasia is coupled with Paneth cell disappearance at the crypt base. CD8-positive intraepithelial lymphocytes initially decrease, then they increase in accordance with the peak of enterocyte apoptosis. We identified alterations in lymphocyte infiltration, mucosal architecture and epithelial cell turnover, which may give a window to mechanisms of small bowel ischemia-reperfusion in humans.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Jejuno/transplante , Neoplasias Faríngeas/cirurgia , Seio Piriforme/cirurgia , Traumatismo por Reperfusão/patologia , Anastomose Cirúrgica , Apoptose , Western Blotting , Proliferação de Células , Feminino , Humanos , Imuno-Histoquímica , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/patologia , Jejuno/irrigação sanguínea , Laringectomia , Pessoa de Meia-Idade , Faringectomia , Procedimentos de Cirurgia Plástica , Retalhos Cirúrgicos/irrigação sanguínea , Técnicas de SuturaRESUMO
BACKGROUND: Refractory celiac disease (RCD) is a preneoplastic condition as many patients develop an enteropathy-type T-cell lymphoma, a mature T-cell receptor α-ß lymphoma arising in the gut with an ominous outcome. Recently, research focused on a population of intraepithelial intestinal lymphocytes expressing the same lymphoma T-cell receptor variable region (V)γ, as shown by polymerase chain reaction (PCR) analysis and sequencing. Meanwhile, the Biomedicine and Health-2 Concerted Action has made available standardized, highly specific, and sensitive PCR assays not only for Vγ but also for Vß. GOALS: We verified whether analyzing both rearrangements in duodenal biopsies from RCD patients increases the diagnostic accuracy of this method. STUDY: Duodenal biopsies were analyzed from 15 RCD patients, 21 negative controls, and 2 positive controls (enteropathy-type T-cell lymphoma complicating celiac disease). Multiplex clonality analyses were performed according to the Biomedicine and Health-2 protocols. PCR products were cloned and sequenced. RESULTS: Monoclonal rearrangements were found in 5/15 samples from patients with RCD (both rearrangements in 2 cases, Vß only in 2, and only 1 solitary Vγ clonality). Monoclonality was found in 4/8 of the RCD patients who subsequently died, whereas only 1/7 of the patients still alive presented a monoclonal rearrangement. Positive controls revealed both monoclonal rearrangements; rearrangements were not detected in 20 of 21 negative controls. Sequencing of the amplified fragments confirmed the results. CONCLUSIONS: The combined analysis of both rearrangements allowed recognition of monoclonal populations in otherwise negative patients, with detection rates from 20% (Vγ only) to 33% (Vγ and Vß), thus raising the likelihood of early identification of RCD patients at high risk of death.
Assuntos
Doença Celíaca/complicações , Doença Celíaca/diagnóstico , Duodeno/imunologia , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T/genética , Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T/genética , Linfoma de Células T/complicações , Linfoma de Células T/diagnóstico , Adolescente , Adulto , Biópsia , Doença Celíaca/imunologia , Doença Celíaca/patologia , Duodeno/metabolismo , Duodeno/patologia , Feminino , Humanos , Linfoma de Células T/imunologia , Linfoma de Células T/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Valor Preditivo dos Testes , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/genética , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Análise de Sequência de DNA , Adulto JovemAssuntos
Carcinoma de Células Pequenas/patologia , Síndrome de Cushing/etiologia , Neoplasias Pulmonares/patologia , Síndrome Nefrótica/etiologia , Síndromes Paraneoplásicas/etiologia , Hormônio Adrenocorticotrópico/metabolismo , Idoso , Síndrome de Cushing/patologia , Humanos , Masculino , Síndrome Nefrótica/patologia , Síndromes Paraneoplásicas/patologiaRESUMO
Bortezomib is the first anticancer proteasome inhibitor introduced into clinical practice. It has been recently approved for the treatment of multiple myeloma, an incurable plasma cell tumour that accounts for 10-15% of all haematologic malignancies and for approximately 20% of deaths. Gastrointestinal toxicity associated with the use of this drug is common but generally mild to moderate. Paralytic ileus in patients undergoing bortezomib treatment has been reported, although a definite attribution to bortezomib administration has not been established. We report a myeloma patient who developed severe paralytic ileus during bortezomib therapy, which presented in the context of progressive constipation without other known causes and which regressed promptly with medical management after drug cessation, suggesting a direct causal relationship. Awareness of the various potential gastrointestinal toxic effects of bortezomib is of relevance given the growing number of patients undergoing treatment with this important and effective new cancer drug.
Assuntos
Antineoplásicos/efeitos adversos , Ácidos Borônicos/efeitos adversos , Pseudo-Obstrução Intestinal/induzido quimicamente , Inibidores de Proteases/efeitos adversos , Pirazinas/efeitos adversos , Antineoplásicos/uso terapêutico , Ácidos Borônicos/uso terapêutico , Bortezomib , Humanos , Pseudo-Obstrução Intestinal/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Inibidores de Proteases/uso terapêutico , Pirazinas/uso terapêutico , RadiografiaRESUMO
BACKGROUND AND OBJECTIVES: High-dose melphalan with autologous peripheral blood stem cell transplantation (ASCT) is an effective treatment for systemic primary amyloidosis. This procedure is, however, associated with substantial toxicity and mortality, particularly if the heart is involved. Refined selection of patients suitable for transplantation and personalized adaptation of the doses of melphalan might improve the outcome. DESIGN AND METHODS: Twenty-two consecutive patients were selected for age, number of organ systems involved, heart and kidney function, and treated with risk-adapted melphalan conditioning. This was first-line therapy in 81% of cases. RESULTS: Fifty-five percent of the patients had amyloid involvement of two organ systems, with renal involvement predominant in half. Approximately 70% received full-dose melphalan. Toxicity was manageable and three transplant-related deaths (14%) occurred only in the early phase of the study. The median overall survival was 68 months. The intent-to-treat hematologic response rate was 55% at +12 months (complete, 36%; partial, 19%), which was accompanied by organ responses in 75%. Survival was positively influenced by: (i) hematologic response at +3 months (complete+partial responses 55%, median not reached, more than 108 months; no response, median 17 months) (p=0.001); (ii) amyloid involvement of a single organ system (p=0.016). Prolonged follow-up demonstrated that remissions are durable, but relapses may occur as 4 of 12 responsive patients (33%) relapsed, three from complete response, between +30 to +38 months. INTERPRETATION AND CONCLUSIONS: The present risk-adapted approach produced acceptable toxicity and peri-transplant mortality with prolonged survival in responsive patients. Additional therapy should be considered if no hematologic response is observed at +3 months after ASCT.