Emergency removal of transplanted graft due to the failure of clinical treatment of serious acute rejection in case of small bowel transplantation: case report

Introduction: Intestinal transplantation is a complex procedure that has become more common in recent years. It can be performed isolated or with other organs of the digestive tract, which characterizes a multivisceral transplantation. Its indication mainly involves patients with irreversible intestinal failure, submitted or not to an enterectomy, and who have complications from parenteral nutrition. Among the main difficulties after transplantation is the immunosuppressive therapy, since the small intestine is an extremely immunogenic organ. Insufficient immunosuppression may cause graft rejection, but excessive immunosuppression may lead to Graft vs. Host Disease, where the intestine’s own immune cells attack Host organs. In Brazil, however, the practical experience with this type of surgery and with the management of immunosuppressive therapy is restricted because of the reduced number of small bowel transplants performed. Objective: To report a case of small bowel transplantation with graft rejection and necessity of surgical removal of the graft. Case Report: A male patient, 21 years old, presented a complicated acute appendicitis in July 2015, being submitted to appendectomy and right colectomy. After the operation, he developed thrombosis and intestinal infarction. This complication affected more than 90% of the patient’s small bowel, requiring extensive enterectomy. The patient developed short bowel syndrome and relied on parenteral nutrition. After 7 months in the home parenteral nutrition regimen, the patient underwent small bowel transplantation due to complications of parenteral nutrition. Immunosuppressive therapy was based on the use of tacrolimus. The patient presented no intercurrences until the 6th postoperative month, when he developed systemic histoplasmosis, staying 33 days in the intensive care unit. He presented resolution of the condition with itraconazole. At the 18th postoperative month, he was admitted with fever and intense diarrhea. The ileoscopy examination showed intestinal ulcers and loss of villi. Graft biopsies were consistent with severe acute T cell mediated rejection. The patient was transferred to our institution to treat the rejection. The combined use of increased tacrolimus, pulse therapy with methylprednisolone, use of thymoglobulin and use of monoclonal antibody against tumor necrosis factor alpha were not effective. The patient`s general condition deteriorated and he had to be submitted to urgent removal of the transplanted graft. The patient returned to the parenteral nutrition regimen and underwent reconstruction of the digestive tract with anastomosis between jejunum and transverse colon 5 months after grafting. Currently, he is in outpatient follow-up using home parenteral nutrition

Acute graft versus host disease after liver transplantation. Do we have an option for treatment of steroid-refractory forms?

Introdução: A forma aguda da doença do enxerto contra o hospedeiro ocorre geralmente até oito semanas após o transplantede fígado, é rara, porém tem mortalidade alta e constitui-se em um grande desafio terapêutico principalmente naqueles casos que são resistentes ao tratamento com corticóides. Objetivo: Discutir a patogênese, tratamento e resultados a longo prazo da Forma Aguda da Doença Enxerto contra o Hospedeiro após Transplante de Fígado. Métodos: Fizemos uma pesquisa na base de dados do PubMed procurando identificar todos os casos de doença Enxertocontra o Hospedeiro após Transplante de Fígado incluindo adultos com mais de 19 anos e crianças. Resultados: Revisamos 102 casos desta doença e encontramos 96 (94,1%) adultos e 6 (5,8%) crianças. Após o tratamento, 24 (25%) adultos e 3 (50%) crianças estavam vivos. Com relação ao tratamento da doença do enxerto contra o hospedeiro em adultos e crianças encontramos respectivamente: globulina anti-timocítica + prednisolona – 19 (19,5%); bloqueador do receptor da interleucina 2 – 17 (17,5%); OKT3 – 12 (12,3%); ciclosporina – 9 (9,2%); outros – 39 (40,2%) e em crianças globulina anti-timocítica – 1 (20%); globulina anti-timocítica + prednisolona – 1 (20%); prednisolona – 1 (20%); globulinaanti-timocítica + prednisolona + bloqueador do receptor da interleucina 2 -1 (20%); não mencionado – 1. Conclusão: Pesquisas devem ser aprofundadas nos mecanismos que desencadeiam esta patologia. Não existe consenso para o tratamento da doença do enxerto contra o hospedeiro após o transplante de fígado naqueles doentes que são refratários ao uso de esteróides.Background: Acute graft-versus-host disease (GVHD) usually occurs by 8 weeks after liver transplantation (LT) usually is an uncommon complication but has both high mortality and major diagnostic challenge in addition most of them are associated with resistance to steroid therapy. Objective: Discuss the pathogenesis, treatment and long-term results of Acute Graft versus Host Diseaseafter Liver Transplantation. Methods: A PubMed search was performed to identify all reported cases of GVHD following LT. The medical subject heading GVHD disease was used in combination with LT, including adults (19 + years) and children. The bibliographiesof the articles found though PubMed were then searched for further reports of GVHD. Results: We reviewed 102 cases of acute GVHD, 96 (94.1%) adults and 6 (5.8%) children. After treatment24 (25%) adults and 3 (50%) children were alive only. As far as the treatment of GVHD is concern the therapy used in adults and in children patients was respectively : anti-thymocyte globulin + prednisolone – 19 (19.5%); interleukin-2 receptor blocker – 17 (17.5%); OKT3 – 12 (12.3%); cyclosporine – 9 (9,2% ); others – 39 (40.2%) and in children anti-thymocyte globulin – 1 (20%); anti-thymocyte globulin + prednisolone – 1 (20%); prednisolone – 1 (20%); anti-thymocyte globulin + prednisolone + interleukin-2 receptor blocker-1 (20%); not mentioned – 1.There was no standard treatment of acute GVHD for both children and adults. Conclusion: Although acute GVHD following LT is rare complication and mortalityis still very high, there is no consensus for the treatment of steroid-refractory forms. Further researches are needed to provide new approach for treating effectively such condition

Review of experimental models for inducing hepatic cirrhosis by bile duct ligation and carbon tetrachloride injection Revisão de modelos experimentais de cirrose hepática induzida por ligadura do ducto biliar e por injeção de tetracloreto de carbono

PURPOSE: To present a review about a comparative study of bile duct ligation versus carbon tetrachloride Injection for inducing experimental liver cirrhosis. METHODS: This research was made through Medline/PubMed and SciELO web sites looking for papers on the content "induction of liver cirrhosis in rats". We have found 107 articles but only 30 were selected from 2004 to 2011. RESULTS: The most common methods used for inducing liver cirrhosis in the rat were administration of carbon tetrachloride (CCl4) and bile duct ligation (BDL). CCl4 has induced cirrhosis from 36 hours to 18 weeks after injection and BDL from seven days to four weeks after surgery. CONCLUSION: For a safer inducing cirrhosis method BDL is better than CCl4 because of the absence of toxicity for researches and shorter time for achieving it.<br>OBJETIVO: Apresentar revisão sobre estudo comparativo da indução de cirrose hepática (CH) experimental com a injeção de tetra-cloreto de carbono (CCl4) comparado à ligadura do ducto biliar (BDL). MÉTODOS: A pesquisa foi realizada nas bases de dados do Medline/PubMed e SciELO procurando trabalhos com as palavras indução de CH e ratos. Foram encontrados 107 artigos, mas somente 30 foram selecionados no período de 2004 à 2011. RESULTADOS: Os procedimentos mais comum para indução de CH em ratos foram a injeção de CCl4 e a BDL. O CCl4 induzia CH no período de 36 horas após a injeção e a DBL de sete dias à quatro semanas após a cirurgia. CONCLUSÃO: A BDL é o método mais seguro para indução de CH quando comparado a injeção de CCl4 pela ausência de toxicidade para os pesquisadores e o menor tempo para se obter a lesão hepática

Sevoflurane Preconditioning plus Postconditioning Decreases Inflammatory Response with Hemodynamic Recovery in Experimental Liver Ischemia Reperfusion

Objective. The inhalation anesthetic sevoflurane has presented numerous biological activities, including anti-inflammatory properties and protective effects against tissue ischemic injury. This study investigated the metabolic, hemodynamic, and inflammatory effects of sevoflurane pre- and postconditioning for short periods in the rescue of liver ischemia-reperfusion (IR) injury using a rat model. Materials and Methods. Twenty Wistar rats were divided into four groups: sham group, control ischemia group (partial warm liver ischemia for 45 min followed by 4 h of reperfusion), SPC group (administration of sevoflurane 2.5% for 15 min with 5 min of washout before liver IR), and SPPoC group (administration of sevoflurane 2.5% for 15 min before ischemia and 20 min during reperfusion). Results. All animals showed a decrease in the mean arterial pressure (MAP) and portal vein blood flow during ischemia. After 4 h of reperfusion, only the SPPoC group had MAP recovery. In both the SPC and SPPoC groups, there was a decrease in the ALT level and an increase in the bicarbonate and potassium serum levels. Only the SPPoC group showed an increase in the arterial blood ionized calcium level and a decrease in the IL-6 level after liver reperfusion. Therefore, this study demonstrated that sevoflurane preconditioning reduces hepatocellular injury and acid-base imbalance in liver ischemia. Furthermore, sevoflurane postconditioning promoted systemic hemodynamic recovery with a decrease in inflammatory response