Microsurgical Technique and Results of Anorectal Transplantation in the Rat.

Anorectal transplantation (ART) is an obvious therapeutic option for treating permanent colostomy and severe fecal incontinence. The rat is the best model for beginning studies of a new surgical procedure. In this article, we review ART techniques in rats. METHODS: We reviewed articles on rat and ART keywords throughout Cochrane Library, MEDLINE, and EMBASE. Five articles were found, of which 2 used autotransplantations, 1 performed only transplantation of the anal canal and extraperitoneal rectum, and another performed transplantation of the entire intestine, including the anus, but only followed for 2 hours. RESULTS: In 2016, we performed the first series of isoART (n = 6) and alloART (n = 9) of the entire anorectal segment and micro-anastomosis of the inferior mesenteric vessels. Two animals died due to surgical complications, and the others survived until the endpoint of the experiment. Five animals with alloART showed clinical signs of immunologic rejection 3 weeks after transplantation, and autopsy histology on postoperative day 30 revealed moderate to severe rejection in the allografts. CONCLUSIONS: In this review, we observed that ART in rats is viable and may allow further physiologic and immunologic studies of this procedure, a potential treatment for severe incontinence and permanent colostomy.

Anatomic and Surgical Aspects of Total Pancreatectomy in Swine.

BACKGROUND: The swine is a valuable model for preclinical research and surgical technique training. Induction of Type I diabetes is achieved by total pancreatectomy, therefore these animals may be used in several research studies, including islet transplantation field. Given the lack of information in the literature, the purpose of this work is to describe anatomic aspects of swine pancreas, the total pancreatectomy surgical technique, intra- and postoperative complications and the autopsy results. MATERIAL AND METHODS: Five hybrid male pigs, 20-35 kg, submitted to total pancreatectomy with duodenum, bile duct, and spleen preservation. Postoperatively, daily clinical assessment and capillary blood glucose collection were performed. At the end of the 30-day period or in the occurrence of serious clinical complications, euthanasia and autopsy were performed. RESULTS: The average duration of surgery was 128 minutes, without intraoperative deaths or anesthesia induction failures. The median survival was 6.6 days. Postoperative complications were weight loss (3), emesis (2), constipation (2), abdominal distension (2), diarrhea (1), and loss of appetite (1). All animals were euthanized due to serious complications. Two animals presented surgical complications (duodenal necrosis with gastroparesis and internal hernia with intestinal necrosis). The other 3 animals presented serious clinical complications related to exocrine pancreatic insufficiency due to deficiency of pancreatic enzymes. Glycemic values above 200 mg/dL were found on the first postoperative day and above 300 mg/dL on the seventh day in all animals. CONCLUSION: A model of total pancreatectomy with duodenum, spleen, and bile duct preservation in pigs was established. All animals became diabetic, however, animals without postoperative complications were euthanized due to serious complications related to pancreas exocrine insufficiency.

Liver Transplantation for Adenomatosis: A Single-Center Experience.

BACKGROUND: Liver adenomatosis is characterized by multiple adenomas diffusely distributed throughout the liver parenchyma. Studies addressing liver transplantation for those cases are scarce, and the criteria used to indicate transplantation are still debatable. OBJECTIVE: To report a single-center experience of liver transplantation for diffuse adenomatosis. METHODS: Single-center retrospective study involving all adult patients who underwent liver transplantation due to adenomatosis from January/2010 to June/2023. RESULTS: A total of 13 patients were identified, corresponding to 0.89% of liver transplants performed during the study period. The mean age was 33 ± 6.55 years, and most of them were female (n = 9, 69.23%). There were 12 transplants with deceased donors and 1 with a right lobe from a living donor. The most frequent reason to preclude liver resection was multiple and large unresectable adenomas in patients without previous liver disease (n = 8, 61.58%), followed by underlying liver disease (Abernethy Malformation, n = 3, 23.07%) and recurrence after liver resection (n = 2, 15.38%). The indications for liver transplantation were high risk of malignant transformation (n = 7, 53.84%), increasing size and number of nodules (n = 3, 23.07%), confirmed malignant transformation (n = 2, 15.38%), and hemorrhage (n = 2, 15.38%). There was 1 perioperative death due to primary non-function. Another patient died during follow-up because of COVID-19. CONCLUSION: Liver adenomatosis is a rare indication for liver transplantation, with acceptable post-transplant outcomes. Unresectable adenomas with high-risk or confirmed malignant transformation are the main indications for transplant. Reasons for unresectability involve underlying liver disease, multiple and large high-risk nodules, and recurrence after previous resection.

En Bloc Simultaneous Liver-Kidney Transplantation Compared to the Traditional Technique: Results From a Single Center.

BACKGROUND: Simultaneous liver-kidney transplantation is indicated for patients with concomitant end-stage liver disease and end-stage renal disease. The traditional technique involves separate implantations of the liver and the kidney. In the en bloc approach, the liver is recovered en bloc with the right kidney and the donor renal artery is anastomosed to the donor splenic artery. We aimed to compare the outcomes of the traditional and en bloc techniques for simultaneous liver-kidney transplantation in a single center. METHODS: This single-center retrospective study involved all adult patients who underwent simultaneous liver-kidney transplantation from brain-dead donors from January 2017 to December 2022. RESULTS: A total of 15 patients were included: 10 transplanted with the traditional technique and 5 with the en bloc approach. Patients in the en bloc group presented higher body mass index, shorter kidney cold and total ischemia times, shorter overall surgical time and longer kidney warm ischemia time (29.07 kg/m2vs 23.20 kg/m2 [P = .048]; 560 minutes vs 880 minutes [P = .026]; 615 minutes vs 908 minutes [P = 0.025]; 405 minutes vs 485 minutes [P = .046]; 46 minutes vs 33.5 minutes [P = 0.027], respectively). Ureteroneocystostomy was performed in 2 patients of the en bloc group and ureteroureterostomy in the remaining 3 patients. One patient in the en bloc group presented stenosis of renal artery anastomosis and underwent percutaneous angioplasty. This same patient eventually developed late urinary fistula. In the traditional technique group, there were 2 cases of renal vein thrombosis and 1 of ureteral stenosis. CONCLUSIONS: Compared with the traditional technique, the en bloc approach is feasible and safe, reducing kidney total ischemia time and overall surgical time.

Liver Transplantation for Benign Massive Hepatomegaly: Results From a Single Center and Contribution of the Left-to-Right Piggyback Approach.

INTRODUCTION: Polycystic liver disease and giant hepatic hemangioma may present with severe symptom burden and indicate orthotopic liver transplantation. The left-to-right piggyback approach is a useful technique for performing total hepatectomy of enlarged livers. OBJECTIVE: The purpose of this study is to analyze the results of liver transplantation in patients with benign massive hepatomegaly. METHODS: This is a single-center retrospective study involving all adult patients who underwent liver transplantation due to benign massive hepatomegaly from January 2002 to June 2023. RESULTS: A total of 22 patients underwent liver transplantation (21 cases of polycystic live disease and 1 case of giant hepatic hemangioma). During the same time, there were 2075 transplants; therefore, benign massive hepatomegaly accounted for 1.06% of cases. Most patients (59.09%) were transplanted using the left-to-right piggyback technique. Seven patients had previous attempted treatment of hepatic cysts. Another patient previously underwent bilateral nephrectomy and living-donor kidney transplantation. Among these patients, in 5 cases there were massive abdominal adhesions with increased bleeding. Four of these 8 patients died in the very early perioperative period. In comparison to patients without previous cysts manipulation, massive adhesions and perioperative death were significantly higher in those cases (62.5 vs 0%, P = .002 and 50% vs 0%, P = .004, respectively). CONCLUSION: Liver transplantation due to polycystic liver disease and giant hemangioma is a rare event. Total hepatectomy is challenging due to the enlarged native liver. The left-to-right piggyback technique is useful, because it avoids vena cava twisting and avulsion of its branches. Massive adhesions due to previous cysts manipulation may lead to increased bleeding, being a risk factor for mortality.

Retransplantation for Late Hepatic Artery Thrombosis: Results from a Single Center.

BACKGROUND: Hepatic artery thrombosis is the most common vascular complication of liver transplantation. When occurring late in the postoperative course, it may have no clinical repercussions, and conservative treatment may be implemented. Some patients, however, will develop severe biliary complications due to ischemic cholangiopathy and require retransplantation. The aim of this study is to report the outcomes of retransplantation in this population. METHODS: This is a single-center retrospective study involving all adult patients who underwent liver retransplantation due to late hepatic artery thrombosis from January/2010 to December/2022. RESULTS: During the study period, 1378 liver transplants were performed in our center; 147 were retransplantations, with 13 cases of late hepatic artery thrombosis (0.94%). All had symptomatic ischemic cholangiopathy. Twelve of them had already presented previous cholangitis, bilomas, or liver abscesses and had undergone biliary stenting or percutaneous drainage. The median time between the first liver transplant and late hepatic artery thrombosis diagnosis and between this diagnosis and retransplantation were 73 and 50 days, respectively. Arterial reconstruction using splenic artery, celiac trunk, or arterial conduit from the aorta was performed in 7 cases, whereas biliary reconstruction was mostly done with choledochojejunostomy (n = 8). There were 4 perioperative deaths, 2 due to primary non-function and 2 due to refractory shock after exceedingly complex retransplants. CONCLUSION: Liver retransplantation due to late hepatic artery thrombosis is a rare condition that should be offered to patients who develop severe biliary complications and recurrent infections. It is nonetheless a challenging procedure associated with significant perioperative mortality.

Modelos pré-clínicos de câncer hepático / Preclinical models of liver câncer

ABSTRACT Background: This manuscript provides an overview of liver carcinogenesis in murine models of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Objective: A review through MEDLINE and EMBASE was performed to assess articles until August 2022. Methods: Search was conducted of the entire electronic databases and the keywords used was HCC, CCA, carcinogenesis, animal models and liver. Articles exclusion was based on the lack of close relation to the subject. Carcinogenesis models of HCC include HCC induced by senescence in transgenic animals, HCC diet-induced, HCC induced by chemotoxicagents, xenograft, oncogenes, and HCC in transgenic animals inoculated with B and C virus. The models of CCA include the use of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), thioacetamide (TAA), and carbon tetrachloride (CCl4). CCA murine models may also be induced by: CCA cells, genetic manipulation, Smad4, PTEN and p53 knockout, xenograft, and DEN-left median bile duct ligation. Results: In this review, we described different murine models of carcinogenesis that reproduce the key points for HCC and CCA genesis allowing a better understanding of its genetic, physiopathological, and environmental abnormalities. Conclusion: Each model has its advantages, disadvantages, similarities, and differences with the corresponding human disease and should be chosen according to the specificity of the study. Ultimately, those models can also be used for testing new anticancer therapeutic approaches.

RESUMO Contexto: Este manuscrito fornece uma visão geral da carcinogênese hepática em modelos murinos de carcinoma hepatocelular (CHC) e colangiocarcinoma (CCA). Objetivo: Realizar uma revisão de artigos científicos até agosto de 2022 utilizando as bases de dados MEDLINE e EMBASE. Métodos: A busca foi realizada em todas as bases de dados eletrônicas e as palavras-chave usadas foram CHC, CCA, carcinogenesis, modelos animais e fígado. A exclusão dos artigos baseou-se na falta de estreita relação com o assunto. Os modelos de carcinogênese do CHC incluíram: CHC induzido por senescência em animais transgênicos, CHC induzido por dieta, CHC induzido por agentes quimiotóxicos, xenoenxerto, oncogenes e CHC em animais transgênicos inoculados com vírus B e C. Os modelos de CCA incluíram: o uso de dimetilnitrosamina (DMN), dietilnitrosamina (DEN), tioacetamida (TAA) e tetracloreto de carbono (CCl4). Os modelos murinos de CCA induzidos por incluir: células de CCA, manipulação genética, animais nocaute para Smad4, PTEN e p53, xenoenxerto e ligadura do ducto biliar mediano esquerdo. Resultados: Nesta revisão, descrevemos diferentes modelos murinos de carcinogênese que reproduzem os pontos-chave para a gênese do CHC e do CCA, permitindo uma melhor compreensão de suas anormalidades genéticas, fisiopatológicas e ambientais. Conclusão: Cada modelo tem suas vantagens, desvantagens, semelhanças e diferenças com a doença humana correspondente e deve ser escolhido de acordo com a especificidade do estudo. Em última análise, esses modelos também podem ser utilizados para testar novas abordagens terapêuticas anticancerígenas.

Study of laser fluorescence spectroscopy in livers of rats with hypothermic ischemia

Purpose: After partial hepatectomy (PH), the remaining liver (RL) undergoes regenerative response proportional to the host. Limited literature exists on hepatic viability after tissue injury during hypothermic preservation. Spectroscopy measures cellular fluorescence and is explored for tissue characterization and parameter investigation. This study aimed to assess fluorescence analysis (spectroscopy) in evaluating liver viability and its relationship with hepatic tissue regeneration 24 hours after PH. Additionally, we analyzed liver regeneration in RL after 70% partial hepatectomy under hypothermic conditions with laser irradiation. Methods: Fifty-six Wistar rats were divided into four groups: total non-perfused liver (control), total perfused liver, partial hepatectomy "in situ", and partial hepatectomy "ex situ". Tissue analysis was performed at 0 and 24 hours using spectroscopy with laser devices emitting at 532 (green) and 405 nm (violet). Results: Spectroscopy identified tissue viability based on consistent results with Ki67 staining. The fluorescence spectra and Ki67 analysis displayed similar patterns, linking proliferative activity and absorption intensity. Conclusions: Fluorescence spectroscopy proves to be promising for real-time analysis of cellular activity and viability. Metabolic activity was observed in groups of live animals and hypothermically preserved samples, indicating cellular function even under blood deprivation and hypothermic conditions.

Experimental model of portal hypertension and esophagogastric varices in minipigs: pressure and endoscopic pilot study

Introduction: Portal hypertension still represents an important health problem worldwide. In the search for knowledge regarding this syndrome, experimental studies with animal models have proven to be useful to point the direction to be taken in future randomized clinical trials. Purpose: To validate the experimental model of portal hypertension and esophagogastric varices in a medium-sized animal. Methods: This study included five minipigs br1. Midline laparotomy with dissection of the portal vein and production of a calibrated stenosis of this vein was performed. Measurement of pressure in the portal venous and digestive endoscopic were performed before and five weeks after the production of a stenosis. Results: All animals were 8 months old, average weight of 17 ± 2.5 kg. The mean pressure of the portal vein immediately before the partial ligation of the portal vein was 8.9 + 1.6 mm Hg, with 26.6 + 5.4 mm Hg in the second measurement five weeks later (p < 0.05). No gastroesophageal varices or hypertensive portal gastropathy were seen at endoscopy procedures in our sample at any time in the study. Conclusion: Portal vein ligation in minipigs has been validated in the production of portal hypertension, but not in the formation of esophageal varices.

Attitude and knowledge of medical students toward donation after circulatory death

SUMMARY OBJECTIVE: A survey among medical students in a Brazilian public university was performed to investigate the acceptance of organ donation in Brazil, particularly donation after circulatory death (DCD). METHODS: A questionnaire including 26 objectives and Likert scale questions was validated and sent to all medical students of our institution. The answers were analyzed considering the whole set of individuals as well as by dividing the medical students into two groups: less graduated students and more graduated students. RESULTS: From 1050 students, 103 spontaneous answers (9.8%) were retrieved after 3 weeks. A total of 89.3% agreed totally with deceased donor organ donation and 8.7% agreed partially. However, only 50.5% of the students agreed totally and 31.1% agreed partially to living donation. Students revealed that 82.6% know the concept of brain death. On the other hand, 71.8% of them declared not knowing the concept of planned withdrawal of life-sustaining therapy, mainly cardiorespiratory support. A total of 85.4% of students agreed totally with donation after brain death and 11.7% agreed partially. However, when questioned about donation in awaiting circulatory death after a planned withdrawal of life-sustaining therapy, only 18.4% agreed totally and 32% agreed partially. Both groups of less and more graduated students showed similar results. CONCLUSIONS: Our study found a clear lack of information and consequently in acceptance of DCD. Education in the field of end-of-life management may improve not only the acceptance of DCD donation but also the whole understanding of planned withdrawal of life-sustaining therapy.

The effect of ileocecal valve removal in a model of short bowel syndrome / Efeito da remoção da válvula ileocecal em modelo de síndrome do intestino curto

ABSTRACT Background : Short bowel syndrome is a harmful condition that needs experimental research. Aim: To assess the impact of the ileocecal valve removal in a model of short bowel syndrome, in order to investigate the evolution of the colon under this circumstance. Method: Fifteen Wistar rats were equitable divided into: Control (Sham), Group I (70% enterectomy preserving ileocecal valve) and Group II (70% enterectomy excluding ileocecal valve). After enterectomy was performed jejunoileal or jejunocecal anastomosis and sacrificed the animals on 30th postoperative day for histomorphometric study of the colon. During this period, was observed the clinical evolution of the animals weekly including body weight measurement. Results: Group I and II presented progressive loss of weight. In Group I was observed diarrhea, perineal hyperemia and purple color of the colon during autopsy. Histomorphometry assay showed hypertrophy and hyperplasia of colon mucosa in Group I. In Group II the colon wall was thicker due to hypertrophy and muscular hyperplasia, and in mucosa vascular proliferation and inflammatory infiltrate were intense. Conclusion : This short bowel syndrome model is relevant and achieve 100% of survival. Animal's weight loss was not altered by the presence or exclusion of the ileocecal valve. Animals with 70% of small bowel removal and presence of the ileocecal valve attained a better clinical evolution and histological colon adaptation than those without ileocecal valve.

RESUMO Racional: Síndrome do intestino curto é condição clínica crítica e que precisa de pesquisa experimental. Objetivo: Avaliar o impacto da remoção da válvula ileocecal em um modelo de síndrome do intestino curto para investigar o comportamento do cólon nesta circunstância. Método: Quinze ratos Wistar foram divididos em três grupos de cinco: Controle (Sham), grupo I (enterectomia de 70% com preservação da válvula ileocecal), e grupo II (70% enterectomia de 70% excluindo a válvula ileocecal). Após a enterectomia foi restabelecido o trânsito com anastomose jejunoileal no grupo I e jejunocecal no grupo II. Os animais foram sacrificados no 30º dia do pós-operatório para histomorfometria do cólon. Durante este período, observou-se a evolução clínica semanal, incluindo a medição do peso corporal. Resultados: Grupos I e II apresentaram perda progressiva de peso. No grupo I houve diarreia, períneo hiperemiado e cor violácea do cólon durante a autópsia. A histomorfometria mostrou hipertrofia e hiperplasia da mucosa do cólon no grupo I. No grupo II a parede do cólon estava mais espessa devido à hipertrofia e hiperplasia das camadas muscular e mucosa onde a proliferação vascular e infiltração inflamatória foi intensa. Conclusão: Este modelo é factível e atingiu 100% de sobrevida. A perda de peso não foi alterada pela presença ou exclusão da válvula ileocecal. Animais com remoção de 70% do intestino delgado e presença da válvula ileocecal apresentaram melhor evolução clínica e adaptação histológica do cólon que os sem válvula ileocecal.

The liver injury following ischemia and reperfusion is worse in experimental knockout heterozygote mouse model for expression of connexin 43

Abstract Purpose: To evaluate that Connexin (Cx43) plays a role in lesions after hepatic ischemia/reperfusion (IR) injury. Methods: We use Cx43 deficient model (heterozygotes mice) and compared to a wild group. The groups underwent 1 hour ischemia and 24 hours reperfusion. The heterozygote genotype was confirmed by PCR. We analyzed the hepatic enzymes (AST, ALT, GGT) and histology. Results: The mice with Cx43 deficiency showed an ALT mean value of 4166 vs. 307 in the control group (p<0.001); AST mean value of 7231 vs. 471 in the control group (p<0.001); GGT mean value of 9.4 vs. 1.7 in the control group (p=0.001); histology showed necrosis and inflammation in the knockout group. Conclusions: This research demonstrated that the deficiency of Cx43 worses the prognosis for liver injury. The topic is a promising target for therapeutics advancements in liver diseases and procedures.

Transplante de intestino delgado / Small bowel transplantation

INTRODUÇÃO: O transplante de intestino delgado, em razão de sua complexidade, apresentou evolução mais lenta que os demais órgãos sólidos. Diversos avanços permitiram sua aplicação clínica. OBJETIVO: Revisão da evolução do transplante de intestino delgado e seu estado atual. MÉTODO: levantamento bibliográfico nas bases de dados MEDLINE e ScIELO. Os termos usados como descritores foram: intestinal failure, intestinal transplant, small bowel transplant, multivisceral transplant. Foram analisados dados sobre evolução histórica, centros, indicações, tipos de enxertos, seleção e captação de órgãos, manejo pós-operatório, complicações e resultados. CONCLUSÃO: Apesar de desenvolvimento mais lento, o transplante intestinal é hoje a terapia para pacientes portadores de falência intestinal irreversível que apresentam complicações da nutrição parenteral. Envolve algumas modalidades: intestino delgado isolado, fígado-intestino, multivisceral e multivisceral modificado. Atualmente a sobrevida é semelhante aos demais órgãos sólidos. A maioria dos pacientes fica livre da nutrição parenteral.

BACKGROUND: Small bowel transplantation evolution, because of its complexity, was slower than other solid organs. Several advances have enabled its clinical application. AIM: To review intestinal transplantation evolution and its current status. METHOD: Search in MEDLINE and ScIELO literature. The terms used as descriptors were: intestinal failure, intestinal transplantation, small bowel transplantation, multivisceral transplantation. Were analyzed data on historical evolution, centers experience, indications, types of grafts, selection and organ procurement, postoperative management, complications and results. CONCLUSION: Despite a slower evolution, intestinal transplantation is currently the standard therapy for patients with intestinal failure and life-threatening parenteral nutrition complications. It involves some modalities: small bowel transplantation, liver-intestinal transplantation, multivisceral transplantation and modified multivisceral transplantation. Currently, survival rate is similar to other solid organs. Most of the patients become free of parenteral nutrition.

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.

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.

Forma aguda da doença enxerto contra o hospedeiro após transplante de fígado: Existe opção terapêutica para as formas refratárias ao tratamento com esteróides? / Acute graft versus host disease after liver transplantation: Do we have an option for treatment of steroid-refractory forms?

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 Disease after 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 bibliographies of 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 treatment 24 (25%) adults and 3 (50%) children were alive only. As faras 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 mortality is still very high, there is no consensus for the treatment ofsteroid-refractory forms. Further researches are needed to providenew approach for treating effectively such condition.

Introdução: A forma aguda da doença do enxerto contra o hospedeiro ocorre geralmente até oito semanas após o transplante de fígado, é rara, porém tem mortalidade alta e constitui-se emum grande desafio terapêutico principalmente naqueles casos quesão 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 Enxerto contra 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 antitimocítica + prednisolona – 1 (20%); prednisolona – 1 (20%); globulina anti-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.

Small bowel transplantation in outbred rats / Transplante de intestino delgado em ratos não-isogênicos

PURPOSE: To investigate the clinical evolution of orthotopic small bowel transplantation in outbred rats. METHODS: Seventy-two outbred Wistar rats weighting from 250 to 300g were used as donor and recipient in 36 consecutives ortothopic small intestine transplantation without immunosuppression. The graft was transplanted into the recipient using end-to-side aortic and portacaval microvascular anastomosis. Procedure duration, animal clinical course and survival were evaluated. Survival shorter than four days was considered technical failure. Recipients were sacrificed with signs of severe graft rejection or survival longer than 120 days. Necropsies were performed in all recipients to access histopathological changes in the graft. RESULTS: Median time for the procedure was 107 minutes. Six recipients (16.7 percent) presented technical failure. Twenty-seven recipients were sacrificed due to rejection, being nineteen (52.7 percent) between 7th and 15th postoperative day and eight (22.2 percent) between 34th and 47th postoperative day. Graft histology confirmed severe acute cellular rejection in those recipients. Uneventful evolution and survival longer than 120 days without rejection were observed in three recipients (8.3 percent). CONCLUSION: Intestinal transplantation in outbred rats without immunosuppressant regiment accomplishes variable clinical evolution.

OBJETIVO: Investigar a evolução clínica do transplante de intestino delgado ortotópico em ratos não-isogênicos. MÉTODOS: Setenta e dois ratos Wistar não-isogênicos, com peso variando entre 250 e 300g, foram utilizados como doadores e receptores em 36 transplantes ortotópicos de intestino delgado sem regime de imunossupressão. Os enxertos foram implantados nos receptores por meio de anastomose microvascular término-lateral aorta-aorta e porto-cava. A duração do procedimento, evolução clínica dos animais e sobrevida foram avaliados. Sobrevida menor que quatro dias foi considerada falha técnica. Os receptores foram sacrificados quando apresentaram sinais de rejeição grave do enxerto ou sobrevida maior que 120 dias. Necropsias foram realizadas em todos os receptores para avaliar alterações histopatológicas no enxerto. RESULTADOS: O tempo médio para o procedimento foi de 107 minutos. Seis receptores (16,7 por cento) apresentaram falha técnica Vinte e sete receptores (75 por cento) foram sacrificados por rejeição sendo dezenove (52,7 por cento) entre o 7º e 15º dia de pós-operatório e oito (22,2 por cento) entre o 34º e 47º. Análise histopatológica confirmou rejeição celular aguda severa nesses recipientes. Evolução sem complicações e sobrevida maior que 120 dias sem sinais de rejeição foi observada em três receptores (8,3 por cento). CONCLUSÃO: O transplante de intestino delgado ortotópico em ratos Wistar não-isogênicos sem regime de imunossupressão apresenta evolução clínica variada.

S-nitroso-N-acetylcysteine ameliorates ischemia-reperfusion injury in the steatotic liver

BACKGROUND: Steatosis is currently the most common chronic liver disease and it can aggravate ischemia-reperfusion (IR) lesions. We hypothesized that S-nitroso-N-acetylcysteine (SNAC), an NO donor component, can ameliorate cell damage from IR injury. In this paper, we report the effect of SNAC on liver IR in rats with normal livers compared to those with steatotic livers. METHODS: Thirty-four rats were divided into five groups: I (n=8), IR in normal liver; II (n=8), IR in normal liver with SNAC; III (n=9), IR in steatotic liver; IV (n=9), IR in steatotic liver with SNAC; and V (n=10), SHAN. Liver steatosis was achieved by administration of a protein-free diet. A SNAC solution was infused intraperitoneally for one hour, beginning 30 min. after partial (70 percent) liver ischemia. The volume of solution infused was 1 ml/100 g body weight. The animals were sacrificed four hours after reperfusion, and the liver and lung were removed for analysis. We assessed hepatic histology, mitochondrial respiration, oxidative stress (MDA), and pulmonary myeloperoxidase. RESULTS: All groups showed significant alterations compared with the group that received SHAN. The results from the steatotic SNAC group revealed a significant improvement in liver mitochondrial respiration and oxidative stress compared to the steatotic group without SNAC. No difference in myeloperoxidase was observed. Histological analysis revealed no difference between the non-steatotic groups. However, the SNAC groups showed less intraparenchymal hemorrhage than groups without SNAC (p=0.02). CONCLUSION: This study suggests that SNAC effectively protects against IR injury in the steatotic liver but not in the normal liver.

Ascite: estado da arte baseado em evidências: [revisão] / Ascite: state of the art based on evidences: [review]

A ascite é o acúmulo de líquido livre de origem patológica na cavidade abdominal, fenômeno presente em várias doenças da prática clínica. A doença mais associada com ascite é a cirrose hepática. Na sua fisiopatologia destacam-se três teorias que ocorrem sempre em determinado paciente, porém em momentos diferentes de sua doença: vasodilatação, "overflow" e "underfill". O conceito mais moderno sugere que as três teorias estão presentes no mesmo paciente com cirrose, dependendo do tempo de evolução de sua doença. A teoria da vasodilatação estaria presente desde a fase pré-ascítica até a ascite de longa data. A teoria do overflow seria predominante nos primeiros meses de ascite e a teoria underfill explicaria a maioria dos achados em pacientes com ascite por longo tempo. Neste artigo são comentadas em detalhes as várias doenças que produzem ascite, os métodos diagnósticos empregados na pesquisa clínica da ascite, as complicações da ascite e as opções terapêuticas disponíveis. Em cada item é mostrado o grau de evidência (A até C) presente na literatura médica.

The accumulation of free fluid of pathological origin in the peritoneal cavity is named ascites, and, in clinical practice this phenomenon is present in several diseases. The most common cause of ascites is liver cirrhosis. In the pathophysiology of ascites three theories are noteworthy: vasodilation, overflow and underfill. The modern concept suggest that these three theories are present in the same patient with cirrhosis depending on the disease evolution time. The vasodilation theory would be important in the pre-ascitic phase as well as during all the ascites evolution time. The overflow theory would be important in the first months of development of ascites in cirrhosis, and the underfill theory would explain most of the findings in patients with ascites for a long time. This article comments in detailed, several diseases that produce ascites, the diagnostic methods employed in clinical investigation of ascites' complication and therapeutics options available. In each item the evidence grade (A to C) found in medical literature is shown.