Recipient Hyperbilirubinemia May Reduce Ischemia-Reperfusion Injury but Fails to Improve Outcome in Clinical Liver Transplantation.

Background. Exogenous bilirubin may reduce experimental ischemia-reperfusion injury (IRI) due to its antioxidant properties. We studied if early graft exposure to high bilirubin levels in the recipient affects the early IRI and outcomes after liver transplantation (LTx). Methods. In 427 LTx patients, the AUROC curve based on bilirubin and AST at day 1 identified a cutoff of 2.04 mg/dL for the recipient pretransplant bilirubin. Recipients were grouped as having low (group L, n = 152) or high (group H, n = 275) bilirubin. Both groups had similar donor-related variables (age, preservation time, donor BMI > 28, and donor risk index (DRI)). Results. Alanine (ALT) and aspartate (AST) aminotransferase levels were higher in group L at day 1; ALT levels remained higher at day 2 in group L. LTx from high risk donors (DRI > 2) revealed a trend towards lower transaminases during the first two days after transplantation in group H. One month and 1-year patient survival were similar in groups L and H. High preoperative bilirubin did not affect the risk for early graft dysfunction (EGD), death, or graft loss during the first year after transplantation nor the incidence of acute rejection. LTx using donors with DRI > 2 resulted in similar rates of EGD in both groups. Conclusion. Increased bilirubin appears to reduce the early IRI after LTx yet this improvement was insufficient to improve the clinical outcome.

Immunosenescence and immune response in organ transplantation.

The immune system undergoes a complex and continuous remodeling with aging. Immunosenescence results into both quantitative and qualitative changes of specific cellular subpopulations that have major impact on allorecognition and alloresponse, and consequently on graft rejection and tolerance. Here, we are going to review the immunological changes associated with the aging process relevant for transplantation. Interventions to selectively target changes associated with the senescence process seem promising therapeutic strategies to improve transplantation outcome.

Assessment of graft function in rodent models of heart transplantation.

Heterotopic heart transplantation in rats and mice is the most commonly used model to study allograft immune response and to test immunosuppressive drugs and tolerance induction protocols. Standardization of both the surgical procedure and the evaluation of graft function is essential for data interpretation. The most popular way to monitor graft function has been the palpation method. However, there are some proposal for more objective assessment methods like electrocardiogram and echocardiogram. Although, complementary tests might add some relevant information when assessing minor effects of immunosuppressive therapy, palpation by an experienced investigator is very predictive and so far the simplest method to determine heart allograft function. Minor complications during the surgical procedure and unreliable assessment can have a major impact on the interpretation of experiment results. Here, the author reviews the literature and presents some suggestions that help eliminating biases on the assessment of heart allograft function.

Hepatic lobectomy and segmentectomy models using microsurgical techniques.

The mouse and rat models are the most commonly utilized experimental models of partial liver resection. Microscope-assisted partial hepatectomy is associated with better outcomes by reducing the risk of vena cava stenosis after ligature and injury to other liver pedicles. In addition, microsurgery allows lobectomies and segmentectomies after individual ligation of intrahepatic vascular branches, including the left and right segments of the median lobe, which has not been reported before. Here, we describe a new technique (catheter-assisted suture technique) and report our experience with partial hepatectomies in rodents using a microsurgical approach.

Surgical anatomy of the liver, hepatic vasculature and bile ducts in the rat.

BACKGROUND: The rat is the most used experimental model in surgical research. Virtually all procedures in clinical liver surgery can be performed in the rat. However, the use of the rat model in liver surgery is limited by its small size and limited knowledge of the liver anatomy. As in humans, the rat liver vasculature and biliary system have many anatomical variations. The development of surgical techniques, and the study of liver function and diseases require detailed knowledge of the regional anatomy. AIM: The objective of this study was to describe and illustrate systematically the surgical anatomy of the rat liver to facilitate the planning and performance of studies in this animal. Knowledge of the diameter and length of liver vessels is also important for the selection of catheters and perivascular devices. METHODS: Twelve Wistar rat livers were dissected using a surgical microscope. Hepatic and extrahepatic anatomical structures were measured under magnification with a millimeter scale. CONCLUSION: In this study, we describe the rat liver topographical anatomy, compare it with the human liver and review the literature. Increased knowledge of the rat liver anatomy and microsurgical skills permit individualized dissection, parenchymal section, embolization and ligature of vascular and biliary branches.

Intraduodenal diverticulum associated with a double common bile duct causing recurrent pancreatitis and cholangitis: report of a case.

Intraduodenal diverticulum (IDD) is a rare congenital anomaly, arising at or near the papilla of Vater. Double common bile duct (DCBD) is another rare congenital anomaly of the biliary system. Recognition of these abnormalities is essential to prevent the development of lesions in the biliary system, as well as to avoid unnecessary surgical intervention. Although both conditions are often asymptomatic, severe clinical conditions may develop. Intraduodenal diverticulum should always be considered as a possible cause of pancreatitis of unknown etiology. We report a rare case of IDD with DCBD in a patient with Lemmel's syndrome, which consists of obstructive jaundice, acute pancreatitis, and suppurative cholangitis. The patient was treated successfully with a Roux-en-Y hepaticojejunostomy.

Basic microsurgery training: comments and proposal.

Microsurgical techniques have been applied in many surgical specialties and have also a broad application in surgical research. It demands high technical skills and continued training. The microsurgical training is lengthy, very expensive and demands high commitment. The microsurgical skills should be first mastered in the lab and only then applied in the clinic. Here, we propose a model of a training course in microsurgery. We also suggest that surgical societies involved with microsurgery promote training courses on a regular basis.

Basic microsurgery training: comments and proposal

Microsurgical techniques have been applied in many surgical specialties and have also a broad application in surgical research. It demands high technical skills and continued training. The microsurgical training is lengthy, very expensive and demands high commitment. The microsurgical skills should be first mastered in the lab and only then applied in the clinic. Here, we propose a model of a training course in microsurgery. We also suggest that surgical societies involved with microsurgery promote training courses on a regular basis.

Microcirurgia tornou-se uma técnica aplicável em uma série de especialidades cirúrgicas e em pesquisa experimental. Microcirurgia exige alta qualidade técnica e treinamento contínuo. No Brasil, existe grande carência de microcirurgiões devido aos custos envolvidos no treinamento e na escassez de serviços que ofereçam treinamento especializado. O treinamento em microcirurgia é longo, caro e exige alto grau de dedicação. O completo domínio das técnicas de microcirurgia deve ser obtido primeiro no laboratório antes de ser empregada na prática clínica. Nesse artigo, propõe-se um modelo de curso teórico-prático em microcirurgia. Também sugere-se que sociedades de especialidades cirúrgicas mais ligadas à microcirurgia fomentem a capacitação de profissionais em microcirurgia através da realização de cursos básicos em microcirurgia.

Induction of carbon monoxide in donor animals prior to organ procurement reduces graft immunogenicity and inhibits chronic allograft dysfunction.

BACKGROUND: Nonspecific inflammatory damages occurring prior to organ transplantation reduce long-term graft survival. Here, we tested the beneficial effects of carbon monoxide (CO) induction by methylene chloride (MC). METHODS: Fischer-344 (F-344 Rat) or Dark Agouti (DA Rat) donor animals were either treated with MC four hours prior to organ removal or remained untreated. Kidneys were transplanted into Lewis (LEW) recipients. The low responder strain combination (F-344-->LEW) was studied for long-term graft changes. Dendritic cells (DCs) migration and early changes were followed in additional groups of a high responding donor/recipient strain combination (DA-->LEW). Native kidneys of uninephrectomized, age-matched normal animals served as controls. RESULTS: Following MC application COHb peaked within two hours in donor animals. Renal function and morphology improved significantly in renal allografts of CO induced donor animals and were comparable to native controls long-term (24 wks). Early after transplantation (24 hr) donor-derived DCs, CD4+ T-cells and alloreactive T-cells were significantly reduced following the engraftment of organs from treated donors. In addition, a trend towards a Th1/Th2 shift and a significant intragraft reduction of CD3 mRNA expression was observed. CONCLUSION: Donor treatment for the induction of CO reduced graft immunogenicity and inhibited chronic allograft nephropathy.

Kidney transplantation in the rat: a modified technique using hydrodissection.

Here, hydrodissection was compared with the conventional blunt instrumental dissection approach in a rat model of orthotopic kidney transplantation. Forty male Fisher and Lewis rats were used as kidney donors and recipients, respectively. After recipient nephrectomy, left kidney grafts were implanted orthotopically using standard microsurgical techniques. Two different methods of dissection of the graft and recipient vessels were used. In method A, the dissection was performed using blunt dissection with cotton-tipped sticks and jeweler's forceps (n = 20), and in method B, dissection was performed using water dissection technique (n = 20). Hydrodissection displayed the correct plane of dissection, reduced the operating time, and reduced the overall complication (P < 0.001) and vasospasm (P < 0.05) rates. This is the first report of the use of hydrodissection in experimental transplantation. This atraumatic dissection technique does not require any special instruments, is fast, safe, demands less surgical skills, and may be useful in other transplantation models.

Organization of a microsurgery laboratory.

Microsurgical techniques have been used in many surgical specialties as well as a broad application in surgical research.. It demands high technical skills and continued training. The microsurgical skills should be first mastered in the lab before to be employed in the clinical practice. The microsurgical lab has a dual role: the training of residents and specialized surgeons and the support for the high qualified scientific research in experimental surgery. Here, it is presented (showed) the organization of a microsurgical lab, including area and equipments, furthermore there is a proposal that school-hospitals that offer microsurgical procedures, should have a microsurgical laboratory.

Organization of a microsurgery laboratory

As técnicas microcirúrgicas têm sido usadas em várias especialidades cirúrgicas, assim como uma ampla aplicação na pesquisa cirúrgica. A realização de microcirurgia exige alta qualidade técnica e treinamento contínuo. O completo domínio das técnicas de microcirurgia deve ser obtido primeiro no laboratório antes de ser empregada na prática clínica. O laboratório de microcirurgia tem uma dupla função: o treinamento de residentes e cirurgiões especialistas e o suporte para a investigação científica em cirurgia experimental. Nesse artigo está apresentado um modelo de laboratório de microcirurgia, incluindo a área e os equipamentos, além da proposta de que os hospitais-escola, que ofereçam procedimentos microcirúrgicos, sejam equipados com laboratório de microcirurgia.

Microsurgical techniques for experimental kidney transplantation and general guidelines to establish studies about transplantation immunology

Experimental models of organ transplantation played a crucial role to establish the principles of transplantation immunology. The renal transplantation in rodents became the most used model to study the mechanisms of allograft rejection. To perform it, it is necessary to master the microsurgery techniques and the research group should cooperate with other specialists in the field. In this article we review the surgical techniques employed in rats, and we draw guidelines to establish studies about transplantation immunology.

Importância da microcirurgia experimental para transplantes de órgãos / Importance of experimental microsurgery for organs transplantation

A microcirurgia experimental é uma área relativamente nova e seu desenvolvimento foi um marco importante para o desenvolvimento da pesquisa imunológica e de técnicas cirúrgicas de transplante, pois permitiu a utilização de modelos animais de pequeno porte; mais apropriados para pesquisa, e com menor custo. A microcirurgia exige bastante habilidade técnica e treinamento continuo. Além disso contribui para formação do cirurgião de transplantes na medida que promove o desenvolvimento de habilidade manual, interesse científico e cooperação interdisciplinar. Esse artigo relata alguns aspectos históricos, a importância e as vantagens e limitações da microcirurgia experimental.