UENIS TANNURI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Pediatria, Faculdade de Medicina - Docente
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/30 - Laboratório de Investigação em Cirurgia Pediát, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/30 - Laboratório de Investigação em Cirurgia Pediát, Hospital das Clínicas, Faculdade de Medicina - Líder
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- Living donor liver transplantation in children: Should the adult donor be operated on by an adult or pediatric surgeon? Experience of a single pediatric center(2014) ANDRADE, Wagner de Castro; VELHOTE, Manoel Carlos Prieto; AYOUB, Ali Ahman; SILVA, Marcos Marques; GIBELLI, Nelson Elias M.; TANNURI, Ana Cristina A.; SANTOS, Maria Merces; PINHO-APEZZATO, Maria Lucia; BARROS, Fabio de; MOREIRA, Daniel Rangel; MIYATANI, Helena T.; PEREIRA, Raimundo Renato; TANNURI, UenisBackground/Purpose: Living donor liver transplantation has become a cornerstone for the treatment of children with end-stage hepatic dysfunction, especially within populations or countries with low rates of organ utilization from deceased donors. The objective is to report our experience with 185 living donors operated on by a team pediatric surgeons in a tertiary center for pediatric liver transplantation. Methods: Retrospective analysis of medical records of donors of hepatic grafts for transplant undergoing surgery between June 1998 and March 2013. Results: Over the last 14 years, 185 liver transplants were performed in pediatric recipients of grafts from living donors. Among the donors, 166 left lateral segments (89.7%), 18 left lobes without the caudate lobe (9.7%) and 1 right lobe (0.5%) were harvested. The donor age ranged from 16 to 53 years, and the weight ranged from 47 to 106 kg. In 10 donors, an additional graft of the donor inferior mesenteric vein was harvested to substitute for a hypoplastic recipient portal vein. The transfusion of blood products was required in 15 donors (8.1%). The mean hospital stay was 5 days. No deaths occurred, but complications were identified in 23 patients (12.4%): 9 patients experienced abdominal pain and severe gastrointestinal symptoms and 3 patients required reoperations. Eight donors presented with minor bile leaks that were treated conservatively, and 3 patients developed extra-peritoneal infections (1 wound collection, 1 phlebitis and 1 pneumonia). Eight grafts (4.3%) showed primary dysfunction resulting in recipient death (3 cases of fulminant hepatitis, 1 patient with metabolic disease, 1 patient with Alagille syndrome and 3 cases of biliary atresia in infants under 1 year old). There was no relation between donor complications and primary graft dysfunction (P = 0.6). Conclusions: Living donor transplantation is safe for the donor and presents a low morbidity. The donor surgery may be performed by a team of trained pediatric surgeons.
- Analysis of the reversibility of biliary cirrhosis in young rats submitted to biliary obstruction(2018) BRAZ, Maria Julia de Aro; CORBI, Leonardo Ervolino; TANNURI, Ana Cristina Aoun; COELHO, Maria Cecilia Mendonca; GONCALVES, Josiane Oliveira; SERAFINI, Suellen; TANNURI, UenisBackground/purpose: Biliary atresia and other liver biliary obstructions are relevant conditions in pediatric surgery due to their progression to biliary cirrhosis and indication for liver transplantation. It is known that the period during which biliary obstruction persists determines the development of cirrhosis and its reversibility after a biliary drainage procedure. However, no time or histological markers of biliary cirrhosis reversibility have been established. Materials and methods: One hundred and twenty-nine young Wistar rats underwent surgery for ligation of the common bile duct and were maintained until 8 weeks. A part of these animals was submitted to biliary drainage surgery at 2, 3, 4, 5, or 6 weeks after the initial procedure. After cyst formation at the site of obstruction, cystjejunal anastomosis was performed to restore bile flow. After biliary obstruction and drainage, liver samples were collected for histological and molecular analysis of the genes responsible for collagen deposition and fibrosis. Results: The mortality rates were 39.8% and 56.7% after the first and second procedures, respectively. Ductular proliferation (p = 0.001) and collagen deposition increased according to the period under obstruction (p = 0.0001), and both alterations were partially reduced after biliary drainage. There were no significant differences in the values of desmin and alpha-actin according to the period during which the animal remained with biliary obstruction (p = 0.09 and p = 0.3, respectively), although increased values of transforming growth factor beta 1 (TGF beta 1) occurred after 8 weeks (p = 0.000). Desmin levels decreased, and alpha-actin and TGF beta 1 levels increased according to the period under obstruction. The molecular alterations were partially reversed after biliary drainage. Conclusions: The histologic and molecular changes in the liver parenchyma promoted by biliary obstruction in the young animal can be partially reversed by a biliary drainage procedure.
- Is maintenance of the ileocecal valve important to the intestinal adaptation mechanisms in a weaning rat model of short bowel?(2018) BARROS, Guilherme Garcia; TANNURI, Ana Cristina Aoun; ROTONDO, Italo Gerardo; VAISBERG, Vitor Van; SARMENTO, Leandro Silveira; NETO, Cicero Mendes; SERAFINI, Suellen; GONCALVES, Josiane de Oliveira; COELHO, Maria Cecilia Mendonca; TANNURI, UenisPurpose To evaluate the role of maintenance of the ileocecal valve (ICV) in intestinal adaptation mechanisms, in a weaning rat experimental model of short bowel. Methods Forty animals were operated on to produce short bowel syndrome. They were divided into five groups: maintenance (MV) or resection of ICV (RV), kill after 4 days (MV4 and RV4) or 21 days (MV21 and RV21), and a control group (21-day-old rats). Body weights, small bowel and colon lengths and diameters, villus heights, crypt depths, lamina propria and muscle layer thickness, as well as the apoptosis index of villi and crypts and expression of pro-and anti-apoptotic genes, were studied. Results Preservation of the ICV promoted increased weight gain (p = 0.0001) and intestinal villus height after 21 days; crypt depth was higher in comparison to controls. It was verified a higher expression of Ki-67 in bowel villi and crypts (p = 0.018 and p = 0.015, respectively) in RV4 group and a higher expression in bowel villi of MV4 group animals (p = 0.03). The maintenance of ICV promoted late increased expression of the anti-apoptotic gene Bcl-XL in the colon (p = 0.043, p = 0.002, p = 0.01). Conclusion The maintenance of the ICV led to positive changes in this model.
- Extensive Hepatectomy as an Alternative to Liver Transplant in Advanced Hepatoblastoma: A New Protocol Used in a Pediatric Liver Transplantation Center(2019) PAGANOTI, G. de Freitas; TANNURI, A. C. A.; MARQUES, A. C. Dantas; TORRES, R. R.; GIBELLI, N. E. Mendes; TANNURI, U.Background. Surgery is a key factor in the treatment of hepatoblastoma, but choosing between an aggressive resection and liver transplant may be an extremely difficult task. The aim of this study was to describe the outcomes of patients with advanced hepatoblastoma: pretreatment extent of disease (PRETEXT)/post-treatment extent of disease (POST-TEXT) III and IV undergoing aggressive resections or living donor liver transplant in cases involving the entire liver. Based on this experience, a new protocol for the treatment of these patients was proposed. Methods. A retrospective study included patients with advanced hepatoblastoma (POST-TEXT III and IV) who were referred for a liver transplant from 2010 to 2017. Results. A total of 24 children were included: 13 (54.2%) were male, with a median age at diagnosis of 42 months (range, 15-120 months), and a history of prematurity was identified in 20.8% of the patients. Ten cases (41.7%) were staged as PRETEXT/POST-TEXT III, and 12 cases (50.0%) were staged as PRETEXT/POST-TEXT IV. Two patients were referred after posthepatectomy recurrence. Five patients underwent a liver transplant, with recurrence and death in 2 patients (40.0%) within a mean period of 6 months. In the extensive hepatectomy group, there was recurrence in 6 patients (31.6%), with disease-free outcomes and overall survival in 63.2% and 94.7% of patients, respectively. Conclusion. In cases of advanced hepatoblastoma, an extensive surgical approach is a valuable option. The fact that the team was fully prepared to proceed with living donor liver transplant allowed the surgeon to be more aggressive and to switch to transplantation when resection was not possible.
- Impact of Three Methods of Ischemic Preconditioning on Ischemia-Reperfusion Injury in a Pig Model of Liver Transplantation(2022) BELON, Alessandro Rodrigo; TANNURI, Ana Cristina Aoun; MOREIRA, Daniel de Albuquerque Rangel; FIGUEIREDO, Jose Luiz; SILVA, Alessandra Matheus da; SERAFINI, Suellen; GUIMARAES, Raimundo Renato; FARIA, Caroline Silverio; ALEXANDRE, Alcione Sanches de; GONCALVES, Josiane Oliveira; PAES, Vitor Ribeiro; TANNURI, UenisBackground Ischemic preconditioning (IPC), either direct (DIPC) or remote (RIPC), is a procedure aimed at reducing the harmful effects of ischemia-reperfusion (I/R) injury. Objectives To assess the local and systemic effects of DIPC, RIPC, and both combined, in the pig liver transplant model. Materials and methods Twenty-four pigs underwent orthotopic liver transplantation and were divided into 4 groups: control, direct donor preconditioning, indirect preconditioning at the recipient, and direct donor with indirect recipient preconditioning. The recorded parameters were: donor and recipient weight, graft-to-recipient weight ratio (GRWR), surgery time, warm and cold ischemia time, and intraoperative hemodynamic values. Blood samples were collected before native liver removal (BL) and at 0 h, 1 h, 3 h, 6 h, 12 h, 18 h, and 24 h post-reperfusion for the biochemical tests: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), creatinine, BUN (blood urea nitrogen), lactate, total and direct bilirubin. Histopathological examination of liver, gut, kidney, and lung fragments were performed, as well as molecular analyses for expression of the apoptosis-related BAX (pro-apoptotic) and Bcl-XL (anti-apoptotic) genes, eNOS (endothelial nitric oxide synthase) gene, and IL-6 gene related to inflammatory ischemia-reperfusion injury, using real-time polymerase chain reaction (RT-PCR). Results There were no differences between the groups regarding biochemical and histopathological parameters. We found a reduced ratio between the expression of the BAX gene and Bcl-XL in the livers of animals with IPC versus the control group. Conclusions DIPC, RIPC or a combination of both, produce beneficial effects at the molecular level without biochemical or histological changes.
- Liver Regeneration Model in Growing Rats With Hepatic Artery Ligation: Histologic and Molecular Studies(2015) BACKES, A. Nadia; TANNURI, A. C. Aoun; COELHO, M. C. Mendonca; GIBELLI, N. E. Mendes; BACKES, F. N.; TANNURI, U.Background. Liver transplantation is an effective treatment for irreversible liver diseases. The incidence of hepatic artery thrombosis remains high. Our objective was to analyze the effect of ligature of the hepatic artery on liver regeneration in a growing animal model. Methods. Seventy-five male Wistar rats were divided into the following 3 groups: group 1 (sham, G1): incision without intervention; group 2 (G2): 70% hepatectomy; group 3 (G3): 70% hepatectomy and ligation of the hepatic artery. Preceding the 70% hepatectomy, a hepatic artery ligature was performed with resection of a segment of the artery. The liver specimens were stained with hematoxylin-eosin, and immunohistochemical staining for Ki-67 was performed. The expression of the interleukin (IL) 6 gene was studied by means of reverse-transcription polymerase chain reaction. Results. G2 and G3 demonstrated similar tendencies toward an increase in the gain weight ratio over time. The mitotic activity was significantly lower at 72 hours in G3 than in G2. There was no difference between Ki-67 staining between G2 and G3. The expression of the IL-6 gene was present in all of the groups, lower in G1, with no difference between G2 and G3. Conclusions. The experimental model was feasible and adequate for these investigations. Hepatectomy stimulated hepatocyte proliferation, and the obstruction of the arterial flow did not affect liver regeneration.
- Pediatric acute liver failure in Brazil: Is living donor liver transplantation the best choice for treatment?(2016) TANNURI, Ana Cristina Aoun; PORTA, Gilda; MIURA, Irene Kazue; SANTOS, Maria Merces; MOREIRA, Daniel de Albuquerque Rangel; REZENDE, Nathassia Mancebo Avila de; MIYATANI, Helena Thie; TANNURI, UenisAcute liver failure (ALF) in children is a life-threatening condition that often leads to urgent liver transplantation (LT). The aim of the present investigation was to describe the experience in Brazil in treating pediatric ALF, with an emphasis on the role of living donor liver transplantation (LDLT) in treating this condition. All children with ALF who fulfilled the criteria for an urgent LT were admitted to the intensive care unit. Patients were divided into 2 groups based on the moment of admission: before and after June 2007, when the LDLT program for ALF was started. Statistical analyses were performed to identify prognostic factors of patients with ALF. For the study, 115 children with ALF were admitted. All patients had some degree of encephalopathy. Among the patients, 26% of them required intracranial pressure monitoring (IPM), 12.8% of the patients required hemodialysis, and 79 patients underwent transplantation (50 deceased donors and 29 living donors) corresponding to 12.4% of all pediatric LTs. Only 9 children recovered without LT. The need for IPM and nonperformance of LT were related to a higher mortality. The mortality rate of patients who underwent LT was significantly lower than that of children with ALF who did not undergo a LT (48.1% versus 75%; P = 0.02). The incidences of primary nonfunction and mortality were statistically higher among deceased donor liver transplantations than LDLTs. Finally, it was verified that the overall survival rate of transplanted patients was increased after the introduction of LDLT (P = 0.02). In conclusion, ALF in children continues to be a severe and devastating condition, and a LT should be performed promptly. The introduction of LDLT could increase the survival rate of patients in Brazil. Liver Transplantation 22 1006-1013 2016 AASLD
- Early type I collagen deposition is associated with prognosis in biliary atresia(2016) LONGO-SANTOS, Luis Ricardo; TEODORO, Walcy Rosolia; MELLO, Evandro Sobroza de; VELOSA, Ana Paula Pereira; PARRA, Edwin Roger; CAPELOZZI, Vera Luiza; TANNURI, UenisBackground: Biliary atresia (BA) is a cholestatic liver disease of children that progresses to hepatic fibrosis. BA is the main indication of pediatric liver transplantation (LTx). Histopathological markers in liver biopsies could be useful for predicting progression to end-stage disease. Objective: To establish histopathological or immunohistochemical markers in liver biopsies of BA patients and correlate those markers with prognosis. Method: Histological analysis of biliary alterations and morphometric assessment of liver fibrosis were performed, in addition to indirect immunofluorescence assays (IF) for type I, III, IV and V collagens in initial and final liver biopsies of 36 patients with BA who underwent Kasai hepatoportoenterostomy (KPE) and LTx in the last 20 years at a single center. Results: Histopathologicalmarkers had no correlation with evolutive time until LTx. The perisinusoidal deposition of type III and V collagens was more prominent in the initial biopsies (p < 0.01), whereas deposition of type I and IV collagens indicated progression (p < 0.01). Patients with large amounts of perisinusoidal type I collagen in the initial biopsies had worse progression time curves until LTx (p = 0.04). Conclusion: Morphometric assessment of perisinusoidal deposition of type I collagen by IF in the initial biopsy can correlate with progression time to LTx in post-surgical BA.
- Effects of local and remote ischemic postconditioning methods on ischemia-reperfusion injury in a young animal model of acute mesenteric ischemia(2023) ABREU, Mateus Souza; TANNURI, Ana Cristina Aoun; RODRIGUES, Rafael Felipe Goncalves; SILVA, Rafael Jose da; GONCALVES, Josiane de Oliveira; SERAFINI, Suellen; TANNURI, UenisPurpose: Acute mesenteric ischemia (AMI) is a condition in pediatric surgery that ranges from intestine necrosis to death. Ischemic postconditioning (IPoC) methods were developed to reduce the damage caused by revascularization. This study aimed to evaluate the efficacy of these methods in an experimental weaning rat model. Methods: Thirty-two 21-day-old Wistar rats were allocated into four groups according to the surgical procedure performed: control, ischemia-reperfusion injury (IRI), local (LIPoC) and remote IPoC (RIPoC). At euthanasia, fragments of the intestine, liver, lungs, and kidneys were submitted to histological, histomorphometric, and molecular analyses. Results: In the duodenum, intestines, and kidneys histological alterations promoted by IRI were reversed by remote postconditioning method. In the distal ileum, the histomorphometric alterations could be reversed by the postconditioning methods with more evident effects promoted by the remote method. The molecular analysis found that the levels of expression of Bax (proapoptotic) and Bcl-XL (antiapoptotic) genes in the intestine were increased by IRI. These alterations were equally reversed by the postconditioning methods, with more evident effects of the remote method. Conclusion: IPoC methods positively reduced the damage caused by IRI in weaning rats.
- Living Related Donor Liver Transplantation in Children(2011) TANNURI, A. C. A.; GIBELLI, N. E. M.; RICARDI, L. R. S.; SANTOS, M. M.; MAKSOUD-FILHO, J. G.; PINHO-APEZZATO, M. L.; SILVA, M. M.; VELHOTE, M. C. P.; AYOUB, A. A. R.; ANDRADE, W. C.; LEAL, A. J.; MIYATANI, H. T.; TANNURI, U.Objective. The objective of this study was to report our experience with pediatric orthotopic liver transplantation (OLT) with living related donors. Methods. We performed a retrospective chart analysis of 121 living related donor liver transplantations (LRDLT) from June 1998 to June 2010. Results. Indications were biliary atresia (BA; n = 81), primary sclerosing cholangitis (n = 5), alpha-1 antitrypsin deficiency (n = 4); cholestasis (n = 9), fulminant hepatic failure (n = 8), autoimmune hepatitis (n = 2), Alagille syndrome (n = 4), hepatoblastoma (n = 3), tyrosinemia (n = 2), and congenital hepatic fibrosis (n = 3). The age of the recipients ranged from 7-174 months (median, 22) and the weights ranged from 6-58 kg (median, 10). Forty-nine children (40.5%) weighed <= 10 kg. The grafts included the left lateral segment (n = 108), the left lobe (n = 12), and the right lobe (n = 1). The donors included 71 mothers, 45 fathers, 2 uncles, 1 grandmother, 1 grandfather, and 1 sister with a median age of 29 years (range, 16-53 ys) and a median weight of 68 kg (range, 47-106). Sixteen patients (12.9%) required retransplantation, most commonly due to hepatic artery thrombosis (HAT; n = 13; 10.7%). The other complications were biliary stenosis (n = 25; 20.6%), portal vein thrombosis (PVT; n = 11; 9.1%), portal vein stenosis (n = 5; 4.1%), hepatic vein stenosis (n = 6; 4.9%), and lymphoproliferative disorders (n = 8; 6.6%). The ultimate survival rate of recipients was 90.3% after 1 year and 75.8% after 3 years. Causes of early death within 1 month were HAT (n = 6), PVT (n = 2), severe graft dysfunction (n = 1), sepsis (n = 1), and intraoperative death in children with acute liver failure (n = 2). Causes of late deaths included lymphoproliferative disease (n = 3), chronic rejection (n = 2), biliary complications (n = 3), and recurrent disease (n = 3; hepatoblastoma and primary sclerosing cholangitis). Conclusions. Despite the heightened possibility of complications (mainly vascular), LRDLT represented a good alternative to transplantation from cadaveric donors in pediatric populations. It was associated with a high survival ratio.