MARIA MERCES SANTOS
Projetos de Pesquisa
Unidades Organizacionais
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina
LIM/30 - Laboratório de Investigação em Cirurgia Pediát, Hospital das Clínicas, Faculdade de Medicina
LIM/30 - Laboratório de Investigação em Cirurgia Pediát, Hospital das Clínicas, Faculdade de Medicina
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- 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
- The role of interleukin-6, endothelins, and apoptotic genes in small bowel transplantation, in a swine model of ischemia and reperfusion injury(2011) PINHO-APEZZATO, Maria Lucia de; MAKSOUD-FILHO, Joao Gilberto; VALINETTI, Emilia Aparecida; SANTOS, Maria Merces; TANNURI, Ana Cristina Aoun; MELLO, Evandro Sobroza; SILVA, Luiz Fernando; COELHO, Maria Cecilia de Mendonca; GIBELLI, Nelson Elias Mendes; ROCHA, Rafael Malagoli; NONOGAKI, Suely; GUIMARAES, Raimundo Renato Nunes; TANNURI, UenisIRI is closely related to sepsis in ITx setting. Complete understanding of the mechanisms involved in IRI development may improve outcomes. Ortothopic ITx without immunosuppression was performed in order to characterize IRI-associated mucosal damage. Twenty pigs underwent ITx. Two groups were assigned to different CI times: G1: 90 min and, G2: 180 min. Euro-Collins was used as preservation solution. Jejunal fragments were collected at donor laparotomy, 30 min, and 3 days after reperfusion. IRI assessment involved: histopathologic analysis, quantification of MPO-positive cells through immunohistochemical studies, quantification of epithelial apoptotic cells using TUNEL staining, and quantification of IL-6, ET-1, Bak, and Bcl-XL genes expression by RT-PCR. Neutrophilic infiltration increased in a similar fashion in both groups, but lasted longer in G2. Apoptosis detected by TUNEL staining increased and anti-apoptotic gene Bcl-XL expression decreased significantly in G1, 3 days after surgery. Endothelin-1 and IL-6 genes expression increased 30 min after the procedure and returned to baseline 3 days after surgery. In conclusion, IL-6 and ET-1 are involved precociously in the development of intestinal IRI. Apoptosis was more frequently detected in G1 grafts by TUNEL-staining and by RT-PCR.
- 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.
- Rex Shunt for Acute Portal Vein Thrombosis After Pediatric Liver Transplantation in Children With Biliary Atresia(2011) GIBELLI, N. E. M.; TANNURI, A. C. A.; TANNURI, U.; SANTOS, M. M.; PINHO-APEZZATO, M. L.; MAKSOUD-FILHO, J. G.; VELHOTE, M. C. P.; AYOUB, A. A. R.; SILVA, M. M.; ANDRADE, W. C.Background/Purpose. Posttransplantation portal vein thrombosis (PVT) can have severe health consequences, and portal hypertension and other consequences of the long-term privation of portal inflow to the graft may be hazardous, especially in young children. The Rex shunt has been used successfully to treat PVT patients since 1998. In 2007, we started to perform this surgery in patients with idiopathic PVT and late posttransplantation PVT. Herein we have reported our experience with this technique in acute posttransplantation PVT. Methods. Three patients of ages 12, 15, and 18 months underwent cadaveric (n = 1) or living donor (n = 2) orthotopic liver transplantation (OLT). All patients had biliary atresia with portal vein hypoplasia; they developed acute PVT on the first postoperative day. They underwent a mesenteric-portal surgical shunt (Rex shunt) using a left internal jugular vein autograft (n = 2) or cadaveric iliac vein graft (n = 1) on the first postoperative day. Results. The 8-month follow-up has confirmed shunt patency by postoperative Doppler ultrasound. There have been no biliary complications to date. Conclusions. The mesenteric-portal shunt (Rex shunt) using an autograft of the left internal jugular or a cadaveric vein graft should be considered for children with acute PVT after OLT. These children usually have small portal veins; reanastomosis is often unsuccessful. In addition, this technique has the advantage to avoid manipulation of the hepatic hilum and biliary anastomosis. Although this study was based on a limited experience, we concluded that this technique is feasible, with great benefits to and low risks for these patients.
- Technique advance to avoid hepatic venous outflow obstruction in pediatric living-donor liver transplantation(2015) TANNURI, Uenis; TANNURI, Ana Cristina A.; SANTOS, Maria M.; MIYATANI, Helena T.HVOO represents a serious critical complication of pediatric living-donor liver transplantation because open surgical repair is virtually impossible. Currently, despite several technical innovations and the introduction of triangulated anastomosis for hepatic vein reconstruction, the reported incidence of HVOO is still considerable. The aim of this study was to propose a new technique for hepatic venous reconstruction that avoids the original orifice of the recipient hepatic veins. Instead, anastomosis is performed in a newly created wide longitudinal orifice in the anterior wall of the recipient inferior vena cava. A total of 210 living related-donor liver transplantations were performed using two methods for reconstruction of the hepatic vein. Group 1 included 69 patients subjected to direct anastomosis of the orifice of the graft hepatic vein and a wide orifice created in the recipient inferior vena cava by the confluence of the orifices of the right, left, and middle hepatic veins. Group 2 included 141 patients in whom the original orifices of the recipient hepatic veins were closed, the inferior vena cava was widely opened, and a long longitudinal anastomosis was performed using two lines of continuous sutures. Diagnosis of HVOO was suspected based on clinical findings and ultrasound studies and then confirmed by liver biopsy and interventional radiology examinations. Among the 69 recipients in group 1, 16 patients died due to graft problems during the postoperative period and eight of the survivors (15.1%) presented with HVOO. In group 2 (141 patients), 21 patients died, and there were no cases of HVOO. A comparison of the incidence of HVOO between groups revealed a significant difference (p=0.01). Hepatic venous reconstruction during pediatric living-donor liver transplantation should be performed using a wide longitudinal incision in the anterior wall of the recipient inferior vena cava because this technique eliminated anastomosis complications.
- Orthotopic Liver Transplantation in Biliary Atresia: A Single-Center Experience(2011) TANNURI, A. C. A.; GIBELLI, N. E. M.; RICARDI, L. R. S.; SILVA, M. M.; SANTOS, M. M.; PINHO-APEZZATO, M. L.; MAKSOUD-FILHO, J. G.; VELHOTE, M. C. P.; AYOUB, A. A. R.; ANDRADE, W. C.; BACKES, A. N.; MIYATANI, H. T.; TANNURI, U.Introduction. Biliary atresia (BA) is the leading indication for orthotopic liver transplantation (OLT) among children. However, there are technical difficulties, including the limited dimensions of anatomical structures, hypoplasia and/or thrombosis of the portal vein and previous portoenterostomy procedures. Objective. The objective of this study was to present our experience of 239 children with BA who underwent OLT between September 1989 and June 2010 compared with OLT performed for other causes. Methods. We performed a retrospective analysis of patient charts and analysis of complications and survival. Results. BA was the most common indication for OLT (207/409; 50.6%). The median age of subjects was 26 months (range, 7-192). Their median weight was 11 kg (range, 5-63) with 110 children (53.1%) weighing <= 10 kg. We performed 126 transplantations from cadaveric donors (60.8%) and 81 from living-related donors (LRD) (39.2%). Retransplantation was required for 31 recipients (14.9%), primarily due to hepatic artery thrombosis (HAT; 64.5%). Other complications included the following: portal vein thrombosis (PVT; 13.0%), biliary stenosis and/or fistula (22.2%), bowel perforation (7.0%), and posttransplantation lymphoproliferative disorder (PTLD; 5.3%). Among the cases of OLT for other causes, the median age of recipients was 81 months (range, 11-17 years), which was higher than that for children with BA. Retransplantation was required in 3.5% of these patients (P < .05), mostly due to HAT. The incidences of PVT, bowel perforation, and PTLD were significantly lower (P < .05). There was no significant difference between biliary complications in the 2 groups. The overall survival rates at 1 versus 5 years were 79.7% versus 68.1% for BA, and 81.2% versus 75.7% for other causes, respectively. Conclusions. Children who undergo OLT for BA are younger than those engrafted for other causes, displaying a higher risk of complications and retransplantations.
- Posterior reversible encephalopathy syndrome after liver transplantation in children: A rare complication related to calcineurin inhibitor effects(2011) SANTOS, Maria M.; TANNURI, Ana Cristina A.; GIBELLI, Nelson E.; AYOUB, Ali A.; MAKSOUD-FILHO, Joao G.; ANDRADE, Wagner C.; VELHOTE, Manoel C. P.; SILVA, Marcos M.; PINHO, Maria L.; MIYATANI, Helena T.; SUSUKI, Liza; TANNURI, UenisPRES is a neuroclinical and radiological syndrome that results from treatment with calcineurin inhibitor immunosuppressives. Severe hypertension is commonly present, but some patients may be normotensive. We report herein two children who received liver transplants, as treatment for biliary atresia in the first case and for Alagille's syndrome in the second one. In the early postoperative, both patients presented hypertension and seizures. In both cases, the image findings suggested the diagnosis of PRES. The CT scan showed alterations in the posterior area of the brain, and brain MRI demonstrated parietal and occipital areas of high signal intensity. Both children were treated by switching the immunosuppressive regimen and controlling arterial blood pressure. They displayed full recuperation without any neurologic sequelae. Probably, the pathophysiology of PRES results from sparse sympathetic innervation of the vertebrobasilar circulation, which is responsible for supplying blood to the posterior areas of the brain. In conclusion, all liver-transplanted children who present with neurological symptoms PRES should be considered in the differential diagnosis, although this is a rare complication. As treatment, we recommend rigorous control of arterial blood pressure and switching the immunosuppressive regimen.
- Hepatic Artery Graft in Pediatric Liver Transplantation: Single-Center Experience With 58 Cases(2011) BACKES, A. N.; GIBELLI, N. E. M.; TANNURI, A. C. A.; SANTOS, M. M.; PINHO-APEZZATO, M. L.; ANDRADE, W. C.; MAKSOUD-FILHO, J. G.; QUEIROZ, A. J. R.; TANNURI, U.Introduction. The use of arterial grafts (AG) in pediatric orthotopic liver transplantation (OLT) is an alternative in cases of poor hepatic arterial inflow, small or anomalous recipient hepatic arteries, and retransplantations (re-OLT) due to hepatic artery thrombosis (HAT). AG have been crucial to the success of the procedure among younger children. Herein we have reported our experience with AG. Methods. We retrospectively reviewed data from June 1989 to June 2010 among OLT in which we used AG, analyzing indications, short-term complications, and long-term outcomes. Results. Among 437 pediatric OLT, 58 children required an AG. A common iliac artery interposition graft was used in 57 cases and a donor carotid artery in 1 case. In 38 children the graft was used primarily, including 94% (36/38) in which it was due to poor hepatic arterial inflow. Ductopenia syndromes (n = 14), biliary atresia (BA; n = 11), and fulminant hepatitis (n = 8) were the main preoperative diagnoses among these children. Their mean weight was 18.4 kg and mean age was 68 months. At the mean follow-up of 27 months, multiple-organ failure and primary graft nonfunction (PNF) were the short-term causes of death in 9 children (26.5%). Among the remaining 29 patients, 2 (6,8%) developed early graft thrombosis requiring re-OLT; 5 (17%) developed biliary complications, and 1 (3.4%) had asymptomatic arterial stenosis. In 20 children, a graft was used during retransplantation. The main indication was HAT (75%). BA (n = 15), ductopenia syndromes (n = 2), and primary sclerosing cholangitis (n = 2) were the main diagnoses. Their mean weight was 16.7 kg and age was 65 months. At a mean follow-up of 53 months, 7 children died due to multiple-organ failure or PNF. Among the remaining 13 patients, 3 developed biliary complications and 1 had arterial stenosis. No thrombosis was observed. Conclusion. The data suggested that use of an AG is useful alternative in pediatric OLT. The technique is safe with a low risk of thrombosis.