CIRRHOTIC PATIENTS WITH ACUTE KIDNEY INJURY (AKI) HAVE HIGHER MORTALITY AFTER ABDOMINAL HERNIA SURGERY.

BACKGROUND: The incidence of abdominal hernia in cirrhotic patients is as higher as 20%; in cases of major ascites the incidence may increase up to 40%. One of the main and most serious complications in cirrhotic postoperative period (PO) is acute kidney injury (AKI). AIM: To analyze the renal function of cirrhotic patients undergoing to hernia surgery and evaluate the factors related to AKI. METHODS: Follow-up of 174 cirrhotic patients who underwent hernia surgery. Laboratory tests including the renal function were collected in the PO.AKI was defined based on the consensus of the ascite´s club. They were divided into two groups: with (AKI PO) and without AKI . RESULTS: All 174 patients were enrolled and AKI occurred in 58 (34.9%). In the AKI PO group, 74.1% had emergency surgery, whereas in the group without AKI PO it was only 34.6%.In the group with AKI PO, 90.4% presented complications, whereas in the group without AKI PO they occurred only in 29.9%. Variables age, baseline MELD, baseline creatinine, creatinine in immediate postoperative (POI), AKI and the presence of ascites were statistically significant for survival. CONCLUSIONS: There is association between AKI PO and emergency surgery and, also, between AKI PO and complications after surgery. The factors related to higher occurrence were initial MELD, basal Cr, Cr POI. The patients with postoperative AKI had a higher rate of complications and higher mortality.

Cirrhotic patients with acute kidney injury (aki) have higher mortality after abdominal hernia surgery / Pacientes cirróticos com lesão renal aguda tem maior mortalidade após cirurgia de hérnia abdominal

ABSTRACT Background: The incidence of abdominal hernia in cirrhotic patients is as higher as 20%; in cases of major ascites the incidence may increase up to 40%. One of the main and most serious complications in cirrhotic postoperative period (PO) is acute kidney injury (AKI). Aim: To analyze the renal function of cirrhotic patients undergoing to hernia surgery and evaluate the factors related to AKI. Methods: Follow-up of 174 cirrhotic patients who underwent hernia surgery. Laboratory tests including the renal function were collected in the PO.AKI was defined based on the consensus of the ascite´s club. They were divided into two groups: with (AKI PO) and without AKI . Results: All 174 patients were enrolled and AKI occurred in 58 (34.9%). In the AKI PO group, 74.1% had emergency surgery, whereas in the group without AKI PO it was only 34.6%.In the group with AKI PO, 90.4% presented complications, whereas in the group without AKI PO they occurred only in 29.9%. Variables age, baseline MELD, baseline creatinine, creatinine in immediate postoperative (POI), AKI and the presence of ascites were statistically significant for survival. Conclusions: There is association between AKI PO and emergency surgery and, also, between AKI PO and complications after surgery. The factors related to higher occurrence were initial MELD, basal Cr, Cr POI. The patients with postoperative AKI had a higher rate of complications and higher mortality.

RESUMO Racional: A incidência de hérnia abdominal em pacientes cirróticos é elevada, em torno de 20%. Em casos de ascite volumosa, a incidência atinge valores até 40%. Uma das principais e mais graves complicações no pós-operatório de correção de hérnias de pacientes cirróticos é a insuficiência renal aguda (IRA). Objetivo: Analisar a função renal de pacientes cirróticos submetidos a herniorrafias, comparando aqueles que apresentavam IRA pós-operatório com os demais, para determinar os fatores relacionados à sua ocorrência. Método: Seguimento de pacientes cirróticos submetidos à cirurgia de hérnia entre 2001 e 2014 no Serviço de Transplante de Fígado. Foram coletados exames laboratoriais para avaliar a função renal no pós-operatório rotineiramente. A IRA foi definida com base no consenso do clube da ascite em 2015. Resultados: Dos 174 pacientes incluídos, ocorreu IRA em 58 pacientes (34,9%). Houve diferença entre grupos para as seguintes variáveis: MELD inicial, creatinina basal e creatinina, o grupo com IRA apresentou medias superiores ao grupo que não apresentou IRA. No grupo IRA PO, 74,1% das cirurgias, foram realizadas em caráter de emergência, enquanto que no grupo sem IRA no pós-operatório, 34,6%. No grupo IRA, 90,4% dos indivíduos apresentaram complicações no pós-operatório, enquanto no grupo sem IRA, 29,9%. As variáveis idade, MELD inicial, creatinina basal e creatinina no pós-operatório inicial foram estatisticamente significantes na análise de sobrevida. Conclusões: Existe uma associação entre IRA pós-operatória e cirurgia de emergência e IRA pós-operatóri e complicações pós-operatórias. Os fatores relacionados à maior ocorrência de IRA em pacientes cirróticos submetidos à cirurgia de hérnia são o MELD inicial, creatinina basal, creatinina pós-operatória inicial. O preparo de pacientes cirróticos com hérnia abdominal antes de procedimentos cirúrgicos deve ocorrer sistematicamente, pois apresentam alta incidência de IRA pós-operatória.

Cholangioscopy-guided steroid injection for refractory post liver transplant anastomotic strictures: a rescue case series.

BACKGROUND AND AIMS: Post liver transplant biliary anastomotic strictures have traditionally been treated with balloon dilation and multiple plastic stents. Fully covered self-expandable metallic stents may be used as an initial alternative or after multiple plastic stents failure. Refractory strictures can occur in 10-22% and require revisional surgery. Alternatively, cholangioscopy allows direct visualization and therapeutic approaches. We aimed to assess the feasibility, safety, and efficacy of balloon dilation combined with cholangioscopy-guided steroid injection for the treatment of refractory anastomotic biliary strictures. METHODS: Three post-orthotopic liver transplant patients who failed standard treatment of their biliary anastomotic strictures underwent endoscopic retrograde cholangiopancreatography with balloon dilation followed by cholangioscopy-guided steroid injection at a tertiary care center. Patients had follow-up with images and laboratorial tests to evaluate for residual stricture. RESULTS: Technical success of balloon dilation + cholangioscopy-guided steroid injection was achieved in all patients. Cholangioscopy permitted accurate evaluation of bile ducts and precise localization for steroid injection. No adverse events occurred. Mean follow-up was 26 months. Two patients are stent free and remain well in follow-up, with no signs of biliary obstruction. No further therapeutic endoscopic procedures or revisional surgery were required. One patient did not respond to balloon dilation + cholangioscopy-guided steroid injection after 11 months of follow-up and required repeat balloon dilation of new strictures above the anastomosis. CONCLUSION: Cholangioscopy-guided steroid injection combined with balloon dilation in the treatment of refractory post liver transplant strictures is feasible and safe. This method may be used as a rescue alternative before surgical approach. Randomized controlled trials comparing balloon dilation + cholangioscopy-guided steroid injection to fully covered self-expandable metallic stents are needed to determine the role of this treatment for anastomotic biliary strictures.

Severe yellow fever in Brazil: clinical characteristics and management.

BACKGROUND: Little is known about clinical characteristics and management of severe yellow fever as previous yellow fever epidemics often occurred in times or areas with little access to intensive care units (ICU). We aim to describe the clinical characteristics of severe yellow fever cases requiring admission to the ICU during the 2018 yellow fever outbreak in São Paulo, Brazil. Furthermore, we report on preliminary lessons learnt regarding clinical management of severe yellow fever. METHODS: Retrospective descriptive cohort study. Demographic data, laboratory test results on admission, clinical follow-up, and clinical outcomes were evaluated. RESULTS: From 10 January to 11 March 2018, 79 patients with laboratory confirmed yellow fever were admitted to the ICU in a tertiary hospital in Sao Paolo because of rapid clinical deterioration. On admission, the median AST was 7,000 IU/L, ALT 3,936 IU/L, total bilirubin 5.3 ml/dL, platelet 74 × 103/mm3, INR 2.24 and factor V 37%. Seizures occurred in 24% of patients, even without substantial intracranial hypertension. The high frequency of pancreatitis and rapidly progressive severe metabolic acidosis were notable findings. 73% of patients required renal replacement therapy. The in-hospital fatality rate was 67%. Patients with diabetes mellitus had a higher case fatality rate (CFR) of 80%, while patients without diabetes had a CFR of 65%. Leading causes of death were severe gastrointestinal bleeding, epileptic status, severe metabolic acidosis, necrohemorrhagic pancreatitis, and multi-organ failure. CONCLUSIONS: Severe yellow fever is associated with a high CFR. The following management lessons were learnt: Anticonvulsant drugs in patients with any symptoms of hepatic encephalopathy or arterial ammonia levels >70 µmol/L was commenced which reduced the frequency of seizures from 28% to 17%. Other new therapy strategies included early institution of plasma exchange. Due to the high frequency of gastric bleeding, therapeutic doses of intravenous proton pump inhibitors should be administered.

Hepatocellular carcinoma recurrence after liver transplantation in a Brazilian multicenter study: clinical profile and prognostic factors of survival.

BACKGROUND: Liver transplantation (LT) is the treatment of choice for patients with unresectable early hepatocellular carcinoma (HCC). Post-LT HCC recurrence rates range from 8 to 20% and still impact on overall survival (OS). The aim of our study was to evaluate the impact of HCC recurrence on post-LT survival and analyze prognostic factors among those patients with recurrence. PATIENTS AND METHODS: We carried out a national, multicenter, retrospective cohort study in Brazil. Medical records of 1119 LT recipients with HCC were collected. Data from patients with post-LT HCC recurrence were analyzed and correlated with post-relapse survival. RESULTS: OS of the 1119 patients included in the study was 63% over 5 years. Post-LT HCC recurrence occurred in 86 (8%) patients. The mean time to recurrence was 12 months. Sites of recurrence were extrahepatic in 55%, hepatic in 27%, and both hepatic and extrahepatic in 18%. Recurrence treatment was performed in 50 (64%) cases, mostly with sorafenib. Post-relapse survival rates were 34% at 1 year and 13% at 5 years. Univariable analysis identified α-fetoprotein more than 1000 ng/ml at relapse, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years as prognostic factors. In multivariable analysis, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years were independent predictors of better survival. CONCLUSION: In a large Brazilian cohort of LT recipients with HCC, post-LT HCC recurrence occurred in 8% and impacted significantly on the OS. Patients with early recurrence presented a worse prognosis. However, treatment of recurrence improved outcomes, highlighting the importance of early diagnosis.

Yellow fever and orthotopic liver transplantation: new insights from the autopsy room for an old but re-emerging disease.

AIMS: The clinical spectrum of yellow fever (YF) ranges from asymptomatic to fulminant hepatitis. During the sylvatic YF epidemic in the metropolitan area of São Paulo, Brazil in 2018, seven orthotopic liver transplantations (OLTs) were performed in our institution to treat fulminant YF hepatitis. Three patients recovered, while four patients died following OLT. The autopsy findings of all these cases are presented herein as the first description of YF in transplanted patients. METHODS AND RESULTS: All patients were men, aged 16-40 years, without vaccination to YF virus (YFV). All organs were examined, with tissue sampling for histopathological analysis. Detection of YF virus antigens (YFV Ag) was performed with two primary antibodies (mouse polyclonal anti-YFV antibody directed to wild strain and a goat anti-YF virus antibody), and RT-PCR assays were utilised to detect YFV-RNA. All the cases depicted typical findings of YF hepatitis in the engrafted liver. The main extrahepatic findings were cerebral oedema, pulmonary haemorrhage, pneumonia, acute tubular necrosis and ischaemic/reperfusion pancreatitis. Of the four cases, the YVF Ag was detected in the heart in one case, liver and testis in three cases, and the kidney and spleen in all four cases. All four cases had YF virus RNA detected by RT-PCR in the liver and in other organs. CONCLUSIONS: Infection of the engrafted liver and other organs by YFV, possibly combined with major ischaemic systemic lesions, may have led to the death of four of the seven patients undergoing OLT.

ß-Blocker therapy for cirrhotic cardiomyopathy: a randomized-controlled trial.

BACKGROUND: Cirrhotic cardiomyopathy is characterized by an attenuated contractile response to stress. Long-term exposure of ß-adrenergic receptors to persistently high levels of catecholamines has been implicated in its pathogenesis. We hypothesized that ß-blockade with metoprolol could reverse the changes in heart function and morphology in cirrhotic cardiomyopathy. PATIENTS AND METHODS: In this prospective randomized trial, we included 78 patients aged between 18 and 60 years with abnormal cardiac output response under dobutamine stress echocardiography, without primary cardiac disease or a history of alcohol intake. Patients were assigned randomly to receive metoprolol or placebo for 6 months. The primary endpoint was the improvement in cardiac output response to stress, measured by an increase in the left ventricle stroke volume more than 30%. RESULTS: Three (7.3%) patients in the metoprolol group and nine (24.3%) patients in the placebo group showed improved stroke volume (P=0.057). Diastolic dysfunction was found in two (4.8%) patients before and in five (15.6%) patients after therapy in the metoprolol group, and in 10 (27%) patients before and nine (31%) patients after therapy in the placebo group (P=0.67). After treatment, no echocardiography parameter of morphology was significantly different between metoprolol or placebo groups. No significant differences were observed in noradrenaline, plasma renin activity, and troponin levels between groups. Cirrhosis-related clinical events, including hospitalizations and mortality, were not significantly different between the two groups. Six months of therapy with ß-blocker did not ameliorate heart function and morphology in patients with cirrhotic cardiomyopathy.

Laparoscopy-assisted versus open and pure laparoscopic approach for liver resection and living donor hepatectomy: a systematic review and meta-analysis.

BACKGROUND: Laparoscopy-assisted (hybrid) liver surgery is considered a minimally invasive technique, however there are doubts regarding loss of the benefits of laparoscopy due to the use of an auxiliary incision. The aim of this study was to compare perioperative results of hybrid vs. open and hybrid vs. pure laparoscopic approach to liver resection for focal lesions and living donation. METHODS: A systematic review was performed in Medline, EMBASE, Cochrane Library Central and LILACS databases. Perioperative outcomes were analyzed. RESULTS: 21 studies were included. Hybrid vs. open: operative time was lower in open group (mean difference [MD] = 34 min; 95%CI: 22-47; P < 0.001; N = 669). Hybrid technique was associated with a reduction in operative blood loss [MD = -43 ml; 95%CI: -74-(-13); P = 0.005, N = 1738]; shorter hospital stay [MD = -1.9 days; 95%CI: -3.2-(-0.5); P = 0.008; N = 833] and lower morbidity [risk difference (RD) = -0.05; 95%CI: -0.10-(-0.01); P = 0.010; N = 1359]. Hybrid vs. pure laparoscopic: There was no difference regarding blood loss, transfusion rate, hospital stay and morbimortality. DISCUSSION: Hybrid technique had perioperative outcomes that were more in keeping with pure laparoscopic outcomes than open surgery. Hybrid liver surgery should be considered a minimally invasive approach.

Living donor liver transplantation for hepatocellular cancer: an (almost) exclusive Eastern procedure?

Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and it is linked with chronic liver disease. Liver transplantation (LT) is the best curative treatment modality, since it can cure simultaneously the underlying liver disease and HCC. Milan criteria (MC) are the benchmark for selecting patients with HCC for LT, achieving up to 91% 1-year survival post transplantation. However, when considering intention-to-treat (ITT) rates are substantially lower, mainly due dropout. Additionally, Milan criteria (MC) are too restrictive and more inclusive criteria have been reported with good outcomes. Mainly, in Eastern countries, deceased donors are scarce, therefore Asian centers have developed living-donor liver transplantation (LDLT) to a state-of-art status. There are many eastern centers reporting huge numbers of LDLT with outstanding results. Regarding HCC patients, they have reported many criteria including more advanced tumors achieving reasonable outcomes. Western countries have well-established deceased-donor liver transplantation (DDLT) programs. However, organ shortage and restrictive criteria for listing patients with HCC endorses LDLT as a good option to offer curative treatment to more HCC patients. However, there are some controversial reports claiming higher rates of HCC recurrence after LDLT than DDLT. An extensive review included 30 studies with cohorts of HCC patients who underwent LDLT in both East and West countries. We reported also the results of our Institution, in Brazil, where it was performed the first LDLT. This review also addresses the eligibility criteria for transplanting patients with HCC developed in Western and Eastern countries.

Adherence to BCLC recommendations for the treatment of hepatocellular carcinoma: impact on survival according to stage.

OBJECTIVES:: This study sought to assess the adherence of newly diagnosed hepatocellular carcinoma patients to the Barcelona Clinic Liver Cancer system treatment guidelines and to examine the impact of adherence on the survival of patients in different stages of the disease. METHODS:: This study included all patients referred for the treatment of hepatocellular carcinoma between 2010 and 2012. Patients (n=364) were classified according to the Barcelona Clinic Liver Cancer guidelines. Deviations from the recommended guidelines were discussed, and treatment was determined by a multidisciplinary team. The overall survival curves were estimated with the Kaplan-Meier method and were compared using the log-rank test. RESULTS:: The overall rate of adherence to the guidelines was 52%. The rate of adherence of patients in each scoring group varied as follows: stage 0, 33%; stage A, 45%; stage B, 78%; stage C, 35%; and stage D, 67%. In stage 0/A, adherent patients had a significantly better overall survival than non-adherent patients (hazard ratio=0.19, 95% confidence interval (CI): 0.09-0.42; p<0.001). Among the stage D patients, the overall survival rate was worse in adherent patients than in non-adherent patients (hazard ratio=4.0, 95% CI: 1.67-9.88; p<0.001), whereas no differences were observed in patients in stages B or C. CONCLUSIONS:: The rate of adherence to the Barcelona Clinic Liver Cancer staging system in clinical practice varies according to clinical disease stage. Adherence to the recommended guidelines positively impacts survival, especially in patients with early-stage disease.

PREOPERATIVE COMPUTED TOMOGRAPHY VOLUMETRY AND GRAFT WEIGHT ESTIMATION IN ADULT LIVING DONOR LIVER TRANSPLANTATION.

Background: Computed tomography volumetry (CTV) is a useful tool for predicting graft weights (GW) for living donor liver transplantation (LDLT). Few studies have examined the correlation between CTV and GW in normal liver parenchyma. Aim: To analyze the correlation between CTV and GW in an adult LDLT population and provide a systematic review of the existing mathematical models to calculate partial liver graft weight. Methods: Between January 2009 and January 2013, 28 consecutive donors undergoing right hepatectomy for LDLT were retrospectively reviewed. All grafts were perfused with HTK solution. Estimated graft volume was estimated by CTV and these values were compared to the actual graft weight, which was measured after liver harvesting and perfusion. Results: Median actual GW was 782.5 g, averaged 791.43±136 g and ranged from 520-1185 g. Median estimated graft volume was 927.5 ml, averaged 944.86±200.74 ml and ranged from 600-1477 ml. Linear regression of estimated graft volume and actual GW was significantly linear (GW=0.82 estimated graft volume, r2=0.98, slope=0.47, standard deviation of 0.024 and p<0.0001). Spearman Linear correlation was 0.65 with 95% CI of 0.45 - 0.99 (p<0.0001). Conclusion: The one-to-one rule did not applied in patients with normal liver parenchyma. A better estimation of graft weight could be reached by multiplying estimated graft volume by 0.82.

Racional: A volumetria por tomografia computadorizada (VTC) é uma ferramenta útil para a previsão do peso do enxerto (PE) para o transplante hepático com doador vivo (TFDV). Poucos estudos examinaram a correlação entre o VTC e PE no parênquima hepático normal. Objetivo: Analisar a correlação entre VTC e PE em uma população adulta de doadores para o TFDV e realização de revisão sistemática dos modelos matemáticos existentes para calcular o peso de enxertos hepáticos parciais. Métodos: Foram revisados retrospectivamente 28 doadores consecutivos submetidos à hepatectomia direita para o TFDV entre janeiro de 2009 a janeiro de 2013. Todos os doadores eram adultos saudáveis ​​com VTC pré-operatório. Os enxertos foram perfundidos com solução de preservação HTK. O volume estimado foi obtido por VTC e estes valores foram comparados com o peso real do enxerto, o qual foi aferido depois da hepatectomia e perfusão do enxerto. Resultados: A mediana do PE real foi de 782,5 g, média de 791,43±136 g, variando de 520-1185 g. A mediana do volume estimado do enxerto foi de 927,5 ml, média de 944,86±200,74 ml e variou de 600-1477 ml. A regressão linear volume estimado do enxerto e PE real foi significativamente linear (PE=0.82 do volume estimado do enxerto, r2=0,98, declive=0,47, desvio-padrão de 0,024 e p<0,0001). Correlação linear de Spearman foi de 0,65, com IC de 95% do 0,45-0,99 (p<0,0001). Conclusão: A regra de "um-para-um" não deve ser empregada em pacientes com parênquima hepático normal. A melhor estimativa do peso do enxerto hepático de doador vivo pode ser alcançado através da multiplicação do VTC por 0,82.

Preoperative computed tomography volumetry and graft weight estimation in adult living donor liver transplantation / Estimativa do peso do enxerto hepático no transplante intervivos através da volumetria realizada por tomografia computadorizada pré-operatória

ABSTRACT Background: Computed tomography volumetry (CTV) is a useful tool for predicting graft weights (GW) for living donor liver transplantation (LDLT). Few studies have examined the correlation between CTV and GW in normal liver parenchyma. Aim: To analyze the correlation between CTV and GW in an adult LDLT population and provide a systematic review of the existing mathematical models to calculate partial liver graft weight. Methods: Between January 2009 and January 2013, 28 consecutive donors undergoing right hepatectomy for LDLT were retrospectively reviewed. All grafts were perfused with HTK solution. Estimated graft volume was estimated by CTV and these values were compared to the actual graft weight, which was measured after liver harvesting and perfusion. Results: Median actual GW was 782.5 g, averaged 791.43±136 g and ranged from 520-1185 g. Median estimated graft volume was 927.5 ml, averaged 944.86±200.74 ml and ranged from 600-1477 ml. Linear regression of estimated graft volume and actual GW was significantly linear (GW=0.82 estimated graft volume, r2=0.98, slope=0.47, standard deviation of 0.024 and p<0.0001). Spearman Linear correlation was 0.65 with 95% CI of 0.45 - 0.99 (p<0.0001). Conclusion: The one-to-one rule did not applied in patients with normal liver parenchyma. A better estimation of graft weight could be reached by multiplying estimated graft volume by 0.82.

RESUMO Racional: A volumetria por tomografia computadorizada (VTC) é uma ferramenta útil para a previsão do peso do enxerto (PE) para o transplante hepático com doador vivo (TFDV). Poucos estudos examinaram a correlação entre o VTC e PE no parênquima hepático normal. Objetivo: Analisar a correlação entre VTC e PE em uma população adulta de doadores para o TFDV e realização de revisão sistemática dos modelos matemáticos existentes para calcular o peso de enxertos hepáticos parciais. Métodos: Foram revisados retrospectivamente 28 doadores consecutivos submetidos à hepatectomia direita para o TFDV entre janeiro de 2009 a janeiro de 2013. Todos os doadores eram adultos saudáveis ​​com VTC pré-operatório. Os enxertos foram perfundidos com solução de preservação HTK. O volume estimado foi obtido por VTC e estes valores foram comparados com o peso real do enxerto, o qual foi aferido depois da hepatectomia e perfusão do enxerto. Resultados: A mediana do PE real foi de 782,5 g, média de 791,43±136 g, variando de 520-1185 g. A mediana do volume estimado do enxerto foi de 927,5 ml, média de 944,86±200,74 ml e variou de 600-1477 ml. A regressão linear volume estimado do enxerto e PE real foi significativamente linear (PE=0.82 do volume estimado do enxerto, r2=0,98, declive=0,47, desvio-padrão de 0,024 e p<0,0001). Correlação linear de Spearman foi de 0,65, com IC de 95% do 0,45-0,99 (p<0,0001). Conclusão: A regra de "um-para-um" não deve ser empregada em pacientes com parênquima hepático normal. A melhor estimativa do peso do enxerto hepático de doador vivo pode ser alcançado através da multiplicação do VTC por 0,82.

Trisulfate Disaccharide Decreases Calcium Overload and Protects Liver Injury Secondary to Liver Ischemia/Reperfusion.

BACKGROUND: Ischemia and reperfusion (I/R) causes tissue damage and intracellular calcium levels are a factor of cell death. Sodium calcium exchanger (NCX) regulates calcium extrusion and Trisulfated Disaccharide (TD) acts on NCX decreasing intracellular calcium through the inhibition of the exchange inhibitory peptide (XIP). OBJECTIVES: The aims of this research are to evaluate TD effects in liver injury secondary to I/R in animals and in vitro action on cytosolic calcium of hepatocytes cultures under calcium overload. METHODS: Wistar rats submitted to partial liver ischemia were divided in groups: CONTROL: (n = 10): surgical manipulation with no liver ischemia; Saline: (n = 15): rats receiving IV saline before reperfusion; and TD: (n = 15): rats receiving IV TD before reperfusion. Four hours after reperfusion, serum levels of AST, ALT, TNF-α, IL-6, and IL-10 were measured. Liver tissue samples were collected for mitochondrial function and malondialdehyde (MDA) content. Pulmonary vascular permeability and histologic parameters of liver were determined. TD effect on cytosolic calcium was evaluated in BRL3A hepatic rat cell cultures stimulated by thapsigargin pre and after treatment with TD. RESULTS: AST, ALT, cytokines, liver MDA, mitochondrial dysfunction and hepatic histologic injury scores were less in TD group when compared to Saline Group (p<0.05) with no differences in pulmonary vascular permeability. In culture cells, TD diminished the intracellular calcium raise and prevented the calcium increase pre and after treatment with thapsigargin, respectively. CONCLUSION: TD decreases liver cell damage, preserves mitochondrial function and increases hepatic tolerance to I/R injury by calcium extrusion in Ca2+ overload situations.

Successful liver allograft inflow reconstruction with the right gastroepiploic vein.

Portal vein thrombosis is a common complication in cirrhotic patients. When portal vein thrombectomy is not a suitable option, a large collateral vessel can be used for allograft venous inflow reconstruction. We describe an unusual case of successful portal revascularization using the right gastroepiploic vein. The patient underwent a cadaveric orthotopic liver transplantation with end-to-end anastomosis of the portal vein to the right gastroepiploic vein. Six months after liver transplantation the patient is well with good liver function. The use of the right gastroepiploic vein for allograft venous reconstruction is feasible and safe, with a great advantage of avoiding the need of venous jump graft.

Pentoxifylline enhances the protective effects of hypertonic saline solution on liver ischemia reperfusion injury through inhibition of oxidative stress.

BACKGROUND: Liver ischemia reperfusion (IR) injury triggers a systemic inflammatory response and is the main cause of organ dysfunction and adverse postoperative outcomes after liver surgery. Pentoxifylline (PTX) and hypertonic saline solution (HTS) have been identified to have beneficial effects against IR injury. This study aimed to investigate if the addition of PTX to HTS is superior to HTS alone for the prevention of liver IR injury. METHODS: Male Wistar rats were allocated into three groups. Control rats underwent 60 minutes of partial liver ischemia, HTS rats were treated with 0.4 mL/kg of intravenous 7.5% NaCl 15 minutes before reperfusion, and HPTX group were treated with 7.5% NaCl plus 25 mg/kg of PTX 15 minutes before reperfusion. Samples were collected after reperfusion for determination of ALT, AST, TNF-alpha, IL-6, IL-10, mitochondrial respiration, lipid peroxidation, pulmonary permeability and myeloperoxidase. RESULTS: HPTX significantly decreased TNF-alpha 30 minutes after reperfusion. HPTX and HTS significantly decreased ALT, AST, IL-6, mitochondrial dysfunction and pulmonary myeloperoxidase 4 hours after reperfusion. Compared with HTS only, HPTX significantly decreased hepatic oxidative stress 4 hours after reperfusion and pulmonary permeability 4 and 12 hours after reperfusion. CONCLUSION: This study showed that PTX added the beneficial effects of HTS on liver IR injury through decreases of hepatic oxidative stress and pulmonary permeability.

Conditioning With Sevoflurane in Liver Transplantation: Results of a Multicenter Randomized Controlled Trial.

BACKGROUND: During times of organ scarcity and extended use of liver grafts, protective strategies in transplantation are gaining importance. We demonstrated in the past that volatile anesthetics such as sevoflurane attenuate ischemia-reperfusion injury during liver resection. In this randomized study, we examined if volatile anesthetics have an effect on acute graft injury and clinical outcomes after liver transplantation. METHODS: Cadaveric liver transplant recipients were enrolled from January 2009 to September 2012 at 3 University Centers (Zurich/Sao Paulo/Ghent). Recipients were randomly assigned to propofol (control group) or sevoflurane anesthesia. Postoperative peak of aspartate transaminase was defined as primary endpoint, secondary endpoints were early allograft dysfunction, in-hospital complications, intensive care unit, and hospital stay. RESULTS: Ninety-eight recipients were randomized to propofol (n = 48) or sevoflurane (n = 50). Median peak aspartate transaminase after transplantation was 925 (interquartile range, 512-3274) in the propofol and 1097 (interquartile range, 540-2633) in the sevoflurane group. In the propofol arm, 11 patients (23%) experienced early allograft dysfunction, 7 (14%) in the sevoflurane one (odds ratio, 0.64 (0.20 to 2.02, P = 0.45). There were 4 mortalities (8.3%) in the propofol and 2 (4.0%) in the sevoflurane group. Overall and major complication rates were not different. An effect on clinical outcomes was observed favoring the sevoflurane group (less severe complications), but without significance. CONCLUSIONS: This first multicenter trial comparing propofol with sevoflurane anesthesia in liver transplantation shows no difference in biochemical markers of acute organ injury and clinical outcomes between the 2 regimens. Sevoflurane has no significant added beneficial effect on ischemia-reperfusion injury compared to propofol.

Severe acute pancreatitis: a possible role of intramyocardial cytokine production.

CONTEXT: Several mechanisms are involved in the development of the local and systemic response in acute pancreatitis. Cardiovascular system may be affected throughout the clinical course of acute pancreatitis. The aim was to evaluate local myocardial cytokine production, as well as, functional and histological myocardial alterations in severe acute pancreatitis. METHODS: The animals were divided into three groups: Group 1: control; Group 2: sham; Group 3: severe acute pancreatitis. Echocardiographic assessment of cardiac function, serum levels of amylase and cytokines (TNF-α, IL-6 and IL-10), and mRNA expression of TNF-α, IL-6 and TGF-ß were measured. Myocardial tissue alterations were analysed by histological examination. RESULTS: The serum TNF-α and IL-10 levels were significant higher in AP 2h group. The mRNA IL-6 levels from group AP 2h were statistically higher. The mRNA TNF-α level from sham group and AP 2h were statistically lower. Significant changes in the left ventricular diameter were found in AP 2h and AP 12h groups. There were statistical changes for vacuolar degeneration, picnosis and loss of nucleus, and lymphocytes. CONCLUSION: We found cardiac and histological changes compatible with the inflammatory process triggered by SAP with the promotion of local myocardial cytokine production.

Serum B-type natriuretic peptide in the initial workup of patients with new onset ascites: a diagnostic accuracy study.

UNLABELLED: Heart failure (HF) is, after cirrhosis, the second-most common cause of ascites. Serum B-type natriuretic peptide (BNP) plays an important role in the diagnosis of HF. Therefore, we hypothesized that BNP would be useful in the differential diagnosis of ascites. Consecutive patients with new onset ascites were prospectively enrolled in this cross-sectional study. All patients had measurements of serum-ascites albumin gradient (SAAG), total protein concentration in ascitic fluid, serum, and ascites BNP. We enrolled 218 consecutive patients with ascites resulting from HF (n = 44), cirrhosis (n = 162), peritoneal disease (n = 10), and constrictive pericarditis (n = 2). Compared to SAAG and/or total protein concentration in ascites, the test that best discriminated HF-related ascites from other causes of ascites was serum BNP. A cutoff of >364 pg/mL (sensitivity 98%, specificity 99%, and diagnostic accuracy 99%) had the highest positive likelihood ratio (168.1); that is, it was the best to rule in HF-related ascites. Conversely, a cutoff ≤ 182 pg/mL had the lowest negative likelihood ratio (0.0) and was the best to rule out HF-related ascites. These findings were confirmed in a 60-patient validation cohort. CONCLUSIONS: Serum BNP is more accurate than ascites analyses in the diagnosis of HF-related ascites. The workup of patients with new onset ascites could be streamlined by obtaining serum BNP as an initial test and could forego the need for diagnostic paracentesis, particularly in cases where the cause of ascites is uncertain and/or could be the result of HF.

Diagnosis and impact of hilar lymph node micrometastases on the outcome of resected colorectal liver metastasis.

BACKGROUND/AIMS: Liver resection is the only curative therapy for metastatic colorectal cancer. However, recurrence occurs in the majority of the cases. Hilar lymph node metastases occur with a high frequency but the methodology for its detection and the impact on the outcome of patients undergoing hepatectomy is still unknown. METHODOLOGY: Twenty-six patients submitted to partial liver resection and systematic lymphadenectomy were studied prospectively. Lymph nodes considered negative by hematoxylin and eosin (H&E) staining were analyzed by serial sectioning and immunohistochemistry (IHC) with anti-human pancytokeratin antibody AE1/AE3. Recurrence-free and overall survivals were compared among LN groups. RESULTS: The mean number of dissected lymph nodes were 6.3 per patient. H&E showed microscopic involvement of LN in 2 patients and 3 patients had metastases identified only by IHC. The median follow-up was 39.3 months. Sixteen patients (61.5%) recurred after liver resection and although no statistical difference in survival was demonstrated there was a trend towards shorter recurrence-free survival among microscopic positive LN. CONCLUSIONS: Microscopic LN metastases may have impact in the outcome of patients submitted to curative hepatectomy. A better definition of micrometastases to LN is warranted, as though the potential benefit of hilar lymphadenectomy and chemotherapy selection by hilar lymph node status.