Molecular Basis of Hyperammonemic Encephalopathy in Fibrolamellar Hepatocellular Carcinoma.

Hyperammonemic encephalopathy is a potentially fatal condition associated with fibrolamellar hepatocellular carcinoma. The mechanism involved in hyperammonemia in patients with fibrolamellar carcinoma was unclear until a possible physiopathological pathway was recently proposed. An ornithine transcarboxylase dysfunction was suggested as a result of increased ornithine decarboxylase activity induced by c-Myc overexpression. This c-Myc overexpression resulted from Aurora kinase A overexpression derived from the activity of a chimeric kinase that is the final transcript of a deletion in chromosome 19, common to all fibrolamellar carcinomas. We performed the analysis of the expression of all enzymes involved and tested for the mutation in chromosome 19 in fresh frozen samples of fibrolamellar hepatocellular carcinoma, non-tumor liver, and hepatic adenomatosis. The specific DNAJB-PRKACA fusion protein that results from the recurrent mutation on chromosome 19 common to all fibrolamellar carcinoma was detected only in the fibrolamellar carcinoma sample. Fibrolamellar carcinoma and adenomyomatosis samples presented increased expression of Aurora kinase A, c-MYC, and ornithine decarboxylase when compared to normal liver, while ornithine transcarbamylase was decreased. The proposed physiopathological pathway is correct and that overexpression of c-Myc may also be responsible for hyperammonemia in patients with other types of rapidly growing hepatomas. This gives further evidence to apply new and adequate treatment to this severe complication.

Acinar cell carcinoma of the pancreas: is the absence of neuroendocrine component related to a more malignant behavior?

BACKGROUND/AIMS: Acinar cell carcinomas are uncommon malignant tumors of the pancreas, accounting for 1-2% of all the cases of exocrine pancreatic tumor. Some authors have estimated acinar cell tumors to be as aggressive as ductal adenocarcinoma of the pancreas whereas other series showed acinar cell tumors to have a favorable clinical outcome. This discrepancy in prognosis may be related to the cellular components of the tumor. METHODOLOGY: With the aim to evaluate the possible relationship between the presence of neuroendocrine differentiation and behavior of these tumors, the authors reviewed all patients presenting acinar cell carcinoma of the pancreas in the last 5 years with emphasis in the immunohistochemical evaluation. RESULTS: Four patients presented neuroendocrine differentiation on immunohistochemical evaluation and had a more benign outcome. Two patients without neuroendocrine component had a disseminated disease at presentation. This data suggests that this tumor is less aggressive than ductal adenocarcinoma and even with nodal involvement, long-term survival after complete resection can be achieved. CONCLUSIONS: It is possible that the absence of neuroendocrine component may be related to a less favorable outcome and adjuvant therapy may be necessary. Due to the rarity of this pancreatic tumor, this relationship remains to be confirmed with a multicentric study including a larger number of patients.

Hipertensão portal esquistossomótica: influência do fluxo sangüíneo portal nos níveis séricos das enzimas hepáticas / Schistosomal portal hypertension: influence of the portal blood flow in serum levels of hepatic enzymes

OBJETIVO: Avaliar a relação entre o fluxo sangüíneo portal e o perfil laboratorial hepático em pacientes com hipertensão portal esquistossomótica. PACIENTES E MÉTODOS: Estudaram-se 64 pacientes com hipertensão portal esquistossomótica, sendo 19 não-operados, 23 submetidos a desconexão ázigo-portal com esplenectomia e 22 submetidos a derivação esplenorrenal distal. Avaliou-se o perfil laboratorial hepático através da dosagem sérica de albumina, transaminases glutâmico-oxalacética e glutâmico-pirúvica, bilirrubinas direta e indireta, fosfatase alcalina, gama-glutamil transferase e avaliação do tempo de protrombina. O fluxo portal foi avaliado por Doppler. Os resultados foram analisados através de regressão linear, coeficiente de correlação de Pearson, teste do Qui-quadrado e análise de variância de um via com pós-teste de Tukey. RESULTADOS: Evidenciou-se que somente a gama-glutamil transferase teve correlação significativa com o fluxo portal. No cotejo dos quartis, também, somente a gama-glutamil transferase mostrou resultado significativo, em que se constatou que o quarto quartil, de maior fluxo portal e formado em sua maioria por pacientes não operados, também foi o de maior valor médio de gama-glutamil transferase e significativamente maior que o primeiro e terceiro quartis. CONCLUSÕES: Estes dados sugerem que: quanto maior o fluxo sangüíneo portal, maior o nível sérico de gama-glutamil transferase; a gama-glutamil transferase é a variável da avaliação do perfil hepático mais representativa da influência do fluxo portal na atividade funcional hepática nos pacientes com esquistossomose hepatoesplênica, e é possível que as cirurgias, através de suas modificações hemodinâmicas (diminuição da congestão), sejam também benéficas por diminuírem o grau de colestase presente ou em regredirem a indução microssomal.

[Schistosomal portal hypertension: influence of the portal blood flow in serum levels of hepatic enzymes]. / Hipertensão portal esquistossomótica: influência do fluxo sangüíneo portal nos níveis séricos das enzimas hepáticas.

AIM: To evaluate relation between the portal blood flow and the laboratory hepatic screening in patients with schistosomal portal hypertension. PATIENTS AND METHODS: Sixty-four patients with schistosomal portal hypertension had studied, being 19 not operated, 23 submitted to esophagogastric devascularization with splenectomy and 22 submitted to distal splenorenal shunt. Evaluated the laboratory hepatic screening through the dosage of albumin, aspartate aminotransferase, alanine aminotransferase, direct bilirubin and indirect bilirubin, alkaline phosphatase, gamma-glutamil transferase and prothrombin time. The portal flow was evaluated for Doppler. The results have been analyzed through linear regression, Pearson correlation coefficient, chi-square and one-way analysis of variance with Tukey's test. RESULTS: It was proven that only gamma-glutamil transferase had significant correlation with the portal flow. In compare of the quartiles, also only gamma-glutamil transferase showed resulted significant, it was evidenced that the fourth quartile, that is bigger portal flow and formed in its majority for patients not operated, also was bigger average of gamma-glutamil transferase and significantly bigger value than first and the third quartiles. CONCLUSIONS: 1. The portal blood flow was bigger in patients that the serum level of GGT was bigger; 2. the gamma-glutamil transferase is the variable of the hepatic screening evaluation more representative of the portal flow influence in hepatic functional activity in patients with hepatosplenic schistosomiasis, and 3. probably, the different surgeries through hemodynamics modifications, are beneficial in to diminish the degree of cholestasis or in decrease the microssomal induction.

Hipertensão portal esquistossomótica avaliação do fluxo sangüíneo portal antes e após tratamento cirúrgico / Schistosomal portal hypertension: assessment of portal bood flow before and after surgical treatment

OBJETIVO: Avaliar o fluxo sangüíneo portal na esquistossomose hepato-esplênica e o efeito tardio do tratamento cirúrgico na hemodinâmica portal. MÉTODO: Foram estudados 64 pacientes por Doppler dúplex: grupo I (pacientes com hipertensão portal esquistossomótica); grupo II (pacientes submetidos a desconexão ázigo-portal com esplenectomia) e grupo III (pacientes submetidos derivação esplenorrenal distal). RESULTADOS: O fluxo da veia porta foi maior no grupo I (1954,46 ± 693,73ml/min) e foi menor no grupo III (639,55 ± 285,86ml/min), neste correlacionou-se com o tempo pós-operatório (r=-0,67, p=0,0005). O fluxo sangüíneo portal do grupo II (1097,18 ± 342,12ml/min) foi semelhante ao de indivíduos normais. As mesmas alterações foram verificadas com relação ao diâmetro da veia porta nos grupos I, II, e III (cm): 1,46 ± 0,23; 1,12 ± 0,22; 0,93 ± 0,20, respectivamente. CONCLUSÕES: Estes dados sugerem que: 1) Existe hiperfluxo portal na fisiopatologia da hipertensão portal esquistossomótica; 2) o tratamento cirúrgico interferiu na hemodinâmica portal, diminuindo o fluxo sangüíneo da veia porta; 3) Esta redução do fluxo sangüíneo portal correlacionou-se com o tempo de seguimento pós-operatório no grupo III mas não no grupo II.

BACKGROUND: Assessment of the portal blood flow in hepatoesplenic schistosomosis and the late effect of surgical treatment on portal hemodynamics. METHOD: Were studied 64 patients by duplex scan: group I (patients with schistosomal portal hypertension); group II (patients who underwent esophagogastric devascularization and splenectomy); group III (patients who underwent distal splenorenal shunt). RESULTS: Portal vein blood flow was the highest in group I (1954.46 ± 693.73 ml/min) and the lowest in group III (639.55 ± 285.86 ml/min) which correlated with follow-up time (r=-0.67, p=0.0005). Group II portal flow (1097.18 ± 342.12 ml/min) was similar to control. The same changes were seen in portal vein diameter in groups I, II, III (cm): 1.46 ± 0.23, 1.12 ± 0.22, 0.93 ± 0.20, respectively. CONCLUSIONS: Our data suggest that: 1) there is portal overflow in the physiopathology of schistosomal portal hypertension; 2) surgical treatment has interfered in hemodynamic reducing portal venous blood flow; 3) portal venous blood flow reduction correlated with follow-up time in group III but not in group II.