Risk Factors for Hepatocellular Carcinoma Recurrence and Survival after Liver Transplantation in Patients with HCV-Related Cirrhosis.

PURPOSE: We aimed to identify prognostic factors for survival and recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) for patients with HCC and hepatitis C virus-related cirrhosis (HCV-cirrhosis). METHODS: This retrospective cohort study followed all adult patients with HCV-cirrhosis who underwent LT because of HCC or had incidental HCC identified through pathologic examination of the explanted liver at a university hospital in Rio de Janeiro, Brazil, over 11 years (1998-2008). We used Cox regression models to assess the following risk factors regarding HCC recurrence or death after LT: age, Model for End-stage Liver Disease score, Child-Pugh classification, alpha-fetoprotein (AFP), whether patients had undergone locoregional treatment before transplantation, the number of packed red blood cell units (PRBCU) transfused during surgery, the number and size of HCC lesions in the explanted liver, and the presence of microvascular invasion and necrotic areas within HCC lesions. RESULTS: Seventy-six patients were followed up for a median (interquartile range (IQR)) of 4.4 (0.7-6.6) years. Thirteen (17%) patients had HCC recurrence during the follow-up period, and 26 (34%) died. The median survival time was 6.6 years (95% CI: 2.4-12.0), and the 5-year survival was 52.5% (95% CI: 42.3-65.0%). The final regression model for overall survival included four variables: age (hazard ratio (HR): 1.02, 95% CI: 0.96-1.08, P = 0.603), transplantation waiting time (HR: 1.00, 95% CI: 1.00-1.00, P = 0.190), preoperative AFP serum levels (HR: 1.01, 95% CI: 1.00-1.02, P = 0.006), and whether >4 PRBCU were transfused during surgery (HR: 1.15, 95% CI: 1.05-1.25, P = 0.001). The final cause-specific Cox regression model for HCC recurrence included only microvascular invasion (HR: 14.86, 95% CI: 4.47-49.39, P < 0.001). CONCLUSION: In this study of LT for HCV-cirrhosis, preoperative AFP levels and the number of PRBCU transfused during surgery were associated with overall survival, whereas microvascular invasion with HCC recurrence.

Assessment of remnant liver function and volume after selective ligation of portal vein and hepatic artery in a rat model.

PURPOSE: To evaluate liver regeneration after selective ligation of portal vein and hepatic artery by 3D Computed Tomography in an experimental model. METHODS: Sixteen Wistar rats were randomized into four equal groups: Group I- control (sham), Group II- isolated selective ligation of the hepatic artery, Group III- isolated selective ligation of the portal vein and Group IV- combined ligation of portal vein and hepatic artery. Before procedure and five days after a 3D CT Scan was performed to analyze the hypertrophy, weight and function of the remnant liver. RESULTS: The largest regeneration rate and increase of weight in the hypertrophied lobe was detected in group IV, the first with an average of 3.99 (p=0.006) and the last varying from 6.10g to 9.64g (p=0.01). However, total liver weight and the R1 ratio (Hypertrophied Lobe Weight/Total Liver Weight) was higher in group III (P<0.001) when compared with groups I, II and IV and showed no difference between them. The immunohistochemical examination with PCNA also found higher percentages with statistical significance differences in rats of groups III and IV. It was possible to confirm a strong correlation between hypertrophied lobe weight and its imaging volumetric study. Liver function tests only showed a significant difference in serum gamma-glutamyltransferase and phosphorous. CONCLUSION: There is a largest liver regeneration after combined ligation of portal vein and hepatic artery and this evidence may improve the knowledge of surgical treatment of liver injuries, with a translational impact in anima nobile.

Assessment of remnant liver function and volume after selective ligation of portal vein and hepatic artery in a rat model

Abstract Purpose: To evaluate liver regeneration after selective ligation of portal vein and hepatic artery by 3D Computed Tomography in an experimental model. Methods: Sixteen Wistar rats were randomized into four equal groups: Group I- control (sham), Group II- isolated selective ligation of the hepatic artery, Group III- isolated selective ligation of the portal vein and Group IV- combined ligation of portal vein and hepatic artery. Before procedure and five days after a 3D CT Scan was performed to analyze the hypertrophy, weight and function of the remnant liver. Results: The largest regeneration rate and increase of weight in the hypertrophied lobe was detected in group IV, the first with an average of 3.99 (p=0.006) and the last varying from 6.10g to 9.64g (p=0.01). However, total liver weight and the R1 ratio (Hypertrophied Lobe Weight/Total Liver Weight) was higher in group III (P<0.001) when compared with groups I, II and IV and showed no difference between them. The immunohistochemical examination with PCNA also found higher percentages with statistical significance differences in rats of groups III and IV. It was possible to confirm a strong correlation between hypertrophied lobe weight and its imaging volumetric study. Liver function tests only showed a significant difference in serum gamma-glutamyltransferase and phosphorous. Conclusion: There is a largest liver regeneration after combined ligation of portal vein and hepatic artery and this evidence may improve the knowledge of surgical treatment of liver injuries, with a translational impact in anima nobile.

Validation of a new technique to freezing and embedding tissue in Mohs surgery, using an animal model

ABSTRACT PURPOSE: To validate the innovative Dry Ice method, comparing it with two standard methods currently used for tissue processing in Mohs surgery, the Heat Sink method and the Miami Special. METHODS: Forty eight samples of pigs kin with the standard beveled Mohs technique were used, and randomly allocated into six groups. Each group was processed with one of the 3 methods and evaluated for: The freezing time, the depth required to cut into the block to obtain a complete section, and the quality of histological slides analyzed with a image software. The statistical analysis was performed with the software SAS(r) System. The inferential analysis was made by one-way ANOVA. RESULTS: The Miami Special showed a processing time significantly shorter than Dry Ice method and Heat Sink method. There was no significant difference in the depth required to cut into the blocks, and area of surgical margins visualized. CONCLUSION: The Dry Ice method was as efficient as the other two methods currently used in Mohs surgery, considering the individual advantages and disadvantages of each method.

THE LARGEST WESTERN EXPERIENCE WITH HEPATOPANCREATODUODENECTOMY: LESSONS LEARNED WITH 35 CASES.

BACKGROUND: Hepatopancreatoduodenectomy is one of the most complex abdominal operations mainly indicated in advanced biliary carcinoma. AIM: To present 10-year experience performing this operation in advanced malignant tumors. METHODS: This is a retrospective descriptive study. From 2004 to 2014, 35 hepatopancreatoduodenectomies were performed in three different institutions. The most common indication was advanced biliary carcinoma in 24 patients (68.5%). RESULTS: Eighteen patients had gallbladder cancer, eight Klatskin tumors, five neuroendocrine tumors with liver metastasis, one colorectal metastasis invading the pancreatic head, one intraductal papillary mucinous neoplasm with liver metastasis, one gastric cancer recurrence with liver involvement and one ocular melanoma with pancreatic head and right liver lobe metastasis. All patients were submitted to pancreatoduodenectomy with a liver resection as follows: eight right trisectionectomies, five right lobectomies, four left lobectomies, 18 central lobectomies (IVb, V and VIII). The overall mortality was 34.2% (12/35) and the overall morbidity rate was 97.4%. CONCLUSION: Very high mortality is seen when major liver resection is performed with pancreatoduodenectomy, including right lobectomy and trisectionectomy. Liver failure in combination with a pancreatic leak is invariably lethal. Efforts to ensure a remnant liver over 40-50% of the total liver volume are the key to obtain patient survival.

The largest western experience with hepatopancreatoduodenectomy: lessons learned with 35 cases / A maior experiência ocidental com hepatopancreatoduodenectomia: lições aprendidas com 35 casos

Background : Hepatopancreatoduodenectomy is one of the most complex abdominal operations mainly indicated in advanced biliary carcinoma. Aim : To present 10-year experience performing this operation in advanced malignant tumors. Methods : This is a retrospective descriptive study. From 2004 to 2014, 35 hepatopancreatoduodenectomies were performed in three different institutions. The most common indication was advanced biliary carcinoma in 24 patients (68.5%). Results: Eighteen patients had gallbladder cancer, eight Klatskin tumors, five neuroendocrine tumors with liver metastasis, one colorectal metastasis invading the pancreatic head, one intraductal papillary mucinous neoplasm with liver metastasis, one gastric cancer recurrence with liver involvement and one ocular melanoma with pancreatic head and right liver lobe metastasis. All patients were submitted to pancreatoduodenectomy with a liver resection as follows: eight right trisectionectomies, five right lobectomies, four left lobectomies, 18 central lobectomies (IVb, V and VIII). The overall mortality was 34.2% (12/35) and the overall morbidity rate was 97.4%. Conclusion : Very high mortality is seen when major liver resection is performed with pancreatoduodenectomy, including right lobectomy and trisectionectomy. Liver failure in combination with a pancreatic leak is invariably lethal. Efforts to ensure a remnant liver over 40-50% of the total liver volume are the key to obtain patient survival.

Racional : Hepatoduodenopancreatectomia é uma das operações abdominais mais complexas indicadas principalmente no carcinoma biliar avançado. Objetivo : Apresentar experiência de 10 anos executando esta operação em tumores malignos avançados. Métodos : Trata-se de estudo descritivo e retrospectivo. De 2004 a 2014, 35 hepatopancreatoduodenectomias foram realizadas em três diferentes instituições. A indicação mais comum foi carcinoma biliar avançado em 24 pacientes (68,5%). Resultados : Dezoito tinham câncer de vesícula biliar, oito tumores de Klatskin, cinco tumores neuroendócrinos com metástase hepática, uma metástase colorretal invadindo a cabeça do pâncreas, uma neoplasia mucinosa papilar intraductal com metástase hepática, uma recorrência do câncer gástrico com comprometimento hepático e um melanoma ocular com metástase na cabeça do pâncreas e no lobo direito do fígado. Todos os pacientes foram submetidos a duodenopancreatectomia com ressecção hepática da seguinte forma: oito triseccionectomias direitas, cinco lobectomias direitas, quatro lobectomias esquerdas, e 18 lobectomias centrais (IVb, V e VIII). A mortalidade global foi de 34,2% (12/35) e a taxa de morbidade global foi de 97,4%. Conclusão : Alta mortalidade é vista quando grande ressecção hepática é realizada junto à duodenopancreatectomia, incluindo lobectomia e triseccionectomia direita. Insuficiência hepática em combinação com deiscência do pâncreas é invariavelmente letal. Esforços para garantir fígado remanescente em 40-50% do volume total são a chave para obter sobrevida.

Survival tree and MELD to predict long term survival in liver transplantation waiting list.

MELD score is a formula based on laboratory variables used as a predictor of short-term mortality index in cirrhotic patients. It is applied to allocate patients in liver transplantation waiting list in many countries. However, MELD score cutoff point accuracy to predict long term mortality has not been statistically evaluated. The aim of this study was to analyze the MELD score and other variables related to long-term mortality using a new model: the Survival Tree analysis. The variables considered in this study were obtained at the time of liver transplantation list enrollment. The graphical representation of the survival trees showed that MELD 16 was the most statistically significant mortality cutoff point. The results were compatible with the MELD cutoff point reported in the clinical literature. This methodology can be extended to identify significant cutoff points related to other diseases whose severity is not necessarily expressed by MELD.

Extrahepatic right hepatic duct diverticulum: a rare entity.

BACKGROUND: Douglas described choledochal cysts in 1852 and Todani proposed an anatomy-based classification in 1977. The classification is the most extensively used, but does not include some rare variations. We present a case of hepatic duct diverticulum, one of the variations, and discuss its diagnosis and treatment. METHODS: A 57-year-old woman presented with upper abdominal pain and discomfort associated with nausea and vomiting. She was finally diagnosed with cholelithiasis and right hepatic duct diverticulum. RESULT: The patient underwent resection of the hepatic duct diverticulum and cholecystectomy, and was asymptomatic 26 months after surgery. CONCLUSIONS: Hepatic duct diverticulum is a rare form of choledochal cyst, not included in Todani's classification. Todani's classification including this and other uncommon variations of choledochal cysts must be reviewed. The best diagnostic imaging methods and treatment for choledochal cysts must be defined.

Orthotopic liver transplantation in glucose-6-phosphatase deficiency--Von Gierke disease--with multiple hepatic adenomas and concomitant focal nodular hyperplasia.

Von Gierke disease is occasionally complicated by hepatic adenomas (HAs) causing great concern owing to the current difficulties in monitoring them regarding malignant transformation. Orthotopic liver transplantation (OLT) is proposed as a therapeutic tool when multiple HAs and poor metabolic control are present, owing to the lack of a clear-cut criterion to detect early malignant transformation, whether or not associated with growth retardation. Focal nodular hyperplasia (FNH) has never been described together with multiple adenomas in von Gierke disease. We report a 26-year-old woman with von Gierke disease complicated by multiple HAs concomitant with FNH who underwent OLT and is now free from disease symptoms with good long-term outcome. In conclusion, although FNH could have been managed clinically, when multiple adenomas are present, OLT should be planned for some patients, mainly for those with poor metabolic control.

Metástase hepática de adenocarcinoma colorretal com disseminação endobiliar: expressão das citoqueratinas 7, 19 e 20 / Hepatic metastasis of colorectal adenocarcinoma with endobiliary growth: expression of cytokeratins 7, 19 and 20

O crescimento endobiliar das neoplasias primárias e metastáticas do fígado é raro, com exceção dos colangiocarcinomas. Nas metástases esse comportamento pode suscitar dificuldade no diagnóstico diferencial com colangiocarcinomas quando são analisadas apenas as características morfológicas das neoplasias e/ou quando há associação com anormalidades que sugiram a origem biliar do tumor. Analisamos a imunoexpressão das citoqueratinas (CKs) 7, 19 e 20 em dois casos de metástase hepática de adenocarcinoma colorretal, com disseminação endobiliar, em fígados com adenoma e hamartomas biliares. Em ambos os casos, além da disseminação endobiliar da neoplasia, o epitélio biliar apresentava-se displásico. A neoplasia foi CK 20 positiva, CK 7 negativa, enquanto a CK 19 foi positiva no epitélio biliar normal, no displásico e na neoplasia. A CK 7 foi positiva no epitélio biliar, hamartomas e adenoma. Concluímos que o emprego da CK 7 e da CK 20 é importante em tumores com essa forma de disseminação, sobretudo quando associados aos hamartomas e adenomas biliares.

Endobiliary growth of primary and metastatic liver neoplasias is rare, with exception of cholangiocarcinoma. This behavior, when occurring in metastatic neoplasias, frequently challenges the differential diagnosis of cholangiocarcinomas, mainly when its analysis is based only in morphological characteristics of the neoplasias and/or there is association with abnormalities which suggest biliary origin of the tumor. We analyzed cytokeratins (CKs) 7, 19 and 20 imunoexpression in two cases of colorectal metastatic adenocarcinoma with endobiliary dissemination in livers with biliary adenoma and hamartoma. In both cases, in addition to endobiliary dissemination, there was also dysplasia in the biliary epithelium. The neoplasia was positive for CK 20, negative for CK 7, while the normal epithelium, the dysplatic epithelium and the neoplasia were all positive for CK 19. The CK 7 was positive in the biliary epithelium, in hamartomas and adenoma. We concluded that the use of CK 7 and CK 20 is important in tumors with this type of dissemination, especially when they are associated with harmatomas and biliary adenomas.

Colonization with methicillin-resistant Staphylococcus aureus after liver transplantation.

Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of infection after orthotopic liver transplantation (OLT). Colonization with MRSA is associated with a higher risk of infection. Previous studies have shown a high prevalence of MRSA colonization among OLT candidates. However, the risk of colonization with MRSA after OLT is still unclear. The objective of this study was to estimate the incidence and the factors associated with colonization with MRSA after OLT. This was a prospective cohort study including patients submitted to OLT between the years 2000 and 2002. Surveillance cultures of nasal swab specimens were performed within the 1st 72 hours of hospital admission and, subsequently, on weeks 2, 6, 13, and 26. Patients whose baseline cultures revealed nasal carriage of MRSA were excluded. A total of 60 patients were included in the study. The median follow-up was 72 days. A total of 9 patients (15%) became colonized. In multiple logistic regression analyses, the use of a urinary catheter for > or =5 days (P = .006), postoperative bleeding at the surgical site (P = .009), and preoperative use of fluoroquinolones (P = .08) were associated with a higher risk of colonization. Patients without any of these risk factors did not become colonized. In conclusion, nasal carriage of MRSA is frequently acquired after OLT. Periodic postoperative screening for MRSA carriage should be an integral component in programs designed to reduce nosocomial MRSA transmission in these patients. Further studies are needed to set up and validate a predictive model that could allow targeting postoperative screening to high-risk OLT recipients.

Detecção imunoistoquímica das oncoproteínas p21ras, c-myc E p53 no carcinoma hepatocelular e no tecido hepático não-neoplásico / Immunohistochemical detection of p21ras, c-myc and p53 oncoproteins in hepatocellular carcinoma and in non-neoplastic liver tissue

RACIONAL: A hepatocarcinogênese é um processo no qual as alterações genéticas e epigenéticas são bem conhecidas em modelos animais, mas carece de estudos no homem. OBJETIVOS: Analisar a freqüência das oncoproteínas p21ras, c-myc e p53 no carcinoma hepatocelular e no fígado não-neoplásico. Verificar ainda a associação destas oncoproteínas com os padrões e graus histológicos, assim como com as infecções pelos vírus das hepatites B e C. MÉTODOS: Foi analisada por método imunoistoquímico a detecção das oncoproteínas p21ras, c-myc e p53 em 47 casos de carcinoma hepatocelular e no tecido não-neoplásico circunjacente ao tumor (40 casos). RESULTADOS: As oncoproteínas p21ras, c-myc e p53 foram detectadas, respectivamente, em 44,7 por cento, 53,2 por cento e 36,2 por cento dos casos de carcinoma hepatocelular. A imunorreatividade do p21ras e c-myc mostrou uma associação significativa. Contudo, não houve associação significativa entre a detecção do p21ras, c-myc e p53 com os diferentes graus e padrões histológicos, nem tampouco com as infecções pelos vírus das hepatites B e C. A mesma associação significativa entre o p21ras e c-myc foi encontrada no tecido não-neoplásico dos casos de cirrose em relação aos que não apresentaram cirrose, enquanto que o p53 foi negativo em todos os casos. CONCLUSÕES: A imunorreatividade das oncoproteínas p21ras, c-myc e p53 corrobora evidências prévias de sua detecção no carcinoma hepatocelular, o que sugere poder haver participação destas proteínas na hepatocarcinogênese humana. A significativa associação entre as proteínas p21ras, c-myc e p53 no carcinoma hepatocelular e na cirrose pode apontar uma interação entre as mesmas, sobretudo na hepatocarcinogênese pela via da cirrose.

[Immunohistochemical detection of p21ras, c-myc and p53 oncoproteins in hepatocellular carcinoma and in non-neoplastic liver tissue]. / Detecção imunoistoquímica das oncoproteínas p21ras, c-myc E p53 no carcinoma hepatocelular e no tecido hepático não-neoplásico.

BACKGROUND: Genetic and epigenetic alterations have been described in animal hepatocarcinogenesis models but need to be studied in human being. AIMS: To assess the immunoreactivity of p21ras, c-myc and p53 oncoproteins in hepatocellular carcinoma and non neoplastic tissue. Association of the immunoreactivity of these markers with histological grades and patterns, hepatitis B and C were additionally studied. METHODS: Detection of oncoproteins p21ras, c-myc and p53 was performed immunohistochemically in hepatocellular carcinoma (47 cases) and surrounding non neoplastic liver tissue (40 cases). RESULTS: Oncoproteins p21ras, c-myc and p53 were detected in 44,7%, 53,2% and 36,2% of the hepatocellular carcinoma cases, respectively. The p21ras and c-myc immunoreactivity has shown a significant association. However there was no association of p21ras, c-myc and p53 detection with hepatitis B and C virus infections, histological grades and patterns. The same significant association between p21ras and c-myc was observed in non-neoplastic tissue with cirrhosis when compared with tissue without it. The p53 immunoreactivity was negative in all non-neoplastic liver tissue samples. CONCLUSIONS: The immunoreactivity detection of p21ras, c-myc and p53 corroborates previous evidence of their detection in hepatocellular carcinoma that suggest the participation of these proteins in human hepatocarcinogenesis. The significant association between p21ras and c-myc oncoproteins in hepatocellular carcinoma and in cirrhosis can point to an interaction between them mainly, in hepatocarcinogenesis that occurs through cirrhosis.

Reavaliaçäo da autotransfusäo de órgäos extirpados / Re-evaluation of the autotransfusion of extirpated organs

Os autores realizaram uma reavaliaçäo da eficácia e da inocuidade do novo método de autotransfusäo proposto por L. Bogossian em 1989, que consiste na reinfusäo imediata no paciente do sangue recuperado de seu baço esplenomegálico recém-extirpado. Foram analisados cinco autotransfusäo de baços removidos no período de 01/01/93 a 31/12/94. Conclui-se que o método é eficaz, inócuo e recupera grandes volumes de sangue, concorrendo para a reduçäo da demanda de transfusöes homólogas e do número de complicaçöes

Hepatectomias / Hepatectomy

Os autores fazem uma revisao dos avancos que permitiram uma maior aplicacao das resseccoes hepaticas, especialmente na ultima decada. Destacam como pontos essenciais: o controle da hemorragia macica que e o grande risco da cirurgia hepatica; a extensao de 90 minutos no limite seguro do tempo de isquemia normotermica e o perfeito conhecimento da segmentacao hepatica e suas relacoes com o pediculo, com as supra-hepaticas e com a veia cava inferior. Como metodos de controle da hemorragia sao revisados o clampeamento do pediculo seletivo ou nao; a exclusao vascular do figado, e a cirurgia "ex-situ" hepatica. Chamam atencao de que o prognostico imediato depende essencialmente do volume da perda sanguinea e da qualidade do parenquima hepatica restante.