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RESUMO Objetivo: Caracterizar uma coorte de pacientes com insuficiencia hepatica cronica agudizada em unidade de terapia intensiva e analisar os fatores de risco da mortalidade global aos 28 dias presentes no dia da admissao e no dia 3. Metodos: Estudo de coorte retrospectiva de pacientes consecutivamente admitidos a unidade de terapia intensiva entre marco de 2013 e dezembro de 2016. Resultados: Incluimos 71 pacientes com idade mediana de 59 (51 - 64) anos, sendo 81,7% do sexo masculino. Consumo de alcool isoladamente (53,5%) foi a etiologia mais frequente de cirrose, e infeccao (53,5%) foi o evento que mais frequentemente precipitou a agudizacao da insuficiencia hepatica cronica. No momento da admissao a unidade de terapia intensiva, os escores de severidade foram: APACHE II 21 (16 - 23), CLIF-SOFA 13 (11 - 15), Child-Pugh 12 (10 - 13) e MELD 27 (20 - 32). Dentre os individuos, 14,1% tiveram escore 1 de insuficiencia hepatica cronica agudizada, 28,2% pontuaram 2, 64,5% pontuaram 3, e 11,3% se apresentaram sem insuficiencia hepatica cronica agudizada. Sobre o numero de falencias de orgaos, 4,2% tiveram um orgao; 42,3%, dois orgaos; 32,4%, tres orgaos; 16,9%, quatro orgaos; e 4,2% cinco orgaos. Foi realizado transplante hepatico em 15,5% dos pacientes. A taxa de mortalidade aos 28 dias foi de 56,3%, e a taxa de mortalidade na unidade de terapia intensiva foi de 49,3%. Foram fatores independentes de risco: falencias do orgaos quando da admissao a unidade de terapia intensiva (p = 0,02; RC 2,1; IC95% 1,2 - 3,9), concentracao de lactato em sangue arterial no dia 3 (p = 0,02; RC 6,3; IC95% 1,4 - 28,6) e RC internacional no dia 3 (p = 0,03; RC 10,2; IC95% 1,3 - 82,8). Conclusao: Pacientes com insuficiencia hepatica cronica agudizada apresentaram elevados niveis de severidade e taxa de mortalidade. O numero de falencias de orgaos no momento da admissao a unidade de terapia intensiva e o nivel de lactato, assim como a razao normalizada internacional no dia 3 de permanencia na unidade foram fatores independentes de risco para a mortalidade ao 28o dia. Consideramos que a terapia intensiva e essencial para pacientes com insuficiencia hepatica cronica agudizada, e a realizacao de um transplante hepatico em tempo adequado foi vital para os pacientes selecionados.

Background This study describes the successful treatment of two clinical settings of grade V pancreaticoduodenal blunt trauma only possible due to the prompt collaboration of a peripheral trauma hospital and a central hepatobiliary and pancreatic unit. Case presentation We reviewed the clinical records of two male patients aged 17 and 47 years old who underwent a two-stage pancreaticoduodenectomy after a previous Damage-Control Surgery (DCS). Both patients were transferred to our Hepatobiliopancreatic Unit 2 days after immediate DCS with haemostasis, debridement, duodenostomy, gastroenterostomy, external drainage and laparostomy. One day after, they both underwent a two-stage Whipple’s procedure with external cannulation of the main bile duct and the main pancreatic duct with seized calibre silicone drains through the skin. The reconstructive phase was performed two weeks later. The first patient had an uneventful post-operative course and was discharged on post-operative day 8. The second patient developed a high debt biliary fistula on post-operative day 5 being submitted to a relaparotomy with extensive peritoneal lavage. After conservative measures the fistula underwent a progressive closure in 15 days, and the patient was discharged at post-operative day 50 without any limitations. Conclusions Pancreaticoduodenectomy is a life-saving operation in selected grade V pancreaticoduodenal trauma lesions. DCS is a salvage approach, often performed in peripheral hospitals, making an early referral to an hepatobiliopancreatic centre mandatory to achieve survival in these severely injured patients. A two-staged Whipple’s operation for severe duodenal / pancreatic trauma can be performed safely and may represent a life-saving option under these very unusual circumstances.

Hepatic transarterial chemoembolization is a widely used technique for the treatment of hepatocellular carcinoma. The most common complication of this procedure is postembolization syndrome. The main objective of this study was to assess risk factors for the development of postembolization syndrome.Single-centre retrospective analysis of 563 hepatic transarterial chemoembolization procedures from January 1st, 2014 - December 31st, 2015. Hepatic transarterial chemoembolization was performed with ½ - 2 vials of 100 - 300 μm microspheres loaded with doxorubicin. Patients who experienced postembolization syndrome were identified based on prolongation of hospitalization due to pain, fever, nausea and/or vomiting. A control group with the patients who did not have postembolization syndrome was randomly created (three controls for one case). Descriptive analysis and multivariate logistic regression were performed.The overall prevalence of postembolization syndrome was 6.2%. Hepatic transarterial chemoembolization with doxorubicin dosage above 75 mg (more than one vial), the size of the largest nodule and female gender had statistically significant relation with development of postembolization syndrome (p = 0.030, p = 0.046 and p = 0.037, respectively).Doxorrubicin dosage above 75 mg is associated with a higher risk of postembolization syndrome. This result can be helpful for decision-making in clinical practice, whenever it is possible to avoid a higher dose without compromising the efficacy of the treatment. The size of the largest nodule and female gender also constitute risk factors for postembolization syndrome. The other variables studied were not related to the development of postembolization syndrome.The dose of doxorrubicin, the size of the largest nodule treated and female gender are potential risk factors for the development of postembolization syndrome after hepatic transarterial chemoembolization for hepatocellular carcinoma.Introdução: A quimioembolização hepática é uma técnica amplamente usada para o tratamento do carcinoma hepatocelular. A principal complicação deste procedimento é a síndrome pós-quimioembolização. O principal objetivo deste estudo foi determinar fatores de risco para síndrome pós-quimioembolização. Material e Métodos: Análise retrospetiva unicêntrica de 563 procedimentos de quimioembolização hepática efetuados entre 1/1/2014-31/12/2015. A quimioembolização hepática foi efetuada com ½ - 2 ampolas de microesferas 100 - 300 μm carregadas com doxorrubicina. Os pacientes que desenvolveram síndrome pós-quimioembolização foram identificados pelo prolongamento do internamento por dor, febre, náuseas e/ou vómitos. Um grupo controlo com os pacientes que não desenvolveram síndrome pós-quimioembolização foi criado de forma randomizada (três controlos para um caso). Foi realizada análise descritiva e regressão logística multivariada. Resultados: A prevalência global de síndrome pós-quimioembolização foi 6,2%. Quimioembolização hepática com dose de doxorrubicina superior a 75 mg (mais de uma ampola), o tamanho do nódulo maior e o género feminino demonstraram relação estatisticamente significativa com o desenvolvimento de síndrome pós-quimioembolização (p = 0,030, p = 0,046 e p = 0,037, respetivamente). Discussão: Doses de doxorrubicina superiores a 75 mg estão associadas a maior risco de síndrome pós-quimioembolização. Este resultado pode ter impacto na prática clínica, sempre que for possível evitar doses maiores sem comprometer a eficácia do tratamento. O tamanho do maior nódulo tratado e o género feminino também constituem fatores de risco para síndrome pós-quimioembolização. As outras variáveis estudadas não demonstraram relação com síndrome pós-quimioembolização. Conclusão: A dose de doxorrubicina, o tamanho do maior nódulo tratado e o género feminino são potenciais fatores de risco para o desenvolvimento de síndrome pós-quimioembolização após quimioembolização hepática para o tratamento de carcinoma hepatocelular.

Acute pancreatitis (AP) is an inflammatory condition with a mild course in most patients, but 20-30% evolve to single or multiple organ dysfunction and pancreatic/peripancreatic necrosis, with potentially infected collections. In the first weeks of disease, a systemic inflammatory syndrome (SIRS) dominates the clinical setting, and early management decisions in this precocious phase can change the course of the disease. Imaging is crucial in the diagnosis, and since the adoption of the revised Atlanta classification, four different types of pancreatic/peripancreatic collections have been defined. The management of the complicated forms of AP has been defined by several treatment guidelines, and the main indication for intervention is local infection, preferably in walled-off necrosis. Open surgery necrosectomy is associated with a very high rate of morbimortality, giving a place to different multidisciplinary methodologies, emphasizing drainage and necrosectomy techniques in a "step-up" approach starting from mini-invasive endoscopic drainage and moving, if needed, to progressively more invasive techniques, including interventional radiology and mini-invasive surgery. With the advent of several new technologies in the specialties involved, the complicated AP cases which need drainage and necrosectomy benefit from a new era of multidisciplinary cooperation, permitting higher efficacy with lower levels of morbimortality and reducing hospital stay and costs. info:eu-repo/semantics/publishedVersion

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by an acute deterioration of a patient with cirrhosis, frequently associated with multi-organ failure and a high short-term mortality rate. We present a retrospective study that aims to characterize the presentation, evolution, and outcome of patients diagnosed with ACLF at our center over the last 3 years, with a comparative analysis between the group of patients that had ACLF precipitated by infectious insults of bacterial origin and the group of those with ACLF triggered by a nonbacterial infectious insult; the incidence of acute kidney injury and its impact on the prognosis of ACLF was also analyzed. Twenty-nine patients were enrolled, the majority of them being male (89.6%), and the mean age was 53 years. Fourteen patients (48.3%) developed ACLF due to a bacterial infectious event, and 9 of them died (64.2%, overall mortality rate 31%); however, no statistical significance was found (p < 0.7). Of the remaining 15 patients (51.7%) with noninfectious triggers, 11 died (73.3%, overall mortality rate 37.9%); again there was no statistical significance (p < 0.7). Twenty-four patients (83%) developed acute kidney injury (overall mortality rate 65.5%; p < 0.022) at the 28-day and 90-day follow-up. Twelve patients had acute kidney injury requiring renal replacement therapy (41.37%; overall mortality rate 37.9%; p < 0.043). Hepatic transplant was performed in 3 patients, with a 100% survival at the 28-day and 90-day follow-up (p < 0.023). Higher grades of ACLF were associated with increased mortality (p < 0.02; overall mortality 69%). Conclusions: ACLF is a heterogeneous syndrome with a variety of precipitant factors and different grades of extrahepatic involvement. Most cases will have some degree of renal dysfunction, with an increased risk of mortality. Hepatic transplant is an efficient form of therapy for this syndrome. A Doença Hepática Crónica Agudizada/Falência é um síndrome caracterizado por uma deterioração aguda de um doente com cirrose, frequentemente associada com falência multiorgânica e elevada mortalidade a curto prazo. Apresentamos estudo retrospetivo que teve como objetivo caracterizar a apresentação, evolução e prognóstico de doentes diagnosticados com Doença Hepática Crónica Agudizada/Falência no nosso Centro nos últimos 3 anos, comparando o grupo de doentes que tiveram Doença Hepática Crónica provocada por infeções bacterianas e os doentes com Doença Hepática Crónica Agudizada/Falência desencadeada por precipitantes que não a infeção bacteriana; foi também analisada a incidência de lesão renal aguda e o seu impacto no prognóstico na Doença Hepática Crónica Agudizada/Falência. Vinte e nove doente foram incluídos no estudo, a maioria do género masculino (89.6%), idade media de 53 anos. Catorze doentes (48.3%) desenvolveram Doença Hepática Crónica Agudizada devido a infeção bacteriana, 9 dos quais faleceram (64.2%, mortalidade global 31%), contudo, sem significado estatístico (p < 0.7); dos restantes 15 (51.7%) sem infeção bacteriana, 11 faleceram (73.3%, mortalidade global 37.9%), também sem significado estatístico (p < 0.7%). Vinte e quatro doentes (83%) desenvolveram lesão renal, mortalidade global de 65.5% (p < 0.022) aos 28 e 90 dias de seguimento. Doze doentes desenvolveram lesão renal aguda com necessidade de terapêutica de substituição da função renal (41.37%), mortalidade global de 37.9% ( p < 0.043). O transplante hepático foi realizado em 3 doentes, com uma sobrevida de 100% aos 28 e 90 dias de seguimento (p < 0.023); Graus elevados de Doença Hepática Crónica Agudizada estão associadas a mortalidade mais elevada (p < 0.02); mortalidade global de 69%. Conclusions: A Doença Hepática Crónica Agudizada é um síndrome heterogéneo, com uma variedade de fatores precipitantes e diferentes graus de envolvimento extra-hepático; a maioria das situações estará associada a disfunção renal, com aumento do risco de mortalidade; O transplante hepático será uma eficaz de tratamento deste síndrome.

Introduction: Hepatic transarterial chemoembolization is a widely used technique for the treatment of hepatocellular carcinoma. The most common complication of this procedure is postembolization syndrome. The main objective of this study was to assess risk factors for the development of postembolization syndrome. Material and Methods: Single-centre retrospective analysis of 563 hepatic transarterial chemoembolization procedures from January 1st, 2014 – December 31st, 2015. Hepatic transarterial chemoembolization was performed with ½ - 2 vials of 100 - 300 μm microspheres loaded with doxorubicin. Patients who experienced postembolization syndrome were identified based on prolongation of hospitalization due to pain, fever, nausea and/or vomiting. A control group with the patients who did not have postembolization syndrome was randomly created (three controls for one case). Descriptive analysis and multivariate logistic regression were performed. Results: The overall prevalence of postembolization syndrome was 6.2%. Hepatic transarterial chemoembolization with doxorubicin dosage above 75 mg (more than one vial), the size of the largest nodule and female gender had statistically significant relation with development of postembolization syndrome (p = 0.030, p = 0.046 and p = 0.037, respectively). Discussion: Doxorrubicin dosage above 75 mg is associated with a higher risk of postembolization syndrome. This result can be helpful for decision-making in clinical practice, whenever it is possible to avoid a higher dose without compromising the efficacy of the treatment. The size of the largest nodule and female gender also constitute risk factors for postembolization syndrome. The other variables studied were not related to the development of postembolization syndrome. Conclusion: The dose of doxorrubicin, the size of the largest nodule treated and female gender are potential risk factors for the development of postembolization syndrome after hepatic transarterial chemoembolization for hepatocellular carcinoma. info:eu-repo/semantics/publishedVersion

Purpose To evaluate the efficacy of portal vein embolization (PVE) with n-Butyl-cyanoacrylate (NBCA) through an ipsilateral approach before major hepatectomy. Secondary end-points were PVE safety, liver resection and patient outcome. Methods Over a 5-year period 50 non-cirrhotic consecutive patients were included with primary or secondary liver cancer treatable by hepatectomy with a liver remnant (FLR) volume less than 25% or less than 40% in diseased livers. Results There were 37 men and 13 women with a mean age of 57 years. Colorectal liver metastases were the most frequent tumor and patients were previously exposed to chemotherapy. FLR increased from 422 ml to 629 ml (P

PURPOSE: Patient outcome after resection of colorectal liver metastases (CLM) following second-line preoperative chemotherapy (PCT) performed for insufficient response or toxicity of the first-line, is little known and has here been compared to the outcome following first-line. PATIENTS AND METHODS: From January 2005 to June 2013, 5624 and 791 consecutive patients of a prospective international cohort received 1 and 2 PCT lines before CLM resection (group 1 and 2, respectively). Survival and prognostic factors were analysed. RESULTS: After a mean follow-up of 30.1 months, there was no difference in survival from CLM diagnosis (median, 3-, and 5-year overall survival [OS]: 58.6 months, 76% and 49% in group 2 versus 58.9 months, 71% and 49% in group 1, respectively, P = 0.32). After hepatectomy, disease-free survival (DFS) was however shorter in group 2: 17.2 months, 27% and 15% versus 19.4 months, 32% and 23%, respectively (P = 0.001). Among the initially unresectable patients of group 1 and 2, no statistical difference in OS or DFS was observed. Independent predictors of worse OS in group 2 were positive primary lymph nodes, extrahepatic disease, tumour progression on second line, R2 resection and number of hepatectomies/year

Clear-cell cholangiocarcinoma is a very uncommon variant of cholangiocarcinoma with a largely unknown natural history and prognosis. We report a case of a 51-year-old previously healthy woman presenting with a large liver nodule found on routine imaging. Needle biopsy of the lesion suggested a non-hepatocellular carcinoma. After extensive workup for other primary neoplasms, the patient underwent a partial hepatectomy. Histopathology was compatible with a moderately differentiated clear-cell cholangiocarcinoma. There was no evidence of liver disease in the remaining tissue. The patient underwent chemotherapy and remains in clinical remission after two years. info:eu-repo/semantics/publishedVersion

Most antidepressant agents have the potential to cause liver injury, even at therapeutic doses. Nevertheless, drug-induced liver injury (DILI) from antidepressant agents is a rare event. There is no way to prevent idiopathic DILI, but the severity of the reaction may be minimized with prompt recognition and early withdrawal of the agent. We describe a rare case of a 63-year-old man presenting with acute liver failure after 3 months of trazodone and diazepam administration at normal therapeutic doses, requiring liver transplantation. This report should increase physicians' awareness of this complication and call attention to the regular monitoring of liver tests in patients taking trazodone, in order to prevent life-threatening complications. info:eu-repo/semantics/publishedVersion

Background and objectives: Aquaporin-5 (AQP5) and -3 (AQP3) are protein channels that showed to be up-regulated in a variety of tumors. Our goal was to investigate the expression pattern of AQP5 and AQP3 in pancreatic ductal adenocarcinomas (PDA) and correlate with cell proliferation, tumor stage and progression, and clinical significance. Methods: 35 PDA samples in different stages of differentiation and locations were analyzed by immunohistochemistry for expression of AQP5, AQP3 and several markers of cell proliferation and tumorigenesis. Results: In PDA samples AQP5 was overexpressed in the apical membrane of intercalated and intralobular ductal cells while AQP3 was expressed at the plasma membrane of ductal cells. AQP5 was also found in infiltrative cancer cells in duodenum. Simultaneous overexpression of EGFR, Ki-67, and CK7, with decreased E-cad and increased Vim that characterize epithelial mesenchymal transition, tumor formation and invasion, strongly suggest AQP3 and AQP5 involvement in cell proliferation and transformation. AQP3 overexpression is reinforced in late and more aggressive PDA stages whereas AQP5 is related with tumor differentiation, suggesting it may represent a novel marker for PDA aggressiveness and intestinal infiltration. Conclusions: These findings suggest AQP3 and AQP5 involvement in PDA development and the usefulness of AQP5 in early PDA diagnosis. info:eu-repo/semantics/publishedVersion

An innovative technique for pancreas transplantation is described. The main aspect consists of the horizontal positioning of the pancreas, which allows a better venous outflow, thus preventing thrombosis and graft loss. The program of pancreas transplantation in this national reference center for pancreatic and liver surgery was started in 2007; the initial results were considered poor, resulting in the loss of half of the grafts due to venous thrombosis. After analyzing the possible causes, this technique was proposed and successfully implemented, reducing the postoperative complications, particularly the problem of venous thrombosis. A detailed description of the new surgical technique is provided. The main clinical and demographic characteristics of the 56 patients who underwent the surgery are analyzed. The incidence of venous thrombosis was 5.3% (3 patients) and graft loss was 3.5% (2 patients). Due to the good results, this technique became the standard surgery for transplantation of the pancreas in our center. The technique proved to be safe and successful. Due to the unique pancreas graft implantation, we called it "transverse pancreas surgery." info:eu-repo/semantics/publishedVersion

BACKGROUND: Data on surgical management of breast liver metastasis are limited. We sought to determine the safety and long-term outcome of patients undergoing hepatic resection of breast cancer liver metastases (BCLM). METHODS: Using a multi-institutional, international database, 131 patients who underwent surgery for BCLM between 1980 and 2014 were identified. Clinicopathologic and outcome data were collected and analyzed. RESULTS: Median tumor size of the primary breast cancer was 2.5 cm (IQR: 2.0-3.2); 58 (59.8%) patients had primary tumor nodal metastasis. The median time from diagnosis of breast cancer to metastasectomy was 34 months (IQR: 16.8-61.3). The mean size of the largest liver lesion was 3.0 cm (2.0-5.0); half of patients (52.0%) had a solitary metastasis. An R0 resection was achieved in most cases (90.8%). Postoperative morbidity and mortality were 22.8% and 0%, respectively. Median and 3-year overall-survival was 53.4 months and 75.2%, respectively. On multivariable analysis, positive surgical margin (HR 3.57, 95% CI 1.40-9.16; p = 0.008) and diameter of the BCLM (HR 1.03, 95% CI 1.01-1.06; p = 0.002) remained associated with worse OS. DISCUSSION: In selected patients, resection of breast cancer liver metastases can be done safely and a subset of patients may derive a relatively long survival, especially from a margin negative resection. info:eu-repo/semantics/publishedVersion

BACKGROUND: Management and outcomes of patients with recurrent intrahepatic cholangiocarcinoma (ICC) following curative-intent surgery are not well documented. We sought to characterize the treatment of patients with recurrent ICC and define therapy-specific outcomes. METHODS: Patients who underwent surgery for ICC from 1990 to 2013 were identified from an international database. Data on clinicopathological characteristics, operative details, recurrence, and recurrence-related management were recorded and analyzed. RESULTS: A total of 563 patients undergoing curative-intent hepatic resection for ICC who met the inclusion criteria were identified. With a median follow-up of 19 months, 400 (71.0 %) patients developed a recurrence. At initial surgery, treatment was resection only (98.8 %) or resection + ablation (1.2 %). Overall 5-year survival was 23.6 %; 400 (71.0 %) patients recurred with a median disease-free survival of 11.2 months. First recurrence site was intrahepatic only (59.8 %), extrahepatic only (14.5 %), or intra- and extrahepatic (25.7 %). Overall, 210 (52.5 %) patients received best supportive care (BSC), whereas 190 (47.5 %) patients received treatment, such as systemic chemotherapy-only (24.2 %) or repeat liver-directed therapy ± systemic chemotherapy (75.8 %). Repeat liver-directed therapy consisted of repeat hepatic resection ± ablation (28.5 %), ablation alone (18.7 %), and intra-arterial therapy (IAT) (52.8 %). Among patients who recurred, median survival from the time of the recurrence was 11.1 months (BSC 8.0 months, systemic chemotherapy-only 16.8 months, liver-directed therapy 18.0 months). The median survival of patients undergoing resection of recurrent ICC was 26.7 months versus 9.6 months for patients who had IAT (p < 0.001). CONCLUSIONS: Recurrence following resection of ICC was common, occurring in up to two-thirds of patients. When there is recurrence, prognosis is poor. Only 9 % of patients underwent repeat liver resection after recurrence, which offered a modest survival benefit. info:eu-repo/semantics/publishedVersion