TACE treatment in hepatocellular carcinoma: What should we do now?

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Drop-out rate from the liver transplant waiting list due to HCC progression in HCV-infected patients treated with direct acting antivirals.

BACKGROUND & AIM: concerns about an increased hepatocellular carcinoma (HCC) recurrence rate following directly acting antiviral (DAA) therapy in cirrhotic patients with a prior complete oncological response have been raised. Data regarding the impact of HCV-treatment with DAAs on waiting list drop-out rates in patients with active HCC and HCV-related cirrhosis awaiting liver transplantation (LT) are lacking. MATERIALS AND METHODS: HCV-HCC patients listed for LT between January 2015 and May 2016 at Padua Liver Transplant Centre were considered eligible for the study. After enrollment patients were divided into 2 groups, depending on whether they underwent DAAs treatment while awaiting LT or not. For each patient clinical, serological and virological data were collected. HCC characteristics were radiologically evaluated at baseline and during follow-up (FU). For transplanted patients, pathological assessment of the explants was performed and recurrence-rates were calculated. RESULTS: twenty-three patients treated with DAAs and 23 controls were enrolled. HCC characteristics at time of LT-listing were comparable between the 2 groups. Median FU was 10 and 7 months, respectively, during which 2/23 (8.7%) and 1/23 (4.3%) drop-out events due to HCC-progression were registered (p = 0.9). No significant differences in terms of radiological progression were highlighted (p = 0.16). Nine out of 23 cases (39%) and 14/23 (61%) controls underwent LT, and histopathological analysis showed no differences in terms of median number and total tumor volume of HCC nodules, tumor differentiation or microvascular invasion. During post-LT FU, 1/8 DAAs treated patient (12,5%) and 1/12 control (8,3%) experienced HCC recurrence (p = 0.6). CONCLUSIONS: Viral eradication does not seem to be associated with an increased risk of drop-out due to neoplastic progression in HCV-HCC patients awaiting LT

Los moluscos del cuaternario marino de Argentina como indicadores de cambios climáticos a escala espacial y temporal

Los moluscos preservados durante episodios altos del nivel en el litoral argentino, entre el Río de la Plata y sur de Patagonia, acumulados durante interglaciales (estadíos isotópicos marinos, MIS) del Pleistoceno (MIS11, 9, 7, 5) y Holoceno (MIS1), muestran utilidad paleoclimática. Muestreos extensos (1982 -2011), estudios previos, información bibliográfica del Atlántico Sudoccidental (Surinam, Brasil, Uruguay) y de colecciones modernas permitieron obtener una extensa base de datos y aplicar métodos comparativos. Se intentó reconocer 1) si existe algún patrón geográfico de biodiversidad y si varió a través del tiempo; 2) áreas de endemismo; 3) posibles causas de eventuales cambios espacio-temporales; 4) un método/s ventajoso para su evaluación.Eje: Clima.Universidad Nacional de La Plat

Los moluscos del cuaternario marino de Argentina como indicadores de cambios climáticos a escala espacial y temporal

Los moluscos preservados durante episodios altos del nivel en el litoral argentino, entre el Río de la Plata y sur de Patagonia, acumulados durante interglaciales (estadíos isotópicos marinos, MIS) del Pleistoceno (MIS11, 9, 7, 5) y Holoceno (MIS1), muestran utilidad paleoclimática. Muestreos extensos (1982 -2011), estudios previos, información bibliográfica del Atlántico Sudoccidental (Surinam, Brasil, Uruguay) y de colecciones modernas permitieron obtener una extensa base de datos y aplicar métodos comparativos. Se intentó reconocer 1) si existe algún patrón geográfico de biodiversidad y si varió a través del tiempo; 2) áreas de endemismo; 3) posibles causas de eventuales cambios espacio-temporales; 4) un método/s ventajoso para su evaluación.Eje: Clima.Universidad Nacional de La Plat

Los moluscos del cuaternario marino de Argentina como indicadores de cambios climáticos a escala espacial y temporal

Los moluscos preservados durante episodios altos del nivel en el litoral argentino, entre el Río de la Plata y sur de Patagonia, acumulados durante interglaciales (estadíos isotópicos marinos, MIS) del Pleistoceno (MIS11, 9, 7, 5) y Holoceno (MIS1), muestran utilidad paleoclimática. Muestreos extensos (1982 -2011), estudios previos, información bibliográfica del Atlántico Sudoccidental (Surinam, Brasil, Uruguay) y de colecciones modernas permitieron obtener una extensa base de datos y aplicar métodos comparativos. Se intentó reconocer 1) si existe algún patrón geográfico de biodiversidad y si varió a través del tiempo; 2) áreas de endemismo; 3) posibles causas de eventuales cambios espacio-temporales; 4) un método/s ventajoso para su evaluación.Eje: Clima.Universidad Nacional de La Plat

Octreotide and hepatocellular carcinoma

[No abstract available

Bax Inhibitor-1 down-regulation in the progression of chronic liver diseases

<p>Abstract</p> <p>Background</p> <p>Bax inhibitor-1 (BI-1) is an evolutionary conserved endoplasmic reticulum protein that, when overexpressed in mammalian cells, suppresses the apoptosis induced by Bax, a pro-apoptotic member of the Bcl-2 family. The aims of this study were: (1) to clarify the role of intrinsic anti- and pro-apoptotic mediators, evaluating Bax and BI-1 mRNA and protein expressions in liver tissues from patients with different degrees of liver damage; (2) to determine whether HCV and HBV infections modulate said expression.</p> <p>Methods</p> <p>We examined 62 patients: 39 with chronic hepatitis (CH) (31 HCV-related and 8 HBV-related); 7 with cirrhosis (6 HCV-related and 1 HBV-related); 13 with hepatocellular carcinoma (HCC) [7 in viral cirrhosis (6 HCV- and 1 HBV-related), 6 in non-viral cirrhosis]; and 3 controls. Bax and BI-1 mRNAs were quantified by real-time PCR, and BI-1 protein expression by Western blot.</p> <p>Results</p> <p>CH tissues expressed significantly higher BI-1 mRNA levels than cirrhotic tissues surrounding HCC (P < 0.0001) or HCC (P < 0.0001). Significantly higher Bax transcripts were observed in HCV-genotype-1-related than in HCV-genotype-3-related CH (P = 0.033). A positive correlation emerged between BI-1 and Bax transcripts in CH tissues, even when HCV-related CH and HCV-genotype-1-related CH were considered alone (P = 0.0007, P = 0.0005 and P = 0.0017, respectively).</p> <p>Conclusions</p> <p>BI-1 expression is down-regulated as liver damage progresses. The high BI-1 mRNAs levels observed in early liver disease may protect virus-infected cells against apoptosis, while their progressive downregulation may facilitate hepatocellular carcinogenesis. HCV genotype seems to have a relevant role in Bax transcript expression.</p

Real-time gastric juice analysis with EndoFaster for H. pylori diagnosis: A large, multicentre study

Background Helicobacter pylori infection is the main cause of the most frequent gastroduodenal diseases. Because its prevalence is decreasing in developed countries, gastric biopsies are negative in several patients. By measuring ammonium in the gastric juice, EndoFaster allows to exclude H. pylori infection during endoscopy. This study aimed to assess the accuracy of device versions working with either 6 ml or 3 ml of gastric juice. Study design This prospective study involved 12 endoscopic units. During endoscopy, EndoFaster testing was performed and standard five gastric biopsies were taken. The accuracy was calculated by considering histological assessment as the gold standard for H. pylori diagnosis. Results Gastric juice analysis was attempted in 1279 patients, but it failed in 131 (15.5%) and in 10 (2.3%), with the 6 ml and the 3 ml device, respectively (P < 0.001). Overall, EndoFaster detected H. pylori infection with an 86.3% sensitivity, 83.3% specificity, 52.7% positive predictive value, 96.6% negative predictive value and 83.8% accuracy. The performance was not affected either by ongoing proton pump inhibitor therapy or a previous H. pylori eradication. No significant difference in accuracy emerged between the two versions of the device. Conclusion The novel version of the EndoFaster device operating with 3 ml gastric juice may be performed in virtually all patients, and it allows excluding H. pylori infection with a very high accuracy. Gastric biopsies can be avoided in a definite portion of cases without endoscopic lesions or other clinical indications

Years of life that could be saved from prevention of hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour 65 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost

Development and validation of a new prognostic system for patients with hepatocellular carcinoma.

Background Prognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.CA) database as a training set, we sought to develop and validate a new prognostic system for patients with HCC. Methods and Findings Prospective collected databases from Italy (training cohort, n = 3,628; internal validation cohort, n = 1,555) and Taiwan (external validation cohort, n = 2,651) were used to develop the ITA.LI.CA prognostic system. We first defined ITA.LI.CA stages (0, A, B1, B2, B3, C) using only tumor characteristics (largest tumor diameter, number of nodules, intra- and extrahepatic macroscopic vascular invasion, extrahepatic metastases). A parametric multivariable survival model was then used to calculate the relative prognostic value of ITA.LI. CA tumor stage, Eastern Cooperative Oncology Group (ECOG) performance status, Child\u2013 Pugh score (CPS), and alpha-fetoprotein (AFP) in predicting individual survival. Based on the model results, an ITA.LI.CA integrated prognostic score (from 0 to 13 points) was constructed, and its prognostic power compared with that of other integrated systems (BCLC, HKLC, MESIAH, CLIP, JIS). Median follow-up was 58 mo for Italian patients (interquartile range, 26\u2013106 mo) and 39 mo for Taiwanese patients (interquartile range, 12\u201361 mo). The ITA.LI.CA integrated prognostic score showed optimal discrimination and calibration abilities in Italian patients. Observed median survival in the training and internal validation sets was 57 and 61 mo, respectively, in quartile 1 (ITA.LI.CA score 1), 43 and 38 mo in quartile 2 (ITA.LI.CA score 2\u20133), 23 and 23 mo in quartile 3 (ITA.LI.CA score 4\u20135), and 9 and 8 mo in quartile 4 (ITA.LI.CA score &gt; 5). Observed and predicted median survival in the training and internal validation sets largely coincided. Although observed and predicted survival estimations were significantly lower (log-rank test, p &lt; 0.001) in Italian than in Taiwanese patients, the ITA.LI.CA score maintained very high discrimination and calibration features also in the external validation cohort. The concordance index (C index) of the ITA.LI.CA score in the internal and external validation cohorts was 0.71 and 0.78, respectively. The ITA.LI.CA score\u2019s prognostic ability was significantly better (p &lt; 0.001) than that of BCLC stage (respective C indexes of 0.64 and 0.73), CLIP score (0.68 and 0.75), JIS stage (0.67 and 0.70), MESIAH score (0.69 and 0.77), and HKLC stage (0.68 and 0.75). The main limitations of this study are its retrospective nature and the intrinsically significant differences between the Taiwanese and Italian groups. Conclusions The ITA.LI.CA prognostic system includes both a tumor staging\u2014stratifying patients with HCC into six main stages (0, A, B1, B2, B3, and C)\u2014and a prognostic score\u2014integrating ITA.LI.CA tumor staging, CPS, ECOG performance status, and AFP. The ITA.LI.CA prognostic system shows a strong ability to predict individual survival in European and Asian populations