Liver transplantation: would it be the best and last chance of cure for hepatocellular carcinoma with major venous invasion?

BackgroundHepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT) signifies advanced disease, whether LT confers any survival superiority over resection remains uncertain.MethodsA propensity score matched (PSM) analysis of liver transplantation (LT) and liver resection (LR) for HCC with PVTT was performed.ResultsA consecutive series of 88 patients who received either LT (10 DDLTs and 3 LDLTs) or LR (n=75) respectively were recruited. Before PSM, the LT group has a higher MELD score (17.3 vs. 7.8, P<0.001), lower serum AFP levels (96 vs. 2,164 ng/mL, P=0.017) and smaller tumour size (4 vs. 10 cm, P<0.001). The 5-year overall survival for LT and LR were 55.4% and 15.9% respectively (P=0.007). After matching for serum AFP levels and tumour size, 1-, 3- and 5-year overall survival for LT were 81 ng/mL, 3.9 cm, 80%, 70% and 70% and the corresponding rates for LR were 1,417 ng/mL, 5.3 cm, 51.8%, 19,6% and 9.8% (P value =0.12, 0.27 and 0.009 respectively).ConclusionsLT is associated with significantly better oncological outcomes in HCC patients with PVTT involving the lobar or segmental level. A modest expansion of selection criteria to include small HCC with segmental PVTT should be considered.     

针刺四关穴治疗偏头痛及其对一氧化氮水平的影响

目的：观察针刺四关穴治疗偏头痛的疗效及其对血浆一氧化氯(N0)水平的影响。方法：对38例偏头痛患者以针刺四关穴治疗，并于治疗前后作血浆N0水平测定。结果：经治疗，患者总有效率78．95％；治疗后血浆N0水平明显升高。结论：四关穴针刺治疗偏头痛有确切疗效，其机理可能与升高血浆N0水平有关。     

光明、太冲穴与中枢神经相关效应的观察

目的:观察针刺光明、太冲穴时,中枢不同区域的相关反应.方法:将19名正常志愿者随机分为1组(视觉刺激加单侧针刺组)7人,2组(视觉刺激加双侧针刺组)6人和3组(单纯针刺双侧穴组)6人.用功能性磁共振(fMRI)观察各组在针刺光明、太冲穴时视觉皮质区与相关脑区的反应.结果:发现视觉刺激及针刺进针时,视觉皮质的血氧饱和水平(BOLD)无明显变化(P＞0.25),但在进行单侧和双侧持续刺激时,发现大脑相关区域有BOLD变化.结论:针刺对单侧和双侧穴位的刺激均能改善大脑相关区域的BOLD,但与进行手法和视觉刺激无关.     

Risk factors for the development of pancreatic cancer in familial pancreatic cancer kindreds

BACKGROUND & AIMS: Approximately 10% of pancreatic cancers are inherited, but the factors that affect tumorigenesis in familial pancreatic cancer are unknown. We sought to determine whether smoking or other factors could predict cancer risk in familial pancreatic cancer kindreds. METHODS: We conducted a nested case-control study including 251 members of 28 families. All families included 2 or more members with pancreatic cancer. We determined the effects of smoking, young age of onset within the family, diabetes mellitus, sex, and number/standing of affected relatives on the risk of pancreatic cancer. RESULTS: Smoking was an independent risk factor for familial pancreatic cancer (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.8-7.6), and the risk was greatest in males and subjects younger than 50 (OR, 5.2 and OR, 7.6, respectively). Smokers developed cancer 1 decade earlier than nonsmokers (59.6 vs. 69.1 years; P = 0.01), and the number of affected first-degree relatives also increased risk (OR, 1.4; 95% CI, 1.1-1.9 for each additional family member). Diabetes was not a risk factor for pancreatic cancer, although diabetes was associated with pancreatic dysplasia. One third of families demonstrated genetic anticipation, as the mean age of onset decreased by 2 decades between generations. CONCLUSIONS: Smoking is a strong risk factor in familial pancreatic cancer kindreds, particularly among males and those under age 50. Persons with multiple affected first-degree relatives are also at increased risk. These factors may be useful in selecting candidates for pancreatic cancer screening. Members of families with multiple pancreatic cancers should be counseled not to smoke.     

Improvement of Risk Prediction After Transcatheter Aortic Valve Replacement by Combining Frailty With Conventional Risk Scores

Objectives

This study sought to evaluate whether frailty improves mortality prediction in combination with the conventional scores.

Abstract Digest—The Cutting Edge

Abstract

This paper describes a rapid protocol for iliac crest biopsies with embedding in LR White plastic to facilitate diagnosis of osteomalacia. Sections were cut and stained for light and electron microscopy using traditional staining methods with minor modifications. Total processing time was within three days. (The J Histotechnol 13:125, 1990)     

N-Terminal Pro–B-Type Natriuretic Peptide in the Emergency Department: The ICON-RELOADED Study

Background

Contemporary reconsideration of diagnostic N-terminal pro–B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed.

MACVIA-LR,Reference site of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) in Languedoc Roussillon

The Région Languedoc-Roussillon is the umbrella organisation for an interconnected and integrated project on AHA covering the 3 pillars of the European Innovation Partnership on Active and Healthy Ageing. All sub-activities (A1: electronic pharmaceutical file, A2: falls prevention initiative, A3: frailty, B3: chronic respiratory diseases, chronic diseases with comorbidities, oral health and hepatitis virus C chronic infection, C2 and D4 active and independent living and handicap) are included in MACVIA-LR that has a strong political commitment and includes all stakeholders (public, private, patients, policy makers). It is one of the Reference Sites of the European Innovation Partnership on Active and Healthy Ageing built around chronic diseases, ageing and handicap. The framework of MACVIA-LR has the vision that the prevention and management of CDs is essential for AHA promotion and for the reduction of handicap. The main objective of MACVIA-LR is to develop innovative solutions for a network of Living Labs in order to improve the care of patients affected by CDs in the Languedoc-Roussillon area and to disseminate the innovation.     

Pharmacological inhibition of TLR4/NF‐κB with TLR4‐IN‐C34 attenuated microcystin‐leucine arginine toxicity in bovine Sertoli cells

This study investigated the pharmacological inhibition of the toll‐like receptor 4 (TLR4) genes as a measure to attenuate microcystin‐LR (MC‐LR) reproductive toxicity. Bovine Sertoli cells were pretreated with TLR4‐IN‐C34 (C34) for 1 hour. Thereafter the pretreated and non‐pretreated Sertoli cells were cultured in medium containing 10% heat‐activated fetal bovine serum + 80 μg/L MC‐LR for 24 hours to assess the ability of TLR4‐IN‐C34 to attenuate the toxic effects of MC‐LR. The results showed that TLR4‐IN‐C34 inhibited MC‐LR‐induced mitochondria membrane damage, mitophagy and downregulation of blood‐testis barrier constituent proteins via TLR4/nuclear factor‐kappaB and mitochondria‐mediated apoptosis signaling pathway blockage. The downregulation of the mitochondria electron transport chain, energy production and DNA replication related genes (mt‐ND2, COX‐1, COX‐2, ACAT, mtTFA) and upregulation of inflammatory cytokines (interleukin [IL]‐6, tumor necrosis factor‐α, IL‐1β, interferon‐γ, IL‐4, IL‐10, IL‐13 and transforming growth factor β1) were modulated by TLR4‐IN‐C34. Taken together, we conclude that TLR4‐IN‐C34 inhibits MC‐LR‐related disruption of mitochondria membrane, mitophagy and downregulation of blood‐testis barrier proteins of the bovine Sertoli cell via cytochrome c release and TLR4 signaling blockage.     

Microcystin‐LR induces protein phosphatase 2A alteration in a human liver cell line

Microcystin‐LR (MC‐LR) is a potent inhibitor of protein phosphatases 1 and 2A, and has potent hepatotoxicity and tumor promotion activity. Numerous studies on MC‐LR toxicity have been conducted in rat hepatocytes, but few studies of the effects of microcystins on human hepatocytes have been done. In this study, HL7702 cells (a human normal liver cell line) were incubated in MC‐LR for 24 h. The existence of MC‐LR in HL7702 cells was confirmed. Furthermore, PP2A activity and the alteration of PP2A subunits were assessed. The results show that PP2A activity decreased from the concentration of 1 μM MC‐LR, showing a concentration‐dependent decline, to about 34% at 10 μM MC‐LR. This activity undergone opposite change with alternations of phosphorylated Y307‐PP2A/C and PP2A/C subunit but showed same change with the alteration of the ratio of methylated L309‐PP2A/C to PP2A/C. B55α, a regulatory subunit of PP2A, was slightly increases in cells treated with the highest concentration of MC‐LR (10 μM), and colocalized increasedly with rearranged‐microtubules after 1 μM MC‐LR exposure. However, the proportion of early apoptotic cells did not show any change at various concentration of MC‐LR for 24 h. To our knowledge, this is the first report showing MC‐LR‐induced alteration of PP2A phosphatase in human cultured hepatocytes, and the mechanism of action seems to be similar as described before in vitro. The alteration of PP2A and microtubule seems to be the early event induced by MC‐LR exposure. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1236–1244, 2014.