396 research outputs found

    External validation of a simplified BCLC staging system for early hepatocellular carcinoma

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    BACKGROUND AND AIMS: The aim was to externally validate the capability of a simplified Barcelona Clinic Liver Cancer (s-BCLC) staging system in allocating patients to hepatic resection (HR) and the effect on survival: S-BCLC was defined by only 2 groups: AA included BCLC A1 + A2 classes with alpha-fetoprotein (AFP) ≤ 20 ng/ml and AB included A1 + A2 with AFP > 20 ng/ml plus A3 + A4 subgroups. METHODS: This study compared a training group (TG) with hepatocellular carcinoma (HCC) submitted to hepatic resection (HR) in Milan with another group of patients, the validation group (VG) in Creteil. All patients underwent ultrasound-guided anatomical resection (<3 segments). RESULTS: Overall survival got worse from A1 to A4 (p = 0.0271) in TG (n = 132), as well as in VG (n = 100) (p = 0.0044) with a more important overlapping of each curves. According s-BCLC classification, the survival curves of TG (p = 0.0001) and VG (p = 0.0250) showed a definitive separation in two different staging groups. The s-BCLC provided the best predictive accuracy and it also presented the highest separability index and C-statistics in both TG and VG. On the other hand, in the evaluation of discriminatory ability for death, measured by ROC curve areas, the s-BCLC system gave better results than the others. CONCLUSION: This experience stressed the high value of BCLC system in staging of HCC, but the s-BCLC system seems to be more useful for therapeutic decision making

    Hepatic resection for hepatocellular carcinoma in patients with Child–Pugh's A cirrhosis: is clinical evidence of portal hypertension a contraindication?

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    AbstractBackgroundAccording to international guidelines [European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD)], portal hypertension (PHTN) is considered a contraindication for liver resection for hepatocellular carcinoma (HCC), and patients should be referred for other treatments. However, this statement remains controversial. The aim of this study was to elucidate surgical outcomes of minor hepatectomies in patients with PHTN (defined by the presence of esophageal varices or a platelet count of <100 000 in association with splenomegaly) and well‐compensated liver disease.MethodsBetween 1997 and 2012, a total of 223 cirrhotic patients [stage A according to the Barcelona Clinic Liver Cancer (BCLC) classification] were eligible for this analysis and were divided into two groups according to the presence (n = 63) or absence (n = 160) of PHTN. The demographic data were comparable in the two patient groups.ResultsOperative mortality was not different (only one patient died in the PHTN group). However, patients with PHTN had higher liver‐related morbidity (29% versus 14%; P = 0.009), without differences in hospital stay (8.8 versus 9.8 days, respectively). The PHTN group showed a worse survival rate only if biochemical signs of liver decompensation existed. Multivariate analysis identified albumin levels as an independent predictive factor for survival.ConclusionsPHTN should not be considered an absolute contraindication to a hepatectomy in cirrhotic patients. Patients with PHTN have short‐ and long‐term results similar to patients with normal portal pressure. A limited hepatic resection for early‐stage tumours is an option for Child–Pugh class A5 patients with PHTN

    Laparoscopic versus open unisegmentectomy in two specialized centers. Feasibility and short-term results

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    Background: Anatomical segmentectomy is defined as the complete removal of the Couinaud's segment. The aim of this study was to compare the perioperative outcomes of laparoscopic (LS) versus open (OS) unisegmentectomy in two high volume centers. Methods: A retrospective review of all consecutive unisegmentectomies from 2007 to 2017 was performed at the Institut Mutualiste Montsouris and at the Hepatobiliary Center of Paul Brousse Hospital. Results: A total of 177 patients underwent unisegmentectomy: 58 LS vs 52 OS in the anterolateral segments, 33 LS vs 34 OS in the posterosuperior segments. HCC were more frequent in the OS group, whereas colorectal liver metastases were more frequently treated with LS. Blood loss (200 vs. 400 ml, p = 0.006), operative time (238 vs. 267 min, p = 0.048) and median length of stay (6 vs. 8 days, p = 0.036) were significantly lower in the LS group. The resection margins (4 mm vs. 2 mm, p = 0.763) and the overall morbidity did not differ between the two groups. In the posterosuperior segment, OS group had more pulmonary complications (9 vs. 29%, p = 0.035). Conclusion: Laparoscopic anatomical unisegmentectomies for selected patients, even with postero-superior based tumors, in specialized centers seems to be safe and feasible

    Upregulation of the Rab27a-Dependent Trafficking and Secretory Mechanisms Improves Lysosomal Transport, Alleviates Endoplasmic Reticulum Stress, and Reduces Lysosome Overload in Cystinosis

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    Cystinosis is a lysosomal storage disorder caused by the accumulation of the amino acid cystine due to genetic defects in the CTNS gene, which encodes cystinosin, the lysosomal cystine transporter. Although many cellular dysfunctions have been described in cystinosis, the mechanisms leading to these defects are not well understood. Here, we show that increased lysosomal overload induced by accumulated cystine leads to cellular abnormalities, including vesicular transport defects and increased endoplasmic reticulum (ER) stress, and that correction of lysosomal transport improves cellular function in cystinosis. We found that Rab27a was expressed in proximal tubular cells (PTCs) and partially colocalized with the lysosomal marker LAMP-1. The expression of Rab27a but not other small GTPases, including Rab3 and Rab7, was downregulated in kidneys from Ctns-/- mice and in human PTCs from cystinotic patients. Using total internal reflection fluorescence microscopy, we found that lysosomal transport is impaired in Ctns-/- cells. Ctns-/- cells showed significant ER expansion and a marked increase in the unfolded protein response-induced chaperones Grp78 and Grp94. Upregulation of the Rab27a-dependent vesicular trafficking mechanisms rescued the defective lysosomal transport phenotype and reduced ER stress in cystinotic cells. Importantly, reconstitution of lysosomal transport mediated by Rab27a led to decreased lysosomal overload, manifested as reduced cystine cellular content. Our data suggest that upregulation of the Rab27a-dependent lysosomal trafficking and secretory pathways contributes to the correction of some of the cellular defects induced by lysosomal overload in cystinosis, including ER stress
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