当前期刊: "肝胆"类期刊
显示样式:        排序: 导出
我的关注
我的收藏
您暂时未登录!
登录
  • Advances in molecular classification and precision oncology in hepatocellular carcinoma
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Sandra Rebouissou; Jean-Charles Nault

    Hepatocellular carcinoma (HCC) arises from hepatocytes through the sequential accumulation of multiple genomic and epigenomic alterations resulting from Darwinian selection. Genes from various signalling pathways such as telomere maintenance, Wnt/β-catenin, P53/cell cycle regulation, oxidative stress, epigenetic modifiers, AKT/mTOR and MAP kinase are frequently mutated in HCC. Several subclasses of HCC have been identified based on transcriptomic dysregulation and genetic alterations that are closely related to risk factors, pathological features and prognosis. Undoubtedly, integration of data obtained from both preclinical models and human studies can help to accelerate the identification of robust predictive biomarkers of response to targeted biotherapy and immunotherapy. The aim of this review is to describe the main advances in HCC in terms of molecular biology and to discuss how this knowledge could be used in clinical practice in the future.

    更新日期:2020-01-15
  • Gut microbiome in HCC – Mechanisms, diagnosis and therapy
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Robert F. Schwabe; Tim F. Greten

    The microbiome exerts essential functions in health and disease, modulating key processes in metabolism, inflammation and immunity. Recent evidence has revealed a key role of the microbiome in carcinogenesis as well as anti-cancer immune responses in mouse models and patients. Herein, we will review functions of the gut microbiome in hepatocellular carcinoma (HCC), the third leading cause of worldwide cancer mortality. The majority of HCC develops in patients with chronic liver disease, caused by viral hepatitis, non-alcoholic fatty liver disease (NAFLD) and alcohol-related fatty liver disease. In this review, we will discuss mechanisms by which the gut-liver axis promotes the development of HCC in mouse models and patients, including dysbiosis, the leaky gut and bacterial metabolites, with a particular focus on NAFLD as the fastest growing cause of HCC development. Moreover, we will review recent progress in harnessing the gut microbiome as a potential diagnostic tool and novel therapeutic target in patients with HCC, in particular in the setting of immunotherapy.

    更新日期:2020-01-15
  • Novel patient-derived preclinical models of liver cancer
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Erin Bresnahan; Pierluigi Ramadori; Mathias Heikenwalder; Lars Zender; Amaia Lujambio

    Preclinical models of cancer based on the use of human cancer cell lines and mouse models have enabled discoveries that have been successfully translated into patients. And yet the majority of clinical trials fail, emphasising the urgent need to improve preclinical research to better interrogate the potential efficacy of each therapy and the patient population most likely to benefit. This is particularly important for liver malignancies, which lack highly efficient treatments and account for hundreds of thousands of deaths around the globe. Given the intricate network of genetic and environmental factors that contribute to liver cancer development and progression, the identification of new druggable targets will mainly depend on establishing preclinical models that mirror the complexity of features observed in patients. The development of new 3D cell culture systems, originating from cells/tissues isolated from patients, might create new opportunities for the generation of more specific and personalised therapies. However, these systems are unable to recapitulate the tumour microenvironment and interactions with the immune system, both proven to be critical influences on therapeutic outcomes. Patient-derived xenografts, in particular with humanised mouse models, more faithfully mimic the physiology of human liver cancer but are costly and time-consuming, which can be prohibitive for personalising therapies in the setting of an aggressive malignancy. In this review, we discuss the latest advances in the development of more accurate preclinical models to better understand liver cancer biology and identify paradigm-changing therapies, stressing the importance of a bi-directional communicative flow between clinicians and researchers to establish reliable model systems and determine how best to apply them to expanding our current knowledge.

    更新日期:2020-01-15
  • Epidemiology and surveillance for hepatocellular carcinoma: New trends
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Amit G. Singal; Pietro Lampertico; Pierre Nahon

    The burden of hepatocellular carcinoma (HCC) is highest in East Asia and Africa, although its incidence and mortality are rapidly rising in the United States and Europe. With the implementation of hepatitis B vaccination and hepatitis C treatment programmes worldwide, the epidemiology of HCC is shifting away from a disease predominated by viral hepatitis – an increasing proportion of cases are now attributable to non-alcoholic steatohepatitis. Surveillance using ultrasound, with or without alpha-fetoprotein, every 6 months has been associated with improved early detection and improved overall survival; however, limitations in implementation lead to a high proportion of HCC being detected at late stages in clinical practice. Herein, we review the current state of HCC surveillance and highlight areas for future research, including improved risk stratification of at-risk patients, surveillance tools with higher sensitivity and specificity for early HCC, and interventions to increase surveillance utilisation.

    更新日期:2020-01-15
  • Advances in resection and transplantation for hepatocellular carcinoma
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Eric Vibert; Myron Schwartz; Kim M. Olthoff

    It would be impossible to summarise all of the significant developments in the surgical management of hepatocellular carcinoma (HCC), even just over the past year, in a manuscript of this scope. Thus, we have selected topics for discussion that are the subject of current controversy and have attempted to present balanced points of view. Hepatic resection and transplantation are both mature modalities, and for the most part technical advances and improvements in candidate selection are incremental. The ability to readily cure hepatitis C stands out as the most impactful development in the field over recent years, especially in Western countries where hepatitis C has long been the chief aetiology underlying HCC and a predictor of poor outcomes after surgery, but its full implications remain to be clarified. The rising incidence of non-alcoholic steatohepatitis-related HCC and what it means with regard to surgical HCC management is an area of great current interest. With advancing technology, non-surgical locoregional treatments are gaining increasing application as potentially curative therapies. In addition, the advances in molecular and genomic assessment of HCC hold promise for personalising treatment and prognostication. The possible role of immunotherapy as an adjuvant to resection is being aggressively investigated. While liver surgery maintains an important role, the care of patients with HCC is more and more a team effort and needs to take place in the context of a well-integrated interdisciplinary programme to achieve the best outcomes for patients.

    更新日期:2020-01-15
  • Role of locoregional therapies in the wake of systemic therapy
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Daniel H. Palmer; Katerina Malagari; Laura M. Kulik

    Multiple systemic agents have recently been approved in the first- and second-line setting for hepatocellular carcinoma (HCC), increasing the therapeutic options for patients and treating physicians. The randomised controlled trials that led to these approvals were predominantly conducted in a population comprised of patients with advanced HCC. However, these trials also included a subset of patients who had progressed after locoregional therapies (LRTs), mostly transarterial chemoembolisation. With a greater number of systemic agents available, the role of LRTs has become a topic of debate, specifically regarding when to transition to systemic therapy in unresectable HCC and the potential opportunities for combining locoregional and systemic therapies. Trials of immuno-oncology agents (notably T cell checkpoint inhibitors) are ongoing in the advanced disease setting and these agents also present opportunities for combination therapies, both with other systemic agents and with LRTs in earlier stage disease. This article will review strategies to guide patient selection for LRT as well as the development of locoregional-systemic combinations based on scientific rationale and the challenges of clinical trial design in this setting.

    更新日期:2020-01-15
  • mRECIST for HCC: Performance and novel refinements
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Josep M. Llovet; Riccardo Lencioni

    In 2010, modified RECIST (mRECIST) criteria were proposed as a way of adapting the RECIST criteria to the particularities of hepatocellular carcinoma (HCC). We intended to overcome some limitations of RECIST in measuring tumour shrinkage with local and systemic therapies, and also to refine the assessment of progression that could be misinterpreted with conventional RECIST 1.1, due to clinical events related to the natural progression of chronic liver disease (development of ascites, enlargement of lymph nodes, etc.). mRECIST has served its purpose since being adopted or included in clinical practice guidelines (European, American and Asian) for the management of HCC; it has also been instrumental for assessing response and time-to-event endpoints in several phase II and III investigations. Nowadays, mRECIST has become the standard tool for measurement of radiological endpoints at early/intermediate stages of HCC. At advanced stages, guidelines recommend both methods. mRECIST has been proven to capture higher objective response rates in tumours treated with molecular therapies and those responses have shown to be independently associated with better survival. With the advent of novel treatment approaches (i.e. immunotherapy) and combination therapies there is a need to further refine and clarify some concepts around the performance of mRECIST. Similarly, changes in the landscape of standard of care at advanced stages of the disease are pointing towards progression-free survival as a potential primary endpoint in some phase III investigations, as effective therapies applied beyond progression might mask overall survival results. Strict recommendations for adopting this endpoint have been reported. Overall, we review the performance of mRECIST during the last decade, incorporating novel clarifications and refinements in light of emerging challenges in the study and management of HCC.

    更新日期:2020-01-15
  • Challenges of combination therapy with immune checkpoint inhibitors for hepatocellular carcinoma
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Ann-Lii Cheng; Chiun Hsu; Stephen L. Chan; Su-Pin Choo; Masatoshi Kudo

    Immune checkpoint inhibitor (ICI) therapy targeting anti-programmed cell death-1 (anti-PD-1) or its ligand (anti-PD-L1) is the backbone of numerous combination regimens aimed at improving the objective response and survival of patients with hepatocellular carcinoma (HCC). Clinical trials of immuno-oncology regimens in other cancer types have shed light on issues of study design, including how to choose candidate regimens based on early-phase trial results, statistical considerations in trials with multiple primary endpoints, and the importance of predictive biomarkers. In this review, the updated data from early-phase trials of combination immunotherapy for HCC are summarised. Since the most extensively tested combination regimens for advanced HCC comprise anti-PD-1/anti-PD-L1 agents plus antiangiogenic agents, the relative benefit and antitumor mechanism of antiangiogenic multikinase inhibitors versus specific VEGF/VEGFR inhibitors are discussed. Other critical issues in the development of combination immunotherapy, including optimal management of immune-related adverse events and the value of ICI therapy in combination with locoregional treatment for HCC, are also explored.

    更新日期:2020-01-15
  • Diagnosis and management of toxicities of immune checkpoint inhibitors in hepatocellular carcinoma
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Bruno Sangro; Stephen L. Chan; Tim Meyer; María Reig; Anthony El-Khoueiry; Peter R. Galle

    Immune checkpoint inhibitors (ICIs) have reshaped cancer therapy. ICIs enhance T cell activation through various mechanisms and may help reverse the exhausted phenotype of tumour-infiltrating lymphocytes. However, disrupting the key role that checkpoint molecules play in immune homeostasis may result in autoimmune complications. A broad range of immune-related adverse events (irAEs) involve almost every organ but mostly affect the skin, digestive system, lung, endocrine glands, nervous system, kidney, blood cells, and musculoskeletal system. They are usually manageable but can be life-threatening. The incidence of irAEs is not very different in patients with hepatocellular carcinoma (HCC) compared to other tumour types, although there is a trend towards a higher incidence of hepatic irAEs. HCC usually develops on a background of cirrhosis with associated systemic manifestations. Extrahepatic organ dysfunction in cirrhosis may cause signs and symptoms that overlap with irAEs or increase their severity. Available guidelines for the management of irAEs have not specifically considered the assessment of toxicities in the context of patients with liver cancer and cirrhosis. This review addresses the toxicity profile of ICIs in patients with HCC, focusing on the challenges that the underlying liver disease poses to their diagnosis and management. Challenges include late recognition, inadequate work-up and delayed treatment, overdiagnosis and inappropriate interruption of ICIs, complications caused by immunosuppressive therapy, and increased cost. A specific algorithm for the management of hepatic irAEs is provided.

    更新日期:2020-01-15
  • Molecular therapies for HCC: Looking outside the box
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Sandrine Faivre; Lorenza Rimassa; Richard S. Finn

    Over the past decade, sorafenib has been the only systemic agent with proven clinical efficacy for patients with unresectable hepatocellular carcinoma (HCC). Recently, lenvatinib was shown to be non-inferior to sorafenib, while regorafenib, cabozantinib, and ramucirumab were shown to be superior to placebo in patients failing sorafenib. In addition, trials of immune checkpoint inhibitors reported encouraging efficacy signals. However, apart from alpha-fetoprotein, which is used to select patients for ramucirumab, no biomarkers are available to identify patients that may respond to a specific treatment. Different synergisms have been postulated based on the potential interplay between antiangiogenic drugs and immunotherapy, with several clinical trials currently testing this hypothesis. Indeed, encouraging preliminary results of phase I studies of bevacizumab plus atezolizumab and lenvatinib plus pembrolizumab have led to the design of ongoing phase III trials, including both antiangiogenics and immune checkpoint inhibitors in the front-line setting. Other important phase II studies have tested molecular therapies directed against different novel targets, such as transforming growth factor-beta, MET (hepatocyte growth factor receptor), and fibroblast growth factor receptor 4. These studies integrated translational research with the aim of better defining the biological tumour profile and identifying tumour and blood biomarkers that select patients who may really benefit from a specific molecular therapy. Importantly, good safety profiles make these drugs suitable for future combinations. In this review, we discuss the most recent data on novel combination strategies and targets, as well as looking ahead to the future role of molecular therapies in the treatment of patients with advanced HCC.

    更新日期:2020-01-15
  • Systemic therapies for intrahepatic cholangiocarcinoma
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Robin Kate Kelley; John Bridgewater; Gregory J. Gores; Andrew X. Zhu

    Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal hepatobiliary neoplasm whose incidence is increasing. Largely neglected for decades as a rare malignancy and frequently misdiagnosed as carcinoma of unknown primary, considerable clinical and investigative attention has recently been focused on iCCA worldwide. The established standard of care includes first-line (gemcitabine and cisplatin), second-line (FOLFOX) and adjuvant (capecitabine) systemic chemotherapy. Compared to hepatocellular carcinoma, iCCA is genetically distinct with several targetable genetic aberrations identified to date. Indeed, FGFR2 and NTRK fusions, and IDH1 and BRAF targetable mutations have been comprehensively characterised and clinical data is emerging on targeting these oncogenic drivers pharmacologically. Also, the role of immunotherapy has been examined and is an area of intense investigation. Herein, in a timely and topical manner, we will review these advances and highlight future directions of research.

    更新日期:2020-01-15
  • Liver resection and transplantation for intrahepatic cholangiocarcinoma
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Vincenzo Mazzaferro; Andre Gorgen; Sasan Roayaie; Michele Droz dit Busset; Gonzalo Sapisochin

    The incidence of intrahepatic cholangiocarcinoma (iCCA) is increasing worldwide. Although several advances have been made in the past decades to better understand this complex malignancy and to develop new treatment strategies, the prognosis of iCCA remains dismal. Liver resection (LR) is the mainstay of treatment but only a minority of patients are amenable to surgery. In most cases, patients with iCCA will require a major hepatectomy for complete resection of the tumour. This may be contraindicated or increase the surgical burden in patients with chronic liver disease and small remnant liver volume. Lymphadenectomy with a minimal harvest of 6 lymph nodes is considered adequate, as microscopic nodal metastases have been shown in more than 40% of patients. Current 5-year overall survival following LR is in the range of 25%–40%. For locally advanced disease not amenable to upfront LR, neoadjuvant locoregional therapies may be used with the aim of converting these patients to resectability or even to transplantation in well-selected cases. Recent studies have shown that liver transplantation (LT) might be a treatment option for patients with unresectable very-early iCCA (i.e. ≤2 cm), with survival outcomes comparable to those of hepatocellular carcinoma. In patients with unresectable, advanced tumours, confined to the liver who achieve sustained response to neoadjuvant treatment, LT may be considered an option within prospective protocols. The role of adjuvant therapies in iCCA is still under debate. Herein, we review the recent advances in the surgical treatment of iCCA and examine its correlation with locoregional therapies, adjuvant and neo-adjuvant strategies.

    更新日期:2020-01-15
  • Long-term outcome of decompensated alcohol-related liver disease with steatohepatitis and Maddrey’s discriminant function <32.
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Delphine Degré; Rudolf E. Stauber; Gaël Englebert; Francesca Sarocchi; Laurine Verset; Florian Rainer; Walter Spindelboeck; Hassane Njimi; Eric Trépo; Thierry Gustot; Carolin Lackner; Pierre Deltenre; Christophe Moreno
    更新日期:2020-01-15
  • Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Michael Praktiknjo; Macarena Simón-Talero; Julia Römer; Davide Roccarina; Javier Martínez; Katharina Lampichler; Anna Baiges; Gavin Low; Elba Llop; Martin H. Maurer; Alexander Zipprich; Michela Triolo; Geert Maleux; Annette Dam Fialla; Claus Dam; Judit Vidal-González; Avik Majumdar; Carmen Picón; Jonel Trebicka
    更新日期:2020-01-15
  • Thyroid hormone inhibits hepatocellular carcinoma progression via induction of differentiation and metabolic reprogramming
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Marta Anna Kowalik; Elisabetta Puliga; Lavinia Cabras; Pia Sulas; Annalisa Petrelli; Andrea Perra; Giovanna Maria Ledda-Columbano; Andrea Morandi; Simone Merlin; Claudia Orrù; Carlos Sanchez-Martin; Francesca Fornari; Laura Gramantieri; Matteo Parri; Andrea Rasola; Sara Erika Bellomo; Carlos Sebastian; Antonia Follenzi; Amedeo Columbano
    更新日期:2020-01-15
  • A dual role for hepatocyte-intrinsic canonical NF-κB signaling in virus control
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Sukumar Namineni; Tracy O‘Connor; Suzanne Faure-Dupuy; Pål Johansen; Tobias Riedl; Kaijing Liu; Haifeng Xu; Indrabahadur Singh; Prashant Shinde; Fanghui Li; Aleksandra Pandyra; Piyush Sharma; Marc Ringelhan; Andreas Muschaweckh; Katharina Borst; Patrick Blank; Sandra Lampl; David Durantel; Mathias Heikenwalder
    更新日期:2020-01-15
  • Physical Activity Compared to Adiposity and Risk of Liver-Related Mortality: Results from Two Prospective, Nationwide Cohorts
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Tracey G. Simon; Mi Na Kim; Xiao Luo; Wanshui Yang; Yanan Ma; Dawn Q. Chong; Charles S. Fuchs; Jeffrey A. Meyerhardt; Kathleen E. Corey; Raymond T. Chung; Meir Stampfer; Xuehong Zhang; Edward L. Giovannucci; Andrew T. Chan
    更新日期:2020-01-15
  • DEVELOPMENT OF CHRONIC KIDNEY DISEASE AFTER ACUTE KIDNEY INJURY IN PATIENTS WITH CIRRHOSIS IS COMMON AND IMPAIRS CLINICAL OUTCOMES
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Octavi Bassegoda; Patricia Huelin; Xavier Ariza; Cristina Solé; Adrià Juanola; Jordi Gratacós-Ginès; Marta Carol; Isabel Graupera; Elisa Pose; Laura Napoleone; Sonia Albertos; Gloria de Prada; Marta Cervera; Javier Fernández; Núria Fabrellas; Esteban Poch; Elsa Solà; Pere Ginès
    更新日期:2020-01-15
  • IL-33/ST2 pathway regulates neutrophil migration and predicts outcome in patients with severe alcoholic hepatitis
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Florent Artru; Mohamed Bou Saleh; François Maggiotto; Guillaume Lassailly; Massih Ningarhari; Julie Demaret; Line-Carolle Ntandja-Wandji; Jean-Paul Pais de Barros; Julien Labreuche; Elodie Drumez; Doumet Georges Helou; Sébastien Dharancy; Emilie Gantier; Axel Périanin; Sylvie Chollet-Martin; Ramon Bataller; Philippe Mathurin; Laurent Dubuquoy; Alexandre Louvet
    更新日期:2020-01-15
  • Preoperative imaging characteristics predict poor survival and inadequate resection for left-sided pancreatic adenocarcinoma: a multi-institutional analysis
    HPB (IF 3.047) Pub Date : 2020-01-11
    Farzad Alemi; Zeljka Jutric; George R. Marshall; Elliot J. Scott; Jan Grendar; Alexandra M. Roch; Lucio L. Pereira; An-Lin Cheng; Paul D. Hansen; Eugene P. Ceppa; Horacio J. Asbun; Susanne Warner; Adnan A. Alseidi

    Background Optimal treatment of pancreatic ductal adenocarcinoma of the neck, body and tail (PDAC-NBT) necessitates R0 surgical resection. Preoperative radiographic identification of patients likely to achieve successful oncologic resection remains difficult. This study seeks to identify preoperative imaging characteristics predictive of non-R0 resections or impaired survival for PDAC-NBT. Methods Patients at five high-volume centers who underwent resection for PDAC-NBT were retrospectively analyzed. The most immediate preoperative cross-sectional scan was assessed along with outcome measures of overall survival and margin status. Results 330 patients were treated between 2001 and 2016. Margin status included 247 R0 (78.2%), 67 R1 (21.2%), and 2 R2 (0.6%). A non-R0 resection predicted worse survival (p = 0.0002). On preoperative imaging, patients with tumors greater than 20 mm, tumor attenuation greater than 70 Hounsfield units, or who demonstrated pancreatic atrophy and/or calcifications also had worse survival (p = 0.010, p = 0.036, p = 0.025 respectively). Patients with tumors interfacing with the splenic artery or vein or extending posteriorly achieved fewer R0 resections (p = 0.0006, p = 0.0004, p = 0.001, respectively). Conclusion Preoperative cross-sectional imaging can identify tumor characteristics associated with poor survival and non-R0 resection. Further investigation is needed to identify the appropriate surgical and treatment modifications necessary to clinically benefit this subset of patients.

    更新日期:2020-01-13
  • Treatment of hepatocarcinoma beyond the milan criteria. A weighted comparative study of surgical resection versus chemoembolization
    HPB (IF 3.047) Pub Date : 2020-01-10
    Simone Famularo; Stefano Di Sandro; Alessandro Giani; Davide P. Bernasconi; Andrea Lauterio; Cristina Ciulli; Antonio G. Rampoldi; Rocco Corso; Riccardo De Carlis; Fabrizio Romano; Marco Braga; Luca Gianotti; Luciano De Carlis

    Background Optimal treatment of hepatocarcinoma (HCC) beyond the Milan criteria (MC) is debated. The aim of the study was to assess overall-survival (OS) and disease-free-survival (DFS) for HCC beyond MC when treated by trans-arterial-chemoembolization (TACE) or surgical resection (SR). Method between 2005 and 2015, all patients with a first diagnosis of HCC beyond MC(1 nodule>5 cm, or 3 nodules>3 cm without macrovascular invasion) were evaluated. Analyses were carried out through Kaplan–Meier, Cox models and the inverse probability weighting (IPW) method to reduce allocation bias. Sub-analyses have been performed for multinodular and single large tumors compared with a MC-IN cohort. Results 226 consecutive patients were evaluated: 118 in SR group and 108 in TACE group. After IPW, the two pseudo-populations were comparable for tumor burden and liver function. In the SR group, 1–5 years OS rates were 72.3% and 35% respectively and 92.7% and 39.3% for TACE (p = 0.500). The median DFS was 8 months (95%CI:8–9) for TACE, and 11 months (95%CI:9–12) for SR (p < 0.001). TACE was an independent predictor for recurrence (HR 1.5; 95%CI: 1.1–2.1; p = 0.015). Solitary tumors > 5 cm and multinodular disease had comparable OS and DFS as Milan-IN group (p > 0.05). Conclusion Surgery allowed a better control than TACE in patient bearing HCC beyond MC. This translated into a significant benefit in terms of DFS but not OS.

    更新日期:2020-01-11
  • New approaches in viraemic organ transplantation and antiviral therapies
    Nat. Rev. Gastroenterol. Hepatol. (IF 23.570) Pub Date : 2020-01-08
    Jacinta A. Holmes; Raymond T. Chung
    更新日期:2020-01-09
  • Correlating serum alpha-fetoprotein in hepatocellular carcinoma with response to Yttrium-90 transarterial radioembolization with glass microspheres (TheraSphere™)
    HPB (IF 3.047) Pub Date : 2020-01-06
    Neal Bhutiani; Stephen J. O'Brien; Erin E. Priddy; Michael E. Egger; Young K. Hong; Megan K. Mercer; Kelly M. McMasters; Robert C.G. Martin; Melissa H. Potts; Charles R. Scoggins

    Background Few studies have assessed the relationship between serum alpha-fetoprotein (AFP) and yttrium-90 (Y-90) radioembolization response in hepatocellular carcinoma (HCC). The objective of the study was to evaluate whether peri-procedural serum AFP was correlated with Y-90 therapy response in HCC. Methods Patients undergoing Y-90 radioembolization with glass microspheres (TheraSphere™) for HCC between 2006 and 2013 at a single center were evaluated. The relationship between AFP and 6-month radiographic improvement (complete or partial response by modified RECIST criteria), overall (OS), and disease-specific survival (DSS) were analyzed. Results Seventy-four patients underwent a total of 124 Y-90 infusions. Median age was 65 years, median AFP was 37 ng/mL (range: 2–112,593 ng/mL) and median model for end-stage liver disease score was 6.2 (range:1.8–11.2). Increased AFP was not associated with radiographic improvement (odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.75–1.30, p = 0.92). Median OS was 15.2 months and was increased in patients with low AFP compared to high AFP (30.8 months vs. 7.8 months, p < 0.001). On multivariable regression analysis, increased AFP was associated with worse OS (OR = 1.11, 95%CI = 1.01–1.22, p = 0.034) and DSS (OR = 1.13, 95%CI = 1.03–1.25, p = 0.018). Conclusion Pre-infusion AFP independently predicted survival after Y-90 treatment for HCC, but not radiographic response, and can help guide treatment decisions.

    更新日期:2020-01-06
  • Harnessing big ‘omics’ data and AI for drug discovery in hepatocellular carcinoma
    Nat. Rev. Gastroenterol. Hepatol. (IF 23.570) Pub Date : 2020-01-03
    Bin Chen; Lana Garmire; Diego F. Calvisi; Mei-Sze Chua; Robin K. Kelley; Xin Chen
    更新日期:2020-01-04
  • Epigenetics of colorectal cancer: biomarker and therapeutic potential
    Nat. Rev. Gastroenterol. Hepatol. (IF 23.570) Pub Date : 2020-01-03
    Gerhard Jung; Eva Hernández-Illán; Leticia Moreira; Francesc Balaguer; Ajay Goel
    更新日期:2020-01-04
  • IL-17 signaling in steatotic hepatocytes and macrophages promotes hepatocellular carcinoma in alcohol-related liver disease
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-31
    Hsiao-Yen Ma; Gen Yamamoto; Jun Xu; Xiao Liu; Daniel Karin; Ju Youn Kim; Ludmil B. Alexandrov; Yukinori Koyama; Takahiro Nishio; Chris Benner; Sven Heinz; Sara B. Rosenthal; Shuang Liang; Mengxi Sun; Gabriel Karin; Peng Zhao; Pnina Brodt; Iain H. Mckillop; Tatiana Kisseleva
    更新日期:2019-12-31
  • Hepatopancreatoduodenectomy –a controversial treatment for bile duct and gallbladder cancer from a European perspective
    HPB (IF 3.047) Pub Date : 2019-12-30
    Melroy A. D'Souza; Valentinus T. Valdimarsson; Tommaso Campagnaro; Francois Cauchy; Nikolaos A. Chatzizacharias; Mathieu D'Hondt; Bobby Dasari; Alessandro Ferrero; Lotte C. Franken; Giuseppe Fusai; Alfredo Guglielmi; Jeroen Hagendoorn; Camila Hidalgo Salinas; Frederik J.H. Hoogwater; Rosa Jorba; Nariman Karanjia; Wolfram T. Knoefel; Philipp Kron; Christian Sturesson

    Background Hepatopancreatoduodenectomy (HPD) is an aggressive operation for treatment of advanced bile duct and gallbladder cancer associated with high perioperative morbidity and mortality, and uncertain oncological benefit in terms of survival. Few reports on HPD from Western centers exist. The purpose of this study was to evaluate safety and efficacy for HPD in European centers. Method Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients operated with HPD for bile duct or gallbladder cancer between January 2003 and January 2018. The patient and tumor characteristics, perioperative and survival outcomes were analyzed. Results In total, 66 patients from 19 European centers were included in the analysis. 90-day mortality rate was 17% and 13% for bile duct and gallbladder cancer respectively. All factors predictive of perioperative mortality were patient and disease-specific. The three-year overall survival excluding 90-day mortality was 80% for bile duct and 30% for gallbladder cancer (P = 0.013). In multivariable analysis R0-resection had a significant impact on overall survival. Conclusion HPD, although being associated with substantial perioperative mortality, can offer a survival benefit in patient subgroups with bile duct cancer and gallbladder cancer. To achieve negative resection margins is paramount for an improved survival outcome.

    更新日期:2019-12-30
  • OGDHL silencing promotes hepatocellular carcinoma by reprogramming glutamine metabolism
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-30
    W.Q. Dai; L. Xu; X.N. Yu; G.C. Zhang; H.Y. Guo; H.L. Liu; G.Q. Song; S.Q. Weng; L. Dong; J.M. Zhu; T.T. Liu; C.Y. Guo; X.Z. Shen
    更新日期:2019-12-30
  • A systematic review and network meta-analysis of phase III randomised controlled trials for adjuvant therapy following resection of pancreatic ductal adenocarcinoma (PDAC)
    HPB (IF 3.047) Pub Date : 2019-12-29
    Sivesh K. Kamarajah; James R. Bundred; Wasfi Alrawashdeh; Derek Manas; Steven A. White

    Background Several randomised controlled trials (RCTs) have reported various systemic adjuvant therapy regimens following resection of pancreatic ductal adenocarcinoma (PDAC). The most commonly applied include modified FOLFRINOX (mFFX), Gemcitabine/Capecitabine (GemCap) and S1, usually compared to gemcitabine (Gem) alone. However, many of these regimens have not been directly compared in RCTs. This network meta-analysis aims to characterise the impact of adjuvant therapies on overall and disease-free survival in patients having resection of PDAC. Methods A systematic review was conducted using MEDLINE, EMBASE, Cochrane Central and American Society of Clinical Oncology (ASCO) abstracts to identify published phase III RCTs articles up to 9th May 2019 that examined adjuvant systemic therapy in resected pancreatic cancer. Data including study characteristics and outcomes including overall survival (OS) and disease-free survival (DFS) were extracted. Indirect comparisons of all regimens were simultaneously compared using random-effects network meta-analyses (NMA) which maintains randomisation within trials. Results Twelve phase III RCTs involving 4947 patients and nine different regimens (5-Flourouracil/Folinic acid (5-FU/FA), Gemcitabine, Gemcitabine/Erlotinib (GemErl), GemCap), mFFX, S1, chemoradiotherapy (CRT), CRT with either 5-FU or Gemcitabine) were identified. S1 was ranked best for overall and disease-free survival followed by mFFX. Whilst there were no significant difference between S1 and mFFX for overall survival (mean difference: 1.6 months, p = 0.8), S1 had significantly longer disease-free survival than mFFX (mean difference: 2.8 months, p < 0.001). Furthermore, S1 was ranked best for lowest overall and haematological grade 3/4 toxicities. Conclusion This network meta-analysis demonstrates that chemotherapy with S1 or mFFX is superior to GemCap for adjuvant treatment for PDAC, improves survival after surgical resection and should be considered as reasonable standard treatment options in the adjuvant setting and as control arm for future adjuvant clinical trials.

    更新日期:2019-12-29
  • Pulmonary metastases in newly diagnosed hepatocellular carcinoma: a population-based retrospective study
    HPB (IF 3.047) Pub Date : 2019-12-28
    Jincheng Feng; Ying He; Junhua Wan; Zhishui Chen

    Background Hepatocellular carcinoma (HCC) is a major form of primary liver cancer with steadily increasing incidence for the decades, and has propensity to have extrahepatic metastases, especially pulmonary metastases (PM). This study aimed to investigate temporal incidence trends, treatment, and survival of patients with HCCPM. Methods Patients with HCCPM were retrospectively reviewed from 2010 to 2016 in US National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results registry (SEER). Results 2242 patients with HCCPM were identified. Overall HCCPM incidence did not change from 2010 to 2016, with an annual percent change (APC) of 0.87% (95% CI = −2.50%–4.35%, P = 0.542). Similar incidence trends patterns were found in subgroup analyses of sex, age, and race. 1-year observed survival for HCCPM was 10.8% (95%CI = 8.9%–12.8%) and relative survival was 11.0% (95%CI = 9.1%–13.1%). Better outcomes were noted among patients who underwent liver-directed surgery, those who treated with chemotherapy, and those who received radiation. Conclusions The incidence of HCCPM does not increase with the increasing incidence of HCC. Patients with HCCPM have a dismal prognosis with low survival rates. Liver-directed surgery, use of chemotherapy, and radiation may be associated with improved outcomes.

    更新日期:2019-12-29
  • The impact of hepatic arterial infusion pump chemotherapy on hepatic recurrences and survival in patients with resected colorectal liver metastases
    HPB (IF 3.047) Pub Date : 2019-12-27
    Florian E. Buisman; Boris Galjart; Eric P. van der Stok; Nancy E. Kemeny; Vinod P. Balachandran; Thomas Boerner; Andrea Cercek; Dirk J. Grünhagen; William R. Jarnagin; T. Peter Kingham; Cornelis Verhoef; B. Groot Koerkamp; Michael I. D'Angelica

    Background The objective was to investigate the impact of adjuvant hepatic arterial infusion pump (HAIP) chemotherapy on the rates and patterns of recurrence and survival in patients with resected colorectal liver metastases (CRLM). Methods Recurrence rates, patterns, and survival were compared between patients treated with and without adjuvant HAIP using competing risk analyses. Results 2128 patients were included, of which 601 patients (28.2%) received adjuvant HAIP and systemic chemotherapy (HAIP + SYS). The overall recurrence rate was similar with HAIP + SYS or SYS (63.5% versus 64.2%,p = 0.74). The 5-year cumulative incidence of initial intrahepatic recurrences was lower with HAIP + SYS (22.9% versus 38.4%,p < 0.001). The 5-year cumulative incidence of initial extrahepatic recurrences was higher with HAIP + SYS (48.5% versus 40.3%,p = 0.005), because patients remained at risk for extrahepatic recurrence in the absence of intrahepatic recurrence, which was largely attributable to more pulmonary recurrences with HAIP + SYS (33.6% versus 23.7%,p < 0.001). HAIP was an independent prognostic factor for DFS (adjusted HR 0.69, 95% CI 0.60–0.79, p < 0.001), and OS (adjusted HR 0.67, 95% CI 0.57–0.78,p < 0.001). Conclusion Adjuvant HAIP chemotherapy is associated with lower intrahepatic recurrence rates and better DFS and OS after resection of CRLM.

    更新日期:2019-12-29
  • Hospital variation in Textbook Outcomes following curative-intent resection of hepatocellular carcinoma: an international multi-institutional analysis
    HPB (IF 3.047) Pub Date : 2019-12-27
    Diamantis I. Tsilimigras; Rittal Mehta; Katiuscha Merath; Fabio Bagante; Anghela Z. Paredes; Ayesha Farooq; Francesca Ratti; Hugo P. Marques; Silvia Silva; Olivier Soubrane; Vincent Lam; George A. Poultsides; Irinel Popescu; Razvan Grigorie; Sorin Alexandrescu; Guillaume Martel; Aklile Workneh; Alfredo Guglielmi; Timothy M. Pawlik

    Background Composite measures such as “Textbook Outcome” (TO) may be superior to individual quality metrics to assess surgical care and hospital performance. However, the incidence and factors associated with TO after resection of HCC remain poorly defined. Methods Hospital variation in the rates of TO, factors associated with achieving a TO and the impact of TO on long-term survival following resection for HCC were examined using an international multi-institutional database. Results Among 605 patients who underwent curative-intent resection of HCC, the unadjusted incidence of TO ranged from 50.9% to 77.7%. While achievement of each individual quality metric was relatively high (range, 74.5–98.0%), an overall TO was achieved among only 62.3% (n = 377) of patients. At the hospital level, TO ranged from 54.3% to 72.9%. Patients with BCLC-0 HCC (referent BCLC-B/C; OR: 4.17, 95%CI: 1.62–10.7) and ALBI grade 1 (referent ALBI grade 2/3; OR: 1.49, 95%CI: 1.06–2.11) had higher odds of achieving a TO. On multivariable analysis, TO was associated with improved overall survival (HR: 0.60, 95% CI: 0.42–0.85). Conclusion Roughly 6 in 10 patients achieved a TO following resection for HCC. When achieved, TO was associated with better long-term outcomes. TO is a simple composite measure of both short- and long-term outcomes among patients undergoing resection for HCC.

    更新日期:2019-12-29
  • A randomized, placebo-controlled trial of emricasan in patients with NASH and F1-F3 fibrosis
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-27
    Stephen A. Harrison; Zachary Goodman; Abdul Jabbar; Ravi Vemulapalli; Ziad H. Younes; Bradley Freilich; Muhammad Y. Sheikh; Jörn M. Schattenberg; Zeid Kayali; Adam Zivony; Aasim Sheikh; Javier Garcia-Samaniego; Sanjaya K. Satapathy; George Therapondos; Edward Mena; Detlef Schuppan; James Robinson; Jean L. Chan; Arun J. Sanyal
    更新日期:2019-12-27
  • Heterogeneous immunogenomic features and distinct escape mechanisms in multifocal hepatocellular carcinoma
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-27
    Liang-qing Dong; Li-hua Peng; Li-jie Ma; Dong-bing Liu; Shu Zhang; Shu-zhen Luo; Jun-hua Rao; Hong-wen Zhu; Shuai-xi Yang; Shui-jun Xi; Min Chen; Fan-fan Xie; Fu-qiang Li; Wen-hui Li; Chen Ye; Li-ya Lin; Yu-jue Wang; Xiao-ying Wang; Qiang Gao
    更新日期:2019-12-27
  • The cardiac output optimisation following liver transplant (COLT) trial: a feasibility randomised controlled trial
    HPB (IF 3.047) Pub Date : 2019-12-23
    Daniel Martin; Rahul Koti; Kurinchi Gurusamy; Louise Longworth; Jeshika Singh; Farid Froghi; Fiammetta Soggiu; Susan Mallett; Nick Schofield; Linda Selves; Douglas Thorburn; Christine Eastgate; Helder Filipe; Margaret McNeil; Zacharias Anastasiou; Brian Davidson

    Background Perioperative goal directed fluid therapy (GDFT) has been shown to reduce postoperative complications following major surgery; this intervention has not been formally evaluated in the setting of liver transplantation. Methods We conducted a prospective trial of GDFT following liver transplantation randomising patients with liver cirrhosis to either 12 h of GDFT using non-invasive cardiac output monitoring or standard care (SC). The primary outcome was feasibility. Secondary outcomes included survival, postoperative complications (Clavien-Dindo), quality of life (by EQ-5D-5L) and resource use. Trial specific follow up occurred at 90 and 180 days after surgery. Results The study was feasible. Of 224 eligible patients, 122 were approached, 114 consented to participate and 60 were enrolled into the trial. The mean (SD) volume of IV crystalloid administered to the GDFT group during the 12-h study period was 3968 (2073) ml for the GDFT group and 2510 (1026) ml for the SC group. As regards secondary outcomes there was no difference in survival or overall complication rates. There was no significant difference in quality of life scores and resource use between the groups. Conclusion A randomised study of GDFT following liver transplantation is feasible. A post-trial stakeholder meeting supported proceeding with a full multi-centre trial.

    更新日期:2019-12-23
  • Balancing the risks and rewards of live biotherapeutics
    Nat. Rev. Gastroenterol. Hepatol. (IF 23.570) Pub Date : 2019-12-23
    Colin Hill

    Live biotherapeutics have been used clinically both as defined probiotics and as undefined faecal microbiota transplants. Two new studies illustrate the risks of administering live microorganisms to highly compromised patients. These risks should be considered in the context of the potential therapeutic value of these treatments.

    更新日期:2019-12-23
  • 更新日期:2019-12-23
  • Randomized Placebo-Controlled Trial of Emricasan in Non-alcoholic Steatohepatitis (NASH) Cirrhosis with Severe Portal Hypertension
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-21
    Guadalupe Garcia-Tsao; Jaime Bosch; Zeid Kayali; Stephen A. Harrison; Manal F. Abdelmalek; Eric Lawitz; Sanjaya K. Satapathy; Marwan Ghabril; Mitchell L. Shiffman; Ziad H. Younes; Paul J. Thuluvath; Annalisa Berzigotti; Agustin Albillos; James M. Robinson; David T. Hagerty; Jean L. Chan; Arun J. Sanyal
    更新日期:2019-12-21
  • Comparison of extracellular and hepatobiliary MR contrast agents for the diagnosis of small HCCs
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-21
    Anita Paisant; Valérie Vilgrain; Jérémie Riou; Frédéric Oberti; Olivier Sutter; Valérie Laurent; Agnès Rodes; Boris Guiu; Christophe Cassinotto; Hervé Trillaud; Yvan Bricault; Sophie Michalak; Onorina Bruno; Maxime Ronot; Christophe Aubé
    更新日期:2019-12-21
  • 更新日期:2019-12-19
  • Interferon-inducible MX2 is a host restriction factor of hepatitis B virus replication
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-18
    Yong-Xiang Wang; Matthias Niklasch; Tiantian Liu; Yang Wang; Bisheng Shi; Wenjie Yuan; Thomas F. Baumert; Zhenghong Yuan; Shuping Tong; Michael Nassal; Yu-Mei Wen
    更新日期:2019-12-19
  • 更新日期:2019-12-18
  • BAP1 mutations define a homogeneous subgroup of hepatocellular carcinoma with fibrolamellar-like features and activated PKA
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-18
    Théo Z. Hirsch; Ana Negulescu; Barkha Gupta; Stefano Caruso; Bénédicte Noblet; Gabrielle Couchy; Quentin Bayard; Léa Meunier; Guillaume Morcrette; Jean-Yves Scoazec; Jean-Frédéric Blanc; Giuliana Amaddeo; Jean-Charles Nault; Paulette Bioulac-Sage; Marianne Ziol; Aurélie Beaufrère; Valérie Paradis; Julien Calderaro; Jessica Zucman-Rossi
    更新日期:2019-12-18
  • High incidence of HCV in HIV-negative men who have sex with men using pre-exposure prophylaxis
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-18
    Elske Hoornenborg; Liza Coyer; Anders Boyd; Roel Christiaan Alfons Achterbergh; Maarten Franciscus Schim van der Loeff; Sylvia Bruisten; Henry John Christiaan de Vries; Jelle Koopsen; Thijs JW. van de Laar; Maria Prins
    更新日期:2019-12-18
  • Clinical validation of the FLIP algorithm and the SAF score in patients with non-alcoholic fatty liver disease
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-17
    Fabio Nascimbeni; Pierre Bedossa; Larysa Fedchuk; Raluca Pais; Frédéric Charlotte; Pascal Lebray; Thierry Poynard; Vlad Ratziu
    更新日期:2019-12-18
  • Pancreaticoduodenectomy in a low-resection volume region: a population-level study examining the impact of hospital-volume on surgical quality and longer-term survival
    HPB (IF 3.047) Pub Date : 2019-12-14
    Aaditya Narendra; Peter D. Baade; Joanne F. Aitken; Jonathan Fawcett; Bernard Mark Smithers

    Background An association between higher hospital-volume and better “quality of surgery” and long-term survival has not been reported following pancreatic cancer surgery in low resection-volume regions such as in Australia. Using a population-level study, we compare “quality of surgery” and two-year survival following pancreaticoduodenectomy between Australian hospitals grouped by resection-volume. Methods Data on all patients undergoing pancreaticoduodenectomy for adenocarcinoma in the Australian state of Queensland, between 2001 and 2015, were obtained from the Queensland Oncology Repository. Hospitals were grouped into high (≥6 resections annually) and low (<6) volume centres. Following adjustment for case-mix, “quality-of-treatment” indicators were compared between hospital groups using multivariate logistic regression and Poisson regression analysis; and two-year cancer-specific and overall survival were compared using multivariate Cox proportional hazard models. Results Compared with high-volume centres, low-volume centres had worse two-year cancer-specific survival (Adjusted HR = 1.31; 95% CI:1.03–1.68), higher 30-day mortality (Adjusted IRR = 3.81; 95% CI: 1.36–10.62) and fewer patients received “high-quality surgery” (Adjusted OR = 0.55; 95% CI: 0.33–0.90). Differences in 30-day mortality, or “quality-of-treatment” indicators did not entirely explain the observed survival difference between hospital-volume groups. Conclusion In an Australian environment, a “high” hospital-volume was significantly associated with better quality surgery and two-year survival following pancreaticoduodenectomy.

    更新日期:2019-12-17
  • Arterial hyperenhancement of small intrahepatic cholangiocarcinomas correlates with microvessel counts and patient survival
    HPB (IF 3.047) Pub Date : 2019-12-14
    Xiang-Hua Zhang; Lei Huo; Cai-Feng Liu; Feng Xu; Xin-Yuan Lu; Bin Huang; Ning-Yang Jia; Lu Wu; Feng Shen

    Background To compare outcomes of patients with arterially hyperenhancing intrahepatic cholangiocarcinomas (ICC) and arterially hypoenhancing ICCs after partial hepatectomy in a cohort with an analysis of prognostic factors. Methods From June 2009 to October 2011, a prospective cohort of 68 patients with single resectable ICCs (≤5 cm in diameter) underwent gadolinium contrast–enhanced dynamic-phase magnetic resonance imaging and were treated with partial hepatectomy. Patients were divided into those with arterially hyperenhancing ICCs (n = 28) or arterially hypoenhancing ICCs (n = 40). Clinic-radiologic-pathologic results and survival of these patients were compared and statistically analyzed. Results The median overall survival (OS) time was significantly longer in the arterially hyperenhancing ICCs (56.8 vs. 37.0 months) (p = 0.044). At pathologic evaluation, arterially hyperenhancing ICCs showed significantly higher microvessel count (MVC) than arterially hypoenhancing ICCs (106.2 ± 47.5 vs. 46.9 ± 21.6/mm2, p = 0.001). Arterial enhancement of ICCs was found to be an independent prognostic factor for longer survival. Conclusion The presence of arterially hyperenhancing ICCs is related to higher MVC and exhibit a better OS time than arterially hypoenhancing ICCs after partial hepatectomy.

    更新日期:2019-12-17
  • Cholecystitis and risk of pancreatic, liver, and biliary tract cancer in patients undergoing cholecystectomy
    HPB (IF 3.047) Pub Date : 2019-12-13
    Nanna M. Uldall Torp; Simon B. Kristensen; Frank V. Mortensen; Jakob Kirkegård

    Background Cholecystitis before cholecystectomy may increase risk of cancers in the hepato-pancreato-biliary area. Methods A population-based cohort study of all patients undergoing cholecystectomy in Denmark during 1996–2015, using nationwide healthcare registries. We retrieved information on cholecystitis within two years before the date of surgery and information on pancreatic cancer, hepatocellular carcinoma (HCC), and biliary tract cancer. We examined cancer risk using a Cox model to calculate the hazard ratios (HRs). We also computed cumulative incidence functions with 95% CIs, comparing patients with and without cholecystitis before cholecystectomy. Results We included 132,794 patients, of which 73.0% were women. In the first five years of follow-up, we observed an increased risk of biliary tract cancer, but not pancreatic cancer or HCC, in patients with prior cholecystitis. After more than five years of follow-up, patients with prior cholecystitis had an increased risk of pancreatic cancer (adjusted HR: 1.26; 95% CI: 0.98–1.63) and possibly biliary tract cancer (adjusted HR: 1.33; 95% CI: 0.64–2.77). Long-term risk of HCC was decreased in patients with prior cholecystitis. For all cancers, the 20-year absolute risks were less than 1%. Conclusion In patients undergoing cholecystectomy, prior cholecystitis was associated with increased risk of pancreatic and possibly biliary tract cancer.

    更新日期:2019-12-17
  • The effect of performing two pancreatoduodenectomies by a single surgical team in one day on surgeons and patient outcomes
    HPB (IF 3.047) Pub Date : 2019-12-13
    Jin-Ming Wu; Hung-Hsuan Yen; Te-Wei Ho; Chien-Hui Wu; Ting-Chun Kuo; Ching-Yao Yang; Yu-Wen Tien

    Background The centralization of pancreatoduodenectomy (PD) has been shown to improve patient outcomes. The scheduling of two PDs in one day is one option to shorten the waiting time for patients referred to high volume centers. The effect on the surgical team or patient outcomes of such an approach have not previously been explored. This study aimed to investigate the effect of scheduling two PDs in one day on the surgeon's workload and patient outcomes. Methods A retrospective review of patients undergoing PD by a single surgeon between 2007 and 2018 was performed. Patients were allocated into: first PD (FIRSTPD group) or second PD (SECONDPD group) according to the position on the surgical operating list. The intraoperative, postoperative outcomes, and workload (the Surgery Task Load Index; SURG-TLX) were assessed between two groups. Results A total of 967 (91%) and 101 (9%) patients were included in the FIRSTPD and SECONDPD group, respectively. There were no differences in the duration of surgery (coefficient = −9.65; 95% confidence interval: −29.26 to 9.94; P = 0.334), incidence of major complications (odds ratio = 1.08; 95% confidence interval: 0.67–1.73; P = 0.739), or 90-day mortality (odds ratio = 1.03; 95% confidence interval: 0.12–8.53; P = 0.978) for those patients in the SECONDPD group as compared to the FIRSTPD group. The mean scores of two (physical and temporal demand) of the six SURG-TLX subscales of surgical workload were recorded as significantly higher by surgeons following two PD's as compared to one PD. Conclusions Although scheduling a second PD in one day shows no association with adverse patient outcomes, there is an increase in the physical and temporal subscales of surgical workload and consideration should be given to how this could be minimized.

    更新日期:2019-12-17
  • Autophagy in hepatic adaptation to stress
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-16
    Younis Hazari; José Manuel Bravo-San Pedro; Claudio Hetz; Lorenzo Galluzzi; Guido Kroemer

    Autophagy is an evolutionarily ancient process whereby eukaryotic cells eliminate disposable or potentially dangerous cytoplasmic material, to support bioenergetic metabolism and adapt to stress. Accumulating evidence indicates that autophagy operates as a critical quality control mechanism for the maintenance of hepatic homeostasis in both parenchymal (hepatocytes) and non-parenchymal (stellate cells, sinusoidal endothelial cells, Kupffer cells) compartments. In line with this notion, insufficient autophagy has been aetiologically involved in the pathogenesis of multiple liver disorders, including alpha-1-antitrypsin deficiency, Wilson disease, non-alcoholic steatohepatitis, liver fibrosis and hepatocellular carcinoma. Here, we critically discuss the importance of functional autophagy for hepatic physiology, as well as the mechanisms whereby defects in autophagy cause liver disease.

    更新日期:2019-12-17
  • Reassessing the accuracy of PAGE-B-related scores to predict hepatocellular carcinoma development in patients with chronic hepatitis B
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-16
    Terry Cheuk-Fung Yip; Grace Lai-Hung Wong; Vincent Wai-Sun Wong; Yee-Kit Tse; Lilian Yan Liang; Vicki Wing-Ki Hui; Hye Won Lee; Grace Chung-Yan Lui; Henry Lik-Yuen Chan
    更新日期:2019-12-17
  • MUC13 promotes intrahepatic cholangiocarcinoma progression via EGFR/PI3K/AKT pathways
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-16
    Tiemin Pei; Fanzheng Meng; Peng Xiao; Jihua Han; Ruipeng Song; Yaliang Lan; Yan Wang; Junlin Xue; Qingfu Lang; Zhefeng He; Jian Li; Zihao Guo; Guoxing Liu; Boshi Sun; Ming Zhao; Qinghui Meng; Desen Liang; Lianxin Liu
    更新日期:2019-12-17
  • ARRB1 inhibits non-alcoholic steatohepatitis progression by promoting GDF15 maturation
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-16
    Zechuan Zhang; Xiaoliang Xu; Wenfang Tian; Runqiu Jiang; Yijun Lu; Qikai Sun; Rao Fu; Qifeng He; Jincheng Wang; Yang Liu; Hailong Yu; Beicheng Sun
    更新日期:2019-12-17
  • Alginate microencapsulated human hepatocytes for the treatment of acute liver failure in children
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-13
    Anil Dhawan; Nataruks Chaijitraruch; Emer Fitzpatrick; Sanjay Bansal; Celine Filippi; Sharon C. Lehec; Nigel D. Heaton; Pauline Kane; Anita Verma; Robin D. Hughes; Ragai R. Mitry
    更新日期:2019-12-17
  • Does tumor size influence the outcome of laparoscopic distal pancreatectomy?
    HPB (IF 3.047) Pub Date : 2019-12-13
    Airazat M. Kazaryan; Ingeborg Solberg; Davit L. Aghayan; Mushegh A. Sahakyan; Ola Reiertsen; Vasiliy I. Semikov; Alexander M. Shulutko; Bjørn Edwin

    Background Laparoscopic distal pancreatectomy (LDP) is a safe procedure, but its role in resection of large pancreatic lesions has been questioned. Methods Patients who underwent LDP for pancreatic solitary tumors in 1997–2017 were included in this study. The patients were divided into three groups in accordance with tumor size: <3.5 cm (group I); from 3.5 cm to 7.0 cm (group II), and ≥7 cm (group III). Results 218, 146 and 58 patients were identified in the groups I, II and III. Median tumor size in the groups I, II and III was 20, 47 and 81.5 mm (p < 0.001). Nine procedures (2.1%) were converted including 1(0.5%), 5(3.4%) and 3(5.2%) in the groups I, II and III (p = 0.036). Median operative time was longer in the group III compared with the groups I and II – 195 vs 158 and 159 min (p = 0.005). Median blood loss did not differ. Regression analysis revealed correlation between tumor size and operative time (R = 0.103; P = 0.035) and no correlation between tumor size and blood loss (R = 0.075; P = 0.125). Hospital stay was 5 days, similar in all groups.Postoperative morbidity was similar – 38.5, 32 and 34% in the group I, II and III. Conclusion LDP can be safely performed laparoscopically with outcomes similar to those for smaller tumors.

    更新日期:2019-12-13
  • Preoperative opioid use is associated with increased length of stay after pancreaticoduodenectomy
    HPB (IF 3.047) Pub Date : 2019-12-12
    EeeLN. Buckarma; Cornelius A. Thiels; Elizabeth B. Habermann; Amy Glasgow; Travis E. Grotz; Sean P. Cleary; Rory L. Smoot; Michael L. Kendrick; David M. Nagorney; Mark J. Truty

    Background Preoperative opioid use in patients undergoing low complexity operations has been associated with increased complications, but its relationship to procedures of greater complexity is unclear. We aimed to assess this impact on outcomes following pancreaticoduodenectomy (PD). Methods A single institution, retrospective cohort of adults undergoing elective PD for cancer (1/2009-9/2015). Preoperative opioid users were defined as patients documented as taking opioids up to 90 days preoperatively. Discharge prescriptions were converted into Oral Morphine Equivalents (OME) and ten-point pain scores were abstracted. Univariate and multivariable analyses compared outcomes of naïve and preoperative opioid users overall and for laparoscopic vs open surgery. Results Of 661 PD patients, 131 (19.8%) were preoperative opioid users. These patients had greater mean pain scores over the first three days after surgery (3.4 ± 1.6, vs 2.8 ± 1.4, p < 0.001), max pain (7.9 ± 1.9 vs 7.2 ± 2.0, p < 0.001), and discharge pain (2.3 ± 1.9 vs 1.8 ± 1.6, p = 0.01) than naïve patients. Preoperative opioid users received more opioids at discharge (mean 496 ± 764 OME) than naïve (320 ± 489 OME, p = 0.03). Thirty-day refill rates were 12.6% (19.1% preoperative vs 10.9% naïve, p = 0.02). After controlling for tumor type, pancreas texture, and duct size, naïve patients had similar odds of clinically significant post-operative pancreatic fistulas (grade B or C) (OR 1.13, p = 0.68) and delayed gastric emptying (OR 1.05, p = 0.87). After controlling for age and complications, preoperative opioid use was associated with increased odds of LOS ≥9 days (OR 1.59, p = 0.04). Conclusion Following PD, preoperative opioid users had worse pain scores, received more opioids at discharge, refilled prescriptions more frequently, and were more likely to have prolonged LOS. As most opioid utilization research has been focused on low complexity surgery, additional work aimed at optimizing opioid use in complex oncologic operations is warranted.

    更新日期:2019-12-13
  • Clinicopathologic analysis of intraductal papillary neoplasm of bile duct: Korean multicenter cohort study
    HPB (IF 3.047) Pub Date : 2019-12-11
    Jae Ri Kim, Kee-Taek Jang, Jin-Young Jang, Kyungbun Lee, Jung Hoon Kim, Haeryoung Kim, Sun-Whe Kim, Wooil Kwon, Dong Wook Choi, JinSeok Heo, In Woong Han, Shin Hwang, Wan-Joon Kim, Seung-Mo Hong, Dong-Sik Kim, Young-Dong Yu, Joo Young Kim, Yang Won Nah, Kang Min Han

    Background IPNB is very rare disease and most previous studies on IPNB were case series with a small number due to low incidence. The aim of this study is to validate previously known clinicopathologic features of intraductal papillary neoplasm of bile duct (IPNB) based on the first largest multicenter cohort. Methods Among 587 patients previously diagnosed with IPNB and similar diseases from each center in Korea, 387 were included in this study after central pathologic review. We also reviewed all preoperative image data. Results Of 387 patients, 176 (45.5%) had invasive carcinoma and 21 (6.0%) lymph node metastasis. The 5-year overall survival was 80.9% for all patients, 88.8% for IPNB with mucosal dysplasia, and 70.5% for IPNB with invasive carcinoma. According to the “Jang & Kim's modified anatomical classification,” 265 (68.5%) were intrahepatic, 103 (26.6%) extrahepatic, and 16 (4.1%) diffuse type. Multivariate analysis revealed that tumor invasiveness was a unique predictor for survival analysis. (p = 0.047 [hazard ratio = 2.116, 95% confidence interval 1.010–4.433]). Conclusions This is the first Korean multicenter study on IPNB through central pathologic and radiologic review process. Although IPNB showed good long-term prognosis, relatively aggressive features were also found in invasive carcinoma and extrahepatic/diffuse type.

    更新日期:2019-12-11
  • Safe implementation of minimally invasive pancreas resection: a systematic review
    HPB (IF 3.047) Pub Date : 2019-12-10
    Alma L. Moekotte, Arab Rawashdeh, Horacio J. Asbun, Felipe J. Coimbra, Barish H. Edil, Nicolás Jarufe, D. Rohan Jeyarajah, Michael L. Kendrick, Patrick Pessaux, Herbert J. Zeh, Marc G. Besselink, Mohammed Abu Hilal, Melissa E. Hogg

    Background Minimally invasive pancreas resection (MIPR) has been expanding in the past decade. Excellent outcomes have been reported, however, safety concerns exist. The aim of this study was to define prerequisites for performing MIPR with the objective to guide safe implementation of MIPR into clinical practice. Methods This systematic review was conducted as part of the 2019 Miami International Evidence-Based Guidelines on Minimally Invasive Pancreas Resection (IG-MIPR). PubMed, Embase and Cochrane databases were searched for literature concerning the implementation of MIPR between 1946 and November 2018. Quality assessment was according to The Scottish Intercollegiate Guidelines Network (SIGN). Results Overall, 1150 studies were screened, of which 32 studies with 8519 patients were included in this systematic review. Training programs for minimally invasive distal pancreatectomy, laparoscopic pancreatoduodenectomy and robotic pancreatoduodenectomy have been described with acceptable outcomes during the learning curve and improved outcomes after training. Learning curve studies have revealed an association between growing experience and improving perioperative outcomes. In addition, the association between higher center volume and lower mortality and morbidity has been reported by several studies. Conclusion When embarking on MIPR, it is recommended to participate in a dedicated training program, to assure a sufficient volume, especially when implementing minimally invasive pancreatoduodenectomy, (20 procedures recommended annually), and prospectively collect and closely monitor outcomes for continuous quality assessment, this can be achieved through institutional databases and participation in national or international registries.

    更新日期:2019-12-11
  • 更新日期:2019-12-11
  • Mechanosensing of food in the gut
    Nat. Rev. Gastroenterol. Hepatol. (IF 23.570) Pub Date : 2019-12-10
    Jordan Hindson
    更新日期:2019-12-11
Contents have been reproduced by permission of the publishers.
导出
全部期刊列表>>
2020新春特辑
限时免费阅读临床医学内容
ACS材料视界
科学报告最新纳米科学与技术研究
清华大学化学系段昊泓
自然科研论文编辑服务
中国科学院大学楚甲祥
中国科学院微生物研究所潘国辉
中国科学院化学研究所
课题组网站
X-MOL
北京大学分子工程苏南研究院
华东师范大学分子机器及功能材料
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug