Thus, whereas the type I IFN receptor is ubiquitous, the type III

Thus, whereas the type I IFN receptor is ubiquitous, the type III IFN receptor is relatively restricted to epithelial cells, including hepatocytes. Importantly, it is only weakly (if at all) expressed by hemopoietic cells. Despite these differences,

the expression of types I and III IFN is elicited by similar stimuli (e.g. via stimulation of Toll-like receptors [TLR] responsive to viral products). Further, the types I and III IFN receptors share common downstream signaling pathways (Janus kinase—signal transducer and activator of transcription) to induce IFN-stimulated gene expression.60 Type III IFN inhibit HCV replication in vitro,60,61 as well as in vivo. This is thought to occur via the upregulation of key IFN-stimulated genes (ISG), including ISG15, MX1 (myxovirus resistance-1), and OAS (2′,5′-oligoadenylate synthetase-like Histone Methyltransferase inhibitor gene), which interrupt HCV replication through processes that include the suppression of viral replication and protein synthesis.60–63

Type III IFN have also been shown to augment natural killer (NK) cell immunity and antigen-specific CD8+ T-cell cytotoxicity.64,65 Recently, increased NK cell inhibitory receptor expression has been associated with the poor-response IL28B genotype and treatment response.66 The role of IFN-λ, and specifically, IL28B, in HCV pathogenesis remains unclear. Furthermore, the biological PD0325901 consequence(s) of IL28B polymorphism is/are not known. There are two key questions: what is the causal variant, and what does it do? This is a fertile area for research, and the field is in its infancy. The functional variant responsible for the IL28B haplotype

association remains medchemexpress unclear. It is unlikely that any of the association tag SNPs are causal, and none are a good functional candidate. Potentially-functional polymorphisms have been identified that are in linkage with the discovery SNP. By sequencing the IL28B region in 96 patients, Ge et al. identified two candidate causal variants.3 One variant was a G > C transition, 37 base pairs upstream from the translation initiation codon (rs28416813), and the other was a non-synonymous SNP encoding an amino-acid substitution in exon 2 (rs8103142, Lys70Arg), which might potentially affect receptor binding or protein stability. These SNPs have also been identified on a common haplotype with rs12979860 in a second study by Di Iulio and colleagues.47 In both studies, the linkage disequilibrium between these SNPs and the discovery tag SNP was so strong that it was not possible for association testing to statistically differentiate which was more strongly associated with SVR. For this reason, it is likely that functional studies will be necessary. A number of studies have considered the relationship between the IL28B genotype and IFN-λ-3 mRNA expression.

1) The incidence rate was 36 of 100 person-years but was lower

1). The incidence rate was 3.6 of 100 person-years but was lower among the more educated, H 89 chemical structure the seroreversion rate was 1.0 of 100 person-years. In their second article focussing on children [5], they investigated adolescents born in 1990. The prevalence of H. pylori was 66.2%, lower in subjects with more educated parents and higher in those having more than one sibling and for smokers. The incidence was 4.1 of 100 person-years. The authors concluded that gastric cancer will remain an important public health problem in this generation of Portuguese. Ueda et al. [6] studied the prevalence of H. pylori infection in Japan

comparing location and birth cohort; 14,716 subjects aged 20 years or more who underwent a health checkup were studied. The overall prevalence of H. pylori infection was 37.6% in women and 43.2% in men. Figure 2 shows the rapid fall in prevalence according to birth cohort. When comparing the prevalence of infection and age-adjusted mortality rates of gastric cancer, they found that H. pylori prevalence generally correlated with gastric cancer mortality rates. Yan et al. [7] reviewed the literature reporting recrudescence and reinfection in patients who had undergone earlier successful treatment. They compared recurrence rates with the

Human Development Index (HDI), a measurement based on life expectancy, education and the prosperity of the community under consideration. In the 92 papers that fulfilled the inclusion criteria, check details 16,827 patients MCE公司 were followed for between 6 months and 10 years. Recurrence varied considerably and was inversely proportional to the HDI (Fig. 3) The study was

unable to distinguish, however, between recrudescence and reinfection. Ferro et al. [8] researched worldwide trends in gastric cancer mortality between 1980 and 2011 using WHO data and made predictions concerning incidence to 2015. Recent annual percent changes have been around −3% for the European Union (EU) and major European countries, as well as in Japan and Korea, and around −2% in North America and major Latin American countries. In the United States of America, European Union and other major countries worldwide, the estimated annual percent changes were lower than in previous years. The predictions for 2015 suggest a levelling off of rates in the USA and a few other countries. The relative contribution of cardia to noncardia gastric cancers is generally higher in countries with lower gastric cancer incidence and mortality rates. This is a valuable article with detailed data. It concludes that despite the global downward trends in gastric cancer mortality, further declines in gastric cancer mortality rates may require more intensive efforts for the prevention and control of H.

1) The incidence rate was 36 of 100 person-years but was lower

1). The incidence rate was 3.6 of 100 person-years but was lower among the more educated, selleckchem the seroreversion rate was 1.0 of 100 person-years. In their second article focussing on children [5], they investigated adolescents born in 1990. The prevalence of H. pylori was 66.2%, lower in subjects with more educated parents and higher in those having more than one sibling and for smokers. The incidence was 4.1 of 100 person-years. The authors concluded that gastric cancer will remain an important public health problem in this generation of Portuguese. Ueda et al. [6] studied the prevalence of H. pylori infection in Japan

comparing location and birth cohort; 14,716 subjects aged 20 years or more who underwent a health checkup were studied. The overall prevalence of H. pylori infection was 37.6% in women and 43.2% in men. Figure 2 shows the rapid fall in prevalence according to birth cohort. When comparing the prevalence of infection and age-adjusted mortality rates of gastric cancer, they found that H. pylori prevalence generally correlated with gastric cancer mortality rates. Yan et al. [7] reviewed the literature reporting recrudescence and reinfection in patients who had undergone earlier successful treatment. They compared recurrence rates with the

Human Development Index (HDI), a measurement based on life expectancy, education and the prosperity of the community under consideration. In the 92 papers that fulfilled the inclusion criteria, Cabozantinib cell line 16,827 patients 上海皓元 were followed for between 6 months and 10 years. Recurrence varied considerably and was inversely proportional to the HDI (Fig. 3) The study was

unable to distinguish, however, between recrudescence and reinfection. Ferro et al. [8] researched worldwide trends in gastric cancer mortality between 1980 and 2011 using WHO data and made predictions concerning incidence to 2015. Recent annual percent changes have been around −3% for the European Union (EU) and major European countries, as well as in Japan and Korea, and around −2% in North America and major Latin American countries. In the United States of America, European Union and other major countries worldwide, the estimated annual percent changes were lower than in previous years. The predictions for 2015 suggest a levelling off of rates in the USA and a few other countries. The relative contribution of cardia to noncardia gastric cancers is generally higher in countries with lower gastric cancer incidence and mortality rates. This is a valuable article with detailed data. It concludes that despite the global downward trends in gastric cancer mortality, further declines in gastric cancer mortality rates may require more intensive efforts for the prevention and control of H.

Catheter-based high frequency intraluminal ultrasound probes rang

Catheter-based high frequency intraluminal ultrasound probes range from 1–3 mm in diameter, and the transducer ROCK inhibitor can provide either linear or cross-sectional images.32–35 The ultrasound is able to dynamically assess esophageal longitudinal muscle contractions, as indicated by an increase in cross-sectional muscle layer thickness.10,35,36 When used in combination with manometry, information on the contractions of both longitudinal and circular muscles can be obtained.37,38 Using high frequency intraluminal ultrasound (HFIUS) in

patients with spastic esophageal disorders including achalasia, diffuse esophageal spasm, and nutcracker esophagus, the baseline esophageal muscle thickness was found to be greater than in healthy volunteers.37 Further, this increase in muscle thickness appeared to correlate with the severity of the underlying disease, i.e. greatest in achalasia and least in nutcracker esophagus.36 In achalasia, swallow-induced longitudinal muscle contraction was found to be a significant contributor to esophageal emptying by increasing pan-esophageal C646 purchase pressure to overcome the poorly relaxing

lower esophageal sphincter.39 HFIUS appears to be a promising technique in measuring esophageal longitudinal muscle contraction, with its role lying predominantly in physiological studies, especially when used in combination with other techniques such as manometry. Operator dependency, and the lack of an automated analysis means its widespread use will be limited. The first step in the evaluation of dysphagia is to take a careful history,

with the aim of distinguishing whether the cause is oropharyngeal or esophageal, and whether it is mechanical or dysmotility. If the cause is deemed likely oropharyngeal, then referral to a neurologist or ENT specialist, with or without speech pathologist involvement, will be appropriate. Unless an esophageal cause can be confidently excluded based on history, then further esophageal assessment must take place, with at least a gastroscopy MCE公司 (provided the patient is fit for such procedure), to exclude important causes such as cancer and stricture, as well as eosinophilic esophagitis; the only exception is when the dysphagia occurs in the context of suspected uncomplicated reflux disease, where an initial trial of acid suppressing therapy would be recommended. The threshold to take biopsies from an apparently normal esophagus should be low. If the patient still suffers from troublesome symptoms despite a normal gastroscopy (and biopsy), dedicated motility testing is warranted. The choice of test depends largely upon the perceived likely diagnosis, patient characteristics and local expertise.

… Speak of me in the

easy way which you always used Put

… Speak of me in the

easy way which you always used. Put no difference into your tone. Wear no forced air of solemnity or sorrow. Laugh as we always laughed at the little jokes that we enjoyed together. Play, smile, think of me, pray for me. Let my name be ever the household word that it always was. Let it be spoken without an effort, without the ghost of a shadow upon it. Life means all that it ever meant. It is the same as it ever was. There is absolute and unbroken continuity. What is this death but a negligible accident? Why should I be out of mind because I am out of sight? I am but waiting for you, for an interval, somewhere very near, just round the Etoposide order corner. All is well. Nothing is hurt; nothing is lost. One brief moment and all will be as it was before. How we shall laugh at the trouble of parting when we meet again! A close friend said of Caroline that she was a unique Southern lady, with the best academic qualities, who had the miraculous ability to communicate with anyone in minutes, and have such an impact as to last a lifetime. “
“Treatment

outcomes are suboptimal for patients undergoing endoscopic treatment of walled-off pancreatic necrosis (WOPN). The objective of this study is to identify factors that impact treatment outcomes in this patient subset. This is a retrospective study of patients with WOPN treated endoscopically over 10 years. Patients underwent placement of stents and nasocystic catheters within the necrotic cavity. In select patients, the multiple transluminal gateway technique (MTGT) was adopted to create several openings in the stomach or duodenum to facilitate drainage http://www.selleckchem.com/products/idasanutlin-rg-7388.html of necrosis. In patients with disconnected pancreatic duct syndrome (DPDS), the transmural stents 上海皓元 were left in place indefinitely to decrease pancreatic fluid collection (PFC) recurrence. Endoscopic treatment was successful in 53 of 76 (69.7%) patients. Treatment success was higher in patients undergoing MTGT than in those in whom conventional

drainage was used (94.4% vs 62.1%, P = 0.009). On multivariate logistic regression analysis, only MTGT (OR 15.8, 95% CI 1.77–140.8; P = 0.01) and fewer endoscopic sessions being needed (OR 4.0, 95% CI 1.16–14.0; P = 0.03) predicted treatment success. PFC recurrence was significantly lower in patients with indwelling transmural stents than in patients in whom the stents were removed (0 vs 20.8%; P = 0.02). Creating multiple gateways for drainage of necrotic debris improves treatment success, and not removing the transmural stents decreases PFC recurrence in patients undergoing endoscopic drainage of WOPN. “
“HCC, hepatocellular carcinoma; ILCA, International Liver Cancer Association. A s I write my final Associate Editor Commentary, I would first like to acknowledge the distinct privilege and honor it has been to be a member of the Associate Editor Board for the “Lindor” years of HEPATOLOGY.

) are expected

) are expected CHIR-99021 price to disclose all relevant financial relationships during the past 12 months. When an unlabeled use of a commercial product or an investigational use not yet approved for any purpose is discussed during an educational

activity, the speaker shall disclose to the audience that the product is not labeled for the use under discussion or that the product is still investigational. All disclosure information is provided to the activity participant prior to the start of the educational activity. In addition, disclosure slides will be the first side in each oral presentation viewed by participants. AASLD will identify and resolve all conflicts of interest prior to program implementation. Invited speakers, course directors, moderators, program planners, abstract reviewers and staff have provided the following disclosures: Afdhal, Nezam H., MD (Abstract Reviewer) Consulting: Abbott, Pharmasett, Gilead, Springbank, GlaxoSmithKline, Idenix, Merck, Vertex Grants/Research Support: Merck, Vertex, Idenix,

GlaxoSmithKline, Springbank, Gilead, Pharmasett, Abbott Adhami, Talal, Gemcitabine cell line MD (Program Evaluation Committee) Speaking and Teaching: Gilead Ahmad, Jawad, MD (Abstract Reviewer) Nothing to disclose Alberti, Alfredo, MD (Abstract Reviewer) Grants/Research Support: Merck, Gilead Advisory Board: Merck, Roche, Gilead Speaking and Teaching: Novartis, Bristol-Myers Squibb Al-Osaimi, Abdullah, 上海皓元 MD (Abstract Reviewer) Nothing to disclose Alvarez, Fernando, MD (Abstract Reviewer) Nothing to disclose Angeli, Paolo, MD, PhD (Abstract Reviewer) Advisory Board: Sequana Medical Aranda-Michel, Jaime, MD (Abstract Reviewer)

Nothing to disclose Arteel, Gavin E., PhD (Basic Research Committee, Abstract Reviewer) Grants/Research Support: NIH Asrani, Sumeet, MD (Abstract Reviewer) Nothing to disclose Aytaman, Ayse, MD (Abstract Reviewer) Nothing to disclose Bajaj, Jasmohan S., MD (Clinical Research Committee, Abstract Reviewer) Grants/Research Support: Salix, Otsuka, Grifols Advisory Board: American College of Gastroenterology, Grifols, Salix, Merz, Otsuka, Ocera Bambha, Kiran, MD (Abstract Reviewer) Nothing to disclose Bass, Nathan M., MD, PhD (Abstract Reviewer) Nothing to disclose Beaven, Simon, MD (Abstract Reviewer) Nothing to disclose Beavers, Kimberly, MD (Program Evaluation Committee) Nothing to disclose Befeler, Alex, MD (Program Evaluation Committee, Abstract Reviewer) Advisory Board: Gilead Stock: Amgen, Gilead Bergasa, Nora V., MD (Abstract Reviewer) Nothing to disclose Beier, Juliane Ingeborg, PhD (Education Committee) Nothing to disclose Berzigotti, Annalisa, MD, PhD (Education Committee) Nothing to disclose Bhamba, Kiran, MD (Clinical Research Committee) Nothing to disclose Biggins, Scott W., MD (Abstract Reviewer) Nothing to disclose Boelsterli, Urs A.

) are expected

) are expected beta-catenin pathway to disclose all relevant financial relationships during the past 12 months. When an unlabeled use of a commercial product or an investigational use not yet approved for any purpose is discussed during an educational

activity, the speaker shall disclose to the audience that the product is not labeled for the use under discussion or that the product is still investigational. All disclosure information is provided to the activity participant prior to the start of the educational activity. In addition, disclosure slides will be the first side in each oral presentation viewed by participants. AASLD will identify and resolve all conflicts of interest prior to program implementation. Invited speakers, course directors, moderators, program planners, abstract reviewers and staff have provided the following disclosures: Afdhal, Nezam H., MD (Abstract Reviewer) Consulting: Abbott, Pharmasett, Gilead, Springbank, GlaxoSmithKline, Idenix, Merck, Vertex Grants/Research Support: Merck, Vertex, Idenix,

GlaxoSmithKline, Springbank, Gilead, Pharmasett, Abbott Adhami, Talal, learn more MD (Program Evaluation Committee) Speaking and Teaching: Gilead Ahmad, Jawad, MD (Abstract Reviewer) Nothing to disclose Alberti, Alfredo, MD (Abstract Reviewer) Grants/Research Support: Merck, Gilead Advisory Board: Merck, Roche, Gilead Speaking and Teaching: Novartis, Bristol-Myers Squibb Al-Osaimi, Abdullah, 上海皓元医药股份有限公司 MD (Abstract Reviewer) Nothing to disclose Alvarez, Fernando, MD (Abstract Reviewer) Nothing to disclose Angeli, Paolo, MD, PhD (Abstract Reviewer) Advisory Board: Sequana Medical Aranda-Michel, Jaime, MD (Abstract Reviewer)

Nothing to disclose Arteel, Gavin E., PhD (Basic Research Committee, Abstract Reviewer) Grants/Research Support: NIH Asrani, Sumeet, MD (Abstract Reviewer) Nothing to disclose Aytaman, Ayse, MD (Abstract Reviewer) Nothing to disclose Bajaj, Jasmohan S., MD (Clinical Research Committee, Abstract Reviewer) Grants/Research Support: Salix, Otsuka, Grifols Advisory Board: American College of Gastroenterology, Grifols, Salix, Merz, Otsuka, Ocera Bambha, Kiran, MD (Abstract Reviewer) Nothing to disclose Bass, Nathan M., MD, PhD (Abstract Reviewer) Nothing to disclose Beaven, Simon, MD (Abstract Reviewer) Nothing to disclose Beavers, Kimberly, MD (Program Evaluation Committee) Nothing to disclose Befeler, Alex, MD (Program Evaluation Committee, Abstract Reviewer) Advisory Board: Gilead Stock: Amgen, Gilead Bergasa, Nora V., MD (Abstract Reviewer) Nothing to disclose Beier, Juliane Ingeborg, PhD (Education Committee) Nothing to disclose Berzigotti, Annalisa, MD, PhD (Education Committee) Nothing to disclose Bhamba, Kiran, MD (Clinical Research Committee) Nothing to disclose Biggins, Scott W., MD (Abstract Reviewer) Nothing to disclose Boelsterli, Urs A.

and Lillian Stratton Basic Research Single Topic Conference “Stem

and Lillian Stratton Basic Research Single Topic Conference “Stem Cells in Liver Diseases and Cancer: Discovery and Promise” brought together a diverse group of investigators to define the status of research on stem cells

and cancer stem cells in the liver and identify problems and solutions on the path to clinical translation. This report summarizes the outcomes of the conference and provides an update on recent research advances. Progress in liver stem cell research includes isolation of primary liver progenitor cells (LPCs), directed http://www.selleckchem.com/products/jq1.html hepatocyte differentiation of primary LPCs and pluripotent stem cells, findings of transdifferentiation, disease-specific considerations for establishing a therapeutically effective cell mass, and disease modeling in cell culture. Tumor-initiating stem-like cells (TISCs) that emerge during chronic liver injury share the expression of signaling pathways, including those organized around transforming growth factor beta and β-catenin, and surface markers with normal LPCs. Recent investigations of the role of TISCs in hepatocellular carcinoma have provided insight into the transcriptional and post-transcriptional selleck chemicals llc regulation of hepatocarcinogenesis. Targeted chemotherapies for TISC are in development as a means to overcome cellular resistance and mechanisms driving disease progression in

liver cancer. (HEPATOLOGY 2012;55:298–306) AFP, alpha-fetoprotein; ATP, alkaline triphosphate; CD, cluster of differentiation; CYP, cytochrome P450; DDC, 3,5-diethoxycarbonyl-1,4-dihydrocollidine; ESCs, embryonic stem cells; EpCAM, epithelial 上海皓元医药股份有限公司 cell adhesion molecule; EZH2, enhancer of zeste homolog 2; FAH, fumarylacetoacetate hydrolase; HCV, hepatitis C virus; HCC, hepatocellular carcinoma; HDAC, histone deacetylase; iPSCs, induced pluripotent stem cells; LPCs, liver progenitor cells; MAPK, mitogen-activated protein kinase; miRNA,

microRNA; PARP, poly(ADP-ribose) polymerase; TGF-β, transforming growth factor beta; TISCs, tumor-initiating stem-like cells; TLR-4, Toll-like receptor-4; YAP1, yes-associated protein 1. Liver stem cell research promises to improve the outcomes of patients with liver diseases. Advances in liver stem cell research may lead to new cell therapies and may facilitate the development of new drugs by providing faithful liver disease models. John Gearhart, who codirected the conference, introduced unanswered questions and technical hurdles that remain to be overcome in stem cell research. In many tissues, stem cells have yet to be specifically identified and isolated. As a consequence, the current understanding of the mechanisms that facilitate proliferation and differentiation of tissue-specific stem cells is limited, which has also hampered the generation of therapeutically effective surrogate cells from alternative cell sources, such as pluripotent stem cells.

However, the utility of high resolution impedance manometry (HRiM

However, the utility of high resolution impedance manometry (HRiM) in the Chinese population has not been evaluated. The study aimed to investigate the normal reference of esophageal motility in healthy volunteers (as defined by Chicago classification) using HRiM. Methods: Healthy, fasted volunteers underwent HRiMin a supine position with ten liquid swallows and ten viscous swallows. Integrated relaxation pressure (IRP), distal contractile integral (DCI), contractile Osimertinib research buy front velocity (CFV),

and distal latency (DL) were calculated. The interquartile ranges and the 95th percentile range for each metric were obtained. Results: Forty-two healthy volunteers were enrolled with 411 total liquid swallows and 398 viscous swallows available for analysis. selleck compound We established 20.5 mmHg of IRP and 3195 mmHg●s●cm of DCI as the 95th percentile for liquid swallows. Using the reference range defined by Chicago

classification, we observed 6.3% (26/411) weak peristalsis and 0.7% (3/411) failed peristalsis for liquid swallows; twelve (28.6%, 12/42) and two (4.7%, 2/42) individuals were diagnosed as esophagogastric junction (EGJ) outflow obstruction and weak peristalsis for liquid swallows. Compared with liquid swallows, viscous swallows had a decreased IRP (P = 0.000) and CFV (P = 0.000), and an unchanged DCI (P = 0.211). Conclusion: We established HRiM normative data of both liquid and viscous swallows from healthy Chinese volunteers. The IRP and CFV were significantly decreased in the viscous swallows compared with those of the liquid swallows. Key Word(s): 1. HRM; Manometric Data Liquid swallow Viscous swallow P value Median (IQR) 95th percenlile Median (IQR) 95th percentile Bolus clearance (%) 91 (90, 100) 100 80 (73, 90) 100 0.000 Bolus transit time (s) 6.9 (6.5, 7.6) 11.0 7.4 (6.9, 8.8) 10.2 0.000 IRP (mmHg) EFT 14.1 (12.3, 16.1) 20.5 12.8 (11.4, 14.3) 23.2 0.000 DCI (mmHg●s●cm)

1527 (1188, 2104) 3195 1476 (1036, 2040) 3198 0.211 CFV (cm/s) 4.6 (4.0, 5.3) 6.9 4.3 (3.5, 4.6) 6.2 0.000 DL(s) 5.2 (4.9, 6.0) 7.1 5.4 (5.0, 6.3) 7.5 0.000 Presenting Author: YAN CHEN Additional Authors: JUANJUAN XU, SHI LIU, XIAOHUA HOU Corresponding Author: SHI LIU Affiliations: Huazhong University MCE of Science and Technology Objective: Loss of interstitial cells of Cajal (ICC) contributes to gastrointestinal motility disorders in diabetic patients. EA at ST36 is an effective therapy to relieve gastrointestinal symptoms. However, little is known about the effects of EA at ST36 on gastric motility and whether ICC was involved in diabetic rats. Methods: Rats were randomized into normal control, DM, DM+SEA, DM+LEA and DM+HEA group. Body weight and blood glucose screened during the experiment. Gastric emptying was studied by the phenol red method.

35,36 The AASLD Guideline recommends that only

single les

35,36 The AASLD Guideline recommends that only

single lesions be offered surgical resection (Fig. 1). Recommendation 11 of the AASLD Guideline states, “Patients who have a single lesion can be offered surgical resection if they are non-cirrhotic or have cirrhosis but still have preserved liver function, normal bilirubin and hepatic vein pressure < 10 mm Hg. The APASL Guideline recommends that HCC that is confined to the liver with a patent main portal vein, and which is technically resectable be treated with liver resection, with the caveat that radiofrequency ablation (RFA) is an acceptable alternative check details for lesions < 3 m (Fig. 2). The APASL recommendation states, “Liver resection is a first-line curative treatment of solitary or multi-focal HCC confined to the liver, anatomically resectable, and with satisfactory liver function. In philosophy and practice it is clear that the recommendations of these two guidelines are

very different. To the non-surgical clinician looking to these guidelines to determine how the patient may be best served, it is useful to examine the underlying assumptions of these LY2157299 purchase two sets of guidelines, which appear to represent the two opposite ends of the philosophical spectrum. Some of the assumptions are mired in history, while the rest are a reflection of the sometimes different clinical experiences of the east and west with regards to HCC, or the lack of robust evidence in “watershed” areas (such as CPT B cases with good ICG clearance). The first edition of the AASLD Guideline MCE published in 200528 was based on an earlier monothematic conference of the European Association for the Study of the Liver (EASL),37 that was subsequently articulated as the updated guideline of the Barcelona Clinic for Liver Cancer (BCLC).4,26,38 Indeed many of the same people were involved. The 2005 AASLD Guideline for liver resection in HCC was identical to that of the BCLC, and these remain unchanged in the 2010 revision of the AASLD Guideline.25 The AASLD recommendation

was for resection to be restricted to single tumor situated at anatomically favorable locations as defined by pre-operative imaging. Size itself was not described as a contraindication. Multi-focal tumors (up to three nodules each less than 3 cm) were to be treated by liver transplantation and trans-arterial chemoembolization was recommended for tumors beyond this (see Fig. 1). The premise of these conservative recommendations was articulated in an earlier publication39 and repeated later,4,26,38 namely that the authors felt that a 50% survival expectancy at 5 years should be the minimal cut-off value to propose surgical resection. In addition it was also suggested that operative mortality should be between 1–3%, and transfusion rate be around 10%. Comparative survival with non-surgical treatment was not described as a consideration.