ETV is the most potent antiviral agent. It can reduce serum HBV DNA by 6.9 log10 in HBeAg-positive patients and by 5 log10 in HBeAg-negative patients. Although more powerful in its antiviral potency, the 1-year HBeAg seroconversion rate is not superior than other NA (21% at 1 year and 31% after 2 years of ETV treatment).26 A phase III clinical trial involving 648 patients randomized to receive

either ETV 0.5 mg/day or LAM 100 mg/day for 48 weeks was conducted to compare the safety and efficacy of ETV versus LAM in patients with HBeAg-negative chronic hepatitis B.27 Patients treated with ETV showed a significantly higher rate of histological improvement, HBV DNA reduction and undetectable HBV DNA (< 60 IU/mL), compared with patients treated with LAM. Of note is the very low resistance rate (1.2%) observed in the nucleoside-naïve Ruxolitinib molecular weight HBeAg-negative patients treated with ETV for up to 5 years. In a randomized LAM-controlled ETV trial in HBeAg-positive patients, the

HBV DNA levels (< 80 vs > 80 IU/mL) at week 24 were also useful in predicting the HBeAg seroconversion rates (30% vs 17%) and undetectable HBV DNA (96% vs 50%) at week 52 of ETV therapy.28 A large-scale phase III trial involving 921 HBeAg-positive and 466 HBeAg-negative patients showed that virological response to Ldt was superior to that for LAM after 1 and 2 years of treatment.17,18 In HBeAg-negative patients, a RG7204 clinical trial higher proportion treated with Ldt than LAM achieved undetectable HBV DNA levels (88% vs 71% at 1 year and 82% vs 57% at 2 years) with the polymerase chain reaction method (COBAS Amplicor HBV Monitor, Roche Molecular Systems) with a detection limit of 60 IU/mL. Ldt was associated with a lower rate of resistance than LAM was. The resistance rates at 1 and 2 years for Ldt were 2.3% and 11%, respectively. Notably, the resistance rate was quite low at 1 year in HBeAg-negative patients who had undetectable HBV DNA levels at week 24, compared with patients whose HBV DNA levels were ≧ 2000 IU/mL (0% vs 30%) (Table 2).17 Further analysis using a multivariate logistic regression model to evaluate baseline and/or early on-treatment

variables showed that: (i) HBeAg-positive selleck patients with baseline HBV DNA < 9 log10 copies/mL, ALT ≧ 2xULN and non-detectable HBV DNA at week 24 achieved undetectable HBV DNA in 89%, HBeAg seroconversion in 52% and Ldt resistance in 1.8% at 2 years; and (ii) HBeAg-negative patients with baseline HBV DNA < 7 log10 copies/mL and undetectable serum HBV DNA at week 24 achieved undetectable HBV DNA in 91% and Ldt resistance in 2.3% at 2 years.29 More recently, a phase III study was reported that involved 266 HBeAg-positive and 375 HBeAg-negative patients who were randomized in a 2:1 ratio to receive TDF 300 mg (n = 176 in HBeAg-positive and 250 in HBeAg-negative) or ADV 10 mg (n = 90 in HBeAg-positive and 125 in HBeAg-negative) for 48 weeks.

ETV is the most potent antiviral agent. It can reduce serum HBV DNA by 6.9 log10 in HBeAg-positive patients and by 5 log10 in HBeAg-negative patients. Although more powerful in its antiviral potency, the 1-year HBeAg seroconversion rate is not superior than other NA (21% at 1 year and 31% after 2 years of ETV treatment).26 A phase III clinical trial involving 648 patients randomized to receive

either ETV 0.5 mg/day or LAM 100 mg/day for 48 weeks was conducted to compare the safety and efficacy of ETV versus LAM in patients with HBeAg-negative chronic hepatitis B.27 Patients treated with ETV showed a significantly higher rate of histological improvement, HBV DNA reduction and undetectable HBV DNA (< 60 IU/mL), compared with patients treated with LAM. Of note is the very low resistance rate (1.2%) observed in the nucleoside-naïve check details HBeAg-negative patients treated with ETV for up to 5 years. In a randomized LAM-controlled ETV trial in HBeAg-positive patients, the

HBV DNA levels (< 80 vs > 80 IU/mL) at week 24 were also useful in predicting the HBeAg seroconversion rates (30% vs 17%) and undetectable HBV DNA (96% vs 50%) at week 52 of ETV therapy.28 A large-scale phase III trial involving 921 HBeAg-positive and 466 HBeAg-negative patients showed that virological response to Ldt was superior to that for LAM after 1 and 2 years of treatment.17,18 In HBeAg-negative patients, a Temsirolimus supplier higher proportion treated with Ldt than LAM achieved undetectable HBV DNA levels (88% vs 71% at 1 year and 82% vs 57% at 2 years) with the polymerase chain reaction method (COBAS Amplicor HBV Monitor, Roche Molecular Systems) with a detection limit of 60 IU/mL. Ldt was associated with a lower rate of resistance than LAM was. The resistance rates at 1 and 2 years for Ldt were 2.3% and 11%, respectively. Notably, the resistance rate was quite low at 1 year in HBeAg-negative patients who had undetectable HBV DNA levels at week 24, compared with patients whose HBV DNA levels were ≧ 2000 IU/mL (0% vs 30%) (Table 2).17 Further analysis using a multivariate logistic regression model to evaluate baseline and/or early on-treatment

variables showed that: (i) HBeAg-positive see more patients with baseline HBV DNA < 9 log10 copies/mL, ALT ≧ 2xULN and non-detectable HBV DNA at week 24 achieved undetectable HBV DNA in 89%, HBeAg seroconversion in 52% and Ldt resistance in 1.8% at 2 years; and (ii) HBeAg-negative patients with baseline HBV DNA < 7 log10 copies/mL and undetectable serum HBV DNA at week 24 achieved undetectable HBV DNA in 91% and Ldt resistance in 2.3% at 2 years.29 More recently, a phase III study was reported that involved 266 HBeAg-positive and 375 HBeAg-negative patients who were randomized in a 2:1 ratio to receive TDF 300 mg (n = 176 in HBeAg-positive and 250 in HBeAg-negative) or ADV 10 mg (n = 90 in HBeAg-positive and 125 in HBeAg-negative) for 48 weeks.

ETV is the most potent antiviral agent. It can reduce serum HBV DNA by 6.9 log10 in HBeAg-positive patients and by 5 log10 in HBeAg-negative patients. Although more powerful in its antiviral potency, the 1-year HBeAg seroconversion rate is not superior than other NA (21% at 1 year and 31% after 2 years of ETV treatment).26 A phase III clinical trial involving 648 patients randomized to receive

either ETV 0.5 mg/day or LAM 100 mg/day for 48 weeks was conducted to compare the safety and efficacy of ETV versus LAM in patients with HBeAg-negative chronic hepatitis B.27 Patients treated with ETV showed a significantly higher rate of histological improvement, HBV DNA reduction and undetectable HBV DNA (< 60 IU/mL), compared with patients treated with LAM. Of note is the very low resistance rate (1.2%) observed in the nucleoside-naïve CH5424802 manufacturer HBeAg-negative patients treated with ETV for up to 5 years. In a randomized LAM-controlled ETV trial in HBeAg-positive patients, the

HBV DNA levels (< 80 vs > 80 IU/mL) at week 24 were also useful in predicting the HBeAg seroconversion rates (30% vs 17%) and undetectable HBV DNA (96% vs 50%) at week 52 of ETV therapy.28 A large-scale phase III trial involving 921 HBeAg-positive and 466 HBeAg-negative patients showed that virological response to Ldt was superior to that for LAM after 1 and 2 years of treatment.17,18 In HBeAg-negative patients, a selleck screening library higher proportion treated with Ldt than LAM achieved undetectable HBV DNA levels (88% vs 71% at 1 year and 82% vs 57% at 2 years) with the polymerase chain reaction method (COBAS Amplicor HBV Monitor, Roche Molecular Systems) with a detection limit of 60 IU/mL. Ldt was associated with a lower rate of resistance than LAM was. The resistance rates at 1 and 2 years for Ldt were 2.3% and 11%, respectively. Notably, the resistance rate was quite low at 1 year in HBeAg-negative patients who had undetectable HBV DNA levels at week 24, compared with patients whose HBV DNA levels were ≧ 2000 IU/mL (0% vs 30%) (Table 2).17 Further analysis using a multivariate logistic regression model to evaluate baseline and/or early on-treatment

variables showed that: (i) HBeAg-positive check details patients with baseline HBV DNA < 9 log10 copies/mL, ALT ≧ 2xULN and non-detectable HBV DNA at week 24 achieved undetectable HBV DNA in 89%, HBeAg seroconversion in 52% and Ldt resistance in 1.8% at 2 years; and (ii) HBeAg-negative patients with baseline HBV DNA < 7 log10 copies/mL and undetectable serum HBV DNA at week 24 achieved undetectable HBV DNA in 91% and Ldt resistance in 2.3% at 2 years.29 More recently, a phase III study was reported that involved 266 HBeAg-positive and 375 HBeAg-negative patients who were randomized in a 2:1 ratio to receive TDF 300 mg (n = 176 in HBeAg-positive and 250 in HBeAg-negative) or ADV 10 mg (n = 90 in HBeAg-positive and 125 in HBeAg-negative) for 48 weeks.

14,100,101 In an extensive and influential review (see Table 2), it was suggested that neural activation releases vasoactive neurotransmitters from their afferent processes, which in turn provokes inflammatory changes in peripheral target tissues (in this instance, cerebral blood vessels).14 In addition, the data suggested that the release of substance

P (a vasodilator) from sensory fibers is important in mediating changes in vessel permeability. The finding in animals explains the unilateral distribution of migraine pain and could challenge the concept that the pain of vascular headache is due to dilating blood vessels. Finally, it selleck chemicals was suggested that there is a sterile inflammation of cranial blood vessels during migraine X-396 mw attacks. Moskowitz concluded that “the relationship of trigeminovascular fibers to the pathogenesis of vascular head pain sheds light on possible mechanisms of migraine and other central nervous system conditions associated with headache and inflammation.”14 Studies along this line were carried out in the subsequent year and in 1987 a model of intracranial neurogenic inflammation was presented for use in rat.102 Electrical stimulation of the trigeminal ganglion resulted in ipsilateral

increase of tracers in the dura. In contrast, there was no extravasation in the brain.102 The neurogenic inflammation model was then used to demonstrate that ergot alkaloids, ergotamine, and dihydroergotamine, inhibited plasma extravasation and it was suggested “that the therapeutic effects of ergots in vascular headaches may result from peripheral blockade of small fiber (C or A-delta)-dependent neurogenic inflammation within the dura.103 Similar results

were obtained for indomethacin and aspirin104 and sumatriptan.105 It was suggested that the effect was mediated by 5-HT1B/1D receptors located on sensory trigeminal neurons.106,107 Up to now all effective, acute antimigraine drugs have indeed been proven to inhibit neurogenic protein extravasation (NPE).105,107,108 click here However, inhibition of NPE was not predictive for the antimigraine effect of all investigated new drug-groups. Thus, in 5 placebo-controlled clinical studies, drugs (eg, endothelin and NK-1 receptor antagonists) with potent inhibitory effect on dural NPE were not effective for acute migraine treatment.109-113 Because specific NPE inhibitors are without an effect in migraine, it has been difficult to find a pivotal role for dural neurogenic inflammation in migraine. It was shown, however, that valproate, which is effective in migraine prophylaxis, blocked plasma extravasion in the meninges.

14,100,101 In an extensive and influential review (see Table 2), it was suggested that neural activation releases vasoactive neurotransmitters from their afferent processes, which in turn provokes inflammatory changes in peripheral target tissues (in this instance, cerebral blood vessels).14 In addition, the data suggested that the release of substance

P (a vasodilator) from sensory fibers is important in mediating changes in vessel permeability. The finding in animals explains the unilateral distribution of migraine pain and could challenge the concept that the pain of vascular headache is due to dilating blood vessels. Finally, it Panobinostat supplier was suggested that there is a sterile inflammation of cranial blood vessels during migraine BMN 673 research buy attacks. Moskowitz concluded that “the relationship of trigeminovascular fibers to the pathogenesis of vascular head pain sheds light on possible mechanisms of migraine and other central nervous system conditions associated with headache and inflammation.”14 Studies along this line were carried out in the subsequent year and in 1987 a model of intracranial neurogenic inflammation was presented for use in rat.102 Electrical stimulation of the trigeminal ganglion resulted in ipsilateral

increase of tracers in the dura. In contrast, there was no extravasation in the brain.102 The neurogenic inflammation model was then used to demonstrate that ergot alkaloids, ergotamine, and dihydroergotamine, inhibited plasma extravasation and it was suggested “that the therapeutic effects of ergots in vascular headaches may result from peripheral blockade of small fiber (C or A-delta)-dependent neurogenic inflammation within the dura.103 Similar results

were obtained for indomethacin and aspirin104 and sumatriptan.105 It was suggested that the effect was mediated by 5-HT1B/1D receptors located on sensory trigeminal neurons.106,107 Up to now all effective, acute antimigraine drugs have indeed been proven to inhibit neurogenic protein extravasation (NPE).105,107,108 check details However, inhibition of NPE was not predictive for the antimigraine effect of all investigated new drug-groups. Thus, in 5 placebo-controlled clinical studies, drugs (eg, endothelin and NK-1 receptor antagonists) with potent inhibitory effect on dural NPE were not effective for acute migraine treatment.109-113 Because specific NPE inhibitors are without an effect in migraine, it has been difficult to find a pivotal role for dural neurogenic inflammation in migraine. It was shown, however, that valproate, which is effective in migraine prophylaxis, blocked plasma extravasion in the meninges.

Several studies have demonstrated the accuracy of CT hepatic angiography (CTHA) in detection of HCC. Our study aims to evaluate the role of CTHA and liver biopsy in this patient group. Methods: A retrospective study of 78 consecutive patients with a first diagnosis of HCC at our institution between January 2008 and May 2014 was performed. Of these, 48 met the inclusion criteria of not meeting European association for study of liver (EASL) guidelines for HCC (Defined as absence of arterial enhancement and portal venous washout). Baseline demographic data was recorded including tumor characteristics,

serum alpha fetoprotein, details ABT-263 clinical trial of radiologic imaging, treatment regime and tumor response using modified response evaluation criteria in solid tumors (mRECIST). Results: There were 48 patients with HCC that had atypical radiological features not fulfilling EASL criteria at initial presentation. The majority were male: 89 % (43/48) with an average age of 66 years (Range 49–84 years). Ultrasound guided biopsy was employed in 45% of cases (22/48), CT hepatic arteriography (CTHA) in 29% (10/48) and conventional angiography in 6% (3/48). No further investigation was performed in 12.5% (6/48) due to poor functional

status and in 14.6% (7/48) treatment was initiated based on enlarging mass and consensus opinion at HCC multidisciplinary meeting. The average diameter of lesions diagnosed using CTHA click here was smaller compared with biopsy Midostaurin ic50 (29 mm (Range: 13–56 mm) vs 56 mm (Range: 13–190 mm) with p = 0.005). The average time to diagnosis of HCC from initial imaging was not significantly different between biopsy

and CTHA : 7 weeks vs 15 weeks (p = 0.13) Of the patients that underwent biopsy for diagnosis 68% (15/22) were treated with complete or partial tumor response seen in 73% (11/15). Of those that underwent CTHA for diagnosis 100% (10/10) were treated achieving a complete or partial tumor response. There was no statistical significance in tumor response rate between the CTHA group compared with biopsy group. Conclusion: CT hepatic angiography provides an alternative to biopsy in the diagnosis of suspected hepatocellular with atypical imaging without the risk of potential tumor seeding associated with biopsy. Smaller lesions can be diagnosed using CTHA and with no adverse difference in time to diagnosis or treatment outcomes. D MANGIRA,1 A CHUANG,2 J CHEN,3 R WOODMAN,4 A WIGG5 1South Australian Liver Transplant Unit, Flinders Drive Bedford Park, Adelaide, 2Flinders University, Bedford Park, SA, Australia Background and Aims: Harmful alcohol drinking impairs long-term survival post liver transplantation (LT). The aim of this study was to investigate the prevalence of harmful relapse to alcohol following LT for alcoholic liver disease (ALD) and to investigate for variables associated with armful relapse, in an Australian LT population.

Several studies have demonstrated the accuracy of CT hepatic angiography (CTHA) in detection of HCC. Our study aims to evaluate the role of CTHA and liver biopsy in this patient group. Methods: A retrospective study of 78 consecutive patients with a first diagnosis of HCC at our institution between January 2008 and May 2014 was performed. Of these, 48 met the inclusion criteria of not meeting European association for study of liver (EASL) guidelines for HCC (Defined as absence of arterial enhancement and portal venous washout). Baseline demographic data was recorded including tumor characteristics,

serum alpha fetoprotein, details BGB324 price of radiologic imaging, treatment regime and tumor response using modified response evaluation criteria in solid tumors (mRECIST). Results: There were 48 patients with HCC that had atypical radiological features not fulfilling EASL criteria at initial presentation. The majority were male: 89 % (43/48) with an average age of 66 years (Range 49–84 years). Ultrasound guided biopsy was employed in 45% of cases (22/48), CT hepatic arteriography (CTHA) in 29% (10/48) and conventional angiography in 6% (3/48). No further investigation was performed in 12.5% (6/48) due to poor functional

status and in 14.6% (7/48) treatment was initiated based on enlarging mass and consensus opinion at HCC multidisciplinary meeting. The average diameter of lesions diagnosed using CTHA this website was smaller compared with biopsy MK0683 chemical structure (29 mm (Range: 13–56 mm) vs 56 mm (Range: 13–190 mm) with p = 0.005). The average time to diagnosis of HCC from initial imaging was not significantly different between biopsy

and CTHA : 7 weeks vs 15 weeks (p = 0.13) Of the patients that underwent biopsy for diagnosis 68% (15/22) were treated with complete or partial tumor response seen in 73% (11/15). Of those that underwent CTHA for diagnosis 100% (10/10) were treated achieving a complete or partial tumor response. There was no statistical significance in tumor response rate between the CTHA group compared with biopsy group. Conclusion: CT hepatic angiography provides an alternative to biopsy in the diagnosis of suspected hepatocellular with atypical imaging without the risk of potential tumor seeding associated with biopsy. Smaller lesions can be diagnosed using CTHA and with no adverse difference in time to diagnosis or treatment outcomes. D MANGIRA,1 A CHUANG,2 J CHEN,3 R WOODMAN,4 A WIGG5 1South Australian Liver Transplant Unit, Flinders Drive Bedford Park, Adelaide, 2Flinders University, Bedford Park, SA, Australia Background and Aims: Harmful alcohol drinking impairs long-term survival post liver transplantation (LT). The aim of this study was to investigate the prevalence of harmful relapse to alcohol following LT for alcoholic liver disease (ALD) and to investigate for variables associated with armful relapse, in an Australian LT population.

Readmissions to ICU and admissions following liver transplantation were excluded. Patients admitted to ICU with and without cirrhosis between January 1, 2000 and December 31, 2011 were compared. Severity of illness on admission SAHA HDAC supplier was assessed using number of organ failures and the Acute Physiology and Chronic Health Evaluation (APACHE) III scoring system (after removal of the coefficient for cirrhosis). Results Patients with cirrhosis accounted

for 1.4% (13 379/958 853) of ICU admissions. In-hospital mortality in the cirrhotic group was 31% compared to 12% in the non-cirrhotic group (p<0.001). Cirrhotic patients had a higher mortality rate with each increase in number of organ failures. Cirrhotic patients with 1 organ failure had a comparable mortality to non-cirrhotic patients with 3 organ failures (20 vs 21%). In-hospital mortality decreased in both groups over time. The cirrhotic group had a 10% absolute reduction in mortality between the 2000-2003 and 2008-2011 time cohorts compared to a 3.8% reduction in the non-cirrhotic group (p <0.001). After adjusting for baseline illness severity using logistic regression, a similar reduction in the odds ratios for mortality over time was demonstrated for both groups

(Figure 1). Conclusion The mortality of critically ill patients with cirrhosis has decreased over time. Survival in this group is better than previous reports. Mortality in cirrhosis increases with number of organ failures. Disclosures: Stuart K. Roberts FK506 nmr – Board Membership: Jannsen, Roche, Gilead, BMS The following people have nothing to disclose: Avik click here Majumdar, Michael J. Bailey, William W. Kemp, David Pilcher Background: Monocyte (Mo) dysfunction is associated with susceptibility to infection in acute-on-chronic liver failure (ACLF). Possible mechanisms include tolerance to persistent microbial stimulation due to increased circulating levels of bacterial products as a consequence of (i) increased translocation

of gut-derived bacteria in association with intestinal barrier dysfunction and (ii) impaired hepatic clearance of these microbial ligands. We sought to examine monocyte innate responses to micro-bial challenges through diverse Toll-like receptor signalling cascades, and the relationship to circulating levels of bacterial DNA (bactDNA). Methods: Patients with ACLF (n=18), cirrhosis (CLD;n=4) and healthy controls (HC;n=9) were studied. Whole blood (WB) was obtained for bactDNA and PBMCs. In a subset of patients undergoing orthotopic liver transplantation (n=8) WB was sampled concurrently from portal (PV), hepatic veins (HV), and peripheral artery for ‘cross-liver’ bactDNA analysis. DNA extraction was performed using QiAMP DNA extraction kit, followed by real-time PCR with a TaqMan probe targeting a 380bp region of bacterial 16s rDNA for bactDNA relative quantification, expressed in pg/mL of WB.

Readmissions to ICU and admissions following liver transplantation were excluded. Patients admitted to ICU with and without cirrhosis between January 1, 2000 and December 31, 2011 were compared. Severity of illness on admission IWR-1 solubility dmso was assessed using number of organ failures and the Acute Physiology and Chronic Health Evaluation (APACHE) III scoring system (after removal of the coefficient for cirrhosis). Results Patients with cirrhosis accounted

for 1.4% (13 379/958 853) of ICU admissions. In-hospital mortality in the cirrhotic group was 31% compared to 12% in the non-cirrhotic group (p<0.001). Cirrhotic patients had a higher mortality rate with each increase in number of organ failures. Cirrhotic patients with 1 organ failure had a comparable mortality to non-cirrhotic patients with 3 organ failures (20 vs 21%). In-hospital mortality decreased in both groups over time. The cirrhotic group had a 10% absolute reduction in mortality between the 2000-2003 and 2008-2011 time cohorts compared to a 3.8% reduction in the non-cirrhotic group (p <0.001). After adjusting for baseline illness severity using logistic regression, a similar reduction in the odds ratios for mortality over time was demonstrated for both groups

(Figure 1). Conclusion The mortality of critically ill patients with cirrhosis has decreased over time. Survival in this group is better than previous reports. Mortality in cirrhosis increases with number of organ failures. Disclosures: Stuart K. Roberts Midostaurin supplier – Board Membership: Jannsen, Roche, Gilead, BMS The following people have nothing to disclose: Avik find more Majumdar, Michael J. Bailey, William W. Kemp, David Pilcher Background: Monocyte (Mo) dysfunction is associated with susceptibility to infection in acute-on-chronic liver failure (ACLF). Possible mechanisms include tolerance to persistent microbial stimulation due to increased circulating levels of bacterial products as a consequence of (i) increased translocation

of gut-derived bacteria in association with intestinal barrier dysfunction and (ii) impaired hepatic clearance of these microbial ligands. We sought to examine monocyte innate responses to micro-bial challenges through diverse Toll-like receptor signalling cascades, and the relationship to circulating levels of bacterial DNA (bactDNA). Methods: Patients with ACLF (n=18), cirrhosis (CLD;n=4) and healthy controls (HC;n=9) were studied. Whole blood (WB) was obtained for bactDNA and PBMCs. In a subset of patients undergoing orthotopic liver transplantation (n=8) WB was sampled concurrently from portal (PV), hepatic veins (HV), and peripheral artery for ‘cross-liver’ bactDNA analysis. DNA extraction was performed using QiAMP DNA extraction kit, followed by real-time PCR with a TaqMan probe targeting a 380bp region of bacterial 16s rDNA for bactDNA relative quantification, expressed in pg/mL of WB.

[70-72] The accuracy of CT and MRI with MRCP for prediction of the extent of ductal involvement, hepatic arterial invasion, portal vein invasion, and lymph node metastasis is in the range of 84–91%, 83–93%, 86–98%, and 74–84%, respectively.[73, 74] Although PET

combined with CT (PET/CT) has been recommended to evaluate the metastasis of many intra-abdominal malignancies, it is premature KU-60019 to state the routine use of PET/CT in HCCA. The sensitivity rate of detecting non-nodal distant metastases by PET and PET/CT in patients with CCA was in the range of 70–100%, while the sensitivity of regional lymph node metastases was only about 12%.[75, 76] 10. Endoscopic ultrasonography (EUS) with FNA in combination with other modalities may improve the diagnostic accuracy for HCCA. Level of agreement: a—47%, b—35%, 12%, d—6%, e—0% Quality of evidence: II-2 Classification of recommendation: B Although CT and MRI are the standard imaging tools to evaluate the presence and resectability of CCA, they may miss some small lesions.[70, 77, 78] EUS has been selleck chemicals proven to detect those small lesions and may help to predict

the unresectability of CCA.[79] However, its sensitivity is significantly higher in distal CCA than in HCCA.[79] Although it is technically difficult due to the tumor’s anatomical position, EUS-FNA in brush-negative HCCA patients has been practiced in many advanced endoscopy centers.[80-82] Original reports in suspected HCCA patients with an inconclusive tissue diagnosis demonstrated that the overall diagnostic accuracy, sensitivity, specificity, PPV, and negative predictive value for EUS-FNA in diagnosing HCCA were 91%, 89%, 100%, 100%, and 67%, respectively.[80-82] Therefore, EUS may be considered, where available, to confirm HCCA diagnosis and to evaluate the selleck screening library resectability in those with inconclusive results after the standard evaluation. 11. EUS has a limited role in local staging of HCCA but may be useful in detecting nodal disease. Level of agreement: a—42%, b—42%, c—16%, d—0%, e—0% Quality of evidence: II-2 Classification of recommendation: B

Complete staging of HCCA with EUS is challenging because of the limited depth of visualization and T staging may be inadequate. EUS is able to detect locoregional lymph nodes in the hepatic hilum and in the coeliac axis, as well as para-aortic lymph nodes.[83] In a study of 47 patients, EUS correctly identified lymph nodes in all the patients and confirmation of malignancy by FNA precluded liver transplantation in 17%, implying that EUS-FNA for regional lymph node staging should be further considered in all resectable HCCA patients predicted by CT or MRI to avoid unnecessary surgery.[84] Intraductal ultrasonography (IDUS) is useful in the evaluation of CCA from inside out. IDUS was found to be superior to EUS for T staging (78% vs 54%).