***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: This document , on the diagnosis and treatment of patients with hepatocellular carcinoma ( HCC ) , was commissioned by the British Society of Gastroenterology as part of a wider initiative to develop guidelines for clinicians in several areas of clinical practice . Cancer care has been the subject of increased scrutiny , with the development of care guidelines forming a major part of the strategy to reduce cancer related mortality in the UK . There is a strong suggestion that HCC is a disease which will be seen more frequently over the next few years , mainly as a result of the hepatitis C virus ( HCV ) epidemic . Previously , HCC has been a relatively rare tumour in the UK and much of the data pertaining to its diagnosis and therapy are derived from studies outside of the UK . Because of the lack of screening programmes and the fact that a significant proportion of HCC presents as symptomatic disease in individuals not known to have liver disease , most non-surgical therapies have been used in patients with advanced disease . There are a significant number of variables known to influence prognosis , with stage of underlying liver disease and tumour size at presentation being the most important . Controlling for these variables is difficult and these factors have contributed to a dearth of r and omised controlled trials of treatment for this tumour . There is however a substantial amount of evidence available which can form the basis of a framework for diagnosis and management . Guidelines are not rigid protocol s and they should not be construed as interfering with local clinical judgement . Hence they do not represent a directive of proscribed routes but a basis on which clinicians can consider the options available more clearly . These guidelines cover two areas of clinical practice relating to HCC : firstly , its diagnosis , including surveillance of high risk individuals ; and AIMS We assessed the role of contrast-enhanced ultrasound ( CEUS ) in the differential diagnosis between benign and malignant portal vein thrombosis ( PVT ) in patients who had liver tumors . METHODS Seventeen consecutive patients who had cirrhosis , liver tumors , and PVT were prospect ively studied with CEUS . CEUS was performed at low mechanical index after intravenous administration of a second-generation contrast agent ( SonoVue , Bracco , Milan , Italy ) . Presence or absence of thrombus enhancement on CEUS were considered diagnostic for malignant or benign PVT . Five patients also underwent percutaneous portal vein fine-needle biopsy under US guidance  . All patients were followed-up . Shrinkage of the thrombus and /or recanalization of the vessels on CDUS during follow-up were considered definitive evidence of the benign nature of the thrombosis , whereas the enlargement of the thrombus , disruption of the vessel wall , and parenchymal infiltration over follow-up were considered consistent with malignancy . RESULTS Follow-up showed signs of malignant thrombosis in 14 of 17 patients . CEUS showed early arterial enhancement of the PVT in 14 patients of 14 malignant PVT , 1 patient of 3 benign PVT and the absence of thrombus enhancement in 2 patients of 3 benign PVT . FNB confirmed the results for malignant PVT in four of five patients , for benign granulomatous inflammation PVT in one of five patients in which CEUS showed early arterial enhancement of the PVT . The sensitivity , specificity and accuracy is 100 % , 66.7 % and 93.3 % at diagnosis of malignant PVT using CEUS . In one patient with intrahepatic bile duct stone , CEUS were positive for malignant PVT , whereas FNB was negative ( benign granulomatous inflammation PVT ) ; follow-up examination confirmed benign PVT . CONCLUSION CEUS seems to be the pretty sensitive and specific test for diagnosing malignant portal vein thrombosis in patients with cirrhosis and tumors Background We assessed the role of contrast-enhanced ultrasound ( CEUS ) in the differential diagnosis between benign and malignant portal vein thrombosis in patients who had cirrhosis with hepatocellular carcinoma ( HCC ) . Methods Fifty-four consecutive patients who had cirrhosis , biopsy-proved HCC , and thrombosis of the main portal vein and /or left/right portal vein on US were prospect ively studied with color Doppler US ( CDUS ) and CEUS . CEUS was performed at low mechanical index after intravenous administration of a second-generation contrast agent ( SonoVue , Bracco , Milan , Italy ) . Presence or absence of CDUS signals or thrombus enhancement on CEUS were considered diagnostic for malignant or benign portal vein thrombosis . Twenty-eight patients also underwent percutaneous portal vein fine-needle biopsy ( FNB )  under US guidance . All patients were followed-up bimonthly by CDUS .  Shrinkage of the thrombus and /or recanalization of the vessels on CDUS during follow-up were considered definitive evidence of the benign nature of the thrombosis , whereas enlargement of the thrombus , disruption of the vessel wall , and parenchymal infiltration over follow-up were considered consistent with malignancy . CDUS  , CEUS , and FNB results were compared with those at follow-up . Results Follow-up ( 4 to 21 months ) showed signs of malignant thrombosis in 34 of 54 patients . FNB produced a true-positive result for malignancy in 19 of 25 patients , a false-negative result in six of 25 patients , and a true-negative result in three of three patients . CDUS was positive in seven of 54 patients . CEUS showed enhancement of the thrombus in 30 of 54 patients . No false-positive result was observed at CDUS , CEUS , and FNB . Sensitivities of CDUS , CEUS , and FNB in detecting malignant thrombi were 20 % , 88 % , and 76 % respectively . Three patients showed negative CDUS and CEUS and positive FNB results ; follow-up confirmed malignant thrombosis in these patients . One patient showed negative CDUS , CEUS , and FNB findings . Howewer , follow-up of the thrombus showed US signs of malignancy . Another FNB confirmed HCC infiltration of the portal vein . Conclusion CEUS seems to be the most sensitive and specific test for diagnosing malignant portal vein thrombosis in patients with cirrhosis OBJECTIVES To select an appropriate treatment regimen , it is essential to accurately characterize the nature of a thrombus . This study prospect ively assessed the ability of contrast-enhanced sonography to differentiate between benign and malignant portal vein thrombosis in a population of high-risk patients . METHODS Fifty-five patients ( 43 men and 12 women ; mean age , 66 years ; range , 55 - 83 years ) with thrombi of the portal venous system were examined by power Doppler sonography and contrast-enhanced sonography with the intravenous contrast agent SH U 508A ( Levovist ; Schering AG , Berlin , Germany ) . Of the thrombi , 40 were characterized as malignant and 15 as benign . Pulsatile flow in the thrombus on power Doppler sonography and positive enhancement of the thrombus on contrast-enhanced sonography were judged as indications of a malignant thrombus . The sensitivity and specificity of both methods in differentiating the nature of the thrombus were evaluated . RESULTS The detection of pulsatile flow in a portal vein thrombus as the criterion for diagnosing malignant portal vein thrombus yielded overall sensitivity of 82.5 % and specificity of 100 % , whereas positive enhancement of the portal vein thrombus itself as a criterion for diagnosing malignancy yielded overall sensitivity and specificity of 100 % for each . CONCLUSIONS Contrast-enhanced sonography can be helpful in discriminating between benign and malignant portal vein thrombi OBJECTIVE The objective of our study was to determine if the detection by Doppler sonography of blood flow in portal vein thrombi occurring in patients with cirrhosis could be used to distinguish benign from malignant portal vein thrombi . SUBJECTS AND METHODS Color and duplex Doppler sonographic examinations were performed in 47 patients with proven cirrhosis and portal vein thrombi . The examinations were directed at the detection of continuous or pulsatile flow within the portal vein thrombi . The nature of the portal vein thrombi was proven histologically in 27 patients and by CT findings and clinical history in 20 patients . The frequency , type , and direction of portal vein thrombus flow was evaluated to determine if there was any correlation with the benign or malignant nature of the portal vein thrombi . RESULTS Of the 47 patients , 26 had malignant portal vein thrombi and 21 had benign portal vein thrombi . Blood flow was detected in 22 of the malignant and in 15 of the benign portal vein thrombi . The blood flow was pulsatile in 16 malignant and three benign portal vein thrombi and continuous in six malignant and 12 benign portal vein thrombi . The direction of the pulsatile flow in the malignant portal vein thrombi was predominantly ( 13/16 ) hepatofugal . All continuous flow in both benign and malignant portal vein thrombi was hepatopetal . The detection of pulsatile flow in portal vein thrombi yielded a 62 % sensitivity and 95 % specificity for the diagnosis of malignant portal vein thrombus . CONCLUSION The detection by Doppler sonography of pulsatile flow in portal vein thrombi occurring in patients with cirrhosis is a moderately sensitive but highly specific sign for the diagnosis of malignant portal vein thrombus . However , continuous flow can be detected in benign and malignant portal vein thrombus and is thus not useful in differentiating between the two BACKGROUND AND OBJECTIVE Publication bias and other sample size effects are issues for meta-analyses of test accuracy , as for r and omized trials . We investigate limitations of st and ard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods . METHODS Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy . RESULTS Type I error rates for the Begg , Egger , and Macaskill tests are inflated for typical diagnostic odds ratios ( DOR ) , when disease prevalence differs from 50 % and when thresholds favor sensitivity over specificity or vice versa . Regression and correlation tests based on functions of effective sample size are valid , if occasionally conservative , tests for sample size effects . Empirical evidence suggests that they have adequate power to be useful tests . When DORs are heterogeneous , however , all tests of funnel plot asymmetry have low power . CONCLUSION Existing tests that use st and ard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy . The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects Malignant portal vein thrombosis is a contraindication for liver transplantation . Patients with cirrhosis and early hepatocellular carcinoma ( HCC ) may have either malignant or benign ( fibrin clot ) portal vein thrombosis . The aim of this study was to assess prospect ively whether well-defined diagnostic criteria would enable the nature of portal vein thrombosis to be established in patients with HCC under consideration for liver transplantation . Benign portal vein thrombosis was diagnosed by the application of the following criteria : lack of vascularization of the thrombus on contrast-enhanced ultrasound and on computed tomography or magnetic resonance imaging , absence of mass-forming features of the thrombus , absence of disruption of the walls of veins , and , if uncertainty persisted , biopsy of the thrombus for histological examination . Patients who did not fulfill the criteria for benign thrombosis were not placed on the transplantation list . In this study , all patients evaluated at our center during 2001 - 2007 with a diagnosis of HCC in whom portal vein thrombosis was concurrently or subsequently diagnosed were discussed by a multidisciplinary group to determine their suitability for liver transplantation .  The outcomes for 33 patients who met the entry criteria of the study were as follows : in 14 patients who were placed on the transplantation list and underwent liver transplantation  , no malignant thrombosis was detected when liver explants were examined histologically ; 5 patients who were placed on the transplantation list either remained on the list or died from causes unrelated to HCC ; in 9 patients , liver transplantation was contraindicated on account of a strong suspicion , or confirmation , of the presence of malignant portal vein thrombosis ; and 5 patients who were initially placed on the transplantation list were subsequently removed from it on account of progression of HCC in the absence of evidence of neoplastic involvement of thrombosis . In conclusion , for a patient with HCC and portal vein thrombosis , appropriate investigations can establish whether the thrombosis is benign ; patients with HCC and benign portal vein thrombosis are c and i date s for liver transplantation BACKGROUND AND AIM We aim ed to vali date the non-invasive criteria for the characterization of portal vein thrombosis ( PVT ) in patients with cirrhosis and hepatocellular carcinoma ( HCC ) . In a prospect i ve study , we examined the impact of arterial hypervascularity , as established by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases recommendations for the non-invasive diagnosis of HCC , as a criterion for characterizing macroscopic PVT ( EASL/AASLD extension criteria ) . METHODS A total of 96 cases of PVT detected using ultrasonography in patients 
    Output:
    
CEUS is highly efficient in differentiating TIV from PVT and is an alternative or a substitute for CT and /or MRI .
PROSPERO registration number : CRD42019138847 • Characterization of portal vein thrombosis ( PVT ) vs tumor-in-vein ( TIV ) is critical for HCC staging . •
CEUS has an excellent safety profile , provides a real-time analysis without any loss in accuracy compared with CT and MRI . •
This meta- analysis demonstrates that contrast-enhanced ultrasound ( CEUS ) is a suitable method for the detection of PVT and distinction with TIV