Endoscopic or percutaneous biliary drainage in hilar cholangiocarcinoma:When and how?

Hilar cholangiocarcinoma (hCCA) is a primary liver tumor associated with a dimprognosis. The role of preoperative and palliative biliary drainage has long beendebated. The most common techniques are endoscopic retrograde cholangiopancreatography(ERCP) and percutaneous transhepatic biliary drainage (PTBD);however, recently developed endoscopic ultrasound-assisted methods are gainingmore atention. Selecting the best available method in any specific scenario iscrucial, yet sometimes challenging. Thus, this review aimed to discuss theavailable techniques, indications, perks, pitfalls, and timing-related issues in themanagement of hCCA. In a preoperative setting, PTBD appears to have someadvantages: low risk of postprocedural complications (namely cholangitis) andbetter priming for surgery. For palliative purposes, we propose ERCP/PTBDdepending on the experience of the operators, but also on other factors: the levelof bilirubin (if very high, rather PTBD), length of the stenosis and the presence ofcholangitis (PTBD), ERCP failure, or altered biliary anatomy.

Viscoelastic tests in liver disease: where do we stand now?

Hemostasis is a complex physiological process based on the balance between procoagulant and anticoagulant systems to avoid pathological bleeding or thrombosis.The changes in standard coagulation tests in liver disease were assumed to reflect an acquired bleeding disorder,and cirrhotic patients were considered naturally anticoagulated.In the light of the new evidence,the theory of rebalanced hemostasis replaced the old concept.According to this model,the hemostatic alteration leads to a unique balance between pro-coagulant,anticoagulant,and fibrinolytic systems.But the balance is fragile and may prone to bleeding or thrombosis depending on various risk factors.The standard coagulation tests[INR(international normalized ratio),platelet count and fibrinogen]only explore parts of the hemostasis,not offering an entire image of the process.Rotational thromboelastometry(ROTEM)and thromboelastography(TEG)are both point of care viscoelastic tests(VET)that provide real-time and dynamic information about the entire hemostasis process,including clot initiation(thrombin generation),clot kinetics,clot strength,and clot stability(lysis).Despite prolonged PT/INR(international normalized ratio of prothrombin time)and low platelet counts,VET is within the normal range in many patients with both acute and chronic liver disease.However,bleeding remains the dominant clinical issue in patients with liver diseases,especially when invasive interventions are required.VET has been shown to asses more appropriately the risk of bleeding than conventional laboratory tests,leading to decrial use of blood products transfusion.Inappropriate clotting is common but often subtle and may be challenging to predict even with the help of VET.Although VET has shown its benefit,more studies are needed to establish cut-off values for TEG and ROTEM in these populations and standardization of transfusion guidelines before invasive interventions in cirrhotic patients/orthotopic liver transplantation.

Novel approaches in search for biomarkers of cholangiocarcinoma

Cholangiocarcinoma(CCA)arises from the ductular epithelium of the biliary tree,either within the liver(intrahepatic CCA)or more commonly from the extrahepatic bile ducts(extrahepatic CCA).This disease has a poor prognosis and a growing worldwide prevalence.The poor outcomes of CCA are partially explained by the fact that a final diagnosis is challenging,especially the differential diagnosis between hepatocellular carcinoma and intrahepatic CCA,or distal CCA and pancreatic head adenocarcinoma.Most patients present with an advanced disease,unresectable disease,and there is a lack in non-surgical therapeutic modalities.Not least,there is an acute lack of prognostic biomarkers which further complicates disease management.Therefore,there is a dire need to find alternative diagnostic and follow-up pathways that can lead to an accurate result,either singlehandedly or combined with other methods.In the"-omics"era,this goal can be attained by various means,as it has been successfully demonstrated in other primary tumors.Numerous variants can reach a biomarker status ranging from circulating nucleic acids to proteins,metabolites,extracellular vesicles,and ultimately circulating tumor cells.However,given the relatively heterogeneous data,extracting clinical meaning from the inconsequential noise might become a tall task.The current review aims to navigate the nascent waters of the non-invasive approach to CCA and provide an evidence-based input to aid clinical decisions and provide grounds for future research.

Contrast-enhanced ultrasound of histologically proven hepatic epithelioid hemangioendothelioma

AIM: To analyze contrast-enhanced ultrasound(CEUS) features of histologically proven hepatic epithelioid hemangioendothelioma(HEHE) in comparison to other multilocular benign focal liver lesions(FLL).METHODS: Twenty-five patients with histologically proven HEHE and 45 patients with histologically proven multilocular benign FLL were retrospectively reviewed. Four radiologists assessed the CEUS enhancement pattern in consensus.RESULTS: HEHE manifested as a single(n = 3) or multinodular(n = 22) FLL. On CEUS, HEHE showed rim-like(18/25, 72%) or heterogeneous hyperenhancement(7/25, 28%) in the arterial phase and hypoenhancement(25/25, 100%) in the portal venous and late phases(PVLP), a sign of malignancy. Eighteen patients showed central unenhanced areas(18/25, 72%); in seven patients(7/25, 28%), more lesions were detected in the PVLP. In contrast, all patients with hemangioma and focal nodular hyperplasia showed hyperenhancement as the most distinctive feature(P < 0.01).CONCLUSION: CEUS allows for characterization of unequivocal FLL. By analyzing the hypoenhancement in the PVLP, CEUS can determine the malignant nature of HEHE.

Combined treatments in hepatocellular carcinoma:Time to put them in the guidelines?

The time for battling cancer has never been more suitable than nowadays and fortunately against hepatocellular carcinoma(HCC)we do have a far-reaching arsenal.Moreover,because liver cancer comprises a plethora of stages-from very early to advanced disease and with many treatment options–from surgery to immunotherapy trials–it leaves the clinician a wide range of options.The scope of our review is to throw light on combination treatments that seem to be beyond guidelines and to highlight these using evidence-based analysis of the most frequently used combination therapies,discussing their advantages and flaws in comparison to the current standard of care.One particular combination therapy seems to be in the forefront:Transarterial chemoembolization plus ablation for medium-size non-resectable HCC(3-5 cm),which is currently at the frontier between Barcelona Clinic Liver Cancer classification A and B.Not only does it improve the outcome in contrast to each individual therapy,but it also seems to have similar results to surgery.Also,the abundance of immune checkpoint inhibitors that have appeared lately in clinical trials are bringing promising results against HCC.Although the path of combination therapies in HCC is still filled with uncertainty and caveats,in the following years the hepatology and oncology fields could witness an HCC guideline revolution.

Nuclear medicine dynamic investigations in the diagnosis of Budd-Chiari syndrome

AIM:To investigate the hepatic hemodynamics in the Budd-Chiari syndrome(BCS) using per-rectal portal scintigraphy(PRPS) and liver angioscintigraphy(LAS).METHODS:Fourteen consecutive patients with BCS were evaluated by PRPS between 2003 and 2012.Ten of them underwent LAS and liver scan(LS) with Tc-99m colloid.Eleven patients had clinical manifestations and three were asymptomatic,incidentally diagnosed at PRPS.The control group included 15 healthy subjects.We used new parameters at PRPS,the liver transit time of portal inflow and the blood circulation time between the right heart and liver.PRPS offered information on the hepatic areas missing venous outflow or portal inflow,length and extent of the lesions,open portosystemic shunts(PSS),involvement of the caudate lobe(CL) as an intrahepatic shunt and flow reversal in the splenic vein.LAS was useful in the differential diagnosis between the BCS and portal obstructions,highlightingthe hepatic artery buffer response and reversed portal flow.LS offered complementary data,especially on the CL.RESULTS:We described three hemodynamic categories of the BCS with several subtypes and stages,based on the finding that perfusion changes depend on the initial number and succession in time of the hepatic veins(HVs) obstructions.Obstruction of one hepatic vein(HV) did not cause opening of PSS.The BCS debuted by common obstruction of two HVs had different hemodynamic aspects in acute and chronic stages after subsequent obstruction of the third HV.In chronic stages,obstruction of two HVs resulted in opening of PSS.The BCS,determined by thrombosis of the terminal part of the inferior vena cava,presented in the acute stage with open PSS with low speed flow.At least several weeks are required in the obstructions of two or three HVs for the spontaneous opening of dynamically efficient PSS.The CL seems to have only a transient important role of intrahepatic shunt in several types of the BCS.CONCLUSION:Dynamic nuclear medicine investigations assess the extent and length of hepatic venous obstructions,open collaterals,areas without portal inflow,hemodynamic function of the CL and reverse venous flow.

Contemporary role of liver biopsy in hepatocellular carcinoma

A correct diagnosis of hepatocellular carcinoma(HCC) in cirrhotic patients with focal liver lesions is one of the most important issues nowadays. Probably one of the oldest debates in the hepatology community is whether to perform liver biopsy(LB) in all cirrhotic patients with focal liver lesions. We now face a time when oncology is moving towards personalized medicine. According to the current European Association for the study of Liver diseases HCC guidelines, LB has only a minor role in the management of HCC. However, the current recommendations were made more than five years ago. As time has passed, the development of high-throughput molecular technologies has helped reveal the main molecular mechanism involved in HCC development and progression. Several subtypes of HCC, with both molecular and histological characterization, have been described. Importantly, some of these subtypes have prognostic impact. In the context of personalized treatment, the role of LB will be carefully reconsidered. Until then, it is mandatory to know the various techniques of LB, their performances, complications and limitations. The balance of risk and benefit defines many of the decisions that we make as providers of medical care. In this review, we discuss not only the risks associated with LB, but also the benefits of biopsy in various clinical scenarios. Not long from now, the role of LB will be reconsidered. It is possible that we will go back in time and once again use biopsy for HCC diagnosis. Then again, we may move back to the future to try to improve the use of liquid biopsy in the follow-up of HCC patients after various treatment modalities.

Extracellular vesicles small RNA clusters:hit the nail on the head of liver cancer detection

There is a very urgent need and clinical demand of robust biomarkers in cancer screening,especially in early hepatocellular carcinoma(HCC)surveillance as outlined by various professional international associations as the European Association for the study of the Liver(EASL),or the Asian Pacific Association for the Study of the Liver(APASL)and national professional organisations as the American Association for the Study of Liver Diseases(AASLD),besides others.Newest data on primarily HCC is still depicting this cancer entity as the sixth most frequently diagnosed cancer,with over 900,000 new cases and over 830,000 deaths worldwide(1).This type of cancer,therefore,remains at the forefront of malignant diseases.Thus,every element of patient management,including early diagnosis and prognosis of treatment response and survival,is a challenge.