Focal Liver Research Articles

Vascular reconstructions and transplant technologies in liver surgery (part I)

To systematize technical aspects of liver resections with reconstruction of afferent and efferent liver blood supply and/or inferior vena cava, as well as to analyze the results of surgical treatment in patients with focal liver lesions. The study included 413 patients with parasitic lesions, primary and secondary liver tumors with great vessel invasion (portal vein, hepatic artery, hepatic veins, inferior vena cava, right atrium). These features excluded radical liver resections without vascular resection and reconstruction, as well as liver autotransplantation in vivo, liver autotransplantation ante situ (ex situ in vivo), extracorporeal liver resections with autotransplantation (ex vivo). Surgical interventions were systematized depending of surgical tactics and techniques, technical complexity, type and number of reconstructed vessels, the use of total vascular isolation and cold preservation techniques, resection and reconstruction of great vessels. Thus, 4 gradations were allocated (Grade I-IV). The definition of transplantation technologies in liver surgery was proposed. Transplantation technologies in liver surgery include liver resections supplemented with vascular reconstruction of afferent and efferent liver blood supply, inferior vena cava including total vascular isolation of liver under normo- or hypothermia. These measures can significantly extend the possibilities of resection.

AASLD practice guidance on drug, herbal, and dietary supplement-induced liver injury.

AASLD practice guidance on drug, herbal, and dietary supplement-induced liver injury.

Focal nodular liver hyperplasia as a late complication that occurs after autologous hematopoietic stem cell transplantation in children with neuroblastoma (clinical case and literature review)

Focal nodular hyperplasia (FNH) is a regenerative volumetric liver formation that can occur as a result of the reaction of hepatocytes to local vascular circulatory disorders and is one of the late complications in patients who received high-dose chemotherapy followed by hematopoietic stem cell transplantation. This article presents a description of two clinical cases of development of liver FNH in patients with high-risk neuroblastoma identified in the late stages from the end of specific treatment. A possible reason for the development of liver FNH in these patients could be the use of alkylating drugs (ifosfamide, threosulfan, busulfan, melphalan).

Clinical and ultrasonographic investigations of 30 water buffaloes (Bubalus bubalis) with hepatomegaly.

Background and Aim:Knowledge of normal ultrasonographic dimensions of the liver and associated vascular structures is an important indicator for the diagnosis of hepatic diseases. Enlargement of the liver beyond its normal dimensions is the term of hepatomegaly and ultrasonography is the primary and the suitable diagnostic technique for this condition. Therefore, this study aimed to describe the clinical and ultrasonographic findings of liver diseases causing hepatomegaly in 30 buffaloes as well as to provide a range of liver dimensions and its blood vessel measurements in normal and diseased buffaloes.Materials and Methods:The study population included 30 buffaloes that were admitted to the clinic of the Faculty of Veterinary Medicine – Zagazig University for investigation of clinical signs associated with gastrointestinal diseases such as anorexia, chronic weight loss, and variable degrees of diarrhea or constipation. The animals were subjected to thorough clinical and ultrasonographic investigations. In addition, 10 healthy buffaloes were investigated ultrasonographically and post-slaughtering for comparison of liver dimensions and physical appearance.Results:Three conditions causing hepatomegaly were identified in this study as multiple focal hepatic lesions, diffuse fatty liver, and hepatic congestion. Clinically, it was difficult to differentiate between each condition while ultrasonography was the ideal tool for diagnosis after comparing with necropsy as a gold standard tool. Hepatomegaly was recorded in all affected animals with a significant decrease in the size of the portal vein (PV) and caudal vena cava (CVC) in animals affected with multiple focal hepatic lesions and fatty liver disease while the size of the PV and CVC was significantly increased in buffaloes with hepatic congestion.Conclusion:Ultrasonography can aid to accurately identify buffaloes with hepatomegaly and differentiate between different lesions involved.

Ductular reaction or hepatic reparative complex: immunohistochemical features in liver cirrhosis in patients with chronic hepatitis

Until recently, a discussion about the mechanisms of development and the biological role of the ductular reaction, which develops in patients with chronic liver diseases continues among hepatologists and pathomorphologists. Purpose of the study. To characterize the pathomorphological features and significance of the ductular response in liver cirrhosis in patients with chronic non-alcoholic, alcoholic and viral hepatitis in hepatobioptats with the use of immunohistochemical (IHC) techniques. Material and methods of investigation. Histological, histochemical and IHC study of the ductular liver reaction in liver biopsies of 52 patients aged 24 to 66 years with cirrhosis of the liver on the background of non-alcoholic steatohepatitis (13 patients), and alcoholic steatohepatitis (13 patients) and on the background of chronic viral hepatitis C (10 patients, 26–47 years), as well as those suffering from severe biliostasis (8 patients) and focal nodular liver hyperplasia (8 patients). Results. The ductular reaction can be detected in the active phase with maximum manifestations in patients with liver cirrhosis on the background of chronic hepatitis, it may have an average or weak degree of severity; in a significant number of patients, the effects of the ductular reaction of the liver are revealed. Cellular chains and groups of cells with the immunophenotype of the progenitor cells of the liver appear in the active phase of the ductular reaction at the periphery of the hepatic lobules in the projection of the Goering canals, in the fibrotically altered portal tracts, in the subcapsular zone of the liver and in the thickened fibrosis septa (c-kit CD117+, CD34+, CD56+ CK7-, CK19-, Hepar-) without presence of figures of mitosis or increased level of expression of Кі-67 in them. In small ductules localized in the projection of the Goering canals, single cells with the expression of c-kit CD 117+, CD44 Std./HCAM+, CD34+, CD56+, expressing the markers of biliary (CK7+, CK19+) and hepatocyte (Hepar+, α-fetoprotein+) differentiation are revealed. Cellular chains and ductules in the intermediate zones of the hepatic lobules are represented by cells of biphasic differentiation: biliary (CK7+, CK19+), hepatocyte (Hepar+) differentiation and intermediate hepatobiliary CK7+ cells. Hepatocyte differentiation of progenitor cells in lobules of the liver is facilitated by local expression of laminin by perisinusoidal stellate cells. New pseudolobes arise in the active phase of the ductular reaction in the lobes with perisinusoidal pericellular fibrosis from disorderly located large hepatocytes without linear perisinusoid spaces and centrolobular veins, with the presence of “intermediate” SC7+ hepatocytes on the periphery. One-two-row chains and ductules from SC7+ and CK19+ cells dominate in the fibro-altered portal tracts, septa and the subcapsular zone of the liver among the collagen fibers of I, III, IV type and the processes of α-SMA+ myofibroblasts, and small short chains from Hepar+ and α- fetoprotein-cells. When the severity of micronodular liver cirrhosis increases, when the area of hepatic lobules and pseudotypes becomes equal to or less than the area of the surrounding fibrosis, there is a parallel increase in the number of Ki-67+ cells in portal-lobular ductules and chains, as well as the number of Ki-67+ hepatocytes in hepatic lobules and pseudolobes. The long-term consequences of the ductular reaction in liver cirrhosis reflect the presence of the different number of bile-free ductules with CK7 + epithelium in the fibrous tissue of portal tracts, septa and under the liver capsule. In the lobules of the liver with perisinusoidal pericellular fibrosis, fuzzy outlines of hepatocyte hyperplasia without ordered sinusoids and liver-celled beams are found. Conclusions. The ductular reaction in liver cirrhosis in patients with chronic non-alcohol, alcoholic and viral hepatitis is the process of activation and evolution of a complex liver repair complex aimed at replenishing the deficit of hepatocytes and biliary structures. The reparative process, activating by liver cirrhosis on the background of the disturbed portal-lobular intercellular matrix and the progressive deficit of hepatocytes, does not provide the reconstruction of full-fledged liver structures, it is discordant towards the creation of new, functionally low-value hepatocellular pseudolobes and the accumulation of biliary terminals in fields of portal-septal fibrosis.

Can tumor coverage evaluated 24\xa0h post-radiofrequency ablation predict local tumor progression of liver metastases?

PurposeTo assess the predictive value for local tumor progression (LTP) of geometrical tumor coverage using the contrast-enhanced (ce-)CT images acquired before and within 24 h after radiofrequency (RF) ablation.MethodsTwenty patients (6 male and 14 female, median age 62 years) with 45 focal hypovascular liver metastases (16 colorectal carcinoma, 3 melanoma and 1 breast carcinoma) underwent RF ablation under CT-guidance and received a ce-PET/CT scan within 24 h post-procedure. Pre- and post-ablation ce-CT-images were aligned using an interactive procedure and used to verify the tumor coverage of the RF ablation. Results were correlated to LTP as recorded during follow-up performed every 2–3 months after the intervention (mean follow-up of 110 weeks) and compared to standard reading performed by three readers of the ce-CT images.ResultsEleven tumors (25%) showed LTP during the follow-up period. One lesion, which did not show LTP, was excluded from analysis due to the poor quality of the alignment. For the remaining, 29 (66%) tumors were completely covered by the ablation zone, 9 (20%) were not, and for 6 (14%) tumors the edges coincided with the edge of the ablation zone. The sensitivity, specificity, PPV and NPV for LTP of having incomplete tumor coverage or no apparent ablative margin versus standard reading of ce-CT were 100, 88, 73 and 100% versus 42, 88, 58 and 82%, respectively.ConclusionsVerifying the tumor coverage of liver metastases by an ablation zone through alignment of pre- and early post-ablation ce-CT images has a high predictive value for LTP.

Diagnosis of the Different Aspects of Fat in the Liver

Liver fat infiltration usually appears as a diffuse abnormality that modifies the signal of the liver homogeneously. But this overload can be heterogeneous in different circumstances and in different ways: heterogeneous and focal steatosis and fatty focal sparing. It is important to know these aspects in order to not misdiagnose these abnormalities. The segmental repartition of the steatosis is easily explained by the different contribution to the portal flow that is both mesenteric or splenic. As portal flow is laminar and helicoidal, it could result in an incomplete mixing of splenic and mesenteric blood in the intraparen chymal liver vascularisation and therefore a preferential uptake of lipids coming from mesenteric blood flow in an area of the liver. Heterogeneous and focal fatty depositions are partially explained by vascular theories. An excess of insulin blood supply (due to an anatomical variant of pancreatic blood vessels) is the most accepted theory, but there are probably other explanations, such as ischemic mechanisms, that take a role in these abnormalities. These focal steatoses have typical semiology: Their signal drops on opposition phase T1 EG sequences. They are geographic margins; they produce no mass effect and vessels are not distorted inside the lesion. The enhancement is homogeneous, and the enhancement ratio between fatty and non-fatty liver is preserved on the different vascular phases. Finally, there is typical distribution in the liver (posterior part of the segment IV, gallbladder fosse, falciform ligament, and subcapsular region). The last type of focal steatosis is nodular steatosis, which is a rare entity, but it is really difficult to differentiate a tumour (benign or malign) from fatty content. In this situation, if there is oncologic context or in case of doubt, a biopsy should be performed. The second way of heterogeneous repartition of the steatosis is the heterogeneous and focal fatty sparing. This lesion is, at present, more frequent than focal steatosis. For this type of lesion, the explanation is quite clear. Anatomical vascular variants lead to a non-portal blood contribution. This is the theory of the third supply. In territory with systemic blood supply rather than portal blood supply, the uptake of lipids is low and there is no steatosis. In opposition phase T1 EG sequence, the signal of the liver is dropped except the signal of the sparing area. The semiology regarding homogeneity, vessels, and enhancement is similar to that of the focal steatosis. Preferential locations are also the same. Nodular fatty sparing is possible. In this situation, such as in the case of nodular steatosis, it is important to eliminate a real liver tumour in a fatty liver. Thus all sequences of the MRI should be carefully analysed to avoid a misdiagnosis, and in case of doubt, a biopsy should be performed. MRI is the key examination for the diagnosis of focal fatty liver or focal fatty sparing, but contrast enhanced ultrasound (CEUS) could be really useful. The enhancement of focal fatty liver or sparing is similar to the surrounding parenchyma. This is a strong argument to make a difference with real tumours. Focal fatty liver and, even more, focal fatty sparing are frequent lesions. They could be in the majority of cases easily diagnosed using CEUS and MRI. But in case of doubt, especially in case of nodular lesion, a biopsy should be performed.

Transjugular Liver Biopsy in a Multiple Myeloma Patient with Hepatomegaly, Portal Hypertension and "Miliary" Liver Lesions: A Case Report.

The present report describes a 50-year-old female recently diagnosed with multiple myeloma who presented with hepatosplenomegaly, miliary-type hyper enhancing liver tumors, and esophageal varices. We performed a transjugular liver biopsy when liver biopsy was requested to evaluate the miliary-type liver lesions. This was done to lower the risk of bleeding given the patient's anemia and probable portal hypertension. This approach was successful in safely providing diagnostic samples for surgical pathology and flow cytometry to assess the nature of focal miliary liver lesions. It also proved portal hypertension.

ULTRASOUND IMAGING OF FATTY LIVER ON GENERAL EXAMINATION PATIENTS AT HUE UNIVERSITY HOSPITAL IN YEAR 2013

Objectives: This study describes the characteristics of hepatic steatosis on ultrasound imaging by grading of Hagen - Assert. Determining the factors related with fatty liver. Methodology: Cross-sectional study. Results: By studying 448 patients went to general examination at Hue University Hospital from 1/5/2013 to 1/9/2013, we have some of comments: 76.1% of patients has hepatic steatosis on ultrasound imaging in the aged of 30-60 years, common in men than women,with male – female ratio:1.23. The majority (96%) hepatic steatosis was complete all lobes, and the remaining 4% patient was focal fatty liver. Grading hepatic steatosis by Hagen-Ansert classification (1995): there were 66.5% grade 1, 30.5% grade 2, and grade 3 of 3.0%. 26 - 32% patients’ hepatic steatosis on ultrasound combinated with increasing of Lipidemia (Cholesterol, Triglycerid and LDL Cholesterol). Conclusion: There were 66.5% patients grading level 1 by Hagen-Ansert classification for hepatic steatosis. Increasing of Lipidemia index represented only 26 – 32% of patients. Our study did not found significant compatible change between the hepatic steatosis on ultrasound imaging and Triglycerid blood concentrations (p > 0.05). Keywords: Image, ultrasound, hepatic steatosis, fatty liver

Functional Imaging of the Liver

Anatomical-based imaging is used widely for the evaluation of diffuse and focal liver, including detection, characterization, and therapy response assessment. However, a limitation of anatomical-based imaging is that structural changes may occur relatively late in a disease process. By applying conventional anatomical-imaging methods in a more functional manner, specific pathophysiologic alterations of the liver may be assessed and quantified. There has been an increasing interest in both the clinical and research settings, with the expectation that functional-imaging techniques may help solve common diagnostic dilemmas that conventional imaging alone cannot. This review considers the most common functional magnetic resonance imaging, computed tomography, and ultrasound imaging techniques that may be applied to the liver.

A Selective Review of Commonly Used Sonography-Guided Hyperthermic Ablative Technologies for Malignant Lesions of the Liver

The use of percutaneous ablation therapy to manage focal malignant liver lesions has been widely embraced and integrated into clinical practice. These minimally invasive procedures offer a successful alternative to surgery for patients limited by poor hepatic reserve or problematic anatomy. Radiofrequency is currently the most commonly performed ablation therapy technique; however, new research in the field of microwave technology suggests certain advantages over radio frequency. This article analyzes the differences between these two technologies and discusses the circumstances in which one method may be preferred over the other for hepatic malignancies.

Neuere Entwicklungen der Leber-MRT

Radiology has gained an exceptional position in medicine because a correct diagnosis is the most crucial issue in determining an accurate and personalized therapeutic strategy. This has a direct influence not only on the individual patient but also on the socio-economic aspects of healthcare services in terms of shortening the time interval to establish a diagnosis and to avoid risk-associated invasive diagnostic methods or long-term, cost-intensive follow-up. Magnetic resonance imaging (MRI) is an excellent example of this which due to continuous technological developments and emerging techniques allows a non-invasive diagnosis of the different hepatic diseases. In this article, we illustrate the direct correlation between the recent technical advances in MRI, such as 3.0T, diffusion-weighted imaging, perfusion imaging, spectroscopy, texture analysis and MR elastography and obtaining a confident non-invasive diagnosis of focal and diffuse liver diseases.

Differentiating focal eosinophilic liver disease from hepatic metastases using unenhanced and gadoxetic acid-enhanced MRI

To examine the differential features of focal eosinophilic liver disease (FELD) from liver metastases on gadoxetic acid-enhanced MRI. Twenty patients with 41 FELD and 20 patients with 55 metastases were enrolled in this study. Liver MRI consisted of precontrast 2D T1-weighted image (T1WI) and gadoxetic acid-enhanced 3D T1WI (arterial, portal, 20 min hepatocyte-selective phases), and a postcontrast T2WI. Images were analyzed for the margin and shape of the lesions; lesion conspicuity on T1- and T2WI; signal intensity of the lesions on 3D T1WI; presence of rim enhancement and misty signs; and presence of significant smaller lesions on the unenhanced T1WI (<50%) compared to hepatocyte phase image. Univariate analysis revealed the following significant parameters to favor FELD: a fuzzy margin, irregular shape, subtle signal intensity changes on T1- and T2WI, absence of target signs on the hepatocyte phase image, presence of misty signs, and size discrepancies on T1WI and hepatocyte phase images. Multivariate analysis revealed only a significantly smaller lesion size on T1WI compared to hepatocyte phase images to be predictive of FELD. A significantly smaller lesion size on T1WI relative to hepatocyte phase image is the best predictor for identifying FELD on gadoxetic acid-enhanced MRI.

Adenoma or Atypical Hepatic Focal Nodular Hyperplasia: Role of Preoperative Imaging and Laparoscopic Treatment

Differentiation of focal nodular hyperplasia (FNH) and other hypervascular liver lesions, such as hepatocellular adenoma (HCA), is important because of the drastically different therapeutic approach. However, FNH can be well distinguished only if it shows a typical aspect; alternatively, in the case of atypical FNH, imaging findings are not specific enough to provide a secure diagnosis and histologic verification of the lesion is required. In addition, HCA cannot be identified conclusively by any current available imaging technique and it can be at best suspected strongly, and this suspicion may lead to liver resection. Herein we report a case of a patient with an unusual FNH nodule presenting at ultrasonographic scanning as an isoechoic mass arising from hepatic segment 4b; the diagnostic indecision between FNH and HCA was not definitively solved even after computed tomography scan and magnetic resonance imaging and the patient was scheduled for a laparoscopic resection. The pathologic examination diagnosed an atypical FNH nodule. The clinical doubt between FNH and HCA remains a problem affecting the clinicians, and more effort should be made in the direction of a better preoperative differentiation of such different conditions. Surgical resection should not be considered as the failure of the preoperative diagnostic attempt, but as the mainstay for a definitive and sure diagnosis.

Liver MRI at 3.0 Tesla in patients with focal or diffuse liver disease: An intraindividual comparative study of T1-, T2- and diffusion weighted imaging using parallel RF transmission with patient-adaptive B1 shimming

Liver MRI at 3.0 Tesla in patients with focal or diffuse liver disease: An intraindividual comparative study of T1-, T2- and diffusion weighted imaging using parallel RF transmission with patient-adaptive B1 shimming

Fluorine-18-FDG PET findings of focal eosinophilic liver disease: correlation with CT and/or MRI, laboratory, and pathologic findings

Fluorine-18-FDG PET findings of focal eosinophilic liver disease: correlation with CT and/or MRI, laboratory, and pathologic findings

Gadolinium-Enhanced Imaging of Liver Tumors and Manifestations of Hepatitis

The ability for contrast-enhanced magnetic resonance imaging to provide significant diagnostic impact to focal and diffuse liver diseases requires knowledge, analysis, and technical optimization of the imaging techniques. Our review outlines the technical requirements needed to perform reproducible contrast-enhanced liver imaging and describes the important imaging features for assessing liver disease with conventional and alternate gadolinium-based contrast media. We present an experimental review of timing and quantification methods in dynamic contrast-enhanced liver imaging, with results of analysis showing perfusion and uptake curves in a series of patients and healthy subjects. An evidence-based methodology for reproducible arterial-phase imaging is detailed for performing a real-time bolus-tracking method. Additional diagnostic imaging features manifest at later imaging phases, in which the kinetic behavior of the contrast media serves to further specify focal lesions, while revealing detailed information of diffuse liver disease, particularly hepatic fibrosis. We review the utility of alternate gadolinium-based contrast media that undergo hepatocyte uptake, for applications related to liver tumor imaging. We also introduce results showing the potential for using alternate hepatocyte uptake agents to detect and quantify liver changes related to acute and chronic hepatitides.

Magnetic resonance imaging of the liver: consensus statement from the 1st International Primovist User Meeting

The role of contrastenhanced liver MRI using the hepatocyte-specific agent gadoliniumethoxybenzyl-diethylene triamine penta-acetic acid (Gd-EOB-DTPA, Primovist, Bayer Schering Pharma, Berlin, Germany) is considered, based on the discussion at the Forum of Liver MRI: The 1st International Primovist User Meeting. Current clinical evidence supports Gd-EOB-DTPA’s use in non-invasive diagnosis of benign and malignant liver lesions and staging of focal and diffuse liver disease. The information thus gained assists in the provision of cost-effective patient management. The pharmacological properties of Gd-EOB-DTPA facilitate the imaging of both the vascular and hepatobiliary phases in the cirrhotic and non-cirrhotic liver and may provide an opportunity for one-stop diagnosis of liver lesions, such as focal nodular hyperplasia, adenomas, haemangiomas, hepatocellular carcinoma and metastases. The currently recommended protocols using Gd-EOB-DTPA are appropriate for the majority of patients, but imaging time points may require modification in specific patient groups. Further experience in routine clinical practice, as opposed to that gained from rigidly designed clinical studies, may provide greater understanding of the potential of Gd-EOB-DTPA for the evaluation of the cirrhotic and non-cirrhotic liver. Additional studies may substantiate the potential of Gd-EOB-DTPA in the imaging of other abdominal organs and in the evaluation of liver function and fibrosis.

In-vivo-31Phosphor-Magnetresonanzspektroskopie von Lebererkrankungen

31P-MR spectroscopy was performed in 12 patients with focal and diffuse liver disease and in ten normal controls, using surface coils. Results so far show a significantly increased concentration of PME/beta-ATP and of PDE/beta-ATP in patients with liver metastases and in one patient with hepatic involvement by malignant lymphoma. The spectra of liver cirrhosis and fatty livers showed no characteristic changes.

Pathologie entlang der sinusoidalen Wegstrecke: sinusendotheliale und perisinusoidale Befunde

Sinusoidal alterations unrelated to primary hepatocellular damage present without characteristic clinical findings and in these cases the liver biopsy is particularly important. Capillarization of sinusoids is characterized by closing of fenestration, formation of a basal membrane and by the expression of CD34 and is typical for active cirrhosis. In nodular regeneratory hyperplasia, capillarization indicates a local or general disturbance of perfusion. In large regenerative nodules, focal nodular hyperplasia and liver cell adenoma CD34-positive capillaries reflect afferent parts and CD34-negative sinusoids the efferent parts of the parenchymal vascular bed. HCC generally have a completely capillarized CD34-positive vascular bed. Hepatic angiosarcomas and epithelioid hemangioendotheliomas can be easily overseen in liver biopsies, if they spread along the sinusoids without detoriation of the acinar architecture and without significant alteration of the surrounding liver cell plates. Toxic damage of endothelial cells, post-sinusoidal stasis and sinusoidal hyperperfusion are the underlying pathogenetic principles of sinusoidal injury. Rupture and loss of the perisinusoidal reticulin fibres lead to peliosis hepatis. In these cases liver biopsy might disclose occlusion of the terminal liver veins (VOD). Perisinusoidal fibrosis can be caused by intrasinusoidal accumulation of pathologic cells, advanced intrasinusoidal macrophagocytic storage diseases and by activation of the vitamin A-storing hepatic stellate cells. Perisinusoidal amyloidosis can be the first sign of an underlying B-cell neoplasia.