Perfusion-Diffusion Ratio: A New IVIM Approach in Differentiating Solid Benign and Malignant Primary Lesions of the Liver

Introduction. In order to improve the efficacy of intravoxel incoherent motion (IVIM) parameters in characterising specific tissues, a new concept is introduced: the perfusion–diffusion ratio (PDR), which expresses the relationship between the signal S b decline rate as a result of IVIM and the rate of signal S b decline due to diffusion. The aim of this study was to investigate this novel approach in the differentiation of solid primary liver lesions. Material and Methods. Eighty-three patients referred for liver MRI between August 2017 and January 2020 with a suspected liver tumour were prospectively examined with the standard liver MRI protocol extended by DWI-IVIM sequence. Patients with no liver lesions, haemangiomas, or metastases were excluded. The final study population consisted of 34 patients with primary solid liver masses, 9 with FNH, 4 with regenerative nodules, 10 with HCC, and 11 with CCC. The PDR coefficient was introduced, defined as the ratio of the rate of signal S b decrease due to the IVIM effect to the rate of signal S b decrease due to the diffusion process, for b = 0 . Results. No significant differences were found between benign and malignant lesions in the case of IVIM parameters ( f , D , or D ∗ ) and ADC. Significant differences were observed only for PDR, with lower values for malignant lesions ( p = 0.03 ). The ROC analysis yielded an AUC value for PDR equal to 0.74, with a cut-off value of 5.06, sensitivity of 81%, specificity of 77%, and accuracy of 79%. Conclusion. PDR proved to be more effective than IVIM parameters and ADC in the differentiation of solid benign and malignant primary liver lesions.

Inflammatory and Non-Inflammatory Mechanisms Controlling Cirrhosis Development

Because the liver is considered to be one of the most important metabolic organs in the body, it is continuously exposed to damaging environmental agents. Upon damage, several complex cellular and molecular mechanisms in charge of liver recovery and regeneration are activated to prevent the failure of the organ. When liver injury becomes chronic, the regenerative response goes awry and impairs the liver function, consequently leading to cirrhosis, a liver disorder that can cause patient death. Cirrhosis has a disrupted liver architecture and zonation, along with the presence of fibrosis and parenchymal nodules, known as regenerative nodules (RNs). Inflammatory cues contribute to the cirrhotic process in response to chronic damaging agents. Cirrhosis can progress to HCC, the most common and one of the most lethal liver cancers with unmet medical needs. Considering the essential role of inflammatory pathways in the development of cirrhosis, further understanding of the relationship between immune cells and the activation of RNs and fibrosis would guide the design of innovative therapeutic strategies to ameliorate the survival of cirrhotic and HCC patients. In this review, we will summarize the inflammatory mechanisms implicated in the development of cirrhosis.

Histopathological Features of the Steatohepatitic Variant of Hepatocellular Carcinoma and Its Relationship with Fatty Liver Disease

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver in adults. Steatohepatitic HCC (SH-HCC) is a recently described, rarer variant of HCC and is associated with nonalcoholic fatty liver disease (NAFLD). The relationship between fatty liver disease and/or steatohepatitis and SH-HCC is now known. This subtype can be confused with lipid-containing nodules (such as cirrhotic nodules, regenerative nodules, focal nodular hyperplasia) clinically, radiologically and histopathologically. Here, the histopathological features of SH-HCC, its relationship with fatty liver disease and briefly its clinical features will be discussed. In addition, histopathological features of this specific variant, immunohistochemical staining of the tumor and diagnostic difficulties in tru-cut biopsies will also be discussed. Actually, I think this article will raise clinicopathological awareness about this rare variant.

Hepatocellular Carcinoma: Diagnosis and Surveillance

Hepatocellular carcinoma arises commonly on the background of liver cirrhosis. Patients presenting with clinical symptoms have advanced stage and often are unsuitable for curative therapies. Diagnosis of hepatocellular carcinoma is commonly performed by multiphase computed tomography (CT) and / or magnetic resonance imag¬ing scans (MRI). Contrast enhanced ultrasound and MRI with hepatobiliary contrast agents are better in characterizing small lesions. Tumor markers play an adjunct role in diagnosis. For HCC in cirrhotic liver biopsy is seldom required and diagnosis is based on typical imaging features of non-rim arterial phase hyperenhancement and washout on delayed phase and pseudocapsule appearance. This is due to differential blood supply of liver parenchyma, regenerative nodules and tumor. Biopsy is only required in noncirrhotic liver, vascular liver diseases, atypical imaging features. Surveillance programs involving high risk groups can help in early detection of lesions which are amenable for curative therapies. Biannual ultrasound with or without alfa fetoprotein are commonly used surveillance tests. Multidisciplinary teams provide platform for care coordination, reassessments of clinical course, and fine changes in treatment plans required for management of this complex group of patients.

Treatment Of Variceal Bleeding

Cirrhosis is termed as the late stage of progressive hepatic fibrosis characterized by the disruption of the hepatic parenchymal structure and the formation of regenerative nodules. Many factors play a role in the etiology of cirrhosis. Currently, mortality is still high and causes significant work loss. The prognosis of patients with cirrhosis is largely due to its complications. Treatment of cirrhosis is limited except liver transplantation. An important cause of the morbidity and mortality associated with cirrhosis is the development of variceal bleeding secondary to portal hypertension. The prognosis of patients with variceal bleeding depends on the bleeding or other complications is associated with underlying chronic liver disease and its management. The mortality rate due to active variceal bleeding is around 20 percent during each bleeding and re-bleeding is observed in 70 percent of patients within one year. Upper gastrointestinal bleeding unrelated to portal hypertension is also common in patients with portal hypertension (eg, peptic ulcer disease). In this article, we will talk about variceal bleeding secondary to portal hypertension and its treatment based on current data.

A Rare Case of Acute Liver Failure Secondary to Diffuse Hepatic Infiltration of Small Cell Neuroendocrine Carcinoma

BackgroundMalignant liver infiltration is an uncommon cause of acute liver failure (ALF) and has rarely been reported.Case PresentationWe present a patient with progressive jaundice and dissociation of bilirubin and aminotransferases, who had no history of relevant liver diseases or tumor except the use of Chinese traditional drugs for a cold. An abdominal computed tomography (CT) scan showed ascites without hepatic focal lesions. Laboratory studies revealed no evidence of hepatitis or underlying autoimmune disorders. Following 8 days of conservative management ALF rapidly worsened. Contrast-enhanced CT revealed diffuse regenerative nodules in the liver. The patient underwent liver biopsy, which demonstrated that the liver was infiltrated by pulmonary neuroendocrine tumor classified as small cell lung cancer. The patient died 13 days after diagnosis.Discussion and ConclusionsThis case represents a rare cause of ALF induced by pulmonary neuroendocrine tumor of small cell type and illustrates the importance of prompt biopsy in an unknown cause of ALF.

Proliferative polyploid cells give rise to tumors via ploidy reduction

Polyploidy is a hallmark of cancer, and closely related to chromosomal instability involved in cancer progression. Importantly, polyploid cells also exist in some normal tissues. Polyploid hepatocytes proliferate and dynamically reduce their ploidy during liver regeneration. This raises the question whether proliferating polyploids are prone to cancer via chromosome missegregation during mitosis and/or ploidy reduction. Conversely polyploids could be resistant to tumor development due to their redundant genomes. Therefore, the tumor-initiation risk of physiologic polyploidy and ploidy reduction is still unclear. Using in vivo lineage tracing we here show that polyploid hepatocytes readily form liver tumors via frequent ploidy reduction. Polyploid hepatocytes give rise to regenerative nodules with chromosome aberrations, which are enhanced by ploidy reduction. Although polyploidy should theoretically prevent tumor suppressor loss, the high frequency of ploidy reduction negates this protection. Importantly, polyploid hepatocytes that undergo multiple rounds of cell division become predominantly mononucleated and are resistant to ploidy reduction. Our results suggest that ploidy reduction is an early step in the initiation of carcinogenesis from polyploid hepatocytes.

Diagnostic value of clusterin immunostaining in hepatocellular carcinoma

Background Histologic distinction between well differentiated hepatocellular carcinoma (HCC) and benign hepatocellular mass lesions is a known challenge. Existing biomarkers are of limited diagnostic value. Our previous studies observed an enhanced canalicular expression pattern of clusterin (CLU) in HCC, which was not observed in benign hepatocellular mass lesions such as hepatocellular adenoma. The aim of this study was to further investigate its diagnostic value for HCC by examining the expression pattern of CLU in a large number of non-hepatocellular tumors, and by comparing it with two other commonly used hepatocellular markers pCEA and CD10 that also show a canalicular staining pattern in HCC. Methods Enhanced canalicular staining patterns of CLU, pCEA and CD10 were analyzed on 54 surgically resected well to moderately differentiated HCCs on whole tissue sections, of which 37 had surrounding regenerative nodules while the remaining 17 had a non-cirrhotic background. CLU immunostaining was also performed on tissue microarray sections that contained 74 HCCs (40 of which were also stained for pCEA and CD10), 55 normal liver tissue samples, and 1305 non-hepatocellular tumors from multiple organs. Results Enhanced CLU canalicular staining was observed in 70% (89/128) HCCs but not in regenerative nodules, normal liver tissues or any non-hepatocellular tumors. The sensitivity and specificity for enhanced canalicular staining pattern of CLU in HCCs were 0.70 and 1.00. This enhanced canalicular pattern was observed in only 26 and 23% HCCs for CD10 and pCEA, respectively. These results further demonstrate that the distinctive enhanced canalicular pattern of CLU is unique to HCC. Conclusions CLU is superior to pCEA and CD10 as a diagnostic immunomarker in that it can help distinguish well to moderately differentiated HCC not only from non-HCC malignancies but also from benign hepatocellular mass lesions.

Glycogen storage disease type VI can progress to cirrhosis: ten Chinese patients with GSD VI and a literature review

ObjectivesThe aim of our study is to systematically describe the genotypic and phenotypic spectrum of Glycogen storage disease type VI (GSD VI), especially in Chinses population. MethodsWe retrospectively analyzed ten Chinese children diagnosed as having GSD VI confirmed by next generation sequencing in Children’s Hospital of Fudan University and Jinshan Hospital of Fudan University. We described the genotypic and phenotypic spectrum of GSD VI through the clinical and genetic data we collected. Moreover, we conducted a literature review, and we compared the genotypic and phenotypic spectrum of GSD VI between Chinese population and non Chinese population. ResultsFor the first time, we found that four Chinese patients showed cirrhosis in liver biopsy characterized by the formation of regenerative nodules. In addition, c.772+1G>A and c.1900G>C, p.(Asp634His) were recurrent in three Chinese families and four European families respectively indicating that the genotypic spectrum of PYGL gene may vary among the population. Furthermore, we identified seven novel variants in PYGL gene. ConclusionsOur study enriched the genotypic and phenotypic spectrum of GSD VI, and provided a new clue for management of GSD VI.