Hepatic Parasitic Abscess Caused by Clonorchiasis: Unusual CT Findings of Clonorchiasis

Clonorchiasis is caused by a chronic infestation of liver flukes, Clonorchis sinensis, and these reside mainly in the medium- and small-sized intrahepatic bile ducts. Therefore, diffuse, uniform, minimal or mild dilatation of these bile ducts, particularly in the periphery, without dilatation of the extrahepatic bile duct is the typical finding on several imaging modalities. We report here on the CT findings of an unusual case of hepatic parasitic abscess that was caused by clonorchiasis; this malady mimicked cholangiocarcinoma, and there was no dilatation of the intrahepatic bile ducts

C-reactive Protein Overexpression in the Background Liver of Hepatitis B Virus–Associated Hepatocellular Carcinoma Is a Prognostic Biomarker

Background Chronic hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC). Peripheral blood C-reactive protein (CRP) concentration and CRP overexpression in HCC cells are proven to be prognostic markers for HCC, but the significance of CRP expression in non-neoplastic hepatocytes, which are the primary origin of CRP, has not been studied. This study was conducted to determine the clinicopathologic significance of CRP immunoreactivity in the background liver of HBV-associated HCC. Methods CRP immunostaining was done on tissue microarrays of non-neoplastic liver tissues obtained from surgically resected, treatment-naïve HBV-associated HCCs (n = 156). The relationship between CRP immunoreactivity and other clinicopathologic parameters including cancer-specific survival was analyzed. CRP immunoreactivity was determined using a 4-tier grading system: grades 0, 1, 2, and 3. Results CRP was positive in 139 of 156 cases (89.1%) of non-neoplastic liver in patients with HCCs: grade 1 in 83 cases (53.2%); grade 2 in 50 cases (32.1%); and grade 3 in six cases (3.8%). The patients with diffuse CRP immunoreactivity (grade 3) had decreased cancer-specific survival (p = .031) and a tendency for shorter interval before early recurrence (p = .050). The degree of CRP immunoreactivity correlated with serum CRP concentration (p < .001). Conclusions CRP immunoreactivity in non-neoplastic liver is a novel biomarker for poor cancer-specific survival of HBV-associated HCC and correlates with serum CRP concentration

A Case of Primary Paraganglioma that Arose in the Pancreas: the Color Doppler Ultrasonography and Dynamic CT Features

Paragangliomas rarely originate from the pancreas and they are characterized on imaging studies as well-marginated, hypervascular masses with cystic areas. We herein report on a case report of pancreatic paraganglioma in a 57-year-old woman, which was confirmed on pathology. Color Doppler ultrasonography and dynamic CT demonstrated a well-demarcated, extremely hypervascular mass with prominent intratumoral vessels and early contrast filling of the draining veins from the mass. Endoscopic retrograde cholangiopancreatography showed that the main pancreatic duct was displaced and mildly dilated

Guanabenz Acetate Induces Endoplasmic Reticulum Stress–Related Cell Death in Hepatocellular Carcinoma Cells

Background Development of chemotherapeutics for the treatment of advanced hepatocellular carcinoma (HCC) has been lagging. Screening of candidate therapeutic agents by using patient-derived preclinical models may facilitate drug discovery for HCC patients. Methods Four primary cultured HCC cells from surgically resected tumor tissues and six HCC cell lines were used for high-throughput screening of 252 drugs from the Prestwick Chemical Library. The efficacy and mechanisms of action of the candidate anti-cancer drug were analyzed via cell viability, cell cycle assays, and western blotting. Results Guanabenz acetate, which has been used as an antihypertensive drug, was screened as a candidate anti-cancer agent for HCC through a drug sensitivity assay by using the primary cultured HCC cells and HCC cell lines. Guanabenz acetate reduced HCC cell viability through apoptosis and autophagy. This occurred via inhibition of growth arrest and DNA damage-inducible protein 34, increased phosphorylation of eukaryotic initiation factor 2α, increased activating transcription factor 4, and cell cycle arrest. Conclusions Guanabenz acetate induces endoplasmic reticulum stress–related cell death in HCC and may be repositioned as an anti-cancer therapeutic agent for HCC patients

Hepatocellular Carcinoma Arising in a Huge Hepatocellular Adenoma with Bone Marrow Metaplasia

Hepatocellular adenoma (HCA) is the most common type of benign liver tumor, and its major complication is malignant transformation to hepatocellular carcinoma (HCC). Here, we report a case of HCC arising in HCA with bone marrow metaplasia in a 24-year-old Korean woman who presented with abdominal discomfort. A huge liver mass was found on abdominal ultrasonography. She underwent surgical hepatic resection, and the resected specimen was entirely involved by a 20-cm-sized tumor. Histological review revealed a well differentiated HCC arising from inflammatory HCA with β-catenin nuclear positivity and bone marrow metaplasia that contained hematopoietic cells. This case was unique because malignant transformation, inflammatory type HCA, β-catenin nuclear staining, and bone marrow metaplasia were simultaneously observed. Additionally, it should be noted that a large HCA with β-catenin activation can undergo malignant transformation and should be surgically resected in a timely manner

Effectiveness of regdanvimab on mortality in COVID-19 infected patients on hemodialysis

Background Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (COVID-19), there are lack of effective and proven treatments for end-stage renal disease (ESRD). The present study aims to evaluate the effectiveness of regdanvimab on mortality in COVID-19–infected patients on hemodialysis (HD). Methods We conducted an observational retrospective study in 230 COVID-19–infected patients on HD, of whom 77 (33.5%) were administered regdanvimab alone or in combination with dexamethasone or remdesivir during hospitalization (regdanvimab group) and 153 patients (66.5%) were not (no regdanvimab group). The primary outcome was in-hospital mortality. We compared mortality rates according to the use of regdanvimab and investigated the factors associated with mortality. Results Fifty-nine deaths occurred during hospitalization, 49 in the no regdanvimab group (32.0%) and 10 in the regdanvimab group (13.0%), and the mortality rate was significantly higher in the no regdanvimab group than that in the regdanvimab group (p = 0.001). Multivariate Cox regression analysis showed that malignancy (p = 0.001), SPO2 of <95% at admission (p = 0.003), and administration of antibiotics and regdanvimab (p = 0.007 and p = 0.002, respectively) were significantly associated factors with mortality. Conclusion Regdanvimab administration is beneficial in improving prognosis in hospitalized COVID-19 patients on HD. Considering the vulnerability to infection and high mortality of ESRD patients, regdanvimab may be considered as a therapeutic option in COVID-19 patients on HD

Role of 15-hydroxyprostaglandin dehydrogenase down-regulation on the prognosis of hepatocellular carcinoma

Background/AimsThe role of prostaglandin E2 (PGE2) in the modulation of cell growth is well established in colorectal cancer. The aim of this study was to elucidate the significance of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) down-regulation on the prognosis of hepatocellular carcinoma (HCC) patients.MethodsThe expression of 15-PGDH in HCC cell lines and resected HCC tissues was investigated, and the correlation between 15-PGDH expression and HCC cell-line proliferation and patient survival was explored.ResultsThe interleukin-1-β-induced suppression of 15-PGDH did not change the proliferation of PLC and Huh-7 cells in the MTS [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The induction of 15-PGDH by transfection in HepG2 cells without baseline 15-PGDH expression was suppressed at day 2 of proliferation compared with empty-vector transfection, but there was no difference at day 3. Among the 153 patients who received curative HCC resection between 2003 and 2004 at our institution, 15-PGDH expression was observed in resected HCC tissues in 56 (36.6%), but the 5-year survival rate did not differ from that of the remaining 97 non-15-PGDH-expressing patients (57.1% vs 59.8%; P=0.93). Among 50 patients who exhibited baseline 15-PGDH expression in adjacent nontumor liver tissues, 28 (56%) exhibited a reduction in 15-PGDH expression score in HCC tissues, and there was a trend toward fewer long-term survivors compared with the remaining 22 with the same or increment in their 15-PGDH expression score in HCC tissues.ConclusionsThe prognostic significance of 15-PGDH down-regulation in HCC was not established in this study. However, maintenance of 15-PGDH expression could be a potential therapeutic target for a subgroup of HCC patients with baseline 15-PGDH expression in adjacent nontumor liver tissue

Platelets generated from human embryonic stem cells are functional in vitro and in the microcirculation of living mice

Platelets play an essential role in hemostasis and atherothrombosis. Owing to their short storage time, there is constant demand for this life-saving blood component. In this study, we report that it is feasible to generate functional megakaryocytes and platelets from human embryonic stem cells (hESCs) on a large scale. Differential-interference contrast and electron microscopy analyses showed that ultrastructural and morphological features of hESC-derived platelets were indistinguishable from those of normal blood platelets. In functional assays, hESC-derived platelets responded to thrombin stimulation, formed microaggregates, and facilitated clot formation/retraction in vitro. Live cell microscopy demonstrated that hESC-platelets formed lamellipodia and filopodia in response to thrombin activation, and tethered to each other as observed in normal blood. Using real-time intravital imaging with high-speed video microscopy, we have also shown that hESC-derived platelets contribute to developing thrombi at sites of laser-induced vascular injury in mice, providing the first evidence for in vivo functionality of hESC-derived platelets. These results represent an important step toward generating an unlimited supply of platelets for transfusion. Since platelets contain no genetic material, they are ideal candidates for early clinical translation involving human pluripotent stem cells

Clinical outcome of surgically resected pancreatic intraductal papillary mucinous neoplasm according to the marginal status: A single center experience

Background: Surgical resection is the treatment of choice of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. However, the benefit of clearing resection margin is still controversial. Methods: We reviewed 281 surgically resected cases of IPMN. The recurrences were compared according to the histologic grade (benign or borderline IPMN, malignant noninvasive IPMN, invasive carcinoma) and size (pancreatic intraepithelial neoplasia, PanIN, less than 0.5 cm in the long axis; and IPMN, greater than or equal to 0.5 cm) of the residual lesions at the resection margin. Results: Sixty cases (21.4%) were invasive carcinoma, and 221 (78.6%) noninvasive cases included 87 (31.0%) benign, 107 (38.1%) borderline and 11 (3.9%) malignant noninvasive IPMN cases. In noninvasive IPMN, increased recurrence in patients with five or more years of follow-up was only related to the involvement of resection margin by severe dysplasia. The recurrence of invasive carcinoma was high (27.3%) even when the resection margin was clear, and was not related to the grade or size of residual tumors at the resection margin. Conclusions: Invasiveness is a strong risk factor for recurrence in IPMN regardless of the status of the resection margin. However, in noninvasive IPMN, histologic grading of residual lesions at the resection margin predicts local recurrence. © 2010. Korean Association of Medical Journal Editors

p63 and p73 expression in extrahepatic bile duct carcinoma and their clinical significance

p53 plays a pivotal role in the prevention of human tumor formation. p73 and p63 are new members of the p53 tumor suppressor family, which are becoming increasingly recognized as important players in human tumorigenesis. However, the roles of these proteins are not well elucidated in extrahepatic bile duct (EBD) carcinoma. We examined expressions of the p63 and p73 genes and proteins in normal biliary epithelia, biliary dysplasias, and EBD carcinomas using immunohistochemistry and RT-PCR analysis. p63 and p73 proteins were overexpressed in 26.3 and 41.0% of EBD carcinomas, respectively. p63 protein expression was more frequent in tumors with vascular invasion (P = 0.002) and distal location (P = 0.04), while p73 expression was more common in cancers with deeper tumor invasion (P = 0.04). Patients with tumors co-expressing both p63 and p73 were found to have a significantly worse overall survival rate compared to those with either p63 or p73 expression (P < 0.05) as determined in univariate and multivariate analyses. Our results strongly imply that the p53 family members have different functions in EBD carcinomas. Our data also indicate that interactions between p63 and p73 play an important role in tumorigenesis of EBD carcinoma